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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.8571 | [
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"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Calcium Signals Driven by Single Channel Noise\nContent:\nAbstract:\nUsually, the occurrence of random cell behavior is appointed to small copy numbers of molecules involved in the stochastic process. Recently, we demonstrated for a variety of cell types that intracellular Ca2+ oscillations are sequences of random spikes despite the involvement of many molecules in spike generation. This randomness arises from the stochastic state transitions of individual Ca2+ release channels and does not average out due to the existence of steep concentration gradients. The system is hierarchical due to the structural levels channel- channel cluster- cell and a corresponding strength of coupling. Concentration gradients introduce microdomains which couple channels of a cluster strongly. But they couple clusters only weakly; too weak to establish deterministic behavior on cell level. Here, we present a multi-scale modelling concept for stochastic hierarchical systems. It simulates active molecules individually as Markov chains and their coupling by deterministic diffusion. Thus, we are able to follow the consequences of random single molecule state changes up to the signal on cell level. To demonstrate the potential of the method, we simulate a variety of experiments. Comparisons of simulated and experimental data of spontaneous oscillations in astrocytes emphasize the role of spatial concentration gradients in Ca2+ signalling. Analysis of extensive simulations indicates that frequency encoding described by the relation between average and standard deviation of interspike intervals is surprisingly robust. This robustness is a property of the random spiking mechanism and not a result of control.\nIntroduction:\nCellular behavior is the dynamics emerging out of molecular properties and molecular interactions. Hence, cells are indispensably subject to intrinsic noise due to the randomness of diffusion and molecule state transitions in gene expression[1],[2], signaling pathways and control mechanisms. It drives noise induced cell differentiation[3], cell-to-cell variability of cloned cells[4] or second messenger dynamics[5]. While noise in gene expression can be attributed to small molecule numbers, we consider here noise in signalling pathways which occurs even in systems with large molecule numbers. Molecular interactions create nonlinear feedback like substrate depletion and allosteric regulation in enzyme kinetics or mutual activation of ion channels in membrane potential dynamics. They also couple active molecules inside cells spatially by diffusion of product and substrate or electric currents. If this coupling is strong enough, cells respond spatially homogeneous. Otherwise, we observe dynamic spatial structures formed by concentrations of molecules in specific states. These structures are often called microdomains[6]–[9]. The existence of these dynamic structures determines in some systems whether the cell obeys deterministic or stochastic mechanisms. The dynamic compartmentalization of the cell by concentration gradients may prevent the establishment of deterministic dynamics by the law of large numbers even if the total number of molecules in the cell would suggest it otherwise. Microdomains are too small to behave deterministically. Not even the whole ensemble of microdomains will behave deterministically, if they are only weakly coupled or if there are only a few of them. Consequently, noise is not averaged out on cell level. To determine whether we deal with a deterministic or stochastic system is important since these regimes may exhibit very different dependencies of behavior on system parameters[10]. For instance, repetitive spiking in intracellular signalling would be restricted to parameter values providing oscillatory dynamics with a deterministic mechanism[11],[12]. It may occur with a stochastic system also for parameters which would lead to bistable or excitable dynamics in the deterministic limit, i. e. for larger or different parameter ranges[13]. In the non-oscillatory parameter ranges, the mechanism creating almost regular spike sequences can be coherence resonance[14]–[16] rather than the existence of a limit cycle in phase space of the local dynamics. Noisy systems with gradients usually show also a dependency of system characteristics on parameters of spatial coupling which spatially homogeneous systems do not exhibit. An example is the dependency of the spiking frequency on diffusion properties( see below and[5]). In summary, the interaction between noise and gradients determines parameter dependencies and mechanisms. Recent experimental and theoretical studies on intracellular dynamics taught us that cells may indeed work in this regime and may exhibit repetitive spiking with non-oscillatory local dynamics. Functionally relevant gradients are also observed with intracellular cAMP[8],[17]–[19], pH[20] and in phosphorylation/dephosphorylation dynamics[21],[22] suggesting that the lessons learned from dynamics may also apply to other systems. One of these lessons is that the randomness of single molecule state changes is carried up from the molecular level to cell level[23],[24]. Cellular concentration spikes form random sequences of interspike intervals( ISIs) and that randomness arises from the randomness of single molecule state transitions[5],[25]. Consequently, the fluctuations of cellular signals contain information on single molecule behavior. It is a task for modelling now to establish the relation between these fluctuations and single molecule properties to decode this information. Systems exhibiting the interaction between noise and gradients require modelling tools which can deal efficiently with the large concentration gradients and with the time scale range from molecular transitions to cell behavior. Here, we present such a modelling concept with the example of intracellular dynamics. It simulates all active molecules as stochastic Markov chains with all the individual state transitions and describes diffusion and some bulk reactions deterministically. Active molecules are those carrying the crucial feedbacks and nonlinearities. That allows for linearization of passive bulk reactions and the application of a multi-component Green's function to solve the partial differential equations in the cell analytically. We combine Green's functions with a local quasi-static approximation for the fast concentration changes and diffusion processes at the location of active molecules. That is possible due to the short diffusion time on the molecular length scale of a few nanometers. Since we use Green's functions for the long range concentration profiles we can restrict the calculation of concentration values to the location of active molecules. That renders this method extremely efficient even in 3 spatial dimensions. We will apply this concept to intracellular dynamics and compare simulated time dependent concentrations with single cell time series obtained from cultured astrocytes all measured under the same condition without any stimulation. is a ubiquitous second messenger in eukaryotic cells that transmits a variety of extracellular signals to intracellular targets. controls fertilization, cell differentiation, gene expression, learning and memory[26]. It triggers secretion in glands, muscle contractions in the heart and transmits apoptosis signals[27],[28]. A main mechanism to increase the cytosolic concentration is release from intracellular stores, especially from the sarcoplasmic reticulum by ryanodine receptor channels( RyRs) or the endoplasmic reticulum( ER) by inositol 1, 4, 5-trisphosphate receptor channels(). These channels open in a dependent fashion- a self amplifying effect known as induced release( CICR)[27],[29]. If a single channel opens, is released into the cytosol, diffuses to adjacent channels and increases their open probability. Thus release may spread into the entire cell leading to a global cytosolic concentration spike. The inositol 1, 4, 5-trisphosphate() pathway initiates release from the ER in many cell types( including astrocytes[30]), since binding of to the primes them for activation by( Figure 1 in Text S1). The spatial arrangement of in channel clusters leads to a hierarchical system with the structural levels channel, channel cluster and cluster array, which is the cell level. pumps and buffers generate large gradients close to open channel clusters. Thus, channels within a cluster are strongly coupled and the coupling between clusters is only weak- the geometrical hierarchy entails a hierarchy of coupling strengths. Stochastic binding of and to the binding sites of leads to random opening of a single channel in a cluster[31],[32]. This causes other channels of the same cluster to open also leading to a puff. An individual cluster is stochastic due to the small number of per cluster[33]–[35]. The opening of a single cluster can only be detected by adjacent clusters due to the strong gradients[23],[24],[27],[36],[37]. Since they are again only a few, it remains random whether they are opened by the initial puff. If a supercritical number of puffs arises, release spreads into the whole cell causing a global spike. Thus, due to the hierarchy of coupling strength, randomness is carried up from the channel level to the cell level. In order to model the hierarchical system, we have to consider the stochastic behavior of individual and the spatial heterogeneity of cells induced by clustering. That leads to a reaction diffusion system( RDS) with local stochastic source terms. For sufficient fast simulations, we decompose the system into local stochastic dynamics comprising channel state transitions and fast local concentration changes and a deterministic global dynamics for which we derive an analytical solution in form of a three component Green's function( Text S1). The solution is driven by stochastic channel behavior described by a hybrid deterministic-stochastic algorithm. We apply the model to a variety of experiments to demonstrate its potential.\nDiscussion:\nBoth the experiments and simulations show a simple linear relation between the standard deviation of ISI and the average ISI. The existence of this linear relation turned out to be surprisingly robust. It survives even an increase of the single channel current by an order of magnitude. This relation describes for each individual cell the response to stimulation changes. Cells shift the spike pattern from slow and irregular to fast and regular along the − relation when we increase stimulation. That supplements the current ideas on frequency encoding[54],[56]. At the same time, the − relation describes the outcome of spiking experiments with a group of cells. In the experiments, we subjected a sample of cells to the same protocol, and we obtained as many different responses as there are cells in the sample[5]. That set of responses is not arbitrarily scattered across the −-plane but aligns along the − relation. All the variability among individual cells with respect to expression levels of pathway components, cell volume, ER volume, shape, ion concentration, etc. does not lead to severe deviations from this − relation. spiking is robust against variability of many pathway components in the sense that the − relation is robust. We learn from the simulations here, that it is rather the stochastic spike generation mechanism than control and regulation which provides for this robustness. If we call the − relation from a single cell obtained by parameter changes individual relation and that obtained from a sample of cells population relation, we can describe our findings as identity of individual and population relation. We could reproduce the variability within a population of cells in simulations by varying cluster array geometry, pump strength, stimulation or buffering conditions. Changing these parameter values simply shifted the system on the − relation and did not modify the relation. But changing the single channel current by one order of magnitude did change the slope of the − relation. That suggests a mathematical definition of robustness which accounts for the fact that cells should be able to execute certain functions( e. g. to spike with a range of ISI), but not necessarily at the same strength of stimulation or normalized values of other parameters. We denote with and two variables describing the function( e. g. and), and with,…, and,…, two sets of parameters( e. g. stimulation strength, temperature, cell volume). The relation between and is robust with respect to value changes of parameters, if it has the structure. The parameters change only the value of while the control also the properties of, i. e. the properties of the pathway. We call this robustness of the function functional robustness( in difference to the robustness of the value of). If we identify the stimulation strength with, all cells distinguished by the values of only can realize frequency encoding with the same − relation by varying. They can realize this function also by varying another-parameter or several of them: function and functional robustness are closely related. The statement on robustness can also be interpreted with respect to identity of pathways converging onto spiking. signals can be caused by many different stimuli. The pathways upstream from responding to the stimuli must differ with respect to their value of the, in order to be distinguishable by pathways downstream from. In summary, cells realize frequency encoding- the function of spiking- by mainly moving up and down the relation between standard deviation and average of ISI and to some degree by modulating the deterministic part of the ISI[52]. The − relation exists for a stochastic process only, since holds for deterministic systems. The − relation turned out to be functionally robust with respect to changes of values of one set of parameters. That set may describe cell variability within one cell type or pathway. Changing substantially another set of parameters modified the − relation. That set appears rather to specify the identity of pathways converging on spiking. Our model predicts that close proximity of clusters is a prerequisite for a spontaneous response to spread throughout a cell. Indeed, there are types of astrocytes in which responses spread within the cell and those, such as Bergmann glia where this is not observed. Interestingly local, subcellular spontaneous responses have been recorded which represent functional microdomains[57]. Complementary to the functional units, morphological units are described which are separated from each other by fine processes[58]. It is well conceivable that these thin processes separate endoplasmic reticulum between microdomains by more than 2 and according to our model this separation would prevent the spread of a local signal to other parts of the cell. In contrast, in cultured astrocytes, the endoplasmic reticulum is preferentially arranged around the cell center without apparent discontinuity[59] and these cells frequently exhibit spontaneous responses. In situ, spontaneous responses are reported for hippocampal astrocytes and these astrocytes are less polarized as compared to Bergmann glial cells and we would predict that they are less compartimentalized. Indeed, morphological studies indicate that hippocampal astrocytes have five to ten main processes from which smaller extensions branch off[60]. The synchronized activity obviously can spread within the volume of the main processes and soma of hippocampal astrocytes. Moreover, in contrast to culture, the endoplasmic reticulum in astrocytes in hippocampus tissue is preferentially located close to the plasma membrane[59]. These different morphological arrangements result in distinct patterns of responses and as a consequence in different gene expression patterns[53]. The rise of cell imaging during the last decades illustrated the spatial structure of cells and protein localization. Obviously, cells are not homogeneous and active molecules coupled by diffusional transport are very common. Concentration gradients are functionally relevant, if they create microdomains inside which a pathway is in a state different from its state at other locations in the cell. They have been shown to exist for ‘the other’ fast diffusing intracellular messenger cAMP and in phosphorylation/dephosphorylation dynamics. Hence, the need for spatially resolved cell models exists and we can apply the modelling concept, if all essential non-linearities are in the discrete active molecules or the boundary conditions and we can linearize remaining bulk reactions. The excellent validity of the linearization for the buffer reactions of dynamics has been shown by Smith et al.[47]. We expect a degradation reaction like the cAMP degradation by PDEs also to be linearizable in good approximation. If local concentrations at active molecules should be outside the range of validity of the linearization, that can be fixed by the choice of the local quasi-static approximation of the diffusion process there in many cases. The non-linearities of cAMP production by membrane-bound adenylyl cyclase can be formulated as boundary condition and Green's function must then be used iteratively with an update of the boundary condition in each time step. These remarks illustrate that there is flexibility in the choice of reactions to be linearized which crucially expands the applicability of the concept.",
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"content": "The number of proteins organizing cellular processes is huge . The challenge for systems biology is to connect the properties of all these proteins to cellular behavior . Do individual state changes of molecules matter for cell behavior despite these large numbers ? Recently , we have experimentally shown for four cell types that intracellular Ca2+ signalling is driven by single channel dynamics . Molecular fluctuations are used constructively for a stochastic spike generation mechanism . The hierarchical structure of Ca2+ signalling prevents averaging of fluctuations and , consequently , the sequence of global spikes still reflects this molecular noise . Here we present a stochastic 3-D multiscale modelling tool living up to these findings by following the consequences of individual channel state changes up to cell level . We simulate the variety of cell responses in different experiments . The stochastic spike generation mechanism is surprisingly robust , providing new insights into the relation of function and robustness . The modelling concept can be applied to a large class of reaction-diffusion processes including other pathways like cAMP .",
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science.medmentions_ner | science.medmentions_ner.882 | [
{
"content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nDeterminants of Engagement in Leisure-time Physical Activity - Dialogue with Senior Athletes This article explores the factors determining whether older adults engage in the Senior Games and related leisure-time physical activity through examining the adults ' salient beliefs. We conducted 10 in-depth interviews with older adults who have participated in the Senior Games. Underpinned by the planned behavior theory's framework, we explored three types of beliefs: advantages and disadvantages (behavioral beliefs), social support and pressure (normative beliefs), and facilitators and impediments (control beliefs). Interview respondents were found to engage in the Senior Games and related physical activity to the extent that they associated various intangible advantages with the games and valued psychological satisfaction. They viewed their peers and families as supporting and approving of their engagement and recognized the physical capabilities required, and structural constraints necessary, to engage in the games and related activity. With these findings, pertinent beliefs can be combined with interventions designed to encourage leisure-time physical activities by older adults.",
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"content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"satisfaction\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"examining\"], \"Food\": [], \"HealthCareActivity\": [\"interventions\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"respondents\", \"peers\", \"Senior\"], \"ProfessionalOrOccupationalGroup\": [\"Athletes\"], \"ResearchActivity\": [], \"SpatialConcept\": [], \"Virus\": []}",
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.15487 | [
{
"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Promiscuous signaling by a regulatory system unique to the pandemic PMEN1 pneumococcal lineage\nContent:\nAbstract:\nStreptococcus pneumoniae( pneumococcus) is a leading cause of death and disease in children and elderly. Genetic variability among isolates from this species is high. These differences, often the product of gene loss or gene acquisition via horizontal gene transfer, can endow strains with new molecular pathways, diverse phenotypes, and ecological advantages. PMEN1 is a widespread and multidrug-resistant pneumococcal lineage. Using comparative genomics we have determined that a regulator-peptide signal transduction system, TprA2/PhrA2, was acquired by a PMEN1 ancestor and is encoded by the vast majority of strains in this lineage. We show that TprA2 is a negative regulator of a PMEN1-specific gene encoding a lanthionine-containing peptide( lcpA). The activity of TprA2 is modulated by its cognate peptide, PhrA2. Expression of phrA2 is density-dependent and its C-terminus relieves TprA2-mediated inhibition leading to expression of lcpA. In the pneumococcal mouse model with intranasal inoculation, TprA2 had no effect on nasopharyngeal colonization but was associated with decreased lung disease via its control of lcpA levels. Furthermore, the TprA2/PhrA2 system has integrated into the pneumococcal regulatory circuitry, as PhrA2 activates TprA/PhrA, a second regulator-peptide signal transduction system widespread among pneumococci. Extracellular PhrA2 can release TprA-mediated inhibition, activating expression of TprA-repressed genes in both PMEN1 cells as well as another pneumococcal lineage. Acquisition of TprA2/PhrA2 has provided PMEN1 isolates with a mechanism to promote commensalism over dissemination and control inter-strain gene regulation.\nIntroduction:\nStreptococcus pneumoniae( pneumococcus) is one of the most important community acquired human pathogens, and is responsible for an estimated 850, 000 deaths annually in children under the age of 5[1]. Pneumococcus colonizes the nasopharynx of young children at very high rates, and is asymptomatic in most cases[2, 3]. However, it can also disseminate from the nasopharynx into tissues leading to diseases such as otitis media, pneumonia, bacteremia, meningitis, and inflammation of the heart[4–6]. The pneumococcal molecules responsible for this transition from a commensal to a pathogen are not well understood. Here we characterize a novel quorum sensing( QS) system( TprA2/PhrA2) that limits pneumococcal disease, without affecting nasopharyngeal colonization. At the genomic level, there is extensive diversity among pneumococccal lineages. These genomic variations contribute to the differences in colonization and virulence potential[7]. Only half of the pangenome is shared across all strains( core set), while the other half is unevenly distributed amongst isolates[8, 9]. The Pneumococcal Molecular Epidemiology Network( PMEN) has grouped strains of multi locus sequencing type( MLST) 81 into the PMEN1 lineage( also known as Spain23F-1 and SPN23F)[10]. Over the past 30 years, PMEN1 has distinguished itself by its worldwide distribution, multi-drug resistant profile, and emergence of vaccine-escape strains. Historically, the PMEN1 lineage was responsible for the Spanish epidemic of the 1980s and has since spread to North and South America, Europe, Asia, Africa, and Australia[2, 10]. Most PMEN1 isolates are resistant to penicillin, chloramphenicol, and tetracycline, and many isolates have additional resistances to fluoroquinilones and macrolides[11, 12]. PMEN1 isolates are predominantly of serotype 23F, but there are also capsular switches to other serotypes, some of which represent vaccine-escape isolates[13]. Further, the PMEN1 lineage has impacted the genome content of the pneumococcal population by virtue of its high frequency of DNA donation, including genes for drug-resistance, to other pneumococcal lineages[14]. The PMEN1 genome encodes an integrative conjugative element( ICESp23FST81)[13, 15, 16]. As described by Croucher and colleagues upon sequencing of the first PMEN1 genome, this ICE encodes drug resistance determinants, a complete lanthionine-peptide gene cluster and a regulator-peptide pair, which in this study we have identified as the TprA2/PhrA2 QS system. Quorum sensing systems serve as a critical, decision-making process in the response of bacteria to the environment, and their ability to colonize and/or disseminate to tissues. The best characterized kind of QS machinery is the two component system, where the signal is sensed by a surface-localized histidine kinase and transferred to a cytosolic response regulator[17]. Streptococci, enterococci and bacilli have been shown to encode a second kind of QS characterized by the emerging RRNPP( Rgg/Rap/NprR/PlcR/PrgX) superfamily of transcriptional regulators and their cognate peptides[18]. In these systems, the secreted peptide is exported from the producer cell, processed, and imported into the cytosol of producing or neighboring cells, where it interacts with the RRNPP regulator[18]. RRNPP-peptide systems have been shown to regulate virulence, biofilm formation, and the production of bacteriocins[19–21]. In pneumococcus, the majority of characterized peptides signal via two component systems[17]. These peptides regulate competence and class II bacteriocin production[22, 23]. The first RRNPP-peptide pair was recently characterized in the pneumococcus strain D39[24]. It is composed of the TprA regulator and its cognate peptide PhrA. PhrA alleviates gene inhibition leading to the expression of physiologically important genes[24]. PhrA levels are repressed by glucose and activated by galactose, consistent with activity in the upper respiratory track where galactose is a major source of energy[25]. In this study we characterize the TprA2/PhrA2 QS system, a novel pneumococcal RRNPP-peptide pair, highly expressed in middle ear effusions. TprA2/PhrA2 is present almost exclusively in PMEN1 isolates where it restrains dissemination. Unlike other lineages, the PMEN1 strains encode both the TprA/PhrA and the TprA2/PhrA2 signaling systems. Extracellular PhrA2 leads to induction of TprA in PMEN1 cells as well as in D39 cells. Thus, horizontal acquisition of TprA2/PhrA2 has provided the PMEN1 lineage with a QS system and associated regulon, as well as the molecular machinery to regulate a widespread cell-cell communication system and in doing so, influence not only its own gene expression but also that of other strains.\nDiscussion:\nOur findings demonstrate that acquisition of the TprA2/PhrA2 QS system by horizontal gene transfer into the PMEN1 lineage has endowed these strains with a virulence determinant and a mechanism to regulate its expression and thereby control disease. PMEN1( ST81) lineage is postulated to have evolved from an ancestor in 1967, and by the end of 1990s it represented an estimated 40% of penicillin resistant strains in US[14, 41]. These strains display very high rates of carriage[2, 3, 41, 42]. PMEN1 also displays very high rates of disease[2, 3, 43]. Is the prevalence of PMEN1 in invasive disease a function of its carriage rates or does it reflect a propensity to cause disease? Multiple studies have shown that sequence types vary regarding their propensity to cause disease[44–47] and Sjostrom et al. show that PMEN1 displays a low propensity to cause invasive disease[47]. Thus, high rates of PMEN1 invasive disease in the population likely reflect high carriage rates, and not heightened virulence potential. In this context, it is possible that acquisition of the TprA2/PhrA2 by PMEN1 strains contributes to its low proclivity to cause invasive disease. TprA2/PhrA2 may provide PMEN1 strains with the means to manipulate gene expression in neighboring strains from other lineages in multi-strain infections. We show that synthetic C-terminal PhrA2 can stimulate expression of the TprA/PhrA system as well as its associated lantibiotic biosynthesis cluster in distantly related strain D39( Figs 11 and 12). We have observed that the expression of PMEN1-phrA2 is six fold that of D39-phrA in rich media, thus exemplifying a condition where PMEN1-phrA2 expression is high when D39-phrA is low( S3 Fig). We are currently investigating this interaction in physiologically relevant conditions. The activation of phrA in response to galactose has led to the conclusion that TprA/PhrA may promote colonization in the nasopharynx where free sugars are rare and pneumococci survive by breaking down host mucins to free complex sugars, most prominently galactose[24]. However, experiments with TprA/PhrA in the murine model demonstrate that this system is a virulence determinant in multiple models of pneumococcal disease( personal communication, Motib and Yesilkaya), in this manner, PhrA2 may trigger a virulence regulon in neighboring strains. We propose that PhrA2 signaling across systems is physiologically relevant in multi-strain infections. We conclude that PhrA2 peptide is secreted by PMEN1-cells, since cell-free culture supernatants reiterate the function of extracellular addition of synthetic PhrA2. We predict that export occurs via the Sec secretion system, consistent with other peptides from the PlcR family of regulator-peptide pairs[48–50]. Import must occur via a relatively widespread transporter, given that PhrA2 can influence D39 gene expression. Further, the high sequence similarity between the functional C-termini of PhrA and PhrA2 suggests common import machinery. The oligopeptide permease amiACDEF has been shown to be required for import of processed PhrA, and its homologues are required for import of PlcR-associated peptides in other species[48–50]. Thus, amiACDEF is a high value candidate for a PhrA2 importer. Sequence comparisons suggest that LcpA is a bacteriocin, however its function remains unknown. We propose that its effect on virulence is not the result of bacteriocidal activity given that mouse experiments where performed with single strains. However, we cannot exclude the possibility that an interaction between LcpA and the natural microbiome of the mouse influences the outcome of the infection. The function of LcpA is under investigation. We have identified and characterized a new quorum sensing system from the emerging RRNPP family. TprA2/PhrA2 consists of a negative regulator of a lanthionine containing peptide and a cognate activating peptide. Our findings suggest that this system has provided PMEN1 with the ability to control LcpA virulence and perhaps influence its propensity to cause invasive disease. Finally, to our knowledge this is the first example of a gene transfer event that has integrated with an ancestral regulatory networks to control inter-strain gene regulation.",
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"content": "Streptococcus pneumoniae ( pneumococcus ) , an important human pathogen , exhibits a dual lifestyle featuring asymptomatic colonization of the host on the one hand as well as infliction of severe local and systemic disease on the other . In pneumococcal strains , differences in gene possession often lead to varied phenotypic outcomes . Epidemiologically , pandemic strains of the PMEN1 lineage show high prevalence in disease as well as carriage , posing an interesting question on the composition and function of the genomic toolkit that leads to their widespread success . Here , we characterize TprA2/PhrA2 sensory system , a genomic region acquired exclusively by the PMEN1 strains . The system consists of a regulator-peptide pair that was horizontally acquired into PMEN1 along with its regulatory circuitry . The regulatory peptide PhrA2 is receptive to cell density of PMEN1 cells and is an example of elegant communication signaling between bacterial cells . The regulatory influence of PhrA2 extends beyond PMEN1 cells such that it controls genes of a widespread signaling system and virulence regulon in non-PMEN1 strains . This work contributes to the knowledge of peptide-communication signals in pneumococcus and further adds a novel mechanism by which an ecologically successful linage may modify the transcriptomic and functional landscape of a multi-strain pneumococcal community .",
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science.craftchem_ner | science.craftchem_ner.1548 | [
{
"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nFigure3",
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science.scitldr_aic | science.scitldr_aic.1720 | [
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"content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nUnderstanding the flow of information in Deep Neural Networks (DNNs) is a challenging problem that has gain increasing attention over the last few years.\nWhile several methods have been proposed to explain network predictions, there have been only a few attempts to compare them from a theoretical perspective.\nWhat is more, no exhaustive empirical comparison has been performed in the past.\nIn this work we analyze four gradient-based attribution methods and formally prove conditions of equivalence and approximation between them.\nBy reformulating two of these methods, we construct a unified framework which enables a direct comparison, as well as an easier implementation.\nFinally, we propose a novel evaluation metric, called Sensitivity-n and test the gradient-based attribution methods alongside with a simple perturbation-based attribution method on several datasets in the domains of image and text classification, using various network architectures.\nWhile DNNs have had a large impact on a variety of different tasks BID10 BID8 BID12 BID21 BID28 , explaining their predictions is still challenging.\nThe lack of tools to inspect the behavior of these black-box models makes DNNs less trustable for those domains where interpretability and reliability are crucial, like autonomous driving, medical applications and finance.In this work, we study the problem of assigning an attribution value, sometimes also called \"relevance\" or \"contribution\", to each input feature of a network.\nMore formally, consider a DNN that takes an input x = [x 1 , ..., x N ] ∈ R N and produces an output S(x) = [S 1 (x), ..., S C (x)], where C is the total number of output neurons.\nGiven a specific target neuron c, the goal of an attribution method is to determine the contribution R c = [R c 1 , ..., R c N ] ∈ R N of each input feature x i to the output S c .\nFor a classification task, the target neuron of interest is usually the output neuron associated with the correct class for a given sample.\nWhen the attributions of all input features are arranged together to have the same shape of the input sample we talk about attribution maps FIG0 , which are usually displayed as heatmaps where red color indicates features that contribute positively to the activation of the target output, and blue color indicates features that have a suppressing effect on it.The problem of finding attributions for deep networks has been tackled in several previous works BID22 BID30 BID24 BID2 BID20 BID25 BID31 .\nUnfortunately, due to slightly different problem formulations, lack of compatibility with the variety of existing DNN architectures and no common benchmark, a comprehensive comparison is not available.\nVarious new attribution methods have been published in the last few years but we believe a better theoretical understanding of their properties is fundamental.\nThe contribution of this work is twofold:1.\nWe prove that -LRP BID2 and DeepLIFT (Rescale) BID20 can be reformulated as computing backpropagation for a modified gradient function (Section 3).\nThis allows the construction of a unified framework that comprises several gradient-based attribution methods, which reveals how these methods are strongly related, if not equivalent under certain conditions.\nWe also show how this formulation enables a more convenient implementation with modern graph computational libraries.2.\nWe introduce the definition of Sensitivity-n, which generalizes the properties of Completeness BID25 and Summation to Delta BID20 and we compare several methods against this metric on widely adopted datasets and architectures.\nWe show how empirical results support our theoretical findings and propose directions for the usage of the attribution methods analyzed (Section 4).\nIn this work, we have analyzed Gradient * Input, -LRP, Integrated Gradients and DeepLIFT (Rescale) from theoretical and practical perspectives.\nWe have shown that these four methods, despite their apparently different formulation, are strongly related, proving conditions of equivalence or approximation between them.\nSecondly, by reformulating -LRP and DeepLIFT (Rescale), we have shown how these can be implemented as easy as other gradient-based methods.\nFinally, we have proposed a metric called Sensitivity-n which helps to uncover properties of existing attribution methods but also traces research directions for more general ones.Nonlinear operations.\nFor a nonlinear operation with a single input of the form x i = f (z i ) (i.e. any nonlinear activation function), the DeepLIFT multiplier (Sec. 3.5.2 in Shrikumar et al. BID20 ) is: DISPLAYFORM0 Nonlinear operations with multiple inputs (eg. 2D pooling) are not addressed in BID20 .\nFor these, we keep the original operations' gradient unmodified as in the DeepLIFT public implementation.\nBy linear model we refer to a model whose target output can be written as S c (x) = i h i (x i ), where all h i are compositions of linear functions.\nAs such, we can write DISPLAYFORM1 for some some a i and b i .\nIf the model is linear only in the restricted domain of a task inputs, the following considerations hold in the domain.\nWe start the proof by showing that, on a linear model, all methods of TAB0 are equivalent.Proof.\nIn the case of Gradient * Input, on a linear model it holds DISPLAYFORM2 , being all other derivatives in the summation zero.\nSince we are considering a linear model, all nonlinearities f are replaced with the identity function and therefore ∀z : g DL (z) = g LRP (z) = f (z) = 1 and the modified chain-rules for LRP and DeepLIFT reduce to the gradient chain-rule.\nThis proves that -LRP and DeepLIFT with a zero baseline are equivalent to Gradient * Input in the linear case.\nFor Integrated Gradients the gradient term is constant and can be taken out of the integral: DISPLAYFORM3 , which completes the proof the proof of equivalence for the methods in TAB0 in the linear case.If we now consider any subset of n features x S ⊆ x, we have for Occlusion-1: DISPLAYFORM4 where the last equality holds because of the definition of linear model (Equation 9 ).\nThis shows that Occlusion-1, and therefore all other equivalent methods, satisfy Sensitivity-n for all n if the model is linear.\nIf, on the contrary, the model is not linear, there must exists two features x i and x j such that DISPLAYFORM5 .\nIn this case, either Sensitivity-1 or Sensitivity-2 must be violated since all methods assign a single attribution value to x i and x j .",
"role": "user"
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"content": "Four existing backpropagation-based attribution methods are fundamentally similar. How to assess it?",
"role": "assistant"
}
]
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science.bioasq_yesno_qa | science.bioasq_yesno_qa.515 | [
{
"content": "Examine the provided biomedical text and determine the answer to the question. Your response should be either \"yes\" or \"no\" based on the information given.\n\nQuestion: Have the promoter regions of the genes implicated in Rett Syndrome been characterized with CAGE?\n\nText: CAGE-defined promoter regions of the genes implicated in Rett Syndrome.\nMutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes.RESULTS: Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum.CONCLUSIONS: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome.\nCAGE-defined promoter regions of the genes implicated in Rett Syndrome\nCAGE-defined promoter regions of the genes implicated in Rett Syndrome.",
"role": "user"
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{
"content": "yes",
"role": "assistant"
}
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science.scientific_papers_summarization_single_doc_arxiv | science.scientific_papers_summarization_single_doc_arxiv.4381 | [
{
"content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nin this paper , we study the problem of discrete polynomial blending , a discretization of the problem of curve blending . in curve blending ,\none approximates a bivariate function by interpolating to a network of curves extracted from the graph of the function .\ndiscrete blending involves a second level of discretization , whereby the blended curves are interpolated at finite sets of points .\nthis is illustrated in fig .\n[ fblend1 ] . in the figure ,\nthe blended interpolant would interpolate to the 9 curves ( 4 horizontal and 5 vertical ) in the network , while the discrete blended surface interpolates at @xmath0 grid points . in our work\n, the term `` interpolation '' can be taken loosely to mean interpolation with respect to a given set of functionals , and may not necessarily imply point evaluation . the grid in fig .\n[ fblend1 ] is not uniform due to gaps between some grid points .\nif we filled in these holes we would have a uniform grid with @xmath1 points that can be interpolated using tensor product polynomials .\nhence , we can interpolate at just @xmath0 points rather than @xmath2 , and in some cases do so with the same ( or nearly the same ) rate of approximation , as we shall show in this paper . in discrete polynomial blending ,\nthe approximating spaces are not generally tensor product polynomial spaces ( although that is a special case ) .\nas it turns out , our approximating spaces are the `` sum of tensor product polynomial spaces '' .\nhence , our study is one of approximation from the sum of tensor product polynomial spaces .\nwhat is known about discrete blending comes mainly from the literature on boolean sum interpolation , sparse grid methods , lower set interpolation and finite elements .\nthe topic was perhaps first studied by biermann @xcite who constructed polynomial interpolants using the bivariate lagrange basis .\nthe book @xcite is an excellent summary of boolean sum methods , including an analysis of biermann interpolation . in @xcite\n, a construction was given that generalized biermann interpolation to interpolation with respect to more general sequences of functionals , much like we will do in this paper .\nbiermann interpolation was generalized to higher dimensions in @xcite , under the title `` d - variate boolean interpolation '' , and more recently to arbitrary `` lower sets '' in @xcite ( which reduces to the results in @xcite for total degree interpolation ) . in this paper\nwe construct a new discrete blended quasi - interpolant based on the bernstein basis .\nto do so , we will bring in some techniques on `` dual basis in subspaces '' that the author has studied in @xcite . from this\nwe construct dual bases for the space of discrete blending , and compute approximation estimates .\none of the main contributions is to show our quasi - interpolants achieve rates of approximation comparable or the same as that of tensor product interpolation on a larger grid , but with much fewer data points .\nthis leads us to the construction of a quasi - interpolant analogous to the serendipity elements in the finite element method .\nthe results presented in this paper originate from a talk by the author at the conference on curves and surfaces in oslo , norway , in 2012 .\nthe remainder of the paper is organized as follows . * the approximating space .\n* quasi - uniform grids . * the bernstein basis and univariate quasi - interpolant .\n* discretely blended bernstein - bzier quasi - interpolants .\n* order of approximation .\n* serendipity elements .\n* examples .\nin discrete polynomial blending , the approximating space is the algebraic sum of tensor product polynomial spaces .\nlet @xmath3 $ ] and @xmath4 $ ] be sequences in @xmath5 , the space of @xmath6-tuples of non - negative integers .\nlet @xmath7 be the tensor product of the spaces @xmath8 and @xmath9 of polynomials of degrees at most @xmath10 and @xmath11 , respectively .\nthen , we define our approximating spaces as @xmath12 we assume that both @xmath13 and @xmath14 are strictly increasing sequences , an assumption that we justify by the following lemma .\nlet @xmath15 be defined as in ( [ e1 ] ) for some @xmath13 and @xmath14 in @xmath5\n. there exists strictly increasing sequences @xmath16 and @xmath17 in @xmath18 for some @xmath19 such that @xmath20 . to begin , let @xmath21 and let @xmath22 and @xmath23 .\nto prove this result , we will rearrange and truncate @xmath16 and @xmath17 until they are strictly increasing .\nsuppose @xmath24 for some @xmath25 and @xmath26 . then either @xmath27 or @xmath28 . in the former case\n, @xmath29 can be removed from the representation in ( [ e1 ] ) without changing @xmath30 , and so we remove @xmath31 and @xmath32 from the sequences @xmath33 and @xmath34 . in the latter case ,\nwe remove @xmath35 and @xmath36 . after removing these unnecessary terms ,\nthe terms left in the revised sequence @xmath33 are distinct .\nthat is , @xmath37 for all @xmath25 and @xmath26 .\nfurther , since @xmath38 is not affected by the ordering of the tensor product terms , we can rearrange the pairs @xmath39 in @xmath40 so that @xmath16 is strictly increasing .\nthus , assume that @xmath16 is strictly increasing .\nnow , if @xmath34 is not strictly increasing , then there exists an index @xmath25 such that @xmath41 and @xmath42 , in which case @xmath43 , and so @xmath29 can be removed from the sum without changing @xmath30 . after trimming away all such terms in the sequence ,\nwe are left with @xmath34 strictly increasing .\nhence , we are left with strictly increasing sequences @xmath33 and @xmath34 in @xmath44 for some @xmath45 such that @xmath46 .\nfurther , since we are not adding new terms , @xmath19 . a polynomial @xmath47 can be represented @xmath48 with @xmath49 .\neach @xmath50 can be expressed @xmath51 for some coefficients @xmath52 .\ntherefore , the power basis for the space @xmath15 is the union @xmath53 however , this union is not disjoint .\nthis basis can visualized by the dots in a _ lower grid _ , which is defined to be the graph of the _ lower set _\n\\times [ 0 , \\ldots , n_{r - k}].\\ ] ] the power basis for @xmath15 is therefore @xmath55 , and the dimension of @xmath15 is the number of dots in the lower grid . by counting the distinct dots in the lower grid , we arrive at the following : [ prop0 ] the space @xmath15 is a vector space of dimension @xmath56 with @xmath57 . in tbl .\n[ f1a ] , the dimension of the approximating space is given for a few choices of @xmath13 and @xmath14 . in fig .\n[ f1b ] , the corresponding lower grids are plotted . .\napproximating spaces for : @xmath58 $ ] , @xmath59 $ ] , @xmath60 $ ] and @xmath61 $ ] . [ cols=\"<,<,<,<\",options=\"header \" , ] [ 6b ]\nin this paper we have constructed a new quasi - interpolant for discrete blended surface approximation based on dual basis functions in the bernstein basis , and we have established error estimates comparable to approximation on full tensor product grids , much like the serendipity elements in the finite element literature . throughout this paper we assumed @xmath62 and @xmath63 .\nif we do not have this , we can still apply our construction by first using degree elevation .\nfor example , if @xmath64 $ ] we would degree elevation to get @xmath65 $ ] , and then proceed as before .\nthe framework for this originates from the talk `` dual bases on subspaces and the approximation from sums of polynomial and spline spaces '' , given by the author at the conference `` mathematical methods for curves and surfaces '' , held in oslo norway , june , 2012 .\nthe talk included constructions for hermite and spline blended elements similar to the construction in this paper .\nour plan is to publish the details of these results in forthcoming papers .",
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"content": "in this paper we study `` discrete polynomial blending , '' a term used to define a certain discretized version of curve blending whereby one approximates from the `` sum of tensor product polynomial spaces '' over certain grids . \n our strategy is to combine the theory of boolean sum methods with dual bases connected to the bernstein basis to construct a new quasi - interpolant for discrete blending . \n our blended element has geometric properties similar to that of the bernstein - bzier tensor product surface patch , and rates of approximation that are comparable with those obtained in tensor product polynomial approximation . \n [ multiblock footnote omitted ]",
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science.scientific_papers_summarization_single_doc_arxiv | science.scientific_papers_summarization_single_doc_arxiv.10709 | [
{
"content": "You will be presented with the full text of a scientific research paper. Write an abstract summarizing the key points. Your response should contain only the abstract without any other text.\n\nArticle text:\nmany studies over the past decade have presented strong evidence for the coevolution of black holes and galaxies based on samples dominated by the low - density field ( e.g. * ? ? ?\n* ; * ? ? ?\n* and references therein ) .\nit is interesting to determine if similar coevolution between agn and galaxies is present in groups and clusters because the physical processes that drive galaxy evolution , such as the available cold gas to fuel star formation and black hole growth , are substantially different from the field .\nin addition , agn in groups and clusters at low - redshift appear to play the critical role in maintaining the temperature of their hot atmospheres ( e.g. * ? ? ? * ) , while agn heating at the epoch of cluster assembly remains a viable explanation for the minimum entropy level in the intracluster medium .\nthese questions have motivated my collaborators and i to systematically search for agn in groups and clusters of galaxies and led to the discovery of large numbers of agn in these dense environments in the local universe @xcite . in this contribution\ni summarize some recently published work on the evolution of agn in clusters of galaxies @xcite and present a new , preliminary analysis of the evolution of agn in the lower - density group environment .\ni conclude with a brief discussion of several future directions .\nthe key requirement to measure the evolution of agn in groups and clusters , as well as perform quantitative comparisons to their galaxy populations , is systematic and unbiased selection .\nwe select agn with x - ray observations obtained by the _\nchandra _ and _ xmm _ satellites because x - ray emission provides a relatively unbiased measure of accretion for luminous objects .\nredshifts of the counterparts to the x - ray sources , obtained from our work or the literature @xcite , are then used to identify the subset of x - ray sources associated with the groups and clusters .\nour final sample includes 17 clusters with @xmath1 and 15 clusters with @xmath2 that are reasonably well - matched in spite of their heterogeneous selection based on available archival data .\nwe systematically characterize the agn population via the agn fraction , which is defined as the fraction of all galaxies brighter than some absolute magnitude that host agn above some luminosity threshold .\ngiven the sensitivity limits of x - ray data and multi - object spectroscopy , the agn fraction in clusters is defined here as the fraction of galaxies brighter than @xmath3 that host agn with hard x - ray [ 2 - 10 kev ] luminosities above @xmath4 erg s@xmath5 . while redshift measurements are nearly complete for the x - ray sources , this is not always the case for the entire galaxy population of the group or cluster .\nin many cases the number of galaxies above the luminosity threshold is estimated from the velocity dispersion and an empirical relation derived from the sdss @xcite . throughout this work\nthe agn fraction is only measured for agn and other galaxies that fall within the projected @xmath6 radius , that is the radius within which the group or cluster is a factor of 200 overdensity .\nfurther details are provided in @xcite .\nthe main result of this analysis is presented in the figure , which demonstrates that the cluster agn fraction increases by a factor of eight from the present to @xmath0 .\nthis evolution is based on 2 luminous agn in 17 clusters at @xmath1 and 17 luminous agn in 15 clusters at @xmath7 .\nthis dramatic evolution is similar to the evolution of the star - forming galaxy population in clusters known as the butcher - oemler effect @xcite .\nhere we have parametrized the agn evolution as @xmath8 where @xmath9 ( _ dashed line _ in the figure ) .\nthis power - law index is consistent with the value of @xmath10 recently measured for star - forming galaxies from mid - infrared observations @xcite and supports the hypothesis that black holes and galaxies coevolve in dense environments .\nto @xmath11 from a sample 17 clusters at @xmath1 and 15 clusters at @xmath7 ( _ filled circles _ ) .\nthese points represent the average fraction of cluster members more luminous than @xmath3 that host agn more luminous than @xmath12 erg / s .\nthe increase in the agn fraction is consistent with a power - law of the form @xmath13 ( _ dashed line _ ) and is approximately an order of magnitude below the field agn fraction ( _ open symbols _ ) over this redshift range .\na preliminary estimate of the group agn fraction suggests their rate of evolution is similar ( _ gray triangle _ at @xmath14 and _ upper limit _ at @xmath15 ) .\nthe group agn fraction is defined as the fraction of @xmath16 erg / s agn in galaxies with @xmath17 mag ( see _ right - hand axis _\nlabel ) . ]\nthe rate of evolution of the agn fraction also appears similar to the lower - density field ( _ open symbols _ ) , although the cluster agn fraction is approximately an order - of - magnitude lower over the entire redshift range .\nthe lower agn fraction in clusters relative to the field strongly suggests that there must be a substantial change in the agn fraction in the intermediate - density group environment .\nobservations of high - redshift groups find a substantial decrease in the agn fraction with increasing overdensity at @xmath0 @xcite and a measured group agn fraction of @xmath18% for agn with broad - band x - ray luminosities @xmath19 erg s@xmath5 in galaxies more luminous than @xmath17 mag ( * ? ? ?\n* _ gray triangle _ in figure ) .\nstudies of low - redshift groups find that the agn fraction is somewhat higher but consistent with the value measured in clusters @xcite ; however , the group sample contains far fewer galaxies and provides only an upper limit on agn as luminous as those in the high - redshift sample ( the _ arrow _ at @xmath15 in the figure represents the 90% confidence limit on the group agn fraction ) .\nthe observations summarized here have shown that the agn fraction in clusters increases by approximately an order of magnitude from the present to @xmath0 .\nthis evolution is also quantitatively similar to the evolution of the star - forming galaxy fraction in clusters , which suggests that cluster galaxies and their central black holes also coevolve , although at a different rate from their counterparts in the field .\na simple comparison between the agn fraction in clusters and the field indicates that the cluster agn fraction is approximately an order of magnitude lower over the entire observed redshift range .\none future direction for this research is to push further into the past toward the epoch of cluster galaxy assembly at @xmath20 .\nnumerous lines of evidence suggest that cluster galaxies formed earlier than their field counterparts , and the hypothesis of black hole and galaxy coevolution predicts that the the agn fraction in dense environments should exceed the field value by this point . at lower redshifts ,\nthe identification of the properties of the `` transition '' group environment , in which the agn fraction drops from the field to the cluster value , can potentially shed substantial light on the nature of the mechanism(s ) responsible for triggering and fueling agn .\nfinally , measurements of star formation and black hole accretion rates in the same cluster samples could reveal the extent of the correlation exhibited by individual galaxies and provide new insights into the physical processes that drive the observed coevolution .\ni am grateful for the contributions of t. arnold , a. berti , t. e. jeltema , d. d. kelson , j. s. mulchaey , g. r. sivakoff , and a. i. zabludoff to the research that i have presented in this conference article .\ni also appreciate the opportunity to speak at the conference and thank the organizers for this stimulating meeting .\nmy research was supported in part by nasa through chandra award number ar8 - 9014x and spitzer grant 1364997 , and nsf via award ast-0705170 , and the department of astronomy at osu .",
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"content": "the evolution of agn in groups and clusters provides important information about how their black holes grow , the extent to which galaxies and black holes coevolve in dense environments , and has implications for feedback in the local universe and at the epoch of cluster assembly . \n i describe new observations and analysis that demonstrates that the agn fraction in clusters increases by a factor of eight from the local universe to @xmath0 and that this evolution is consistent with the evolution of star - forming galaxies in clusters . \n the cluster agn fraction remains approximately an order of magnitude below the field agn fraction over this entire range , while a preliminary analysis of groups indicates that they too undergo substantial evolution . \n address = department of astronomy and center for cosmology and astroparticle physics , + the ohio state university , columbus , oh , usa",
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science.healthver_entailment | science.healthver_entailment.4263 | [
{
"content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: disposable ear loop masks do not provide any protection against the novel coronavirus.\n\nResearch Abstract:\nWe use the synthetic control method to analyze the effect of face masks on the spread of Covid-19 in Germany.\nOur identification approach exploits regional variation in the point in time when face masks became compulsory.\nDepending on the region we analyse, we find that face masks reduced the cumulative number of registered Covid-19 cases between 2.3% and 13% over a period of 10 days after they became compulsory.\nAssessing the credibility of the various estimates, we conclude that face masks reduce the daily growth rate of reported infections by around 40%.",
"role": "user"
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"content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Depending on the region we analyse, we find that face masks reduced the cumulative number of registered Covid-19 cases between 2.3% and 13% over a period of 10 days after they became compulsory.\", \"Assessing the credibility of the various estimates, we conclude that face masks reduce the daily growth rate of reported infections by around 40%.\"]}",
"role": "assistant"
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science.pico_ner | science.pico_ner.889 | [
{
"content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\n[ Rilmenidine sympatholytic activity preserves mental and orthostatic sympathetic response and epinephrine secretion ] . BACKGROUND Heightened central sympathetic nervous outflow is common in essential hypertension , contributing to hypertension development and perhaps also to complications . Acute sympathetic nervous activation is a proven trigger for adverse cardiovascular events . Accordingly , antihypertensive drugs inhibiting sympathetic outflow represent a theoretically attractive therapeutic option . OBJECTIVES To study the sympatholytic and blood pressure lowering activity of the imidazoline binding agent rilmenidine at rest and during reflex sympathetic activation . DESIGN AND METHODS The HERA study ( Hyperium Effect on the sympathetic Reflex activation and Adrenaline ) is a randomised , double-blind , 6-week cross-over trial , with a 1-week placebo run-in period , two 2-week active treatment intervals ( rilmenidine 1 mg bid , placebo ) and intervening one week placebo wash-out . In 15 hypertensive patients , noradrenaline and adrenaline plasma kinetics and intra-arterial blood pressure measurements were performed at rest , after mental stress ( difficult mental arithmetic ) and during head-up tilting , at the end of the 2-week dosing periods . RESULTS The noradrenaline spillover rate , indicative of whole body sympathetic activity , was reduced 35 % by rilmenidine at rest ( p < 0.01 ) and remained significantly lower during mental stress and tilting , although the increases in noradrenaline spillover with both stimuli were preserved . The effects on intraarterial blood pressure ran in parallel , a fall in supine resting pressure , but no reduction in BP rise during mental stress and a lack of fall in BP with tilting . On placebo , adrenaline secretion was 162 +/- 27 ng/min ( mean , SE ) at rest , increased by 77 +/- 42 ng/min with mental stress ( p=0.019 ) and was unchanged with tilting . Rilmenidine left adrenaline secretion untouched under all conditions . CONCLUSIONS This study confirms a sympatholytic effect of rilmenidine during supine rest but demonstrates that sympathetic responses during mental stress and tilting are preserved , the latter underlying a perhaps surprising absence of postural hypotension on the drug . The absence of suppression of reflexive sympathetic responses contrasts with the effects of rilmenidine in experimental animals , and emphasises the previously demonstrated unique importance in humans of suprabulbar noradrenergic neuronal projections from the brainstem , which are inhibited by imidazoline binding agents , in regulating tonic sympathetic activity in essential hypertension . Sympathetic nervous inhibition with rilmenidine contrasted with an absence of suppression of the secretion of adrenaline affirming that here , as elsewhere , sympathetic nervous and adrenal medullary function can be disconnected .",
"role": "user"
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"content": "{\"Intervention\": [\"rilmenidine\", \"Rilmenidine\", \"placebo\"], \"Outcome\": [\"adverse cardiovascular events\", \"intraarterial blood pressure\", \"and adrenal medullary function\", \"sympathetic nervous\", \"mental and orthostatic sympathetic response\", \"noradrenaline and adrenaline plasma kinetics and intra-arterial blood pressure measurements\", \"tonic sympathetic activity\", \"sympatholytic and blood pressure lowering activity\", \"BP rise\", \"noradrenaline spillover\", \"epinephrine secretion ]\", \"BP\", \"adrenaline secretion\", \"sympathetic responses\"], \"Participant\": [\"hypertensive patients\", \"15\"]}",
"role": "assistant"
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science.pico_ner | science.pico_ner.4468 | [
{
"content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nInhibition of epidural morphine-induced pruritus by intravenous droperidol . The effect of increasing the doses of morphine and of droperidol . BACKGROUND AND OBJECTIVES Because the mechanism of inhibition of epidural morphine-induced pruritus by droperidol is not clear , this study was undertaken to determine the effects of larger doses of droperidol or morphine , or both . METHODS A double-blind study was performed in 210 ASA I or II patients undergoing cesarean delivery , who were randomly assigned to six groups . All patients received epidural anesthesia with 0.5 % bupivacaine containing 1:200,000 epinephrine , to which 2 mg ( groups 1 , 2 , and 3 ) or 4 mg ( groups 4 , 5 , and 6 ) morphine sulfate was added . Just after delivery , 2.5 mg droperidol was given intravenously to groups 2 and 5 , and 5 mg was given to groups 3 and 6 . During the postoperative period , the patients were assessed for the occurrence and severity of pruritus ( classified as absent , mild , moderate , or severe ) or other untoward symptoms . The groups were compared for the incidence of pruritus by the Mann-Whitney nonparametric test . RESULTS The incidence of pruritus was significantly reduced only when the control group . ( no droperidol ) was compared with the group that received 2.5 mg droperidol , both when 2 mg and when 4 mg morphine was used . A 5-mg dose of droperidol had no inhibitory effect . There was no difference in the incidence of pruritus between use of 2 mg and 4 mg morphine . Other untoward effects of morphine either could not be observed or occurred with an incidence unaffected by either dose of droperidol . CONCLUSION Pruritus caused by epidural use of 2 or 4 mg of morphine is inhibited by the intravenous use of 2.5 mg droperidol but not by a larger dose .",
"role": "user"
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"content": "{\"Intervention\": [\"droperidol\", \"morphine sulfate\", \"epinephrine\", \"epidural anesthesia\", \"morphine\", \"bupivacaine\"], \"Outcome\": [\"inhibitory effect\", \"Pruritus\", \"epidural morphine-induced pruritus\", \"untoward effects\", \"occurrence and severity of pruritus\", \"incidence of pruritus\", \"other untoward symptoms\"], \"Participant\": [\"ASA I or II patients undergoing cesarean delivery\", \"randomly assigned to six groups\", \"210\"]}",
"role": "assistant"
}
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.4755 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nDetecting small objects over large areas remains a significant challenge in satellite imagery analytics. Among the challenges is the sheer number of pixels and geographical extent per image: a single DigitalGlobe satellite image encompasses over 64 km2 and over 250 million pixels. Another challenge is that objects of interest are often minuscule ( pixels in extent even for the highest resolution imagery), which complicates traditional computer vision techniques. To address these issues, we propose a pipeline (SIMRDWN) that evaluates satellite images of arbitrarily large size at native resolution at a rate of > 0.2 km2 s. Building upon the tensorflow object detection API paper, this pipeline offers a unified approach to multiple object detection frameworks that can run inference on images of arbitrary size. The SIMRDWN pipeline includes a modified version of YOLO (known as YOLT), along with the models of the tensorflow object detection API: SSD, Faster R-CNN, and R-FCN. The proposed approach allows comparison of the performance of these four frameworks, and can rapidly detect objects of vastly different scales with relatively little training data over multiple sensors. For objects of very different scales (e.g. airplanes versus airports) we find that using two different detectors at different scales is very effective with negligible runtime cost.We evaluate large test images at native resolution and find mAP scores of 0.2 to 0.8 for vehicle localization, with the YOLT architecture achieving both the highest mAP and fastest inference speed.\n\nCited Works Summary:\n[1]: We evaluated how deep convolutional neural networks (DCNN) could assist in the labor-intensive process of human visual searches for objects of interest in high-resolution imagery over large areas of the Earth’s surface. Various DCNN were trained and tested using fewer than 100 positive training examples (China only) from a worldwide surface-to-air-missile (SAM) site dataset. A ResNet-101 DCNN achieved a 98.2 average accuracy for the China SAM site data. The ResNet-101 DCNN was used to process ∼19.6 M image chips over a large study area in southeastern China. DCNN chip detections (∼9300) were postprocessed with a spatial clustering algorithm to produce a ranked list of ∼2100 candidate SAM site locations. The combination of DCNN processing and spatial clustering effectively reduced the search area by ∼660X (0.15 of the DCNN-processed land area). An efficient web interface was used to facilitate a rapid serial human review of the candidate SAM sites in the China study area. Four novice imagery analysts with no prior imagery analysis experience were able to complete a DCNN-assisted SAM site search in an average time of ∼42 min. This search was ∼81X faster than a traditional visual search over an equivalent land area of ∼88,640 km2 while achieving nearly identical statistical accuracy (∼90 F1).\n\n[2]: In this paper, we focus on tackling the problem of automatic accurate localization of detected objects in high-resolution remote sensing images. The two major problems for object localization in remote sensing images caused by the complex context information such images contain are achieving generalizability of the features used to describe objects and achieving accurate object locations. To address these challenges, we propose a new object localization framework, which can be divided into three processes: region proposal, classification, and accurate object localization process. First, a region proposal method is used to generate candidate regions with the aim of detecting all objects of interest within these images. Then, generic image features from a local image corresponding to each region proposal are extracted by a combination model of 2-D reduction convolutional neural networks (CNNs). Finally, to improve the location accuracy, we propose an unsupervised score-based bounding box regression (USB-BBR) algorithm, combined with a nonmaximum suppression algorithm to optimize the bounding boxes of regions that detected as objects. Experiments show that the dimension-reduction model performs better than the retrained and fine-tuned models and the detection precision of the combined CNN model is much higher than that of any single model. Also our proposed USB-BBR algorithm can more accurately locate objects within an image. Compared with traditional features extraction methods, such as elliptic Fourier transform-based histogram of oriented gradients and local binary pattern histogram Fourier, our proposed localization framework shows robustness when dealing with different complex backgrounds.",
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"content": "Many recent papers that apply advanced machine learning techniques to aerial or satellite imagery focus on a slightly different problem than the one we attempt to address. For example, [2] showed good performance on localizing objects in overhead imagery; yet with an inference speed of @math seconds per @math pixel image chip this approach will not scale to large area inference. Efforts to localize surface to-air-missile sites [1] with satellite imagery and sliding window classifiers work if one only is interested in a single object size of hundreds of meters. Running a sliding window classifier across the image to search for small objects of interest quickly becomes computationally intractable, however, since multiple window sizes will be required for each object size. For perspective, one must evaluate over one million sliding window cutouts if the target is a 10 meter boat in a DigitalGlobe image.",
"role": "assistant"
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science.scitldr_aic | science.scitldr_aic.1557 | [
{
"content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nHierarchical agents have the potential to solve sequential decision making tasks with greater sample efficiency than their non-hierarchical counterparts because hierarchical agents can break down tasks into sets of subtasks that only require short sequences of decisions. \nIn order to realize this potential of faster learning, hierarchical agents need to be able to learn their multiple levels of policies in parallel so these simpler subproblems can be solved simultaneously. \nYet, learning multiple levels of policies in parallel is hard because it is inherently unstable: changes in a policy at one level of the hierarchy may cause changes in the transition and reward functions at higher levels in the hierarchy, making it difficult to jointly learn multiple levels of policies. \nIn this paper, we introduce a new Hierarchical Reinforcement Learning (HRL) framework, Hierarchical Actor-Critic (HAC), that can overcome the instability issues that arise when agents try to jointly learn multiple levels of policies. \nThe main idea behind HAC is to train each level of the hierarchy independently of the lower levels by training each level as if the lower level policies are already optimal. \nWe demonstrate experimentally in both grid world and simulated robotics domains that our approach can significantly accelerate learning relative to other non-hierarchical and hierarchical methods. \nIndeed, our framework is the first to successfully learn 3-level hierarchies in parallel in tasks with continuous state and action spaces.\nHierarchy has the potential to accelerate learning in sequential decision making tasks because hierarchical agents can decompose problems into smaller subproblems.\nIn order to take advantage of these shorter horizon subproblems and realize the potential of HRL, an HRL algorithm must be able to learn the multiple levels within the hierarchy in parallel.\nThat is, at the same time one level in the hierarchy is learning the sequence of subtasks needed to solve a task, the level below should be learning the sequence of shorter time scale actions needed to solve each subtask.\nYet the existing HRL algorithms that are capable of automatically learning hierarchies in continuous domains BID11 BID4 BID1 BID15 BID9 do not efficiently learn the multiple levels within the hierarchy in parallel.\nInstead, these algorithms often resort to learning the hierarchy one level at a time in a bottom-up fashion.Learning multiple levels of policies in parallel is challenging due to non-stationary state transition functions.\nIn nested, multi-level hierarchies, the transition function for any level above the ground level depends on the current policies below that level.\nFor instance, in a 2-level hierarchy, the Figure 1: An ant agent uses a 3-level hierarchy to traverse though rooms to reach its goal, represented by the yellow cube.\nΠ 2 uses as input the current state (joint positions θ and velocitiesθ) and goal state (yellow box) and outputs a subgoal state (green box) for Π 1 to achieve.\nΠ 1 takes in the current state and its goal state (green box) and outputs a subgoal state (purple box) for Π 0 to achieve.\nΠ 0 takes in the current state and goal state (purple box) and outputs a vector of joint torques.high-level policy may output a subgoal state for the low level to achieve, and the state to which this subgoal state leads will depend on the current low-level policy.\nWhen all policies within the hierarchy are trained simultaneously, the transition function at each level above ground level will continue to change as long as the policies below that level continue to be updated.\nIn this setting of non-stationary transition functions, RL will likely struggle to learn the above ground level policies in the hierarchy because in order for RL methods to effectively value actions, the distribution of states to which those actions lead should be stable.\nHowever, learning multiple policies in parallel is still possible because the transition function for each level above ground level will stabilize once all lower level policies have converged to optimal or near optimal policies.\nThus, RL can be used to learn all policies in parallel if each level above ground level had a way to simulate a transition function that uses the optimal versions of lower level policies.\nOur framework is able to simulate a transition function that uses an optimal lower level policy hierarchy and thus can learn multiple levels of policies in parallel.We introduce a new HRL framework, Hierarchical Actor-Critic (HAC), that can significantly accelerate learning by enabling hierarchical agents to jointly learn a hierarchy of policies.\nOur framework is primarily comprised of two components:\n(i) a particular hierarchical architecture and\n(ii) a method for learning the multiple levels of policies in parallel given sparse rewards.The hierarchies produced by HAC have a specific architecture consisting of a set of nested, goalconditioned policies that use the state space as the mechanism for breaking down a task into subtasks.\nThe hierarchy of nested policies works as follows.\nThe highest level policy takes as input the current state and goal state provided by the task and outputs a subgoal state.\nThis state is used as the goal state for the policy at the next level down.\nThe policy at that level takes as input the current state and the goal state provided by the level above and outputs its own subgoal state for the next level below to achieve.\nThis process continues until the lowest level is reached.\nThe lowest level then takes as input the current state and the goal state provided by the level above and outputs a primitive action.\nFurther, each level has a certain number of attempts to achieve its goal state.\nWhen the level either runs out of attempts or achieves its goal state, execution at that level ceases and the level above outputs another subgoal.\nFigure 1 shows how an ant agent trained with HAC uses its 3-level policy hierarchy (π 2 , π 1 , π 0 ) to move through rooms to reach its goal.\nAt the beginning of the episode, the ant's highest level policy, π 2 , takes as input the current state, which in this case is a vector containing the ant's joint positions and velocities ([θ,θ] ), and its goal state, represented by the yellow box.\nπ 2 then outputs a subgoal state, represented by the green box, for π 1 to achieve.\nπ 1 takes as input the current state and its goal state represented by the green box and outputs the subgoal state represented by the purple box.\nFinally, π 0 takes as input the current state and the goal state represented by purple box and outputs a primitive action, which in this case is a vector of joint torques.\nπ 0 has a fixed number of attempts to move to the purple box before π 1 outputs another subgoal state.\nSimilarly, π 1 has a fixed number of subgoal states that it can output to try to move the agent to the green box before π 2 outputs another subgoal.In addition, HAC enables agents to learn multiple policies in parallel using only sparse reward functions as a result of two types of hindsight transitions.\nHindsight action transitions help agents learn multiple levels of policies simultaneously by training each subgoal policy with respect to a transition function that simulates the optimal lower level policy hierarchy.\nHindsight action transitions are implemented by using the subgoal state achieved in hindsight instead of the original subgoal state as the action component in the transition.\nFor instance, when a subgoal level proposes subgoal state A, but the next level policy is unsuccessful and the agent ends in state B after a certain number of attempts, the subgoal level receives a transition in which the state B is the action component, not state A. The key outcome is that now the action and next state components in the transition are the same, as if the optimal lower level policy hierarchy had been used to achieve subgoal state B.Training with respect to a transition function that uses the optimal lower level policy hierarchy is critical to learning multiple policies in parallel, because the subgoal policies can be learned independently of the changing lower level policies.\nWith hindsight action transitions, a subgoal level can focus on learning the sequences of subgoal states that can reach a goal state, while the lower level policies focus on learning the sequences of actions to achieve those subgoal states.\nThe second type of hindsight transition, hindsight goal transitions, helps each level learn a goal-conditioned policy in sparse reward tasks by extending the idea of Hindsight Experience Replay BID0 ) to the hierarchical setting.\nIn these transitions, one of the states achieved in hindsight is used as the goal state in the transition instead of the original goal state.We evaluated our approach on both grid world tasks and more complex simulated robotics environments.\nFor each task, we evaluated agents with 1, 2, and 3 levels of hierarchy.\nIn all tasks, agents using multiple levels of hierarchy substantially outperformed agents that learned a single policy.\nFurther, in all tasks, agents using 3 levels of hierarchy outperformed agents using 2 levels of hierarchy.\nIndeed, our framework is the first to show empirically that it can jointly learn 3-level hierarchical policies in tasks with continuous state and action spaces.\nIn addition, our approach outperformed another leading HRL algorithm, HIRO BID9 , on three simulated robotics tasks.\nHierarchy has the potential to accelerate learning but in order to realize this potential, hierarchical agents need to be able to learn their multiple levels of policies in parallel.\nWe present a new HRL framework that can efficiently learn multiple levels of policies simultaneously.\nHAC can overcome the instability issues that arise when agents try to learn to make decisions at multiple time scales because the framework trains each level of the hierarchy as if the lower levels are already optimal.\nOur results in several discrete and continuous domains, which include the first 3-level agents in tasks with continuous state and action spaces, confirm that HAC can significantly improve sample efficiency.ONR through N000141410047, Amazon through an ARA to Platt, Google through a FRA to Platt, and DARPA.\n• Key agent parameters: number of levels in hierarchy k, maximum subgoal horizon H, and subgoal testing frequency λ.\nOutput:• k trained actor and critic functions π 0 , ..., DISPLAYFORM0 Sample initial state and task goal DISPLAYFORM1 Begin training Update all actor and critic networks end for function TRAIN-LEVEL(i :: level, s :: state, g :: goal) s i ← s, g i ← g Set current state and goal for level i for H attempts or until g n , i ≤ n < k achieved do DISPLAYFORM2 DISPLAYFORM3 Replace original action with action executed in hindsight end ifEvaluate executed action on current goal and hindsight goals DISPLAYFORM4 Replay Buf f er i ← Perform HER using HER Storage i transitions return s iOutput current state end function",
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"content": "We introduce the first Hierarchical RL approach to successfully learn 3-level hierarchies in parallel in tasks with continuous state and action spaces.",
"role": "assistant"
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.2787 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: RGB-D-Based Object Recognition Using Multimodal Convolutional Neural Networks: A Survey \nChapter Title: A. DATASETS FOR RGB-D OBJECT RECOGNITION \n1. Abstract of Cited Paper (BIB001): Categorization of objects solely based on shape and appearance is still a largely unresolved issue. With the advent of new sensor technologies, such as consumer-level range sensors, new possibilities for shape processing have become available for a range of new application domains. In the first part of this paper, we introduce a novel, large dataset containing 18 categories of objects found in typical household and office environments—we envision this dataset to be useful in many applications ranging from robotics to computer vision. The second part of the paper presents computational experiments on object categorization with classifiers exploiting both two-dimensional and three-dimensional information. We evaluate categorization performance for both modalities in separate and combined representations and demonstrate the advantages of using range data for object and shape processing skills. \n2. Abstract of Cited Paper (BIB002): We address the problems of contour detection, bottom-up grouping and semantic segmentation using RGB-D data. We focus on the challenging setting of cluttered indoor scenes, and evaluate our approach on the recently introduced NYU-Depth V2 (NYUD2) dataset [27]. We propose algorithms for object boundary detection and hierarchical segmentation that generalize the gPb-ucm approach of [2] by making effective use of depth information. We show that our system can label each contour with its type (depth, normal or albedo). We also propose a generic method for long-range amodal completion of surfaces and show its effectiveness in grouping. We then turn to the problem of semantic segmentation and propose a simple approach that classifies super pixels into the 40 dominant object categories in NYUD2. We use both generic and class-specific features to encode the appearance and geometry of objects. We also show how our approach can be used for scene classification, and how this contextual information in turn improves object recognition. In all of these tasks, we report significant improvements over the state-of-the-art. \n3. Abstract of Cited Paper (BIB003): With the rapid development of range image acquisition techniques, 3D computer vision has became a popular research area. It has numerous applications in various domains including robotics, biometrics, remote sensing, entertainment, civil construction, and medical treatment. Recently, a large number of algorithms have been proposed to address specific problems in the area of 3D computer vision. Meanwhile, several benchmark datasets have also been released to stimulate the research in this area. The availability of benchmark datasets plays an significant role in the process of technological progress. In this paper, we first introduce several major 3D acquisition techniques. We also present an overview on various popular topics in 3D computer vision including 3D object modeling, 3D model retrieval, 3D object recognition, 3D face recognition, RGB-D vision, and 3D remote sensing. Moreover, we present a contemporary summary of the existing benchmark datasets in 3D computer vision. This paper can therefore, serve as a handbook for those who are working in the related areas. \n4. Abstract of Cited Paper (BIB004): In this paper, we address the problems of contour detection, bottom-up grouping, object detection and semantic segmentation on RGB-D data. We focus on the challenging setting of cluttered indoor scenes, and evaluate our approach on the recently introduced NYU-Depth V2 (NYUD2) dataset (Silberman et al., ECCV, 2012). We propose algorithms for object boundary detection and hierarchical segmentation that generalize the $$gPb-ucm$$gPb-ucm approach of Arbelaez et al. (TPAMI, 2011) by making effective use of depth information. We show that our system can label each contour with its type (depth, normal or albedo). We also propose a generic method for long-range amodal completion of surfaces and show its effectiveness in grouping. We train RGB-D object detectors by analyzing and computing histogram of oriented gradients on the depth image and using them with deformable part models (Felzenszwalb et al., TPAMI, 2010). We observe that this simple strategy for training object detectors significantly outperforms more complicated models in the literature. We then turn to the problem of semantic segmentation for which we propose an approach that classifies superpixels into the dominant object categories in the NYUD2 dataset. We design generic and class-specific features to encode the appearance and geometry of objects. We also show that additional features computed from RGB-D object detectors and scene classifiers further improves semantic segmentation accuracy. In all of these tasks, we report significant improvements over the state-of-the-art. \n5. Abstract of Cited Paper (BIB005): Object recognition has many applications in human-machine interaction and multimedia retrieval. However, due to large intra-class variability and inter-class similarity, accurate recognition relying only on RGB data is still a big challenge. Recently, with the emergence of inexpensive RGB-D devices, this challenge can be better addressed by leveraging additional depth information. A very special yet important case of object recognition is hand-held object recognition, as manipulating objects with hands is common and intuitive in human-human and human-machine interactions. In this paper, we study this problem and introduce an effective framework to address it. This framework first detects and segments the hand-held object by exploiting skeleton information combined with depth information. In the object recognition stage, this work exploits heterogeneous features extracted from different modalities and fuses them to improve the recognition accuracy. In particular, we incorporate handcrafted and deep learned features and study several multi-step fusion variants. Experimental evaluations validate the effectiveness of the proposed method. \n6. Abstract of Cited Paper (BIB006): Hand-held objects play an important role in human-human and human-machine interaction. It can be used as a reference for understanding user intentions or user requirements. In this technical demonstration, we introduce an object recognition system called Hand-Object Sense that can automatically recognize the object held by user. This system first detects and segments the hand-held object by exploiting skeleton information combined with depth information. Second, in the object recognition stage, this system exploits features computed in different ways and fuses them to improve the recognition accuracy. Our system can recognize objects in real-time and have a good tolerance to angle and scale transformation. Furthermore, it has a good generalization capability for unknown objects. \n7. Abstract of Cited Paper (BIB007): Object recognition systems have shown great progress over recent years. However, creating object representations that are robust to changes in viewpoint while capturing local visual details continues to be a challenge. In particular, recent convolutional architectures employ spatial pooling to achieve scale and shift invariances, but they are still sensitive to out-of-plane rotations. In this paper, we formulate a probabilistic framework for analyzing the performance of pooling. This framework suggests two directions for improvement. First, we apply multiple scales of filters coupled with different pooling granularities, and second we make use of color as an additional pooling domain, thereby reducing the sensitivity to spatial deformations. We evaluate our algorithm on the object instance recognition task using two independent publicly available RGB-D datasets, and demonstrate significant improvements over the current state-of-the-art. In addition, we present a new dataset for industrial objects to further validate the effectiveness of our approach versus other state-of-the-art approaches for object recognition using RGB-D data. \n8. Abstract of Cited Paper (BIB008): RGB-D data has turned out to be a very useful representation of an indoor scene for solving fundamental computer vision problems. It takes the advantages of the color image that provides appearance information of an object and also the depth image that is immune to the variations in color, illumination, rotation angle and scale. With the invention of the low-cost Microsoft Kinect sensor, which was initially used for gaming and later became a popular device for computer vision, high quality RGB-D data can be acquired easily. In recent years, more and more RGB-D image/video datasets dedicated to various applications have become available, which are of great importance to benchmark the state-of-the-art. In this paper, we systematically survey popular RGB-D datasets for different applications including object recognition, scene classification, hand gesture recognition, 3D-simultaneous localization and mapping, and pose estimation. We provide the insights into the characteristics of each important dataset, and compare the popularity and the difficulty of those datasets. Overall, the main goal of this survey is to give a comprehensive description about the available RGB-D datasets and thus to guide researchers in the selection of suitable datasets for evaluating their algorithms. \n9. Abstract of Cited Paper (BIB009): Since the launch of the Microsoft Kinect, scores of RGBD datasets have been released. These have propelled advances in areas from reconstruction to gesture recognition. In this paper we explore the field, reviewing datasets across eight categories: semantics, object pose estimation, camera tracking, scene reconstruction, object tracking, human actions, faces and identification. By extracting relevant information in each category we help researchers to find appropriate data for their needs, and we consider which datasets have succeeded in driving computer vision forward and why. ::: Finally, we examine the future of RGBD datasets. We identify key areas which are currently underexplored, and suggest that future directions may include synthetic data and dense reconstructions of static and dynamic scenes. \n10. Abstract of Cited Paper (BIB010): Densely cluttered scenes are composed of multiple objects which are in close contact and heavily occlude each other. Few existing 3D object recognition systems are capable of accurately predicting object poses in such scenarios. This is mainly due to the presence of objects with textureless surfaces, similar appearances and the difficulty of object instance segmentation. In this paper, we present a hierarchical semantic segmentation algorithm which partitions a densely cluttered scene into different object regions. A RANSAC-based registration method is subsequently applied to estimate 6-DoF object poses within each object class. Part of this algorithm includes a generalized pooling scheme used to construct robust and discriminative object representations from a convolutional architecture with multiple pooling domains. We also provide a new RGB-D dataset which serves as a benchmark for object pose estimation in densely cluttered scenes. This dataset contains five thousand scene frames and over twenty thousand labeled poses of ten common hand tools. We show that our method demonstrates improved performance of pose estimation on this new dataset compared with other state-of-the-art methods. \n11. Abstract of Cited Paper (BIB011): The ability to classify objects is fundamental for robots. Besides knowledge about their visual appearance, captured by the RGB channel, robots heavily need also depth information to make sense of the world. While the use of deep networks on RGB robot images has benefited from the plethora of results obtained on databases like ImageNet, using convnets on depth images requires mapping them into three dimensional channels. This transfer learning procedure makes them processable by pre-trained deep architectures. Current mappings are based on heuristic assumptions over preprocessing steps and on what depth properties should be most preserved, resulting often in cumbersome data visualizations, and in sub-optimal performance in terms of generality and recognition results. Here we take an alternative route and we attempt instead to learn an optimal colorization mapping for any given pre-trained architecture, using as training data a reference RGB-D database. We propose a deep network architecture, exploiting the residual paradigm, that learns how to map depth data to three channel images. A qualitative analysis of the images obtained with this approach clearly indicates that learning the optimal mapping preserves the richness of depth information better than current hand-crafted approaches. Experiments on the Washington, JHUIT-50 and BigBIRD public benchmark databases, using CaffeNet, VGG16, GoogleNet, and ResNet50 clearly showcase the power of our approach, with gains in performance of up to 16% compared to state of the art competitors on the depth channel only, leading to top performances when dealing with RGB-D data\n\nReview Chapter:",
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"content": "A number of RGB-D benchmark datasets have been collected and made publicly available BIB009 , BIB010 , BIB004 . Firman BIB010 discovered a considerable quantity of RGB-D datasets available for researchers to use. Guo et al. BIB004 presented a contemporary summary of the existing benchmark datasets in 3D computer vision. Cai et al. BIB009 systematically surveyed popular RGB-D datasets for different applications including object recognition, scene classification, hand gesture recognition, 3D-simultaneous localization, and pose estimation. Although many RGB-D object datasets exist in the literature, the datasets appropriate for object recognition evaluation are still limited. There are many reasons behind the situation. Some RGB-D datasets, e.g. SUN RGB-D , NYU V1 BIB001 , NYU V2 BIB003 , Cornell RGB-D were built for scene recognition tasks. Some datasets are not public accessible, for example, a hand-held RGB-D object dataset (HOD) by Lv et al. BIB006 - BIB007 . BigBIRD dataset is one of the biggest RGB-D object datasets we considered which contains 121 object instances and 75000 images. Unfortunately, it is hard to evaluate the depth features with this dataset because many objects are extremely similar, and many are boxes, which are indistinguishable without texture information BIB012 . To the best of our knowledge, only Li et al. BIB008 evaluated the object recognition performance on this dataset. Therefore, we review three public and most used RGB-D datasets for object recognition evaluation, namely, Washington RGB-D object dataset , 2D/3D object dataset BIB002 and JHUIT-50 object dataset BIB011 . (1) Washington RGB-D object dataset 1 Washington RGB-D object dataset is the most widely used dataset for RGB-D object recognition which was collected by University of Washington in 2011. This dataset contained color and depth information of 300 objects from 51 categories of household objects which were organized in a hierarchical structure manner. Images were captured with a Kinect style camera at a resolution of 640 × 480. Each object was recorded from 3 viewing heights (30 • , 45 • and 60 • above the horizon). Each video sequence was recorded at 20 Hz and contained around 250 frames, giving 150 views per object and nearly 210,000 RGB-D images. Each sample consisted of a pair of a portable network graphics (PNG) file and the corresponding point cloud data (PCD) file. Meanwhile, the objects provided in the dataset had been previously segmented from their background. Fig. 26 illustrates some selected objects from this dataset as well as the examples of RGB-D images. (2) 2D/3D object dataset BIB005 The 2D/3D object dataset was collected by Browatzki et al. BIB002 Cybernetics, Germany in 2011. It contained 154 objects with 14 categories that were likely to be encountered by a robot operating in a household environment. Each object was put on a step-motor-controlled turntable and it was recorded every 10 • around the vertical axis, yielding 36 views per object by a PMD TM CamCube2.0 time-offlight camera. In total, the dataset contained 5,544 views with every view consisting of two RGB images (1388 × 1038) and depth images (204 × 204) . The 2D/3D dataset is very challenging for object recognition because of the huge variance of views. Fig. 27 shows some RGB images and the corresponding depth images from the 2D/3D object dataset. (3) JHUIT-50 object dataset 3 JHUIT-50 BIB011 was collected by Johns Hopkins University. It contained 14,698 RGB-D images capturing 50 common workshop tools, such as clamps and screw drivers, as shown in Fig. 28 . The PrimeSense Carmine 1.08 depth sensor was used to capture the depth images. All the objects were segmented from the background. Training sequences were captured under three fixed viewing angles (30 • , 45 • and 60 • ) and testing sequences were collected under random view points of the camera. JHUIT-50 is a challenging dataset that focuses on the problem of fine-grained classification.",
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.13483 | [
{
"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment\nContent:\nAbstract:\nRNA interference( RNAi) related pathways are essential for germline development and fertility in metazoa and can contribute to inter- and trans-generational inheritance. In the nematode Caenorhabditis elegans, environmental double-stranded RNA provided by feeding can lead to heritable changes in phenotype and gene expression. Notably, transmission efficiency differs between the male and female germline, yet the underlying mechanisms remain elusive. Here we use high-throughput sequencing of dissected gonads to quantify sex-specific endogenous piRNAs, miRNAs and siRNAs in the C. elegans germline and the somatic gonad. We identify genes with exceptionally high levels of secondary 22G RNAs that are associated with low mRNA expression, a signature compatible with silencing. We further demonstrate that contrary to the hermaphrodite germline, the male germline, but not male soma, is resistant to environmental RNAi triggers provided by feeding, in line with previous work. This sex-difference in silencing efficacy is associated with lower levels of gonadal RNAi amplification products. Moreover, this tissue- and sex-specific RNAi resistance is regulated by the germline, since mutant males with a feminized germline are RNAi sensitive. This study provides important sex- and tissue-specific expression data of miRNA, piRNA and siRNA as well as mechanistic insights into sex-differences of gene regulation in response to environmental cues.\nIntroduction:\nThe environment can induce changes in phenotype and gene expression that persist across multiple generations[reviewed in 1]. Such intra- and trans-generational inheritance can pass both through the male and female germlines. Several studies have revealed sex-differences in transmission efficiency of heritable phenotypic changes, yet the underlying molecular mechanisms remain unknown[2–6]. In the nematode Caenorhabditis elegans, environmental cues such as starvation, viral RNA or environmental RNA can trigger heritable phenotypic changes that are transmitted via small RNA[7–9]. The mechanisms of trans-generational inheritance are best understood from studies of environmental RNA[5–7, 10–12]. In C. elegans phenotypic changes induced by environmental RNAi require a double stranded RNA( dsRNA) entering the animal via a dedicated dsRNA transporter[13, 14]. Thereafter, exogenous dsRNAs are processed by the conserved nuclease Dicer into ~22 nucleotide( nt) primary small interfering RNAs( siRNA) and incorporated into Argonaute proteins to form the RNA-induced silencing complex( RISC)[15, 16]. This protein-RNA complex binds complementary mRNA sequences and initiates the production of secondary siRNA by RNA-dependent RNA polymerases( RdRP)( Fig 1A)[17–19]. Such secondary siRNAs are 22 nt with a 5’ guanine, thus named 22G RNAs[20]. Depending on the Argonaute, primary and secondary siRNA may trigger systemic gene silencing of complementary sequences through destabilization of mRNA or translational repression( Fig 1A)[21–23]. Once established, phenotypic changes induced by exogenous dsRNA can be transmitted over multiple generations[10, 12, 23, 24]. On top of their role in trans-generational inheritance, some endogenous small RNA types–such as miRNA, piRNA and siRNA–are essential for development and fertility in both sexes of C. elegans. Albeit distinguishable, those small RNA types share some biogenesis and silencing mechanisms( Fig 1A). One major class of small RNA, miRNAs, regulates translation of mRNA targets via partially complementary base-pairing. Many miRNAs are expressed in a tissue- and sex-specific specific manner reflecting functional sex-differences[25–28]. For instance, miR-35 family activity in the female germline is important for progeny viability and fecundity[29–31]. Furthermore, distinct Argonaute proteins associate with additional types of endogenous siRNAs in the male and female germline, suggesting functional sex-differences[20, 32–36]. Importantly, germline-expressed PIWI-bound small RNA( piRNA) populations target mRNA and thus maintain genome stability in hermaphrodites and males[37–40]. Such piRNAs come in two flavours: type I piRNA are expressed from two genomic loci and have a conserved upstream motif, whereas type II piRNAs lack an apparent upstream motif and are dispersed throughout the genome[41]. In C. elegans, another group of endogenous small RNAs are expressed in the gonads of both sexes. Such siRNAs can be distinguished by length and are either( i) primary products of the RNAse III enzyme Dicer/DCR-1( e. g., 26G RNA) or( ii) secondary products of RNA-dependent RNA polymerases( e. g., 22G RNA)( Fig 1A). Both types of endogenous siRNAs modulate gene expression and are essential for fertility, but very little is known about potential sex-differences in their gonadal expression[32, 34, 35]. The reproductive tissue of C. elegans consists of the germline surrounded by the somatic gonad, and development of both tissues is coordinated by multiple mechanisms[42]. Notably, miRNA activity in the somatic gonad is essential for gonad development and germline proliferation, and thus fertility[43, 44]. However, a comprehensive tissue- and sex-specific expression study of gonadal siRNA is lacking. Males and females also present germline sex-specific differences in response to environmental cues. First, RNAi in hermaphrodite gonads induces very strong knockdown phenotypes[2, 45–47], in contrast to anecdotal evidence for mostly no detectable RNAi phenotypes in C. elegans sperm[6, 45, 48, 49]. Second, siRNA induced trans-generational silencing is often more efficient through the female than the male germline[2–6]. The underlying mechanisms causing these sex-differences are not well understood. Here we provide a comprehensive study of both the sex-determined small RNAome and environmentally-induced siRNA silencing. First, we quantify sex-biased expression of miRNA, piRNA and siRNA in isolated male and female gonads. We further ascribe small RNA sex-differences to the germline or somatic gonad by comparing gonads of each sex to mutant male gonads( fog-3) with a female germline. Quantitative analysis of gonadal expression of mRNA and 22G RNA identified genes with low mRNA expression and high 22G RNA levels, a signature compatible with silencing. Moreover, there was lower mRNA expression of WAGO than non-WAGO targets, further supporting the notion of endogenous silencing. Second, using environmental RNAi targeting a GFP-sensor we show that germline RNAi silencing efficacy is determined by germline sex, in line with previous work[6, 45, 48, 49]. This tissue-specific sex-difference in silencing efficacy was associated with lower levels of RNAi amplification products in male than female gonads. These data provide a mechanistic basis for sex-differences in germline RNAi efficacy with implications for trans-generational inheritance.\nDiscussion:\nmiRNA regulation, notably via the conserved miR-35 family is crucial for embryonic viability, proliferation of the germline and is implicated in sex-determination[29, 30, 43, 74]. In addition, miRNAs expressed in the C. elegans somatic gonad maintain germline proliferation and differentiation[43]. We identified female germline-biased expression of the miR35-41 cluster in isolated gonads, which is in line with studies conducted on whole animals[29, 31, 75]. The transgene reporter for miR-246 expression, which typically escapes germline expression, was previously observed in hermaphrodite gonadal sheath cells[25]. Here we establish sex-biased expression of endogenous miR-246 specifically in the hermaphrodite somatic gonad as opposed to the germline or the male gonad. Since miR-246 expression positively correlates with lifespan[76, 77], it will be interesting to identify miR-246 targets in the somatic gonad or germline. Thus, small RNA sequencing of isolated gonads and comparison of expression differences between wild-type and sex-transformed mutant gonads captures known sex-differences in expression and in addition provides more detailed, tissue-specific information. Our data provide the first tissue-specific analysis of miRNA expression in males. Of the 46 male-biased miRNAs with searchable names in miRBase detected in whole animals[26], 13 miRNAs showed male-biased gonad expression, underlining the importance of a tissue-specific approach. Thus, sex-biased miRNA expression occurs in both soma and gonad. Some miRNAs with male-biased gonad expression were previously not detected as sex-biased[26] and could have been masked by somatic expression in both sexes. In contrast to miRNAs, the piRNA pathway acts exclusively in the germline. Since the germline makes up about half of the adult C. elegans cells[78], whole worm sequencing is a good proxy for germline-restricted piRNA expression. Our analysis of sex-biased piRNA expression thus complements previous studies on whole animals that reported distinct piRNA expression in hermaphrodites and males[26, 39]. While the cloning method applied here causes relatively low( 5’-monophasphate) piRNA detection level compared to a previous study[39], it also causes preferential cloning of 5’-triphosphate RNA species and thus high coverage of endogenous siRNA. The tissue-specific analysis of endogenous 22G RNA and mRNA identified transcripts that are potentially regulated by RNAi. Importantly, hermaphrodites and males share common as well as distinct siRNA targeted gene sets in gonadal tissue. Most gonadal sex-differences in siRNA expression stem from the germline, which represents the vast majority of the gonadal tissue. Further comparison of gonadal siRNA and corresponding mRNA uncovers uncoupling of siRNA and mRNA levels, indicative of RNAi silencing. It will be interesting to investigate this regulation in the future. Our study provides novel insights into how the sex of an animal influences RNA-induced environmental changes in the phenotype. In particular, using environmental dsRNA triggers, we demonstrated that RNAi resistance affects exclusively the male germline. Sequencing primary and secondary siRNA with unique SNPs in isolated gonads from males and hermaphrodites allowed us to quantitatively compare steady-state levels. We detected similar levels of primary siRNAs in gonads of both sexes, suggesting functional transport of RNAi trigger from the environment to the soma and processing of primary siRNA in the male germline. In contrast, we discovered low levels of secondary siRNA amplification products in males compared to hermaphrodites. Thus, RNAi resistance in the male germline affects downstream processes that likely impact sex-differences in secondary siRNA processing or siRNA stability. It follows that RNAi is generally not suitable for functional studies of the C. elegans male germline if provided during one generation only. Since RNAi silencing is efficient in sperm of hermaphrodites, such animals are more suitable for reverse genetics targeting the germline. What determines the sex-differences of gene regulation in response to environmental cues? It is conceivable that sex-differences in gonadal mRNA expression of RNAi regulators impact RNAi efficiency. In hermaphrodite gonads, RNAi genes having diverse functions–such as transport, processing or negative regulators–were expressed more highly than in male gonads. Notably, the endoribonuclease RDE-8, which is essential for amplification of siRNA products and silencing, was expressed predominantly in hermaphrodite gonads[70]. Thus, RNAi resistance in male germlines may possibly be linked to reduced RDE-8 activity. Alternatively, competition between endogenous and exogenous RNAi pathways may cause male-specific germline RNAi resistance. Intriguingly, male-specific gonad expression affected most prominently four Argonautes. In addition to ALG-3/-4 that are implicated in spermatogenesis[34], we detected male-specific expression of WAGO-10 and WAGO-5. Although the molecular functions of WAGO-10 and WAGO-5 remain to be determined, their sex-specific expression suggests a role in male small RNA regulation. Also, sex-differences in localization may affect RNAi efficacy. Notably CID-1, a poly( U)-polymerase modulating germline RNAi efficacy shows distinct subcellular localization in male and female germlines–perinuclear and chromosomal, respectively—that may affect function[79]. Intriguingly, in addition, multiple sex-differences are well described for the Argonaute CSR-1 that targets endogenous germline transcripts via secondary 22G RNAs[20, 36]. First, males and hermaphrodites express distinct CSR-1 isoforms[36, 78]. Second, csr-1 mutant hermaphrodites are mostly sterile, while csr-1 mutant males show only modestly reduced fertility over multiple generations[35, 56]. Thus, sex-differences in CSR-1 function may contribute to the observed sex-difference in RNAi sensitivity, in line with CSR-1 function in germline RNAi[80]. Overall, multiple mechanisms may contribute to sex-specific gene regulation and untangling the individual contributions will provide exiting answers on male and female biology. In conclusion, this study provides the tissue-specific small RNAome of C. elegans hermaphrodite and male gonads and identifies quantitative sex-differences in miRNA, piRNA and siRNA expression. Furthermore, we demonstrate that the male germline is resistant to RNAi triggers taken up from the environment and accumulates lower levels of RNAi amplification products. We thus provide mechanistic insights into sex-differences of gene regulation in response to environmental cues that may play a role in transgenerational inheritance.",
"role": "user"
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{
"content": "Environmental factors such as heat or pathogens influence living organisms , and in some cases these experiences can be passed on to the next generation . One such environmental factor is double stranded RNA that can be taken up by some animals and induce changes in gene expression via small RNA mediated silencing . Here , we use the roundworm Caenorhabditis elegans to show that the female and male germline react differently to the presence of such an environmental factor that may affect transmission to following generations . Sequencing of gonadal small RNA suggests that the underlying sex-differences affect downstream processing but not uptake . Furthermore , we describe the naturally occurring small RNA populations of female and male gonads and use genetic mutants to assign small RNAs to the two tissues of the gonad , namely the somatic gonad or the germline . These sex-and tissue-specific small RNA expression data provide an important resource for future research . In addition , this work reveals mechanistic insights into sex-differences in response to environmental cues .",
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science.chemdner_ner | science.chemdner_ner.1731 | [
{
"content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nImpairment of regulatory T cell function in autoimmune thyroid disease. Background: Autoimmune thyroid disease (AITD) pathogenesis may result from a loss of immune tolerance to thyroid antigens. Regulatory T cells (Tregs) control immune responses, prevent excessive inflammation, and may be dysfunctional in AITD. We investigated the role of Tregs in Hashimoto's thyroiditis (HT) and Graves' disease (GD). Our goal was to identify differences in CD4+CD25hi Treg function or number in patients with GD and HT, compared to healthy controls (HC). Methods: Treg number was assessed by flow cytometric analysis in samples from twenty AITD patients (7 GD, 13 HT), 9 HC, and 7 individuals with Down syndrome (DS), a genetic disorder associated with multiple autoimmune disorders including AITD. Treg function was assessed by the inhibition of proliferation (radioactive thymidine incorporation into DNA) of blood-derived T effector cells (Teff) by Tregs in a co-culture. Various methods of stimulation were contrasted. Cytokine levels were determined in conditioned media from the co-cultures. Results: No differences were found in the frequency of Tregs as a percentage of CD4+ cells between AITD and HC. AITD Tregs were less capable of inhibiting the proliferation of Teff cells when compared to HC, however, the impairment was dependent on the type of stimulation used. DS patients without AITD exhibited normal Treg function. We observed few differences in cytokine production between HC and AITD patients. Conclusions: Tregs from AITD patients are partly dysfunctional, possibly explaining their autoimmunity. Future work will elucidate the diagnostic potential and pathophysiology of Tregs in AITD.",
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"content": "{\"Chemical\": []}",
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science.healthver_entailment | science.healthver_entailment.1411 | [
{
"content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Favipiravir at high doses has potent antiviral activity in SARS-CoV-2 infected hamsters, whereas hydroxychloroquine lacks activity\n\nResearch Abstract:\nThe outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has posed the world at a pandemic risk.\nCoronavirus-19 disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which causes pneumonia, requires intensive care unit hospitalization in about 10% of cases and can lead to a fatal outcome.\nSeveral efforts are currently made to find a treatment for COVID-19 patients.\nSo far, several anti-viral and immunosuppressive or immunomodulating drugs have demonstrated some efficacy on COVID-19 both in vitro and in animal models as well as in cases series.\nIn COVID-19 patients a pro-inflammatory status with high levels of interleukin (IL)-1B, IL-1 receptor (R)A and tumor necrosis factor (TNF)-α has been demonstrated.\nMoreover, high levels of IL-6 and TNF-α have been observed in patients requiring intensive-care-unit hospitalization.\nThis provided rationale for the use of anti-rheumatic drugs as potential treatments for this severe viral infection.\nOther agents, such as hydroxychloroquine and chloroquine might have a direct anti-viral effect.\nThe anti-viral aspect of immunosuppressants towards a variety of viruses has been known since long time and it is herein discussed in the view of searching for a potential treatment for SARS-CoV-2 infection.",
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"content": "{\"verdict\": \"NEI\", \"evidence\": []}",
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science.healthver_entailment | science.healthver_entailment.4083 | [
{
"content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: alcohol does not protect against infection or illness relating to COVID-19.\n\nResearch Abstract:\nWhile it remains much too early to determine precisely how alcohol use might affect risk for or progression of COVID‐19, any efforts to connect the dots from past alcohol research would suggest it wise for nondrinkers and low‐risk drinkers to maintain that status during this public health crisis.\nIt's already known that disaster can result in increased alcohol consumption based on the work of Deborah Hasin, Ph.D., after 9/11 (see “Alcohol and isolation: Experts comment on drinking behavior during COVID‐19,” ADAW March 30; https://onlinelibrary.wiley.com/doi/10.1002/adaw.32670).",
"role": "user"
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{
"content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"It's already known that disaster can result in increased alcohol consumption based on the work of Deborah Hasin, Ph.D., after 9/11 (see \\u201cAlcohol and isolation: Experts comment on drinking behavior during COVID\\u201019,\\u201d ADAW March 30; https://onlinelibrary.wiley.com/doi/10.1002/adaw.32670).\"]}",
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.2899 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: I want to train a supervised model for musicological research from music data.\n\nKeywords: musicological research\n\nDataset Information:\nGYAFC: Grammarly’s Yahoo Answers Formality Corpus (GYAFC) is the largest dataset for any style containing a total of 110K informal / formal sentence pairs. Yahoo Answers is a question answering forum, contains a large number of informal sentences and allows redistribution of data.\nConvAI2: The ConvAI2 NeurIPS competition aimed at finding approaches to creating high-quality dialogue agents capable of meaningful open domain conversation. The ConvAI2 dataset for training models is based on the PERSONA-CHAT dataset.\nDBpedia: DBpedia (from \"DB\" for \"database\") is a project aiming to extract structured content from the information created in the Wikipedia project. DBpedia allows users to semantically query relationships and properties of Wikipedia resources, including links to other related datasets.\nMusic21: Music21 is an untrimmed video dataset crawled by keyword query from Youtube. It contains music performances belonging to 21 categories.\n\nAvailable Datasets: A: GYAFC B: ConvAI2 C: DBpedia D: Music21",
"role": "user"
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"content": "DBpedia",
"role": "assistant"
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.31135 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nObservation of Surface Plasmon Coupled Emission using Thin Platinum Films\n\nContent Extracts:\n\n<p>During the past several years there has been a growing interest in the interactions of fluorophores with metallic surfaces and particles [1–3]. Several laboratories have reported on favorable spectral changes such as increase intensity, photostability and [4–8] increased distances for fluorescence resonance energy transfer [9–10]. Excited state fluorophores can also resonantly interact with smooth thin metal attached to glass prisms that can lead to the generation of surface plasmons and the highly directional emission of the spectral properties of the excited fluorophores on the glass side [11–14]. This phenomenon is called surface plasmon-coupled emission (SPCE). Most of the previous reports showed SPCE and metal-enhanced fluorescence (MEF) with metallic silver surfaces and particles. It was also found that both SPCE and MEF could occur with both gold and aluminum, thereby, increasing the versatility of SPCE and MEF. Gold was found to be more useful at longer wavelengths [15–18] and aluminum found to be useful in the near-UV [19–20]</p><p>Because of our interest in SPCE and MEF we tested different metals such as silver, gold and aluminum. During the past several years of our research on metal-fluorophore interactions we found that SPCE generally occurs over longer distances than MEF [21–24]. For fluorophores near a smooth metal surface there appears to be three possible processes. The fluorophore can be quenched, can couple to surface plasmons or can emit into free-space. If the fluorophore is close to the surface (< 10 nm) there is a high rate for radiationless deactivation and the emission appears to be quenched. At distances between 10 to 100 nm the dominant decay rate is expected to be due to coupling to the surface plasmons. This is important for the applications of SPCE because coupling will occur over a significant volume in the sample allowing detection of lower overall analyte concentrations. At longer distances (> 100 nm) the reflected field interferes constructively or destructively, resulting in the oscillatory behavior reported for fluorophores in front of mirrors [25].</p><p>In the present report we show that SPCE can occur with thin platinum films at green and red wavelengths. The most convincing demonstration of SPCE can be obtained with reverse Kretchmann (RK) excitation where the incident light cannot induce surface plasmons. In RK configuration, the fluorophores are excited from the air side of the sample and the emission is observed on the distal glass/quartz side of the substrate. In this case, the incident light would not create surface plasmons and there is no evanescent field due to the incident light. An excited fluorophore near the metal film would not know how it was excited; that is, the emission should be the same whether the fluorophore is excited by evanescent field (Kretchmann configuration) or from a light source not coupled to the surface plasmon (RK configuration). In the RK geometry, the fluorophores are excited uniformly across the sample. However, only those fluorophores within a fractional wavelength distant from the metal will couple to the surface and result in SPCE. This allows the use of SPCE without the surface plasmon excitation, which can simplify the devices based on this phenomenon. Since fluorophores distant from the metal will not couple, autofluorescence from molecules not localized by the surface chemistry should be suppressed in the SPCE signal. We believe there will soon be a variety of metallic nanostructures for use in genomics, proteomics and medical testing. Our observation suggests that platinum nanostructures can be part of these novel bioanalysis surfaces.</p>\n\nExperimental Section\n<p>40 nm of platinum were deposited on quartz slides using an AJA sputtering system under high vacuum. The metal deposition step was followed by the deposition of 5 nm of silica via evaporation without breaking vacuum. This step served to protect the metal surface and also it adds a distance of 5 nm from the metal surface. The Pt-coated slides were spin coated with a solution of ~ 50 μM fluorescein or rhodamine B in 0.5% PVA. The dye/PVA film is estimated to be approximately 15 nm in thickness. Figure 1 presents a schematic representation of the sample configuration.</p><p>The metal coated slides containing the samples were attached to a hemicylindrical prism made from quartz and the refractive index was matched using spectrophotometric grade glycerol between the back of the quartz slide (uncoated side) and the prism. This unit was then placed on a precise 360° rotatory stage. The rotatory stage allowed the collection of light at all angles around the sample chamber (shown in Figure 1). The excitation source used is a diode pumped solid state continuous-wave laser lasing at 532 nm. An Ocean Optics low OH 600 μm diameter optical fiber with NA of 0.22 (Dunedin, FL) used for collecting the SPCE and free space signals was mounted on a holder that was screwed on to the base of the rotatory stage. SPCE and free space spectra were collected using a model SD 2000 Ocean Optics spectrometer connected to the optical fiber. The spectra were collected with an integration time of 1 second. Unpolarized, p and s-polarized signal information were collected for the SPCE signal (from 0 – 90° and 270 – 360° with respect to the front of the prism) and the Free-Space (FS) signal (from 90 – 270° with respect to the front of the prism). Figure 1 presents a geometrical scheme for the measurement of angle-dependent emission. All data processing was performed using OriginPro 7. Time-resolved intensity decays were recorded using a PicoQuant Fluotime 100 time-correlated single-photon counting fluorescence lifetime spectrometer. The excitation source was a pulsed laser diode (PicoQuant PDL800-B) with a 20 MHz repetition rate. The Instrument Response Function (IRF) is about 60 ps.</p><p>The fluorescence intensity decays were analyzed in terms of the multi-exponential model as the sum of individual single exponential decays: (1)I(t)=∑i=1nαiexp(−t/τi) In this expression τi are the decay times and αi are the amplitudes. The fractional contribution of each component to the steady-state intensity is described by: (2)fi=αiτi∑jαjτj The average lifetime is represented by: (3)τ¯=∑ifiτi The values of αi and τi were determined using the PicoQuant Fluofit 4.1 software with the deconvolution of instrument response function and nonlinear least squares fitting. The goodness-of-fit was determined by the χ2 value.</p>\n\nResults and Discussion\n<p>We measured the emission intensities for all accessible angles around the z-axis in the plane of the Pt films. We used RK excitation since the incident light from this direction cannot excite surface plasmons. Fig. 2 shows polar intensity plots showing the SPCE and free space emission of PVA films containing fluorescein (top panel) and rhodamine B (bottom panel) respectively on 40-nm platinum films. The emission is sharply directed back into the hemicylinder and is distributed equally on both sides of the normal axis as shown in Figure 2. The emission was sharply distributed at 50° and 48° for fluorescein and rhodamine respectively. Figure 2 also shows the highly directional and predominantly p-polarized SPCE emission on Pt films, suggesting that the observed signal is due to surface plasmons. This is in stark contrast to the free-space emission which does not show any polarization or directional preference. It can be seen that the p-polarized signal intensity at the SPCE peak angle is lower in magnitude than the unpolarized signal. This occurs because the sheet polarizers used in the experiment have less than 100 % peak transmission efficiency for p- and s- polarizations. It is important to note that the angular distribution shown in Figure 2 is much sharper than those found for fluorophores on uncoated glass, and sharper than those due to reflections above a mirror.</p><p>We measured emission spectra of thin PVA films containing either fluorescein or rhodamine B on Pt films in both free-space and SPCE configuration to confirm the absence of scattered light. The emission spectra were recorded at the angle of maximum emission as shown in Figure 3. The emission spectra on the SPCE side are spectrally equivalent to the free-space emission spectra for both fluorescein and rhodamine B samples (Fig. 3a and 3b). We have also recorded the SPCE spectra through a polarizer as shown in Fig. 3c and 3d. The SPCE was almost completely polarized in the horizontal direction, which is p-polarized. The high polarization value demonstrates that SPCE signal is due to plasmons which, because of the wavevector matching conditions are created by the excited–state fluorophores. Furthermore, the SPCE signal is p-polarized irrespective of the polarization of the incident light. The sharp angular distribution and p-polarization are characteristic of SPCE [11–14]. Our SPCE observations with reverse- Kretschmann (RK) configuration support that the surface plasmon coupling occurs in the excited state and that the SPCE is not directly created by the incident light. This suggests that the SPCE emission observed with thin Pt films is not due to direct transmission of fluorescence, but rather due to increased electromagnetic coupling efficiency between the excited state fluorophores and smooth Pt films.</p><p>Figure 4 shows intensity decays for the free-space emission and the SPCE emission for thin PVA films of fluorescein and rhodamine B on thin platinum films. We carefully considered possible artifacts and the effects of sample geometry, while recording the intensity decays. The most important conclusion from these intensity decay measurements is that the lifetimes of SPCE and the free space emission are essentially the same.</p><p>In summary, we have examined fluorescein and rhodamine B in thin polymer films on 40 nm thick Pt films on quartz substrates. We observed efficient SPCE through thin Pt films. This suggests that the energy effectively coupled through the Pt film into the quartz substrate at a sharply defined angle. A significant portion of the total emission appeared as SPCE. The SPCE emission was p-polarized with different wavelengths appearing at different angles. The high polarization indicates that the emission is probably due to surface plasmons which radiate into the prism. The emission lifetimes of fluorophores were mostly unchanged in the free-space and SPCE modes.</p><p>The phenomenon of SPCE has now been reported for four metals Al, Ag, Au and Pt. These metals are biologically benign and if needed can be coated with silica for which there is a great deal of surface chemistry available for linking biomolecules. Additionally, these metals are easily used in nanofabrication methods such as focused ion beam (FIB) and e-beam nanolithography (EBL). We expect SPCE to become widely used in devices for DNA and protein assays, and in diagnostic systems.</p>\n\n\n<p>This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.</p>",
"role": "user"
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"content": "Surface plasmon-coupled emission (SPCE) is the directional radiation of light into a glass substrate due to excited fluorophores above a thin metal film. The sharp angular distribution of SPCE is a striking phenomenon and is in stark contrast with the isotropic fluorescence emission. In this paper, we show that SPCE can occur with thin platinum films at green and red wavelengths and was found to be mostly p-polarized. This SPCE emission is the result of near-field interactions of the excited fluorophores with the thin platinum film, and is not simply a reflective or transmissive phenomenon. Our preliminary observation suggests that platinum nanostructures can be part of several novel bio-analysis surfaces.",
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science.ddi_ner | science.ddi_ner.160 | [
{
"content": "Examine the provided biomedical abstract. Identify and list entities based on the specified categories: [\"Brand\", \"Drug\", \"DrugGroup\", \"UnapprovedDrug\"].\n\nFormat your findings as a JSON object: {\"Brand\": [\"Aspirin\", ...], \"DrugGroup\": [\"Salicylate\", ...], \"Drug\": [\"Phenobarbital\", ...], \"UnapprovedDrug\": [\"Heroin\", ...]}. Each key represents an entity type, and the corresponding value is a list of entities. If no entities are found for a type, use an empty list [].\n\nFocus solely on producing the JSON object.\n\nSource Text:\n\nInteractions for Vitamin B3 (Niacin): Antihypertensive Therapy: Nicotinic acid may potentiate the effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension. Aspirin: Concomitant aspirin may decrease the metabolic clearance of nicotinic acid. The clinical relevance of this finding is unclear. Other: Concomitant alcohol or hot drinks may increase the side effects of flushing and pruritus and should be avoided at the time of drug ingestion.",
"role": "user"
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{
"content": "{\"Brand\": [\"Aspirin\", \"aspirin\"], \"Drug\": [\"Niacin\", \"Vitamin B3\", \"Nicotinic acid\", \"nicotinic acid\", \"alcohol\"], \"DrugGroup\": [\"Antihypertensive\", \"ganglionic blocking agents\"], \"UnapprovedDrug\": []}",
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science.scicite_classification | science.scicite_classification.3988 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nA recent study indicated that COX-2 was related to UA-activated proliferation of smooth muscle cells possibly via TXA2 [7].",
"role": "user"
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{
"content": "Background",
"role": "assistant"
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.19910 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nChain Walking of Allylrhodium Species Towards Esters During Rhodium‐Catalyzed Nucleophilic Allylations of Imines\n\nContent Extracts:\n\n<p>J. I. Martínez, J. J. Smith, H. B. Hepburn, H. W. Lam, Angew. Chem. Int. Ed.\n2016, 55, 1108.</p><p>The migration of metal centers along carbon chains occurs in several important reactions.1, 2, 3, 4, 5, 6, 7 Many of these migrations take place by β‐hydride elimination and hydrometalation sequences, in which the direction of travel is controlled by thermodynamics, a ligand, or a nearby functional group. With few exceptions,4b–4f these migrations involve simple alkylmetal species. The ability to chain walk a metal together with a second functional group has significant synthetic opportunities, but this mode of reactivity remains largely underdeveloped. Herein, we describe, to our knowledge, the first examples of allylrhodium chain walking, and its application in the preparation of enantioenriched products.</p><p>During our studies of enantioselective Rh‐catalyzed nucleophilic allylations of imines,8 the reaction of imine 1 a with racemic allyltrifluoroborate 2 a\n9 in the presence of [{Rh(cod)Cl}2] (1.5 mol %) and iPrOH (5.0 equiv) was conducted (Scheme 1). Surprisingly, allylation at the α‐ or γ‐carbon atoms relative to the boron atom of 2 a was not observed. Instead, this reaction gave homoallylic sulfamates 3 a (68 % yield) and 4 a (6 % yield), each in >95:5 d.r. (Scheme 1).10, 11, 12 This result suggests the reactive intermediates are allylrhodium species 5 and 6, formed from migration of the allylrhodium species generated initially from transmetalation of 2 a with rhodium.</p><p>Discovery of allylrhodium chain walking.</p><p>The scope of this unexpected reaction was extended to include aldimines bearing methyl, methoxy, bromo, or dioxozole groups, which gave products with high diastereoselectivities in 65–72 % yield (Table 1, entries 1–5). Ketimines containing linear alkyl groups at the imine carbon were also effective (entries 6–9). However, an isopropyl‐substituted imine was recovered unchanged (entry 10). With one exception (entry 3), no products of allylation at the α‐ or γ‐carbons relative to the boron atom of 2 a were obtained. Furthermore, except for the reactions producing 3 a and 3 d (entries 1 and 4), the alternative regioisomers were difficult to detect by 1H NMR spectroscopy.</p><p>Investigation of imine scope.[a]</p><p>[a] Reactions were conducted using 0.30 mmol of 1. The diastereomeric ratios were confirmed by 1H NMR analysis of the unpurified reactions. [b] Yield of isolated products. [c] The regioisomer 4 a was isolated in 6 % yield (Scheme 1). [d] In the unpurified reaction, traces of a product derived from allylation without chain walking were detected. [e] Isolated as an 87:13 mixture of 3 d with the regioisomeric product 4 d. See Ref. 13.</p><p>Next, the potassium allyltrifluoroborate was varied (Table 2). As well as ethyl esters (Table 1) and benzyl esters (Table 2, entries 1–5, 7, and 8), a 2‐naphthyl ester was accommodated (Table 2, entry 6). Regarding the substituent α to the boron atom, alkyl (entries 1, 2, 7, and 8) and chloroalkyl groups (entry 3) were tolerated. Product 3 l was isolated along with a product of allylation without chain walking, in a 95:5 ratio (entry 2).13 Alkyl substituents containing phenyl or benzyloxy groups resulted in lower conversions and yields (entries 4 and 5).</p><p>Investigation of allyltrifluoroborate scope.[a]</p><p>[a] Reactions were conducted using 0.30 mmol of 1. The diastereomeric ratios were confirmed by 1H NMR analysis of the unpurified reactions. [b] Yield of isolated products. [c] Isolated as a 95:5 mixture of 3 l and the product of allylation without allylrhodium chain walking. See Ref. 13. [d] Using 2.5 mol % of [{Rh(cod)Cl}2]. [e] Yields in parentheses were determined by 1H NMR spectroscopy using 1,3,5‐trimethoxybenzene as an internal standard. [f] Attempts to purify 3 o by column chromatography were unsuccessful. A pure sample was obtained by preparative TLC.</p><p>The reaction of 1 b with allyltrifluoroborate 2 h, in which boron is bonded to a primary rather than a secondary carbon, gave not only 3 s, but also a significant quantity of product 7 in 80:20 d.r., derived from allylation without chain walking [Eq. [Link]].14 Products 3 s and 7 could not be completely separated by column chromatography, and their yields were determined by 1H NMR analysis using an internal standard.</p><p>Interestingly, the reaction of Z‐allyltrifluoroborate 8\n9 with aldimine 1 b gave 3 b in 70 % yield (Scheme 2, top), which is the same product obtained from the corresponding E‐isomer 2 a (Table 1, entry 2). Furthermore, despite possessing a substitution pattern different to all allyltrifluoroborates employed until this point, allyltrifluoroborate 9 reacted in the same manner to give 3 t (Scheme 2, bottom).10 These results suggest that regardless of the geometrical or positional isomerism of the allyltrifluoroborate within the β to δ carbons, the reactions proceed through common types of allylrhodium intermediates. However, homoallylic boron reagents were unreactive.13, 15</p><p>Effect of geometrical and positional isomerism of the allyltrifluoroborate.</p><p>Because these reactions provide chiral products from chiral substrates, we investigated whether enantioenriched allyltrifluoroborates would give enantioenriched products. However, the reactions of (R)‐2 a (94 % ee)9 with aldimine 1 b and ketimine 1 f gave (S,S)‐3 b and (S,S)‐3 f, respectively, with low‐to‐moderate enantiomeric excesses (Scheme 3). Although chain walking of alkylmetal species can proceed with high stereospecificity,7c poor absolute stereochemical transfer is observed in the reactions described herein.</p><p>Investigation of absolute stereochemical transfer with (R)‐2 a.</p><p>Next, chiral rhodium complexes were investigated for their ability to provide enantioenriched products from racemic allyltrifluoroborates (Scheme 4).8b Although several chiral dienes16 gave poor conversions13 in the reaction of aldimine 1 b with 2 a, diene L1\n17 gave (S,S)‐3 b in 72 % yield and 98 % ee. Several other products (S,S)‐3 k, (S,S)‐3 m, and (S,S)‐3 p were also prepared in the same manner. However, the yields of some of these reactions were low, and the scope is more limited than when using [{Rh(cod)Cl}2]. For example, enantioselective additions to ketimines were unsuccessful.</p><p>Enantioselective allylations. Reactions were conducted using 0.30 mmol of 1 b. The diastereomeric ratios were confirmed by 1H NMR analysis of the unpurified reactions. Yields are of isolated products. Enantiomeric excesses were determined by HPLC analysis on a chiral stationary phase. [a] Using 2.5 equivalents of allyltrifluoroborate 2 g.</p><p>Interestingly, a pronounced matched/mismatched effect was observed with enantioenriched allyltrifluoroborates. The reaction of 1 b with (R)‐2 a (94 % ee) using chiral diene L1 gave (S,S)‐3 b with results identical to the reaction using racemic 2 a (Scheme 5, top; compare with Scheme 4). However, the corresponding reaction with (S)‐2 a (94 % ee) gave a complex mixture; although 3 b was detected in small but unquantifiable amounts by 1H NMR analysis, it could not be isolated. Currently, it is unclear which steps of the proposed mechanism (see below) are rendered inefficient by the stereochemical mismatch of the ligand and the allyltrifluoroborate.</p><p>Investigation of matched/mismatched effects.</p><p>A proposed mechanism, using imine 1 a and allyltrifluoroborate 2 a as representative substrates, is shown in Scheme 6. The reaction of 2 a with iPrOH can reversibly generate a mixed alkoxide/fluoride boron ate complex 11, which transmetalates with rhodium complex 10\n18, 19 to give interconverting allylrhodium species 12 and 13. β‐Hydride elimination of 13 then gives a rhodium hydride species bound to ethyl sorbate (as in 14).20, 21 Hydrorhodation of the alkene distal to the ester then provides interconverting allylrhodium species 5 and 6. A possible driving force for this chain walking migration is the formation of a more stable, more conjugated allylrhodium species 5. Nucleophilic allylation of 1 a by 5 through a chairlike conformation 15, in which the ethyl group is pseudoaxial to avoid unfavorable interactions with the cyclooctadiene ligand,8c, 22 gives 16.23 Finally, protonolysis of 16 with HX (X=Cl, F, or OiPr) releases the product 3 a and regenerates 10. The minor regioisomer 4 a is the result of allylation of 1 a with allylrhodium species 6.</p><p>Proposed catalytic cycle.</p><p>Support for this mechanism was provided by the reaction of aldimine 1 b, allyltrifluoroborate 2 c (1.5 equiv), and ethyl sorbate (17, 1.5 equiv), using [{Rh(C2H4)2Cl}2] as a precatalyst [Eq. [Link]]. This reaction gave mostly unreacted 1 b and 17, along with unidentified products resulting from decomposition of 2 c. However, by HPLC‐MS, small quantities of the expected product 3 l derived from allyltrifluoroborate 2 c (0.4 % yield), the crossover product 3 a derived from ethyl sorbate (17, 3.4 % yield), and α,β,γ,δ‐unsaturated benzyl ester 18 (2.7 % yield) were also detected.13</p><p>Presumably, the initial catalytic species in this reaction is a complex of rhodium and ethyl sorbate (17), possibly the s‐cis‐η4 complex 19, which reacts with 2 c according to the mechanism shown in Scheme 6 to give the rhodium hydride 20 (Scheme 7). Hydrorhodation of the α,β,γ,δ‐unsaturated benzyl ester would give allylrhodium species 21, which reacts with 1 b to give the expected product 3 l. Alternatively, a structural reorganization of 20 could give 22, which can then undergo hydrorhodation of ethyl sorbate to give allylrhodium species 5 and the crossover product 3 a.</p><p>Rationale for the formation of crossover product 3 a.</p><p>In summary, we have reported the chain walking of allylrhodium species derived from δ‐trifluoroboryl β,γ‐unsaturated esters during the rhodium‐catalyzed nucleophilic allylation of imines, which gives products with two new stereocenters and a Z‐alkene. Enantioselective catalysis is possible using a chiral diene ligand, where a strong matched/mismatched effect was observed. Further exploration of this new mode of reactivity is underway in our laboratories.</p><p>As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.</p><p>Supplementary</p><p>Click here for additional data file.</p>",
"role": "user"
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{
"content": "AbstractAllylrhodium species derived from δ‐trifluoroboryl β,γ‐unsaturated esters undergo chain walking towards the ester moiety. The resulting allylrhodium species react with imines to give products containing two new stereocenters and a Z‐alkene. By using a chiral diene ligand, products can be obtained with high enantioselectivities, where a pronounced matched/mismatched effect with the chirality of the allyltrifluoroborate is evident.",
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science.gnormplus_ner | science.gnormplus_ner.8 | [
{
"content": "Examine the text provided from a scientific article. Identify entities and classify them.\n\nPresent your findings in a JSON format: {\"Gene\": [\"SSX\", ...]}. If no entities are found, use an empty list.\n\nText:\n\nA common polymorphic allele of the human luteinizing hormone beta-subunit gene: additional mutations and differential function of the promoter sequence. A common genetic variant (V) of the human luteinizing hormone (LH) beta-subunit gene was recently discovered. The V-LH molecules have higher bioactivity in vitro, but shorter half-life in circulation, which apparently is related to the alterations of LH function observed in individuals homo- and heterozygous for the V-LHbeta allele. We have now studied whether additional mutations in the V-LHbeta promoter sequence could contribute to the altered physiology of the LH variant molecules. The 661 bp 5'-flanking region of the V-LHbeta gene, retrieved from human genomic DNA by PCR, contained eight single-nucleotide changes, as compared with the wild-type (wt) LHbeta promoter. The finding was consistent in DNA samples of different ethnic groups. Reporter constructs with various lengths of the wt- and V-LH promoter sequences, driving the firefly luciferase reporter gene, were transfected into an immortalized mouse pituitary cell line, LbetaT(2), known to express the endogenous LHbeta gene, and into a non-endocrine human embryonic kidney cell line, HEK 293. Basal expression levels of the V-LHbeta promoter constructs were on average 36% higher in LbetaT(2)cells ( P < 0.001; n = 29), and 40% higher in HEK 293 cells ( P < 0.001; n = 16), as compared with the respective wt sequences. Numerous qualitative and quantitative differences were found between the two cell lines in responses of the two promoter sequences to stimulation with 12- O -tetradecanoylphorbol-13-acetate, forskolin, 8-bromo-cAMP, progesterone and gonado- tropin-releasing hormone. In conclusion, the V-LHbeta promoter has higher basal activity, and differs in response to hormonal stimulation, as compared with the wt-LHbeta promoter. The altered promoter function of the V-LHbeta gene provides evidence for differences in regulation of the wt- and V-LHbeta genes, which may contribute to the differences observed in pituitary-gonadal function between carriers of the two LHbeta alleles. The findings also suggest a novel evolutionary mechanism whereby polymorphic changes resulting in altered bioactivity of a gene product may be compensated for by additional mutations in the cognate promoter sequence, changing transcription of the same gene.",
"role": "user"
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"content": "{\"Gene\": [\"gonado- tropin-releasing hormone\", \"LHbeta\", \"12- O -tetradecanoylphorbol-13-acetate\", \"luteinizing hormone beta-subunit\", \"forskolin\", \"progesterone\", \"8-bromo-cAMP\", \"luteinizing hormone (LH) beta-subunit\"]}",
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.2568 | [
{
"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: A Novel Actin mRNA Splice Variant Regulates ACTG1 Expression\nContent:\nAbstract:\nCytoplasmic actins are abundant, ubiquitous proteins in nucleated cells. However, actin expression is regulated in a tissue- and development-specific manner. We identified a novel cytoplasmic-γ-actin( Actg1) transcript that includes a previously unidentified exon( 3a). Inclusion of this exon introduces an in-frame termination codon. We hypothesized this alternatively-spliced transcript down-regulates γ-actin production by targeting these transcripts for nonsense-mediated decay( NMD). To address this, we investigated conservation between mammals, tissue-specificity in mice, and developmental regulation using C2C12 cell culture. Exon 3a is 80% similar among mammals and varies in length from 41 nucleotides in humans to 45 in mice. Though the predicted amino acid sequences are not similar between all species, inclusion of exon 3a consistently results in the in the introduction of a premature termination codon within the alternative Actg1 transcript. Of twelve tissues examined, exon 3a is predominantly expressed in skeletal muscle, cardiac muscle, and diaphragm. Splicing to include exon 3a is concomitant with previously described down-regulation of Actg1 in differentiating C2C12 cells. Treatment of differentiated C2C12 cells with an inhibitor of NMD results in a 7-fold increase in exon 3a-containing transcripts. Therefore, splicing to generate exon 3a-containing transcripts may be one component of Actg1 regulation. We propose that this post-transcriptional regulation occurs via NMD, in a process previously described as “regulated unproductive splicing and translation”( RUST).\nIntroduction:\nAll mammals express six isoforms of actin: α-cardiac( Actc1, NM_009608), α-skeletal( Acta1, NM_009606), α-aortic( Acta2, NM_007392), γ-enteric( Actg2, NM_009610), β-cytoplasmic( Actb, NM_007393), and γ-cytoplasmic( Actg1, NM_009609). Each actin is encoded on a separate chromosome but the coding sequence of the actins are 71% identical and there is 92% amino acid sequence identity between actin proteins. This degree of conservation is indicative of intolerance of these proteins to changes in amino acid composition, presumably because of the large number of proteins that interact directly with actin. Although the coding sequences are similar between actin isoforms, the genomic architecture of actin isoforms differs between the cytoplasmic( six exons), smooth muscle( nine exons), and cardiac and skeletal isoforms( seven exons). The genomic sequence of Actg1 was first described in 1986 by Erba and colleagues[1] and no splice variants of this gene have been reported. In most dividing cells the two cytoplasmic actins are expressed at high levels. For example, mature skeletal and cardiac muscle derive from myoblasts, which express high levels of β- and γ-actin in their undifferentiated form. However, during differentiation, and in mature skeletal and cardiac muscle, the cytoplasmic actins are down-regulated to comprise only a small fraction of the total actin content, and α-skeletal and α-cardiac actins, respectively, become the predominant isoforms[2]–[4]. Nevertheless Actg1-null mice demonstrate that γ-actin is crucial for the normal function of mature skeletal muscle, as its complete absence results in a progressive myopathy in adult mice[5],[6]. C2C12 mouse myoblast cell culture is widely used to study the expression and regulation of genes during skeletal muscle development. In this system, myoblasts proliferate until induced to differentiate either via serum-starvation or substitution of horse serum into the growth medium. Differentiation of myoblasts involves exit from the cell cycle, fusion with neighboring cells, elongation into myotubes, and movement of the nuclei to the periphery of the myotubes. Subsequent maturation is characterized by bundling of α-actin thin filaments to form myofibrils. Down-regulation of Actb in differentiated C2C12 cells was previously attributed to a 40 nucleotide long conserved element in the 3′ UTR of the Actb transcript[7]. In contrast, Actg1 down-regulation was proposed to involve inhibition of splicing of intron 3 from the primary Actg1 transcript, thus preventing the production of a mature RNA[2]. A potentially relevant mechanism for post-transcriptional down-regulation is Regulated Unproductive Splicing and Translation[8]. RUST occurs by alternative splicing to include a regulatory exon which either contains, or creates via frameshift, a premature termination codon( PTC). Introduction of a PTC results in subsequent degradation of the mRNA by nonsense-mediated decay( NMD). Recent evidence suggests that as many as 4% of transcripts include alternatively spliced exons with PTCs, though there is some debate as to whether this splicing is functional or an artifact of highly active splicing factors in cells and therefore should be considered transcriptional noise[9],[10]. To help resolve this, Zhang and colleagues proposed criteria for deciding whether a splicing event is functional or noise. Briefly, they have suggested that alternative splicing is likely to be functional if the exon is: 1) conserved among species, 2) developmentally regulated, and 3) tissue specific[11]. We identified an alternatively spliced exon in Actg1 transcripts from mouse skeletal muscle cDNA. This alternative transcript includes a novel 45 bp exon( exon 3a) located in the middle of Actg1 intron 3 that introduces a PTC. A similar alternative Actg1 transcript is found in skeletal muscle from multiple other mammals. In mouse, splicing to include this exon is regulated in a tissue and development specific manner. Here we demonstrate that inclusion of exon 3a results in post-transcriptional down-regulation of Actg1 by RUST.\nDiscussion:\nIn this study, we identified a novel Actg1 splice variant enriched in cardiac and skeletal muscle. We propose that production of this alternative transcript is regulated and functional. Despite the fact that cytoplasmic actins are well-studied and widely used as reference genes, this is the first report of alternative splicing for any actin transcript. Why might exon 3a containing transcripts have been overlooked? The most divergent sequence for distinguishing between actin transcripts reside in the 5′ and 3′ UTRs. PCR primers designed to specifically amplify one isoform are typically in the UTRs and inclusion of a small exon, such as the 41–45 nt exon 3a, is likely to be overlooked in a large, >1 kb PCR product. Furthermore, short PCR products in which a 41–45 nt difference could be resolved are unlikely to involve exons 3–5 of the actin transcript because the high degree of nucleotide similarity between actin isoforms in these exons. Given that the alternative exon appears to be specific to γ-actin, a product corresponding to the alternative transcript would be lost among the abundance of the other actin cDNAs amplified. Previous studies suggested that the phenomenon of retention of intron 3 in the primary Actg1 RNA would be responsible for the down-regulation of γ-actin during differentiation of myoblasts[2],[17]. Here we add support for this hypothesis and provide evidence for regulated splicing to incorporate an additional exon situated in the middle of intron 3 which is sufficient for down-regulation of Actg1 via a mechanism not previously shown for an actin transcript. Cycloheximide inhibition of translation results in an elevation in the level of exon 3a-containing transcripts, a finding that is consistent with translation-dependent NMD. Cycloheximide is commonly used as an inhibitor of NMD[16],[18],[19], however there exists the possibility that the increase in exon 3a-containing transcripts is the result of another effect of the cycloheximide treatment rather than a direct correlation with inhibition of the NMD pathway. Therefore, assuming no additional effects of treatment with cycloheximide, we hypothesize that γ-actin is down-regulated via alternative splicing to introduce a PTC, leading to the degradation of Actg1 transcripts via NMD[8],[20]. We considered the possibility that the presence of the alternatively spliced Actg1 transcript is the result of ‘noisy splicing’. Large-scale analyses indicate that the majority of alternatively spliced transcripts are likely generated in error because of their low abundance across multiple tissues and lack of correlation with expression differences in the genes examined[9],[21],[22]. However, several examples of RUST as a mechanism of post-translational down-regulation exist[23]–[26]. Using the guidelines established by Zhang and colleagues to distinguish between noisy and functional splicing, we evaluated whether inclusion of exon 3a in Actg1 transcripts is likely to be spurious[11],[22]. A primary feature of ‘noisy splicing’ is lack of conservation of the alternative splice form in other species. However, we find that, similar to the normal coding exons of Actg1, exon 3a is highly conserved in mammals. Furthermore, in agreement with criteria for functional splice variants, we demonstrated that the alternative splice form is abundant only in skeletal and cardiac muscle, and that this splicing event is differentially regulated in developing myotubes. Splicing to include exon 3a in Actg1 transcripts maintains the proper reading frame in most species, however in primates exon 3a is only 41 nucleotides, thereby creating a frameshift. This subtle difference in the sequence of exon 3a between primates and lower mammals further supports the regulatory hypothesis in that it is the generation of a PTC and not a translated product that is evolutionarily conserved. Previous studies of RUST indicate that this type of regulation is not only conserved across species, but is typically found as a regulatory mechanism for members of the same gene family. We believe RUST may post-transcriptionally regulate both cytoplasmic actins, γ and β. Both cytoplasmic actins have a similar genomic structure and similar to γ-actin, β-actin has high degree of conservation in a portion of intron 3[27]. In addition, it was recently demonstrated that an expression construct utilizing the β-actin promoter in combination with the 3′ UTR resulted in high level expression in skeletal muscle[28],[29]. It is possible the conserved region of intron 3 of β-actin may confer an additional level of regulation in addition to the previously reported conserved 40 nt element in the 3′UTR[7]. The genomic structure of the non-cytoplasmic actins is markedly different from the cytoplasmic actins, and lack the high degree conservation observed in Actg1 and Actb intron 3. Therefore, RUST is an unlikely mechanism of regulation for the non-cytoplasmic actin isoforms. The premise of RUST seems counter-intuitive as a regulatory mechanism, since the most efficient means of down-regulation would be at the transcriptional level. However, Soergel et al note that the production of large transcripts in any instance can be an inherently wasteful endeavor, as introns can constitute up to 95% of a primary RNA transcript[30],[31]. It is possible that RUST can serve as a mechanism to quickly modulate expression of genes that are typically highly expressed, form very stable transcripts, or are essential in the cell. When a particular environmental or physiologic change dictates that only moderate levels of protein are required, production can be down-regulated without entirely switching-off transcription. In such an instance, post-transcriptional degradation of a portion of excess transcripts produced via NMD may be more energy efficient for the cell than either switching on or off transcription or post-translational degradation of unnecessary proteins. This model is suitable for γ-actin in muscle, as it is expressed at high levels in proliferating myoblasts, but is also necessary at lower levels in differentiated myotubes and developed skeletal muscle. RUST due to inclusion of exon 3a is unlikely to be the only mechanism of regulation for cytoplasmic actin transcripts. Though oftentimes used as a constitutive promoter in in vitro systems, the Actb and Actg1 promoters may also supply further control to the down-regulation of actin at a transcriptional level. Furthermore, retention of the entire intron 3 of the immature Actg1 message may contribute to delayed processing of mature transcripts[2]. Indeed, the increased abundance of incompletely spliced heterogeneous RNA observed when exon 3a-containing transcripts were present( figures 1B, 2C, 4a) may suggest a role for intron retention in down-regulation. While the alternative transcript is enriched in skeletal and cardiac muscle, we were also able to detect very low levels in brain, eye, and intestine; tissues which also expressed normal Actg1 at high levels. Regulation of β-actin synthesis was previously shown to be influenced by the levels of actin monomers in cells treated with an actin depolymerizing agent, latrunculin A[32]. We speculate that γ-actin expression may also involve an auto-regulatory mechanism by which an excess of free actin monomers in the cell induces splicing to include exon 3a of the Actg1 transcript, thus temporarily halting production in cell types which normally require high levels of actin. In such a situation, very low levels of exon 3a-containing transcipts would be expected in tissues with a high cytoplasmic actin content. In skeletal and cardiac muscle, exon 3a splicing may be regulated by splicing enhancer or splicing repressor elements. The intronic region immediately adjacent to the 5′ donor site of exon 3a is well conserved among mammals( Figure 6). During differentiation of myoblasts, multiple transcription and splicing factors are required to coordinate changes in gene expression crucial for differentiation. As such, the intronic conservation immediately 3′ of exon 3a may contain recognition motifs for splicing enhancers or repressors. Indeed, an exon splicing enhancer prediction software, ESE Finder v3. 0, identified several splicing enhancer recognition motifs( Figure 6). Of particular interest are the recognition motifs for SF2/ASF and SC35, which were shown previously to effect alternative splicing of β-tropomyosin in a tissue-specific manner[33]. In closing, this report documents the first identification and characterization of an alternatively spliced actin transcript. These data provide evidence for the dynamic regulation of Actg1 and further functional evidence for RUST.",
"role": "user"
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"content": "Actin is a well-studied protein that plays an essential role in nearly all cell types . Cytoplasmic actins are considered to be ubiquitously expressed in most tissues of the body with the exception of developing skeletal muscle , where muscle specific actins are up-regulated and γ-actin is repressed . Interest in the regulation of this transcript led to the hypothesis that intron retention is responsible for down-regulation of cytoplasmic γ-actin in skeletal muscle during development . Since the publication of the sequence of γ-actin cDNA over two and a half decades ago , no additional splice variants or cDNAs of this gene have been described . In this paper , we identify an alternatively spliced transcript in muscle that allowed us to elucidate how the γ-actin is downregulated during the important transition from myoblast to differentiated muscle cells . This is the first description of regulation of an actin transcript by regulated unproductive splicing and translation .",
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science.medmentions_ner | science.medmentions_ner.1498 | [
{
"content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nMesenteric lipoblastoma presenting as a small intestinal volvulus in an infant: A case report and literature review A 1-year-old boy with no underlying disorder presented with non-bilious vomiting since 4 days before admission. He was referred to our hospital and was diagnosed with a small bowel obstruction due to an intraabdominal tumor. Laparotomy revealed an intestinal volvulus with a soft and lobulated tumor arising from the mesentery. The resected tumor with a small part of the small bowel was diagnosed as lipoblastoma histologically. From a literature review, mesenteric lipoblastoma with an intestinal volvulus showed different characteristics such as greater frequency of vomiting and less frequency of abdominal mass as clinical symptoms, and the size of the tumor was smaller than that of the tumor without the intestinal volvulus.",
"role": "user"
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"content": "{\"AnatomicalStructure\": [\"small bowel\"], \"Bacterium\": [], \"BiologicFunction\": [\"soft\", \"lobulated tumor\", \"disorder\", \"small intestinal volvulus\", \"intestinal volvulus\", \"lipoblastoma\", \"tumor\", \"intraabdominal tumor\", \"small bowel obstruction\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"frequency of vomiting\", \"diagnosed\", \"symptoms\", \"abdominal mass\", \"non-bilious vomiting\"], \"Food\": [], \"HealthCareActivity\": [\"admission\", \"Laparotomy\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"literature review\", \"case report\"], \"MedicalDevice\": [], \"Organization\": [\"hospital\"], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [], \"SpatialConcept\": [\"size of the tumor\", \"mesenteric\", \"Mesenteric\", \"mesentery\"], \"Virus\": []}",
"role": "assistant"
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science.acl_arc_intent_classification | science.acl_arc_intent_classification.771 | [
{
"content": "Examine the given text from a research paper in the field of NLP. Your task is to identify the role of the citation within the context provided. Focus on understanding the intent behind the citation and classify it accordingly.\n\nSection Title:\nexperiments\n\nText Before Citation:\nFor our experiments we used the standard division of the WSJ (Marcus et al. 1993), with sections 2 through 21 for training (approx.\n\nCitation Text:\nFor our experiments we used the standard division of the WSJ ( Marcus et al. 1993 ) , with sections 2 through 21 for training ( approx .\n\nText After Citation:\n40,000 sentences) and section 23 for testing (2416 sentences 100 words); section 22 was used as development set. As usual, all trees were stripped off their semantic tags, co-reference information and quotation marks. Without loss of generality, all trees were converted to binary branching (and were reconverted to n-ary trees after parsing). We employed the same unknown (category) word model as in Bod (2001), based on statistics on word-endings, hyphenation and capitalization in combination with Good-Turing (Bod 1998: 85 87).",
"role": "user"
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{
"content": "Uses",
"role": "assistant"
}
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.11840 | [
{
"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome\nContent:\nAbstract:\nIn flat-faced dog breeds, air resistance caused by skull conformation is believed to be a major determinant of Brachycephalic Obstructive Airway Syndrome( BOAS). The clinical presentation of BOAS is heterogeneous, suggesting determinants independent of skull conformation contribute to airway disease. Norwich Terriers, a mesocephalic breed, are predisposed to Upper Airway Syndrome( UAS), a disease whose pathological features overlap with BOAS. Our health screening clinic examined and scored the airways of 401 Norwich terriers by laryngoscopy. Genome-wide association analyses of UAS-related pathologies revealed a genetic association on canine chromosome 13( rs9043975, p = 7. 79x10-16). Whole genome resequencing was used to identify causal variant( s) within a 414 kb critical interval. This approach highlighted an error in the CanFam3. 1 dog assembly, which when resolved, led to the discovery of a c. 2786G>A missense variant in exon 20 of the positional candidate gene, ADAM metallopeptidase with thrombospondin type 1 motif 3( ADAMTS3). In addition to segregating with UAS amongst Norwich Terriers, the ADAMTS3 c. 2786G>A risk allele frequency was enriched among the BOAS-susceptible French and( English) Bulldogs. Previous studies indicate that ADAMTS3 loss of function results in lymphoedema. Our results suggest a new paradigm in the understanding of canine upper airway disease aetiology: airway oedema caused by disruption of ADAMTS3 predisposes dogs to respiratory obstruction. These findings will enhance breeding practices and could refine the prognostics of surgical interventions that are often used to treat airway obstruction.\nIntroduction:\nAmongst dogs, brachycephaly describes the head conformation of many popular breeds including the Bulldog, French Bulldog and Pug. This trait is grossly characterised by the concurrent rostrocaudal shortening and mediolateral widening of the skull and is accompanied by skin folds of the face. The structural discordance between the reduced facial skeleton and its overlying soft tissues such as the wrinkled skin folds underpins these breeds’ iconic looks, but these artificially selected aesthetics are under increasing scrutiny for their association with health problems including breathing difficulties. It is thought that soft tissues of the upper respiratory tract such as the nostrils, nasal mucosa of the turbinates and soft palate do not scale proportionately with reductions in the midface skeleton[1]. Misconfiguration of respiratory soft tissue restricts airflow and increases negative pressure within the airway[1, 2]. This predisposes brachycephalic dogs to Brachycephalic Obstructive Airway Syndrome( BOAS). Dogs diagnosed with BOAS can have stenotic nares, elongated soft palates and oversized, caudally protruding nasal turbinates[2–7]. Airway resistance caused by these tissue anomalies is believed to induce pathological remodelling of additional tissues including tonsil and laryngeal saccule eversion, oedema of the nasopharynx, laryngeal collapse, tracheal hypoplasia and exacerbation of the thickening and elongation of the soft palate[2, 8, 9]. Collectively, these perturbations severely impact the wellbeing of affected individuals by increasing their respiratory effort, resulting in laboured breathing, intolerance to heat/exercise, cyanosis and collapse[6, 7]. The clinical assessment of the respiratory obstruction is often based on the grading of clinical symptoms, diagnostic imaging, and more recently, whole-body barometric plethysmography[6, 10, 11]. Treatment options for BOAS include anti-inflammatory medication which can reduce swelling/oedema acutely, however corrective surgery is often required to alleviate the condition[12]. Rhinoplasty of the nares, excision of the caudal aspect of the soft palate and aberrant turbinates, removal of the laryngeal saccules and tonsillectomy are the most common surgical procedures, which generally have mixed prognoses[2, 3, 6, 12–14]. The number of patients requiring surgical treatment is expected to rise notably with the rapid increase in popularity of brachycephalic breeds. The costs and morbidity of surgical treatment are a welfare concern for both owners and their dogs, with complications reported in up to 25% and mortality in as many as 5% of cases treated surgically[14]. We and others have studied the underlying genetics of canine skull shape variation[15–19]. Variants in the BMP3 and SMOC2 genes are associated with canine brachycephaly, however the contribution of these variants to BOAS pathogenesis is unclear. Moreover, variants in both of these genes appear largely fixed among brachycephalic breeds that are at greatest risk of developing BOAS and yet the incidence and severity of BOAS differs between them[11, 20]. BOAS heterogeneity may also be influenced by environmental and epigenetic factors, as well as other genetic modifiers segregating among dog populations. Under this premise, we became interested in the presentation of a respiratory condition remarkably similar to BOAS which has been identified in Norwich Terriers. As their name suggests, Norwich Terriers originate from south eastern UK where they were used for rodent control. Today, Norwich Terriers are recognised by all major kennel clubs and are known for their short, stocky build and prick ears. Dietschi et al. first described the presentation of Upper Airway Syndrome( UAS) in the Norwich Terrier. Although they are not considered a brachycephalic breed, affected Norwich Terriers present many of the hallmarks of BOAS including elongated and thickened soft palates, oedema of the nasopharynx and everted laryngeal saccules[21, 22]. The closely related Norfolk Terrier, a breed that officially split from the Norwich Terrier in 1964, is seemingly unaffected by UAS, suggesting genetic predisposition in the Norwich Terriers. Moreover, anecdotes from breeders regarding more recent dog generations, suggested that some Norwich Terriers appeared shorter-faced than those from earlier generations( personal communication to JS). Indeed, Koch et al. postulated that selective breeding is driving Norwich Terriers to become brachycephalic[9, 23, 24]. Spurred on by these observations, and the possibility of uncovering genetic modifiers that increase respiratory obstruction risk, we sought to understand the genetic basis of Norwich Terrier UAS.\nDiscussion:\nThe incidence of UAS amongst the Norwich Terrier population presented a unique opportunity to identify disease modifiers that may be shared across brachycephalic and non-brachycephalic breeds alike. Leveraging laryngoscopic phenotyping, we identified and refined a QTL to an interval that encompasses a single positional candidate gene, ADAMTS3. Following the correction of a local error in the canine reference sequence, we identified an ADAMTS3 c. 2786G>A missense variant that is associated with cases of UAS in the Norwich Terrier. Subsequently the French Bulldog and Bulldog, breeds susceptible to brachycephalic obstructive airway syndrome, were also identified as carriers of the ADAMTS3 missense allele. The ADAMTS proteins are a large family of protease enzymes[28, 29]. The procollagen N-proteinases, which includes ADAMTS3, are a subgroup of this family which were first shown to be expressed in cartilage amongst other tissues[30–32]. Within cartilage, ADAMTS3 has a substrate specificity for procollagen type II, which it cleaves to stimulate the maturation into collagen II, the major isoform of cartilage[33–37]. ADAMTS3 also has an important signalling function, as it proteolytically activates vascular endothelial growth factor-C( VEGF-C), which in turn promotes lymphangiogenesis[38, 39]. Loss of this signalling function in humans causes Hennekam lymphangiectasia-lymphedema syndrome 3, a condition characterised by lymphedema and distinct facial features including hypertelorism and a flat nasal bridge[40–42]. This oedematous human phenotype is recapitulated in two different Adamts3 knockout mouse lines which were reported to have severe defects in lymphatic development[43–45]. Both knockout lines resulted in perinatal lethality with Ogino et al., reporting death was due to apparent breathing problems. Interestingly, this line also presented with abnormal rib development and significantly rostrocaudally shortened skulls[43]. Whilst these studies did not specifically examine the tissues of the upper airways, the oedematous phenotype draws parallels with our observations in affected Norwich Terriers which carry the ADAMTS3 c. 2786G>A variant. Interestingly, in both the ADAMTS3 knock out mouse and cases of human Hennekam lymphangiectasia-lymphedema, craniofacial abnormalities are reported in conjunction with aberrant lymphatic development. Based on our analysis of rostra, we did not detect morphological differences between affected and unaffected Norwich Terriers, nor Norfolk Terriers. Similarly, there were no distinguishable differences in height or weight between the disease groups. Given the limitations of these assessments( e. g. limited skull scans, imprecise postcranial measurements), it is possible that morphological differences between disease groups were undetected. Traditionally, the brachycephalic skull conformation has been considered the major predisposing factor to airway obstruction in brachycephalic breeds such as the( English) Bulldog and French Bulldog. The parallels in the upper airway oedematous phenotype in both brachycephalic dogs and the Norwich Terrier, along with the high prevalence of the ADAMTS3 c. 2786G>A variant in brachycephalic breeds raises the possibility that it promotes airway disease in these other breeds. This presents a new paradigm in our understanding of obstructive airway disease in that both a compromising skull conformation and a predisposition to oedema of the airway contributes to disease presentation. Complex genetic effects, which may include ADAMTS3 c. 2786G>A could explain the varying susceptibility to BOAS across brachycephalic breeds. The ADAMTS3 c. 2786G>A variant could not be separated from a further seventy-nine SNVs and small indels during filtering due to the long-range LD[46, 47]. However, none of the additional intronic variants were compelling based on their position of cross-species conservation. Conversely, the arginine 929 residue in ADAMTS3 is highly conserved across orthologs and its close paralogs, ADAMTS2 and ADAMTS14, from diverse vertebrates. Arginine 929 is located in the third of four thrombospondin type 1 repeats( TSR1) within ADAMTS3. The TSR1 repeats are thought to contribute to substrate binding and interactions with the extracellular matrix[48, 49]. Although the variant site is outside the catalytically active metalloproteinase domain of ADAMTS3, the canine Arg929His substitution might change or even disrupt the correct folding of the third TSR1 repeat. It has been shown that several arginine residues within the TSR1 domain contribute to the so-called central arginine layer, an important element of the three-dimensional structure of TSR1 repeats[50]. Thus, it is plausible that p. Arg929His might alter the functional properties of ADAMTS3. The exact functional impact of the Arg929His substitution requires further investigation. The identification of ADAMTS3 in obstructive airway syndrome across dogs suggests a likely new role for the gene in effective respiratory function. This discovery warrants further longitudinal studies to assess possible correlations between the risk allele and complications during corrective upper airway surgery, where oedema of the upper airway can predispose dogs to post-operative complications. Identification of the ADAMTS3 c. 2786G>A risk allele is a critically important step to understanding the aetiology of airway disease, which at present is poorly understood. Future studies are warranted to understand the potential of the c. 2786G>A allele’s potential use as a diagnostic marker of disease.",
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"content": "Respiratory diseases are prevalent across dog breeds , particularly in brachycephalic breeds such as the Bulldog and French bulldog . The flat facial conformation of these breeds has long been assumed to be the major predisposing factor , however , the underlying genetics of their respiratory condition has never been elucidated . We became interested in the Norwich Terrier , a breed presenting with many of the same respiratory disease symptoms as the Bulldog . A distinction , however , is that the Norwich terrier is not considered to be a brachycephalic breed and so presented an opportunity to dissociate respiratory disease from head conformation . We performed a genome-wide association analysis for respiratory disease severity in the Norwich Terrier and resolved an association on chromosome 13 to a missense mutation in ADAMTS3 . Variants in this gene were previously shown to cause an oedematous phenotype–a disease characteristic in the airways of affected Norwich Terriers and brachycephalic dogs alike . We screened over 100 breeds for the ADAMTS3 variant and found that it is enriched in the Norwich Terrier , Bulldog and French Bulldog . This discovery changes how we view respiratory disease predisposition in the dog , offers potential genetic screens and highlights a new biological function for ADAMTS3 .",
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science.acl_arc_intent_classification | science.acl_arc_intent_classification.1301 | [
{
"content": "Examine the given text from a research paper in the field of NLP. Your task is to identify the role of the citation within the context provided. Focus on understanding the intent behind the citation and classify it accordingly.\n\nSection Title:\nintroduction\n\nText Before Citation:\nThe ability to explicitly identify these sections in unstructured text could play an important role in applications such as document summarization (Teufel and Moens, 2000), information retrieval (Tbahriti et al., 2005), information extraction (Mizuta et al., 2005), and question answering. fields generally follow the pattern of âintroductionâ, âmethodsâ, âresultsâ, and âconclusionsâ (SalangerMeyer, 1990; Swales, 1990; OrËasan, 2001). As an example, scientific abstracts across many different\n\nCitation Text:\nThe ability to explicitly identify these sections in unstructured text could play an important role in applications such as document summarization ( Teufel and Moens , 2000 ) , information retrieval ( Tbahriti et al. , 2005 ) , information extraction ( Mizuta et al. , 2005 ) , and question answering .\n\nText After Citation:\nAlthough there is a trend towards analysis of full article texts, we believe that abstracts still provide a tremendous amount of information, and much value can still be extracted from them. For example, Gay et al. (2005) experimented with abstracts and full article texts in the task of automatically generating index term recommendations and discovered that using full article texts yields at most a 7.4% improvement in F-score. Demner-Fushman et al. (2005) found a correlation between the quality and strength of clinical conclusions in the full article texts and abstracts. This paper presents experiments with generative content models for analyzing the discourse structure of medical abstracts, which has been confirmed to follow the four-section pattern discussed above (Salanger-Meyer, 1990).",
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"content": "Background",
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.9180 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We consider the problem of multi-antenna transmission from a base station (BS)\n\nKeywords: multi-antenna communications\n\nDataset Information:\nA2D: A2D (Actor-Action Dataset) is a dataset for simultaneously inferring actors and actions in videos. A2D has seven actor classes (adult, baby, ball, bird, car, cat, and dog) and eight action classes (climb, crawl, eat, fly, jump, roll, run, and walk) not including the no-action class, which we also consider.\nGRID Dataset: The QMUL underGround Re-IDentification (GRID) dataset contains 250 pedestrian image pairs. Each pair contains two images of the same individual seen from different camera views.\nMovieLens: The MovieLens datasets, first released in 1998, describe people’s expressed preferences for movies. These preferences take the form of tuples, each the result of a person expressing a preference (a 0-5 star rating) for a movie at a particular time.\nRailEye3D Dataset: The RailEye3D dataset, a collection of train-platform scenarios for applications targeting passenger safety and automation of train dispatching, consists of 10 image sequences captured at 6 railway stations in Austria. Annotations for multi-object tracking are provided in both an unified format as well as the ground-truth format used in the MOTChallenge.\n\nAvailable Datasets: A: A2D B: GRID Dataset C: MovieLens D: RailEye3D Dataset",
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"content": "MovieLens",
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science.scientific_papers_summarization_single_doc_arxiv | science.scientific_papers_summarization_single_doc_arxiv.79549 | [
{
"content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\ncontinuous - variable ( cv ) quantum information ( qi ) is a research field that has been increasingly growing in the past few years @xcite .\nthe need to cover larger hilbert spaces is motivated by qi protocols , such as quantum key distribution ( qkd ) , that has advantages when implemented in higher dimensions @xcite .\nthe extension of many qi protocols , first proposed considering discrete quantum systems , to the realm of cv systems has been heavily based on gaussian states @xcite .\nthis is due to the fact that their covariance matrices are fully determined by the first and second order moments @xcite , and also because of the practicality in the creation , manipulation and detection of gaussian states @xcite .\nnevertheless , several recent works have shown the relevance of non - gaussian states and operations @xcite .\nfor instance , they are required for quantum computation with cluster states @xcite , entanglement distillation @xcite , quantum error correction @xcite and loophole - free bell tests @xcite . besides\n, they provide advantages to the quantum teleportation , quantum cloning and state estimation tasks @xcite . in this work ,\nwe show that the einstein - podolsky - rosen ( epr ) steering inequality @xcite can be used to obtain a witness for the non - gaussianity of pure bipartite cv quantum states .\nwhile the scenario require pure states , we show its broad relevance by reporting the observation of the non - gaussianity of the cv two - photon state generated in the process of spontaneous parametric down - conversion ( spdc)@xcite . spdc is up to date the most used source for experimental investigations in the field of quantum information , and our work highlights the simplicity of using this source for new applications in cv - qi .\nthe generated down - converted photons are correlated in their transverse momenta and can be used to test the epr - paradox @xcite . the observed non - gaussianity is due only to the intrinsic phase - matching conditions of the spdc process @xcite , thus , highlighting the simplicity of using spdc sources for new applications of cv - qi .\nconsider a bipartite system described by a pure cv - state @xmath0 , and a generic pair of complementary noncommuting observables @xmath1 and @xmath2 , with @xmath3 used to denote the operation at each subsystem .\nthe spectral decomposition of @xmath1 and @xmath2 is a infinite set of continuous variables . in ref .\n@xcite it was introduced the epr - steering criterion as @xmath4 , where @xmath5 is is a value that depends on the chosen observables .\nthe violation of this inequality implies the implementation of a epr - paradox @xcite .\nthe _ inferred _ variances are given by @xmath6 where @xmath7 is the variance of the conditional probability distribution @xmath8 , and @xmath9 is the marginal probability distribution of one party s outcomes .\nnow , let us consider a general continuous variable two mode pure state described by a gaussian amplitude @xmath10 , where the vectors @xmath11 and @xmath12 are the outputs of the observable @xmath13 on each party @xmath14 with @xmath15 and @xmath16 being the widths of the corresponding gaussian functions .\nseveral cv physical systems can be modelled in this way , for example : an atomic ensemble interacting with an electromagnetic field , two entangled photons sent through gaussian channels , photoionization of atoms and photodissociation of molecules @xcite , spontaneous emission of a photon by an atom @xcite , and multiphoton pair production @xcite .\nsince gaussian amplitudes have the same functional form in both transverse directions we can , without loss of generality , work in one dimension and consider only its scalar form . from eq .\n( [ eq : def_varinf ] ) one can obtain the limit of @xmath5 for eq .\n( [ gstate ] ) @xcite .\nnote that @xmath17 .\none can also find the inferred variance of the complementary observable @xmath18 , and it is given by @xmath19 .\ntherefore , the epr - steering inequality reads @xmath20 let us define one parameter @xmath21 for simplicity .\nthe schmidt number @xmath22 for the general gaussian state of eq .\n( [ gstate ] ) is given by @xcite @xmath23 thus , the epr - steering inequality can be written as @xmath24 note that due to the symmetry of eq .\n( [ gstate ] ) one has that @xmath25 , where @xmath26 represents the schmidt number in the transverse direction @xmath27 @xcite . thus , one may further simplify the epr - steering inequality for gaussian states to @xmath28 thus , one may test it by performing the measurements in only one transverse direction .\nmoreover , it does not depend of the values chosen for @xmath29 and @xmath30 . when @xmath31 , @xmath32 and the gaussian state is a product state . in fig .\n[ fig1](a ) [ fig .\n[ fig1](b ) ] we show @xmath33 ( @xmath34 ) with a solid blue line , while varying @xmath35 . ) ] , while varying @xmath35 and considering one transverse direction of @xmath36 .\n( b ) the values of @xmath34 plotted in terms of @xmath35 .\n[ fig1],scaledwidth=48.0% ]\nfrom the results obtained above it is possible to envisage a simple and practical way to determine if a certain bipartite pure state is gaussian or not .\nnote from eq .\n( [ epr - gauss2 ] ) and fig .\n[ fig1](b ) that pure bipartite gaussian states will always violate the epr - steering inequality .\nthe reason is that they are in general entangled states [ see fig .\n[ fig1](a ) ] .\nthe only exception is the point marked with the horizontal dashed line in fig .\n[ fig1](b ) , which represents the point where the gaussian state is a product state . in this case\n, we have that @xmath37 , which corresponds to the upper quantum bound for pure bipartite gaussian states .\nthus , the observation of a value greater than 0.25 for @xmath34 with pure entangled states can only be achieved while considering non - gaussian states .\nwhile the scenario require pure states , now we show its broad relevance by reporting the observation of the non - gaussianity of the cv spatial two - photon state generated in the process of spdc @xcite .\nwhen perfect colinear phase - matching is considered and neglecting effects of anysotropy , we can write the spatial two - photon state as @xcite @xmath38 represents one photon in mode @xmath39 ( @xmath3 ) usually called signal or idler , and with the transverse momentum @xmath40 .\n@xmath41 is the angular spectrum of the pump beam .\nusual experimental configurations adopt a gaussian pump beam and in this case @xmath42 $ ] .\n@xmath43 represents the beam radius at the crystal plane .\n@xmath44 defines the phase - matching conditions of the spdc process , with @xmath45 .\n@xmath46 is defined by @xmath47 , where @xmath48 is the crystal length , and @xmath49 the wavenumber of the down - converted photons . in terms of these definitions\n, @xmath35 reads @xmath50 .\nthis state can be rewritten in the complementary transverse position representation as @xcite @xmath51 and @xmath52 are the fourier transform of @xmath41 and @xmath53 .\nthus , @xmath54 $ ] and @xmath55 , where @xmath56 . here ,\nthe transverse position @xmath57 and transverse momentum @xmath58 are the complementary observables for the epr - steering inequality test @xcite . clearly , the cv spatial two - photon state of spdc is a non - gaussian state @xcite .\nan experimental observation of the effects that arise form the phase - matching conditions , namely , the non - gaussianity of @xmath59 , was reported in ref .\nthey demonstrated how the spatial correlations in the near field plane of a non - linear crystal changes when the phase matching conditions varies .\nnow , we demonstrate experimentally how @xmath34 can be used to detect the non - gaussianity of this state .\nthe demonstration is based on the fact that the spatial state of spdc process is pure and entangled @xcite , even considering a post - selected one transverse direction @xcite .\nthis means that for any value of @xmath35 , the schmidt number @xmath60 is always greater than 1 . in fig .\n[ fig1](a ) [ fig .\n[ fig1](b ) ] we show @xmath61 ( @xmath34 ) with a dashed red line , while varying @xmath35 for the state @xmath59 .\none can see that for some values of @xmath35 ( @xmath62 ) the values of @xmath34 are greater than @xmath63 , thus , witnessing the non - gaussianity of this state .\nthe experimental setup is illustrated in fig .\nwe used a solid - state laser source , at @xmath64 , to pump a @xmath65-barium - borate type - ii ( bbo - ii ) non - linear crystal ( @xmath66 ) for the generation of the down - converted photons .\ninitially , the gaussian pump beam had a waist of @xmath67 at the crystal plane . however ,\nto experimentally observe the dependence of @xmath34 with @xmath35 [ see fig . [ fig1](b ) ] , we generated five more different states by changing the waist of the beam at the crystal plane .\nthis has been done by using a configurable set of doublet achromatic lenses placed before the non - linear crystal [ see fig .\n[ fig2](a ) ] .\nthe corresponding values of @xmath35 for the six generated states are shown in tab .\n[ tabla1:estados ] .\n.corresponding values of @xmath35 for the generated states.[tabla1:estados ] [ cols=\"^,^,^\",options=\"header \" , ] in order to test the @xmath34 witness , and then certify the non - gaussian feature of the cv spatial state of spdc , we compute the variances of the conditional coincidence measurements at the near- and far - field planes for the six generated states .\nthe results of all the conditional variances measured are shown in tab .\n[ tabla2:resultados ] .\nthe errors of the variances were obtained by minimizing the squared two - norm of the residuals between the analytical and experimental results ( see fig . [ fig3 ] ) .\nfor the six generated states .\nthe continuous ( black ) line corresponds to the theoretical value of the inequality for the spatial spdc state .\nthe dashed ( blue ) line shows the gaussian bound .\n[ fig5],scaledwidth=40.0% ] figure [ fig5 ] shows the values of the @xmath34 values for each state generated .\nthe continuous ( black ) line indicate the predicted theoretical value of the inequality when we consider the spatial state of spdc .\nthe dotted ( blue ) line is the upper limit for this inequality for gaussian states .\nfor the first three entangled states , the values obtained for this inequality are below the gaussian limit as predicted by theory . however , for the last three entangled states , there is a clear experimental violation of this bound . due to momentum conservation , the spatial state of the spdc process is always entangled @xcite\n[ see fig .\n[ fig1](a ) ] and , thus , we have a clear experimental demonstration of the non - gaussianity of the cv two - photon spatial state of spdc .\nwe have introduced a novel application for the epr - steering inequality by showing that it can be used for witnessing the non - gaussianity of cv quantum states . to demonstrated this we performed an experiment using the cv spatial state of entangled down - converted photons . due to the phase - matching conditions of the spdc process , the generated is state\nis naturally a pure entangled non - gaussian state . a clear violation of the gaussian bound of the epr - steering inequality has been observed .\nsince non - gaussian states are required for many new protocols of cv - qi , our work highlights the simplicity and relevance of using spdc sources for new applications in cv quantum information processing .\nwe thank c. h. monken for discussions of this paper .\nthis work was supported by grants fondecyt 1120067 , milenio p10 - 030-f and conicyt fb0824/2008 .\ne. s. g. and g. c. acknowledge the financial support of conicyt .\nw. a. t. n. thanks cnpq ( brazil ) for financial support .",
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"content": "due to practical reasons , experimental and theoretical continuous - variable ( cv ) quantum information ( qi ) has been heavily based on gaussian states . \n nevertheless , many cv - qi protocols require the use of non - gaussian states and operations . here , we show that the einstein - podolsky - rosen steering inequality can be used to obtain a practical witness for the generation of pure bipartite non - gaussian states . \n while the scenario require pure states , we show its broad relevance by reporting the experimental observation of the non - gaussianity of the cv two - photon state generated in the process of spontaneous parametric down - conversion ( spdc ) . the observed non - gaussianity is due only to the intrinsic phase - matching conditions of spdc .",
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science.mslr2022_cochrane_multidoc_summarization | science.mslr2022_cochrane_multidoc_summarization.1270 | [
{
"content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nUse of castor oil in pregnancies at term.\nReport Abstract 1:\nDespite wide use of castor oil to initiate labor, the obstetric literature contains few references to this botanical laxative. Derived from the castor plant Ricinus communis, castor oil may possess properties that are useful in post-term pregnancies.\n To evaluate the relationship between the use of castor oil and the onset of labor.\n Prospective evaluation.\n A community hospital in Brooklyn, NY.\n A total of 103 singleton pregnancies with intact membranes at 40 to 42 weeks referred for antepartum testing. Inclusion criteria included cervical examination, Bishop score of 4 or less, and no evidence of regular uterine contractions.\n Patients were alternately assigned to 1 of 2 study groups: a single oral dose of castor oil (60 mL) or no treatment.\n Castor oil was considered successful if labor began within 24 hours after dosing. Groups were compared for onset of labor in 24 hours, method of delivery, presence of meconium-stained amniotic fluid, Apgar score, and birth weight.\n Fifty-two women received castor oil and 48 were assigned no treatment. Following administration of castor oil, 30 of 52 women (57.7%) began active labor compared to 2 of 48 (4.2%) receiving no treatment. When castor oil was successful, 83.3% (25/30) of the women delivered vaginally.\n Women who receive castor oil have an increased likelihood of initiation of labor within 24 hours compared to women who receive no treatment. Castor oil use in pregnancy is underreported worldwide. This small series represents the first attempt to evaluate the medication.",
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"content": "The only trial included in this review attempts to address the role of castor oil as an induction agent. The trial was small and of poor methodological quality. Further research is needed to attempt to quantify the efficacy of castor oil as an induction agent.\n[Note: The six citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]",
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science.medmentions_ner | science.medmentions_ner.635 | [
{
"content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nAtypical periprosthetic femoral fracture: a case report We report an 82-year-old woman who underwent fixation with a long-spanning cable-plate for a bisphosphonate - induced Vancouver B1 periprosthetic femoral fracture. Non-union and breakage of the plate occurred at 16 months and necessitated revision surgery using a long-stem femoral prosthesis augmented with a cable-plate construct. Bone union was achieved eventually after 10 months.",
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"content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"Non-union and breakage of the plate\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"bisphosphonate\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"Bone union\"], \"Food\": [], \"HealthCareActivity\": [\"revision surgery\", \"underwent fixation\"], \"InjuryOrPoisoning\": [\"periprosthetic\", \"femoral fracture\"], \"IntellectualProduct\": [\"Vancouver B1\", \"case report\"], \"MedicalDevice\": [\"long-spanning cable-plate\", \"cable-plate construct\", \"long-stem femoral prosthesis\"], \"Organization\": [], \"PopulationGroup\": [\"woman\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [], \"SpatialConcept\": [], \"Virus\": []}",
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science.healthver_entailment | science.healthver_entailment.2247 | [
{
"content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Note: SARS-CoV-2 is the name of the virus, COVID-19 is the name of the illness.\n\nResearch Abstract:\nThe recently emerged SARS-CoV-2 (Coronaviridae; Betacoronavirus) is the underlying cause of COVID-19 disease.\nHere we assessed SARS-CoV2 from the Kingdom of Saudi Arabia alongside sequences of SARS-CoV, bat SARS-like CoVs and MERS-CoV, the latter currently detected in this region.\nPhylogenetic analysis, natural selection investigation and genome recombination analysis were performed.\nOur analysis showed that all Saudi SARS-CoV-2 sequences are of the same origin and closer proximity to bat SARS-like CoVs, followed by SARS-CoVs, however quite distant to MERS-CoV. Moreover, genome recombination analysis revealed two recombination events between SARS-CoV-2 and bat SARS-like CoVs.\nThis was further assessed by S gene recombination analysis.\nThese recombination events may be relevant to the emergence of this novel virus.\nMoreover, positive selection pressure was detected between SARS-CoV-2, bat SL-CoV isolates and human SARS-CoV isolates.\nHowever, the highest positive selection occurred between SARS-CoV-2 isolates and 2 bat-SL-CoV isolates (Bat-SL-RsSHC014 and Bat-SL-CoVZC45).\nThis further indicates that SARS-CoV-2 isolates were adaptively evolved from bat SARS-like isolates, and that a virus with originating from bats triggered this pandemic.\nThis study thuds sheds further light on the origin of this virus.\nAUTHOR SUMMARY The emergence and subsequent pandemic of SARS-CoV-2 is a unique challenge to countries all over the world, including Saudi Arabia where cases of the related MERS are still being reported.\nSaudi SARS-CoV-2 sequences were found to be likely of the same or similar origin.\nIn our analysis, SARS-CoV-2 were more closely related to bat SARS-like CoVs rather than to MERS-CoV (which originated in Saudi Arabia) or SARS-CoV, confirming other phylogenetic efforts on this pathogen.\nRecombination and positive selection analysis further suggest that bat coronaviruses may be at the origin of SARS-CoV-2 sequences.\nThe data shown here give hints on the origin of this virus and may inform efforts on transmissibility, host adaptation and other biological aspects of this virus.",
"role": "user"
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{
"content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"The recently emerged SARS-CoV-2 (Coronaviridae; Betacoronavirus) is the underlying cause of COVID-19 disease.\"]}",
"role": "assistant"
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science.medmentions_ner | science.medmentions_ner.584 | [
{
"content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nFitness implications of seasonal climate variation in Columbian ground squirrels The influence of climate change on the fitness of wild populations is often studied in the context of the spring onset of the reproductive season. This focus is relevant for climate influences on reproductive success, but neglects other fitness -relevant periods (e.g., autumn preparation for overwintering). We examined variation in climate variables (temperature, rainfall, snowfall, and snowpack) across the full annual cycle of Columbian ground squirrels (Urocitellus columbianus) for 21 years. We investigated seasonal climate variables that were associated with fitness variables, climate variables that exhibited directional changes across the study period, and finally observed declines in fitness (-0.03 units/year; total decline = 37%) that were associated with directional changes in climate variables. Annual fitness of adult female ground squirrels was positively associated with spring temperature (r = 0.69) and early summer rainfall (r = 0.56) and negatively associated with spring snow conditions (r = -0.44 to -0.66). Across the 21 years, spring snowmelt has become significantly delayed (r = 0.48) and summer rainfall became significantly reduced (r = -0.53). Using a standardized partial regression model, we found that directional changes in the timing of spring snowmelt and early summer rainfall (i.e., progressively drier summers) had moderate influences on annual fitness, with the latter statistically significant (ρ = -0.314 and 0.437, respectively). The summer period corresponds to prehibernation fattening of young and adult ground squirrels. Had we focused on a single point in time (viz. the onset of the breeding season), we would have underestimated the influences of climate change on our population. Rather, we obtained a comprehensive understanding of the influences of climate change on individual fitness by investigating the full lifecycle.",
"role": "user"
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"content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"breeding\", \"reproductive\", \"prehibernation fattening\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [\"ground squirrels\", \"Urocitellus columbianus\", \"Columbian ground squirrels\"], \"Finding\": [], \"Food\": [], \"HealthCareActivity\": [], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"standardized partial regression model\", \"wild\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"populations\", \"population\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [], \"SpatialConcept\": [\"directional\"], \"Virus\": []}",
"role": "assistant"
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science.mslr2022_ms2_multidoc_summarization | science.mslr2022_ms2_multidoc_summarization.2647 | [
{
"content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: Comparative results of bracing and interlocking nailing in the treatment of humeral shaft fractures\nSummary: Summary . A comparison was made between 44 humeral fractures treated conservatively with functional bracing ( Group 1 ) and 45 treated by operation with a locking nail ( Group 2 ) . Thirty-eight of the 44 patients in Group 1 ( 86 % ) and 22 of the 45 patients in Group 2 ( 47 % ) regained full movement of the shoulder joint . The functional end results were somewhat better in Group 1 although over 90 % of patients in both groups were able to clasp their fingers behind their necks and to reach up their backs without restriction . Two patients developed a pseudarthrosis in Group 1 , and 2 patients in Group 2 required operative revision due to a haematoma in 1 case and as a result of an infection in the other . There were 6 cases of primary radial nerve damage in both groups , and 6 had to be decompressed operatively . Residual sensory and motor disturbance remained in 2 patients in Group 1 . Both methods are useful for the treatment of humeral shaft fractures . We advocate functional bracing as the method of choice if no contraindications exist . Résumé . 99 fractures de la diaphyse humérale ont été analysées , do nt 44 ont été traitées par brassard et 45 par clou intramédullaire . 86 % du groupe : traitement conservateur et 47 % du groupe : traitement opératoire présentaient un mouvement illimité de l’épaule , t and is que plus de 90 % des deux groupes arrivaient à toucher la nuque ( rotation externe en abduction ) et la sacrum ( rotation interne en adduction ) avec la main du bras blessé . Il y a eut deux pseudarthroses dans le groupe conservateur . Dans le groupe opératoire deux interventions chirurgicales ont été nécessaires en raison d’une infection et d’une hémorragie . Les deux groupes présentaient chacun 6 cas de paralysie primaire du nerf radial avec une décompression chirurgicale consécutive dans 6 cas . Des déficits moteurs et sensitifs persistaient chez deux malades du groupe conservateur . Les deux méthodes sont efficaces pour le traitement des fractures de la diaphyse de l’humérus . En cas d’absence des contre-indications nous recomm and ons le traitement par brassard comme traitement de premier choix\n\n\nReport 2:\nTitle: [The treatment of humeral shaft fractures. Results of a prospective AO multicenter study].\nSummary: This prospect i ve multicenter study conducted by the German section of the AO International analyzes 302 fractures of the humeral shaft , 170 ( 56 % ) of which were operated upon and 132 ( 44 % ) , treated conservatively . Among those operated upon , 3.5 % developed infections and 10 % showed paresis of the radial nerve . In contrast , the only complication in the group treated conservatively was pseudarthrosis , in 1 case . However , further analysis revealed that complications were distributed unequally among the centers and the most complications were reported from only a few hospitals . We were able to contact 173 ( 57 % ) patients for follow-up . Results of operative and conservative treatment were compared for similar fractures . Both techniques result ed in predominantly good to excellent results . The somewhat inferior results in the group operated upon were explained by the higher percentage of associated local injuries and concomitant injuries to other organs . The results of this study were compared with those of other recent studies , and recommendations were established for the operative and conservative treatment of fractures of the humeral shaft",
"role": "user"
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{
"content": "There is no evidence available from r and omised controlled trials to ascertain whether surgical intervention of humeral shaft fractures gives a better or worse outcome than no surgery .",
"role": "assistant"
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science.data_reco_mcq_mc | science.data_reco_mcq_mc.64 | [
{
"content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: I want to study the effect of training on multiple languages, and improve upon the state-of\n\nKey Terms: multilingual nli text\n\nDataset Summaries:\nLibriSpeech: The LibriSpeech corpus is a collection of approximately 1,000 hours of audiobooks that are a part of the LibriVox project. Most of the audiobooks come from the Project Gutenberg.\nGLUE: General Language Understanding Evaluation (GLUE) benchmark is a collection of nine natural language understanding tasks, including single-sentence tasks CoLA and SST-2, similarity and paraphrasing tasks MRPC, STS-B and QQP, and natural language inference tasks MNLI, QNLI, RTE and WNLI.\nDialogue State Tracking Challenge: The Dialog State Tracking Challenges 2 & 3 (DSTC2&3) were research challenge focused on improving the state of the art in tracking the state of spoken dialog systems. State tracking, sometimes called belief tracking, refers to accurately estimating the user's goal as a dialog progresses.\nSNIPS: The SNIPS Natural Language Understanding benchmark is a dataset of over 16,000 crowdsourced queries distributed among 7 user intents of various complexity: SearchCreativeWork (e.g. Find me the I, Robot television show), GetWeather (e.g.\nSuperGLUE: SuperGLUE is a benchmark dataset designed to pose a more rigorous test of language understanding than GLUE. SuperGLUE has the same high-level motivation as GLUE: to provide a simple, hard-to-game measure of progress toward general-purpose language understanding technologies for English.\nMultiNLI: The Multi-Genre Natural Language Inference (MultiNLI) dataset has 433K sentence pairs. Its size and mode of collection are modeled closely like SNLI.\n\nDataset Options: A: LibriSpeech B: GLUE C: Dialogue State Tracking Challenge D: SNIPS E: SuperGLUE F: MultiNLI",
"role": "user"
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{
"content": "[\"GLUE\", \"MultiNLI\"]",
"role": "assistant"
}
]
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.3639 | [
{
"content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nPrior studies indicate the protective role of Ultraviolet-B (UVB) radiation in human health, mediated by vitamin D synthesis. In this observational study, we empirically outline a negative association of UVB radiation as measured by ultraviolet index (UVI) with the number of COVID-19 deaths. We apply a fixed-effect log-linear regression model to a panel dataset of 152 countries over 108 days (n = 6524). We use the cumulative number of COVID-19 deaths and case-fatality rate (CFR) as the main dependent variables and isolate the UVI effect from potential confounding factors. After controlling for time-constant and time-varying factors, we find that a permanent unit increase in UVI is associated with a 1.2 percentage points decline in daily growth rates of cumulative COVID-19 deaths [p < 0.01] and a 1.0 percentage points decline in the CFR daily growth rate [p < 0.05]. These results represent a significant percentage reduction in terms of daily growth rates of cumulative COVID-19 deaths (- 12%) and CFR (- 38%). We find a significant negative association between UVI and COVID-19 deaths, indicating evidence of the protective role of UVB in mitigating COVID-19 deaths. If confirmed via clinical studies, then the possibility of mitigating COVID-19 deaths via sensible sunlight exposure or vitamin D intervention would be very attractive.",
"role": "user"
},
{
"content": "[\"Prevention\"]",
"role": "assistant"
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]
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science.genia_ner | science.genia_ner.1376 | [
{
"content": "Analyze the provided text excerpt from a scientific document. Identify and extract distinct entities based on predefined categories.\n\nDeliver the results as a JSON structure where each key represents an entity category, and the associated value is a list of identified entities. If no entities are found for a category, return an empty list.\n\nText Excerpt:\n\nLow CD3 + CD28-induced interleukin-2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells. The capacity of neonatal T cells to secrete interleukin-2 (IL-2) has been reported to be variable. We analysed IL-2 production in purified neonatal and adult T cells using polyclonal activator phorbol ester + calcium ionophore (PDBu + iono) or receptor-mediated anti-CD3 / anti-CD3 + anti-CD28 stimulation. PDBu + iono induced equally high IL-2 levels in both groups and, when stimulated with plate-bound anti-CD3 monoclonal antibody (mAb), the IL-2 secretion by neonatal cells was undetectable and adult cells produced low amounts of IL-2 (mean 331 + /-86 pg / ml). The addition of anti-CD28 mAb to anti-CD3-stimulated cells markedly increased IL-2 production in both cell types, but levels of IL-2 in neonatal T cells remained clearly lower than those of adult T cells (respective mean values: 385 + /-109 pg / ml and 4494 + /-1199 pg / ml). As NF-kappa B is a critical transcription factor in the control of IL-2 expression, we next analysed its nuclear translocation in neonatal and adult T cells using the electrophoretic mobility shift assay and, because induction of reactive oxygen intermediates (ROI) is required for the activation of NF-kappa B, we also analysed levels of intracellular ROI in these cells using the ROI-reactive fluorochrome DCFH-DA and flow cytometry. In neonatal T cells NF-kappa B activation and ROI formation after anti-CD3 stimulation were low compared with adult T cells and, although addition of anti-CD28 mAb increased induction of NF-kappa B and ROI formation, levels similar to those of adults were not achieved. After PDBu + iono stimulation, the cells showed similar ROI formation and IL-2 secretion. Our results suggest that reduced IL-2 production by neonatal T cells is specific for anti-CD3 and anti-CD3 + anti-CD28-mediated stimulation and that these activators can not effectively activate the ROI-NF-kappa B signalling pathway in neonatal T cells.",
"role": "user"
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{
"content": "{\"CellLine\": [\"anti - CD3 - stimulated cells\"], \"CellType\": [\"neonatal cells\", \"adult cells\", \"adult T cells\", \"neonatal and adult T cells\", \"neonatal T cells\"], \"DNA\": [], \"Protein\": [\"anti - CD28\", \"anti - CD3 monoclonal antibody\", \"IL - 2\", \"anti - CD3\", \"interleukin - 2\", \"transcription factor\", \"mAb\", \"NF - kappa B\", \"anti - CD28 mAb\", \"- NF - kappa B\"], \"RNA\": []}",
"role": "assistant"
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science.annotated_materials_syntheses_events | science.annotated_materials_syntheses_events.142 | [
{
"content": "Analyze the provided abstract from a materials science paper. Identify synthesis events and represent them in JSON format. Each event should be captured as an object with:\n\n- \"trigger\": The verb indicating the synthesis action, directly quoted from the text.\n- \"arguments\": A list of pairs, each containing the text of an argument and its type, both extracted from the abstract. The types are predefined: [\"Atmospheric_Material\", \"Recipe_Precursor\", \"Solvent_Material\", \"Participant_Material\", \"Recipe_Target\"].\n\nAbstract:\n10.1002/app.40112\nComparison of the effects of phenyl dichlorophosphate modified and unmodified β-iron(III) oxide hydroxide on the thermal, combustion, and mechanical properties of ethylene-vinyl acetate/magnesium hydroxide composites\nPhenyl dichlorophosphate (PDCP), iron(III) chloride hexahydrate (FeCl3*6H2O), and tetrahydrofuran were purchased from Sinopharm Chemical Reagent Co., Ltd. These reagents were of analytical grade and were used without further purification. MH was kindly provided by KeYan Co. (Hefei, China). The EVA copolymer, containing 28 wt % VA, was supplied by Hanwha CO., Ltd. (Korea).\nβ-Fe(O)OH was prepared by a typical experiment,[10, 11] FeCl3 (0.487 g) was dissolved in distilled water (30 mL) under stirring. Then, the mixture was transferred to a 40-mL Teflon-lined autoclave. Hydrothermal synthesis was carried out in an oven at 110degC for 2 h. The products were collected by filtration, washed with distilled water and ethanol several times, and then dried in an oven at 60degC for 6 h.\nSurface modification of β-Fe(O)OH was prepared by the mixture of 10 mL of PDCP with 1 g of β-Fe(O)OH. After it was shaken for a short time, the mixture was moved into a three-necked, round-bottom flask. Then, water (20 mL) was slowly added in to the three-necked, round-bottom flask at 10degC for 5 h. Thereafter, the product was filtered and washed with low-density polyethylene on a Soxhlet extractor for over 36 h. Finally, the particles were dried at 60degC in an oven for 24 h. The obtained particles were labeled β-Fe(O)OPDCP.",
"role": "user"
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{
"content": "[{\"arguments\": [[\"tetrahydrofuran\", \"Recipe_Precursor\"], [\"iron(III) chloride hexahydrate\", \"Recipe_Precursor\"], [\"Phenyl dichlorophosphate\", \"Recipe_Precursor\"]], \"trigger\": \"purchased\"}, {\"arguments\": [[\"reagents\", \"Participant_Material\"]], \"trigger\": \"used\"}, {\"arguments\": [[\"MH\", \"Recipe_Precursor\"]], \"trigger\": \"provided\"}, {\"arguments\": [[\"EVA\", \"Recipe_Precursor\"]], \"trigger\": \"supplied\"}, {\"arguments\": [[\"\\u03b2-Fe(O)OH\", \"Recipe_Target\"]], \"trigger\": \"prepared\"}, {\"arguments\": [[\"water\", \"Solvent_Material\"], [\"FeCl3\", \"Recipe_Precursor\"]], \"trigger\": \"dissolved\"}, {\"arguments\": [[\"mixture\", \"Participant_Material\"]], \"trigger\": \"transferred\"}, {\"arguments\": [[\"products\", \"Participant_Material\"]], \"trigger\": \"collected\"}, {\"arguments\": [[\"ethanol\", \"Participant_Material\"], [\"water\", \"Participant_Material\"]], \"trigger\": \"washed\"}, {\"arguments\": [[\"mixture\", \"Participant_Material\"]], \"trigger\": \"moved\"}, {\"arguments\": [[\"water\", \"Recipe_Precursor\"]], \"trigger\": \"added\"}, {\"arguments\": [[\"product\", \"Participant_Material\"]], \"trigger\": \"filtered\"}, {\"arguments\": [[\"polyethylene\", \"Participant_Material\"]], \"trigger\": \"washed\"}, {\"arguments\": [[\"particles\", \"Participant_Material\"]], \"trigger\": \"dried\"}, {\"arguments\": [[\"\\u03b2-Fe(O)OPDCP\", \"Recipe_Target\"], [\"particles\", \"Participant_Material\"]], \"trigger\": \"labeled\"}, {\"arguments\": [[\"particles\", \"Participant_Material\"]], \"trigger\": \"obtained\"}]",
"role": "assistant"
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science.qasper_extractive_qa | science.qasper_extractive_qa.467.2 | [
{
"content": "Analyze the given research paper excerpts and address the question provided. Extract the necessary information directly from the text. Your answer should be formatted as a JSON object with the following structure:\n\n\"answer\": A list of text segments from the paper that directly respond to the question.\n\"evidence\": A list of text segments from the paper where the answer can be found.\n\nIf the question cannot be answered with the given text, return \"null\".\n\nDocument: Large Arabic Twitter Dataset on COVID-19\n\nThe 2019 coronavirus disease (COVID-19), emerged late December 2019 in China, is now rapidly spreading across the globe. At the time of writing this paper, the number of global confirmed cases has passed one million and half with over 75,000 fatalities. Many countries have enforced strict social distancing policies to contain the spread of the virus. This has changed the daily life of tens of millions of people, and urged people to turn their discussions online, e.g., via online social media sites like Twitter. In this work, we describe the first Arabic tweets dataset on COVID-19 that we have been collecting since March 1st, 2020. The dataset would help researchers and policy makers in studying different societal issues related to the pandemic. Many other tasks related to behavioral change, information sharing, misinformation and rumors spreading can also be analyzed.\n\nIntroduction\nOn December 31, 2019, Chinese public health authorities reported several cases of a respiratory syndrome caused by an unknown disease, which subsequently became known as COVID-19 in the city of Wuhan, China. This highly contagious disease continued to spread worldwide, leading the World Health Organization (WHO) to declare a global health emergency on January 30, 2020. On March 11, 2020 the disease has been identified as pandemic by WHO, and many countries around the world including Saudi Arabia, United States, United Kingdom, Italy, Canada, and Germany have continued reporting more cases of the disease BIBREF0. As the time of writing this paper, this pandemic is affecting more than 208 countries around the globe with more than one million and half confirmed cases BIBREF1.\nSince the outbreak of COVID-19, many governments around the world enforced different measures to contain the spread of the virus. The measures include travel restrictions, curfews, ban of mass gatherings, social distancing, and probably cities lock-down. This has impacted the routine of people around the globe, and many of them have turned to social media platforms for both news and communication. Since the emergence of COVID-19, Twitter platform plays a significant role in crisis communications where millions of tweets related to the virus are posted daily. Arabic is the official language of more than 22 countries with nearly 300 million native speakers worldwide. Furthermore, there is a large daily Arabic content in Twitter as millions of Arabic users use the social media network to communicate. For instance, Saudi Arabia alone has nearly 15 million Twitter users as of January, 2020 BIBREF2. Hence, it is important to analyze the Arabic users' behavior and sentiment during this pandemic. Other Twitter COVID-19 datasets have been recently proposed BIBREF3, BIBREF4 but with no significant content for the Arabic language.\nIn this work, we provide the first dataset dedicated to Arabic tweets related to COVID-19. The dataset is available at https://github.com/SarahAlqurashi/COVID-19-Arabic-Tweets-Dataset. We have been collecting data in real-time from Twitter API since January 1, 2020, by tracking COVID-19 related keywords which resulted in more than 3,934,610 Arabic tweets so far. The presented dataset is believed to be helpful for both researchers and policy makers in studying the pandemic from social perspective, as well as analyzing the human behaviour and information spreading during pandemics.\nIn what follows, we describe the dataset and the collection methods, present the initial data statistics, and provide information about how to use the dataset.\n\nDataset Description\nWe collected COVID-19 related Arabic tweets from January 1, 2020 until April 15, 2020, using Twitter streaming API and the Tweepy Python library. We have collected more than 3,934,610 million tweets so far. In our dataset, we store the full tweet object including the id of the tweet, username, hashtags, and geolocation of the tweet. We created a list of the most common Arabic keywords associated with COVID-19. Using Twitter’s streaming API, we searched for any tweet containing the keyword(s) in the text of the tweet. Table TABREF1 shows the list of keywords used along with the starting date of tracking each keyword. Furthermore, Table TABREF2 shows the list of hashtags we have been tracking along with the number of tweets collected from each hashtag. Indeed, some tweets were irrelevant, and we kept only those that were relevant to the pandemic.\nA summary over the dataset is given in Table TABREF3. While collecting data, we have observed that the number of retweets increased significantly in late March. This is likely due to the exponential increase in confirmed COVID-19 cases worldwide, including the Arabic speaking countries. A relatively small percentage of tweets were geotagged. Figure FIGREF6 presents the location of tweets observed as of 14 April 2020.\n\nDataset Access\nThe dataset is accessible on GitHub at this address: https://github.com/SarahAlqurashi/COVID-19-Arabic-Tweets-Dataset\nHowever, to comply with Twitter’s content redistribution policy, we are distributing only the IDs of the collected tweets. There are several tools (such as Hydrator) that can be used to retrieve the full tweet object. We also plan to provide more details on the pre-processing phase in the GitHub page.\n\nFuture Work\nWe are continuously updating the dataset to maintain more aspects of COVID-19 Arabic conversations and discussions happening on Twitter. We also plan to study how different groups respond to the pandemic and analyze information sharing behavior among the users.\n\nAcknowledgements\nThe authors wish to express their thanks to Batool Mohammed Hmawi for her help in data collection.\n\nTable 2: Hashtags used in collecting this dataset.\n\nTable 1: The list of keywords that we used to collect the tweets.\n\nTable 3: Summary statistics for the collected tweets\n\nFigure 1: The location of geotagged tweets\n\nInquiry: How big is the dataset?",
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{
"content": "{\"answer\": [\"more than 3,934,610 million tweets\"], \"evidence\": [\"We collected COVID-19 related Arabic tweets from January 1, 2020 until April 15, 2020, using Twitter streaming API and the Tweepy Python library. We have collected more than 3,934,610 million tweets so far. In our dataset, we store the full tweet object including the id of the tweet, username, hashtags, and geolocation of the tweet. We created a list of the most common Arabic keywords associated with COVID-19. Using Twitter\\u2019s streaming API, we searched for any tweet containing the keyword(s) in the text of the tweet. Table TABREF1 shows the list of keywords used along with the starting date of tracking each keyword. Furthermore, Table TABREF2 shows the list of hashtags we have been tracking along with the number of tweets collected from each hashtag. Indeed, some tweets were irrelevant, and we kept only those that were relevant to the pandemic.\"]}",
"role": "assistant"
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]
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.2242 | [
{
"content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nSince December 2019, the outbreak of COVID-19 in Wuhan has spread rapidly due to population movement during the Spring Festival holidays. Since January 23rd, 2020, the strategies of containment and contact tracing followed by quarantine and isolation has been implemented extensively in mainland China, and the rates of detection and confirmation have been continuously increased, which have effectively suppressed the rapid spread of the epidemic. In the early stage of the outbreak of COVID-19, it is of great practical significance to analyze the transmission risk of the epidemic and evaluate the effectiveness and timeliness of prevention and control strategies by using mathematical models and combining with a small amount of real-time updated multi-source data. On the basis of our previous research, we systematically introduce how to establish the transmission dynamic models in line with current Chinese prevention and control strategies step by step, according to the different epidemic stages and the improvement of the data. By summarized our modelling and assessing ideas, the model formulations vary from autonomous to non-autonomous dynamic systems, the risk assessment index changes from the basic regeneration number to the effective regeneration number, and the epidemic development and assessment evolve from the early SEIHR transmission model-based dynamics to the recent dynamics which are mainly associated with the variation of the isolated and suspected population sizes.",
"role": "user"
},
{
"content": "[\"Epidemic Forecasting\", \"Transmission\", \"Prevention\"]",
"role": "assistant"
}
]
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science.pico_ner | science.pico_ner.4210 | [
{
"content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nEvaluation of an intervention to change benzodiazepine-prescribing behavior in a prepaid group practice setting . To determine the effect of two levels of educational intervention on benzodiazepine-prescribing behavior in an elderly population in a controlled prepaid group practice ( PPGP ) setting , we designed a prospective controlled trial , with six-month follow-up . Our setting was a 270,000 member group-model PPGP in Colorado , from 1990 to 1991 . Participants included 91 physicians , 62 men and 29 women ; median age was 38.7 years . Group 1 received a one-on-one educational presentation by a clinical pharmacist , written educational materials , a brief follow-up visit , and feedback with recommendations . Group 2 received only a face-to-face presentation , given to departmental groups , as well as the same written educational materials used in group 1 . Controls received no intervention . Our primary outcome measure was the benzodiazepine \" on/off \" status of the elderly PPGP members . The secondary outcome measure was the median change ( preintervention minus postintervention ) in a standardized amount of benzodiazepines prescribed per physician . Logistic regression analysis failed to show a significant effect on postintervention benzodiazepine on/off status between study groups , when controlling for preintervention on/off status , PPGP-member age , PPGP-member gender , and all possible interactions . Analysis of variance failed to demonstrate an effect of either intervention on the median change in standardized amount of benzodiazepines prescribed per physician , with groups 1 , 2 , and controls yielding values of -278 ( range : -4,137 , 2,844 ) , -330 ( -1,531 , 1,358 ) , and -541 ( range : -3,716 , 2,185 ) , respectively . We conclude that strategies effective in changing physician prescribing behavior in other settings may not be effective in a PPGP setting with benzodiazepines in the elderly as the target for change .",
"role": "user"
},
{
"content": "{\"Intervention\": [\"educational intervention on benzodiazepine-prescribing behavior\", \"one-on-one educational presentation by a clinical pharmacist , written educational materials , a brief follow-up visit , and feedback with recommendations .\", \"no intervention .\", \"face-to-face presentation , given to departmental groups , as well as the same written educational materials used in group 1 .\"], \"Outcome\": [\"median change in standardized amount of benzodiazepines\", \"benzodiazepine on/off status\", \"median change ( preintervention minus postintervention ) in a standardized amount of benzodiazepines prescribed per physician\", \"benzodiazepine \\\" on/off \\\" status of the elderly PPGP members\"], \"Participant\": []}",
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science.mslr2022_ms2_multidoc_summarization | science.mslr2022_ms2_multidoc_summarization.12948 | [
{
"content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas.\nSummary: PURPOSE Little progress has been made in the treatment of adult high- grade gliomas over the last two decades , thus necessitating a search for novel therapeutic strategies . Malignant gliomas are vascular or angiogenic tumors , which leads to the supposition that angiogenesis inhibition may represent a potentially promising strategy in the treatment of these tumors . We present the results of a phase II trial of thalidomide , a putative inhibitor of angiogenesis , in the treatment of adults with previously irradiated , recurrent high- grade gliomas . PATIENTS AND METHODS Patients with a histologic diagnosis of anaplastic mixed glioma , anaplastic astrocytoma , or glioblastoma multiforme who had radiographic demonstration of tumor progression after st and ard external-beam radiotherapy with or without chemotherapy were eligible . Patients were initially treated with thalidomide 800 mg/d with increases in dose by 200 mg/d every 2 weeks until a final daily dose of 1,200 mg was achieved . Patients were evaluated every 8 weeks for response by both clinical and radiographic criteria . RESULTS A total of 39 patients were accrued , with 36 patients being assessable for both toxicity and response . Thalidomide was well tolerated , with constipation and sedation being the major toxicities . One patient developed a grade 2 peripheral neuropathy after treatment with thalidomide for nearly a year . There were two objective radiographic partial responses ( 6 % ) , two minor responses ( 6 % ) , and 12 patients with stable disease ( 33 % ) . Eight patients were alive more than 1 year after starting thalidomide , although almost all with tumor progression . Changes in serum levels of basic fibroblastic growth factor ( bFGF ) were correlated with time to tumor progression and overall survival . CONCLUSION Thalidomide is a generally well-tolerated drug that may have antitumor activity in a minority of patients with recurrent high- grade gliomas . Future studies will better define the usefulness of thalidomide in newly diagnosed patients with malignant gliomas and in combination with radiotherapy and chemotherapy . Additionally , studies will be needed to confirm the potential utility of changes in serum bFGF as a marker of antiangiogenic activity and /or glioma growth",
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"content": "The benefit of antineoplastic combined with whole brain radiation for brain metastases was not concerned , either in the brain metastases from unselected primary tumors or lung cancer",
"role": "assistant"
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.201 | [
{
"content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nBackground Clinical characteristics of patients with the coronavirus disease 2019 (COVID-19) may present differently within and outside the epicenter of Wuhan, China. More clinical investigations are needed. Objective The study was aimed to describe the clinical characteristics, laboratory parameters, and therapeutic methods of COVID-19 patients in Hunan, China. Setting The First Hospital of Changsha, First People's Hospital of Huaihua, and the Central Hospital of Loudi, Hunan province, China. Methods This was a retrospective multi-center case-series analysis. Patients with confirmed COVID-19 diagnosis hospitalized at the study centers from January 17 to February 10, 2020, were included. The following data were obtained from electronic medical records: demographics, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, computer tomography scans, and treatment measures. Main outcome measure Epidemiological, clinical, laboratory, and radiological characteristics and treatments. Results A total of 54 patients were included (51 had the common-type COVID-19, three had the severe-type), the median age was 41, and 52% of them were men. The median time from the first symptoms to hospital admission was seven days. Among patients with the common-type COVID-19, the median length of stay was nine days, and 21 days among patients with severe COVID-19. The most common symptoms at the onset of illness were fever (74.5%), cough (56.9%), and fatigue (43.1%) among patients in the common-type group. Fourteen patients (37.8%) had a reduced WBC count, 23 (62.2%) had reduced eosinophil ratio, and 21 (56.76%) had decreased eosinophil count. The most common patterns on chest-computed tomography were ground-glass opacity (52.2%) and patchy bilateral shadowing (73.9%). Pharmacotherapy included recombinant human interferon alpha2b, lopinavir/ritonavir, novaferon, antibiotics, systematic corticosteroids and traditional Chinese medicine prescription. The outcome of treatment indicated that in patients with the common-type COVID-19, interferon-alpha2b, but not novaferon, had some benefits, antibiotics treatment was not needed, and corticosteroids should be used cautiously. Conclusion As of February 10, 2020, the symptoms of COVID-19 patients in Hunan province were relatively mild comparing to patients in Wuhan, the epicenter. We observed some treatment benefits with interferon-alpha2b and corticosteroid therapies but not with novaferon and antibiotic treatment in our study population.",
"role": "user"
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{
"content": "[\"Treatment\", \"Diagnosis\"]",
"role": "assistant"
}
]
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science.pico_ner | science.pico_ner.3014 | [
{
"content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\n18F-FDG PET/CT for early prediction of response to neoadjuvant lapatinib , trastuzumab , and their combination in HER2-positive breast cancer : results from Neo-ALTTO . UNLABELLED Molecular imaging receives increased attention for selecting patients who will benefit from targeted anticancer therapies . Neo-ALTTO ( Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation ) enrolled 455 women with invasive human epidermal growth factor receptor 2 ( HER2 ) -positive breast cancer and compared rates of pathologic complete response ( pCR ) to neoadjuvant lapatinib , trastuzumab , and their combination . Each anti-HER2 therapy was given alone for 6 wk , followed by 12 wk of the same therapy plus weekly paclitaxel . The early metabolic effects of the anti-HER2 therapies on the primary tumors and their predictive values for pCR were assessed in a subset of patients . METHODS Eighty-six patients underwent ( 18 ) F-FDG PET/CT at baseline and weeks 2 and 6 of anti-HER2 treatment . An imaging core laboratory provided central validation , and 2 independent reviewers , masked to assigned treatment arm and clinical outcomes , performed consensus ( 18 ) F-FDG PET/CT readings . Maximum standardized uptake value ( SUVmax ) reductions from baseline were used to measure metabolic response . RESULTS Seventy-seven of the 86 enrolled patients presented an evaluable baseline ( 18 ) F-FDG PET/CT scan ; of these , 68 and 66 were evaluable at weeks 2 and 6 , respectively . Metabolic responses in the primary tumors were evident after 2 wk of targeted therapy and correlated highly with metabolic responses at week 6 ( R ( 2 ) = 0.81 ) . pCRs were associated with greater SUVmax reductions at both time points . Mean SUVmax reductions for pCR and non-pCR , respectively , were 54.3 % versus 32.8 % at week 2 ( P = 0.02 ) and 61.5 % versus 34.1 % at week 6 ( P = 0.02 ) . ( 18 ) F-FDG PET/CT metabolic response rates at weeks 2 and 6 were 71.6 % and 60 % , respectively using European Organization for Research and Treatment of Cancer criteria ; pCR rates were twice as high for ( 18 ) F-FDG PET/CT responders than nonresponders ( week 2 : 42 % vs. 21 % , P = 0.12 ; week 6 : 44 % vs. 19 % , P = 0.05 ) . CONCLUSION Early metabolic assessment using ( 18 ) F-FDG PET/CT can identify patients with an increased likelihood of pCR after neoadjuvant trastuzumab , lapatinib , or their combination when given with chemotherapy .",
"role": "user"
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{
"content": "{\"Intervention\": [\"anti-HER2 therapies\", \"neoadjuvant lapatinib\", \"trastuzumab\", \"neoadjuvant trastuzumab\", \"their combination\", \"Neo-ALTTO\", \"combination\", \"anti-HER2 treatment\", \"Trastuzumab\", \"paclitaxel\", \"chemotherapy\", \"anti-HER2 therapy\", \"lapatinib\", \"Neoadjuvant Lapatinib\"], \"Outcome\": [\"( 18 ) F-FDG PET/CT metabolic response rates\", \"standardized uptake value ( SUVmax ) reductions from baseline\", \"Metabolic responses\", \"metabolic effects\"], \"Participant\": [\"assessed in a subset of patients .\", \"HER2-positive breast cancer :\", \"455 women with invasive human epidermal growth factor receptor 2 ( HER2 ) -positive breast cancer\", \"patients who will benefit from targeted anticancer therapies .\", \"Eighty-six patients underwent ( 18 ) F-FDG PET/CT\"]}",
"role": "assistant"
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science.ncbi_ner | science.ncbi_ner.139 | [
{
"content": "Examine the text below and extract disease-related entities. Present your findings in a structured JSON format.\n\nYour response should be a JSON object with keys as entity types and values as lists of entities. If no entities are found, return an empty list for that type.\n\nContent:\n\nThe intron 7 donor splice site transition: a second Tay-Sachs disease mutation in French Canada. Mutations at the hexosaminidase A (HEXA) gene which cause Tay-Sachs disease (TSD) have elevated frequency in the Ashkenazi Jewish and French-Canadian populations. We report a novel TSD allele in the French-Canadian population associated with the infantile form of the disease. The mutation, a G-- > A transition at the + 1 position of intron 7, abolishes the donor splice site. Cultured human fibroblasts from a compound heterozygote for this transition (and for a deletion mutation) produce no detectable HEXA mRNA. The intron 7 + 1 mutation occurs in the base adjacent to the site of the adult-onset TSD mutation (G805A). In both mutations a restriction site for the endonuclease EcoRII is abolished. Unambiguous diagnosis, therefore, requires allele-specific oligonucleotide hybridization to distinguish between these two mutant alleles. The intron 7 + 1 mutation has been detected in three unrelated families. Obligate heterozygotes for the intron 7 + 1 mutation were born in the Saguenay-Lac-St-Jean region of Quebec. The most recent ancestors common to obligate carriers of this mutation were from the Charlevoix region of the province of Quebec. This mutation thus has a different geographic centre of diffusion and is probably less common than the exon 1 deletion TSD mutation in French Canadians. Neither mutation has been detected in France, the ancestral homeland of French Canada..",
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{
"content": "{\"Disease\": [\"TSD\", \"Tay-Sachs disease\"]}",
"role": "assistant"
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.3983 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nBuilding applications that perceive the world around them is challenging. A developer needs to (a) select and develop corresponding machine learning algorithms and models, (b) build a series of prototypes and demos, (c) balance resource consumption against the quality of the solutions, and finally (d) identify and mitigate problematic cases. The MediaPipe framework addresses all of these challenges. A developer can use MediaPipe to build prototypes by combining existing perception components, to advance them to polished cross-platform applications and measure system performance and resource consumption on target platforms. We show that these features enable a developer to focus on the algorithm or model development and use MediaPipe as an environment for iteratively improving their application with results reproducible across different devices and platforms. MediaPipe will be open-sourced at this https URL.\n\nCited Works Summary:\n[1]: MXNet is a multi-language machine learning (ML) library to ease the development of ML algorithms, especially for deep neural networks. Embedded in the host language, it blends declarative symbolic expression with imperative tensor computation. It offers auto differentiation to derive gradients. MXNet is computation and memory efficient and runs on various heterogeneous systems, ranging from mobile devices to distributed GPU clusters. This paper describes both the API design and the system implementation of MXNet, and explains how embedding of both symbolic expression and tensor operation is handled in a unified fashion. Our preliminary experiments reveal promising results on large scale deep neural network applications using multiple GPU machines.\n\n[2]: TensorFlow is a machine learning system that operates at large scale and in heterogeneous environments. Tensor-Flow uses dataflow graphs to represent computation, shared state, and the operations that mutate that state. It maps the nodes of a dataflow graph across many machines in a cluster, and within a machine across multiple computational devices, including multicore CPUs, general-purpose GPUs, and custom-designed ASICs known as Tensor Processing Units (TPUs). This architecture gives flexibility to the application developer: whereas in previous \"parameter server\" designs the management of shared state is built into the system, TensorFlow enables developers to experiment with novel optimizations and training algorithms. TensorFlow supports a variety of applications, with a focus on training and inference on deep neural networks. Several Google services use TensorFlow in production, we have released it as an open-source project, and it has become widely used for machine learning research. In this paper, we describe the TensorFlow dataflow model and demonstrate the compelling performance that TensorFlow achieves for several real-world applications.\n\n[3]: \n\n[4]: This tutorial will introduce the Computational Network Toolkit, or CNTK, Microsoft's cutting-edge open-source deep-learning toolkit for Windows and Linux. CNTK is a powerful computation-graph based deep-learning toolkit for training and evaluating deep neural networks. Microsoft product groups use CNTK, for example to create the Cortana speech models and web ranking. CNTK supports feed-forward, convolutional, and recurrent networks for speech, image, and text workloads, also in combination. Popular network types are supported either natively (convolution) or can be described as a CNTK configuration (LSTM, sequence-to-sequence). CNTK scales to multiple GPU servers and is designed around efficiency. The tutorial will give an overview of CNTK's general architecture and describe the specific methods and algorithms used for automatic differentiation, recurrent-loop inference and execution, memory sharing, on-the-fly randomization of large corpora, and multi-server parallelization. We will then show how typical uses looks like for relevant tasks like image recognition, sequence-to-sequence modeling, and speech recognition.",
"role": "user"
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"content": "Media analysis is an active area of research in both academia and industry. Typically, a media file or camera input containing both audio and video is extracted into separate streams via a media decoder which are then analyzed separately. Neural net engines like TensorFlow [2] , PyTorch [3] , CNTK [4] , MXNet [1] represent their neural networks in forms of directed graphs whose nodes are simple and deterministic, one input generates one output, which allows very efficient execution of the compute graph consisting of such lower level semantics. MediaPipe on the other hand, operates at much higher level semantics and allows more complex and dynamic behavior, one input can generate zero, one or multiple outputs, which cannot be modeled with neural networks. This complexity allows MediaPipe to excel at analyzing media at higher semantics.",
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science.genia_ner | science.genia_ner.1236 | [
{
"content": "Analyze the provided text excerpt from a scientific document. Identify and extract distinct entities based on predefined categories.\n\nDeliver the results as a JSON structure where each key represents an entity category, and the associated value is a list of identified entities. If no entities are found for a category, return an empty list.\n\nText Excerpt:\n\nThe predominant E2F complex in human primary haemopoietic cells and in AML blasts contains E2F-4, DP-1 and p130. The E2F family of transcription factors are thought to play an important role in the control of cell cycle progression. There is now also increasing evidence that some family members may act as oncogenes or tumour suppressor genes. The characterization of these proteins in human primary haemopoietic cells and acute myeloid leukaemia (AML) blasts may thus give an insight to the molecular mechanisms governing proliferation and leukaemogenesis in these cells. Therefore we analysed the expression of E2F-DNA binding activity and the constituent proteins found in the complexes in human primary haemopoietic cells of various lineages. We also studied blasts from 18 patients with acute myeloid leukaemia (AML). On electromobility shift assays (EMSA) a single E2F-DNA binding complex was detected in T cells, B cells and monocytes which was shown to contain E2F-4, DP-1 and p130, indicating that all quiescent haemopoietic cells have the same complex. Examination of 18 AML samples by EMSA revealed the presence of E2F binding and no gross abnormalities were detected. An E2F-4 / p130 complex was detected in representative samples of all FAB types analysed. Thus abnormalities of E2F function are unlikely to play a primary pathogenic role in AML.",
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"content": "{\"CellLine\": [], \"CellType\": [\"monocytes\", \"acute myeloid leukaemia (AML) blasts\", \"AML\", \"B cells\", \"quiescent haemopoietic cells\", \"T cells\", \"human primary haemopoietic cells\", \"AML blasts\"], \"DNA\": [\"tumour suppressor genes\", \"oncogenes\"], \"Protein\": [\"E2F complex\", \"E2F\", \"p130\", \"DP - 1\", \"E2F - 4 / p130 complex\", \"E2F - 4\", \"E2F family\", \"FAB\", \"transcription factors\", \"E2F - DNA binding complex\", \"/ p130\"], \"RNA\": []}",
"role": "assistant"
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science.data_reco_mcq_mc | science.data_reco_mcq_mc.1870 | [
{
"content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: I want to train a supervised model for facial landmark detection from images.\n\nKey Terms: facial landmark detection images\n\nDataset Summaries:\nLS3D-W: A 3D facial landmark dataset of around 230,000 images.\n300W: The 300-W is a face dataset that consists of 300 Indoor and 300 Outdoor in-the-wild images. It covers a large variation of identity, expression, illumination conditions, pose, occlusion and face size.\nFaceForensics: FaceForensics is a video dataset consisting of more than 500,000 frames containing faces from 1004 videos that can be used to study image or video forgeries. All videos are downloaded from Youtube and are cut down to short continuous clips that contain mostly frontal faces.\nAFW: AFW (Annotated Faces in the Wild) is a face detection dataset that contains 205 images with 468 faces. Each face image is labeled with at most 6 landmarks with visibility labels, as well as a bounding box.\nAFLW: The Annotated Facial Landmarks in the Wild (AFLW) is a large-scale collection of annotated face images gathered from Flickr, exhibiting a large variety in appearance (e.g., pose, expression, ethnicity, age, gender) as well as general imaging and environmental conditions. In total about 25K faces are annotated with up to 21 landmarks per image.\n\nDataset Options: A: LS3D-W B: 300W C: FaceForensics D: AFW E: AFLW",
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{
"content": "[\"300W\", \"AFW\"]",
"role": "assistant"
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science.pico_ner | science.pico_ner.266 | [
{
"content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nInterferential therapy electrode placement technique in acute low back pain : a preliminary investigation . OBJECTIVE To determine the efficacy of interferential therapy ( IFT ) electrode placement technique compared with a control treatment in subjects with acute low back pain ( LBP ) . DESIGN Single-blind , randomized , controlled trial with a 3-month follow-up . SETTING Outpatient physiotherapy departments in hospital and university settings . PATIENTS A random sample of 60 eligible patients with back pain ( 28 men , 32 women ) were recruited by general practitioners and self-referral for physiotherapy treatment and randomly assigned to 1 of 3 groups . INTERVENTIONS ( 1 ) \" IFT painful area \" and The Back Book , ( 2 ) \" IFT spinal nerve \" and The Back Book , and ( 3 ) \" Control , \" The Back Book only . Standardized IFT stimulation parameters were used : carrier frequency 3.85 kHz ; 140 Hz constant ; pulse duration 130 micros ; 30 minutes ' duration . MAIN OUTCOME MEASURES Pain Rating Index , Roland-Morris Disability Questionnaire ( RMDQ ) , and EuroQol were completed by subjects pretreatment , at discharge , and 3-month follow-up . RESULTS All groups had significant improvements in all outcomes at follow-up . Subjects managed by IFT spinal nerve and The Back Book displayed both a statistically significant ( p = .030 ) and clinically meaningful reduction in functional disability ( RMDQ ) , compared with management via IFT painful area and The Back Book combined or The Back Book alone . CONCLUSIONS The findings showed that IFT electrode placement technique affects LBP-specific functional disability , providing preliminary implications for future clinical studies .",
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"content": "{\"Intervention\": [\"and\", \"IFT painful area \\\" and The Back Book\", \"IFT\", \"interferential therapy ( IFT ) electrode placement technique\", \"Interferential therapy electrode placement technique\", \"IFT electrode placement technique\", \"\\\" Control , \\\" The Back Book\", \"control treatment\", \"\\\" IFT spinal nerve \\\"\", \"The Back Book\"], \"Outcome\": [\"Pain Rating Index , Roland-Morris Disability Questionnaire ( RMDQ ) , and EuroQol\", \"reduction in functional disability ( RMDQ )\"], \"Participant\": [\"acute low back pain :\"]}",
"role": "assistant"
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.4933 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A survey of dual-feasible and superadditive functions \nChapter Title: DFF and valid inequalities \n1. Abstract of Cited Paper (BIB001): The cutting stock problem is that of finding a cutting of stock material to meet demands for small pieces of prescribed dimensions while minimising the amount of waste. Because changing over from one cutting pattern to another involves significant setups, an auxiliary problem is to minimise the number of different patterns that are used. The pattern minimisation problem is significantly more complex, but it is of great practical importance. In this paper, we propose an integer programming formulation for the problem that involves an exponential number of binary variables and associated columns, each of which corresponds to selecting a fixed number of copies of a specific cutting pattern. The integer program is solved using a column generation approach where the subproblem is a nonlinear integer program that can be decomposed into multiple bounded integer knapsack problems. At each node of the branch-and-bound tree, the linear programming relaxation of our formulation is made tighter by adding super-additive inequalities. Branching rules are presented that yield a balanced tree. Incumbent solutions are obtained using a rounding heuristic. The resulting branch-and-price-and-cut procedure is used to produce optimal or approximately optimal solutions for a set of real-life problems. \n2. Abstract of Cited Paper (BIB002): Abstract The two-dimensional orthogonal non-guillotine cutting problem (NGCP) appears in many industries (like wood and steel industries) and consists in cutting a rectangular master surface into a number of rectangular pieces, each with a given size and value. The pieces must be cut with their edges always parallel or orthogonal to the edges of the master surface ( orthogonal cuts ). The objective is to maximize the total value of the pieces cut. In this paper, we propose a two-level approach for solving the NGCP, where, at the first level, we select the subset of pieces to be packed into the master surface without specifying the layout, while at a second level we check only if a feasible packing layout exists. This approach has been already proposed by Fekete and Schepers [S.P. Fekete, J. Schepers, A new exact algorithm for general orthogonal d -dimensional knapsack problems, ESA 97, Springer Lecture Notes in Computer Science 1284 (1997) 144–156; S.P. Fekete, J. Schepers, On more-dimensional packing III: Exact algorithms, Tech. Rep. 97.290, Universitat zu Koln, Germany, 2000; S.P. Fekete, J. Schepers, J.C. van der Veen, An exact algorithm for higher-dimensional orthogonal packing, Tech. Rep. Under revision on Operations Research, Braunschweig University of Technology, Germany, 2004] and Caprara and Monaci [A. Caprara, M. Monaci, On the two-dimensional knapsack problem, Operations Research Letters 32 (2004) 2–14]. We propose improved reduction tests for the NGCP and a cutting-plane approach to be used in the first level of the tree search to compute effective upper bounds. Computational tests on problems derived from the literature show the effectiveness of the proposed approach, that is able to reduce the number of nodes generated at the first level of the tree search and the number of times the existence of a feasible packing layout is tested. \n3. Abstract of Cited Paper (BIB003): In cutting stock problems, after an optimal (minimal stock usage) cutting plan has been devised, one might want to further reduce the operational costs by minimizing the number of setups. A setup operation occurs each time a different cutting pattern begins to be produced. The related optimization problem is known as the Pattern Minimization Problem, and it is particularly hard to solve exactly. In this paper, we present different techniques to strengthen a formulation proposed in the literature. Dual feasible functions are used for the first time to derive valid inequalities from different constraints of the model, and from linear combinations of constraints. A new arc flow formulation is also proposed. This formulation is used to define the branching scheme of our branch-and-price-and-cut algorithm, and it allows the generation of even stronger cuts by combining the branching constraints with other constraints of the model. The computational experiments conducted on instances from the literature show that our algorithm finds optimal integer solutions faster than other approaches. A set of computational results on random instances is also reported.\n\nReview Chapter:",
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"content": "Apart from computing fast lower bounds, any dual-feasible function can be used to generate valid inequalities for integer programs defined over the sets S = {x ∈ Z n + : This property is stated formally in the sequel. Given Proposition 1, this result generalizes (and hence is stronger than) an earlier result presented in Nemhauser and Wolsey BIB001 . Any valid inequality for S can be obtained either through a superadditive function or is dominated by an inequality that has been computed this way BIB001 . Cuts that are generated by a superadditive function are commonly referred to as superadditive inequalities. Among these cuts, those that are not dominated by any other inequality are said to be maximal. Clearly, the facets of the integer hull of S belong to this set. Maximal valid inequalities are necessarily superadditive, and can be obtained by functions that have the additional property of symmetry. The dominant families of dual-feasible functions are characterized exactly by the same set of properties. Any maximal inequality for S can be obtained through the Gomory procedure which is based on recursive linear combinations and rounding of other inequalities for S. The problem is that in order to get these maximal cuts, it might be necessary to use a very long recursion. In BIB001 , the basic superadditive function underlying the Gomory procedure was given. Nemhauser and Wolsey made the assumption that other superadditive functions, eventually more complex, might generate these maximal cuts using shorter recursions, hence the relevance of research on dual-feasible functions as tools to compute valid inequalities for integer programs. In other works, alternative characterizations of the integer hull of S in terms of a finite set of superadditive inequalities were proposed . However, even it is finite, the set of cuts required remains very large. To the best of our knowledge, the first experiences on using explicitly dual-feasible functions to generate valid inequalities for integer programs was done in BIB004 and in BIB003 . The authors applied dualfeasible functions that were used before only for lower bounding in packing problems. The optimization problem addressed in BIB004 was the PMP. In a previous paper BIB002 , Vanderbeck used a set of superadditive functions (see Section 4.4) to strengthen a column generation model for the PMP. He proved that the resulting valid inequalities were stronger than the rank 1 Chvátal-Gomory cuts, but as shown in BIB004 , the functions that he used are not maximal. In Section 5, we report on computational experiments on the PMP in order to gain more insight on the ability of the DFF addressed in this paper to generate good valid inequalities for this problem.",
"role": "assistant"
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.1235 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nWe present a variation of the Autoencoder (AE) that explicitly maximizes the mutual information between the input data and the hidden representation. The proposed model, the InfoMax Autoencoder (IMAE), by construction is able to learn a robust representation and good prototypes of the data. IMAE is compared both theoretically and then computationally with the state of the art models: the Denoising and Contractive Autoencoders in the one-hidden layer setting and the Variational Autoencoder in the multi-layer case. Computational experiments are performed with the MNIST and Fashion-MNIST datasets and demonstrate particularly the strong clusterization performance of IMAE.\n\nCited Works Summary:\n[1]: The emergence of a feature-analyzing function from the development rules of simple, multilayered networks is explored. It is shown that even a single developing cell of a layered network exhibits a remarkable set of optimization properties that are closely related to issues in statistics, theoretical physics, adaptive signal processing, the formation of knowledge representation in artificial intelligence, and information theory. The network studied is based on the visual system. These results are used to infer an information-theoretic principle that can be applied to the network as a whole, rather than a single cell. The organizing principle proposed is that the network connections develop in such a way as to maximize the amount of information that is preserved when signals are transformed at each processing stage, subject to certain constraints. The operation of this principle is illustrated for some simple cases. >\n\n[2]: We derive a new self-organizing learning algorithm that maximizes the information transferred in a network of nonlinear units. The algorithm does not assume any knowledge of the input distributions, and is defined here for the zero-noise limit. Under these conditions, information maximization has extra properties not found in the linear case (Linsker 1989). The nonlinearities in the transfer function are able to pick up higher-order moments of the input distributions and perform something akin to true redundancy reduction between units in the output representation. This enables the network to separate statistically independent components in the inputs: a higher-order generalization of principal components analysis. We apply the network to the source separation (or cocktail party) problem, successfully separating unknown mixtures of up to 10 speakers. We also show that a variant on the network architecture is able to perform blind deconvolution (cancellation of unknown echoes and reverberation in a speech signal). Finally, we derive dependencies of information transfer on time delays. We suggest that information maximization provides a unifying framework for problems in \"blind\" signal processing.",
"role": "user"
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{
"content": "The first neural network defined to explicitly maximize the information between the input and the hidden layer was proposed by Linsker [1] , giving to the objective function the name, . This model is a linear model that actually maximizes only the entropy of the representation, performing Principal Component Analysis (PCA) in the case of Gaussian distributed data. The same objective function was applied by Bell and Sejnowsky [2] , showing that a 1-layer neural network with sigmoid activation performs Independent Component Analysis (ICA).",
"role": "assistant"
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science.mslr2022_cochrane_multidoc_summarization | science.mslr2022_cochrane_multidoc_summarization.3025 | [
{
"content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nRandomized controlled trial of heparin for prevention of blockage of peripherally inserted central catheters in neonates.\nReport Abstract 1:\nTo determine whether the addition of heparin to total parenteral nutrition (TPN) fluid would prevent blockage of peripherally inserted central catheters (PICCs) in neonates.\n This was a randomized, double-blind, controlled study of 66 eligible neonates with PICCs inserted for the administration of TPN. Infants were randomized to receive TPN containing either 1 IU ml(-1) of heparin (n = 35) or no heparin (n = 31).\n There was no significant difference in the incidence of blocked catheters between the two groups of infants (heparin: 14.3%; no-heparin: 22.6%, p = 0.4). Although a higher percentage (62.9%) of infants in the heparin group received a complete course of TPN successfully via PICC than those in the no-heparin group (48.4%), the difference was not statistically significant (p = 0.3). There were no significant differences in the incidence of catheter-related sepsis, hypertriglyceridaemia, hyperbilirubinaemia, coagulopathy or intraventricular haemorrhage between the two groups.\n Addition of heparin to TPN fluid was not associated with a significant reduction in the incidence of blocked PICCs. However, the sample size of this study was too small to exclude even rather marked differences between the groups.\n\n\nReport Title 2:\nA randomised, controlled trial of heparin in total parenteral nutrition to prevent sepsis associated with neonatal long lines: the Heparin in Long Line Total Parenteral Nutrition (HILLTOP) trial.\nReport Abstract 2:\nInfections are common complications of neonatal long lines. Heparin has been shown to prolong the effective duration of neonatal long lines and to reduce the ability of bacteria to adhere to foreign surfaces, but the effect of heparin on rates of infection is uncertain.\n The goal of this study was to evaluate the effect of heparin on the frequency of episodes of catheter-related sepsis (CRS) in infants receiving total parenteral nutrition (TPN) through a neonatal long line.\n This randomised, controlled, double blind, single-centre clinical trial compared heparin at 0.5 IU/ml with no heparin in TPN infused through a neonatal long line, with episodes of CRS as the primary outcome.\n 210 infants were enrolled (TPN with heparin n=102, TPN without heparin n=108). There was a statistically significant reduction in all episodes of culture-positive CRS in those infants with heparin added to the TPN compared with those without heparin (p=0.04; RR 0.57, 95% CI 0.32 to 0.98; number needed to treat 9, 95% CI 4.6 to 212.4).\n The addition of heparin at 0.5 IU/ml to TPN infused through a neonatal long line reduces the incidence of culture-positive CRS.\n\n\nReport Title 3:\nA randomized, controlled trial of heparin versus placebo infusion to prolong the usability of peripherally placed percutaneous central venous catheters (PCVCs) in neonates: the HIP (Heparin Infusion for PCVC) study.\nReport Abstract 3:\nMechanical and infectious complications shorten the effective duration of peripherally inserted central venous catheters. Heparin use to prevent such complications and prolong the usability of peripherally inserted central venous catheters is inconclusive.\n Our goal was to evaluate the effectiveness of heparin in prolonging the usability of peripherally inserted central venous catheters in neonates.\n We performed a multicenter, randomized, controlled trial of heparin infusion (0.5 U/kg per hour) versus placebo for peripherally inserted central venous catheters in neonates. The primary outcome was duration of catheter use. Secondary outcomes were occlusion, catheter-related sepsis, thrombosis, and adverse effects of heparin. To detect a 168-hour (1-week) difference in the duration of catheter use, 192 patients were needed. Kaplan-Meier and Cox regression analyses were performed.\n A total of 201 neonates were enrolled (heparin group: n = 100; control group: n = 101). Baseline demographics were similar between the groups. Duration of catheter use was longer in the infants in the heparin versus the placebo group. Study center, gender, birth weight, and type and position of the catheter were not predictors of duration of catheter use. For those in the heparin versus the placebo group, the incidence of elective catheter removal (therapy completed) was 63% vs 42%, of occlusion was 6% vs 31%, of thrombosis was 20% vs 21%, and of catheter-related sepsis was 10% vs 6%, respectively. No adverse events were noted.\n Heparin infusion prolonged the duration of peripherally inserted central venous catheter usability, which permitted a higher percentage of neonates to complete therapy without increasing adverse effects.",
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"content": "Prophylactic use of heparin for peripherally placed PCVC allows a greater number of infants to complete their intended use (complete therapy) by reducing occlusion. Evidence from this systematic review support the prophylactic use of heparin for PCVC in neonates. None of these studies was powered to evaluate a lower incidence rate of adverse events. If this therapy is adopted in routine practice, monitoring of side effects is indicated.",
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science.pubmedqa_qa | science.pubmedqa_qa.140 | [
{
"content": "Analyze the given text and respond to the inquiry. Choose from: \"YES\", \"NO\", or \"MAYBE\".\n\nText:\n(BACKGROUND) It has been suggested that increasing obesity levels in young women lead to intrauterine environments that, in turn, stimulate increased obesity among their offspring, generating an intergenerational acceleration of obesity levels. If this mechanism is important, the association of maternal body mass index (BMI) with offspring BMI should be stronger than the association of paternal with offspring BMI.\n(OBJECTIVE) To compare the relative strengths of association of maternal and paternal BMI with offspring BMI at age 7.5, taking into account the possible effect of non-paternity.\n(METHODS) We compared strength of association for maternal-offspring and paternal-offspring BMI for 4654 complete parent-offspring trios in the Avon Longitudinal Study of Parents and Children (ALSPAC), using unstandardised and standardised regression analysis. We carried out a sensitivity analysis to investigate the influence of non-paternity on these associations.\n(RESULTS) The strength of association between parental BMI and offspring BMI at age 7.5 was similar for both parents. Taking into account correlations between maternal and paternal BMI, performing standardised rather than unstandardised regression and carrying out a sensitivity analysis for non-paternity emphasised the robustness of the general similarity of the associations. The associations between high parental BMI (top decile) and offspring BMI are also similar for both parents.\n\nInquiry:\nIs there an intrauterine influence on obesity?\n\nResponse:",
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"content": "NO",
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science.healthver_entailment | science.healthver_entailment.1145 | [
{
"content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Cytokine storm is now seen as a likely major cause of mortality in the 1918-20 Spanish flu-which killed more than 50 million people worldwide and the H1N1 swine flu and H5N1 bird flu of recent years-and now COVID-19.\n\nResearch Abstract:\nPatients with COVID-19 who require ICU admission might have the cytokine storm.\nIt is a state of out-of-control release of a variety of inflammatory cytokines.\nThe molecular mechanism of the cytokine storm has not been explored extensively yet.\nThe attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation.\nFour molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work.\nThe virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components.\nThe molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome.",
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"content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Patients with COVID-19 who require ICU admission might have the cytokine storm.\"]}",
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.3802 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Graphics processing units and genetic programming: An overview \nChapter Title: Interpreted, Parallel Populations \n1. Abstract of Cited Paper (BIB001): Mackey-Glass chaotic time series prediction and non-nuclear protein classification show the feasibility of evaluating genetic programming populations on SPMD parallel computing consumer gaming graphics processing units. The C++ framework with a regular disk less Linux KDE desktop equipped with a single leading nVidia GeForce 8800 GTX graphics processing unit card is demonstrated evolving programs at Giga GP operation per second (895 million GPops). The RapidMind general processing on GPU (GPGPU) framework supports evaluating an entire population of a quarter of a million individual programs on a non-trivial problem in 4 seconds. An efficient reverse polish notation (RPN) tree based GP is given. \n2. Abstract of Cited Paper (BIB002): A Single Instruction Multiple Thread CUDA interpreter provides SIMD like parallel evaluation of the whole GP population of quarter of a million RPN expressions on graphics cards and nVidia Tesla T10P. Using sub-machine code GP a sustain peak performance of 212 billion GP operations per second (3300 speed up) and an average of 4.5 peta GP ops per day is reported for a single card on a Boolean induction benchmark never attempted before, let alone solved.\n\nReview Chapter:",
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"content": "Genetic programming and other population based approaches have been called \"embarrassingly parallel\" from the ease with which they can be run on traditional parallel computers and their ability to make good use of the hardware. Since each member of the population can be tested on its own, the whole population can be run in parallel. (GP populations range from a few hundred individuals up to a few millions.) To get the best of modern GPU's containing hundreds of stream processors it is necessary to run thousands or tens of thousands of parallel computation threads. There are two main causes for this. 1) The depth of the computation hardware pipeline in each stream processor. Depending on the type of the instructions, a stream processor may be capable of overlapping the execution of up to four instructions simultaneously. 2) Threads are often paused because they are waiting for off-chip data to arrive. If other threads are ready to execute (because their data has arrived), the stream processors can start them immediately, rather than becoming idle. While somewhat application and GPU dependent it seems at least twenty computation threads per stream processor are needed to get near to the GPU's best performance. (NVIDIA's G80 architecture allows up to 512 threads per multi-processor block of eight or more stream processors. Version 2.0 allows up to 1024 threads per block.) Apart from waiting for off-chip data, another major cause for GPUs not delivering their peak performance in practice, is that the stream processors in a multiprocessor block are inherently locked in step. Each of them execute exactly the same instruction at the same time, albeit on different data items. This is known as the Single Instruction Multiple Data (SIMD) parallelism BIB001 . SIMD parallelism works well for many graphics applications, where exactly the same transformations are needed for many different data items (e.g. pixels). The GPU architecture causes a problem where a program contains branches (if statements, switch, case, etc.) and different threads take different branches. This is known as thread divergence. The GPU hardware will pause the divergent thread, and run the others. At some point, it will pause them and restart the divergent threads. Only when all threads reach the end of the branch and return to running the same code in lock-step will the GPU be able to deliver its full power. In many of the cases described in Section 2 the algorithms do indeed perform the same action on each datum and so threads can operate in lock-step and not diverge. This is also sometimes true of the early GP approaches in Sections 3 and 3.1. In these approaches typically a single program is run in parallel threads which simultaneously act upon different parts of the training set. However even threads running a single GP program can diverge. For example: 1) because IF-like branches are included in the function set. 2) Optimisations allow short cuts. For example, when implementing AND and OR, it is common to evaluate only one argument, if by doing so, it is known that the other argument can have no effect. E.g. AND(x=0,y) will be false, so there is no need to evaluate y. Thus a thread where x=0 will take a different path to one where x=1. (The same thing could even happen in symbolic regression problems using the traditional four functions: +, −, × and ÷, since ÷ is usually \"protected\" by treating divide by zero as a special case. However the GPU floating point hardware can recognise divide by zero and generate and propagate special values NaN. So on GPUs, the GP function set may not be explicitly \"protected\".) involves running something else which diverges. E.g. fitness is calculated by running a simulator. In some cases it is possible to avoid divergence by having each thread perform both sides of the branch and using a data indexing operation to select the appropriate branch's answer. In principle avoiding divergence could have benefits, like allowing global memory access to be coalesced and keeping instruction pipelines full, which could more than pay back for the extra computation. However the hardware scheduling and resumption of stalled threads appears to be sufficiently smooth that there may be little to be gained BIB003 . However Arora et al. [30, p3683] advocates replacing a simple IF with a more complicated algebraic expression (which effectively does both branches of the IF). Regardless of whether the program diverges, the GP approaches in Sections 3 and 3.1 test one compiled GP program at a time. This restricts the number of simultaneous threads they can use, typically to the number of fitness test cases. With more powerful GPUs with more stream processors per multi-processor block this becomes more serious. Our GPU SIMD interpreter approach BIB002 took the opposite approach. It avoids the (surprisingly high) cost of compiling GP individuals by using an interpreter and secondly it processes the whole population in parallel. (See Figure 3 .) You will notice the main SIMD interpreter loop contains an IF statement for every instruction that can appear in the GP language. So even though we can have a huge number of threads (at least one per member of the population) the interpreter can suffer from divergence. Juille and Pollack originally proposed a SIMD GP interpreter for the MasPar MP-2. They recognised on the MP-2 [50, Sec. 17.2.3] the SIMD architecture lead to an overhead \"directly related to the size of the instruction set interpreted by the virtual processor\". However the GPU SIMD interpreter approach primarily wins because it allows many threads which in turn allows the GPU to better overlap reading its own memory. It turns out moving data around within the GPU can be much more expensive than computing with it after it has arrived. The size of the instruction set depends upon the application but in GP between five and ten is common. However rather than thread divergence imposing a 5-10 fold overhead, this is masked by overlapping other GPU operations (such as reading memory). Therefore an overhead of about 2.5 is more usual. Where multiple test cases are needed the divergence overhead can be made negligible (see next section).",
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.412 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A Review and Evaluation of Multiobjective Algorithms for the Flowshop Scheduling Problem \nChapter Title: Benchmark and computational evaluation details \n1. Abstract of Cited Paper (BIB001): The problem of scheduling in static flowshops is considered with the objective of minimizing mean or total tardiness of jobs. A heuristic algorithm based on the simulated annealing (SA) technique is developed. The salient features of the proposed SA algorithm are the development of two new perturbation schemes for use in the proposed SA algorithm and a new improvement scheme to improve the quality of the solutions. The proposed algorithm is evaluated by using the benchmark problems available in the literature. The performance of the proposed SA algorithm is found to be very good, and the proposed heuristic performs better than the existing heuristics.\n\nReview Chapter:",
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"content": "Each one of the 23 proposed algorithms is tested against a new benchmark set. There are no known comprehensive benchmarks in the literature for the multi-objective PFSP. The only reference we know of is the work of Basseur (2005) where a small set of 14 instances is proposed. In order to carry out a comprehensive and sound analysis, a much larger set is needed. We augment the well known instances of BIB001 . This benchmark is organized in 12 groups with 10 instances each. The groups contain different combinations of the number of jobs n and the number of machines m. The n × m combinations are: {20, 50, 100} × {5, 10, 20}, 200 × {10, 20} and 500 × 20. The processing times (p ij ) in Taillard's instances are generated from a uniform distribution in the range [1, 99] . We take the first 110 instances and drop the last 10 instances in the 500 × 20 group since this size is deemed as too large for the experiments. As regards the due dates for the tardiness criterion we use the same approach of BIB002 . In this work, a tight due date d j is assigned to each job j ∈ N following the expression: p ij is the sum of the processing times over all machines for job j and random is a random number uniformly distributed in [0, 1] . This method of generating due dates results in very tight to relatively tight due dates depending on the actual value of random for each job, i.e., if random is close to 0, then the due date of the job is going to be really tight as it would be more or less the sum of its processing times. As a result, the job will have to be sequenced very early to avoid any tardiness. These 110 augmented instances can be downloaded from http://www.upv.es/gio/rruiz. Each algorithm has been carefully re-implemented following all the explanations given by the authors in the original papers. We have re-implemented all the algorithms in Delphi 2006. It should be noted that all methods share most structures and functions and the same level of coding has been used, i.e., all of them contain most common optimizations and speed-ups. Fast Non-Dominated Sorting (F N DS) is frequently used for most methods. Unless indicated differently by the authors in the original papers, the crossover and mutation operators used for the genetic methods are the two point order crossover and insertion mutation, respectively. Unless explicitly stated, all algorithms incorporate a duplicate-deletion procedure in the populations as well as in the non-dominated archives. The stopping criterion for most algorithms and is given by a time limit depending on the size of the instance. The algorithms are stopped after a CPU running time of n · m/2 · t milliseconds, where t is an input parameter. Giving more time to larger instances is a natural way of separating the results from the lurking \"total CPU time\" variable. Otherwise, if worse results are obtained for large instances, it would not be possible to tell if it is due to the limited CPU time or due to the instance size. Every algorithm is run 10 different independent times (replicates) on each instance with three different stopping criteria: t = 100, 150 and 200 milliseconds. This means that for the largest instances of 200 × 20 a maximum of 400 seconds of real CPU time (not wall time) are allowed. For every instance, stoping time and replicate we use the same random seed as a common variance reduction technique. We run every algorithm on a cluster of 12 identical computers with Intel Core 2 Duo E6600 processors running at 2.4 GHz with 1 Gbyte of RAM. For the tests, each algorithm and instance replicate is randomly assigned to a single computer and the results are collected at the end. According to Section 2, the three most common criteria for the PFSP are makespan, total completion time and total tardiness. All these criteria are of the minimization type. Therefore, all experiments are conducted for the three following criteria combinations: 1) makespan and total tardiness, 2) total completion time and total tardiness and finally, 3) makespan and total completion time. A total of 75,900 data points are collected per criteria combination if we consider the 23 algorithms, 110 instances, 10 replicates per instance and three different stopping time criteria. In reality, each data point is an approximated Pareto front containing a set of vectors with the objective values. In total there are 75, 900 · 3 = 227, 700 Pareto fronts taking into account the three criteria combinations. The experiments have required approximately 5,100 CPU hours. From the 23 · 10 · 3 = 690 available Pareto front approximations for each instance and criteria combination, a F N DS is carried out and the best non-dominated Pareto front is stored. These \"best\" 110 Pareto fronts for each criteria combination are available for future use of the research community and are also downloadable from http://www.upv.es/gio/rruiz. Additionally, a set of best Pareto fronts are available for the three different stopping time criteria. These last Pareto fronts are also used for obtaining the reference points for the hypervolume (I H ) indicator and are fixed to 1.2 times the worst known value for each objective. Also, these best Pareto fronts are also used as the reference set in the multiplicative epsilon indicator (I 1 ε ).",
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science.mslr2022_ms2_multidoc_summarization | science.mslr2022_ms2_multidoc_summarization.10524 | [
{
"content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: The relationship between impulsivity, aggression, and impulsive-aggression in borderline personality disorder: an empirical analysis of self-report measures.\nSummary: Impulsivity has been repeatedly identified as a key construct in BPD ; however , its precise definition seems to vary especially regarding the overlap with aggression . The term impulsive-aggression , also generally seen as central to an underst and ing of BPD , seems to address itself to the interface between the two , but has itself been used inconsistently in the literature , sometimes having reference to a unitary phenotypic dimension , and at other times suggesting some combination of distinct traits . This study examined the relationship between multiple measures of impulsivity , aggression , and impulsive-aggression in a BPD sample ( N = 92 ) in order to clarify the relationship between these measured constructs in this clinical population . Results show little relationship between measures of aggression and impulsivity in BPD , with measures of impulsive-aggression correlating strongly with measures of aggression only . Implication s of the present results for future research and clinical work with BPD are discussed\n\n\nReport 2:\nTitle: Adolescent personality disorders associated with violence and criminal behavior during adolescence and early adulthood.\nSummary: OBJECTIVE A community-based , longitudinal prospect i ve study was conducted to investigate whether personality disorders during adolescence are associated with elevated risk for violent behavior during adolescence and early adulthood . METHOD A community-based sample of 717 youths from upstate New York and their mothers were interviewed in 1983 , 1985 - 1986 , and 1991 - 1993 . Axis I and II disorders were assessed in 1983 and 1985 - 1986 . Antisocial personality disorder was not assessed because most participants were less than 18 years of age in 1983 and 1985 - 1986 . Violent behavior was assessed in 1985 - 1986 and 1991 - 1993 . RESULTS Adolescents with a greater number of DSM-IV cluster A or cluster B personality disorder symptoms were more likely than other adolescents in the community to commit violent acts during adolescence and early adulthood , including arson , assault , breaking and entering , initiating physical fights , robbery , and threats to injure others . These associations remained significant after controlling for the youths ' age and sex , for parental psychopathology and socioeconomic status , and for co-occurring psychiatric disorders during adolescence . Paranoid , narcissistic , and passive-aggressive personality disorder symptoms during adolescence were independently associated with risk for violent acts and criminal behavior during adolescence and early adulthood after the covariates were controlled . CONCLUSIONS Cluster A and cluster B personality disorders and paranoid , narcissistic , and passive-aggressive personality disorder symptoms during adolescence may increase risk for violent behavior that persists into early adulthood\n\n\nReport 3:\nTitle: Risk factors and correlates of violence among acutely ill adult psychiatric inpatients.\nSummary: OBJECTIVE The purpose of the study was to identify risk factors and correlates of violence committed by patients in an acute adult psychiatric inpatient unit in a district general hospital of the United Kingdom 's National Health Service . METHODS Incidents of violence committed by in patients over a one-year period in 1997 - 1998 were retrospectively analyzed . The clinical characteristics of 49 violent patients were compared with those of all patients admitted to the unit during the study period ( N=474 ) and with a r and om sample of nonviolent patients ( N=140 ) . Logistic regression analysis was used to identify clinical variables that predicted violent behavior . RESULTS Violence was not positively associated with schizophrenia or negatively associated with depression . Frequent medication change , high use of sedative drugs , past violent behavior , an ICD-10 diagnosis of dissocial personality disorder or emotionally unstable personality disorder ( DSM-IV antisocial personality disorder or borderline personality disorder ) , and long hospitalization were the most powerful predictors of violence . Together these variables had a sensitivity of 76 percent , a specificity of 97 percent , and a positive predictive value of 90 percent in predicting which patients became violent . Compulsory ( involuntary ) admission , comorbid diagnoses , past self-harm , and nonalcohol drug abuse were also associated with violent behavior . CONCLUSIONS Clinicians ' judgment about an inpatient 's potential for violence may be augmented by knowledge of the risk factors identified in this study . Medication variables could be especially useful predictors , particularly when information about other risk factors is not available . Factors other than mental illness per se may be crucial determinants of violence in acute inpatient setting\n\n\nReport 4:\nTitle: Personality diagnoses in adolescence: DSM-IV axis II diagnoses and an empirically derived alternative.\nSummary: OBJECTIVE The study of personality pathology in adolescence is in its infancy . This article examined the applicability and limits of DSM-IV axis II personality disorder diagnoses in adolescents , assessed the validity of a method for assessing adolescent personality pathology , and began to develop an empirically grounded classification . METHOD A total of 296 r and omly selected clinicians described a patient age 14 - 18 in treatment for maladaptive personality patterns using axis II ratings scales and the Shedler-Westen Assessment Procedure-200 for Adolescents ( SWAP-200-A ) , a Q-sort instrument for assessing adolescent personality pathology . After examining the nature and frequency of axis II disorders in the sample , the authors used Q-factor analysis to identify naturally occurring groupings of patients on the basis of shared personality features . RESULTS Axis II diagnoses in adolescents resembled those in adults , although application of DSM-IV criteria appeared to overdiagnose antisocial and avoidant personality disorder in adolescents . Q analysis with the SWAP-200-A isolated five personality disorders ( antisocial-psychopathic , emotionally dysregulated , avoidant-constricted , narcissistic , and histrionic ) and one personality style . Patients ' dimensional scores on each diagnostic prototype showed predictable associations with ratings of current axis II disorders , measures of adaptive functioning , and symptoms assessed with the Child Behavior Checklist . CONCLUSIONS With some exceptions , personality pathology in adolescence resembles that in adults and is diagnosable in adolescents ages 14 - 18 . Categories and criteria developed for adults may not be the optimal way of diagnosing adolescents . Data from sample s of adolescents may prove useful in developing an empirically and clinical ly grounded classification of personality pathology in adolescents\n\n\nReport 5:\nTitle: Personality disorders and violence potential.\nSummary: Violence associated with personality disorders is usually best viewed separately from psychiatric diagnosis , as a syndrome of violence rather than a syndrome of diagnosis . The authors describe eight categories of violence associated with personality disorders that may help clinicians choose treatment or management techniques : purpose ful , instrumental violence ; purpose ful , non-instrumental violence ; purpose ful , targeted , defensive violence ; targeted , impulsive violence ; nontargeted , impulsive violence incidental to emotional escape ; r and om but purpose ful violence ; violence related to perceived or feared loss or ab and onment ; and violence related to chronic paranoia or related misconceptions . The categories are not completely mutually exclusive , nor do they represent a \" decision tree . \" We also point out three important principles about the relationship between personality disorders and violence : 1 ) Personality disorders are rarely ego dystonic ; 2 ) Most patients and violent situations that come to clinical attention involve comorbid conditions . 3 ) Violence and violence risk are often associated with intoxication\n\n\nReport 6:\nTitle: Assessment of life history of aggression: development and psychometric characteristics\nSummary: The Life History of Aggression ( LHA ) assessment was administered to up to 252 subjects . In addition to a total LHA score , subscale scores for Aggression , Social Consequences and Antisocial Behavior , and Self-directed Aggression were calculated . Test-retest stability , interrater agreement , and internal consistency reliability were excellent both for the LHA Total score and the LHA Aggression subscore . There were moderately strong correlations between these scores and both self-reports of aggressive tendency ( Buss-Durkee Hostility Inventory : n = 214 ) and recent overt aggression ( Overt Aggression Scale-Modified for Out- patients : n = 61 ) . LHA Total scores were highest among subjects with Antisocial or Borderline Personality Disorder . These results support the use of the LHA assessment , and especially the LHA Aggression subscore , as a measure of life history of aggressive behavior\n\n\nReport 7:\nTitle: The relationship between personality psychopathology and aggressive behavior in research volunteers.\nSummary: Theorists and clinicians have long believed that personality psychopathology is a risk factor for aggressive behavior . Previous investigations in this area , however , have provided mixed results . In this study , the relationship between personality psychopathology and aggressive behavior was examined in 137 research volunteers . The influences of gender and coexisting major mental disorders were statistically controlled . Aggressive behavior was associated with criteria for 7 of the 11 personality disorders listed in the Diagnostic and Statistical Manual of Mental Disorders ( 3rd ed . , rev . ) . Except for schizoid criteria , all relationships with aggressive behavior were in the positive direction . When all personality disorders were considered simultaneously , paranoid and passive-aggressive criteria were significant predictors of aggressive behavior",
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"content": "Results indicate that BPD does not appear to be independently associated with increased risk of violence in the general population .\nHistory of childhood maltreatment , history of violence or criminality , and comorbid psychopathy or antisocial personality disorder appear to be predictors of violence in patients with BPD .\nThis review concludes that the current evidence suggests that patients with BPD are not more violent than individuals in the general population .",
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science.qasper_extractive_qa | science.qasper_extractive_qa.388.2 | [
{
"content": "Analyze the given research paper excerpts and address the question provided. Extract the necessary information directly from the text. Your answer should be formatted as a JSON object with the following structure:\n\n\"answer\": A list of text segments from the paper that directly respond to the question.\n\"evidence\": A list of text segments from the paper where the answer can be found.\n\nIf the question cannot be answered with the given text, return \"null\".\n\nDocument: IIIDYT at SemEval-2018 Task 3: Irony detection in English tweets\n\nIn this paper we introduce our system for the task of Irony detection in English tweets, a part of SemEval 2018. We propose representation learning approach that relies on a multi-layered bidirectional LSTM, without using external features that provide additional semantic information. Although our model is able to outperform the baseline in the validation set, our results show limited generalization power over the test set. Given the limited size of the dataset, we think the usage of more pre-training schemes would greatly improve the obtained results.\n\nIntroduction\nSentiment analysis and emotion recognition, as two closely related subfields of affective computing, play a key role in the advancement of artificial intelligence BIBREF0 . However, the complexity and ambiguity of natural language constitutes a wide range of challenges for computational systems.\nIn the past years irony and sarcasm detection have received great traction within the machine learning and NLP community BIBREF1 , mainly due to the high frequency of sarcastic and ironic expressions in social media. Their linguistic collocation inclines to flip polarity in the context of sentiment analysis, which makes machine-based irony detection critical for sentiment analysis BIBREF2 , BIBREF3 . Irony is a profoundly pragmatic and versatile linguistic phenomenon. As its foundations usually lay beyond explicit linguistic patterns in re-constructing contextual dependencies and latent meaning, such as shared knowledge or common knowledge BIBREF1 , automatically detecting it remains a challenging task in natural language processing.\nIn this paper, we introduce our system for the shared task of Irony detection in English tweets, a part of the 2018 SemEval BIBREF4 . We note that computational approaches to automatically detecting irony often deploy expensive feature-engineered systems which rely on a rich body of linguistic and contextual cues BIBREF5 , BIBREF6 . The advent of Deep Learning applied to NLP has introduced models that have succeeded in large part because they learn and use their own continuous numeric representations BIBREF7 of words BIBREF8 , offering us the dream of forgetting manually-designed features. To this extent, in this paper we propose a representation learning approach for irony detection, which relies on a bidirectional LSTM and pre-trained word embeddings.\n\nData and pre-processing\nFor the shared task, a balanced dataset of 2,396 ironic and 2,396 non-ironic tweets is provided. The ironic corpus was constructed by collecting self-annotated tweets with the hashtags #irony, #sarcasm and #not. The tweets were then cleaned and manually checked and labeled, using a fine-grained annotation scheme BIBREF3 . The corpus comprises different types of irony:\nVerbal irony is often referred to as an utterance that conveys the opposite meaning of what of literally expressed BIBREF9 , BIBREF10 , e.g. I love annoying people. Situational irony appears in settings, that diverge from the expected BIBREF11 , e.g. an old man who won the lottery and died the next day. The latter does not necessarily exhibit polarity contrast or other typical linguistic features, which makes it particularly difficult to classify correctly.\nFor the pre-processing we used the Natural Language Toolkit BIBREF12 . As a first step, we removed the following words and hashtagged words: not, sarc, sarcasm, irony, ironic, sarcastic and sarcast, in order to ascertain a clean corpus without topic-related triggers. To ease the tokenizing process with the NLTK TweetTokenizer, we replaced two spaces with one space and removed usernames and urls, as they do not generally provide any useful information for detecting irony.\nWe do not stem or lowercase the tokens, since some patterns within that scope might serve as an indicator for ironic tweets, for instance a word or a sequence of words, in which all letters are capitalized BIBREF13 .\n\nProposed Approach\nThe goal of the subtask A was to build a binary classification system that predicts if a tweet is ironic or non-ironic. In the following sections, we first describe the dataset provided for the task and our pre-processing pipeline. Later, we lay out the proposed model architecture, our experiments and results.\n\nWord representation\nRepresentation learning approaches usually require extensive amounts of data to derive proper results. Moreover, previous studies have shown that initializing representations using random values generally causes the performance to drop. For these reasons, we rely on pre-trained word embeddings as a means of providing the model the adequate setting. We experiment with GloVe BIBREF14 for small sizes, namely 25, 50 and 100. This is based on previous work showing that representation learning models based on convolutional neural networks perform well compared to traditional machine learning methods with a significantly smaller feature vector size, while at the same time preventing over-fitting and accelerates computation (e.g BIBREF2 .\nGloVe embeddings are trained on a dataset of 2B tweets, with a total vocabulary of 1.2 M tokens. However, we observed a significant overlap with the vocabulary extracted from the shared task dataset. To deal with out-of-vocabulary terms that have a frequency above a given threshold, we create a new vector which is initialized based on the space described by the infrequent words in GloVe. Concretely, we uniformly sample a vector from a sphere centered in the centroid of the 10% less frequent words in the GloVe vocabulary, whose radius is the mean distance between the centroid and all the words in the low frequency set. For the other case, we use the special UNK token.\nTo maximize the knowledge that may be recovered from the pre-trained embeddings, specially for out-of-vocabulary terms, we add several token-level and sentence-level binary features derived from simple linguistic patterns, which are concatenated to the corresponding vectors.\nIf the token is fully lowercased.\nIf the Token is fully uppercased.\nIf only the first letter is capitalized.\nIf the token contains digits.\nIf any token is fully lowercased.\nIf any token is fully uppercased.\nIf any token appears more than once.\n\nModel architecture\nRecurrent neural networks are powerful sequence learning models that have achieved excellent results for a variety of difficult NLP tasks BIBREF15 . In particular, we use the last hidden state of a bidirectional LSTM architecture BIBREF16 to obtain our tweet representations. This setting is currently regarded as the state-of-the-art BIBREF17 for the task on other datasets. To avoid over-fitting we use Dropout BIBREF18 and for training we set binary cross-entropy as a loss function. For evaluation we use our own wrappers of the the official evaluation scripts provided for the shared tasks, which are based on accuracy, precision, recall and F1-score.\n\nExperimental setup\nOur model is implemented in PyTorch BIBREF19 , which allowed us to easily deal with the variable tweet length due to the dynamic nature of the platform. We experimented with different values for the LSTM hidden state size, as well as for the dropout probability, obtaining best results for a dropout probability of INLINEFORM0 and 150 units for the the hidden vector. We trained our models using 80% of the provided data, while the remaining 20% was used for model development. We used Adam BIBREF20 , with a learning rate of INLINEFORM1 and early stopping when performance did not improve on the development set. Using embeddings of size 100 provided better results in practice. Our final best model is an ensemble of four models with the same architecture but different random initialization.\nTo compare our results, we use the provided baseline, which is a non-parameter optimized linear-kernel SVM that uses TF-IDF bag-of-word vectors as inputs. For pre-processing, in this case we do not preserve casing and delete English stopwords.\n\nResults\nTo understand how our strategies to recover more information from the pre-trained word embeddings affected the results, we ran ablation studies to compare how the token-level and sentence-level features contributed to the performance. Table TABREF16 summarizes the impact of these features in terms of F1-score on the validation set.\nWe see that sentence-level features had a positive yet small impact, while token-level features seemed to actually hurt the performance. We think that since the task is performed at the sentence-level, probably features that capture linguistic phenomena at the same level provide useful information to the model, while the contributions of other finer granularity features seem to be too specific for the model to leverage on.\nTable TABREF17 summarizes our best single-model results on the validation set (20% of the provided data) compared to the baseline, as well as the official results of our model ensemble on the test data.\nOut of 43 teams our system ranked 421st with an official F1-score of 0.2905 on the test set. Although our model outperforms the baseline in the validation set in terms of F1-score, we observe important drops for all metrics compared to the test set, showing that the architecture seems to be unable to generalize well. We think these results highlight the necessity of an ad-hoc architecture for the task as well as the relevance of additional information. The work of BIBREF21 offers interesting contributions in these two aspects, achieving good results for a range of tasks that include sarcasm detection, using an additional attention layer over a BiLSTM like ours, while also pre-training their model on an emoji-based dataset of 1246 million tweets.\nMoreover, we think that due to the complexity of the problem and the size of the training data in the context of deep learning better results could be obtained with additional resources for pre-training. Concretely, we see transfer learning as one option to add knowledge from a larger, related dataset could significantly improve the results BIBREF22 . Manually labeling and checking data is a vastly time-consuming effort. Even if noisy, collecting a considerably larger self-annotated dataset such as in BIBREF23 could potentially boost model performance.\n\nConclusion\nIn this paper we presented our system to SemEval-2018 shared task on irony detection in English tweets (subtask A), which leverages on a BiLSTM and pre-trained word embeddings for representation learning, without using human-engineered features. Our results showed that although the generalization capabilities of the model are limited, there are clear future directions to improve. In particular, access to more training data and the deployment of methods like transfer learning seem to be promising directions for future research in representation learning-based sarcasm detection.\n\nTable 2: Summary of the obtained best results on the valid/test sets.\n\nInquiry: What was the baseline model?",
"role": "user"
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"content": "{\"answer\": [\"a non-parameter optimized linear-kernel SVM that uses TF-IDF bag-of-word vectors as inputs\"], \"evidence\": [\"To compare our results, we use the provided baseline, which is a non-parameter optimized linear-kernel SVM that uses TF-IDF bag-of-word vectors as inputs. For pre-processing, in this case we do not preserve casing and delete English stopwords.\"]}",
"role": "assistant"
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science.pico_ner | science.pico_ner.1561 | [
{
"content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nRandomized , comparative study of the efficacy and safety of artesunate plus amodiaquine , administered as a single daily intake versus two daily intakes in the treatment of uncomplicated falciparum malaria . BACKGROUND Artesunate plus amodiaquine is a coblistered ACT , given as a single daily intake . It has been suggested that , in view of the number of tablets to be taken ( particularly in adults ) , it may be possible to improve compliance by allowing patients to divide the daily dose . The objectives of this randomized , comparative , open-label , multicentre study , conducted in Senegal and in Cameroon in 2005 , was to demonstrate the non-inferiority and to compare the safety of artesunate plus amodiaquine , as a single daily intake versus two daily intakes . METHODS A three-day treatment period and 14-day follow-up period was performed in any subject weighting more than 10 kg , presenting with a malaria paroxysm confirmed by parasitaemia > or = 1,000/microl , after informed consent . Patients were randomly allocated into one of the two regimens , with dosage according to bodyweight range . All products were administered by an authorized person , blinded to both the investigating physician and the biologist . The primary endpoint was an adequate response to treatment on D14 ( WHO definition ) . The two-sided 90 % confidence interval of the difference was calculated on intent to treat ( ITT ) population ; the acceptance limit for non-inferiority was 3 % . The safety was evaluated by incidence of adverse events . RESULTS Three-hundred and sixteen patients were included in the study . The two patient groups were strictly comparable on D0 . The adequate responses to treatment were similar for the two treatment regimens on D14 , PCR-corrected ( 99,4 % in the one-daily intake group versus 99,3 % in the comparative group ) . The statistical analyses demonstrated the non-inferiority of administering artesunate/amodiaquine as two intakes . The drug was well tolerated . The main adverse events were gastrointestinal disorders ( 2.5 % ) and pruritus ( 2.5 % ) ; safety profiles were similar in the two groups . CONCLUSION This pilot study confirms the efficacy and good tolerability of artesunate plus amodiaquine , administrated either in one or in two daily intakes .",
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"content": "{\"Intervention\": [\"amodiaquine\", \"artesunate plus amodiaquine\"], \"Outcome\": [\"adequate responses to treatment\", \"safety\", \"compliance\", \"well tolerated\", \"adequate response to treatment on D14\", \"gastrointestinal disorders\", \"safety of artesunate plus amodiaquine\", \"non-inferiority\", \"efficacy\", \"incidence of adverse events\"], \"Participant\": [\"uncomplicated falciparum malaria .\", \"Three-hundred and sixteen\"]}",
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science.pubmedqa_qa | science.pubmedqa_qa.130 | [
{
"content": "Analyze the given text and respond to the inquiry. Choose from: \"YES\", \"NO\", or \"MAYBE\".\n\nText:\n(BACKGROUND) Studies have identified clinical predictors to guide radiologic evaluation of the cervical spine in geriatric patients. We hypothesized that clinical predictors are not adequate in the identification of cervical spine fractures in geriatric blunt trauma patients with low-energy mechanism.\n(METHODS) A retrospective case-control study was performed on geriatric blunt trauma patients sustaining low-energy trauma from January 2000 to January 2006. A data form including 8 clinical predictors was completed for each group.\n(RESULTS) There were 35 study and 64 control patients identified. Both groups were similar in age (study 83.6 vs control 81.2) and injury severity score (study 9.06 vs control 9.61). Only neck tenderness exceeded the expected occurrence in the presence of a cervical spine injury (chi(2) = 18.1, P = .001) in just 45.5% of the study group.\n\nInquiry:\nCervical spine fractures in geriatric blunt trauma patients with low-energy mechanism: are clinical predictors adequate?\n\nResponse:",
"role": "user"
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{
"content": "NO",
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science.pubmedqa_qa | science.pubmedqa_qa.364 | [
{
"content": "Analyze the given text and respond to the inquiry. Choose from: \"YES\", \"NO\", or \"MAYBE\".\n\nText:\n(BACKGROUND) Deaths from injury and poisoning (suicide, accidents, undetermined deaths, and homicide) are the major cause of death among young men aged 15-39 years in England and Wales and have been increasing in recent years.AIM: To describe common characteristics among young men who die from injury and poisoning.\n(DESIGN) We employed a retrospective survey methodology to investigate factors associated with deaths by injury and poisoning among young men aged 15-39 years (n = 268) in Merseyside and Cheshire during 1995. Data were collected from Coroner's inquest notes and General Practitioner records.\n(MAIN RESULTS) The most common cause of death was poisoning by alcohol and drugs (29.1%, n = 78). A high proportion of cases were unemployed (39.4%, n = 106). Cases were also more likely to be single compared to the general population (74.2% vs 55.5%). Self-destructive behaviour was evident in 77% of deaths (n = 206).\n\nInquiry:\nInjury and poisoning mortality among young men--are there any common factors amenable to prevention?\n\nResponse:",
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{
"content": "YES",
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science.mslr2022_ms2_multidoc_summarization | science.mslr2022_ms2_multidoc_summarization.2005 | [
{
"content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: Assessment of patient outcome with the Minnesota Living with Heart Failure questionnaire: reliability and validity during a randomized, double-blind, placebo-controlled trial of pimobendan. Pimobendan Multicenter Research Group.\nSummary: To determine the reliability and validity of a patient outcome question naire for chronic heart failure , a r and omized , double-blind , placebo-controlled , 3-month trial of pimobendan , an investigational medication with inotropic and vasodilator activities , was performed . Evaluated were 198 ambulatory patients with primarily New York Heart Association ( NYHA ) class III heart failure from 20 referral centers . Baseline therapy included digoxin , diuretics and , in 80 % , a converting enzyme inhibitor . Oral pimobendan at 2.5 ( n = 49 ) , 5.0 ( n = 51 ) , or 10 ( n = 49 ) mg daily or matching placebo ( n = 49 ) was administered . The Minnesota Living with Heart Failure ( LIhFE ) question naire was a primary outcome measure , along with an exercise test . Interitem correlations identified subgroups of questions representing physical and emotional dimensions . Repeated baseline scores were highly correlated ( r = 0.93 ) , as were the physical ( r = 0.89 ) and emotional ( r = 0.88 ) dimension scores . Placebo did not have a significant effect with median ( 25th , 75th percentile ) changes from baseline scores of 1 ( -3 , 5 ) , 1 ( -2 , 3 ) , and 0 ( -1 , 2 ) , respectively ( all p values greater than 0.10 ) . The 5 mg dose significantly improved the total score , 7.5 ( 0 , 18 ; p = 0.01 ) and the physical dimension , 4 ( 0 , 8 ; p = 0.01 ) , compared with placebo . Changes in the total ( r = 0.33 ; p less than 0.01 ) and physical ( r = 0.35 ; p less than 0.01 ) scores were weakly related to changes in exercise times , but corresponded well with changes in patients ' ratings of dyspnea and fatigue . ( ABSTRACT TRUNCATED AT 250 WORDS\n\n\nReport 2:\nTitle: Self-Efficacy and Self-Reported Functional Status in Coronary Heart Disease: A Six-Month Prospective Study\nSummary: Objective We examine prospect ively the role of specific forms of self-efficacy in the physical and role function for patients with coronary heart disease after controlling for the effects of anxiety and depression . Methods A 6-month prospect i ve cohort study was conducted after cardiac catheterization of 198 HMO members , demonstrating clinical ly significant coronary disease . Coronary disease severity was assessed through cardiac catheterization ; physical function , role function , anxiety , depression , and self-efficacy were assessed through question naires . Results The Cardiac Self-Efficacy Scale had two factors ( maintain function and control symptoms ) with high internal consistency and good convergent and discriminant validity . In multiple regression models , the self-efficacy scales significantly predicted physical function , social function , and family function after controlling for baseline function , baseline anxiety , and other significant correlates . Conclusions Self-efficacy to maintain function and to control symptoms helps predict the physical function and role function , after accounting for coronary disease severity , anxiety , and depression in patients with clinical ly significant coronary disease . Interventions to improve self-efficacy may have a broader applicability in the heart disease population than previously appreciated\n\n\nReport 3:\nTitle: Change in health-related quality of life as a predictor of mortality in the older adults\nSummary: Purpose We examined whether changes in health-related quality of life ( HRQL ) predict subsequent mortality among the Spanish elderly . Methods Prospect i ve cohort study of 2,373 persons , representative of the Spanish population aged 60 and older . HRQL was measured in 2001 and 2003 using the SF-36 health question naire . Cox regression models were used to examine the association of changes in the physical and mental component summary ( PCS and MCS ) scores of HRQL from 2001 to 2003 with all-cause mortality through 2007 . Results Two hundred twelve deaths were ascertained from 2003 to 2007 . The hazard ratios for mortality across categories of PCS change were as follows : 2.12 ( 95 % confidence interval [ CI ] 1.39–3.24 ) for a > 10-point decline ; 1.51 ( 1.01–2.28 ) for a 6- to 10-point decline ; 1 for the reference category , a change of −5 to + 5 points ; 0.83 ( 0.51–1.34 ) for a 6- to 9-point improvement and 0.68 ( 0.42–1.09 ) for a > 10-point improvement ; P for linear trend < 0.001 . The associations between changes in the MCS and mortality showed the same direction , but were of a lower magnitude and attained statistical significance ( P < 0.05 ) only for a > 10-point decline in MCS . Conclusions Changes in HRQL predict mortality in the older adults . A decline in HRQL should alert to a worse vital prognosis and stimulate the search for the possible determinants of such decline\n\n\nReport 4:\nTitle: The PedsQL 4.0 as a pediatric population health measure: feasibility, reliability, and validity.\nSummary: BACKGROUND The application of health-related quality of life ( HRQOL ) as a pediatric population health measure may facilitate risk assessment and re source allocation , the tracking of community health , the identification of health disparities , and the determination of health outcomes from interventions and policy decisions . OBJECTIVE To determine the feasibility , reliability , and validity of the 23-item PedsQL 4.0 ( Pediatric Quality of Life Inventory ) Generic Core Scales as a measure of pediatric population health for children and adolescents . DESIGN Mail survey in February and March 2001 to 20 031 families with children ages 2 - 16 years throughout the State of California encompassing all new enrollees in the State 's Children 's Health Insurance Program ( SCHIP ) for those months and targeted language groups . METHODS The PedsQL 4.0 Generic Core Scales ( Physical , Emotional , Social , School Functioning ) were completed by 10 241 families through a statewide mail survey to evaluate the HRQOL of new enrollees in SCHIP . RESULTS The PedsQL 4.0 evidence d minimal missing responses , achieved excellent reliability for the Total Scale Score ( alpha = .89 child;.92 parent report ) , and distinguished between healthy children and children with chronic health conditions . The PedsQL 4.0 was also related to indicators of health care access , days missed from school , days sick in bed or too ill to play , and days needing care . CONCLUSION The results demonstrate the feasibility , reliability , and validity of the PedsQL 4.0 as a pediatric population health outcome . Measuring pediatric HRQOL may be a way to evaluate the health outcomes of SCHIP",
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"content": "Self-efficacy – HRQOL associations were similar in strength across age groups , regardless of presence of cardiovascular surgery , and among patients diagnosed with different forms of CVD .\nConclusions / Implication s : General and exercise-specific self-efficacy are moderately related with HRQOL among people with CVD after surgery or during rehabilitation .",
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.4231 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Process Flexibility: a Survey of Contemporary Approaches \nChapter Title: Related work \n1. Abstract of Cited Paper (BIB001): Flexibility has recently grown to be one of the major research topics in the area of workflow management. In this paper we focus on flexibility of workflow management applications, in contrast to flexibility of the implementation of workflow management systems. In a case study we show the necessity of flexibility in workflow management applications. This flexibility can roughly be classified into flexibility, which is provided by the workflow type, and flexibility, which goes beyond the scope of the workflow type and has additionally to be provided by a workflow management system. We call this flexibility by selection and flexibility by adaption, respectively. We point out that the modeling process as a main aspect of flexibility by adaption has to be treated as a CSCW scenario. The classification leads to a structured overall concept for flexibility in workflow management applications. \n2. Abstract of Cited Paper (BIB002): It is argued in this position paper that a workflow management system is potentially a powerful solution to bring more flexibility to the management of business processes. At the same time, the technical difficulties of integrating such systems in a business environment prevent this advantage to materialize up to this day. \n3. Abstract of Cited Paper (BIB003): Gil Regev, Pnina Soffer, Rainer Schmidt The aim of this working paper is to suggest a taxonomy of flexibility in business processes. The taxonomy should be generic. Hence, it relies on a minimal set of assumptions. We consider business processes as the dynamic aspect of an organization. Business processes can be addressed using the two layers of instance, and type. A process instance layer is an actual occurrence in the organization. The process type layer aggregates the instances as a template they all should fit. Business process flexibility Flexibility is the ability to yield to change without disappearing, i.e. without losing identity [ReWe05]. A business process is flexible if it is possible to change it without replacing it completely. Business process flexibility [Bide05], [Soff05], [Schm05] is the capability to implement changes in the business process type and instances by changing only those parts that need to be changed and keeping other parts stable. \n4. Abstract of Cited Paper (BIB004): 1 Visiting Professor, Department of Information Systems, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong http://fbweb.cityu.edu.hk/staff_info/staff_cv2.cfm?sno=kkumar 2 Professor of IS Research, RSM, Erasmus University, NL 3 Professor of IS, Florida International University, Miami, USA Associate Professor, Department of Information Systems, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong http://fbweb.cityu.edu.hk/scripts/staff_cv2.cfm?sno=ISMOHAN \n5. Abstract of Cited Paper (BIB005): The ability of businesses to develop is frequently hampered by difficulties in changing underlying software systems. An example is the need to change when business partnerships are formed, or dissolved. This article is concerned with the architecture of business process support systems in the context of change, and particularly with the need for such systems to facilitate software change. The viable system model (VSM) is a cybernetic model of organisations that change. It provides an inclusive architecture in which both operational and development components are described within an organisation. This article illustrates, through a business supply chain example, the use of the VSM as an architecture for flexible process support systems. This architecture is systemic and inclusive: it incorporates the ongoing development of both the business and its underlying software. Copyright � 2006 John Wiley & Sons, Ltd. \n6. Abstract of Cited Paper (BIB006): The assumption made in this article is that flexible processes require specific design methods. The choice of a method for modelling flexible processes depends on many criteria and situations that we gathered in a benchmarking framework. The user can use it as a decision support tool to choose the appropriate method in order to design flexible business processes in a given project situation. This framework also includes managerial concerns such as the time and the budget of the project. We use three enterprise modelling techniques to illustrate how to use the proposed framework. Copyright © 2006 John Wiley & Sons, Ltd. \n7. Abstract of Cited Paper (BIB007): Enterprise survival is about maintaining an identity that is separate from other enterprises. We define flexibility as the ability to change without losing identity. The identity of an enterprise can be analyzed as a set of norms and beliefs about these norms held by its stakeholders, such as customers, employees, suppliers, and investors. Business processes and their support systems maintain invariants that are the result of compromises between the often conflicting norms and beliefs of these stakeholders. We formalize these invariants as values in a state space. Identifying a minimum set of invariants provides a basis for defining flexible processes and support systems. We illustrate the use of this framework with production business process support (BPS) systems. \n8. Abstract of Cited Paper (BIB008): Effective business processes must be able to accommodate changes to the environment in which they operate, e.g., new laws, changes in business strategy. The ability to encompass such changes is termed process flexibility. In this paper, we take a deeper look into the various ways in which flexibility can be achieved and propose a comprehensive taxonomy of these methods which identifies both the manner in which each of them is facilitated, and also the various configuration options and alternatives that exist in each case. This taxonomy is subsequently used to evaluate a selection of process-aware information systems and identify their potential to deploy flexible business processes.\n\nReview Chapter:",
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"content": "The need for process flexibility has long been recognised BIB002 BIB003 in the workflow and process technology communities as a critical quality of effective business processes in order for organisations to adapt to changing business circumstances. It ensures that the \"fit\" between actual business processes and the technologies that support them are maintained in changing environments. The notion of flexibility is often viewed in terms of the ability of an organisation's processes and supporting technologies to adapt to these changes BIB006 BIB007 . An alternate view advanced by Regev and Wegmann BIB008 is that flexibility should be considered from the opposite perspective i.e., in terms of what stays the same not what changes. Indeed, a process can only be considered to be flexible if it is possible to change it without needing to replace it completely BIB004 . Hence flexibility is effectively a balance between change and stability that ensures that the identity of the process is retained BIB008 . There have been a series of proposals for classifying flexibility, both in terms of the factors which motivate it and the ways in which it can be achieved within business processes. Snowdon et al. BIB006 identify three causal factors: type flexibility (arising from the diversity of information being handled), volume flexibility (arising from the amount of information types) and structural flexibility (arising from the need to operate in different ways). Soffer differentiates between short-term flexibility, which involves a temporary deviation from the standard way of working, and long-term flexibility, which involves changes to the usual way of working. Kumar and Narasipuram BIB005 distinguish pre-designed flexibility which is anticipated by the designer and forms part of the process definition and just-in-time responsive flexibility which requires an \"intelligent process manager\" to deal with the variation as it arises at runtime. Carlsen et al. BIB001 identify a series of desirable flexibility features for workflow systems based on an examination of five workflow offerings using a quality evaluation framework. Heinl et al. BIB002 propose a classification scheme with distinct approaches -flexibility by selection, where a variety of alternative execution paths are designed into a process, and flexibility by adaption, where a workflow is \"adapted\" (i.e., modified) to meet with the new requirements. Two distinct approaches to achieving each of these approaches are recognised: flexibility by selection can be implemented either by advance modelling (before execution time) or late modelling (during execution time) where as flexibility by adaption can be handled either by type or instance adaption. Van der Aalst and Jablonski [2] adopt a similar strategy for supporting flexibility. Moreover they propose a scheme for classifying workflow changes in detail based on six criteria: (1) reason for change, (2) effect of change, (3) perspectives affected, (4) kind of change, (5) when are changes allowed and BIB001 what to do with existing process instances. Regev et al. BIB004 provide an initial attempt at defining a taxonomy of the concepts relevant to business process flexibility. This taxonomy has three orthogonal dimensions: the abstraction level of the change, the subject of the change and the properties of the change. Whilst it incorporates elements of the research initiatives discussed above, it is not comprehensive in form and does not describe the relationships that exist between these concepts or link them to possible realisation approaches. The individual flexibility types discussed in this paper are informed by a multitude of research initiatives in the workflow and BPM fields. It is not possible to discuss these in detail in the confines of this paper, however there is a detailed literature review of the area in BIB009 .",
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.911 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nWe consider multi-agent transport task problems where, e.g. in a factory setting, items have to be delivered from a given start to a goal pose while the delivering robots need to avoid collisions with each other on the floor. We introduce a Task Conflict-Based Search (TCBS) Algorithm to solve the combined delivery task allocation and multi-agent path planning problem optimally. The problem is known to be NP-hard and the optimal solver cannot scale. However, we introduce it as a baseline to evaluate the sub-optimality of other approaches. We show experimental results that compare our solver with different sub-optimal ones in terms of regret.\n\nCited Works Summary:\n[1]: The multi-agent path-finding (MAPF) problem has recently received a lot of attention. However, it does not capture important characteristics of many real-world domains, such as automated warehouses, where agents are constantly engaged with new tasks. In this paper, we therefore study a lifelong version of the MAPF problem, called the multi-agent pickup and delivery (MAPD) problem. In the MAPD problem, agents have to attend to a stream of delivery tasks in an online setting. One agent has to be assigned to each delivery task. This agent has to first move to a given pickup location and then to a given delivery location while avoiding collisions with other agents. We present two decoupled MAPD algorithms, Token Passing (TP) and Token Passing with Task Swaps (TPTS). Theoretically, we show that they solve all well-formed MAPD instances, a realistic subclass of MAPD instances. Experimentally, we compare them against a centralized strawman MAPD algorithm without this guarantee in a simulated warehouse system. TP can easily be extended to a fully distributed MAPD algorithm and is the best choice when real-time computation is of primary concern since it remains efficient for MAPD instances with hundreds of agents and tasks. TPTS requires limited communication among agents and balances well between TP and the centralized MAPD algorithm.\n\n[2]: Robotics technology has recently matured sufficiently to deploy autonomous robotic systems for daily use in several applications: from disaster response to environmental monitoring and logistics. In such applications, robots must establish collaborative interactions so to achieve their individual and collective goals and a key problem is for robots to make individual decisions so to optimize a system wide objective function. This problem is typically referred to as coordination. In this paper, we first describe modern optimization techniques for coordination in multiRobot systems. Specifically, we focus on approaches that are based on algorithms widely used to solve graphical models and constraint optimization problems, such as the max-sum algorithm. We then analyze the coordination problem faced by a set of robots operating in a warehouse logistic application. In this context robots must transport items from loading to unloading bays so to complete packages to be delivered to customers. Robots must cooperate to maximize the number of packages completed in the unit of time. To this end a crucial component is to avoid interferences when moving in the environment. We show how such problem can be formalized as a Distributed Constrained Optimization problem and we provide a solution based on the binary max-sum algorithm. Finally, we provide a quantitative evaluation of our approach in a simulated scenario using standard robotics tools (ROS and Gazebo).\n\n[3]:",
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"content": "Similar problems have recently also been formulated by [2] , [1] and [3] for domains that do not involve transport tasks as we consider them. Both find interesting sub-optimal solutions for TPTS [1] , based on DCOP [2] and using answer set programming (ASP) [3] . All of these approaches may solve the sub-problems optimally but they do not solve the combined problem optimally. This would require taking the implications that the task assignment makes into the path finding problem and vice versa.",
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science.scientific_papers_summarization_single_doc_arxiv | science.scientific_papers_summarization_single_doc_arxiv.6117 | [
{
"content": "You will be presented with the full text of a scientific research paper. Write an abstract summarizing the key points. Your response should contain only the abstract without any other text.\n\nArticle text:\nthere are geological evidence that earth had to face multiple episodes of global ( or quasi - global ) glaciation , at the end of the archean 2.45 - 2.22 gyrs ago and during the neoproterozoic era 710 and 650 myears ago @xcite .\nit is widely believed that the carbonate@xmath0silicate cycle @xcite was the main agent to trigger deglaciations on past earth .\nin particular , on a completely frozen planet , also called hard snowball , the weathering of co@xmath1 is stopped ; continuous volcanic outgassing builds up atmospheric co@xmath1 , which warms up the climate until liquid water is produced in the equatorial regions . by extension\n, this mechanism may be crucial to stabilize the climate of earth - like exoplanets .\nit is even central for the definition of the classical habitable zone @xcite , which assumes that planets can build up co@xmath1 atmospheres ( as massive as wanted ) suitable for the stability of surface liquid water .\nplanets near the outer edge of the habitable zone may suffer , as earth did , episodes of total glaciation .\nrecent work by @xcite has even shown that , in case of planets lacking land vascular plants , temperate climates may not be stable , because at high co@xmath1 partial pressure , the increased weathering rate does not allow temperate stable solutions .\nthis effect , enhanced for planets weakly irradiated by their star , may drive systematically earth - like exoplanets toward episodes of glaciation . can earth - like planets in the habitable zone of their star always escape from episodes of glaciation ? in this work ,\nwe use 3d - global climate model simulations of snowball planets to study the ability of the increased co@xmath1 greenhouse effect resulting from the carbonate - silicate cycle to drive them out of glaciation . as\nthe co@xmath1 outgassed by volcanoes accumulate in the atmosphere , the temperature of condensation of co@xmath1 can exceed the surface temperature of the poles .\nthis lead to the trapping of extra outgassed co@xmath1 , forming permanent co@xmath1 polar ice caps , and therefore seriously limits the efficiency of the carbonate@xmath0silicate cycle .\nthis possibility has already been suggested by @xcite and @xcite , but has never been explored yet .\nwe propose in this paper a detailed study of this scenario .\nwe use in this paper the 3-dimensions lmd generic global climate model to study the deglaciation of earth - like planets orbiting circularly around a sun - like star ( sun spectrum and luminosity ) in response to increasing amount of atmospheric co@xmath1 ( from 0.01 to 3 bars ) , and for orbital distances ranging from 1.10 to 1.45 astronomical units ( au ) .\ndetailed information on the model can be found in appendix [ appen_lmd_model ] .\nour simulations were designed to represent completely frozen earth - like planet characteristics .\nthese include the radius ( 6370 km ) , the gravity field ( 9.81 m s@xmath4 ) , the obliquity ( 23.5@xmath8 ) and the rotation speed ( 7.28@xmath1310@xmath14 rad s@xmath15 ) .\nthe roles of obliquity , planetary mass and rotation rate on the ability of planets to escape glaciation episodes are discussed in sections [ null_obliquity_section ] and [ sensitivity ] .\neventually , most of the simulations were performed for a uniformly flat topography .\nthe effect of topography is discussed in section [ topography ] .\nall the simulations performed in this study were forced initially in a cold and dry state , which assumes : 1 . a uniform and complete ice cover .\n2 . atmospheric temperatures arbitrarily fixed to 230 kelvins everywhere .\nno water vapor , no clouds .\ndepending on co@xmath1 partial pressure , obliquity , or parameterization of clouds , the simulations evolve in different steady state climate regimes that are discussed in the next section .\n[ cols= \" < , < \" , ] \\1 . melting , freezing , condensation , evaporation , sublimation and precipitation of h@xmath1o physical processes are all included in the model . in the atmosphere\n, water vapor can condense into water ice particles clouds . at the surface\n, we fix the h@xmath1o ice albedo at 0.6 and we use an emissivity of 1 . \\2 . in our model , co@xmath1 can condense to form co@xmath1 ice clouds and surface frost if the temperature drops below the saturation temperature .\natmospheric co@xmath1 ice particles are sedimented and thus can accumulate at the surface .\nthe co@xmath1 ice layer formed at the surface can sublimate and recycle the co@xmath1 in the atmosphere .\nthe co@xmath1 ice on the surface contributes to the surface albedo calculation : if the co@xmath1 ice layer exceeds a threshold value of 1 mm thickness , then the local surface albedo is set immediately to the albedo of co@xmath1 ice ( 0.6 in this work ) . on mars ,\nthe albedo of co@xmath1 ice can substantially vary @xcite with insolation and presence of dust . without dust ,\nthe albedo can become very high so that 0.6 is probably a lower estimate .\nfor co@xmath1 ice , we use an emissivity of 0.9 .\nthe radiative effect of co@xmath1 ice clouds is discussed in details in section [ co2_cloud_section ] physical parameters used for both co@xmath1 and h@xmath1o ices are summarized in table [ param_ices ] .\nwhat happens once co@xmath1 ice caps have reached their maximum size , as calculated in section [ max_reservoir_co2 ] ? using calculations , we show in the following lines that , depending on few parameters , the co@xmath1 ice caps when full may ( or may not ) be stable . the total mass of co@xmath1 available at the surface and in the atmosphere is : @xmath16 with a the area of the co@xmath1 ice caps , s the total area of the surface ( i.e. 4@xmath17r@xmath18 ) and @xmath19 the thickness of the co@xmath1 ice caps averaged over a. when co@xmath1 ice caps are full , @xmath20 .\nlet s assume that the system initially with full co@xmath1 ice caps is sightly perturbated from @xmath21 to @xmath22 . by conservation of co@xmath1 mass ,\nthe new mass of co@xmath1 ice caps is @xmath23 $ ] = @xmath24\\footnote{hereafter , ' [ ' and ' ] ' are used to bracket variables . }\n$ ] .\nwe know first from gcm simulations that the area of the ice caps a is not a monotonic function of @xmath33 ( see figure [ condens_plots ] ) .\ninstead , as @xmath33 grows , @xmath34 should be positive and then at some point become negative .\nfigure [ condens_plots]b ( 23.5@xmath35 obliquity , inactive co@xmath1 clouds ) tells us that the maximum of a(@xmath33 ) should roughly lie at 1 bar in this specific configuration .\nit is possible to derive an analytical - complicated yet - expression of @xmath36 using the relation that served to compute figure [ 2d_basal_melting ] .\nit tells us that , whatever the configuration , @xmath36 is in fact always negative , because as pco@xmath1 increases , surface temperature also increases , which limits the thickness of co@xmath1 ice caps shows that the mean thickness of co@xmath1 ice caps is proportional to the maximum thickness calculated by basal melting . ] ( see equation [ conductivity ] ) . for the experiment described in previous section ( 1.30 au\n, 23.5@xmath35 obliquity , inactive co@xmath1 clouds , co@xmath1 partial pressure of 1 bar ) , we assume @xmath37 and we have therefore ( with @xmath38 , see section [ co2_rad_extent ] ) : @xmath39 from our calculations , this condition is valid for internal heat flux lower than 80 mw m@xmath4 .\nit means that , for internal heat flux lower than 80 mw m@xmath4 : ( 1 ) co@xmath1 ice caps when full would not be stable , and ( 2 ) the maximum amount of co@xmath1 that can be trapped in the @xmath40surface , atmosphere@xmath41 system is attained for pco@xmath1 lower than 1 bar . for internal heat flux\nhigher than 80 mw m@xmath4 , because a significant fraction of co@xmath1 is in the gaseous phase : ( 1 ) co@xmath1 ice caps when full would be stable ( until @xmath34 term becomes significant ) , and ( 2 ) the maximum amount of co@xmath1 trapped in the @xmath40surface , atmosphere@xmath41 system occurs for pco@xmath1 larger than 1 bar . ,\nb. , forget , f. , wordsworth , r. , leconte , j. , millour , e. , codron , f. , and spiga , a. ( 2013 ) . exploring the faint young sun problem and the possible climates of the archean earth with a 3-d gcm .\n, 118:414431 . , f. , musat , i. , bony , s. , braconnot , p. , codron , f. , dufresne , j .- l . ,\nfairhead , l. , filiberti , m .- a .\n, friedlingstein , p. , grandpeix , j .- y . , krinner , g. , levan , p. , li , z .- x . , and lott , f. ( 2006 ) . .\n, 27:787813 . , l. s. , gordon , i. e. , babikov , y. , barbe , a. , benner , d. c. , bernath , p. f. , birk , m. , bizzocchi , l. , boudon , v. , brown , l. r. , campargue , a. , chance , k. , coudert , l. h. , devi , v. m. , drouin , b. j. , fayt , a. , flaud , j .-\nm . , gamache , r. r. , harrison , j. j. , hartmann , j. m. , hill , c. , hodges , j. t. , jacquemart , d. , jolly , a. , lamouroux , j. , le roi , r. j. , li , g. , long , d. a. , lyulin , o. m. , mackie , c. j. , massie , s. t. , mikhailenko , s. , mller , h. s. p. , naumenko , o. v. , nikitin , a. v. , orphal , j. , perevalov , v. i. , perrin , a. , polovtseva , e. r. , richard , c. , smith , m. a. h. , starikova , e. , sung , k. , tashkun , s. a. , tennyson , j. , toon , g. c. , tyuterev , v. g. , and wagner , g. ( 2013 ) . .\n, 130:455 .\ntoon , o. b. , mckay , c. p. , ackerman , t. p. , and santhanam , k. ( 1989 ) .\nrapid calculation of radiative heating rates and photodissociation rates in inhomogeneous multiple scattering atmospheres .\n, 94:16,28716,301 .",
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"content": "it is widely believed that the carbonate@xmath0silicate cycle @xcite is the main agent - through volcanism - to trigger deglaciations by co@xmath1 greenhouse warming on earth and on earth - like planets when they get in frozen state . \n here we use a 3d global climate model ( gcm ) to simulate the ability of planets initially completely frozen to escape from glaciation episodes by accumulating enough gaseous co@xmath1 . \n the model includes co@xmath1 condensation and sublimation processes and the water cycle . \n we find that planets with earth - like characteristics ( size , mass , obliquity , rotation rate , ... ) orbiting a sun - like star may never be able to escape from a glaciation era , if their orbital distance is greater than @xmath2 1.27 astronomical units ( flux @xmath3 847 w m@xmath4 , s@xmath5 @xmath3 0.62 ) , because co@xmath1 would condense at the poles here the cold traps forming permanent co@xmath1 ice caps . \n this limits the amount of co@xmath1 in the atmosphere and thus its greenhouse effect . \n furthermore , our results indicate that for ( 1 ) high rotation rates ( p@xmath624 h ) , ( 2 ) low obliquity ( [email protected]@xmath8 ) , ( 3 ) low background gas partial pressures ( @xmath91bar ) , and ( 4 ) high water ice albedo ( h@xmath1o [email protected] ) , this critical limit could occur for significantly lower equivalent distance ( or higher insolation ) . for each possible configuration \n , we show that the amount of co@xmath1 that can be trapped in the polar caps depends on the efficiency of co@xmath1 ice to flow laterally as well as its graviational stability relative to subsurface water ice . \n the flow of co@xmath1 ice from polar regions to the equator is mostly controlled by the bottom temperature , and hence by the internal heat flux of the planet . \n we find that a frozen earth - like planet located at 1.30 au of a sun - like star could store as much as 1.5/4.5/15 bars of dry ice at the poles , for internal heat fluxes of 100/30/10 mw m@xmath4 . \n but these amounts are in fact lower limits . for planets with a significant water ice cover , \n we show that co@xmath1 ice deposits should be gravitationnally unstable . \n they get burried beneath the water ice cover in very short timescales of 10@xmath11 - 10@xmath12 yrs , mainly controlled by the viscosity of water ice . for water ice cover exceeding about 300 meters , \n we show that the co@xmath1 would be permanently sequestred underneath the water ice cover , in the form of co@xmath1 liquids , co@xmath1 clathrate hydrates and/or dissolved in subglacial water reservoirs ( if any ) . \n this would considerably increase the amount of co@xmath1 trapped and further reduce the probability of deglaciation . \n our results may have implications for the search for life - suitable extrasolar planets orbiting in the habitable zone of sun - like stars .",
"role": "assistant"
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science.scitldr_aic | science.scitldr_aic.1391 | [
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"content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nA weakly supervised learning based clustering framework is proposed in this paper.\nAs the core of this framework, we introduce a novel multiple instance learning task based on a bag level label called unique class count (ucc), which is the number of unique classes among all instances inside the bag.\nIn this task, no annotations on individual instances inside the bag are needed during training of the models.\nWe mathematically prove that with a perfect ucc classifier, perfect clustering of individual instances inside the bags is possible even when no annotations on individual instances are given during training.\nWe have constructed a neural network based ucc classifier and experimentally shown that the clustering performance of our framework with our weakly supervised ucc classifier is comparable to that of fully supervised learning models where labels for all instances are known.\nFurthermore, we have tested the applicability of our framework to a real world task of semantic segmentation of breast cancer metastases in histological lymph node sections and shown that the performance of our weakly supervised framework is comparable to the performance of a fully supervised Unet model.\nIn machine learning, there are two main learning tasks on two ends of scale bar: unsupervised learning and supervised learning.\nGenerally, performance of supervised models is better than that of unsupervised models since the mapping between data and associated labels is provided explicitly in supervised learning.\nThis performance advantage of supervised learning requires a lot of labelled data, which is expensive.\nAny other learning tasks reside in between these two tasks, so are their performances.\nWeakly supervised learning is an example of such tasks.\nThere are three types of supervision in weakly supervised learning: incomplete, inexact and inaccurate supervision.\nMultiple instance learning (MIL) is a special type of weakly supervised learning and a typical example of inexact supervision (Zhou, 2017) .\nIn MIL, data consists of bags of instances and their corresponding bag level labels.\nAlthough the labels are somehow related to instances inside the bags, the instances are not explicitly labeled.\nIn traditional MIL, given the bags and corresponding bag level labels, task is to learn the mapping between bags and labels while the goal is to predict labels of unseen bags (Dietterich et al., 1997; Foulds & Frank, 2010) .\nIn this paper, we explore the feasibility of finding out labels of individual instances inside the bags only given the bag level labels, i.e. there is no individual instance level labels.\nOne important application of this task is semantic segmentation of breast cancer metastases in histological lymph node sections, which is a crucial step in staging of breast cancer (Brierley et al., 2016) .\nIn this task, each pathology image of a lymph node section is a bag and each pixel inside that image is an instance.\nThen, given the bag level label that whether the image contains metastases or not, the task is to label each pixel as either metastases or normal.\nThis task can be achieved by asking experts to exhaustively annotate each metastases region in each image.\nHowever, this exhaustive annotation process is tedious, time consuming and more importantly not a part of clinical workflow.\nIn many complex systems, such as in many types of cancers, measurements can only be obtained at coarse level (bag level), but information at fine level (individual instance level) is of paramount importance.\nTo achieve this, we propose a weakly supervised learning based clustering framework.\nGiven a dataset consisting of instances with unknown labels, our ultimate objective is to cluster the instances in this dataset.\nTo achieve this objective, we introduce a novel MIL task based on a new kind of bag level label called unique class count (ucc) , which is the number of unique classes or the number of clusters among all the instances inside the bag.\nWe organize the dataset into non-empty bags, where each bag is a subset of individual instances from this dataset.\nEach bag is associated with a bag level ucc label.\nThen, our MIL task is to learn mapping between the bags and their associated bag level ucc labels and then to predict the ucc labels of unseen bags.\nWe mathematically show that a ucc classifier trained on this task can be used to perform unsupervised clustering on individual instances in the dataset.\nIntuitively, for a ucc classifier to count the number of unique classes in a bag, it has to first learn discriminant features for underlying classes.\nThen, it can group the features obtained from the bag and count the number of groups, so the number of unique classes.\nOur weakly supervised clustering framework is illustrated in Figure 1 .\nIt consists of a neural network based ucc classifier, which is called as Unique Class Count (U CC) model, and an unsupervised clustering branch.\nThe U CC model accepts any bag of instances as input and uses ucc labels for supervised training.\nThen, the trained U CC model is used as a feature extractor and unsupervised clustering is performed on the extracted features of individual instances inside the bags in the clustering branch.\nOne application of our framework is the semantic segmentation of breast cancer metastases in lymph node sections (see Figure 4) .\nThe problem can be formulated as follows.\nThe input is a set of images.\nEach image (bag) has a label of ucc1 (image is fully normal or fully metastases) or ucc2 (image is a mixture of normal and metastases).\nOur aim is to segment the pixels (instances) in the image into normal and metastases.\nA U CC model can be trained to predict ucc labels of individual images in a fully supervised manner; and the trained model can be used to extract features of pixels (intances) inside the images (bags).\nThen, semantic segmentation masks can be obtained by unsupervised clustering of the pixels (each is represented by the extracted features) into two clusters (metastases or normal).\nNote that ucc does not directly provide an exact label for each individual instance.\nTherefore, our framework is a weakly supervised clustering framework.\nFinally, we have constructed ucc classifiers and experimentally shown that clustering performance of our framework with our ucc classifiers is better than the performance of unsupervised models and comparable to performance of fully supervised learning models.\nWe have also tested the performance of our model on the real world task of semantic segmentation of breast cancer metastases in lymph node sections.\nWe have compared the performance of our model with the performance of popular medical image segmentation architecture of U net (Ronneberger et al., 2015) and shown that our weakly supervised model approximates the performance of fully supervised U net model 1 .\nHence, there are three main contributions of this paper:\n1. We have defined unique class count as a bag level label in MIL setup and mathematically proved that a perfect ucc classifier, in principle, can be used to perfectly cluster the individual instances inside the bags.\n2. We have constructed a neural network based ucc classifier by incorporating kernel density estimation (KDE) (Parzen, 1962) as a layer into our model architecture, which provided us with end-to-end training capability.\n3. We have experimentally shown that clustering performance of our framework is better than the performance of unsupervised models and comparable to performance of fully supervised learning models.\nThe rest of the paper is organized such that related work is in Section 2, details of our weakly supervised clustering framework are in Section 3, results of the experiments on MNIST, CIFAR10 and CIFAR100 datasets are in Section 4, the results of the experiments in semantic segmentation of breast cancer metastases are in Section 5, and Section 6 concludes the paper.\nIn this paper, we proposed a weakly supervised learning based clustering framework and introduce a novel MIL task as the core of this framework.\nWe defined ucc as a bag level label in MIL setup and mathematically proved that a perfect ucc classifier can be used to perfectly cluster individual instances inside the bags.\nWe designed a neural network based ucc classifer and experimentally showed that clustering performance of our framework with our ucc classifiers are better than the performance of unsupervised models and comparable to performance of fully supervised learning models.\nFinally, we showed that our weakly supervised unique class count model, U CC segment , can be used for semantic segmentation of breast cancer metastases in histological lymph node sections.\nWe compared the performance of our model U CC segment with the performance of a U net model and showed that our weakly supervised model approximates the performance of fully supervised U net model.\nIn the future, we want to check the performance of our U CC segment model with other medical image datasets and use it to discover new morphological patterns in cancer that had been overlooked in traditional pathology workflow.",
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"content": "A weakly supervised learning based clustering framework performs comparable to that of fully supervised learning models by exploiting unique class count.",
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.11077 | [
{
"content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nsubfoveal choroidal neovascularization ( cnv ) is a leading cause of visual loss in the geriatric population .\nperipapillary cnv membranes ( ppcnvm ) have been associated with multiple etiologies [ 2 , 3 ] .\nwhile ppcnvm , associated with optic nerve head drusen ( onhd ) , is a well - described entity in the pediatric population , it is not reported in the adult population ( pubmed search november 29 , 2014 ) .\nherein , we report a case of ppcnvm associated with onhd impacting the macula , which required treatment with an anti - vascular endothelial growth factor ( anti - vegf ) agent .\na 75-year - old male presented with a chief complaint of blurry vision in the right eye ( od ) of 3 months duration .\nthe patient 's past medical and ocular history were significant only for herpes zoster ophthalmicus on the left side years prior . on examination ,\nhis treatment was initiated with 3 ranibizumab injections , administered every 5 weeks , without any impact on the amount of subfoveal fluid .\nsubsequent treatment with a single aflibercept injection resulted in complete resolution of subfoveal fluid ( fig .\nthe patient 's visual acuity has been stable for 15 months with no recurrence of subfoveal fluid .\nthe association of onhd with macular threatening ppcnvm and its favorable response to anti - vegf agents is already known in the pediatric population [ 2 , 3 , 4 ] .\nthe natural course of ppcnvm is variable and unpredictable ; however , macular threatening ppcnvm requires treatment .\nwhile the role of anti - vegf therapy as a treatment for this specific subset of choroidal neovascular membranes was not studied as part of the major neovascular age - related macular degeneration ( amd ) studies , its use for the treatment of other forms of cnv is well established .\nbevacizumab , ranibizumab and aflibercept are 3 anti - vegf agents used for the treatment of neovascular amd .\nranibizumab and bevacizumab are monoclonal antibodies that selectively bind to vegfa [ 7 , 8 ] .\naflibercept , however , is a fusion protein composed of the binding domains of vegf receptor 1 , vegf receptor 2 , and the fc portion of igg that selectively binds to vegfa , vegfb , and platelet growth factor ( pigf ) .\naflibercept has been shown to have a greater affinity for vegf and a longer half - life than both ranibizumab and bevacizumab .\nthe comparison of age - related macular degeneration treatment trials ( catt ) demonstrated equivalence in efficacy between ranibizumab and bevacizumab in the treatment of wet amd , as did the inhibition of vegf in the age - related choroidal neovascularization ( ivan ) trial . the vegf trap - eye : investigation of efficacy and safety in wet amd ( view 1 and view 2 ) trials similarly demonstrated an equivalence between ranibizumab and aflibercept in treating wet amd .\ninadequate response to 1 anti - vegf agent is not uncommon when treating cnv , and , on occasion , changing to an alternate anti - vegf agent has demonstrated efficacy . currently , there are no studies that have investigated the response of aflibercept in treatment - resistant peripapillary cnv , likely due to the rarity of this presentation .\nprevious studies have concluded that aflibercept may provide an efficacious therapeutic response in cases of cnv due to amd that initially failed to respond to bevacizumab and ranibizumab .\nfurther studies are required to investigate whether aflibercept is an equally efficacious therapeutic alternative to treatment resistant peripapillary cnv . based upon our experience , an individualized treatment plan for adult patients with ppcnvm , associated with onhd ,",
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"content": "optic nerve head drusen can be associated with peripapillary choroidal neovascularization , in both the pediatric and adult population . \n these membranes can involve the macula , causing significant visual loss . herein , we present a case that required treatment with an anti - vegf agent . \n the patient failed to respond to the initial agent , but subsequently responded to a change of agent . \n adult patients with macular degeneration involving peripapillary choroidal neovascularization associated with optic nerve head drusen may require individualized treatment plans .",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.46224 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nCytotoxic Benzophenanthridine and Furoquinoline Alkaloids from Zanthoxylum buesgenii (Rutaceae)\n\nContent Extracts:\nBackground\n<p>Formerly named Fagara buesgenii, Zanthoxylum buesgenii is a shrub or small tree of about 4 m height with leaves about 20 to 75 cm long [1,2]. In Sierra Leone, roots are used as remedy to cure venereal diseases, arthritis, and rheumatism whereas leaves and barks are employed to treat leprosy and to relieve pain [2]. In South West Region of Cameroon, Z. buesgenii locally called \"Mbem\" by Lewoh-Lebang community, is orally given to patients as aphrodisiac decoction and to increase sperm count [3]. Previous chemical studies on Zanthoxylum species reported the identification of lignans, coumarins, diterpenes, sesquiterpenes, steroids, alkaloids [4] and benzopropanoids [5]. Interestingly, alkaloids represent the largest group of secondary metabolites obtained from the genus Zanthoxylum with structurally diverse scaffolds including oxoaporphines [6], aporphines, quinolinones, furoquinolines [4], indolopyridoquinazolines, β-carbolines, and benzophenanthridines [4,7]. Besides bioactivities such as trypanocidal [8], antileishmanial [9], antimycobacterial [10] effects, most of these alkaloids have shown from moderate to significant cytotoxicity against several cancer cell lines [11-13]. Therefore, we investigated the alkaloidal constituents of Z. buesgenii. In the course of the study, two benzophenanthridines were identified among them one new. Alongside, three known furoquinolines were also obtained.</p><p>We herein report the structure elucidation of the new compound and the cytotoxic potentiality of the identified secondary metabolites against a series of multidrugs-resistant cancer cell lines.</p>\n\nChemistry\n<p>A Dragendorff reagent-guided isolation of the aerial part of Zanthoxylum buesgenii yielded five alkaloids identified as benzophenanthridines (1 and 2) and furoquinolines (3–5).</p>\n\n\n<p>NMR data of compound 1 (C\n5\nD\n5\nN, 400 MHZ)</p><p>δH, and δC are chemical shifts of protons and carbons, respectively in ppm.</p><p>COSY (bold) and HMBC (arrow) correlations of compound 1.</p><p>NOESY correlations of compound 1.</p><p>Structure of the isolated compounds.</p>\n\nChemistry\n<p>The known compounds (Figure 3) were identified as isofagaridine 2 [15], maculine 3 [16], kokusaginine 4 [17] and teclearverdoornine 5 [18] based on their NMR data and by comparison with those previously reported.</p>\n\n\n<p>Cytotoxicity of the studied compounds towards sensitive and drug-resistant cancer cell lines and normal cells as determined by the resazurin assay</p>\n\nConclusions\n<p>The purification of the aerial part of Z. buesgenii monitored by TLC and Dragendorff reagent as alkaloids indicator led to the isolation of one new benzophenanthridine (buegenine, 1) along with four known metabolites namely a benzophenanthridine (isofagaridine, 2) and three furoquinolines (maculine 3, kokusaginine 4, and teclearverdoornine 5). Compounds (1–4) in substantial amount were evaluated for cytotoxicity activities and the obtained secondary metabolites showed from moderate to strong bioactivities. The observed activities corroborated those previously reported on similar benzophenanthridine alkaloids [19-22] indicating that compounds 1 and 2 can be chemically explored to develop other chemotherapeutic agents.</p>\n\nGeneral procedure\n<p>Optical rotation: JASCO P-2000 polarimeter; IR (KBr disc): JASCO A-302 spectrophotometer; HR-ESI-MS: JOEL MS apparatus; 1 and 2D NMR: Brüker DRX-400 MHz with TMS as internal reference. Thin layer chromatography (TLC) was performed over silica gel aluminum plates 60 F254. Silica gel 40–63 μm were used for columns chromatography (CC) separation. The melting point (m.p.) was measured by an Electro thermal IA 9000 digital melting point apparatus: uncorrected.</p>\n\nPlant collection\n<p>The aerial of Z. buesgenii was collected in Buea, South West region of Cameroon, in January 2014. Voucher specimens (BUD 0510) were deposited in the Herbarium of the Botany Department of the University of Dschang, Cameroon.</p>\n\nExtraction and isolation\n<p>The dried aerial part (1.8 kg) of Z. buesgenii was cut into small pieces, crushed and the powder was extracted for two days with a sufficient volume of methylene chloride (DCM)/MeOH (1:1). The solid residue was further extracted with MeOH for 24 h. Both solutions were pooled together and evaporated in vacuo to afford 50 g of crude extract. This latter was subjected to a liquid–solid extraction using successively n-hexane (hex), ethyl acetate (EA) and MeOH as the liquid part. Hex and EA fractions were pooled together based on the TLC profile to give fraction A (35 g). TLC of fractions A and B (MeOH) sprayed with Dragendorff's reagent, revealed the presence of alkaloids in A. Therefore, this latter was purified by silica gel CC eluted with hex, hex/EA (gradient) and EA yielding six sub-fractions (A1-A6). Maculine (3, 1.5 mg) was isolated from A2 eluted with hex/EA (95:5). A3 [5.2 g, hex/EA (3:1)] was further chromatographed on silica gel column eluted with hex/EA in gradient conditions. 60 sub-fractions were collected and isofagaridine (2, 3.1 mg) was filtered from the sub-fractions 10–15 eluted with hex/EA (9:1) while kokusaginine (4, 5.1 mg) was obtained from the sub-fractions 17–23 eluted with the same mixture of solvent. Compound 1 (3.7 mg) was further isolated from sub-fractions 26–33 eluted with hex/EA (85:15). A4 [10.2 g, hex/EA (1:1)] followed the same purification process under isocratic conditions of hex/EA (3:1) used as eluent to give teclearverdoornine (5, 0.7 mg). This latter (0.21 mg) was further obtained from the purification of A5 [8.7 g, hex/EA (1:3)] by using Hex/EA in the gradient condition.</p>\n\nBuesgenine, 1-methoxy-12-methyl-12,13-dihydro-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-c]phenanthridine-2,13-diol (1)\n<p>Red powder, m.p. 177°C; [α]D –7 [c 0.37, CH3OH]; IR (KBr), νmax 3450, 3074, 1540, 1480, 1475, 1404, 1385, 1321, 1284, 1257, 1203, 1161, 1126, 1082 cm−1; 1H (C5D5N, 400 MHZ) and 13C (C5D5N, 100 MHZ) NMR data see Table 1 and these data have been compiled in the Additional file 1 provided as supporting information; HR-ESIMS: m/z 374.1003 [C20H17NO5 + Na]+ (calcd. 374.1004).</p>\n\nCytotoxicity assay\n<p>The resazurin reduction assay [23] was performed to assess the cytotoxicity of compounds and doxorubicin as control drug towards various sensitive and drug-resistant cancer cell lines, including the CCRF-CEM and CEM/ADR5000 leukemia, MDA-MB231 breast cancer cells and its resistant subline MDA-MB231/BCRP, HCT116p53+/+ colon cancer cells and its resistant subline HCT116p53−/−, U87MG glioblastoma cells and its resistant subline U87MG. ΔEGFR and HepG2 hepatocarcinoma cells and normal AML12 hepatocytes. The assay is based on the reduction of the indicator dye, resazurin, to the highly fluorescent resorufin by viable cells. Non-viable cells rapidly lose their metabolic capacity to reduce resazurin and, thus, do not produce fluorescent signals anymore. Briefly, adherent cells were detached by treatment with 0.25% trypsin/EDTA (Invitrogen, Darmstadt Germany) and an aliquot of 1 × 104 cells was placed in each well of a 96-well cell culture plate (Thermo Scientific, Langenselbold, Germany) in a total volume of 200 μL. Cells were allowed to attach overnight and then were treated with different concentrations of compounds. For suspension cells, aliquots of 2 × 104 cells per well were seeded in 96-well-plates in a total volume of 100 μL. The studied compounds were immediately added in varying concentrations in an additional 100 μL of culture medium to obtain a total volume of 200 μL/well. After 72 h, resazurin (Sigma-Aldrich, Schnelldorf, Germany) (20 μL, 0.01% w/v) in distilled H2O was added to each well and the plates were incubated at 37°C for 4 h. Fluorescence was measured on an Infinite M2000 ProTM plate reader (Tecan, Crailsheim, Germany) using an excitation wavelength of 544 nm and an emission wavelength of 590 nm. Each assay was done at least twice with six replicates each. The viability was evaluated based on a comparison with untreated cells. IC50 values represent the compound concentrations required to inhibit 50% of cell proliferation and were calculated from a calibration curve by linear regression using Microsoft Excel [24].</p>\n\n\n<p>NMR spectra of the new compound have been provided as an online file.</p><p>Competing interests</p><p>The authors declare that they have no competing interests.</p><p>Authors' contributions</p><p>RST and SLP isolated the compounds, SLP elucidated the structure and wrote the manuscript, VK carried out the bio-assays, TE and BTN read and brought some corrections to the paper. All authors read and approved the final manuscript.</p>",
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"content": "BackgroundZanthoxylum buesgenii is a shrub used in Sierra Leone as remedy to cure venereal diseases, arthritis, and rheumatism whereas leaves and barks are employed to treat leprosy and to relieve pain. In South West Region of Cameroon, the plant locally called “Mbem” by Lewoh-Lebang community, is orally given to patients as aphrodisiac decoction and to increase sperm count. Previous chemical studies on Zanthoxylum species reported the identification of lignans, coumarins, diterpenes, sesquiterpenes, steroids, alkaloids and benzopropanoids. Besides, structurally diverse compounds belonging to these classes of secondary metabolites have been reported as trypanocidal, antileishmanial, antimycobacterial and cytotoxic metabolites.ResultsWe therefore investigated the alkaloidal constituents of Z. buesgenii. In the course of the study, two benzophenanthridines [1-methoxy-12-methyl-12,13-dihydro-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-c]phenanthridine-2,13-diol (1) and isofagaridine (2)] were identified among them one new. Alongside, three known furoquinolines [maculine (3), kokusaginine (4) and teclearverdoornine (5)] were also obtained and their structures were established on the basis of their NMR data and by comparison with those previously reported. Furthermore, the cytotoxicities of metabolites (1–4) isolated in substantial amount were evaluated against a series of multidrugs-resistant cancer cell lines. While compounds 2–4 showed selective cytotoxicities, compound 1 displayed activities against all cancer cells.ConclusionsThe observed activities corroborate those previously reported on similar benzophenanthridine alkaloids indicating that compounds 1 and 2 can chemically be explored to develop other chemotherapeutic agents.Graphical abstractCytotoxic Benzophenanthridine and Furoquinoline Alkaloids from Zanthoxylum buesgenii (Rutaceae).Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-014-0061-4) contains supplementary material, which is available to authorized users.",
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science.medmentions_ner | science.medmentions_ner.1170 | [
{
"content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nProstate and Colorectal Cancer Screening Uptake among US and Foreign-Born Males: Evidence from the 2015 NHIS Survey Research suggests that prostate and colorectal cancers disproportionately affect men in the US, but little is known about the determinants of prostate-specific antigen (PSA) and colorectal cancer (CRC) screening uptake among US and foreign-born males. The purpose of this study was to investigate what factors influence prostate and colorectal cancer screening uptake among US-native born and foreign-born men. Using the 2015 National Health Interview Survey, we conducted bivariate and multivariate analyses to highlight factors associated with the uptake of prostate and colorectal cancer screening among US-native born and foreign-born men. The sample size consisted of 5651 men respondents, with the mean age of 59.7 years (SD = 12.1). Of these, more than two-fifths (42%) were aged 50-64 years old. With respect to race / ethnicity, the sample was predominantly non-Hispanic Whites (65.5%), 863 (15.6%) Hispanics, and 710 (12.4%) Blacks. Our analysis found higher rates of both US-born and foreign-born men aged 65 years or older, who had either a PSA or CRC screening tests than those aged <65 years. Results of the general multivariate model suggest that men under 50 years old, US-born and foreign-born alike, are statistically significantly less likely to have prostate or colorectal cancer screenings than men aged 65 years or above. This study highlights the influencing factors that encourage or discourage PSA and CRC screening uptake between US-native born and foreign-born men. The results of this inquiry provide an evidence -based blueprint for policymakers and interventionists seeking to address prostate and colorectal cancer among men.",
"role": "user"
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"content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"Colorectal Cancer\", \"Prostate\", \"CRC\", \"colorectal cancer\", \"prostate\", \"colorectal cancers\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"determinants\", \"PSA\", \"prostate-specific antigen\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"mean age of 59.7 years\"], \"Food\": [], \"HealthCareActivity\": [\"screening\", \"screenings\", \"screening tests\", \"Screening\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"National Health Interview Survey\", \"Survey\", \"NHIS\", \"address\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"men\", \"ethnicity\", \"US\", \"Hispanics\", \"Blacks\", \"non-Hispanic\", \"US-born\", \"males\", \"Foreign-Born\", \"Males\", \"US-native born\", \"race\", \"respondents\", \"foreign-born\"], \"ProfessionalOrOccupationalGroup\": [\"interventionists\", \"policymakers\"], \"ResearchActivity\": [\"analysis\", \"study\", \"inquiry\", \"Research\"], \"SpatialConcept\": [\"US\"], \"Virus\": []}",
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science.medmentions_ner | science.medmentions_ner.1716 | [
{
"content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nGlobal Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 report focuses primarily on the revised and novel parts of the document. The most significant changes include: (1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (2) for each of the groups A to D, escalation strategies for pharmacologic treatments are proposed; (3) the concept of deescalation of therapy is introduced in the treatment assessment scheme; (4) nonpharmacologic therapies are comprehensively presented; and (5) the importance of comorbid conditions in managing chronic obstructive pulmonary disease is reviewed.",
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"content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"COPD\", \"Chronic Obstructive Lung Disease\", \"chronic obstructive pulmonary disease\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"history of\", \"comorbid conditions\", \"exacerbations\"], \"Food\": [], \"HealthCareActivity\": [\"symptom evaluation\", \"treatment\", \"therapy\", \"Management\", \"treatments\", \"revised\", \"spirometric assessment\", \"assessment\", \"deescalation\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"report\", \"GOLD Executive Summary\", \"Executive Summary\", \"scheme\", \"GOLD\", \"Global Initiative for Chronic Obstructive Lung Disease\", \"document\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"groups\", \"ABCD groups\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"Global Strategy\", \"strategies\", \"Diagnosis\", \"Prevention\"], \"SpatialConcept\": [], \"Virus\": []}",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.6343 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nSynthesis and Evaluation of 4-(Substituted styryl/alkenyl) -3,5-Bis(4-hydroxyphenyl)-isoxazoles as Ligands for the Estrogen Receptor\n\nContent Extracts:\n1. Introduction\n<p>The estrogen receptor displays the capacity to bind a wide variety of nonsteroidal ligands and to generate diverse biological responses as a consequence of that binding interaction.[1] A number of investigators have undertaken efforts to systematically prepare and evaluate non-steroidal ligand cores. The strategy, exemplified by the work of Katzenellenbogen and others, typically involved the preparation of a bis(4-hydroxyphenyl) heteroarene to mimic the estradiol skeleton and the incorporation of additional functional groups (R1/R2) that would enhance ER affinity and influence efficacy.[2–18][Figure 1] Relative binding affinities (RBA) for these derivatives ranged from 0.01–140% (compared to estradiol-100%), depending both upon the nature of the heteroaryl group and the R1/R2 substituents.</p><p>As part of our program to identify new structural motifs that elicit the desired ER response, we also focused on the preparation of new di- and tri-aryl heteroarenes. Although 3,5-diaryl isoxazoles are electronically similar to the 3,5-diaryl pyrazoles, isoxazole analogs had not been as extensively evaluated for estrogen ligand development as the corresponding pyrazoles.[10,18]. We noted that incorporation of a CH2-, C=O or CH2O-linker between the isoxazole ring and the aryl group gave products with significant ER affinity, however, none of the derivatives had employed a vinyl group to link the isoxazole core with the terminal (substituted phenyl) moiety. We hypothesized that an appropriate styryl/alkylvinyl group would yield derivatives that retain signicant affinity for the ERα-LBD. [Figure 2] In addition, the synthetic approach should contain elements that would make it amenable to combinatorial chemistry, thereby permitting rapid exploitation of the chemical space. This paper describes the synthesis and receptor binding results with this series of new 4-(styryl/alkenyl)-isoxazole derivatives.</p>\n\n2. Results and Discussion\n<p>Our synthetic objective involved the development of a direct, reliable synthetic route to the preparation of the target compounds. We examined two approaches, based upon a 4-iodo-3,5-bis(4-methoxyphenyl)-isoxazole intermediate, either of which could be expanded to combinatorial/parallel synthesis. In the first approach [Scheme 1] we converted the 4-iodo intermediate 1 [18] to the 4-vinyl boronic acid derivative 2 using the Sonogashira reaction,[19,20] followed by catechol hydroboration and hydrolysis. Subsequent Suzuki coupling with substituted aryl halides gave 4-(substituted styryl)-3,5-bis(4-methoxyphenyl) isoxazoles 3. The Sonogashira reaction, however, proceeded in low yield (~30%) and was accompanied by side products that required careful separation. Although the yield for the hydroboration step was satisfactory (77%), the yields for the subsequent Suzuki reactions to give the 4-(substituted styryl)-3,5-bis(4-methoxyphenyl) isoxazoles 3 were low (20–40%). Therefore we developed the second approach, (Scheme 2) in which we coupled the 4-iodo intermediate 1 with a series of commercially available substituted styryl and alkylvinyl boronic acids. In this case, the yields for the Suzuki reaction were very good (56–98%). Subsequent O-demethylation of the intermediates 3a–m, using boron tribromide or aluminum trichloride-ethyl mercaptan gave the initial series of target compounds 4a–m in good yields (53–98%).</p><p>Although the second approach was synthetically more successful, it is limited by the availability of coupling partners, i.e., arylvinyl boronic acids are not as readily available as aryl halides. As a basis for chemical library design, we demonstrated that other arylvinyl boronic acids could be readily accessed for use in this synthetic strategy. Conversion of aryl halides to the corresponding aryl acetylenes using the Sonogashira reaction has been well described. For our study, we used three such alkynes and converted them to the corresponding aryl vinyl boronic acids [21] and subsequently to the isoxazole derivatives. [Scheme 3] The yields for the catechol hydroboration, hydrolysis (43–61%) and coupling steps for the representative compounds 5n–p [22–24] were very satisfactory (43–61%). Conversion to the isoxazole derivatives 3n–p also proceeded in good yields (73–93%).</p><p>The initial series of 4-(substituted styryl/alkenyl)-3,5-bis(4-hydroxyphenyl)isoxazoles 4a–4m were evaluated as ligands for ERα-LBD using a competitive binding assay [25,26]. The relative binding affinity (RBA) values for the new compounds are shown in Table 1, where estradiol has a value of 100%. All of the compounds demonstrated significant affinity for the ERα-LBD, with values ranging from <1–16% that of estradiol. The highest affinity was observed for the 4-hydroxystyryl derivative 4h (16.4 %), with the 3-hydroxy isomer 4i (8.7%) slightly lower. Substitution of the ring at the 4-position with alkyl or halogenated groups (4c–g) reduced binding affinity (RBA <1%-5.3%) and as did replacement of the aromatic ring by alkyl groups (4j–m, RBA =1.3–4.3%). The Z-styryl isomer 4b appeared to be a slightly better ligand for ERα-LBD than the E-isomer 4a (8.7 vs 4%). Because substitution on the phenyl ring with groups other than hydroxyl appeared to reduce the binding affinity, we did not convert isoxazole derivatives 3n–3p to the corresponding bis(4-hydroxyphenyl) analogs 4n–4p for evaluation.</p><p>The binding properties of this series of tri-substituted isoxazoles compares favorably with previous studies on tris(4-hydroxyphenyl) five membered heterocycles. For example, the Chiron patent [18] reported a relative binding affinity (RBA) of 30% for 3,4,5- tris(4-hydroxyphenyl) isoxazole. In our case, introduction of the vinyl group between the isoxazole ring and the aryl group at the 4-position appears to be well tolerated in terms of ERα-LBD binding. The binding of the new compounds also compares favorably with the other heterocyclic analogs. Most of the tris(4-hydroxyphenyl) substituted pyrazoles reported by Katzenellenbogen also have RBA values in the 5–25% range. [3,5,8,10,11] Figure 3 presents the RBA value for 4h compared to two of the more potent isoxazole and pyrazole compounds.</p><p>The RBA values for the 4- and 3-hydroxyphenyl derivatives 4h and 4i are also comparable to the highest values observed for the tri- and tetrasubstituted pyrrole ER ligands recently reported by Gust. [14,15] It should be noted that pyrazoles and furans which have higher reported RBA values than 4h may achieve the enhanced affinity through the additional fourth substituent. This is not possible with the isoxazole scaffold. By comparison, the substituted isoxazoles described in this study generally were better than the previously reported imidazoles, oxazoles and thiazole which had very low RBA (<1%) values for ER. [10]</p><p>Based prior studies of the interaction between nonsteroidal ligands and ERα-LBD, we proposed a binding mode for the new ligands that provides a rationale for the structure-activity relationship. We illustrated this mode using compound 4d whose RBA value is less than that of the highest affinity agent 4h but somewhat more than the less active alkyl vinyl derivatives. [27] As with most nonsteroidal ligands of this type, the 3,5-bis(4- hydroxyphenyl)-isoxazole scaffold mimics the internal steroidal core of estradiol. The vinyl moiety at the 4-position experiences torsional strain due to the neighboring (4-fluorophenyl) groups and adopts a non-coplanar conformation that will reduce the steric strain. The more distal vinyl-aryl bond can also undergo rotation to achieve the most effective ligand-ERα-LBD contacts and further lower the energy of the complex. Our study (Figure 4) suggests that the terminal 4-fluoro-group interacts with residues Leu-540(helix-12) and Trp-383(helix5), as well as Thr-347 (helix-3), which is not see in this depiction. Hydrogen bonding by either the 4-hydroxyl (4h) or 3-hydroxyl (4i) group provides additional stabilization within this pocket. Hydrophobic substituents such as choro- (4e), methyl (4c) or trifluoromethyl (4f,4g) are tolerated but not favored. The alkyl vinl derivatives 4j–4m are also accommodated within this hydrophobic pocket, but provide no additional interactions that would strengthen binding. Other modeling studies have identified Thr-347 as the residue in the 11β-pocket most likely to establish hydrogen bonding with the distal phenolic hydroxyl.[4,5] This would appear to be the case as the two ligands with the highest RBA values were the 4- and 3-hydroxystyryl isoxazoles 4h and 4i. Substitution with non-hydrogen bonding or hydrophobic groups reduces the binding interaction, but conformation mobility may result in alternative binding modes that generate stable complexes. One interesting observation in this series was the difference between the 4-E- and 4-Z-styryl isoxazoles where the Z-isomer 4b had a slightly higher affinity than the E-isomer 4a (8.7% vs 4%). It is possible that the terminal phenyl group of the Z-derivative can access a slightly different and/or more favorable binding pocket than the E-counterpart.</p>\n\n3. Conclusions\n<p>In this study we developed an approach to the synthesis of 4-(substituted styryl)-3,5-bis(4-hydroxyphenyl) isoxazoles that is efficient and can be extended to combinatorial expansion. Although limited by the availabaility of the substituted styryl boronic acids, such reagents can be prepared from commercially available starting materials. The resultant products demonstrate significant binding affinity for the ERα-LBD that is comparable to previously described bis- and tris-(4-hydroxyphenyl) isoxazole, pyrazole and furan derivatives. The presence of the vinyl group at the 4-position is well tolerated and may permit the distal 3-/4-hydroxyphenyl moiety, present in compounds 4h and 4i, to adopt conformations that can access complementary residues, such as Thr-347, Trp-383, and Leu-540 in the 11β-binding pocket. The results provide the basis for future studies that evaluate the relationship between the 4-substituent and estrogenic potency. Studies in which the 4-styryl group is substituted with dialkylaminoethoxy groups are in progress as well.</p>",
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"content": "A series of 3,5-bis (4-hydroxyphenyl) isoxazoles bearing a styryl/alkyl vinyl group at the 4-position were prepared and evaluated as ligands for the estrogen receptor-alpha (ER\\xce\\xb1). The target compounds were prepared using the Suzuki reaction to couple an iodo-isoxazole intermediate with a series of styryl/alkenyl boronic acids, followed by O-demethylation. The products were evaluated for their estrogen receptor-\\xce\\xb1 ligand binding domain (ER\\xce\\xb1-LBD) binding affinity using a competitive binding assay. The 4-(4-hydroxystyryl) derivative 4h displays binding properties similar to those of the previously described pyrazole class of ER ligands, indicating that the ER\\xce\\xb1-LBD tolerates the presence of the added vinyl group at the 4-position of the isoxazole ring.",
"role": "assistant"
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.4061 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nTwo distinct limits for deep learning as the net width @math have been proposed, depending on how the weights of the last layer scale with @math . In the \"lazy-learning\" regime, the dynamics becomes linear in the weights and is described by a Neural Tangent Kernel @math . By contrast, in the \"feature-learning\" regime, the dynamics can be expressed in terms of the density distribution of the weights. Understanding which regime describes accurately practical architectures and which one leads to better performance remains a challenge. We answer these questions and produce new characterizations of these regimes for the MNIST data set, by considering deep nets @math whose last layer of weights scales as @math at initialization, where @math is a parameter we vary. We performed systematic experiments on two setups (A) fully-connected Softplus momentum full batch and (B) convolutional ReLU momentum stochastic. We find that (1) @math separates the two regimes. (2) for (A) and (B) feature learning outperforms lazy learning, a difference in performance that decreases with @math and becomes hardly detectable asymptotically for (A) but is very significant for (B). (3) In both regimes, the fluctuations @math induced by initial conditions on the learned function follow @math , leading to a performance that increases with @math . This improvement can be instead obtained at intermediate @math values by ensemble averaging different networks. (4) In the feature regime there exists a time scale @math , such that for @math the dynamics is linear. At @math , the output has grown by a magnitude @math and the changes of the tangent kernel @math become significant. Ultimately, it follows @math for ReLU and Softplus activation, with @math & @math when depth grows.\n\nCited Works Summary:\n[1]: Can multilayer neural networks -- typically constructed as highly complex structures with many nonlinearly activated neurons across layers -- behave in a non-trivial way that yet simplifies away a major part of their complexities? In this work, we uncover a phenomenon in which the behavior of these complex networks -- under suitable scalings and stochastic gradient descent dynamics -- becomes independent of the number of neurons as this number grows sufficiently large. We develop a formalism in which this many-neurons limiting behavior is captured by a set of equations, thereby exposing a previously unknown operating regime of these networks. While the current pursuit is mathematically non-rigorous, it is complemented with several experiments that validate the existence of this behavior.\n\n[2]: Many tasks in machine learning and signal processing can be solved by minimizing a convex function of a measure. This includes sparse spikes deconvolution or training a neural network with a single hidden layer. For these problems, we study a simple minimization method: the unknown measure is discretized into a mixture of particles and a continuous-time gradient descent is performed on their weights and positions. This is an idealization of the usual way to train neural networks with a large hidden layer. We show that, when initialized correctly and in the many-particle limit, this gradient flow, although non-convex, converges to global minimizers. The proof involves Wasserstein gradient flows, a by-product of optimal transport theory. Numerical experiments show that this asymptotic behavior is already at play for a reasonable number of particles, even in high dimension.\n\n[3]: Neural networks, a central tool in machine learning, have demonstrated remarkable, high fidelity performance on image recognition and classification tasks. These successes evince an ability to accurately represent high dimensional functions, potentially of great use in computational and applied mathematics. That said, there are few rigorous results about the representation error and trainability of neural networks. Here we characterize both the error and the scaling of the error with the size of the network by reinterpreting the standard optimization algorithm used in machine learning applications, stochastic gradient descent, as the evolution of a particle system with interactions governed by a potential related to the objective or \"loss\" function used to train the network. We show that, when the number @math of parameters is large, the empirical distribution of the particles descends on a convex landscape towards a minimizer at a rate independent of @math . We establish a Law of Large Numbers and a Central Limit Theorem for the empirical distribution, which together show that the approximation error of the network universally scales as @math . Remarkably, these properties do not depend on the dimensionality of the domain of the function that we seek to represent. Our analysis also quantifies the scale and nature of the noise introduced by stochastic gradient descent and provides guidelines for the step size and batch size to use when training a neural network. We illustrate our findings on examples in which we train neural network to learn the energy function of the continuous 3-spin model on the sphere. The approximation error scales as our analysis predicts in as high a dimension as @math .\n\n[4]: Multi-layer neural networks are among the most powerful models in machine learning, yet the fundamental reasons for this success defy mathematical understanding. Learning a neural network requires to optimize a non-convex high-dimensional objective (risk function), a problem which is usually attacked using stochastic gradient descent (SGD). Does SGD converge to a global optimum of the risk or only to a local optimum? In the first case, does this happen because local minima are absent, or because SGD somehow avoids them? In the second, why do local minima reached by SGD have good generalization properties? In this paper we consider a simple case, namely two-layers neural networks, and prove that -in a suitable scaling limit- SGD dynamics is captured by a certain non-linear partial differential equation (PDE) that we call distributional dynamics (DD). We then consider several specific examples, and show how DD can be used to prove convergence of SGD to networks with nearly ideal generalization error. This description allows to 'average-out' some of the complexities of the landscape of neural networks, and can be used to prove a general convergence result for noisy SGD.\n\n[5]: Machine learning, and in particular neural network models, have revolutionized fields such as image, text, and speech recognition. Today, many important real-world applications in these areas are driven by neural networks. There are also growing applications in engineering, robotics, medicine, and finance. Despite their immense success in practice, there is limited mathematical understanding of neural networks. This paper illustrates how neural networks can be studied via stochastic analysis, and develops approaches for addressing some of the technical challenges which arise. We analyze one-layer neural networks in the asymptotic regime of simultaneously (A) large network sizes and (B) large numbers of stochastic gradient descent training iterations. We rigorously prove that the empirical distribution of the neural network parameters converges to the solution of a nonlinear partial differential equation. This result can be considered a law of large numbers for neural networks. In addition, a consequence of our analysis is that the trained parameters of the neural network asymptotically become independent, a property which is commonly called \"propagation of chaos\".\n\n[6]: We consider learning two layer neural networks using stochastic gradient descent. The mean-field description of this learning dynamics approximates the evolution of the network weights by an evolution in the space of probability distributions in @math (where @math is the number of parameters associated to each neuron). This evolution can be defined through a partial differential equation or, equivalently, as the gradient flow in the Wasserstein space of probability distributions. Earlier work shows that (under some regularity assumptions), the mean field description is accurate as soon as the number of hidden units is much larger than the dimension @math . In this paper we establish stronger and more general approximation guarantees. First of all, we show that the number of hidden units only needs to be larger than a quantity dependent on the regularity properties of the data, and independent of the dimensions. Next, we generalize this analysis to the case of unbounded activation functions, which was not covered by earlier bounds. We extend our results to noisy stochastic gradient descent. Finally, we show that kernel ridge regression can be recovered as a special limit of the mean field analysis.",
"role": "user"
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"content": "Another limit, feature learning also called mean field in the literature, has been studied in several works focusing mostly on one-hidden layer networks [4] [3] [2] [5] [6] [1] . In this setting the output function of the network with @math hidden neurons corresponding to an input @math is: where @math is the non-linear activation function and @math are the parameters associated with a hidden neuron. Note that the last layer of weights scales as @math , which differs from the @math scaling used in the NTK setting. The network can be described in terms of the empirical distribution of a neuron's parameters As @math , this distribution tends to a probability distribution @math , 111 can be written as an integral, and the training dynamics is then controlled by a differential equation for @math .",
"role": "assistant"
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science.scientific_lay_summarisation_elife_single_doc_summ | science.scientific_lay_summarisation_elife_single_doc_summ.3260 | [
{
"content": "Transform the provided sections of a biomedical research paper into a digestible summary for a general audience. Focus on simplifying complex ideas while retaining key scientific insights.\n\nResearch Title: Tyr1 phosphorylation promotes phosphorylation of Ser2 on the C-terminal domain of eukaryotic RNA polymerase II by P-TEFb\nContent Overview:\nAbstract:\nThe Positive Transcription Elongation Factor b( P-TEFb) phosphorylates Ser2 residues of the C-terminal domain( CTD) of the largest subunit( RPB1) of RNA polymerase II and is essential for the transition from transcription initiation to elongation in vivo. Surprisingly, P-TEFb exhibits Ser5 phosphorylation activity in vitro. The mechanism garnering Ser2 specificity to P-TEFb remains elusive and hinders understanding of the transition from transcription initiation to elongation. Through in vitro reconstruction of CTD phosphorylation, mass spectrometry analysis, and chromatin immunoprecipitation sequencing( ChIP-seq) analysis, we uncover a mechanism by which Tyr1 phosphorylation directs the kinase activity of P-TEFb and alters its specificity from Ser5 to Ser2. The loss of Tyr1 phosphorylation causes an accumulation of RNA polymerase II in the promoter region as detected by ChIP-seq. We demonstrate the ability of Tyr1 phosphorylation to generate a heterogeneous CTD modification landscape that expands the CTD’s coding potential. These findings provide direct experimental evidence for a combinatorial CTD phosphorylation code wherein previously installed modifications direct the identity and abundance of subsequent coding events by influencing the behavior of downstream enzymes.\nIntroduction:\nThe C-terminal domain of the RPB1 subunit of RNA polymerase II( CTD) is composed of a species-specific number of repeats of the consensus amino acid heptad YSPTSPS( arbitrarily numbered as Tyr1, Ser2, Pro3, Thr4, Ser5, Pro6, and Ser7)( Jeronimo et al., 2016). The CTD undergoes extensive post-translational modification( PTM) that recruits RNA processing and transcription factors that regulate progression through the various stages of transcription. These modification events are dynamic, highly regulated, and maintained through the complex interplay of CTD modification enzymes. Collectively these PTMs and recruited protein factors constitute the ‘CTD Code’ for eukaryotic transcription( Buratowski, 2003). Chromatin immunoprecipitation and next-generation sequencing technologies have revealed how phosphorylation levels of CTD residues change temporally and spatially during each transcription cycle( Eick and Geyer, 2013). The major sites of phosphorylation are Ser5 and Ser2, directed by Transcription Factor II H( TFIIH)( Feaver et al., 1994) and P-TEFb in mammals( Marshall et al., 1996), respectively. The other three phosphate-accepting residues( Tyr1, Thr4, and Ser7) are also subject to modification, although their functions are less well-understood( Jeronimo et al., 2013). In mammalian cells, the phosphorylations of Tyr1 and Ser7 rise and peak near the promoter along with Ser5 and gradually decrease as transcription progresses towards termination. The phosphorylation of Thr4 and Ser2, on the other hand, don’t appear until later in the transcription cycle during elongation( Eick and Geyer, 2013). The molecular underpinnings resulting in this orchestration are poorly defined. A particularly apparent gap in current knowledge is if sequence divergence from the consensus heptad or previously installed PTMs influence coding events. The CTD code is generated through the interplay of CTD modifying enzymes such as kinases, phosphatases, and prolyl isomerases( Bataille et al., 2012). Disruption of this process is implicated in various disease states. P-TEFb is of particular interest due to its overexpression in multiple tumor types and role in HIV infection( Franco et al., 2018). As a major CTD kinase, P-TEFb promotes transcription by contributing to the release of RNA polymerase II from the promoter-proximal pause through its phosphorylation of Negative Elongation Factor( NELF), DRB Sensitivity Inducing Factor( DSIF), and Ser2 of the CTD( Wada et al., 1998). Interestingly, P-TEFb seems to phosphorylate Ser5 of the CTD in vitro and mutation of Ser5 to alanine prevents the phosphorylation of CTD substrates. However, mutation of Ser2 to alanine did not result in this abolishment( Czudnochowski et al., 2012). These results are in contrast to in vivo studies of P-TEFb specificity, where compromised P-TEFb kinase activity results in a specific reduction in levels of Ser2 phosphorylation( Marshall et al., 1996). The discrepancies between P-TEFb specificity in vitro and in vivo make it difficult to reconcile P-TEFb’s function as a CTD Ser2 kinases( Bartkowiak et al., 2010; Czudnochowski et al., 2012). To resolve these inconsistencies, we utilize a multi-disciplinary approach to investigate the specificity of P-TEFb. Identification of phosphorylation sites was carried out using ultraviolet photodissociation( UVPD) mass spectrometry establishing the specificity of P-TEFb in vitro in single residue resolution. We reveal the tyrosine kinase c-Abl phosphorylates consensus and full-length CTD substrates in a conservative fashion, with only half of the available sites phosphorylated. The unique phosphorylation pattern of Tyr1 by tyrosine kinases like c-Abl directs the specificity of P-TEFb to Ser2. The priming effect of pTyr1 on P-TEFb extends to human cells, where small-molecule inhibition of c-Abl-like Tyr1 kinase activities leads to a reduction of Tyr1 phosphorylation. Further ChIP-seq analysis shows that the loss of tyrosine phosphorylation increases promoter-proximal pausing with an accumulation of RNA polymerase II at the promoter region of the gene. Overall, our results reconcile the discrepancy of P-TEFb kinase activity in vitro and in cells, showing that Tyr1 phosphorylation can prime P-TEFb and alter its specificity to Ser2. Importantly, these findings provide direct experimental evidence for a combinatorial CTD phosphorylation code wherein previously installed modifications direct the identity and abundance of subsequent coding events, resulting in a varied PTM landscape along the CTD allowing for diversified co-transcriptional signaling.\nDiscussion:\nOur discovery that Tyr1 phosphorylation of the CTD alters the preference of P-TEFb from Ser5 to Ser2 resolves the controversy surrounding P-TEFb’s specificity( Bartkowiak et al., 2010; Czudnochowski et al., 2012). P-TEFb was initially identified as a CTD kinase that controls the elongation potential of RNA polymerase II, is required for the majority of RNA polymerase II transcription, and is specific for Ser2 in vivo( Chao and Price, 2001; Marshall et al., 1996; Ni et al., 2004). However, these early conclusions are at odds with in vitro data demonstrating P-TEFb is incapable of phosphorylating Ser2 of CTD peptides in vitro( Czudnochowski et al., 2012). Two other kinases, CDK12 and CDK13, display Ser2 kinase activity in cells but do not seem to play a major role in Ser2 phosphorylation in early transcriptional events( Bartkowiak et al., 2010; Chen et al., 2007). Investigations on the effect of CTD phosphorylations on P-TEFb specificity have revealed that Ser7( Czudnochowski et al., 2012) and Ser5( this manuscript) do not alter its preference for Ser5. Using direct methods, like mass spectrometry confirmed by immunoblotting and EMSA, we identified that Tyr1 phosphorylation could alter the specificity of P-TEFb from Ser5 to Ser2 in vitro. It should be stressed that continuous heptad repeats with phosphorylated pTyr1 inhibit subsequent CTD modification by P-TEFb( Czudnochowski et al., 2012). However, when treated biochemically with c-Abl, the pTyr1 pattern not only allows for P-TEFb phosphorylation but also shift the substrate preference from Ser5 to Ser2. Furthermore, inhibition of Tyr1 phosphorylation leads to the reduction of Ser2 phosphorylation in human cells and the accumulation of Pol II in the promoter-proximal pausing stage of transcription. Therefore, we show that Tyr1 phosphorylation potentiates Ser2 phosphorylation of the CTD by altering P-TEFb specificity. The PTM state of the CTD has been correlated to the progression of transcription( Jeronimo et al., 2016). Traditionally, such analyses are interpreted through a paradigm considering heptads phosphorylated on a single isolated residue with Ser5 phosphorylation dominating the initiation stage of transcription and Ser2 phosphorylation dominating elongation and termination( Corden, 2013). However, this simplification of CTD modification cannot explain the well-coordinated recruitment of the myriad CTD binding factors currently implicated in eukaryotic transcription( Ebmeier et al., 2017; Eick and Geyer, 2013; Harlen and Churchman, 2017). Data presented here point to a sophisticated model in which the phosphorylation of Tyr1 at the beginning of transcription sets the stage for future coding events. This interplay between c-Abl and P-TEFb results in a chemically distinct phospho-CTD landscape compared to CTD phosphorylated by a single kinase. The combination of these modification modes likely contributes to a heterogeneous collection of modified heptads, which recruits the diverse array of CTD binding partners in a coordinated manner. These results are in good agreement with the ‘CTD code’ hypothesis proposed decades ago where different combinations of post-translational events result in different transcriptional outcomes. Tyr1 phosphorylation has been implicated in stabilizing RNA polymerase II in cells( Hsin et al., 2014), transcription termination( Mayer et al., 2012) and anti-sense transcription( Descostes et al., 2014) but a coherent molecular basis for these disparate functions remains elusive. Our analysis provides a molecular mechanism demonstrating how Tyr1 phosphorylation can affect subsequent phosphorylation events carried out by other CTD kinases. The ability of Tyr1 phosphorylation to redirect signaling and influence subsequent modifications along the CTD, as revealed for P-TEFb, suggests these various roles for pTyr1 may arise indirectly. It can function through its impact on downstream CTD modifiers, highlighting integrated, indirect, and context-specific mechanisms for pTyr1 during co-transcriptional signaling. The final accumulation of individual species is dependent on the dynamic interplay of CTD kinases and phosphatases throughout the transcription cycle. Tyr1 phosphorylation is relatively transient, appearing at the transition from initiation to elongation and decreasing rapidly through the action of phosphatase( s)( Eick and Geyer, 2013). Despite this transient nature, pTyr1 is positioned in a vital window to alter P-TEFb specificity and regulate its phosphorylation pattern along RNA polymerase II. The adjustability of P-TEFb specificity by nearby Tyr1 phosphorylation reveals a novel mechanism for the regulation of P-TEFb kinase activity. With many binding partners in cells for P-TEFb, there might be additional regulators promoting the pSer2 activity of P-TEFb independent of or cooperatively with Tyr1 phosphorylation. The data presented reconcile P-TEFb’s in vitro and in vivo specificity and inspires new queries fundamental to CTD biology. P-TEFb is ubiquitously important for transcription across eukaryotic cells and often co-opted in disease states like HIV infection and cancer( Franco et al., 2018). The integrated CTD code revealed here represents a unique mechanism to manipulate P-TEFb and potentially other CTD modifiers. Future inquiries using similar multi-disciplinary approaches will hopefully reveal CTD modification patterns in greater detail at different stages of the transcription process in single amino acid resolution. Information such as this will define the temporal and spatial signaling allowing for the recruitment of transcriptional regulators during active transcription. Overall, our findings support a model in which cross-talk between CTD modification enzymes increases the diversity and coding potential of CTD heptads. This expands the lexicon of phosphorylation marks and can provide more specific recruitment of transcription regulators allowing for the precise control of eukaryotic transcription.",
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"content": "DNA contains the instructions for making proteins , which build and maintain our cells . So that the information encoded in DNA can be used , a molecular machine called RNA polymerase II makes copies of specific genes . These copies , in the form of a molecule called RNA , convey the instructions for making proteins to the rest of the cell . To ensure that RNA polymerase II copies the correct genes at the correct time , a group of regulatory proteins are needed to control its activity . Many of these proteins interact with RNA polymerase II at a region known as the C-terminal domain , or CTD for short . For example , before RNA polymerase can make a full copy of a gene , a small molecule called a phosphate group must first be added to CTD at specific units known as Ser2 . The regulatory protein P-TEFb was thought to be responsible for phosphorylating Ser2 . However , it was previously not known how P-TEFb added this phosphate group , and why it did not also add phosphate groups to other positions in the CTD domain that are structurally similar to Ser2 . To investigate this , Mayfield , Irani et al . mixed the CTD domain with different regulatory proteins , and used various biochemical approaches to examine which specific positions of the domain had phosphate groups attached . These experiments revealed a previously unknown aspect of P-TEFb activity: its specificity for Ser2 increased dramatically if a different regulatory protein first added a phosphate group to a nearby location in CTD . This additional phosphate group directed P-TEFb to then add its phosphate specifically at Ser2 . To confirm the activity of this mechanism in living human cells , Mayfield , Irani et al . used a drug that prevented the first phosphate from being added . In the drug treated cells , RNA polymerase II was found more frequently ‘stalled’ at positions on the DNA just before a gene starts . This suggests that living cells needs this two-phosphate code system in order for RNA polymerase II to progress and make copies of specific genes . These results are a step forward in understanding the complex control mechanisms cells use to make proteins from their DNA . Moreover , the model presented here – one phosphate addition priming a second specific phosphate addition – provides a template that may underlie similar regulatory processes .",
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science.mslr2022_ms2_multidoc_summarization | science.mslr2022_ms2_multidoc_summarization.14005 | [
{
"content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization.\nSummary: Reactivation of hepatitis B virus ( HBV ) during chemotherapy is well documented . However , there are limited data on this complication in patients with hepatocellular carcinoma ( HCC ) undergoing transarterial chemotherapy . The aim of this study was to evaluate the efficacy of preemptive lamivudine therapy in reducing hepatitis due to HBV reactivation in patients with HCC undergoing transarterial chemo-lipiodolization ( TACL ) and to seek predictors of this event . A total of 73 consecutive HCC patients undergoing TACL using epirubicin 50 mg/m2 and cisplatin 60 mg/m2 at monthly intervals were prospect ively and r and omly assigned to receive lamivudine 100 mg daily from the start of TACL ( preemptive group ) or not ( control group ) . During the study , 11 ( 29.7 % ) of 37 patients in the control group and 1 ( 2.8 % ) of 36 patients in the preemptive group developed hepatitis due to HBV reactivation ( P = .002 ) . In addition , there were significantly more incidences of overall hepatitis ( P = .021 ) and severe grade of hepatitis ( P = .035 ) in the control group . With multivariate Cox regression model , a baseline HBV DNA level of more than 10(4 ) copies/mL was the only independent predictor of hepatitis due to HBV reactivation during chemo-lipiodolization ( P = .046 ) . In conclusion , preemptive lamivudine therapy demonstrated excellent efficacy in reducing hepatitis due to HBV reactivation and hepatic morbidity during TACL . Preemptive therapy should be considered in HCC patients with an HBV DNA level of more than 10(4 ) copies/mL. Further studies are needed to confirm the value of this approach in patients with low-level viremia\n\n\nReport 2:\nTitle: Sorafenib for Egyptian patients with advanced hepatocellular carcinoma; single center experience.\nSummary: BACKGROUND According to the results of a number of phase 3 r and omized studies , sorafenib is the only approved systemic therapy for advanced HCC ; however the issue of high economic cost remains challenging ; thus we have conducted this retrospective analysis of our HCC patients treated with sorafenib . METHODS HCC patients treated at Ain Shams University Hospitals , in the period between 2010 and 2012 were review ed . Eligible patients were those who had received sorafenib for advanced HCC not eligible for or progressed after surgery or locoregional therapy . We investigated the impact of baseline clinicopathological factors ( age , gender , child status , performance score , BCLC tumor stage , cause of chronic liver disease , median baseline alpha fetoprotein level and previous treatment received for HCC ) on overall survival ( OS ) in an adjusted Cox regression model . RESULTS 41 patients were included in the analysis fulfilling the inclusion criteria . At a median follow up period of 13 months , the median PFS for the whole group was 4 months ; the median OS for the whole group is 6.25 months . Multivariate analysis identified three baseline characteristics that were prognostic indicators for overall survival : ECOG performance status ( median OS for ECOG 1=7.01 months and for ECOG 2=3.03 months ) , Child-Pugh status ( median OS for child A=12.04 months and for child B=5.23 months ) , and median baseline levels of alpha-fetoprotein . CONCLUSIONS In limited re source countries like Egypt , we suggest that the use of sorafenib for the treatment of advanced HCC cases should be restricted to a highly selected subgroup of patients with good performance and child\n\n\nReport 3:\nTitle: Sorafenib versus capecitabine in the management of advanced hepatocellular carcinoma\nSummary: The only approved systemic therapy for patients with advanced hepatocellular carcinoma ( HCC ) till now is sorafenib . A preliminary study suggested that capecitabine , an oral fluoropyrimidine , may be effective in advanced HCC . We have tested this hypothesis in this phase 2 study . In this single-center , phase 2 , open-label trial , we r and omly assigned 52 patients with advanced HCC who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or capecitabine ( 1,000 mg/m2 twice daily ) ( day 1–day 14 ) . Primary outcome was progression-free survival . Secondary outcomes included the overall survival and safety . Median overall survival was 7.05 months in the sorafenib group and 5.07 months in the capecitabine group ( hazard ratio in the capecitabine group 2.36 ; 95 % confidence interval 1.174–4.74 ; P < 0.016 ) . The median progression-free survival was 6 months in the sorafenib group and 4 months in the capecitabine group ( P < 0.005 ) . Three patients in the sorafenib group ( 11.5 % ) and one patient in the capecitabine group ( 3 % ) had a partial response ; one patient ( 3 % ) had a complete response in the sorafenib group . H and –foot skin reaction was more frequent in the sorafenib group , hyperbilirubinemia was more common in the capecitabine group , and diarrhea was equivalent between both groups . In patients with advanced HCC , capecitabine is inferior to sorafenib in terms of median progression-free survival and overall survival , and it should not be used alone for the treatment of advanced HCC , but rather , combination therapy with sorafenib should be considered\n\n\nReport 4:\nTitle: Combination therapy with transarterial chemoembolization and interferon-alpha compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma.\nSummary: BACKGROUND AND AIMS The present study was carried out to test the hypothesis that interferon-alpha ( IFN-alpha ) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization ( TACE ) treatment of hepatitis B virus ( HBV ) related unresectable hepatocellular carcinoma ( HCC ) . METHODS 216 patients with unresectable HBV-related HCC were r and omized into a TACE group and a TACE-IFN group , each group had 108 patients . In the TACE-IFN group , patients received IFN-alpha1b at a dose of 3 million units ( mu ) three times a week by intramuscular injection one week after/before TACE treatment , for 48 weeks . RESULTS The median disease-free survival in the TACE-IFN treatment group was 23.6 months ( 95 % CI : 21.4 - 25.8 ) and 20.3 months ( 95 % CI : 15.8 - 24.8 ) in the TACE group ( P = 0.027 ) . The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group ( 39.8 % vs 59.3 % , P = 0.004 ) . The median overall survival was 29 months ( 95 % CI : 27.5 - 32.1 ) in the TACE-IFN group and 26 months ( 95 % CI : 20.1 - 31.9 ) in the TACE group ( P = 0.003 ) . The 2-year overall survival in the TACE-IFN group was higher than in the TACE group ( 72.2 % vs 52.8 % , P = 0.003 ) . CONCLUSIONS IFN-alpha treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC , with acceptable toxicities\n\n\nReport 5:\nTitle: [Therapeutic effect and prognosis of interferon therapy after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma associated with hepatitis B virus].\nSummary: OBJECTIVE To evaluate the therapeutic effect of interferon therapy after transcatheter arterial chemoembolization ( TACE ) in patients with hepatocellular carcinoma associated with hepatitis B virus . METHODS Sixty-two patients with advanced primary hepatocellular carcinoma associated with hepatitis B virus was r and omly divided into 2 groups . Thirty-one cases were treated with TACE and Interferon . Thirty-one cases with TACE only . HBV DNA , clinical effect , intrahepatic tumor recurrence rate and survival rate were studied . RESULTS Of the 31 patients in TACE+IFN group , 17 ( 54.8 % ) were negative for HBV DNA at the end of treatment . None of TACE group was negative for HBV DNA . The intrahepatic tumor recurrence rate at 1 year and 2 years in TACE+IFN group was 16.1 % , 29.0 % , compared with 38.7 % , 61.3 % in TACE group ( chi-square = 3.97 , chi-square 6.51 , P < 0.05 ) . The survival rate in the former was 83.9 % and 74.2 % respectively , compared with that of 61.3 % and 38.7 % in the latter ( chi-square = 3.97 , chi-square = 7.94 , P < 0.05 ) . CONCLUSION Interferon therapy after transcatheter arterial chemoembolization result ed low recurrence and long survival in patients with hepatocellular carcinoma associated with hepatitis B virus . This method showed fewer side effects and should be recommended\n\n\nReport 6:\nTitle: Chemotherapy-induced hepatitis B reactivation in lymphoma patients with resolved HBV infection: a prospective study.\nSummary: UNLABELLED Fatal hepatitis B virus ( HBV ) reactivation in lymphoma patients with \" resolved \" HBV infection ( hepatitis B surface antigen [ HBsAg ] negative and hepatitis B core antibody [ anti-HBc ] positive ) can occur , but the true incidence and severity remain unclear . From June 2009 to December 2011 , 150 newly diagnosed lymphoma patients with resolved HBV infection who were to receive rituximab-CHOP ( cyclophosphamide , doxorubicin , vincristine , prednisolone)-based chemotherapy were prospect ively followed . HBV DNA was checked at baseline , at the start of each cycle of chemotherapy , and every 4 weeks for 1 year after completion of rituximab-CHOP chemotherapy . Patients with documented HBV reactivation were treated with entecavir at a dosage of 0.5 mg/day for 48 weeks . HBV reactivation was defined as a greater than 10-fold increase in HBV DNA , compared with previous nadir levels , and hepatitis flare was defined as a greater than 3-fold increase in alanine aminotransferase ( ALT ) that exceeded 100 IU/L. Incidence of HBV reactivation and HBV-related hepatitis flares was 10.4 and 6.4 per 100 person-year , respectively . Severe HBV-related hepatitis ( ALT > 10-fold of upper limit of normal ) occurred in 4 patients , despite entecavir treatment . Patients with hepatitis flare exhibited significantly higher incidence of reappearance of HBsAg after HBV reactivation ( 100 % vs. 28.5 % ; P=0.003 ) . CONCLUSION In lymphoma patients with resolved HBV infections , chemotherapy-induced HBV reactivation is not uncommon , but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy . Serological breakthrough ( i.e. , reappearance of HBsAg ) is the most important predictor of HBV-related hepatitis flare . ( Hepatology 2014;59:2092 - 2100 )",
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"content": "An antiviral/TACE combination shows promise as an effective and tolerable treatment strategy for intermediate-stage HCC .\nThe reported efficacy and toxicity of the antiviral/TACE combination appears to compare favorably with TACE monotherapy , the most commonly implemented strategy for intermediate-stage HCC .",
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.705 | [
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"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: A Functional Bacterium-to-Plant DNA Transfer Machinery of Rhizobium etli\nContent:\nAbstract:\nDifferent strains and species of the soil phytopathogen Agrobacterium possess the ability to transfer and integrate a segment of DNA( T-DNA) into the genome of their eukaryotic hosts, which is mainly mediated by a set of virulence( vir) genes located on the bacterial Ti-plasmid that also contains the T-DNA. To date, Agrobacterium is considered to be unique in its capacity to mediate genetic transformation of eukaryotes. However, close homologs of the vir genes are encoded by the p42a plasmid of Rhizobium etli; this microorganism is related to Agrobacterium, but known only as a symbiotic bacterium that forms nitrogen-fixing nodules in several species of beans. Here, we show that R. etli can mediate functional DNA transfer and stable genetic transformation of plant cells, when provided with a plasmid containing a T-DNA segment. Thus, R. etli represents another bacterial species, besides Agrobacterium, that encodes a protein machinery for DNA transfer to eukaryotic cells and their subsequent genetic modification.\nIntroduction:\nThe Rhizobiales order contains many species of plant-associated bacteria, such as the related genera Agrobacterium and Rhizobium. Phylogenetic analyses based on 16S rDNA sequences led to the idea that Agrobacterium and Rhizobium could be regrouped into one genus[1]. Yet their lifestyles are very different. Agrobacterium comprises species that are often, but not always[2, 3], pathogenic and can genetically transform their host plant cells by transferring a segment of their own plasmid, the T-DNA, and induce neoplastic growths that synthesize small molecules used as nutrients by the bacteria[4–6]. This Agrobacterium capability to modify genetically their host cells is widely used in research and biotechnology for generating transgenic plants[7] as well as fungi[8]. In contrast, Rhizobium belongs to a group of very diverse symbiotic bacteria( collectively termed rhizobia) that form nitrogen-fixing nodules on the roots of legume plants[9–12]. Rhizobium and Agrobacterium species have complex genomes composed of one or two chromosomes and several plasmids[13–16]; the chromosomes are designed as “core” components defining the species as opposed to the “accessory” components that are the plasmids[17]. The outcome of interactions of these bacteria with plants is essentially determined by large specialized plasmids, the tumor inducing( Ti) plasmid for Agrobacterium, and symbiotic( pSym) plasmid for Rhizobium. Indeed, introducing an Agrobacterium Ti plasmid into some rhizobia species resulted in virulent bacteria capable of inducing tumors in host plants[18]. In general, rhizobia species are known to gain T-DNA transfer ability only when provided with the virulence( vir) genes[4, 5] of the Agrobacterium Ti plasmid[19, 20]. Rhizobium, therefore, is thought to possess chromosomal, but not plasmid-based factors required for plant genetic transformation, and because of that lack endogenous DNA transfer capacity. Intriguingly, however, many Rhizobium species harbor different sets of homologs of the Agrobacterium vir genes; specifically, R. etli carries a complete set of vir genes[15, 21] whereas the closely related R. leguminosarum lacks such degree of homology. Here, we show that R. etli can independently mediate functional DNA transfer and stable genetic transformation of plant cells, when provided with a plasmid containing a T-DNA segment. Thus, R. etli represents another bacterial species, in addition to Agrobacterium, capable of genetic modification of plants.\nDiscussion:\nOur results demonstrate that R. etli within its p42a plasmid contains a complete and functional vir region, encoding a set of Vir proteins able to mediate functional T-DNA transfer into plant cells. Whereas it has been known that the vir genes from Agrobacterium can function in several rhizobia species[18, 19], this is the first time that an endogenous virulence system encoded by a non-Agrobacterium species is shown to be functional in DNA transfer and stable genetic transformation. The virE2 and virG mutants, which render R. etli unable to promote genetic transformation, previously have been shown to have no effect on formation of nitrogen-fixing nodules or on nodulation competitiveness[21]. Thus, the vir genes likely fulfill a function unrelated to symbiosis. Two factors might account for the presence of a functional vir region in R. etli. First, the ability to transform host plant cells may have been widespread among bacterial species in the past, and not restricted to the Agrobacterium genus. That we could not identify T-DNA-like sequences in R. etli suggests that Rhizobium-mediated plant transformation does not occur at present, although it cannot be ruled out that other Rhizobium strains, not yet sequenced, harbor a T-DNA. Furthermore, proteins from other rhizobia, such as Mesorhizobium loti R7A( see S1 Table for Vir protein sequence homologies with M. loti R7A), can be recognized by the Agrobacterium VirB/D4 type IV secretion system( T4SS) and exported to plant cells[25], suggesting that T4SS could substitute for the type III secretion system( T3SS) during effector protein translocation in some rhizobia species. Thus, the VirB/D4 T4SS encoded by p42a could also function to translocate protein effectors in R. etli. Second, because the p42a plasmid is transmissible between Rhizobium and Agrobacterium[21], this plasmid may belong to an “interspecies plasmid pool”, and R. etli may function as a “vector” for p42a which is then transferred to Agrobacterium and only then used for plant genetic transformation. It would be interesting to examine whether quorum sensing signals that activate conjugative transfer of plasmids between Agrobacterium cells also induce conjugation between Rhizobium and Agrobacterium. Indeed, in natural Agrobacterium populations, Ti-plasmids are not present in all cells[2, 3], but, in response to bacterial and plant signals via a quorum sensing mechanism, conjugative plasmid transfer can be activated[26]. The need to identify or even generate non-Agrobacterium bacterial species that could be used as a vector for plant genetic transformation has been emphatically articulated[27]. First, a non-Agrobacterium vector might be more efficient in some hosts that are difficult to transform by Agrobacterium. Indeed, although the efficiency of R. etli mediated transformation of Nicotiana species was very low compared to Agrobacterium, R. etli might be more efficient with other plant species, such as its native hosts. Second, several aspects of plant genetic transformation methods are legally limited by existing patents, and using a different bacterial species may help to circumvent these limitation and avoid litigation[28]. In conclusion, we demonstrate that R. etli, a symbiotic Rhizobium species different from the phytopathogenic Agrobacterium, contains the complete molecular machinery able to transfer DNA to the plant genome, which has implications for evolution and origin of the Agrobacterium virulence system as well as for potential utilization in biotechnology.",
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"content": "Since the discovery of gene transfer from Agrobacterium to host plants in the late 1970s , this bacterial pathogen has been widely used in research and biotechnology to generate transgenic plants . Agrobacterium’s infection process relies on a set of virulence proteins that mediate the transfer of a segment of its own DNA ( T-DNA ) into the host cell genome . To date , Agrobacterium is believed to be the only prokaryote with the capability of cross-kingdoms gene transfer . However , homologs of the Agrobacterium’s virulence proteins are found in some symbiotic plant-associated bacterial species , belonging to the Rhizobium genus . Here we show that one of these species , Rhizobium etli , encodes a complete set of virulence proteins and is able to mediate transfer and integration of DNA into host-plant cell genome , when provided with a T-DNA . This is the first time that a bacterium-to-plant DNA transfer machinery encoded by a non-Agrobacterium species is shown to be functional .",
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science.scicite_classification | science.scicite_classification.343 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nThe PCR reactions were multiplex PCR using three sets of primers: Mycgen-F, Mycgen-R, Mycav-R; RD4F, RD4R, RD4intF; and RD10F, RD10R, RD10intR [28].",
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"content": "Background",
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science.scientific_papers_summarization_single_doc_arxiv | science.scientific_papers_summarization_single_doc_arxiv.3006 | [
{
"content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nwe use a pre - computed database of 46800 synthetic flux and polarization spectra for field strengths of 1400 mg and a wide range of effective temperatures to generate synthetic zeeman spectra , which we subject to an automatic optimization scheme with the aim to recover the parameters describing the original magnetic field configuration .\nwe adopt input field geometries which involve the sum of non - aligned dipole and quadrupole components .\nwe also provide for off - centre shifts of the configuration . by adding gaussian noise we create input spectra with and 20 , respectively .\n= 0.80 off - centred dipole - quadrupole combinations are reliably recovered even for by our code , which can handle up to 12 free parameters but becomes inefficient if higher multipoles are included .\nthe poor convergence is caused by the complexity of the @xmath0-landscape , which develops an increasing number of secondary minima for more complex field geometries ( for a detailed investigation , see euchner et al . , 2002 ) .\nwe find that a given set of phase - resolved zeeman spectra can be reproduced within the noise by quite different formal representations of the field , which , however , all seem to describe rather similar actual field geometries\n. we are confident , therefore , that observed phase - resolved zeeman spectra can provide quite definite information on the field structure .\n= 0.85 the magnetic field structure over the surface of accreting white dwarfs in cataclysmic binaries becomes accessible to observation only in states of low or switched - off accretion .\nfollowing the first detection of zeeman lines in the polar eferidani ( @xmath1 = 81 min ) by wheatley & ramsay ( 1998 ) , we obtained phase - resolved flux and circular polarization spectra of this object with fors1 at the eso vlt on 22 nov 2000 .\nfig.1 shows the spectra collected in four almost equal phase bins after removal of a slight rotational temperature variation .\nthere is no obvious variation of the zeeman structures with phase .\nfits of inclined multipole field models with the angle @xmath2 between magnetic and rotational axis left free yielded .\nthe lack of phase dependence of the zeeman features further suggests that the tesseral / sectoral multipole components are weak .\nwe fitted the mean flux and polarization spectra , therefore , with an expansion including only the zonal components up to a maximum degree .\nfig.2 shows the dipole+quadrupole fit , which is substantially better than the pure dipole ( not shown ) .\nfig.3 depicts the result for the expansion up to .\nthe dipole is replaced by large coefficients for the higher - order multipole components which substantially improve the fit . while the higher - order multipole fit accounts for many of the observed details all the wiggles in the blue are genuine zeeman features \nthere are still noticeable discrepancies : ( i ) the observed lack of circular polarization around 5700 requires that a larger fraction of the field occurs at negative @xmath3 ( angle between line of sight and field direction ) , and ( ii ) the observed narrow spectral feature at 5120 can be fitted by additional field contributions with @xmath4 between 60 and 100 mg pointing away from the observer , possibly generated by a steeper rise of @xmath4 towards the lower ( unseen ) pole than provided by the model .",
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"content": "we have developed a new method to derive the magnetic field distribution on the surfaces of rotating magnetic white dwarfs from phase - resolved flux and circular polarization spectra . \n an optimization code based on an evolutionary strategy is used to fit synthetic zeeman spectra for a variety of model geometries described in the framework of a truncated multipole expansion . \n we demonstrate that the code allows the reconstruction of relatively complex fields using noise - added synthetic input spectra . as a first application \n , we analyze flux and circular polarization spectra of the polar eferi in a low state of accretion taken with fors1 at the eso vlt .",
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science.bioasq_factoid_qa | science.bioasq_factoid_qa.217 | [
{
"content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: In which kingdom do microsporidia belong, according to their current classification scheme?\n\nPassages: Microsporidia are a diverse group of obligate, intracellular, eukaryotic, spore-forming parasites. Traditionally, these were considered as protozoans but recently have been reclassified as fungi.\nMicrosporidia are ubiquitous fungi with genomes that have undergone a strong reduction\nMicrosporidia are unicellular fungi that are obligate endoparasites.\nPhylogenomics supports microsporidia as the earliest diverging clade of sequenced fungi.\nA combined analysis of thousands of gene trees supports a topology in which microsporidia is a sister group to all other sequenced fungi.\nAltogether, our data strongly support a scenario in which microsporidia is the earliest-diverging clade of sequenced fungi.\nMicrosporidia are a large diverse group of intracellular parasites now considered as fungi.\nThe unique genomic hallmarks between microsporidia and fungi are independent of sequence based phylogenetic comparisons and further contribute to define the borders of the fungal kingdom and support the classification of microsporidia as unusual derived fungi.\nThe kingdom Fungi is expanded by adding Microsporidia, because of protein sequence evidence that these amitochondrial intracellular parasites are related to conventional Fungi, not Protozoa.\nThe preponderance of evidence as to the origin of the microsporidia reveals a close relationship with the fungi, either within the kingdom or as a sister group to it.\nIn a subsequent analysis, we excluded the other Microsporidia from the analysis to look for relationships before the divergence of Microsporidia, and found that 43% of the microsporidial genes scored highest with fungal genes, and a higher mean LPI was found with Fungi than with other kingdoms, suggesting that Microsporidia is closely related to Fungi at the genomic level.\nCONCLUSION/SIGNIFICANCE: The unique genomic hallmarks between microsporidia and fungi are independent of sequence based phylogenetic comparisons and further contribute to define the borders of the fungal kingdom and support the classification of microsporidia as unusual derived fungi.\nThe unique genomic hallmarks between microsporidia and fungi are independent of sequence based phylogenetic comparisons and further contribute to define the borders of the fungal kingdom and support the classification of microsporidia as unusual derived fungi.\nThe kingdom Fungi is expanded by adding Microsporidia, because of protein sequence evidence that these amitochondrial intracellular parasites are related to conventional Fungi, not Protozoa.\nMicroorganisms of the microsporidia group are obligated intracellular protozoa that belong to the phylum Microspora; currently they are considered to be related or belong to the fungi reign",
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"content": "Fungi",
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science.pico_ner | science.pico_ner.4059 | [
{
"content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nCorticosteroid-induced osteopenia and vitamin D metabolism . Effect of vitamin D2 , calcium phosphate and sodium fluoride administration . Thirty-one patients scheduled for long-term ( 24 weeks ) treatment with prednisone in comparatively high doses were randomly allocated to two further treatment groups . Group A received prednisone plus 'triple-treatment ' ( vitamin D2 45000 iu twice weekly , sodium fluoride 50 mg and calcium phosphate 4.5 g daily ) , group B received only prednisone . The study was undertaken in order to evaluate the effect of prednisone- and triple-treatment upon bone mineral content ( BMC ) and vitamin D metabolism . The groups were comparable with regard to age , sex and prednisone dose . BMC fell rapidly and similarly in both groups , demonstrating that the triple-treatment has no preventive effect on corticosteroid induced osteopenia . Serum concentrations of 25OHD2 , 25OHD3 and 1,25 ( OH ) 2D were unchanged in group B ( without triple-treatment ) , whereas in group A 25OHD2 increased enormously , 25OHD3 was suppressed possibly by substrate competition for hydroxylation in the liver and 1,25 ( OH ) 2D was halved . The suppression of 1,25 ( OH ) 2D may be an effect of raised 25OHD2 alone , or in combination with corticosteroid excess .",
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"content": "{\"Intervention\": [\"vitamin D2 , calcium phosphate\", \"sodium fluoride\", \"Group A received prednisone plus \\u0027triple-treatment \\u0027 ( vitamin D2 45000 iu twice weekly , sodium fluoride 50 mg and calcium phosphate 4.5 g daily ) , group B received only prednisone\", \"triple-treatment\", \"prednisone-\", \"prednisone\"], \"Outcome\": [\"bone mineral content ( BMC )\", \"BMC\", \"25OHD2\", \"1,25 ( OH ) 2D\", \"Serum concentrations of 25OHD2 , 25OHD3 and 1,25 ( OH ) 2D\", \"25OHD3\", \"osteopenia\", \"vitamin D metabolism\"], \"Participant\": [\"Thirty-one\"]}",
"role": "assistant"
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.25579 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nTotal Synthesis of Aurofusarin: Studies on the Atropisomeric Stability of Bis-Naphthoquinones\n\nContent Extracts:\n\n<p>Naphthopyranone natural products[1] are widely found in nature and typically possess the 1H-naphtho-[2,3-c]pyran-1-one core structure as present in the dimer xanthomegnin (1)[2] (Figure 1). Aurofusarin (2)[3] and the bis-epoxyquinol diaporine (4),[4] an inhibitor of macrophage differentiation that induces conversion from the M2 (\"repair-type\") to the M1 (\"kill-type\") phenotype, are likely derived from the monomeric naphtho-γ-pyrone rubrofusarin (3).[5] Such γ-naphthopyranone scaffolds are difficult to access and there are few reported syntheses to date. For example, rubrofusarin (3) was previously synthesized in 14 steps in low yield[6] and a formal synthesis of 1 was achieved from a monomeric precursor (semi-vioxanthin).[2]</p><p>Herein, we report a concise synthesis of the γ-naphthopyranone monomeric unit and its Pd-catalyzed dehydrogenative dimerization to a biaryl precursor for aurofusarin. Based on the work of Thomson and co-workers concerning bismurrayaquinoneA (5)[7] and seminal work by Shair and coworkers on dimeric methoxyquinone-containing natural products,[8d] we wondered whether the atropisomers of bisnaphthoquinones such as (1)[2] and (2) are configurationally stable. Accordingly, we studied the axial chirality of 2 because it is crucial for the enantioselective synthesis of the congener diaporine (4).</p><p>Retrosynthetically, we envisioned that aurofusarin (2) may be accessed through oxidation of biaryl precursor 6 (Scheme 1). Construction of biaryl 6 requires highly selective conditions for oxidative dimerization, considering possible oxidation of 7 to a naphthoquinone. We proposed that monomer 7 may be obtained from aryl pyrone 8, a compound derived from tandem Michael addition/Dieckmann condensation of methoxy benzoquinone 9[8] and dienol ether 10. Compound 10 may be accessed from the commercially available dimethyl γ-pyrone 11.</p><p>To prepare substituted pyrone 8, we envisioned that treatment of 11 with trimethylsilyl triflate (TMSOTf) should afford a siloxypyrylium intermediate[9] that may be deprotonated under basic conditions. Accordingly, 11 was consecutively treated with TMSOTf and 2,6-lutidine, followed by addition of quinone 9.[10] Acidic conditions for workup (aq. HCl) were found to be crucial for the formation of 8, since a basic workup using tetra-N-butylammonium fluoride (TBAF) afforded an undesired benzofuran product[11] (Scheme 2). To overcome difficulties encountered in the monomethylation of 8, γ-pyrone 12 was synthesized through a double-methylation/selective demethylation sequence and was further converted intoMOMether 13. We next evaluated Dieckmann cyclization of 13. To our delight, use of lithium diisopropylamide (LDA) as base produced a 30% yield of the desired product 14, which was further improved to 77% by using degassed solvent. Methylation of 14 with Cs2CO3/dimethyl sulfate (Me2SO4) in degassed acetone led to 15, which was treated with trifluoroacetic acid (TFA) in CH2Cl2 to afford monomer 16 for dimerization studies.</p><p>Inspired by studies on the biosynthesis of aurofusarin, in which dimerization was shown to be catalyzed by Gip1, a copper-containing laccase enzyme,[12] we wished to mimic this process by using metal-mediated oxidative conditions. Accordingly, we initiated dimerization studies using copper salts with diamine ligands,[13a] which have been widely used in biaryl couplings. However, in general, conditions employing single-electron-oxidation metal catalysts such as NH4VO3, FeCl3, SnCl4, and AgOTFA only led to the production of a monomeric naphthoquinone product.[11, 13]</p><p>We reasoned that the electron-rich substrate 16 may require milder oxidative coupling conditions, which prompted our investigation of palladium-mediated dehydrogenative coupling.[14] After considerable experimentation, we found that treatment of 16 with Pd(OAc)2 (10 mol%) in DMSO afforded dimer (±)-17 (Table 1, entry 1). However, to achieve full conversion, a stoichiometric amount of Pd(OAc)2 was required. Encouraged by these results, we evaluated a number of ligands to facilitate catalyst turnover. Yu and co-workers[15] have demonstrated that monoprotected amino acids can be utilized as chiral ligands in asymmetric C–H bond activation. Accordingly, we evaluated the use of monoprotected amino acids with Pd(OAc)2. Treatment of 16 with catalytic Pd(OAc)2 and N-acetyl-l-leucine under aerobic conditions led to dimer (±)-17 after heating at 70 °C for 4 h (entry 2). The structure of (±)-17 was unambiguously confirmed by X-ray crystallographic analysis.[16] Evaluation of solvents showed that anhydrous DMSO provided optimal results, while non-coordinating solvents such as dichloroethane (DCE) (entry 3) led to lower reactivity. Other monoprotected amino acid ligands were found to be less effective for the transformation (entries 5–6). Among the chiral amino acid ligands evaluated, we unfortunately did not observe atropselectivity for the biaryl product 17.[17]</p><p>Attention was next turned to the synthesis of aurofusarin (2; Scheme 3). Treatment of (±)-17 with ceric ammonium nitrate (CAN) led to formation of bis-naphthoquinone 18 (88% yield). Synthesis of aurofusarin (2) was achieved on a gram scale in 78%yield through selective demethylation of 18 using BBr3. To study the atropisomeric stability of the bisnaphthoquinone moiety, a gram-scale synthesis of (±)-17 (see Table 1) was achieved and the compound subjected to deracemization using CuI/(+)-sparteine.[18] Optimal conditions involved in situ generation of a stoichiometric copper- (II)/sparteine complex, which led to 71% mass recovery and (−)-17 in 95% ee ([α]d25= −45°, c = 0.1, CH2Cl2; Scheme 4). Determination of the absolute configuration of (−)-17 was attempted using X-ray crystallography, but only a chiral, racemic crystal of (±)-17 was obtained. Presumably, photoracemization of (−)-17 (λmax = 405 nm) may occur during crystallization through excited-state intramolecular proton transfer.[11, 19]</p><p>To determine whether the atropisomers of bis-naphthoquinone 18 are configurationally stable, (−)-17 was oxidized with CAN (Scheme 5a). Analytical chiral HPLC analysis of the resulting bis-quinone 18 did not reveal enantiomer separation, and additionally, no optical rotation was observed.[11] Accordingly, further derivatization of 18 to epoxide 19 was performed. Epoxidation by NaOCl afforded bis-epoxide 19 as a single diastereomer. However, from chiral HPLC analysis, compound 19 derived from (−)-17 was racemic, which further supports the idea that the atropisomers of 18 are likely rapidly interconverting. The relative stereochemistry of bis-epoxide 19 was further studied with the model reaction shown in Scheme 5b. Model bis-quinone 20[20] was treated with NaOCl in CH3CN to afford epoxide 22 as a single diastereomer in 78% yield and the relative stereochemistry of 22 was determined by X-ray crystallographic analysis.[16] From this model reaction, it appears that the cisrelationship of the epoxides in 22 is derived from epoxidations anti to the methoxy groups in the bisected bis-quinone conformer 21.</p><p>Based on the reactivity observed, we envisioned that asymmetric epoxidation of 18 derived from (±)-17 could be utilized to further validate our hypothesis for atropisomeric instability of 18.[20] Asymmetric nucleophilic epoxidations of enones have been extensively studied[21] but are generally conducted on simple monomeric quinones.[22] Accordingly, a series of phase-transfer catalysts (PTCs) were examined, and the cinchonine-derived catalysts 23 and the corresponding dimeric cinchonine catalyst 24 provided up to 75%ee. We ultimately identified the Maruoka phase-transfer catalyst 25[23] (Scheme 6) as a suitable catalyst for asymmetric epoxidation, which afforded bis-epoxide (−)-19 in 62% yield and 97% ee as a single diastereomer. The absolute configuration of (−)-19 was determined by comparison of the experimental electronic circular dichroism (ECD) spectrum with calculated spectra.[11] In this reaction, four stereocenters are formed with high selectivity.</p><p>A number of factors have been cited as contributing to atropisomeric stability of bis-quinones, including carbonyl bond lengths[7] and out-of-plane-distortions.[7] Shair and coworkers have provided a rationale for the pH-dependent atropisomerism of the methoxyquinone-containing natural product hibarimicinone, which involves cross-conjugated resonance structures.[8d] While related contributing zwitterionic structures and deviation of the quinone carbonyl group from planarity may be relevant for xanthomegnin 1 and aurofusarin methyl ether 18,[11] a comparison of the X-ray structures of 1 and 5 along with a DFT model of 18 (Figure 2) also shows shortening of the C–OCH3 bond of 1 and 18 (1.342 Å and 1.345 Å) in comparison to the C–CH3 bond length of 5 (1.479 Å). This bond shortening appears to be a factor in lowering the barrier for atropisomerization of 2. The calculated barrier for 18 (24.6 kcal mol−1, B3LYP/6-31G(d))[11, 24] is also similar to the energy barrier for the interconversion of atropisomers (22.2 kcal mol−1) suggested by Ōki.[25]</p><p>In summary, we have developed an efficient annulation involving pyrone addition to a quinone for rapid assembly of a γ-naphthopyrone monomer en route to the natural product aurofusarin. Dimerization of the γ-naphthopyrone was achieved through PdII-mediated dehydrogenative coupling wherein a simple mono-protected amino acid was found to be a suitable ligand for a catalytic process. In addition, asymmetric nucleophilic epoxidation of aurofusarin derivative 18 supports the hypothesis that the atropisomers of bismethoxy naphthoquinones such as aurofusarin are not configurationally stable. Extension of the method to access an enantioenriched bis-epoxide intermediate for the synthesis of diaporine is currently in progress and will be reported in due course.</p>",
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"content": "An efficient annulation involving pyrone addition to a quinone and Dieckmann condensation was developed for rapid assembly of a \\xce\\xb3-naphthopyrone monomeric precursor to the bis-naphthoquinone natural product aurofusarin. Dimerization was achieved through PdII-catalyzed dehydrogenative coupling. Further studies employing asymmetric nucleophilic epoxidation indicate that the atropisomers of aurofusarin and derivatives are not configurationally stable at ambient temperature.",
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science.mslr2022_cochrane_multidoc_summarization | science.mslr2022_cochrane_multidoc_summarization.623 | [
{
"content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nEffects of individualized versus classical \"relaxation\" music on the frequency of agitation in elderly persons with Alzheimer's disease and related disorders.\nReport Abstract 1:\nConfusion and agitation in elderly patients are crucial problems. This study tested Gerdner's mid-range theory of individualized music intervention for agitation. An experimental repeated measures pretest-posttest crossover design compared the immediate and residual effects of individualized music to classical \"relaxation\" music relative to baseline on the frequency of agitated behaviors in elderly persons with Alzheimer's disease and related disorders (ADRD). Thirty-nine subjects were recruited from six long-term-care facilities in Iowa. The sample consisted of 30 women and 9 men (mean age 82 years) with severe cognitive impairment. Baseline data were collected for 3 weeks. Findings from the Modified Hartsock Music Preference Questionnaire guided the selection of individualized music. Group A (n = 16) received individualized music for 6 weeks followed by a 2-week \"washout\" period and 6 weeks of classical \"relaxation\" music. Group B (n = 23) received the same protocol but in reverse order. Music interventions were presented for 30 minutes, two times per week. The Modified Cohen-Mansfield Agitation Inventory measured the dependent variable. A repeated measures analysis of variance with Bonferroni post hoc test showed a significant reduction in agitation during and following individualized music compared to classical music. This study expands science by testing and supporting a theoretically based intervention for agitation in persons with ADRD.\n\n\nReport Title 2:\nEfficacy of music therapy in the treatment of behavioral and psychiatric symptoms of dementia.\nReport Abstract 2:\nMusic therapy (MT) has been proposed as valid approach for behavioral and psychologic symptoms (BPSD) of dementia. However, studies demonstrating the effectiveness of this approach are lacking.\n To assess MT effectiveness in reducing BPSD in subjects with dementia.\n Fifty-nine persons with dementia were enrolled in this study. All of them underwent a multidimensional assessment including Mini Mental State Examination, Barthel Index and Neuropsychiatry Inventory at enrollment and after 8, 16, and 20 weeks. Subjects were randomly assigned to experimental (n=30) or control (n=29) group. The MT sessions were evaluated with standardized criteria. The experimental group received 30 MT sessions (16 wk of treatment), whereas the control group received educational support or entertainment activities.\n NPI total score significantly decreased in the experimental group at 8th, 16th, and 20th weeks (interaction time x group: F3,165=5.06, P=0.002). Specific BPSD (ie, delusions, agitation, anxiety, apathy, irritability, aberrant motor activity, and night-time disturbances) significantly improved. The empathetic relationship and the patients' active participation in the MT approach, also improved in the experimental group.\n The study shows that MT is effective to reduce BPSD in patients with moderate-severe dementia.\n\n\nReport Title 3:\nThe impact of music therapy on language functioning in dementia.\nReport Abstract 3:\nDementias, such as Alzheimer's disease, include a progressive deterioration of language functioning. While some researchers have reported an increase in patients' self-expression following music therapy, it is not clear whether these changes specifically reflect improved language skills or whether simple interpersonal interaction with a therapist could account for the improvement. In this study, the effects of music therapy were compared to conversational sessions on language functioning in dementia patients. Participants were selected according to the following criteria: (a) residing in a facility specializing in Alzheimer's and related disorders; (b) possessing sufficient verbal ability to answer simple questions and to comply with requests to speak, participate, or sit down; and (c) attaining the written consent of the patient's guardian or representative. All participants had been in music therapy twice per week for at least 3 months prior to the study onset. One week prior to the beginning of the study, subjects were assessed for cognitive functioning using the Mini-Mental State Examination (MMSE), and language ability via the Western Aphasia Battery (WAB). A within-subjects design was used, with order of condition (music or group conversation first) counter-balanced between participants. Subjects participated in groups of 2 to 4, twice per week for 20-30 minutes for a total of 8 sessions (4 music therapy and 4 conversation sessions or vice-versa), and were re-tested on the WAB at the end of each 2 week (4 session) interval. Results from 20 participants revealed that music therapy significantly improved performance on both speech content and fluency dimensions of the spontaneous speech subscale of the WAB (p =.01). While the difference in overall Aphasia Quotient (AQ) for music and conversation sessions (mean AQ = 76 vs. 70, respectively) did not reach statistical significance, data were only available for 10 participants (5 per condition). Hopefully, these findings will stimulate additional research on the use of music therapy interventions with demented patients, as it may offer a noninvasive mechanism to enhance communication between victims and their caregivers.\n\n\nReport Title 4:\nEffects of music on Alzheimer patients.\nReport Abstract 4:\nFrom a large nursing care facility, 60 elderly patients diagnosed as having Alzheimer disease were randomly separated into three groups of equal size and given tests to measure their mood and mental state. For music Group 1, \"Big Band\" music from the 1920s and 1930s was played during their daily recreation period while Group 2 were given puzzle exercises during their activity sessions. Members of Group 3 participated in the standard recreational activities of drawing and painting. After six months, the questionnaire was again given to all participants. Analysis of variance showed the individuals in Group 1 were more alert, happier, and had higher recall of past personal history than patients in the other two groups. This suggests that music can be of therapeutic value to Alzheimer patients.\n\n\nReport Title 5:\nUse of music to decrease aggressive behaviors in people with dementia.\nReport Abstract 5:\nThe purpose of this study was to examine the effects of recorded, preferred music in decreasing occurrences of aggressive behavior among individuals with Alzheimer's type dementia during bathing episodes. Eighteen older adults, age 55 to 95, with severe levels of cognitive impairment, participated in the study. They were randomly scheduled for observation during bath time under either a control (no music) condition or an experimental condition in which recorded selections of preferred music were played via audiotape recorder during the bathing episode. Following a 2-week (10 episode) observation period, conditions were reversed. A total of 20 observations were recorded for each individual. Results indicated that during the music condition, decreases occurred in 12 of 15 identified aggressive behaviors. Decreases were significant (p < 0.05) for the total number of observed behaviors and for hitting behaviors. During the music condition, caregivers frequently reported improved affect and a general increase in cooperation with the bathing task. The implications of these findings for improving the overall quality of care for severely cognitively impaired older adults are discussed.\n\n\nReport Title 6:\nMusic therapy in moderate and severe dementia of Alzheimer's type: a case-control study.\nReport Abstract 6:\nMusic therapy is a potential non-pharmacological treatment for the behavioral and psychological symptoms of dementia, but although some studies have found it to be helpful, most are small and uncontrolled.\n This case-control study was carried out by qualified music therapists in two nursing homes and two psychogeriatric wards. The participants were 38 patients with moderate or severe Alzheimer's disease (AD) assigned randomly to a music therapy group and a control group.\n The study showed a significant reduction in activity disturbances in the music therapy group during a 6-week period measured with the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). There was also a significant reduction in the sum of scores of activity disturbances, aggressiveness and anxiety. Other symptoms rated by subscales of the BEHAVE-AD did not decrease significantly. Four weeks later the effects had mostly disappeared.\n Music therapy is a safe and effective method for treating agitation and anxiety in moderately severe and severe AD. This is in line with the results of some non-controlled studies on music therapy in dementia.\n\n\nReport Title 7:\nEffect of music therapy on anxiety and depression in patients with Alzheimer's type dementia: randomised, controlled study.\nReport Abstract 7:\nNumerous studies have indicated the value of music therapy in the management of patients with Alzheimer's disease. A recent pilot study demonstrated the feasibility and usefulness of a new music therapy technique. The aim of this controlled, randomised study was to assess the effects of this new music therapy technique on anxiety and depression in patients with mild to moderate Alzheimer-type dementia.\n This was a single-centre, comparative, controlled, randomised study, with blinded assessment of its results. The duration of follow-up was 24 weeks. The treated group (n = 15) participated in weekly sessions of individual, receptive music therapy. The musical style of the session was chosen by the patient. The validated 'U' technique was employed. The control group (n = 15) participated under the same conditions in reading sessions. The principal endpoint, measured at weeks 1, 4, 8, 16 and 24, was the level of anxiety (Hamilton Scale). Changes in the depression score (Geriatric Depression Scale) were also analyzed as a secondary endpoint.\n Significant improvements in anxiety (p < 0.01) and depression (p < 0.01) were observed in the music therapy group as from week 4 and until week 16. The effect of music therapy was sustained for up to 8 weeks after the discontinuation of sessions between weeks 16 and 24 (p < 0.01).\n These results confirm the valuable effect of music therapy on anxiety and depression in patients with mild to moderate Alzheimer's disease. This new music therapy technique is simple to implement and can easily be integrated in a multidisciplinary programme for the management of Alzheimer's disease.\n Copyright 2009 S. Karger AG, Basel.",
"role": "user"
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{
"content": "The methodological quality and the reporting of the included studies were too poor to draw any useful conclusions.",
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science.data_reco_mcq_mc | science.data_reco_mcq_mc.977 | [
{
"content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: An unsupervised stereo matching algorithm that can significantly reduce the search space and speed up existing tree-based non-\n\nKey Terms: depth estimation images\n\nDataset Summaries:\nSydney Urban Objects: This dataset contains a variety of common urban road objects scanned with a Velodyne HDL-64E LIDAR, collected in the CBD of Sydney, Australia. There are 631 individual scans of objects across classes of vehicles, pedestrians, signs and trees.\nMiddlebury: The Middlebury Stereo dataset consists of high-resolution stereo sequences with complex geometry and pixel-accurate ground-truth disparity data. The ground-truth disparities are acquired using a novel technique that employs structured lighting and does not require the calibration of the light projectors.\nMVSEC: The Multi Vehicle Stereo Event Camera (MVSEC) dataset is a collection of data designed for the development of novel 3D perception algorithms for event based cameras. Stereo event data is collected from car, motorbike, hexacopter and handheld data, and fused with lidar, IMU, motion capture and GPS to provide ground truth pose and depth images.\nKITTI: KITTI (Karlsruhe Institute of Technology and Toyota Technological Institute) is one of the most popular datasets for use in mobile robotics and autonomous driving. It consists of hours of traffic scenarios recorded with a variety of sensor modalities, including high-resolution RGB, grayscale stereo cameras, and a 3D laser scanner.\nRarePlanes Dataset: The dataset specifically focuses on the value of synthetic data to aid computer vision algorithms in their ability to automatically detect aircraft and their attributes in satellite imagery. Although other synthetic/real combination datasets exist, RarePlanes is the largest openly-available very-high resolution dataset built to test the value of synthetic data from an overhead perspective.\nGVGAI: The General Video Game AI (GVGAI) framework is widely used in research which features a corpus of over 100 single-player games and 60 two-player games. These are fairly small games, each focusing on specific mechanics or skills the players should be able to demonstrate, including clones of classic arcade games such as Space Invaders, puzzle games like Sokoban, adventure games like Zelda or game-theory problems such as the Iterative Prisoners Dilemma.\n\nDataset Options: A: Sydney Urban Objects B: Middlebury C: MVSEC D: KITTI E: RarePlanes Dataset F: GVGAI",
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"content": "[\"Middlebury\", \"KITTI\"]",
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science.anat_em_ner | science.anat_em_ner.449 | [
{
"content": "Analyze the provided text from a biomedical study. Your task is to detect and list entities based on predefined categories.\n\nPresent your results in a JSON format: {\"AnatomicalEntity\": [\"entity1\", \"entity2\", ...]}. Each category should have a corresponding list of identified entities. \n\nText:\n\nResearch advances of endostatin and its short internal fragments.\nEndostatin, the C-terminal fragment of collagen XVIII, is a potent angiogenesis inhibitor. At present, there are a large number of research papers on endostatin. However, the action mechanism of endostatin is still a matter of ongoing discussion. The objective of this review is to elucidate its origin and elementary structure, and to discuss its structure basis of activity and action mechanisms based on the latest research. Furthermore, some published studies reporting the antiangiogenic effects of endostatin-derived peptides were also reviewed. It is proposed that the amino acid sequence of endostatin contains both angiosuppressive and angiostimulatory domains. Short endostatin fragments may be exploited as a new angiogenesis inhibitor for therapeutic applications, in substitution of the full length endostatin. These studies on endostatin fragments also shed light on our understanding of the molecular action mechanisms of endostatin.",
"role": "user"
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{
"content": "{\"AnatomicalEntity\": []}",
"role": "assistant"
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science.healthver_entailment | science.healthver_entailment.1847 | [
{
"content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: In rare cases, a coronavirus jumps from animals to humans. This is thought to have happened for the virus that causes COVID-19, as well as two other types of deadly coronaviruses, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). All three originated in bats. \n\nResearch Abstract:\nSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--the virus that causes coronavirus disease (COVID-19)--has been detected in domestic dogs and cats, raising concerns of transmission from, to, or between these animals.\nThere is currently no indication that feline- or canine-to-human transmission can occur, though there is rising evidence of the reverse.\nTo explore the extent of animal-related transmission, we aggregated 17 case reports on confirmed SARS-CoV-2 infections in animals as of 15 May 2020.\nAll but two animals fully recovered and had only mild respiratory or digestive symptoms.\nUsing data from probable cat-to-cat transmission in Wuhan, China, we estimated the basic reproduction number R0 under this scenario at 1.09 (95% confidence interval: 1.05, 1.13).\nThis value is much lower than the R0 reported for humans and close to one, indicating that the sustained transmission between cats is unlikely to occur.\nOur results support the view that the pet owners and other persons with COVID-19 in close contact with animals should be cautious of the way they interact with them.",
"role": "user"
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{
"content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"There is currently no indication that feline- or canine-to-human transmission can occur, though there is rising evidence of the reverse.\"]}",
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science.anat_em_ner | science.anat_em_ner.480 | [
{
"content": "Analyze the provided text from a biomedical study. Your task is to detect and list entities based on predefined categories.\n\nPresent your results in a JSON format: {\"AnatomicalEntity\": [\"entity1\", \"entity2\", ...]}. Each category should have a corresponding list of identified entities. \n\nText:\n\nEndothelial cell migration and vascular endothelial growth factor expression are the result of loss of breast tissue polarity.\nRecruiting a new blood supply is a rate-limiting step in tumor progression. In a three-dimensional model of breast carcinogenesis, disorganized, proliferative transformed breast epithelial cells express significantly higher expression of angiogenic genes compared with their polarized, growth-arrested nonmalignant counterparts. Elevated vascular endothelial growth factor (VEGF) secretion by malignant cells enhanced recruitment of endothelial cells (EC) in heterotypic cocultures. Significantly, phenotypic reversion of malignant cells via reexpression of HoxD10, which is lost in malignant progression, significantly attenuated VEGF expression in a hypoxia-inducible factor 1alpha-independent fashion and reduced EC migration. This was due primarily to restoring polarity: forced proliferation of polarized, nonmalignant cells did not induce VEGF expression and EC recruitment, whereas disrupting the architecture of growth-arrested, reverted cells did. These data show that disrupting cytostructure activates the angiogenic switch even in the absence of proliferation and/or hypoxia and restoring organization of malignant clusters reduces VEGF expression and EC activation to levels found in quiescent nonmalignant epithelium. These data confirm the importance of tissue architecture and polarity in malignant progression.",
"role": "user"
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"content": "{\"AnatomicalEntity\": [\"nonmalignant counterparts\", \"nonmalignant epithelium\", \"tissue\", \"breast epithelial cells\", \"cytostructure\", \"endothelial cells\", \"malignant clusters\", \"nonmalignant cells\", \"cells\", \"EC\", \"blood\", \"tumor\", \"breast\", \"Endothelial cell\", \"malignant cells\", \"breast tissue\"]}",
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science.mslr2022_ms2_multidoc_summarization | science.mslr2022_ms2_multidoc_summarization.11729 | [
{
"content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: Bolus Weekly Vitamin D3 Supplementation Impacts Gut and Airway Microbiota in Adults With Cystic Fibrosis: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial\nSummary: Context Disruption of gut microbiota may exacerbate severity of cystic fibrosis ( CF ) . Vitamin D deficiency is a common comorbidity in patients with CF that may influence composition of the gut microbiota . Objectives Compare microbiota of vitamin D-sufficient and -insufficient CF patients and assess impact of a weekly high-dose vitamin D3 bolus regimen on gut and airway microbiome in adults with CF and vitamin D insufficiency ( 25-hydroxyvitamin D < 30 ng/mL ) . Design Forty-one subjects with CF were classified into two groups : vitamin D insufficient ( n = 23 ) and vitamin D sufficient ( n = 18 ) . Subjects with vitamin D insufficiency were r and omized to receive 50,000 IU of oral vitamin D3 or placebo weekly for 12 weeks . Sputum and stool sample s were obtained pre- and postintervention and 16S ribosomal RNA genes sequenced using Illumina MiSeq technology . Results Gut microbiota differed significantly based on vitamin D status with Gammaproteobacteria , which contain numerous , potentially pathogenic species enriched in the vitamin D-insufficient group . Principal coordinates analysis showed differential gut microbiota composition within the vitamin D-insufficient patients following 12 weeks treatment with placebo or vitamin D3 ( permutation multivariate analysis of variance = 0.024 ) , with Lactococcus significantly enriched in subjects treated with vitamin D3 , whereas Veillonella and Erysipelotrichaceae were significantly enriched in patients treated with placebo . Conclusion This exploratory study suggests that vitamin D insufficiency is associated with alterations in microbiota composition that may promote inflammation and that supplementation with vitamin D has the potential to impact microbiota composition . Additional studies to determine the impact of vitamin D on microbiota benefit clinical outcomes in CF are warranted\n\n\nReport 2:\nTitle: Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans.\nSummary: The importance of gut microbiota in pathogenesis of diabetes remains unknown . This study investigated the relationship between microbiota and metabolic markers in African American men ( AAM ) with prediabetes and hypovitaminosis D. The study was ancillary to a r and omized trial of vitamin D supplementation with weekly ergocalciferol ( 50,000 IU ) conducted in AAM veterans over 12 months ( D Intervention in Veterans Affairs ) . Glycemic groups ( Gr ) were characterized based on changes in oral glucose tolerance between baseline and exit . Subjects with stable normal glucose tolerance were assigned to Gr-1 and those with stable prediabetes ( impaired glucose tolerance and impaired fasting glucose ) to Gr-2 . Microbiota composition was analyzed in stool collected at the exit ( n = 115 ) and compared between Gr-1 and Gr-2 , as well as between the lowest and highest quartiles of dietary intake of energy and fat , hemoglobin A1c , and serum 25-hydroxyvitamin D ( 25[OH]D ) level . Differences between Gr-1 and Gr-2 included the Bacteroidetes/Firmicutes and Bacteroidales/Clostridia ratios and differences in genera such as Ruminococcus and Dialister . Changes in specific taxa associated with the lowest and highest quartiles of 25(OH)D ( eg , Ruminococcus , Roseburia , Blautia , Dorea ) were clearly distinct from those of dietary intake ( eg , Bacteroides , Bacteroides/Prevotella ratio ) or A1c ( eg , Faecalibacterium , Catenibacterium , Streptococcus ) . These findings suggest a novel interaction between microbiota and vitamin D and a role for microbiota in early stages of diabetes development . Although results suggest that specific taxa are associated with glycemic stability over time , a causative relationship between microbiota makeup and dysglycemia is still to be demonstrated\n\n\nReport 3:\nTitle: Influence of vitamin D on key bacterial taxa in infant microbiota in the KOALA Birth Cohort Study\nSummary: Vitamin D has immunomodulatory properties giving it the potential to affect microbial colonization of the intestinal tract . We investigated whether maternal vitamin D supplemention , maternal plasma 25-hydroxyvitamin D concentration , or direct supplementation of the infant influences key bacterial taxa within microbiota of one month old infants . Infant and maternal vitamin D supplement use was ascertained via question naires . Maternal plasma 25-hydroxyvitamin D was determined at approximately the 36th week of pregnancy . In 913 one month old infants in the prospect i ve KOALA Birth Cohort Study , fecal Bifidobacterium spp . , Escherichia coli , Clostridium difficile , Bacteroides fragilis group , Lactobacillus spp . and total bacteria were quantified with real-time polymerase chain reaction assays targeting 16S rRNA gene sequences . The association between vitamin D exposure and prevalence or abundance of a specific bacterial group or species was analyzed using logistic or linear regression , respectively . There was a statistically significant negative linear trend between counts of Bifidobacterium spp . and levels of maternal vitamin D supplementation and maternal 25-hydroxyvitamin D quintiles , respectively . In addition , a positive linear trend between quintile groups and B. fragilis group counts was observed . Lower counts of C. difficile were associated with vitamin D supplementation of breast fed infants whose mothers were more likely to adhere to an alternative lifestyle in terms of , e.g. , dietary habits . These data suggest that vitamin D influences the abundance of several key bacterial taxa within the infant microbiota . Given that intestinal microbiotic homeostasis may be an important factor in the prevention of immune mediated diseases and that vitamin D status is a modifiable factor , further investigation of the impact of postnatal vitamin D supplementation should be conducted in older infants\n\n\nReport 4:\nTitle: Factors influencing the infant gut microbiome at age 3‐6 months: Findings from the ethnically diverse Vitamin D Antenatal Asthma Reduction Trial (VDAART)\nSummary: Background : The gut microbiome in infancy influences immune system maturation , and may have an important impact on allergic disease risk . Objective : We sought to determine how prenatal and early life factors impact the gut microbiome in a relatively large , ethnically diverse study population of infants at age 3 to 6 months , who were enrolled in Vitamin D Antenatal Asthma Reduction Trial , a clinical trial of vitamin D supplementation in pregnancy to prevent asthma and allergies in offspring . Methods : We performed 16S rRNA gene sequencing on 333 infants ' stool sample s. Microbial diversity was computed using the Shannon index . Factor analysis applied to the top 25 most abundant taxa revealed 4 underlying bacterial coabundance groups ; the first dominated by Firmicutes ( Lachnospiraceae/Clostridiales ) , the second by Proteobacteria ( Klebsiella/Enterobacter ) , the third by Bacteriodetes , and the fourth by Veillonella . Scores for coabundance groups were used as outcomes in regression models , with prenatal/birth and demographic characteristics as independent predictors . Multivariate analysis , using all microbial community members , was also conducted . Results : White race/ethnicity was associated with lower diversity but higher Bacteroidetes coabundance scores . C‐section birth was associated with higher diversity , but decreased Bacteroidetes coabundance scores . Firmicutes scores were higher for infants born by C‐section . Breast‐fed infants had lower proportions of Clostridiales . Cord blood vitamin D was linked to increased Lachnobacterium , but decreased Lactococcus . Conclusions : The findings presented here suggest that race , mode of delivery , breast‐feeding , and cord blood vitamin D levels are associated with infant gut microbiome composition , with possible long‐term implication s for immune system modulation and asthma/allergic disease incidence",
"role": "user"
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{
"content": "Conclusions Despite substantial heterogeneity , we found evidence to support the hypothesis that vitamin D influences the composition of the gastrointestinal microbiome .",
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science.qasper_extractive_qa | science.qasper_extractive_qa.491.0 | [
{
"content": "Analyze the given research paper excerpts and address the question provided. Extract the necessary information directly from the text. Your answer should be formatted as a JSON object with the following structure:\n\n\"answer\": A list of text segments from the paper that directly respond to the question.\n\"evidence\": A list of text segments from the paper where the answer can be found.\n\nIf the question cannot be answered with the given text, return \"null\".\n\nDocument: A Joint Model for Question Answering and Question Generation\n\nWe propose a generative machine comprehension model that learns jointly to ask and answer questions based on documents. The proposed model uses a sequence-to-sequence framework that encodes the document and generates a question (answer) given an answer (question). Significant improvement in model performance is observed empirically on the SQuAD corpus, confirming our hypothesis that the model benefits from jointly learning to perform both tasks. We believe the joint model's novelty offers a new perspective on machine comprehension beyond architectural engineering, and serves as a first step towards autonomous information seeking.\n\nIntroduction\nQuestion answering (QA) is the task of automatically producing an answer to a question given a corresponding document. It not only provides humans with efficient access to vast amounts of information, but also acts as an important proxy task to assess machine literacy via reading comprehension. Thanks to the recent release of several large-scale machine comprehension/QA datasets BIBREF0 , BIBREF1 , BIBREF2 , BIBREF3 , BIBREF4 , the field has undergone significant advancement, with an array of neural models rapidly approaching human parity on some of these benchmarks BIBREF5 , BIBREF6 , BIBREF7 . However, previous models do not treat QA as a task of natural language generation (NLG), but of pointing to an answer span within a document.\nAlongside QA, question generation has also gained increased popularity BIBREF8 , BIBREF9 . The task is to generate a natural-language question conditioned on an answer and the corresponding document. Among its many applications, question generation has been used to improve QA systems BIBREF10 , BIBREF11 , BIBREF12 . A recurring theme among previous studies is to augment existing labeled data with machine-generated questions; to our knowledge, the direct (though implicit) effect of asking questions on answering questions has not yet been explored.\nIn this work, we propose a joint model that both asks and answers questions, and investigate how this joint-training setup affects the individual tasks. We hypothesize that question generation can help models achieve better QA performance. This is motivated partly by observations made in psychology that devising questions while reading can increase scores on comprehension tests BIBREF13 . Our joint model also serves as a novel framework for improving QA performance outside of the network-architectural engineering that characterizes most previous studies.\nAlthough the question answering and asking tasks appear symmetric, there are some key differences. First, answering the questions in most existing QA datasets is extractive — it requires selecting some span of text within the document — while question asking is comparatively abstractive — it requires generation of text that may not appear in the document. Furthermore, a (document, question) pair typically specifies a unique answer. Conversely, a typical (document, answer) pair may be associated with multiple questions, since a valid question can be formed from any information or relations which uniquely specify the given answer.\nTo tackle the joint task, we construct an attention-based BIBREF14 sequence-to-sequence model BIBREF15 that takes a document as input and generates a question (answer) conditioned on an answer (question) as output. To address the mixed extractive/abstractive nature of the generative targets, we use the pointer-softmax mechanism BIBREF16 that learns to switch between copying words from the document and generating words from a prescribed vocabulary. Joint training is realized by alternating the input data between question-answering and question-generating examples for the same model. We demonstrate empirically that this model's QA performance on SQuAD, while not state of the art, improves by about 10% with joint training. A key novelty of our joint model is that it can generate (partially) abstractive answers.\n\nRelated Work\nJoint-learning on multiple related tasks has been explored previously BIBREF17 , BIBREF18 . In machine translation, for instance, BIBREF18 demonstrated that translation quality clearly improves over models trained with a single language pair when the attention mechanism in a neural translation model is shared and jointly trained on multiple language pairs.\nIn question answering, BIBREF19 proposed one of the first neural models for the SQuAD dataset. SQuAD defines an extractive QA task wherein answers consist of word spans in the corresponding document. BIBREF19 demonstrated that learning to point to answer boundaries is more effective than learning to point sequentially to the tokens making up an answer span. Many later studies adopted this boundary model and achieved near-human performance on the task BIBREF5 , BIBREF6 , BIBREF7 . However, the boundary-pointing mechanism is not suitable for more open-ended tasks, including abstractive QA BIBREF4 and question generation. While “forcing” the extractive boundary model onto abstractive datasets currently yields state-of-the-art results BIBREF5 , this is mainly because current generative models are poor and NLG evaluation is unsolved.\nEarlier work on question generation has resorted to either rule-based reordering methods BIBREF20 , BIBREF21 , BIBREF22 or slot-filling with question templates BIBREF23 , BIBREF24 , BIBREF25 . These techniques often involve pipelines of independent components that are difficult to tune for final performance measures. Partly to address this limitation, end-to-end-trainable neural models have recently been proposed for question generation in both vision BIBREF26 and language. For example, BIBREF8 used a sequence-to-sequence model with an attention mechanism derived from the encoder states. BIBREF9 proposed a similar architecture but in addition improved model performance through policy gradient techniques.\nSeveral neural models with a questioning component have been proposed for the purpose of improving QA models, an objective shared by this study. BIBREF12 devised a semi-supervised training framework that trained a QA model BIBREF27 on both labeled data and artificial data generated by a separate generative component. BIBREF10 used policy gradient with a QA reward to train a sequence-to-sequence paraphrase model to reformulate questions in an existing QA dataset BIBREF2 . The generated questions were then used to further train an existing QA model BIBREF7 . A key distinction of our model is that we harness the process of asking questions to benefit question answering, without training the model to answer the generated questions.\n\nModel Description\nOur proposed model adopts a sequence-to-sequence framework BIBREF15 with an attention mechanism BIBREF14 and a pointer-softmax decoder BIBREF16 . Specifically, the model takes a document (i.e., a word sequence) $D = (w^d_1,\\dots ,w^d_{n_d})$ and a condition sequence $C = (w^c_1,\\dots ,w^c_{n_c})$ as input, and outputs a target sequence $Y^{\\lbrace q,a\\rbrace } = (\\hat{w}_1,\\dots ,\\hat{w}_{n_p})$ . The condition corresponds to the question word sequence in answer-generation mode (a-gen), and the answer word sequence in question-generation mode (q-gen). We also attach a binary variable to indicate whether a data-point is intended for a-gen or q-gen. Intuitively, this should help the model learn the two modalities more easily. Empirically, QA performance improves slightly with this addition.\n\nEncoder\nA word $w_i$ in an input sequence is first embedded with an embedding layer into vector ${\\bf e}^w_i$ . Character-level information is captured with the final states ${\\bf e}^{ch}_i$ of a bidirectional Long Short-Term Memory model BIBREF28 on the character sequences of $w_i$ . The final representation for a word token ${\\bf e}_i=\\langle {\\bf e}^w_i,{\\bf e}^{ch}_i\\rangle $ concatenates the word- and character-level embeddings. These are subsequently encoded with another BiLSTM into annotation vectors ${\\bf h}^d_i$ and ${\\bf h}^c_j$ (for the document and the condition sequence, respectively).\nTo better encode the condition, we also extract the encodings of the document words that appear in the condition sequence. This procedure is particularly helpful in q-gen mode, where the condition (answer) sequence is typically extractive. These extracted vectors are then fed into a condition aggregation BiLSTM to produce the extractive condition encoding ${\\bf h}^e_k$ . We specifically take the final states of the condition encodings ${\\bf h}^c_J$ and ${\\bf h}^e_K$ . To account for the different extractive vs. abstractive nature of questions vs. answers, we use ${\\bf h}^c_J$ in a-gen mode (for encoding questions) and ${\\bf h}^e_K$ in q-gen mode (for encoding answers).\n\nTraining and Inference\nThe optimization objective for updating the model parameters $\\theta $ is to maximize the negative log likelihood of the generated sequences with respect to the training data $\\mathcal {D}$ : $\n\\mathcal {L}=-\\sum _{x\\in \\mathcal {D}}\\log p(\\hat{w}_t|w_{<t},x;\\theta ).\n$ \nHere, $w_{<t}$ corresponds to the embeddings ${\\bf y}^{(t-1)}$ in Equation ( 1 ) and ( 3 ). During training, gold targets are used to teacher-force the sequence generation for training, i.e., $w_{<t}=w^{\\lbrace q,a\\rbrace }_{<t}$ , while during inference, generation is conditioned on the previously generated words, i.e., $w_{<t}=\\hat{w}_{<t}$ .\nFor words with multiple occurrence, since their exact references in the document cannot be reiabled determined, we aggregate the probability of these words in the encoder and the pointing decoder (similar to BIBREF29 ). At test time, beam search is used to enhance fluency in the question-generation output. The decoder also keeps an explicit history of previously generated words to avoid repetition in the output.\n\nDataset\nWe conduct our experiments on the SQuAD corpus BIBREF1 , a machine comprehension dataset consisting of over 100k crowd-sourced question-answer pairs on 536 Wikipedia articles. Simple preprocessing is performed, including lower-casing all texts in the dataset and using NLTK BIBREF30 for word tokenization. The test split of SQuAD is hidden from the public. We therefore take 5,158 question-answer pairs (self-contained in 23 Wikipedia articles) from the training set as validation set, and use the official development data to report test results. Note that answers in this dataset are strictly extractive, and we therefore constrain the pointer-softmax module to point at all decoding steps in answer generation mode.\n\nBaseline Models\nWe first establish two baselines without multi-task training. Specifically, model A-gen is trained only to generate an answer given a document and a question, i.e., as a conventional QA model. Analogously, model Q-gen is trained only to generate questions from documents and answers. Joint-training (in model JointQA) is realized by feeding answer-generation and question-generation data to the model in an alternating fashion between mini-batches.\nIn addition, we compare answer-generation performance with the sequence model variant of the match-LSTM (mLSTM) model BIBREF19 . As mentioned earlier, in contrast to existing neural QA models that point to the start and end boundaries of extractive answers, this model predicts a sequence of document positions as the answer. This makes it most comparable to our QA setup. Note, however, that our model has the additional capacity to generate abstractively from the decoder vocabulary.\n\nQuantitative Evaluation\nWe use F1 and Exact Match (EM, BIBREF1 ) against the gold answer sequences to evaluate answer generation, and BLEU BIBREF31 against the gold question sequences to evaluate question generation. However, existing studies have shown that the task of question generation often exhibits linguistic variance that is semantically admissible; this renders it inappropriate to judge a generated question solely by matching against a gold sequence BIBREF9 . We therefore opt to assess the quality of generated questions $Y^q$ with two pretrained neural models as well: we use a language model to compute the perplexity of $Y^q$ , and a QA model to answer $Y^q$ . We measure the F1 score of the answer produced by this QA model.\nWe choose mLSTM as the pretrained QA model and train it on SQuAD with the same split as mentioned in Section \"Dataset\" . Performance on the test set (i.e., the official validation set of SQuAD) is 73.78 F1 and 62.7 EM. For the pretrained language model, we train a single-layer LSTM language model on the combination of the text8 corpus, the Quora Question Pairs corpus, and the gold questions from SQuAD. The latter two corpora were included to tailor to our purpose of assessing question fluency, and for this reason, we ignore the semantic equivalence labels in the Quora dataset. Validation perplexity is 67.2 for the pretrained language model.\n\nImplementation Details\nImplementation details of the proposed model are as follows. The encoder vocabulary indexes all words in the dataset. The decoder vocabulary uses the top 100 words sorted by their frequency in the gold questions in the training data. This encourages the model to generate frequent words (e.g. wh-words and function words) from the decoder vocabulary and copy less frequent ones (e.g., topical words and entities) from the document.\nThe word embedding matrix is initialized with the 300-dimensional GloVe vectors BIBREF33 . The dimensionality of the character representations is 32. The number of hidden units is 384 for both of the encoder/decoder RNN cells. Dropout is applied at a rate of 0.3 to all embedding layers as well as between the hidden states in the encoder/decoder RNNs across time steps.\nWe use adam BIBREF34 as the step rule for optimization with mini-batch size 32. The initial learning rate is $2e-4$ , which is decayed at a rate of 0.5 when the validation loss increases for two consecutive epochs.\nThe model is implemented using Keras BIBREF35 with the Theano BIBREF36 backend.\n\nConclusion\nWe proposed a neural machine comprehension model that can jointly ask and answer questions given a document. We hypothesized that question answering can benefit from synergistic interaction between the two tasks through parameter sharing and joint training under this multitask setting. Our proposed model adopts an attention-based sequence-to-sequence architecture that learns to dynamically switch between copying words from the document and generating words from a vocabulary. Experiments with the model confirm our hypothesis: the joint model outperforms its QA-only counterpart by a significant margin on the SQuAD dataset.\nAlthough evaluation scores are still lower than the state-of-the-art results achieved by dedicated QA models, the proposed model nonetheless demonstrates the effectiveness of joint training between QA and question generation, and thus offers a novel perspective and a promising direction for advancing the study of QA.\n\nTable 1. Model evaluation on question- and answer-generation.\n\nFigure 1. Comparison between A-gen and JointQA stratified by answer types. The dashed curve indicates period-2 moving average of the performance difference between the models.\n\nTable 2. Examples of QA behaviour changes possibly induced by joint training. Gold answers correspond to text spans in green. In both the positive and the negative cases, the answers produced by the joint model are highly related (and thus presumably influenced) by the generated questions.\n\nInquiry: Which components of QA and QG models are shared during training?",
"role": "user"
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"content": "{\"answer\": [\"parameter sharing\"], \"evidence\": [\"We proposed a neural machine comprehension model that can jointly ask and answer questions given a document. We hypothesized that question answering can benefit from synergistic interaction between the two tasks through parameter sharing and joint training under this multitask setting. Our proposed model adopts an attention-based sequence-to-sequence architecture that learns to dynamically switch between copying words from the document and generating words from a vocabulary. Experiments with the model confirm our hypothesis: the joint model outperforms its QA-only counterpart by a significant margin on the SQuAD dataset.\"]}",
"role": "assistant"
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science.pico_ner | science.pico_ner.2483 | [
{
"content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nEarly intervention for autism with a parent-delivered Qigong massage program : a randomized controlled trial . A recent randomized controlled trial ( RCT ) of a dual parent and trainer-delivered qigong massage intervention for young children with autism resulted in improvement of measures of autism as well as improvement of abnormal sensory responses and self-regulation . The RCT evaluated the effects of the parent-delivered component of the intervention . Forty-seven children were randomly assigned to treatment and wait-list control groups . Treatment group children received the parent-delivered program for 4 mo . Trained therapists provided parent training and support . Improvement was evaluated in two settings -- preschool and home -- by teachers ( blind to group ) and parents . Results showed that the parent-delivered program was effective in improving measures of autism ( medium effect size ) and sensory and self-regulatory responses ( large effect size ) . Teacher data on measures of autism were confirmed by parent data . Results indicate that the parent-delivered component of the program provided effective early intervention for autism that was suitable for delivery at home .",
"role": "user"
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"content": "{\"Intervention\": [\"parent training and support\", \"parent-delivered component\", \"dual parent and trainer-delivered qigong massage\", \"parent-delivered program for 4 mo\", \"parent-delivered Qigong massage program\"], \"Outcome\": [\"abnormal sensory responses\", \"autism\", \"self-regulation .\", \"sensory and self-regulatory responses\"], \"Participant\": [\"autism\", \"Forty-seven\", \"children\", \"young children\"]}",
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science.scientific_lay_summarisation_elife_single_doc_summ | science.scientific_lay_summarisation_elife_single_doc_summ.596 | [
{
"content": "Transform the provided sections of a biomedical research paper into a digestible summary for a general audience. Focus on simplifying complex ideas while retaining key scientific insights.\n\nResearch Title: Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma\nContent Overview:\nAbstract:\nHLA-restricted T cell responses can induce antitumor effects in cancer patients. Previous human T cell research has largely focused on the few HLA alleles prevalent in a subset of ethnic groups. Here, using a panel of newly developed peptide-exchangeable peptide/HLA multimers and artificial antigen-presenting cells for 25 different class I alleles and greater than 800 peptides, we systematically and comprehensively mapped shared antigenic epitopes recognized by tumor-infiltrating T lymphocytes( TILs) from eight melanoma patients for all their class I alleles. We were able to determine the specificity, on average, of 12. 2% of the TILs recognizing a mean of 3. 1 shared antigen-derived epitopes across HLA-A, B, and C. Furthermore, we isolated a number of cognate T cell receptor genes with tumor reactivity. Our novel strategy allows for a more complete examination of the immune response and development of novel cancer immunotherapy not limited by HLA allele prevalence or tumor mutation burden.\nIntroduction:\nCancer immunotherapy is a cancer treatment that is designed to harness the power of the body's immune system to fight cancer( Finn, 2018a). The magnitude and breadth of T cell responses can serve as a critical biomarker in cancer immunotherapy and conventional cancer treatments, such as chemotherapy and radiation( Schumacher et al., 2015). Immunotherapy is now widely considered a game-changer, as it is rapidly becoming the 4th pillar of cancer treatment, following surgery, radiotherapy, and chemotherapy. The adoptive transfer of antitumor T cells can induce clinical responses in cancer patients( Feldman et al., 2015; Hu et al., 2018; Karpanen and Olweus, 2015; Rapoport et al., 2015; Robbins et al., 2015; Sahin and Türeci, 2018; Tran et al., 2016; Tran et al., 2017). However, comprehensive analysis of the specificity of antitumor T cell responses against mutated or non-mutated tumor antigens is lacking. This deficit is exacerbated by the fact that non-mutated antigens are greater in number than mutated antigens by multiple orders of magnitude( Finn and Rammensee, 2018) and the high polymorphism of HLA genes( Shao et al., 2018). The clinical importance of identifying antitumor T cell responses is highlighted by the results of recent clinical trials which attest that a shared antigen, such as NY-ESO-1, can be targeted with potent on-target efficacy and minimal off-target toxicity in T cell receptor( TCR) gene therapy( Rapoport et al., 2015; Robbins et al., 2015; Thomas et al., 2018). Unlike shared antigens, the vast majority of neoantigens are unique to each patient( Coulie et al., 2014; Finn, 2018b). The elucidation of T cell epitopes derived from shared antigens may facilitate the robust development of an efficacious and safe adoptive T cell therapy that is readily available to a larger cohort of cancer patients. Analysis of antigen-specific T cells using peptide/HLA( pHLA) multimers has been utilized as a standard technique in immunology over the past two decades( Bentzen and Hadrup, 2017; Dey et al., 2019; Dolton et al., 2015). Recent progress in multimer technology has enabled the high-throughput analysis of antigen-specific T cells during immune responses( Bentzen and Hadrup, 2017). However, the production of each multimer is still cumbersome and expensive because in vitro peptide exchange of generated complete pHLA proteins requires multiple complicated steps( Toebes et al., 2006) and some class I alleles are not easily produced in bacteria( Migueles et al., 2000). Therefore, further advancements in multimer technology are needed to investigate the multitude of potential tumor-associated antigen( TAA) peptides presented by any given class I allele. The combination of pHLA multimer-based analysis and functional assays are utilized to measure antigen-specific T cell responses. We have developed a novel peptide-exchangeable pHLA class I multimer technology that can be applied for any given class I allele and bound peptide. Unlike comparable methods( Andersen et al., 2012; Migueles et al., 2000), our novel pHLA multimer technology enables a one-step peptide exchange in one tube and is more effective in class I alleles that are difficult to produce in bacteria. These technical advantages allow for a rapid, versatile, and less labor-intensive examination of the immune response. In addition, to functionally detect HLA-restricted antigen-specific T cell responses, we previously demonstrated the versatility of gene-engineered artificial antigen-presenting cells( APCs) individually expressing various class I alleles as a single HLA allele( Butler and Hirano, 2014). Our strategy using a paired library of the novel pHLA multimer and human cell-based artificial APC system enables identification of novel class I epitopes and detection of cognate T cells in a comprehensive and systematic way.\nDiscussion:\nHLA-restricted T cell responses toward immunogenic peptides, mutated or non-mutated, can induce antitumor effects in cancer patients( Feldman et al., 2015; Rapoport et al., 2015; Robbins et al., 2015; Tran et al., 2016). Since the HLA gene is the most polymorphic gene in the human genome( Shao et al., 2018), previous human T cell research has largely been limited to the few HLA alleles that are prevalent in a subset of ethnic groups. Therefore, a precise and comprehensive understanding of the antigen specificity for antitumor T cell responses remains lacking, including against non-mutated tumor antigens and infrequent HLA alleles. The sheer number of potential non-mutated antigens and the high polymorphism of HLA genes may have hampered comprehensive analysis of the specificity of antitumor T cell responses. The adoptive transfer of tumor-reactive T cells, such as TILs or T cells transduced with high-affinity TCR genes, can induce sustained tumor regression in some cancer patients( Feldman et al., 2015; Rapoport et al., 2015; Robbins et al., 2015; Tran et al., 2016). In this study, using a library of the paired pHLA multimers and artificial APCs for 25 different class I alleles and greater than 800 peptides, we systematically and comprehensively mapped shared antigenic epitopes recognized by TILs from eight melanoma patients for all their class I alleles. Furthermore, we isolated multiple TCR genes highly tumor-reactive to shared antigens from the TILs. In particular, NY-ESO-1 is one of the shared antigens that have been most promising and extensively studied, and many clinical trials using A*02:01/NY-ESO-1157-165 TCR genes are ongoing. The use of these newly cloned tumor-reactive B*07:02, B*40:01, and C*03:04-restricted NY-ESO-1 TCR genes may widen the applicability of anti-NY-ESO-1 TCR gene therapy and immune mobilizing monoclonal TCRs against cancer( ImmTAC) therapy beyond HLA-A*02:01-positive cancer patients. ImmTAC therapy trials targeting A*02:01/gp100 are also ongoing in patients with metastatic uveal melanoma( Liddy et al., 2012). The newly cloned tumor-reactive gp100 TCRs restricted by four different class I alleles( A*24:02, B*40:01, C*06:02, and C*07:01) could substantially extend the applicability of ImmTAC therapy targeting gp100. The strategy employed in this study has enabled us to decipher the antigen specificity of tumor-specific T cells for any given HLA class I allele, regardless of allele frequency( Supplementary file 4), and for a very large number of peptides. Although we studied T cell responses to greater than 800 peptides derived from more than 90 proteins across all the 25 class I alleles expressed by eight melanoma patients, our study is still limited. Additional comprehensive studies are required to elucidate the full spectrum of antitumor T cell response in TILs. Since in vitro expanded TILs were studied in the current study, further assessment of TIL directly ex vivo is needed in future studies. Our strategy has also allowed us to build a large database of class I-restricted peptides and cognate tumor-reactive TCR genes at an unprecedented scale. This database will facilitate individual examination of the personal immune response with precision as well as the identification and validation of biomarkers to aid in patient-based selection of a cancer immunotherapy regimen. Furthermore, this database will help the robust development of novel cancer vaccines, TCR gene therapies, and ImmTAC therapies for patients without being limited by HLA allele prevalence or tumor mutation burden.",
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"content": "The immune system is the body’s way of defending itself , offering protection against diseases such as cancer . But to remove the cancer cells , the immune system must be able to identify them as different from the rest of the body . All cells break down proteins into shorter fragments , known as peptides , that are displayed on the cell surface by a protein called human leukocyte antigen , HLA for short . Cancer cells display distinctive peptides on their surface as they generate different proteins to those of healthy cells . Immune cells called T cells use these abnormal peptides to identify the cancer so that it can be destroyed . Sometimes T cells can lack the right equipment to detect abnormal peptides , allowing cancer cells to hide from the immune system . However , T cells can be trained through a treatment called immunotherapy , which provides T cells with new tools so that they can spot the peptides displayed by HLA on the previously ‘hidden’ cancer cells . There are many different forms of HLA , each of which can display different peptides . Current research in immunotherapy commonly targets only a subset of HLA forms , and not all cancer patients have these types . This means that immunotherapy research is only likely to be of most benefit to a limited number of patients . Immunotherapy could be made effective for more people if new cancer peptides that are displayed by the other ‘under-represented’ forms of HLA were identified . Murata , Nakatsugawa et al . have now used T cells that were taken from tumors in eight patients with melanoma , which is a type of skin cancer . A library of fluorescent HLA-peptides was generated – using a new , simplified methodology – with 25 forms of HLA that displayed over 800 peptides . T cells were then mixed with the library to identify which HLA-peptides they can target . As a result , Murata , Nakatsugawa et al . found the cancer targets of around 12% of the tumor-infiltrating T cells tested , including those from under-represented forms of HLA . Consequently , these findings could be used to develop new immunotherapies that can treat more patients .",
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science.bioasq_yesno_qa | science.bioasq_yesno_qa.660 | [
{
"content": "Examine the provided biomedical text and determine the answer to the question. Your response should be either \"yes\" or \"no\" based on the information given.\n\nQuestion: Is Solanezumab effective for Alzheimer's Disease?\n\nText: An analysis of publicly available data from the Phase II studies for bapineuzumab and solanezumab indicates that neither compound produced compelling evidence of drug-like behavior that would justify their progression into pivotal trials.\nNotably, a recent study of solanezumab, an amyloid β monoclonal antibody, raises hope for the further therapeutic potential of immunotherapy, not only in Alzheimer's disease, but also for other neurodegenerative disorders, including Parkinson's disease.\nFor example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer's drug solanezumab which failed to reach statistical significance.\nAreas covered: This contradiction prompted us to review all study phases of Intravenous Immunoglobulin (IVIG), Bapineuzumab, Solanezumab, Avagacestat and Dimebolin to shed more light on these recent failures.\nResults from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD.\nSecondary analyses of EXPEDITION studies suggested a smaller functional effect of solanezumab relative to cognition. An increasing effect of solanezumab over 18 months was shown for cognition and function.\nRESULTS: In the mild AD population, less cognitive and functional decline was observed with solanezumab (n = 659) versus placebo (n = 663), measured by Alzheimer's Disease Assessment Scale Cognitive subscale, Mini-Mental State Examination, and Alzheimer's Disease Cooperative Study-Activities of Daily Living functional scale Instrumental ADLs.\nThe promising results obtained with aducanumab and solanezumab against Alzheimer's disease (AD) strengthen the vaccine approach to prevent AD, despite of the many clinical setbacks.\nCONCLUSIONS: Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability.\nResults from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing.",
"role": "user"
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{
"content": "no",
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science.covid_deepset_qa | science.covid_deepset_qa.574 | [
{
"content": "Analyze the following excerpt from a biomedical text. Identify the relevant information needed to respond to the inquiry. Provide only the necessary details in your answer.\n\nContext: Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in Réunion Island, 2011-2012\n\nhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031398/\n\nSHA: f5ff89ebfdd0375d034c112c6c1c7e163fa69a0c\n\nAuthors: Brottet, Elise; Jaffar-Bandjee, Marie-Christine; Li-Pat-Yuen, Ghislaine; Filleul, Laurent\nDate: 2016-09-21\nDOI: 10.1371/journal.pone.0163377\nLicense: cc-by\n\nAbstract: In Réunion Island, despite an influenza surveillance established since 1996 by the sentinel general practitioner’s network, little is known about the etiology of Influenza like-illness (ILI) that differs from influenza viruses in a tropical area. We set up a retrospective study using nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012. A total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) including research of 18 viruses and 4 bacteria. We detected respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses. We observed important seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter. In conclusion, this study highlights a substantial circulation of multiple respiratory pathogens in Réunion Island throughout the year. It shows that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI. Text: Influenza like-illness (ILI) or acute respiratory infections can be caused by several types of respiratory viruses or bacteria in humans [1] . Influenza viruses, Respiratory Syncytial viruses (RSV) and Parainfluenza viruses are identified as major viruses mostly responsible for ILI and pneumonia in several studies [2] . However practitioners cannot diagnose the infection without a biological test confirmation. Unfortunately, these infections causes are identified in less than 50% [3] . Réunion Island, a French overseas territory with 850,000 inhabitants, is located in the southern hemisphere between Madagascar and Mauritius in the Indian Ocean (Latitude: 21°05.2920 S Longitude: 55°36.4380 E.). The island benefits from a healthcare system similar to mainland France and epidemiological surveillance has been developed by the regional office of the French Institute for Public Health Surveillance (Cire OI), based on the surveillance system of mainland France [4] . Influenza activity generally increases during austral winter, corresponding to summer in Europe [5] . Since 2011, influenza vaccination campaign in Reunion Island starts in April and the vaccine used corresponds to World Health Organization recommendations for the southern hemisphere. Since 1996, clinical and biological influenza surveillance has been based on a sentinel practitioner's network [6] . In 2014, this network was composed of 58 general practitioners (GPs) spread over the island and represented around 7% of all Réunion Island GPs. Nasal swabs are randomly collected all along the year and are tested by RT-PCR for influenza viruses. Among these surveillance samples, 40 to 50% are tested positive for influenza A virus, A(H1N1)pdm09 or B virus by the virological laboratory of the University Hospital Center of Réunion. Thus ILI samples tested negative for influenza are of unknown etiology. Several biological tools allow identifying respiratory pathogens from nasal swab. In recent years, multiplex reverse transcriptase polymerase chain reaction (RT-PCR) has been developed to identify several viruses simultaneously [7] [8] [9] [10] . We therefore used this new method to set up a retrospective study using swabs collected by sentinel GPs from 2011 to 2012. The main objective of our study was to characterize respiratory pathogens responsible for ILI consultations in sentinel GPs in 2011 and 2012. Secondary objectives were to highlight seasonal trends on respiratory pathogens circulation and to describe occurrence of co-infections, especially during the flu season. ILI was defined as a sudden onset of fever more than 38 degrees Celsius and cough, associated or not with other symptoms such as breathing difficulty, headache, etc. Every week, all GPs of the sentinel network were encouraged to collect a nasal swab from the first two patients who presented ILI since less than three days. After being tested for influenza viruses, the 994 swabs collected in 2011 and 2012 are frozen at -80°C at the university hospital center (CHU) laboratory. Based on the budget, a season-stratified sample of 250 swabs was randomly selected in order to describe circulating viruses including outside flu season. Random sampling was performed with Excel 1 using the anonymized surveillance database of the Cire OI. The sampling frame contained identification number of swab assigned by Cire OI, laboratory identification number, sex, age, date of onset of symptoms, date of swab collection and result of influenza RT-PCR. \n\nWe used Respifinder 1 Smart 22 kits a multiplex RT-PCR (PathoFinder, Maastricht, The Netherlands) which can detect 22 respiratory pathogens. This assay is based on the multiplex ligation-dependent probe amplification (MLPA) technology. The reverse transcription and preamplification steps were performed on the epgradient Mastercycler 1 (Eppendorf) and the hybridization, ligation and detection steps on the LightCycler 1 480 system (Roche Applied Science). This method was chosen because of its high specificity, compared to other same methods (78% versus 33%) [3, 11] . Multiplex analysis allows for rapid production of diagnostic results. It thus allows highlighted the possible presence of eighteen respiratory viruses and four bacteria in one reaction by melt curve analysis: Influenza A not (H1N1 \n\nStatistical analyses were performed with Stata 1 and Excel 1 . Two seasons were defined to identify possible seasonal trends in circulation of the viruses: winter season during weeks 23 to 39 between June and September and summer season during the rest of the year. Data and swabs result from a surveillance system that received regulatory approvals, including the CNIL (National Commission for Information Technology and Civil Liberties Number 1592205) approval in July 2012. All the patients have received oral information and gave their consent for swab and data collection. Data were collected for surveillance purpose and are totally anonymous. Among the 250 randomly-selected swabs, 26 were not available anymore as they were sent to Influenza Reference Center for confirmation and characterization of the pathogenic agent. According to the sensitivity of the assay two samples could be discordant results between Influenza PCR initially realized and Multiplex PCR. Thus they were deleted from the analysis: one is positive for Influenza in singleplex and negative for all tested pathogens in multiplex and one is positive for Influenza in singleplex and positive for PIV2 in multiplex. In total, 222 analyses were considered. Moreover, 53 samples were negative for all analyzed respiratory pathogens (23.9%) and 169 samples had at least one detected pathogen (76.1%), finally a total of 178 pathogens was identified. During the study period, a minority of the weeks (21 i.e. 20%) did not include any sampled swab, mainly outside flu season. Patients' sex-ratio was 0.63 (86 men and 136 women) and mean age was 28.4 years [min 0; max 81]. Ten percent had less than 5 years, 24% 5-15 years, 63% 15-65 years and only 3% were 65 and older. The respiratory pathogens most frequently identified in ILI swabs were rhinovirus (23.4%), influenza A not H1N1 (21.2%) and influenza B (12.6%) ( Table 1) . Among the 22 respiratory pathogens tested by the multiplex, only three were not found in any analyzed sample: Parainfluenza3, Legionella pneumophila and Bordetella pertussis. Regarding co-infections, nine swabs revealed the presence of two viruses, among which6 involved influenza viruses (Table 2) . Analyses showed that some viruses are possibly seasonal and were circulating during a specific period of the year. They are detected only in summer for Human Metapneumovirus, RSV A and B, and influenza A(H1N1)pdm09. For the latter, it is specific to the studied period since the influenza A(H1N1)pdm09 virus reappeared in Réunion Island in October 2012 and was no longer circulating since late 2010. On the opposite, Parainfluenza 1,2 and 4 viruses were identified only in winter. For other pathogens, no specific period of detection was observed. A weekly description of samples was realized to study the distribution of respiratory pathogens in 2011 and 2012 (Fig 1) . Results of biological analyses were compared with data of ILI consultations declared by sentinel GPs in 2011 and 2012. We observed in 2011, after a first wave in June mainly due to influenza A not H1N1 virus, a second wave of ILI consultations with mainly identification of Parainfluenza viruses and not influenza viruses. In 2012, the second epidemic wave at the end of austral winter coincided with Influenza viruses and Rhinovirus circulation. Regarding negative swabs (Fig 2) , we observed no seasonality during the study period with a similar proportion whatever the season. This retrospective study based on a sentinel GPs network showed that not only influenza viruses are responsible for ILI consultations. Indeed, an important circulation of multiple pathogens was observed throughout the year, with 12 different types of pathogens identified in 2011 and 2012. Respiratory viral pathogens were present in 76.1% of samples, which is largely above results from annual influenza surveillance [12] . After influenza viruses, Rhinovirus and Coronavirus were the most common respiratory viruses in Réunion Island. Although samples were not taken every week, sample was representative of ILI activity and consistent with flu season. Nevertheless, according to the low number of samples, it is difficult to conclude about seasonality. However in our study, RSV was circulating in summer season which is hot and rainy, which is confirmed by other studies in tropical region [13] . This study also highlighted several co-infections, showing that concomitant the multiple etiology of ILI. Co-circulation was already observed in Réunion Island during the A(H1N1) pdm09 pandemic in addition to influenza virus, with identification of other respiratory viruses such as Rhinovirus or Coronavirus [14] . In mainland France, during this pandemic, circulation of major respiratory viruses was found, such as Rhinovirus, Parainfluenza, Coronavirus, Human Metapneumovirus, like in our publication [15] [16] . In our study, only 5.3% of positive swabs were co-infections whereas in two studies in Madagascar co-infections represented 27.3% and 29.4% [17] [18] . Despite the distance of 9,300 km between Réunion and France, the island is directly connected to Europe with four daily flights to France. These exchanges can impact respiratory pathogens circulation in southern and northern hemisphere. Results of this study can therefore be of interest to both Indian Ocean and Europe countries. Among the 148 swabs initially negative for influenza because not previously tested for any other viruses, the study found an etiology for 95 swabs. In total, only 53 swabs, representing 24% of the sample, remained without etiology with negative multiplex PCR results all along the year. Multiple hypotheses can explain this result: a poor quality of swabs, preventing from identifying a pathogen, noninfectious causes or other pathogens not included in the multiplex PCR. However, we couldn't test the negative swabs for RNAse P, a marker of human cells, which could provide a modicum of assurance that the swab contained human cells. Concerning the two samples divergent for influenza identification between the multiplex and singleplex PCR, we discarded them for the analysis; one was positive in Influenza with singleplex and positive in PIV with multiplex. It could be a false positive result from singleplex. Indeed, as the multiplex PCR assay has a good sensitivity and is considered as a gold-standard, we decided to keep seven negative results for Influenza in singleplex and positive in Influenza in multiplex [7] [8] [9] [10] . No case of Bordetella pertussis which causes whooping cough and Legionella pneumophila which causes Legionnaires' disease was identified in this study. However, these diseases are rare in Réunion Island, around three cases of Legionnaires' disease are declared each year. A limit of the study is that no clinical data were available in the virological surveillance system of influenza in Réunion Island. It was impossible to compare clinical symptoms according to each pathogen and to know if there are different pathogens which cause for instance rhinitis, laryngitis or bronchitis (diseases included in ILI). A specific prospective study including clinical data might provide useful elements in the semiotics of diseases. In conclusion, this study highlighted an important circulation of multiple pathogens in Réunion Island throughout the year. It shows that ILI is not specific to influenza and so it is essential to have biological results in order to establish the differential diagnosis and thus explain the etiology of symptoms. For a better understanding of respiratory pathogens circulating in Réunion Island, information from this study may also be useful to practitioners who see many patients in consultation with ILI. As the use of multiplex RT-PCR showed its efficacy in the ILI surveillance and allowed to highlight the circulation of other viruses and bacterial causes of respiratory infections, it is now used routinely in the surveillance of ILI. Moreover, it would be interesting to repeat this study every 3 or 5 years adding clinical data to monitor the evolution of respiratory pathogens in Réunion Island over time.\n\nInquiry: How was random sampling performed?",
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"content": "with Excel 1 using the anonymized surveillance database of the Cire OI. The sampling frame contained identification number of swab assigned by Cire OI, laboratory identification number, sex, age, date of onset of symptoms, date of swab collection and result of influenza RT-PCR.",
"role": "assistant"
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science.chemdner_ner | science.chemdner_ner.1606 | [
{
"content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nInactivation of Lrp5 in osteocytes reduces young's modulus and responsiveness to the mechanical loading. Low-density-lipoprotein receptor-related protein 5 (Lrp5) is a co-receptor in Wnt signaling, which plays a critical role in development and maintenance of bone. Osteoporosis-pseudoglioma syndrome, for instance, arises from loss-of-function mutations in Lrp5, and global deletion of Lrp5 in mice results in significantly lower bone mineral density. Since osteocytes are proposed to act as a mechanosensor in the bone, we addressed a question whether a conditional loss-of-function mutation of Lrp5 selective to osteocytes (Dmp1-Cre;Lrp5(f/f)) would alter responses to ulna loading. Loading was applied to the right ulna for 3 min (360 cycles at 2Hz) at a peak force of 2.65 N for 3 consecutive days, and the contralateral ulna was used as a non-loaded control. Young's modulus was determined using a midshaft section of the femur. The results showed that compared to age-matched littermate controls, mice lacking Lrp5 in osteocytes exhibited smaller skeletal size with reduced bone mineral density and content. Compared to controls, Lrp5 deletion in osteocytes also led to a 4.6-fold reduction in Young's modulus. In response to ulna loading, mineralizing surface, mineral apposition rate, and bone formation rate were diminished in mice lacking Lrp5 in osteocytes by 52%, 85%, and 69%, respectively. Collectively, the results support the notion that the loss-of-function mutation of Lrp5 in osteocytes causes suppression of mechanoresponsiveness and reduces bone mass and Young's modulus. In summary, Lrp5-mediated Wnt signaling significantly contributes to maintenance of mechanical properties and bone mass.",
"role": "user"
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{
"content": "{\"Chemical\": []}",
"role": "assistant"
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science.mslr2022_ms2_multidoc_summarization | science.mslr2022_ms2_multidoc_summarization.1022 | [
{
"content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: Randomized, Double-blind 6-Month Comparison of Olanzapine and Quetiapine in Patients With Schizophrenia or Schizoaffective Disorder With Prominent Negative Symptoms and Poor Functioning\nSummary: Abstract : This study compared the effects of olanzapine ( OLZ ) with those of quetiapine ( QUE ) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning . In this 6-month , multicenter , double-blind clinical trial , patients were r and omized to treatment with OLZ ( n = 171 , 10 - 20 mg/d ) or QUE ( n = 175 , 300 - 700 mg/d ) . Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans . The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms . Secondary measures assessed changes in functioning , psychopathology , and treatment tolerability . Treatment with OLZ or QUE led to a significant reduction in negative symptoms , with no between-group difference ( P = 0.09 ) . Both treatment groups also showed significant improvement on most efficacy measures . Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale , Quality of Life Instrumental Role domain , and level of effort in psychosocial or occupational rehabilitation programs . Significantly more OLZ-treated patients completed the study ( 52.6 % OLZ , 37.7 % QUE , P = 0.007 ) . Treatment differences in safety were relatively small and not thought to be clinical ly relevant . Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE . Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy\n\n\nReport 2:\nTitle: A double-blind randomized study assessing safety and efficacy following one-year adjunctive treatment with bitopertin, a glycine reuptake inhibitor, in Japanese patients with schizophrenia\nSummary: Background Bitopertin , a glycine reuptake inhibitor , was investigated as a novel treatment for schizophrenia . We report all the results of a double-blind r and omized study assessing safety and efficacy following 52-week adjunctive treatment with bitopertin in Japanese patients with schizophrenia . Methods This study enrolled Japanese out patients with schizophrenia who met criteria for either “ negative symptoms ” , i.e. , patients with persistent , predominant negative symptoms of schizophrenia even after long-term treatment with antipsychotics or “ sub-optimally controlled symptoms ” , i.e. , patients with insufficiently improved symptoms of schizophrenia even after long-term treatment with antipsychotics , respectively . One hundred sixty-one patients were r and omly assigned to receive 52-week treatments with bitopertin doses of 5 , 10 , or 20 mg/day at ratio of 1:5:5 , where existing antipsychotics were concomitantly administered . Efficacy endpoints included Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impression ( CGI ) , and Personal and Social Performance ( PSP ) . The purpose of the present study is primarily to evaluate the safety , and secondarily to investigate the clinical efficacy of bitopertin . Results One hundred fourteen patients ( 71 % ) completed 52-week treatment with bitopertin . Most of the adverse events were mild or moderate in their severity . The patients in the 20-mg group experienced more adverse events than the patients in the other two groups . Common dose-dependent adverse events were somnolence and insomnia associated with worsening schizophrenia . The blood hemoglobin levels gradually decreased from baseline in a dose-dependent manner , but there were no patients with the decrease below 10 g/dL that would have led to their discontinuation . All the efficacy endpoints gradually improved in all the treatment groups for both of the two symptoms , while there were no clear differences among the three dose groups . Conclusions Altogether , bitopertin was found to be generally safe and well-tolerated for the treatment of patients with schizophrenia . All three bitopertin treated groups showed improvements in all the efficacy endpoints for both of the two symptoms , i.e. , “ negative symptoms ” and “ sub-optimally controlled symptoms ” , throughout the duration of the study .Trial registration Japan Pharmaceutical Information Center , number JapicCTI-111627 ( registered on September 20 , 2011\n\n\nReport 3:\nTitle: Application and Results of the Manchester Short Assessment of Quality of Life (Mansa)\nSummary: Background Based on experiences and empirical evidence gained in studies using the Lancashire Quality of Life Profile ( LQLP ) , the Manchester Short Assessment of Quality of Life ( MANSA ) has been developed as a condensed and slightly modified instrument for assessing quality of life . Its properties have been tested in a sample of community care patients . Method Fifty-five r and omly selected patients on the Care Programme Approach were interviewed using the LQLP , the MANSA and the Brief Psychiatric Rating Scale . Results Correlations between subjective quality of life scores on MANSA and LQLP were all 0.83 or higher ( 0.94 for the satisfaction mean score ) . Cronbach 's alpha for satisfaction ratings was 0.74 , and association with psychopathology was in line with results for LQLP as reported in the literature . Conclusions The MANSA is a brief instrument for assessing quality of life focusing on satisfaction with life as a whole and with life domains . Its psychometric properties appear satisfactory\n\n\nReport 4:\nTitle: Development and validation of a patient-based health-related quality of life questionnaire in schizophrenia: the S-QoL\nSummary: We developed a self-administered instrument to assess health-related quality of life ( HRQL ) among people with schizophrenia . The S-QoL , based on Calman 's approach to the subject 's point of view , is a multidimensional instrument that is sensitive to change . The scale is a 41-item question naire with eight subscales ( psychological well-being , self-esteem , family relationships , relationships with friends , resilience , physical well-being , autonomy and sentimental life ) and a total score . In-depth interviews with patients determined the pertinent issues for item development . The validation study , performed with 207 patients , showed high internal consistency reliability , reproducibility and responsiveness . Construct validity was confirmed using established clinical and HRQL measures . S-QoL covers domains that differ from areas tapped in other measures , with greater responsiveness . The S-QoL is an efficient instrument for the measurement of the impact of schizophrenia on individuals ' lives\n\n\nReport 5:\nTitle: Improvement of schizophrenic patients’ subjective well-being under atypical antipsychotic drugs\nSummary: Recent research indicates that subjective well-being is a major determinant of medication compliance in schizophrenia . However , it is yet unresolved whether atypical neuroleptics differ regarding subjective side-effects . A self-report instrument has been constructed to evaluate ' subjective well-being under neuroleptics ' ( SWN ) . The primary aims of the present study were to develop a short form of the SWN and to investigate the extent to which the atypical antipsychotic improves the patient 's subjective well-being . The short form of the SWN was constructed following an item analysis based on data from 212 schizophrenic patients medicated with either typical or atypical antipsychotics . The short form of the SWN showed sufficient internal consistency and good construct validity . The SWN was only moderately correlated with positive and negative syndrome scale ( PANSS ) scores or changes in psychopathology ( r=-0.20 to -0.37 ) . SWN-ratings in patients receiving olanzapine were superior compared to those of patients medicated with either clozapine or risperidone on three of five domains of well-being . Clozapine reduced global psychiatric symptoms significantly more than risperidone . It is concluded that the assessment of subjective well-being under antipsychotic treatment provides an independent outcome measure which is relevant to compliance\n\n\nReport 6:\nTitle: Repetitive transcranial magnetic stimulation for the treatment of negative symptoms in residual schizophrenia: rationale and design of a sham-controlled, randomized multicenter study\nSummary: Current meta- analysis revealed small , but significant effects of repetitive transcranial magnetic stimulation ( rTMS ) on negative symptoms in patients with schizophrenia . There is a need for further controlled , multicenter trials to assess the clinical efficacy of rTMS on negative symptoms in schizophrenia in a larger sample of patients . The objective of this multicenter , r and omized , sham-controlled , rater- and patient-blind clinical trial is to investigate the efficacy of 3-week 10-Hz high frequency rTMS add on to antipsychotic therapy , 15 sessions per 3 weeks , 1,000 stimuli per session , stimulation intensity 110 % of the individual motor threshold ) of the left dorsolateral prefrontal cortex for treating negative symptoms in schizophrenia , and to evaluate the effect during a 12 weeks of follow-up . The primary efficacy endpoint is a reduction of negative symptoms as assessed by the negative sum score of the positive and negative symptom score ( PANSS ) . A sample size of 63 in each group will have 80 % power to detect an effect size of 0.50 . Data analysis will be based on the intention to treat population . The study will be conducted at three university hospitals in Germany . This study will provide information about the efficacy of rTMS in the treatment of negative symptoms . In addition to psychopathology , other outcome measures such as neurocognition , social functioning , quality of life and neurobiological parameters will be assessed to investigate basic mechanisms of rTMS in schizophrenia . Main limitations of the trial are the potential influence of antipsychotic dosage changes and the difficulty to ensure adequate blinding\n\n\nReport 7:\nTitle: The Selective Glycine Uptake Inhibitor Org 25935 as an Adjunctive Treatment to Atypical Antipsychotics in Predominant Persistent Negative Symptoms of Schizophrenia: Results From the GIANT Trial\nSummary: Abstract Using a selective glycine uptake inhibitor as adjunctive to second-generation antipsychotic ( SGA ) was hypothesized to ameliorate negative and /or cognitive symptoms in subjects with schizophrenia . Subjects with predominant persistent negative symptoms ( previously stabilized ≥3 months on an SGA ) were enrolled in a r and omized , placebo-controlled trial to investigate adjunctive treatment with Org 25935 , a selective inhibitor of type 1 glycine transporter , over 12 weeks in a flexible dose design . Org 25935 was tested at 4 to 8 mg twice daily and 12 to 16 mg twice daily versus placebo . Primary efficacy outcome was mean change from baseline in Scale for Assessment of Negative Symptoms composite score . Secondary efficacy end points were Positive and Negative Syndrome Scale total and subscale scores , depressive symptoms ( Calgary Depression Scale for Schizophrenia ) , global functioning ( Global Assessment of Functioning scale ) , and cognitive measures using a computerized battery ( Central Nervous System Vital Signs ) . Responder rates were assessed post hoc . A total of 215 subjects were r and omized , of which 187 ( 87 % ) completed the trial . Both dose groups of Org 25935 did not differ significantly from placebo on Scale for Assessment of Negative Symptoms , Positive and Negative Syndrome Scale ( total or subscale scores ) , Global Assessment of Functioning , or the majority of tested cognitive domains . Org 25935 was generally well tolerated within the tested dose range , with no meaningful effects on extrapyramidal symptoms and some reports of reversible visual adverse effects . Org 25935 did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning when administered as adjunctive treatment to SGA . In our study population , Org 25935 appeared to be well tolerated in the tested dose ranges\n\n\nReport 8:\nTitle: Identifying clinically meaningful symptom response cut-off values on the SANS in predominant negative symptoms\nSummary: BACKGROUND The treatment and measurement of negative symptoms are currently at issue in schizophrenia , but the clinical meaning of symptom severity and change is unclear . AIM To offer a clinical ly meaningful interpretation of severity and change scores on the Scale for the Assessment of Negative Symptoms ( SANS ) . METHOD Patients were intention-to-treat participants ( n=383 ) in two double-blind r and omized placebo-controlled clinical trials that compared amisulpride with placebo for the treatment of predominant negative symptoms . Equipercentile linking was used to examine extrapolation from ( a ) CGI-S to SANS severity ratings , and ( b ) CGI-I to SANS percentage change ( n=383 ) . Linking was conducted at baseline , 8 - 14 days , 28 - 30 days , and 56 - 60 days of the trials . RESULTS Across visits , CGI-S ratings of ' not ill ' linked to SANS scores of 0 - 13 , and ranged to ' extreme ' ratings that linked to SANS scores of 102 - 105 . The relationship between the CGI-S and the SANS severity scores assumed a linear trend ( 1=0 - 13 , 2=15 - 56 , 3=37 - 61 , 4=49 - 66 , 5=63 - 75 , 6=79 - 89 , 7=102 - 105 ) . Similarly the relationship between CGI-I ratings and SANS percentage change followed a linear trend . For instance , CGI-I ratings of ' very much improved ' were linked to SANS percent changes of -90 to -67 , ' much improved ' to -50 to -42 , and ' minimally improved ' to -21 to -13 . CONCLUSIONS The current results uniquely contribute to the debate surrounding negative symptoms by providing clinical meaning to SANS severity and change scores and so offer direction regarding clinical ly meaningful response cut-off scores to guide treatment targets of predominant negative symptoms",
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"content": "Conclusion : No HRQoL instrument has been vali date d in patients with SNS only ; for the remaining instruments identified , it remains unclear whether they were intended to capture HRQoL in patients with SNS",
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science.qasper_extractive_qa | science.qasper_extractive_qa.389.0 | [
{
"content": "Analyze the given research paper excerpts and address the question provided. Extract the necessary information directly from the text. Your answer should be formatted as a JSON object with the following structure:\n\n\"answer\": A list of text segments from the paper that directly respond to the question.\n\"evidence\": A list of text segments from the paper where the answer can be found.\n\nIf the question cannot be answered with the given text, return \"null\".\n\nDocument: Asking and Answering Questions to Evaluate the Factual Consistency of Summaries\n\nPractical applications of abstractive summarization models are limited by frequent factual inconsistencies with respect to their input. Existing automatic evaluation metrics for summarization are largely insensitive to such errors. We propose an automatic evaluation protocol called QAGS (pronounced\"kags\") that is designed to identify factual inconsistencies in a generated summary. QAGS is based on the intuition that if we ask questions about a summary and its source, we will receive similar answers if the summary is factually consistent with the source. To evaluate QAGS, we collect human judgments of factual consistency on model-generated summaries for the CNN/DailyMail (Hermann et al., 2015) and XSUM (Narayan et al., 2018) summarization datasets. QAGS has substantially higher correlations with these judgments than other automatic evaluation metrics. Also, QAGS offers a natural form of interpretability: The answers and questions generated while computing QAGS indicate which tokens of a summary are inconsistent and why. We believe QAGS is a promising tool in automatically generating usable and factually consistent text.\n\nA Framework for Automatically Evaluating Factual Consistency\nWe introduce a framework for automatically detecting factual inconsistencies in generated text while also addressing the deficiencies of current approaches. Let $X$ and $Y$ be sequences of tokens coming from a vocabulary $V$ where $X$ is a source text and $Y$ is a summary of $X$. We define $p(Q|Y)$ as a distribution over all possible questions $Q$ given summary $Y$, and $p(A|Q, X)$ and $p(A|Q, Y)$ as distributions over all possible answers $A$ to a particular question $Q$ given either the source $X$ or the summary $Y$. We constrain the questions $Q$ and answers $A$ to also be sequences of tokens from $V$. Then the factual consistency of the summary $Y$ is\nwhere $D$ is some function measuring the similarity of the two answer distributions. This expression is maximized when $Y$ contains a subset of the information in $X$ such that it produces the same answer for any question from $p(Q|Y)$. This happens trivially when $Y=X$, e.g. we take $X$ as its own summary, but we usually have other desiderata of $Y$ such that this solution is undesirable.\nThis framework addresses the two issues with $n$-gram based approaches. Instead of requiring a reference to compare against, our framework asks questions based on the generation itself, and compares answers with the provided source text. Also, the use of questions focuses the metric on the semantically relevant parts of the generated text, rather than weighting all parts of the text equally.\nIn practice, exactly computing the expectation in Equation DISPLAY_FORM4 is intractable due to the large space of possible questions. One potential workaround is to randomly sample questions from $p(Q|Y)$, but this suffers from high variance and requires many samples to obtain a good estimate. Instead, we focus on producing highly probable questions, e.g. as produced by beam search, which may be biased in the limit, but will require fewer questions to estimate because of the higher quality of the questions.\n\nQAGS ::: Question Answering\nWe instantiate the answer distributions $p(A|Q,*)$ as extractive QA models, for simplicity. We use extractive QA because we assume the facts are represented as text spans in the article and summary. Future work should explore using abstractive QA models, which could match paraphrases of the same answer.\n\nExperiments ::: Human Evaluation\nWe test whether QAGS accurately measures the factual consistency of a summary with respect to a source article by computing correlations with human judgments of factual consistency.\n\nExperiments ::: Human Evaluation ::: Annotation Protocol\nWe collect human judgments on Amazon Mechanical Turk via ParlAI BIBREF18. We present summaries one sentence at a time, along with the entire article. For each summary sentence, the annotator makes a binary decision as to whether the sentence is factually consistent with the article. Workers are instructed to mark non-grammatical sentences as not consistent, and copies of article sentences as consistent. Workers are paid $1 per full summary annotated. See Appendix SECREF10 for further details.\nWe collect 3 annotations per summary. To obtain a single “correctness” score per summary, we first take the majority vote for each sentence, then average the binary scores across summary sentences.\nInter-annotator agreement as measured by Krippendorff's $\\alpha $ is 0.51 and 0.34 for CNN/DM and XSUM, respectively indicating “moderate” and “fair” agreement BIBREF19. While not perfect, these agreement numbers are in-line with similar figures from previous work on summarization evaluation BIBREF4.\n\nExperiments ::: Ablations\nA potential issue with model-based evaluation is that the quality of the evaluation metric may depend heavily on specific hyperparameter settings. We explore whether this is true with QAGS by performing ablations on several factors.\n\nExperiments ::: Ablations ::: Model Quality\nWe first consider the degree to which the quality of the underlying models impacts their evaluation capabilities.\nFor QA quality, we answer this question by training QA models of varying quality by fine-tuning different versions of BERT on SQuAD. We present results in Table . The QA models perform similarly despite substantially different performances on the SQuAD development set. Surprisingly, using the best QA model (bert-large-wwm) does not lead to the best correlations with human judgments. On CNN/DM, bert-large-wwm slightly underperforms bert-base and bert-large. On XSUM, bert-base slightly outperforms the other two BERT variants. These results indicate that QAGS is fairly robust to the quality of the underlying QA model, though we note that BERT is a strong QA baseline, and using weaker QA models might lead to larger performance dropoffs.\nTo ablate QG quality, we use models with increasing perplexity on the NewsQA development set. Results in Table show that QAGS is robust to the QG model quality, with some decrease in correlation with human judgments as perplexity increases on CNN/DM, and no clear trend on XSUM. Even the weakest QG model still significantly outperforms all other automatic metrics in Table .\n\nExperiments ::: Ablations ::: Domain Effects\nOur approach relies on having a labeled dataset to train QG and QA models. However, for relatively niche domains, such a labeled QA/QG dataset may not exist. Instead, we may need to resort to using models trained on out-of-domain data, leading to domain shift effects that negatively impact the quality of the QAGS scores. We simulate this setting by fine-tuning the QG model on SQuAD, which is of similar size to NewsQA but drawn from Wikipedia articles rather than CNN articles, which exactly matches the genre of the summarization datasets.\nEvaluating with this QG model, we get correlations of 51.53 and 15.28 with human judgments on CNN/DM and XSUM respectively, versus 54.53 and 17.49 when using the NewsQA-tuned QG model. The drop in performance indicates a negative domain shift effect. However using the SQuAD-tuned QG model still substantially outperforms all other automatic metrics, again pointing to the robustness of QAGS.\n\nExperiments ::: Ablations ::: Number of Questions\nNext, we investigate the correlation with human judgments when varying the number of questions used. Results in Table show that increasing the number of questions used improves correlations with human judgments. We observe a large increase when moving from 10 to 20 questions, and a smaller increase from 20 to 50 questions, indicating decreasing marginal benefit moving beyond 50 questions. With just 5 questions, QAGS still substantially outperforms other automatic metrics, indicating its robustness.\n\nExperiments ::: Ablations ::: Answer Similarity Metric\nFinally, we consider using exact match as an alternative answer similarity metric. Exact match is another common evaluation metric for extractive QA, and is more restrictive than F1. When using EM, we obtain Pearson correlations with human judgments of 45.97 and 18.10 on CNN/DM and XSUM, as opposed to 54.53 and 17.49 when using F1.\n\nRelated Work\nAutomatic summarization and its evaluation are long-standing lines of work in NLP, dating at least as far back as the Document Understanding Conferences BIBREF30. The primary evaluation metric then and now is ROUGE BIBREF8, though much work has demonstrated the limited ability of ROUGE and its relatives to evaluate summaries BIBREF31, BIBREF32, BIBREF33. Other metrics have focused on specific aspects of summarization quality, including content selection BIBREF34, relevance prediction BIBREF4, and many more.\nThere has been a recent resurgence of work leveraging NLU models for evaluating the factuality of generated text. BIBREF35 use information extraction models to measure factual overlap, but facts are restricted to pre-defined schemas. BIBREF16 investigate the use of NLI models to evaluate the factual correctness of CNN/DM summaries, and conclude that current NLI models are too brittle to be reliably used in this manner. BIBREF5 train a NLI-based fact-checking model by building a dataset of factual inconsistencies based on noise heuristic. Our QA approach allows a finer-grained analysis, because NLI operates on complete sentences, whereas QAGS can ask many questions about the same sentence.\nMost relatedly, BIBREF36 and BIBREF37 use QA models to evaluate summarization. We diverge from these works in two important ways. First, both works use Cloze-style questions, which are generated by masking entities in either the source document or the reference summary. We instead generate the questions with a model, allowing a much greater range of questions. Second, we produce questions conditioned on the generated summary, rather than the reference summary or source article. Producing questions from the generated summary is more appropriate for verifying the accuracy of the text, whereas using the reference or source measures content selection.\n\nHuman Evaluation Task Design\nWe restrict our pool of workers to US-based workers. Workeres are required to have at least 1000 approved HITs with an acceptance rate of at least 98%.\nThe base reward for our task is $0.15. For each summary, we include automatic quality checks including\nTime checks: workers who complete the task under 30s fail the check\nAttention checks: we include exact copies of article sentences and corrupted mixtures of two article sentences as positive and negative control task. If a worker fails to answer both of these examples correctly, they fail the check\nExplanation checks: For each sentence in the summary, the worker is required to provide a short explanation of their decision\nIf a worker passes all checks, they are awarded a $0.85 bonus, totalling $1.00 per correct annotation. According to turkerview.com, workers of our HIT are paid well in excess of $15.00 on average.\nWe show our annotation interfaces for the annotation task for CNN/DM and XSUM respectively in Figures FIGREF27 and FIGREF28. We use slightly different instructions to accommodate for the quirks of each dataset. For XSUM, we prepend the reference “summary” back onto the source article, as without it, workers were struggling to identify factual inconsistencies.\n\nModel and Generation Details ::: Question Generation\nWe fine-tune BART for question generation using the same tuning hyperparameters as the original work. We optimize label smoothed cross entropy with smoothing parameter 0.1 BIBREF41 and a peak learning rate of 2e-5. We optimize for 100k steps with 5k warmup steps, and use the model with the best perplexity on the development set.\nTo turn NewsQA into an answer conditional QG dataset, we concatenate the answer to the source article with a special marker token in between. We then concatenate another special marker token and the question. At test time, we get 10 named entities and noun phrases as answer candidates using the en-web-sm spaCy model. We downsampling if there are more than 10 and randomly duplicating some answers if there are more than 10. The model predicts the question after seeing an answer and the article.\nDuring decoding, we use beam search with beam size 10, length penalty 1.0, and trigram repetition blocking. We experimented with top-$k$ BIBREF39 and top-$p$ BIBREF38, but the outputted questions, while diverse, were quite noisy. Generations have minimum length 8 and max length 60.\nTo filter the questions, we first use simple heuristics, including removing\neverything after the first question mark in a question\nexact duplicates\nquestions shorter than three tokens long\nFor the remaining questions, we use our QA model to answer each question and we remove questions for which the QA model deems unanswerable. We then take the top 20 most probable questions, random sampling some of the filtered questions if there were too few.\n\nModel and Generation Details ::: Question Answering\nWe fine-tune BERT for question answering following the original work. We optimize using AdamW BIBREF40 with initial learning rate 5e-5. We train for 3 epochs, with a warmup ratio of 0.1. We use the model with the best development set performance.\nWe use SQuAD2.0 because we found the unanswerable questions useful for filtering out questions and questions based on hallucinated facts in the summary should be unanswerable using the source article. Similar to the QG setting, we append the question and answer to the source article with intervening special marker tokens.\n\nFigure 1: Overview of QAGS. A set of questions is generated based on the summary. The questions are then answered using both the source article and the summary. Corresponding answers are compared using a similarity function and averaged across questions to produce the final QAGS score.\n\nTable 1: Summary-level Pearson correlation coefficients between various automatic metrics and human judgments of correctness for summarization datasets. QAGS obtains substantially higher correlations than all other automatic metrics.\n\nTable 2: Pearson correlations between human judgments of factual consistency and QAGS using QA models of different qualities, as measured by performance on the SQuAD2.0 development set (F1). The correlations are stable across QA model quality.\n\nTable 5: Results on the sentence ranking task from Falke et al. (2019). Results using BERT NLI and ESIM are from Falke et al. (2019); FactCC is from Kryscinski et al. (2019b). QAGS outperforms previous work.\n\nFigure 2: Annotation interface and instructions for CNN/DM factual consistency task.\n\nInquiry: What models are evaluated with QAGS?",
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"content": "{\"answer\": [\"bert-large-wwm\", \"bert-base\", \"bert-large\"], \"evidence\": [\"For QA quality, we answer this question by training QA models of varying quality by fine-tuning different versions of BERT on SQuAD. We present results in Table . The QA models perform similarly despite substantially different performances on the SQuAD development set. Surprisingly, using the best QA model (bert-large-wwm) does not lead to the best correlations with human judgments. On CNN/DM, bert-large-wwm slightly underperforms bert-base and bert-large. On XSUM, bert-base slightly outperforms the other two BERT variants. These results indicate that QAGS is fairly robust to the quality of the underlying QA model, though we note that BERT is a strong QA baseline, and using weaker QA models might lead to larger performance dropoffs.\"]}",
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science.bioasq_general_qa | science.bioasq_general_qa.222 | [
{
"content": "Review the provided biomedical excerpts and respond to the question concisely. Ensure your answer is derived solely from the given context and avoid adding any extraneous information.\n\nQuestion: What is Piebaldism?\n\nExcerpts: Human piebaldism is a rare autosomal dominant condition characterized by congenital white forelock and depigmented patches of s\nPiebaldism is a rare genodermatosis caused by KIT mutations.\nPiebaldism is a rare autosomal dominant disorder of melanocyte development characterized by a congenital white forelock and multiple symmetrical stable hypopigmented or depigmented macules.\nPiebaldism is an autosomal dominant disorder characterized by congenital hypopigmented patches of skin and hair and has been found to be associated with mutations in the KIT or SLUG genes.\nPiebaldism is a rare autosomal dominant skin disorder characterized by a white forelock and depigmented patches of skin, generally located on the forehead, central chest and abdomen, upper arms, and lower extremities.\nPiebaldism is a rare genodermatosis in which depigmented skin areas are unresponsive to topical or light treatment.\nPiebaldism is a rare disorder present at birth and inherited as an autosomal dominant trait. It results from a mutation in the c-kit proto-oncogene and is associated with a defect in the migration and differentiation of melanoblasts from the neural crest.\nPiebaldism is an autosomal dominant genetic disorder of pigmentation characterized by white patches of skin and hair. Melanocytes are lacking in these hypopigmented regions, the result of mutations of the KIT gene, which encodes the cell surface receptor for steel factor (SLF).\nPiebaldism is an autosomal dominant genetic disorder of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Piebaldism results from mutations of the KIT proto-oncogene, which encodes the cell-surface receptor transmembrane tyrosine kinase for an embryonic growth factor, Steel factor. Several pathologic mutations of the KIT gene have now been identified in different patients with piebaldism.\nPiebaldism is an autosomal dominant disorder of melanocyte development characterized by white skin (leukoderma) and white hair (poliosis).",
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"content": "Piebaldism is a rare autosomal dominant disorder of melanocyte development characterized by a congenital white forelock and multiple symmetrical stable hypopigmented or depigmented macules.",
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science.craftchem_ner | science.craftchem_ner.1300 | [
{
"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nContinuingthescreenwouldhaveresultedincDNAsfromadditionalolfactoryreceptors,butwereachedapointoflimitingreturns:ourfinalbatchof45olfactoryreceptor-positivesequencesrepresented33differentolfactoryreceptors,ofwhichonlyfourhadnotbeenencounteredpreviouslyinourscreen.",
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"content": "[]",
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science.data_reco_mcq_mc | science.data_reco_mcq_mc.1330 | [
{
"content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: I want to apply a deep learning model to learn a discriminative metric for person re-identification.\n\nKey Terms: person re-identification images\n\nDataset Summaries:\nAirport: The Airport dataset is a dataset for person re-identification which consists of 39,902 images and 9,651 identities across six cameras.\nSYSU-MM01: The SYSU-MM01 is a dataset collected for the Visible-Infrared Re-identification problem. The images in the dataset were obtained from 491 different persons by recording them using 4 RGB and 2 infrared cameras.\nVeRi-776: VeRi-776 is a vehicle re-identification dataset which contains 49,357 images of 776 vehicles from 20 cameras. The dataset is collected in the real traffic scenario, which is close to the setting of CityFlow.\nVIPeR: The Viewpoint Invariant Pedestrian Recognition (VIPeR) dataset includes 632 people and two outdoor cameras under different viewpoints and light conditions. Each person has one image per camera and each image has been scaled to be 128×48 pixels.\nCUHK03: The CUHK03 consists of 14,097 images of 1,467 different identities, where 6 campus cameras were deployed for image collection and each identity is captured by 2 campus cameras. This dataset provides two types of annotations, one by manually labelled bounding boxes and the other by bounding boxes produced by an automatic detector.\nDukeMTMC-reID: The DukeMTMC-reID (Duke Multi-Tracking Multi-Camera ReIDentification) dataset is a subset of the DukeMTMC for image-based person re-ID. The dataset is created from high-resolution videos from 8 different cameras.\n\nDataset Options: A: Airport B: SYSU-MM01 C: VeRi-776 D: VIPeR E: CUHK03 F: DukeMTMC-reID",
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"content": "[\"VIPeR\", \"CUHK03\"]",
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.7506 | [
{
"content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nossification of the posterior longitudinal ligament ( opll ) , a result of heterotopic ossification , can induce spinal canal stenosis and lead to the development of severe myelopathy .\nthere have been numerous studies of surgical techniques or clinical outcomes for opll of the cervical spine.1 in contrast , there are only a few reports regarding opll of the lumbar spine , and its clinical characteristics have not yet been well established because the number of patients who require surgical treatment is quite low.2 to our knowledge , there has been only six reports of surgically treated lumbar opll published in english.7 according to the data in the database for the spinal injuries center in fukuoka , japan , during the past 27 years , although 6,192 patients underwent operations for degenerative lumbar spine diseases , only ten underwent surgery for lumbar opll.2 thus , the frequency of lumbar opll requiring surgical treatment was remarkably low , indicating a lack of awareness of the disease even among orthopedic surgeons .\nwe have recently witnessed that radiculopathy due to lumbar opll was found to be the cause of chronic right lower abdominal pain in a japanese man.8 after encountering this unusual case , we thought that lumbar opll should be considered to be a factor for not only orthopedic symptoms but also abdominal symptoms . because abdominal symptoms are common in the primary care setting,9 we tried to clarify the incidence of lumbar opll in an outpatient clinic in japan where primary care physicians are working .\nwe analyzed consecutive outpatients making their first visit to the department of general medicine , asahikawa medical university hospital , between april 2009 and march 2012 .\nas we have recently demonstrated,913 the hospital consists of 602 beds in which approximately 250 doctors are working to address almost all medical problems . among them , four or five primary care physicians are working in the department of general medicine . during the period , we analyzed the patients ( n = 393 ) who received abdominal and pelvic computed tomography ( ct ) scan to clarify their several problems such as abdominal symptoms , origins of fever , high level of tumor markers , and so on .\nsince it has been widely established that ct is a useful tool for detecting and accurately locating opll,14 lumbar opll was diagnosed by the ct scan according to a previous report.2 all data were drawn from medical records and the computerized physician order entry system in the hospital .\neach parameter such as age , sex , body mass index ( bmi ) , and clinical presentation was investigated from the source .\nanalyzed comorbid conditions included diabetes mellitus , systemic hypertension , dyslipidemia , and cigarette smoking .\nstatistical analysis was performed by fisher s exact test , and student s t - test for age and bmi . a level of p < 0.05 was considered to be statistically significant .\nstatistical analysis was performed by fisher s exact test , and student s t - test for age and bmi . a level of p < 0.05 was considered to be statistically significant .\nlumbar opll was diagnosed by ct according to a previous report.2 representative images are shown in figure 1 . as shown in this figure , opll was diagnosed when an apparent ossification of the ligament causing more than 10% canal stenosis was revealed with ct . out of 393 patients who underwent abdominal and pelvic ct scan , 33 ( 8.4% ) were diagnosed with lumbar opll .\nall 33 patients diagnosed with lumbar opll detected by ct scan did not complain of main symptoms related to spinal stenosis , such as intermittent claudication .\ntable 1 shows the clinical characteristics of 33 patients with lumbar opll in this study .\nwhen compared with patients without lumbar opll ( n = 360 ) , there was no significant difference in gender , bmi , presence of hypertension , diabetes mellitus or hyperlipidemia , and smoking habit , while a significant difference was identified in age in patients with lumbar opll .\nas clearly demonstrated in table 2 , the incidence of lumbar opll increased in the elderly .\nthe highest incidence was observed in male patients aged 5069 years and female patients aged 7089 years . among 33 opll patients ,\nseven patients complained of lower abdominal pain as their chief complaint . in the unique case mentioned earlier ,\nthe patient s pain was considered to be dependent on lumbar opll as reported in our recent publication;8 in another case , advanced colon cancer was considered to be the cause of abdominal pain . in the remaining five cases , the pain was diagnosed as functional gastrointestinal disorders after careful examination , but we could not completely exclude the possibility that the abdominal pain in the five patients was related to lumbar opll .\n, lumbar opll might be involved in the symptom , and was followed by consultation with the department of orthopedic surgery in our hospital .\nopll is more common in east asian populations , particularly in the japanese;15 the prevalence of opll is highest in japan , at a rate of 1.9%4.3%.16 although a number of authors have reported on opll of the cervical spine , few have discussed opll of the lumber spine.7 the number of reports regarding lumbar opll has been limited , and its prevalence and regional difference remain unclear .\na lack of evidence may be a result of a large majority of lumbar opll possibly being asymptomatic , as described below .\nclinical presentations in patients with opll correspond to the level and magnitude of spinal cord compression .\ncervical and thoracic opll typically manifests with signs and symptoms of myelopathy , while the lumbar disease usually manifests with signs and symptoms related to spinal stenosis.3,17,18 matsunaga et al17 have demonstrated that after 30 years , myelopathy - free rates as high as 71% have been reported among patients who had no myelopathy when the cervical opll was first diagnosed .\nalthough we do not have any evidence that the time - course changes in lumbar opll are similar to cervical opll , these results led us to speculate that a large majority of lumbar opll patients are asymptomatic .\nin fact , all patients with lumbar opll detected in this study did not complain of spinal stenosis - mediated symptoms as described above .\nwe do not know at this moment whether lumbar opll is indeed rare in the general population , or whether physicians are not aware of the presence of lumbar opll . in the present study , out of 393 patients who underwent abdominal and pelvic ct scans , 33 ( 8.4% )\nwere diagnosed as lumbar opll , indicating for the first time the incidence of lumbar opll in japan . according to previous data ,\nthe prevalence of cervical and thoracic opll in japanese and east asian countries has ranged from 1.9%4.3%.15 these results suggest that the frequency of lumbar opll is not much lower than that of cervical and thoracic opll.1 kobashi et al have demonstrated a higher frequency of diabetes mellitus among japanese men and women with opll,19 suggesting that diabetes mellitus may play a role in the development of opll .\nthe present results demonstrated that there was no relationship between the presence of diabetes mellitus and lumbar opll .\nthe discrepancy may be due to the difference in pathophysiology between cervical and lumbar opll .\nbecause of a lack of evidence whether pathogenesis is common in patients with cervical and lumbar opll , further studies on this issue are needed .\nthe present study also showed a lack of association of hypertension , hyperlipidemia , and bmi with lumbar opll .\nthe present study clearly demonstrated for the first time that lumbar opll is highly identified in elderly people . based on these findings\n, we should pay special attention in elderly patients and work to determine whether they may have lumbar opll .\nalthough the presence of lumbar opll by itself does not necessarily mean a clinical problem , we should keep in mind that lumbar opll is possibly involved in not only spinal stenosis - mediated symptoms , but also radiculopathy - related symptoms seen in the primary care setting , such as abdominal pain.8",
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{
"content": "purposelittle is known about the prevalence and epidemiological characteristics of lumbar ossification of the posterior longitudinal ligament ( opll ) . \n we analyzed the rate of lumbar opll in an outpatient unit where primary care physicians are working in japan , to better understand the epidemiological characteristics of the disease.methodswe analyzed consecutive , first - time visiting outpatients who received abdominal and pelvic computed tomography ( ct ) scan at the department of general medicine , asahikawa medical university hospital , japan , between april 2009 and march 2012 . \n each parameter such as age , sex , and clinical presentation was investigated.resultsout of 393 patients who underwent abdominal and pelvic ct scan , 33 ( 8.4% ) were diagnosed as lumbar opll . \n when compared with patients without lumbar opll ( n = 360 ) , there was no significant difference in gender , body mass index ( bmi ) , presence of hypertension , diabetes mellitus or hyperlipidemia , and smoking habit , while the age in patients with lumbar opll was significantly higher.conclusionthese results suggest for the first time that lumbar opll is frequently observed in elderly people in the primary care setting , in japan .",
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