[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The myocardial cell lineage originally develops from cardiac progenitors of exclusively endodermal origin.

Document title: Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population

Abstract sentences:
[0] The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells.
[1] Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1+ (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages.
[2] To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures.
[3] Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid bodies generate a KDRlow/C-KIT(CD117)neg population that displays cardiac, endothelial and vascular smooth muscle potential in vitro and, after transplantation, in vivo.
[4] When plated in monolayer cultures, these KDRlow/C-KITneg cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes.
[5] Populations derived from the KDRlow/C-KITneg fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures.
[6] Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colony-forming cell.
[7] Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1+ (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The number of unfertilized oocytes in mated hermaphrodites increases with age.

Document title: TGF-β and Insulin Signaling Regulate Reproductive Aging via Oocyte and Germline Quality Maintenance

Abstract sentences:
[0] Reproductive cessation is perhaps the earliest aging phenotype that humans experience.
[1] Similarly, reproduction of Caenorhabditis elegans ceases in mid-adulthood.
[2] Although somatic aging has been studied in both worms and humans, mechanisms regulating reproductive aging are not yet understood.
[3] Here, we show that TGF-β Sma/Mab and Insulin/IGF-1 signaling regulate C. elegans reproductive aging by modulating multiple aspects of the reproductive process, including embryo integrity, oocyte fertilizability, chromosome segregation fidelity, DNA damage resistance, and oocyte and germline morphology.
[4] TGF-β activity regulates reproductive span and germline/oocyte quality noncell-autonomously and is temporally and transcriptionally separable from its regulation of growth.
[5] Chromosome segregation, cell cycle, and DNA damage response genes are upregulated in TGF-β mutant oocytes, decline in aged mammalian oocytes, and are critical for oocyte quality maintenance.
[6] Our data suggest that C. elegans and humans share many aspects of reproductive aging, including the correlation between reproductive aging and declining oocyte quality and mechanisms determining oocyte quality.

[Assistant]
Label: NOT ENOUGH INFORMATION
Rationale sentence ids: []
Explanation: The provided abstract does not contain direct evidence to support or contradict the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The one-child policy has created a hospitable environment for female infants.

Document title: Perinatal mortality in rural China: retrospective cohort study.

Abstract sentences:
[0] OBJECTIVES To explore the use of local civil registration data to assess the perinatal mortality in a typical rural county in a less developed province in China, 1999-2000.
[1] DESIGN Retrospective cohort study.
[2] Pregnancies in a cohort of women followed from registration of pregnancy to outcome of infant seven days after birth.
[3] SETTING Routine family planning records in 20 rural townships in eastern China.
[4] SUBJECTS 3697 pregnancies registered by the local family planning system during 1999.
[5] MAIN OUTCOME MEASURES Abortions, stillbirths, early neonatal mortality, perinatal mortality.
[6] RESULTS Only three cases were lost to follow up.
[7] The average age of the women at pregnancy was 25.9 years.
[8] Three hundred and twelve pregnancies were aborted and 240 ended in miscarriage (total 552, 15%).
[9] The perinatal mortality rate was 69 per 1000 births, the rate of stillbirth was 24 per 1000 births, and the early neonatal mortality was 46 per 1000 live births.
[10] The early neonatal mortality was 29 in boys and 69 in girls per 1000 live births.
[11] The perinatal mortality rate increased notably with parity and was higher in townships having lower income per capita.
[12] CONCLUSIONS The family planning system at the most local level is a useful data source for studying perinatal mortality in rural China.
[13] The perinatal mortality rate in the study county was higher than previously reported for both rural and urban areas in China.
[14] The results by parity and sex of the infant raise concern over the impact of the one child policy.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10]
Explanation: Evidence states: "The early neonatal mortality was 29 in boys and 69 in girls per 1000 live births.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The origin of the CRF01_1b2k protein occurred between 1923 and 1956.

Document title: The Global Spread of Hepatitis C Virus 1a and 1b: A Phylodynamic and Phylogeographic Analysis

Abstract sentences:
[0] BACKGROUND Hepatitis C virus (HCV) is estimated to affect 130-180 million people worldwide.
[1] Although its origin is unknown, patterns of viral diversity suggest that HCV genotype 1 probably originated from West Africa.
[2] Previous attempts to estimate the spatiotemporal parameters of the virus, both globally and regionally, have suggested that epidemic HCV transmission began in 1900 and grew steadily until the late 1980s.
[3] However, epidemiological data suggest that the expansion of HCV may have occurred after the Second World War.
[4] The aim of our study was to elucidate the timescale and route of the global spread of HCV.
[5] METHODS AND FINDINGS We show that the rarely sequenced HCV region (E2P7NS2) is more informative for molecular epidemiology studies than the more commonly used NS5B region.
[6] We applied phylodynamic methods to a substantial set of new E2P7NS2 and NS5B sequences, together with all available global HCV sequences with information in both of these genomic regions, in order to estimate the timescale and nature of the global expansion of the most prevalent HCV subtypes, 1a and 1b.
[7] We showed that transmission of subtypes 1a and 1b "exploded" between 1940 and 1980, with the spread of 1b preceding that of 1a by at least 16 y (95% confidence interval 15-17).
[8] Phylogeographic analysis of all available NS5B sequences suggests that HCV subtypes 1a and 1b disseminated from the developed world to the developing countries.
[9] CONCLUSIONS The evolutionary rate of HCV appears faster than previously suggested.
[10] The global spread of HCV coincided with the widespread use of transfused blood and blood products and with the expansion of intravenous drug use but slowed prior to the wide implementation of anti-HCV screening.
[11] Differences in the transmission routes associated with subtypes 1a and 1b provide an explanation of the relatively earlier expansion of 1b.
[12] Our data show that the most plausible route of the HCV dispersal was from developed countries to the developing world.
[13] Please see later in the article for the Editors' Summary.

[Assistant]
Label: NOT ENOUGH INFORMATION
Rationale sentence ids: []
Explanation: The provided abstract does not contain direct evidence to support or contradict the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The peak incidence of fractures occurs during pubertal growth spurt in early adolescents.

Document title: Incidence of childhood distal forearm fractures over 30 years: a population-based study.

Abstract sentences:
[0] CONTEXT The incidence of distal forearm fractures in children peaks around the time of the pubertal growth spurt, possibly because physical activity increases at the time of a transient deficit in cortical bone mass due to the increased calcium demand during maximal skeletal growth.
[1] Changes in physical activity or diet may therefore influence risk of forearm fracture.
[2] OBJECTIVE To determine whether there has been a change in the incidence of distal forearm fractures in children in recent years.
[3] DESIGN, SETTING, AND PATIENTS Population-based study among Rochester, Minn, residents younger than 35 years with distal forearm fractures in 1969-1971, 1979-1981, 1989-1991, and 1999-2001.
[4] MAIN OUTCOME MEASURE Estimated incidence of distal forearm fractures in 4 time periods.
[5] RESULTS Comparably age- and sex-adjusted annual incidence rates per 100 000 increased from 263.3 (95% confidence interval [CI], 231.1-295.4) in 1969-1971 to 322.3 (95% CI, 285.3-359.4) in 1979-1981 and to 399.8 (95% CI, 361.0-438.6) in 1989-1991 before leveling off at 372.9 (95% CI, 339.1-406.7) in 1999-2001.
[6] Age-adjusted incidence rates per 100 000 were 32% greater among male residents in 1999-2001 compared with 1969-1971 (409.4 [95% CI, 359.9-459.0] vs 309.4 [95% CI, 259.3-359.5]; P =.01) and 56% greater among female residents in the same time periods (334.3 [95% CI, 288.6-380.1] vs 214.6 [95% CI, 174.9-254.4]; P<.001).
[7] The peak incidence and greatest increase occurred between ages 11 and 14 years in boys and 8 and 11 years in girls.
[8] CONCLUSIONS There has been a statistically significant increase in the incidence of distal forearm fractures in children and adolescents, but whether this is due to changing patterns of physical activity, decreased bone acquisition due to poor calcium intake, or both is unclear at present.
[9] Given the large number of childhood fractures, however, studies are needed to define the cause(s) of this increase.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "CONTEXT The incidence of distal forearm fractures in children peaks around the time of the pubertal growth spurt, possibly because physical activity increases at the time of a transient deficit in cortical bone mass due to the increased calcium demand during maximal skeletal growth.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The peak incidence of fractures occurs in toddlers.

Document title: Incidence of childhood distal forearm fractures over 30 years: a population-based study.

Abstract sentences:
[0] CONTEXT The incidence of distal forearm fractures in children peaks around the time of the pubertal growth spurt, possibly because physical activity increases at the time of a transient deficit in cortical bone mass due to the increased calcium demand during maximal skeletal growth.
[1] Changes in physical activity or diet may therefore influence risk of forearm fracture.
[2] OBJECTIVE To determine whether there has been a change in the incidence of distal forearm fractures in children in recent years.
[3] DESIGN, SETTING, AND PATIENTS Population-based study among Rochester, Minn, residents younger than 35 years with distal forearm fractures in 1969-1971, 1979-1981, 1989-1991, and 1999-2001.
[4] MAIN OUTCOME MEASURE Estimated incidence of distal forearm fractures in 4 time periods.
[5] RESULTS Comparably age- and sex-adjusted annual incidence rates per 100 000 increased from 263.3 (95% confidence interval [CI], 231.1-295.4) in 1969-1971 to 322.3 (95% CI, 285.3-359.4) in 1979-1981 and to 399.8 (95% CI, 361.0-438.6) in 1989-1991 before leveling off at 372.9 (95% CI, 339.1-406.7) in 1999-2001.
[6] Age-adjusted incidence rates per 100 000 were 32% greater among male residents in 1999-2001 compared with 1969-1971 (409.4 [95% CI, 359.9-459.0] vs 309.4 [95% CI, 259.3-359.5]; P =.01) and 56% greater among female residents in the same time periods (334.3 [95% CI, 288.6-380.1] vs 214.6 [95% CI, 174.9-254.4]; P<.001).
[7] The peak incidence and greatest increase occurred between ages 11 and 14 years in boys and 8 and 11 years in girls.
[8] CONCLUSIONS There has been a statistically significant increase in the incidence of distal forearm fractures in children and adolescents, but whether this is due to changing patterns of physical activity, decreased bone acquisition due to poor calcium intake, or both is unclear at present.
[9] Given the large number of childhood fractures, however, studies are needed to define the cause(s) of this increase.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [0]
Explanation: Evidence states: "CONTEXT The incidence of distal forearm fractures in children peaks around the time of the pubertal growth spurt, possibly because physical activity increases at the time of a transient deficit in cortical bone mass due to the increased calcium demand during maximal skeletal growth.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The predominant localization of Linc00173 is in mononuclear macrophage nuclei.

Document title: The non-coding RNA landscape of human hematopoiesis and leukemia

Abstract sentences:
[0] Non-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions.
[1] However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood.
[2] Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system.
[3] Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs-such as LINC00173 in granulocytes-and assign these to critical regulatory circuits involved in blood homeostasis.
[4] Following the incorporation of acute myeloid leukemia samples into the landscape, we further uncover prognostically relevant non-coding RNA stem cell signatures shared between acute myeloid leukemia blasts and healthy hematopoietic stem cells.
[5] Our findings highlight the importance of the non-coding transcriptome in the formation and maintenance of the human blood hierarchy.
[6] While micro-RNAs are known regulators of haematopoiesis and leukemogenesis, the role of long non-coding RNAs is less clear.
[7] Here the authors provide a non-coding RNA expression landscape of the human hematopoietic system, highlighting their role in the formation and maintenance of the human blood hierarchy.

[Assistant]
Label: NOT ENOUGH INFORMATION
Rationale sentence ids: []
Explanation: The provided abstract does not contain direct evidence to support or contradict the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The proliferative capacity of neural progenitors differs across species.

Document title: 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

Abstract sentences:
[0] Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals.
[1] Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems.
[2] Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins.
[3] The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell.
[4] We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The proliferative capacity of neural progenitors differs across species.

Document title: 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

Abstract sentences:
[0] Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals.
[1] Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems.
[2] Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins.
[3] The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell.
[4] We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The proliferative capacity of progenitors is regulated cell-autonomously.

Document title: 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

Abstract sentences:
[0] Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals.
[1] Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems.
[2] Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins.
[3] The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell.
[4] We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The proportion of people with visual difficulty is two times higher in low-income countries than in high-income countries.

Document title: Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Abstract sentences:
[0] BACKGROUND Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs).
[1] We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development.
[2] METHODS We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015.
[3] We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year.
[4] We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita.
[5] We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate.
[6] FINDINGS Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs).
[7] Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs.
[8] Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined.
[9] Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies.
[10] From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9-3·0) for men and 3·5 years (3·4-3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78-0·92) and 1·2 years (1·1-1·3), respectively.
[11] Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability.
[12] Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI.
[13] At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs.
[14] INTERPRETATION Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity.
[15] The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility.
[16] Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress.
[17] Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
[18] FUNDING Bill & Melinda Gates Foundation.

[Assistant]
Label: NOT ENOUGH INFORMATION
Rationale sentence ids: []
Explanation: The provided abstract does not contain direct evidence to support or contradict the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The recruitment of Wdr5 to its target loci depends on Kat8.

Document title: The histone acetyltransferase MOF is a key regulator of the embryonic stem cell core transcriptional network.

Abstract sentences:
[0] Pluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential for rapid response to differentiation cues.
[1] Both ESC features are subject to epigenetic regulation.
[2] Here we show that the histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and pluripotency.
[3] ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining, and differentiation potential.
[4] They also have aberrant expression of the core transcription factors Nanog, Oct4, and Sox2.
[5] Importantly, the phenotypes of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting the idea that Mof functions as an upstream regulator of Nanog in ESCs.
[6] Genome-wide ChIP-sequencing and transcriptome analyses further demonstrate that Mof is an integral component of the ESC core transcriptional network and that Mof primes genes for diverse developmental programs.
[7] Mof is also required for Wdr5 recruitment and H3K4 methylation at key regulatory loci, highlighting the complexity and interconnectivity of various chromatin regulators in ESCs.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "Mof is also required for Wdr5 recruitment and H3K4 methylation at key regulatory loci, highlighting the complexity and interconnectivity of various chromatin regulators in ESCs.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The relationship between a breast cancer patient's capacity to metabolize tamoxifen and treatment outcome is independent of the patient's genetic make-up.

Document title: Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen.

Abstract sentences:
[0] CONTEXT The growth inhibitory effect of tamoxifen, which is used for the treatment of hormone receptor-positive breast cancer, is mediated by its metabolites, 4-hydroxytamoxifen and endoxifen.
[1] The formation of active metabolites is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme.
[2] OBJECTIVE To determine whether CYP2D6 variation is associated with clinical outcomes in women receiving adjuvant tamoxifen.
[3] DESIGN, SETTING, AND PATIENTS Retrospective analysis of German and US cohorts of patients treated with adjuvant tamoxifen for early stage breast cancer.
[4] The 1325 patients had diagnoses between 1986 and 2005 of stage I through III breast cancer and were mainly postmenopausal (95.4%).
[5] Last follow-up was in December 2008; inclusion criteria were hormone receptor positivity, no metastatic disease at diagnosis, adjuvant tamoxifen therapy, and no chemotherapy.
[6] DNA from tumor tissue or blood was genotyped for CYP2D6 variants associated with reduced (*10, *41) or absent (*3, *4, *5) enzyme activity.
[7] Women were classified as having an extensive (n=609), heterozygous extensive/intermediate (n=637), or poor (n=79) CYP2D6 metabolism.
[8] MAIN OUTCOME MEASURES Time to recurrence, event-free survival, disease-free survival, and overall survival.
[9] RESULTS Median follow-up was 6.3 years.
[10] At 9 years of follow-up, the recurrence rates were 14.9% for extensive metabolizers, 20.9% for heterozygous extensive/intermediate metabolizers, and 29.0% for poor metabolizers, and all-cause mortality rates were 16.7%, 18.0%, and 22.8%, respectively.
[11] Compared with extensive metabolizers, there was a significantly increased risk of recurrence for heterozygous extensive/intermediate metabolizers (time to recurrence adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.04-1.90) and for poor metabolizers (time to recurrence HR, 1.90; 95% CI, 1.10-3.28).
[12] Compared with extensive metabolizers, those with decreased CYP2D6 activity (heterozygous extensive/intermediate and poor metabolism) had worse event-free survival (HR, 1.33; 95% CI, 1.06-1.68) and disease-free survival (HR, 1.29; 95% CI, 1.03-1.61), but there was no significant difference in overall survival (HR, 1.15; 95% CI, 0.88-1.51).
[13] CONCLUSION Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [11]
Explanation: Evidence states: "Compared with extensive metabolizers, there was a significantly increased risk of recurrence for heterozygous extensive/intermediate metabolizers (time to recurrence adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.04-1.90) and for poor metabolizers (time to recurrence HR, 1.90; 95% CI, 1.10-3.28).". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The relationship between a breast cancer patient's capacity to metabolize tamoxifen and treatment outcome is independent of the patient's genetic make-up.

Document title: Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen.

Abstract sentences:
[0] CONTEXT The growth inhibitory effect of tamoxifen, which is used for the treatment of hormone receptor-positive breast cancer, is mediated by its metabolites, 4-hydroxytamoxifen and endoxifen.
[1] The formation of active metabolites is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme.
[2] OBJECTIVE To determine whether CYP2D6 variation is associated with clinical outcomes in women receiving adjuvant tamoxifen.
[3] DESIGN, SETTING, AND PATIENTS Retrospective analysis of German and US cohorts of patients treated with adjuvant tamoxifen for early stage breast cancer.
[4] The 1325 patients had diagnoses between 1986 and 2005 of stage I through III breast cancer and were mainly postmenopausal (95.4%).
[5] Last follow-up was in December 2008; inclusion criteria were hormone receptor positivity, no metastatic disease at diagnosis, adjuvant tamoxifen therapy, and no chemotherapy.
[6] DNA from tumor tissue or blood was genotyped for CYP2D6 variants associated with reduced (*10, *41) or absent (*3, *4, *5) enzyme activity.
[7] Women were classified as having an extensive (n=609), heterozygous extensive/intermediate (n=637), or poor (n=79) CYP2D6 metabolism.
[8] MAIN OUTCOME MEASURES Time to recurrence, event-free survival, disease-free survival, and overall survival.
[9] RESULTS Median follow-up was 6.3 years.
[10] At 9 years of follow-up, the recurrence rates were 14.9% for extensive metabolizers, 20.9% for heterozygous extensive/intermediate metabolizers, and 29.0% for poor metabolizers, and all-cause mortality rates were 16.7%, 18.0%, and 22.8%, respectively.
[11] Compared with extensive metabolizers, there was a significantly increased risk of recurrence for heterozygous extensive/intermediate metabolizers (time to recurrence adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.04-1.90) and for poor metabolizers (time to recurrence HR, 1.90; 95% CI, 1.10-3.28).
[12] Compared with extensive metabolizers, those with decreased CYP2D6 activity (heterozygous extensive/intermediate and poor metabolism) had worse event-free survival (HR, 1.33; 95% CI, 1.06-1.68) and disease-free survival (HR, 1.29; 95% CI, 1.03-1.61), but there was no significant difference in overall survival (HR, 1.15; 95% CI, 0.88-1.51).
[13] CONCLUSION Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [12]
Explanation: Evidence states: "Compared with extensive metabolizers, those with decreased CYP2D6 activity (heterozygous extensive/intermediate and poor metabolism) had worse event-free survival (HR, 1.33; 95% CI, 1.06-1.68) and disease-free survival (HR, 1.29; 95% CI, 1.03-1.61), but there was no significant difference in overall survival (HR, 1.15; 95% CI, 0.88-1.51).". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The relationship between a breast cancer patient's capacity to metabolize tamoxifen and treatment outcome is independent of the patient's genetic make-up.

Document title: Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen.

Abstract sentences:
[0] CONTEXT The growth inhibitory effect of tamoxifen, which is used for the treatment of hormone receptor-positive breast cancer, is mediated by its metabolites, 4-hydroxytamoxifen and endoxifen.
[1] The formation of active metabolites is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme.
[2] OBJECTIVE To determine whether CYP2D6 variation is associated with clinical outcomes in women receiving adjuvant tamoxifen.
[3] DESIGN, SETTING, AND PATIENTS Retrospective analysis of German and US cohorts of patients treated with adjuvant tamoxifen for early stage breast cancer.
[4] The 1325 patients had diagnoses between 1986 and 2005 of stage I through III breast cancer and were mainly postmenopausal (95.4%).
[5] Last follow-up was in December 2008; inclusion criteria were hormone receptor positivity, no metastatic disease at diagnosis, adjuvant tamoxifen therapy, and no chemotherapy.
[6] DNA from tumor tissue or blood was genotyped for CYP2D6 variants associated with reduced (*10, *41) or absent (*3, *4, *5) enzyme activity.
[7] Women were classified as having an extensive (n=609), heterozygous extensive/intermediate (n=637), or poor (n=79) CYP2D6 metabolism.
[8] MAIN OUTCOME MEASURES Time to recurrence, event-free survival, disease-free survival, and overall survival.
[9] RESULTS Median follow-up was 6.3 years.
[10] At 9 years of follow-up, the recurrence rates were 14.9% for extensive metabolizers, 20.9% for heterozygous extensive/intermediate metabolizers, and 29.0% for poor metabolizers, and all-cause mortality rates were 16.7%, 18.0%, and 22.8%, respectively.
[11] Compared with extensive metabolizers, there was a significantly increased risk of recurrence for heterozygous extensive/intermediate metabolizers (time to recurrence adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.04-1.90) and for poor metabolizers (time to recurrence HR, 1.90; 95% CI, 1.10-3.28).
[12] Compared with extensive metabolizers, those with decreased CYP2D6 activity (heterozygous extensive/intermediate and poor metabolism) had worse event-free survival (HR, 1.33; 95% CI, 1.06-1.68) and disease-free survival (HR, 1.29; 95% CI, 1.03-1.61), but there was no significant difference in overall survival (HR, 1.15; 95% CI, 0.88-1.51).
[13] CONCLUSION Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [13]
Explanation: Evidence states: "CONCLUSION Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The removal of reactive oxygen species by activated oncogenes contributes to the increased genomic instability of leukaemia cells.

Document title: BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks.

Abstract sentences:
[0] The oncogenic BCR/ABL tyrosine kinase induces constitutive DNA damage in Philadelphia chromosome (Ph)-positive leukemia cells.
[1] We find that BCR/ABL-induced reactive oxygen species (ROSs) cause chronic oxidative DNA damage resulting in double-strand breaks (DSBs) in S and G(2)/M cell cycle phases.
[2] These lesions are repaired by BCR/ABL-stimulated homologous recombination repair (HRR) and nonhomologous end-joining (NHEJ) mechanisms.
[3] A high mutation rate is detected in HRR products in BCR/ABL-positive cells, but not in the normal counterparts.
[4] In addition, large deletions are found in NHEJ products exclusively in BCR/ABL cells.
[5] We propose that the following series of events may contribute to genomic instability of Ph-positive leukemias: BCR/ABL --> ROSs --> oxidative DNA damage --> DSBs in proliferating cells --> unfaithful HRR and NHEJ repair.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [0, 1]
Explanation: Evidence states: "The oncogenic BCR/ABL tyrosine kinase induces constitutive DNA damage in Philadelphia chromosome (Ph)-positive leukemia cells. We find that BCR/ABL-induced reactive oxygen species (ROSs) cause chronic oxidative DNA damage resulting in double-strand breaks (DSBs) in S and G(2)/M cell cycle phases.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The removal of reactive oxygen species by activated oncogenes contributes to the increased genomic instability of leukaemia cells.

Document title: BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks.

Abstract sentences:
[0] The oncogenic BCR/ABL tyrosine kinase induces constitutive DNA damage in Philadelphia chromosome (Ph)-positive leukemia cells.
[1] We find that BCR/ABL-induced reactive oxygen species (ROSs) cause chronic oxidative DNA damage resulting in double-strand breaks (DSBs) in S and G(2)/M cell cycle phases.
[2] These lesions are repaired by BCR/ABL-stimulated homologous recombination repair (HRR) and nonhomologous end-joining (NHEJ) mechanisms.
[3] A high mutation rate is detected in HRR products in BCR/ABL-positive cells, but not in the normal counterparts.
[4] In addition, large deletions are found in NHEJ products exclusively in BCR/ABL cells.
[5] We propose that the following series of events may contribute to genomic instability of Ph-positive leukemias: BCR/ABL --> ROSs --> oxidative DNA damage --> DSBs in proliferating cells --> unfaithful HRR and NHEJ repair.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "We propose that the following series of events may contribute to genomic instability of Ph-positive leukemias: BCR/ABL --> ROSs --> oxidative DNA damage --> DSBs in proliferating cells --> unfaithful HRR and NHEJ repair.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The repeat-variable diresidue (RVD) in the loop of Transcription-Activator Like (TAL) effectors specifies the nucleotides-amino acid contact at the target promoter element.

Document title: Structural basis for sequence-specific recognition of DNA by TAL effectors.

Abstract sentences:
[0] TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats.
[1] Each repeat comprises 33 to 35 conserved amino acids and targets a specific base pair by using two hypervariable residues [known as repeat variable diresidues (RVDs)] at positions 12 and 13.
[2] Here, we report the crystal structures of an 11.5-repeat TAL effector in both DNA-free and DNA-bound states.
[3] Each TAL repeat comprises two helices connected by a short RVD-containing loop.
[4] The 11.5 repeats form a right-handed, superhelical structure that tracks along the sense strand of DNA duplex, with RVDs contacting the major groove.
[5] The 12th residue stabilizes the RVD loop, whereas the 13th residue makes a base-specific contact.
[6] Understanding DNA recognition by TAL effectors may facilitate rational design of DNA-binding proteins with biotechnological applications.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0, 1]
Explanation: Evidence states: "TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved amino acids and targets a specific base pair by using two hypervariable residues [known as repeat variable diresidues (RVDs)] at positions 12 and 13.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The risk of breast cancer among parous women decreases with placental weight of pregnancies.

Document title: Pregnancy characteristics and maternal risk of breast cancer.

Abstract sentences:
[0] CONTEXT During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life.
[1] Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy.
[2] During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother.
[3] OBJECTIVE To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer.
[4] DESIGN AND SETTING Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes.
[5] PARTICIPANTS Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age.
[6] Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001).
[7] Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer.
[8] MAIN OUTCOME MEASURE Incidence of invasive breast cancer.
[9] RESULTS Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years.
[10] Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64).
[11] A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59).
[12] CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer.
[13] These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10]
Explanation: Evidence states: "Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64).". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The risk of breast cancer among parous women decreases with placental weight of pregnancies.

Document title: Pregnancy characteristics and maternal risk of breast cancer.

Abstract sentences:
[0] CONTEXT During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life.
[1] Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy.
[2] During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother.
[3] OBJECTIVE To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer.
[4] DESIGN AND SETTING Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes.
[5] PARTICIPANTS Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age.
[6] Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001).
[7] Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer.
[8] MAIN OUTCOME MEASURE Incidence of invasive breast cancer.
[9] RESULTS Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years.
[10] Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64).
[11] A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59).
[12] CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer.
[13] These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [12]
Explanation: Evidence states: "CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The risk of cancer rises with level of alcohol consumption.

Document title: Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Abstract sentences:
[0] Summary Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions.
[1] With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.
[2] Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs.
[3] We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.
[4] Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5–3·0) of age-standardised female deaths and 6·8% (5·8–8·0) of age-standardised male deaths.
[5] Among the population aged 15–49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2–4·3) of female deaths and 12·2% (10·8–13·6) of male deaths attributable to alcohol use.
[6] For the population aged 15–49 years, female attributable DALYs were 2·3% (95% UI 2·0–2·6) and male attributable DALYs were 8·9% (7·8–9·9).
[7] The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0–1·7] of total deaths), road injuries (1·2% [0·7–1·9]), and self-harm (1·1% [0·6–1·5]).
[8] For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2–33·3) of total alcohol-attributable female deaths and 18·9% (15·3–22·6) of male deaths.
[9] The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0–0·8) standard drinks per week.
[10] Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss.
[11] We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero.
[12] These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
[13] Funding Bill & Melinda Gates Foundation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2–33·3) of total alcohol-attributable female deaths and 18·9% (15·3–22·6) of male deaths.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The risk of cancer rises with level of alcohol consumption.

Document title: Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Abstract sentences:
[0] Summary Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions.
[1] With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.
[2] Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs.
[3] We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.
[4] Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5–3·0) of age-standardised female deaths and 6·8% (5·8–8·0) of age-standardised male deaths.
[5] Among the population aged 15–49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2–4·3) of female deaths and 12·2% (10·8–13·6) of male deaths attributable to alcohol use.
[6] For the population aged 15–49 years, female attributable DALYs were 2·3% (95% UI 2·0–2·6) and male attributable DALYs were 8·9% (7·8–9·9).
[7] The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0–1·7] of total deaths), road injuries (1·2% [0·7–1·9]), and self-harm (1·1% [0·6–1·5]).
[8] For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2–33·3) of total alcohol-attributable female deaths and 18·9% (15·3–22·6) of male deaths.
[9] The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0–0·8) standard drinks per week.
[10] Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss.
[11] We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero.
[12] These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
[13] Funding Bill & Melinda Gates Foundation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [11]
Explanation: Evidence states: "We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The risk of female prisoners harming themselves is ten times that of male prisoners.

Document title: Self-harm in prisons in England and Wales: an epidemiological study of prevalence, risk factors, clustering, and subsequent suicide

Abstract sentences:
[0] BACKGROUND Self-harm and suicide are common in prisoners, yet robust information on the full extent and characteristics of people at risk of self-harm is scant.
[1] Furthermore, understanding how frequently self-harm is followed by suicide, and in which prisoners this progression is most likely to happen, is important.
[2] We did a case-control study of all prisoners in England and Wales to ascertain the prevalence of self-harm in this population, associated risk factors, clustering effects, and risk of subsequent suicide after self-harm.
[3] METHODS Records of self-harm incidents in all prisons in England and Wales were gathered routinely between January, 2004, and December, 2009.
[4] We did a case-control comparison of prisoners who self-harmed and those who did not between January, 2006, and December, 2009.
[5] We also used a Bayesian approach to look at clustering of people who self-harmed.
[6] Prisoners who self-harmed and subsequently died by suicide in prison were compared with other inmates who self-harmed.
[7] FINDINGS 139,195 self-harm incidents were recorded in 26,510 individual prisoners between 2004 and 2009; 5-6% of male prisoners and 20-24% of female inmates self-harmed every year.
[8] Self-harm rates were more than ten times higher in female prisoners than in male inmates.
[9] Repetition of self-harm was common, particularly in women and teenage girls, in whom a subgroup of 102 prisoners accounted for 17,307 episodes.
[10] In both sexes, self-harm was associated with younger age, white ethnic origin, prison type, and a life sentence or being unsentenced; in female inmates, committing a violent offence against an individual was also a factor.
[11] Substantial evidence was noted of clustering in time and location of prisoners who self-harmed (adjusted intra-class correlation 0·15, 95% CI 0·11-0·18).
[12] 109 subsequent suicides in prison were reported in individuals who self-harmed; the risk was higher in those who self-harmed than in the general prison population, and more than half the deaths occurred within a month of self-harm.
[13] Risk factors for suicide after self-harm in male prisoners were older age and a previous self-harm incident of high or moderate lethality; in female inmates, a history of more than five self-harm incidents within a year was associated with subsequent suicide.
[14] INTERPRETATION The burden of self-harm in prisoners is substantial, particularly in women.
[15] Self-harm in prison is associated with subsequent suicide in this setting.
[16] Prevention and treatment of self-harm in prisoners is an essential component of suicide prevention in prisons.
[17] FUNDING Wellcome Trust, National Institute for Health Research, National Offender Management Service, and Department of Health.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "FINDINGS 139,195 self-harm incidents were recorded in 26,510 individual prisoners between 2004 and 2009; 5-6% of male prisoners and 20-24% of female inmates self-harmed every year.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The risk of female prisoners harming themselves is ten times that of male prisoners.

Document title: Self-harm in prisons in England and Wales: an epidemiological study of prevalence, risk factors, clustering, and subsequent suicide

Abstract sentences:
[0] BACKGROUND Self-harm and suicide are common in prisoners, yet robust information on the full extent and characteristics of people at risk of self-harm is scant.
[1] Furthermore, understanding how frequently self-harm is followed by suicide, and in which prisoners this progression is most likely to happen, is important.
[2] We did a case-control study of all prisoners in England and Wales to ascertain the prevalence of self-harm in this population, associated risk factors, clustering effects, and risk of subsequent suicide after self-harm.
[3] METHODS Records of self-harm incidents in all prisons in England and Wales were gathered routinely between January, 2004, and December, 2009.
[4] We did a case-control comparison of prisoners who self-harmed and those who did not between January, 2006, and December, 2009.
[5] We also used a Bayesian approach to look at clustering of people who self-harmed.
[6] Prisoners who self-harmed and subsequently died by suicide in prison were compared with other inmates who self-harmed.
[7] FINDINGS 139,195 self-harm incidents were recorded in 26,510 individual prisoners between 2004 and 2009; 5-6% of male prisoners and 20-24% of female inmates self-harmed every year.
[8] Self-harm rates were more than ten times higher in female prisoners than in male inmates.
[9] Repetition of self-harm was common, particularly in women and teenage girls, in whom a subgroup of 102 prisoners accounted for 17,307 episodes.
[10] In both sexes, self-harm was associated with younger age, white ethnic origin, prison type, and a life sentence or being unsentenced; in female inmates, committing a violent offence against an individual was also a factor.
[11] Substantial evidence was noted of clustering in time and location of prisoners who self-harmed (adjusted intra-class correlation 0·15, 95% CI 0·11-0·18).
[12] 109 subsequent suicides in prison were reported in individuals who self-harmed; the risk was higher in those who self-harmed than in the general prison population, and more than half the deaths occurred within a month of self-harm.
[13] Risk factors for suicide after self-harm in male prisoners were older age and a previous self-harm incident of high or moderate lethality; in female inmates, a history of more than five self-harm incidents within a year was associated with subsequent suicide.
[14] INTERPRETATION The burden of self-harm in prisoners is substantial, particularly in women.
[15] Self-harm in prison is associated with subsequent suicide in this setting.
[16] Prevention and treatment of self-harm in prisoners is an essential component of suicide prevention in prisons.
[17] FUNDING Wellcome Trust, National Institute for Health Research, National Offender Management Service, and Department of Health.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "Self-harm rates were more than ten times higher in female prisoners than in male inmates.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The tip of the inner tube of the toxic type VI secretion system (T6SS) antibacterial effector in Escherichia coli (E. coli) is decorated with VgrG and PAAR proteins.

Document title: A view to a kill: the bacterial type VI secretion system.

Abstract sentences:
[0] The bacterial type VI secretion system (T6SS) is an organelle that is structurally and mechanistically analogous to an intracellular membrane-attached contractile phage tail.
[1] Recent studies determined that a rapid conformational change in the structure of a sheath protein complex propels T6SS spike and tube components along with antibacterial and antieukaryotic effectors out of predatory T6SS(+) cells and into prey cells.
[2] The contracted organelle is then recycled in an ATP-dependent process.
[3] T6SS is regulated at transcriptional and posttranslational levels, the latter involving detection of membrane perturbation in some species.
[4] In addition to directly targeting eukaryotic cells, the T6SS can also target other bacteria coinfecting a mammalian host, highlighting the importance of the T6SS not only for bacterial survival in environmental ecosystems, but also in the context of infection and disease.
[5] This review highlights these and other advances in our understanding of the structure, mechanical function, assembly, and regulation of the T6SS.

[Assistant]
Label: NOT ENOUGH INFORMATION
Rationale sentence ids: []
Explanation: The provided abstract does not contain direct evidence to support or contradict the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: The tissue surrounding the granuloma in an immune cell induces an anti-inflammatory immune response.

Document title: Inflammatory signaling in human Tuberculosis granulomas is spatially organized

Abstract sentences:
[0] Granulomas are the pathological hallmark of tuberculosis (TB).
[1] However, their function and mechanisms of formation remain poorly understood.
[2] To understand the role of granulomas in TB, we analyzed the proteomes of granulomas from subjects with tuberculosis in an unbiased manner.
[3] Using laser-capture microdissection, mass spectrometry and confocal microscopy, we generated detailed molecular maps of human granulomas.
[4] We found that the centers of granulomas have a pro-inflammatory environment that is characterized by the presence of antimicrobial peptides, reactive oxygen species and pro-inflammatory eicosanoids.
[5] Conversely, the tissue surrounding the caseum has a comparatively anti-inflammatory signature.
[6] These findings are consistent across a set of six human subjects and in rabbits.
[7] Although the balance between systemic pro- and anti-inflammatory signals is crucial to TB disease outcome, here we find that these signals are physically segregated within each granuloma.
[8] From the protein and lipid snapshots of human and rabbit lesions analyzed here, we hypothesize that the pathologic response to TB is shaped by the precise anatomical localization of these inflammatory pathways during the development of the granuloma.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Conversely, the tissue surrounding the caseum has a comparatively anti-inflammatory signature.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: Therapeutics receiving accelerated approval encounter a lower frequency of post-marketing safety events

Document title: Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010

Abstract sentences:
[0] Importance Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics.
[1] These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making.
[2] Objectives To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk.
[3] Design and Setting Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017.
[4] Exposures Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near–regulatory deadline approval, and regulatory review time.
[5] Main Outcomes and Measures A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications.
[6] Results From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics).
[7] There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics.
[8] The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%).
[9] In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near–regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02).
[10] Conclusions and Relevance Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event.
[11] Biologics, psychiatric therapeutics, and accelerated and near–regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [9]
Explanation: Evidence states: "In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near–regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02).". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: There is a positive correlation between hip fractures and statin use.

Document title: HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.

Abstract sentences:
[0] CONTEXT Recent animal studies have found that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lipid-lowering drugs (statins) substantially increase bone formation, but whether statin use in humans results in clinically meaningful bone formation or a reduction in the risk of osteoporotic fractures is not known.
[1] OBJECTIVE To determine whether the use of statins is associated with reduced hip fracture risk.
[2] DESIGN Case-control study.
[3] SETTING AND PATIENTS A total of 6110 New Jersey residents aged 65 years or older and enrolled in Medicare and either Medicaid or the Pharmacy Assistance for the Aged and Disabled program.
[4] Case patients (n=1222) underwent surgical repair of a hip fracture in 1994.
[5] Control patients (n=4888) were identified at a ratio of 4:1 and frequency-matched to case patients for age and sex.
[6] MAIN OUTCOME MEASURE Adjusted odds ratio (OR) of hip fracture by statin use in the 180 days and 3 years prior to the index date (the earliest date of admission for surgery), adjusted for demographic and clinical characteristics and health care utilization.
[7] RESULTS Use of statins in either the prior 180 days (adjusted OR, 0.50; 95% confidence interval [CI], 0.33-0.76) or prior 3 years (adjusted OR, 0.57; 95% CI, 0.40-0.82) was associated with a significant reduction in the risk of hip fracture, even after controlling for variables such as race, insurance status, psychoactive medications, estrogen and thiazide use, ischemic heart disease, cancer, and diabetes mellitus.
[8] No significant relationship was observed between use of nonstatin lipid-lowering agents and hip fracture risk.
[9] Clear relationships were observed between the degree of reduction in hip fracture risk and the extent of statin use; there was no evidence of such relationships with nonstatin lipid-lowering agents.
[10] After adjusting for extent of statin use in the prior 3 years, current use (on the index date) was associated with a 71% reduction in risk (adjusted OR, 0.29; 95% CI, 0.10-0.81).
[11] The relationship between statin use and hip fracture risk persisted after controlling for variables such as the number of medications, the Charlson comorbidity index score, and hospitalization or nursing home stay in the last 180 days, as well as after excluding patients who were in a nursing home prior to their index date or who died in the year after their index date.
[12] Use of nonstatin lipid-lowering agents was not observed to be associated with reduction in hip fracture risk in any of these alternative models or analyses.
[13] CONCLUSIONS These findings support an association between statin use by elderly patients and reduction in the risk of hip fracture.
[14] Controlled trials are needed to exclude the possibility of unmeasured confounders.
[15] JAMA.
[16] 2000;283:3211-3216

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "RESULTS Use of statins in either the prior 180 days (adjusted OR, 0.50; 95% confidence interval [CI], 0.33-0.76) or prior 3 years (adjusted OR, 0.57; 95% CI, 0.40-0.82) was associated with a significant reduction in the risk of hip fracture, even after controlling for variables such as race, insurance status, psychoactive medications, estrogen and thiazide use, ischemic heart disease, cancer, and diabetes mellitus.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: There is a positive correlation between hip fractures and statin use.

Document title: HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.

Abstract sentences:
[0] CONTEXT Recent animal studies have found that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lipid-lowering drugs (statins) substantially increase bone formation, but whether statin use in humans results in clinically meaningful bone formation or a reduction in the risk of osteoporotic fractures is not known.
[1] OBJECTIVE To determine whether the use of statins is associated with reduced hip fracture risk.
[2] DESIGN Case-control study.
[3] SETTING AND PATIENTS A total of 6110 New Jersey residents aged 65 years or older and enrolled in Medicare and either Medicaid or the Pharmacy Assistance for the Aged and Disabled program.
[4] Case patients (n=1222) underwent surgical repair of a hip fracture in 1994.
[5] Control patients (n=4888) were identified at a ratio of 4:1 and frequency-matched to case patients for age and sex.
[6] MAIN OUTCOME MEASURE Adjusted odds ratio (OR) of hip fracture by statin use in the 180 days and 3 years prior to the index date (the earliest date of admission for surgery), adjusted for demographic and clinical characteristics and health care utilization.
[7] RESULTS Use of statins in either the prior 180 days (adjusted OR, 0.50; 95% confidence interval [CI], 0.33-0.76) or prior 3 years (adjusted OR, 0.57; 95% CI, 0.40-0.82) was associated with a significant reduction in the risk of hip fracture, even after controlling for variables such as race, insurance status, psychoactive medications, estrogen and thiazide use, ischemic heart disease, cancer, and diabetes mellitus.
[8] No significant relationship was observed between use of nonstatin lipid-lowering agents and hip fracture risk.
[9] Clear relationships were observed between the degree of reduction in hip fracture risk and the extent of statin use; there was no evidence of such relationships with nonstatin lipid-lowering agents.
[10] After adjusting for extent of statin use in the prior 3 years, current use (on the index date) was associated with a 71% reduction in risk (adjusted OR, 0.29; 95% CI, 0.10-0.81).
[11] The relationship between statin use and hip fracture risk persisted after controlling for variables such as the number of medications, the Charlson comorbidity index score, and hospitalization or nursing home stay in the last 180 days, as well as after excluding patients who were in a nursing home prior to their index date or who died in the year after their index date.
[12] Use of nonstatin lipid-lowering agents was not observed to be associated with reduction in hip fracture risk in any of these alternative models or analyses.
[13] CONCLUSIONS These findings support an association between statin use by elderly patients and reduction in the risk of hip fracture.
[14] Controlled trials are needed to exclude the possibility of unmeasured confounders.
[15] JAMA.
[16] 2000;283:3211-3216

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [9]
Explanation: Evidence states: "Clear relationships were observed between the degree of reduction in hip fracture risk and the extent of statin use; there was no evidence of such relationships with nonstatin lipid-lowering agents.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: There is a positive correlation between hip fractures and statin use.

Document title: HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.

Abstract sentences:
[0] CONTEXT Recent animal studies have found that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lipid-lowering drugs (statins) substantially increase bone formation, but whether statin use in humans results in clinically meaningful bone formation or a reduction in the risk of osteoporotic fractures is not known.
[1] OBJECTIVE To determine whether the use of statins is associated with reduced hip fracture risk.
[2] DESIGN Case-control study.
[3] SETTING AND PATIENTS A total of 6110 New Jersey residents aged 65 years or older and enrolled in Medicare and either Medicaid or the Pharmacy Assistance for the Aged and Disabled program.
[4] Case patients (n=1222) underwent surgical repair of a hip fracture in 1994.
[5] Control patients (n=4888) were identified at a ratio of 4:1 and frequency-matched to case patients for age and sex.
[6] MAIN OUTCOME MEASURE Adjusted odds ratio (OR) of hip fracture by statin use in the 180 days and 3 years prior to the index date (the earliest date of admission for surgery), adjusted for demographic and clinical characteristics and health care utilization.
[7] RESULTS Use of statins in either the prior 180 days (adjusted OR, 0.50; 95% confidence interval [CI], 0.33-0.76) or prior 3 years (adjusted OR, 0.57; 95% CI, 0.40-0.82) was associated with a significant reduction in the risk of hip fracture, even after controlling for variables such as race, insurance status, psychoactive medications, estrogen and thiazide use, ischemic heart disease, cancer, and diabetes mellitus.
[8] No significant relationship was observed between use of nonstatin lipid-lowering agents and hip fracture risk.
[9] Clear relationships were observed between the degree of reduction in hip fracture risk and the extent of statin use; there was no evidence of such relationships with nonstatin lipid-lowering agents.
[10] After adjusting for extent of statin use in the prior 3 years, current use (on the index date) was associated with a 71% reduction in risk (adjusted OR, 0.29; 95% CI, 0.10-0.81).
[11] The relationship between statin use and hip fracture risk persisted after controlling for variables such as the number of medications, the Charlson comorbidity index score, and hospitalization or nursing home stay in the last 180 days, as well as after excluding patients who were in a nursing home prior to their index date or who died in the year after their index date.
[12] Use of nonstatin lipid-lowering agents was not observed to be associated with reduction in hip fracture risk in any of these alternative models or analyses.
[13] CONCLUSIONS These findings support an association between statin use by elderly patients and reduction in the risk of hip fracture.
[14] Controlled trials are needed to exclude the possibility of unmeasured confounders.
[15] JAMA.
[16] 2000;283:3211-3216

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10]
Explanation: Evidence states: "After adjusting for extent of statin use in the prior 3 years, current use (on the index date) was associated with a 71% reduction in risk (adjusted OR, 0.29; 95% CI, 0.10-0.81).". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: There is a positive correlation between hip fractures and statin use.

Document title: HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients.

Abstract sentences:
[0] CONTEXT Recent animal studies have found that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lipid-lowering drugs (statins) substantially increase bone formation, but whether statin use in humans results in clinically meaningful bone formation or a reduction in the risk of osteoporotic fractures is not known.
[1] OBJECTIVE To determine whether the use of statins is associated with reduced hip fracture risk.
[2] DESIGN Case-control study.
[3] SETTING AND PATIENTS A total of 6110 New Jersey residents aged 65 years or older and enrolled in Medicare and either Medicaid or the Pharmacy Assistance for the Aged and Disabled program.
[4] Case patients (n=1222) underwent surgical repair of a hip fracture in 1994.
[5] Control patients (n=4888) were identified at a ratio of 4:1 and frequency-matched to case patients for age and sex.
[6] MAIN OUTCOME MEASURE Adjusted odds ratio (OR) of hip fracture by statin use in the 180 days and 3 years prior to the index date (the earliest date of admission for surgery), adjusted for demographic and clinical characteristics and health care utilization.
[7] RESULTS Use of statins in either the prior 180 days (adjusted OR, 0.50; 95% confidence interval [CI], 0.33-0.76) or prior 3 years (adjusted OR, 0.57; 95% CI, 0.40-0.82) was associated with a significant reduction in the risk of hip fracture, even after controlling for variables such as race, insurance status, psychoactive medications, estrogen and thiazide use, ischemic heart disease, cancer, and diabetes mellitus.
[8] No significant relationship was observed between use of nonstatin lipid-lowering agents and hip fracture risk.
[9] Clear relationships were observed between the degree of reduction in hip fracture risk and the extent of statin use; there was no evidence of such relationships with nonstatin lipid-lowering agents.
[10] After adjusting for extent of statin use in the prior 3 years, current use (on the index date) was associated with a 71% reduction in risk (adjusted OR, 0.29; 95% CI, 0.10-0.81).
[11] The relationship between statin use and hip fracture risk persisted after controlling for variables such as the number of medications, the Charlson comorbidity index score, and hospitalization or nursing home stay in the last 180 days, as well as after excluding patients who were in a nursing home prior to their index date or who died in the year after their index date.
[12] Use of nonstatin lipid-lowering agents was not observed to be associated with reduction in hip fracture risk in any of these alternative models or analyses.
[13] CONCLUSIONS These findings support an association between statin use by elderly patients and reduction in the risk of hip fracture.
[14] Controlled trials are needed to exclude the possibility of unmeasured confounders.
[15] JAMA.
[16] 2000;283:3211-3216

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [13]
Explanation: Evidence states: "CONCLUSIONS These findings support an association between statin use by elderly patients and reduction in the risk of hip fracture.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: There is a relation between Erythromycin use and hypertrophic pyloric stenosis.

Document title: Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort study

Abstract sentences:
[0] OBJECTIVE To assess the association between use of macrolide antibiotics in mothers and infants from pregnancy onset until 120 days after birth and infantile hypertrophic pyloric stenosis (IHPS).
[1] DESIGN Nationwide register based cohort study.
[2] SETTING Denmark, 1996-2011.
[3] PARTICIPANTS 999,378 liveborn singletons and linked individual level information on macrolide prescriptions (maternal use during pregnancy, n=30,091; maternal use after birth, n=21,557; use in infants, n=6591), surgery for IHPS, and potential confounders.
[4] MAIN OUTCOME MEASURES Surgery for IHPS by three categories of macrolide use: in mothers during pregnancy, in mothers after birth, and in infants after birth.
[5] RESULTS 880 infants developed IHPS (0.9 cases per 1000 births).
[6] Compared with infants with no use of macrolides, the adjusted rate ratio for IHPS in infants with use of macrolides during days 0 to 13 after birth was 29.8 (95% confidence interval 16.4 to 54.1) and during days 14 to 120 was 3.24 (1.20 to 8.74); the corresponding absolute risk differences were 24.4 (95% confidence interval 13.0 to 44.1) and 0.65 (0.06 to 2.21) cases per 1000 infants exposed to macrolides, respectively.
[7] The rate ratio for maternal use of macrolides for days 0 to 13 after birth was 3.49 (1.92 to 6.34) and for days 14 to 120 was 0.70 (0.26 to 1.90); the corresponding absolute risk differences were 2.15 (0.82 to 4.64) and -0.11 (-0.26 to 0.31).
[8] The rate ratios for maternal use of macrolides during pregnancy were 1.02 (0.65 to 1.59) for weeks 0 to 27 and 1.77 (0.95 to 3.31) for weeks 28 to birth; the corresponding absolute risk differences were 0.01 (-0.31 to 0.50) and 0.67 (-0.06 to 2.02).
[9] CONCLUSIONS Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk.
[10] Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS.
[11] A possible association was also found with use during late pregnancy.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "CONCLUSIONS Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: There is a relation between Erythromycin use and hypertrophic pyloric stenosis.

Document title: Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort study

Abstract sentences:
[0] OBJECTIVE To assess the association between use of macrolide antibiotics in mothers and infants from pregnancy onset until 120 days after birth and infantile hypertrophic pyloric stenosis (IHPS).
[1] DESIGN Nationwide register based cohort study.
[2] SETTING Denmark, 1996-2011.
[3] PARTICIPANTS 999,378 liveborn singletons and linked individual level information on macrolide prescriptions (maternal use during pregnancy, n=30,091; maternal use after birth, n=21,557; use in infants, n=6591), surgery for IHPS, and potential confounders.
[4] MAIN OUTCOME MEASURES Surgery for IHPS by three categories of macrolide use: in mothers during pregnancy, in mothers after birth, and in infants after birth.
[5] RESULTS 880 infants developed IHPS (0.9 cases per 1000 births).
[6] Compared with infants with no use of macrolides, the adjusted rate ratio for IHPS in infants with use of macrolides during days 0 to 13 after birth was 29.8 (95% confidence interval 16.4 to 54.1) and during days 14 to 120 was 3.24 (1.20 to 8.74); the corresponding absolute risk differences were 24.4 (95% confidence interval 13.0 to 44.1) and 0.65 (0.06 to 2.21) cases per 1000 infants exposed to macrolides, respectively.
[7] The rate ratio for maternal use of macrolides for days 0 to 13 after birth was 3.49 (1.92 to 6.34) and for days 14 to 120 was 0.70 (0.26 to 1.90); the corresponding absolute risk differences were 2.15 (0.82 to 4.64) and -0.11 (-0.26 to 0.31).
[8] The rate ratios for maternal use of macrolides during pregnancy were 1.02 (0.65 to 1.59) for weeks 0 to 27 and 1.77 (0.95 to 3.31) for weeks 28 to birth; the corresponding absolute risk differences were 0.01 (-0.31 to 0.50) and 0.67 (-0.06 to 2.02).
[9] CONCLUSIONS Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk.
[10] Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS.
[11] A possible association was also found with use during late pregnancy.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: There is no association between HNF4A mutations and diabetes risks.

Document title: Macrosomia and Hyperinsulinaemic Hypoglycaemia in Patients with Heterozygous Mutations in the HNF4A Gene

Abstract sentences:
[0] Background  Macrosomia is associated with considerable neonatal and maternal morbidity.
[1] Factors that predict macrosomia are poorly understood.
[2] The increased rate of macrosomia in the offspring of pregnant women with diabetes and in congenital hyperinsulinaemia is mediated by increased foetal insulin secretion.
[3] We assessed the in utero and neonatal role of two key regulators of pancreatic insulin secretion by studying birthweight and the incidence of neonatal hypoglycaemia in patients with heterozygous mutations in the maturity-onset diabetes of the young (MODY) genes HNF4A (encoding HNF-4α) and HNF1A/TCF1 (encoding HNF-1α), and the effect of pancreatic deletion of Hnf4a on foetal and neonatal insulin secretion in mice.

[Assistant]
Label: NOT ENOUGH INFORMATION
Rationale sentence ids: []
Explanation: The provided abstract does not contain direct evidence to support or contradict the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: There is no increased risk of hypospadias with clomiphene.

Document title: Use of clomifene during early pregnancy and risk of hypospadias: population based case-control study.

Abstract sentences:
[0] Clomifene is widely used for inducing ovulation.1 It is structurally related to diethylstilbestrol, which has been linked to vaginal and cervical clear cell adenocarcinoma in women exposed in utero.
[1] The adverse effect is less severe in sons, although links to testicular cancer and urogenital anomalies, such as epididymal cysts, have been reported.2 3 A recent study also found an increased risk of hypospadias in the sons of women exposed to diethylstilbestrol in utero.4 Clomifene has a half life of about five days, but its metabolites have been found in blood samples on day 22 of the menstrual cycle and in faeces up to six weeks after administration.5 The occurrence of hypospadias may be increasing.
[2] Little is known about the risk of hypospadias in boys born to women who have used clomifene to induce ovulation.
[3] ### Methods and results  Our case-control study was done in the Danish counties of North Jutland, Aarhus, Viborg, and …

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [1]
Explanation: Evidence states: "The adverse effect is less severe in sons, although links to testicular cancer and urogenital anomalies, such as epididymal cysts, have been reported.2 3 A recent study also found an increased risk of hypospadias in the sons of women exposed to diethylstilbestrol in utero.4 Clomifene has a half life of about five days, but its metabolites have been found in blood samples on day 22 of the menstrual cycle and in faeces up to six weeks after administration.5 The occurrence of hypospadias may be increasing.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: There is no known interaction between Pioneer factor OCT3/4 and major chromatin remodeling factors.

Document title: Oct4 links multiple epigenetic pathways to the pluripotency network

Abstract sentences:
[0] Oct4 is a well-known transcription factor that plays fundamental roles in stem cell self-renewal, pluripotency, and somatic cell reprogramming.
[1] However, limited information is available on Oct4-associated protein complexes and their intrinsic protein-protein interactions that dictate Oct4's critical regulatory activities.
[2] Here we employed an improved affinity purification approach combined with mass spectrometry to purify Oct4 protein complexes in mouse embryonic stem cells (mESCs), and discovered many novel Oct4 partners important for self-renewal and pluripotency of mESCs.
[3] Notably, we found that Oct4 is associated with multiple chromatin-modifying complexes with documented as well as newly proved functional significance in stem cell maintenance and somatic cell reprogramming.
[4] Our study establishes a solid biochemical basis for genetic and epigenetic regulation of stem cell pluripotency and provides a framework for exploring alternative factor-based reprogramming strategies.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Notably, we found that Oct4 is associated with multiple chromatin-modifying complexes with documented as well as newly proved functional significance in stem cell maintenance and somatic cell reprogramming.". This contradicts the claim.