[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: Taxation of sugar-sweetened beverages had no effect on the incidence rate of type II diabetes in India.

Document title: Averting Obesity and Type 2 Diabetes in India through Sugar-Sweetened Beverage Taxation: An Economic-Epidemiologic Modeling Study

Abstract sentences:
[0] BACKGROUND Taxing sugar-sweetened beverages (SSBs) has been proposed in high-income countries to reduce obesity and type 2 diabetes.
[1] We sought to estimate the potential health effects of such a fiscal strategy in the middle-income country of India, where there is heterogeneity in SSB consumption, patterns of substitution between SSBs and other beverages after tax increases, and vast differences in chronic disease risk within the population.
[2] METHODS AND FINDINGS Using consumption and price variations data from a nationally representative survey of 100,855 Indian households, we first calculated how changes in SSB price alter per capita consumption of SSBs and substitution with other beverages.
[3] We then incorporated SSB sales trends, body mass index (BMI), and diabetes incidence data stratified by age, sex, income, and urban/rural residence into a validated microsimulation of caloric consumption, glycemic load, overweight/obesity prevalence, and type 2 diabetes incidence among Indian subpopulations facing a 20% SSB excise tax.
[4] The 20% SSB tax was anticipated to reduce overweight and obesity prevalence by 3.0% (95% CI 1.6%-5.9%) and type 2 diabetes incidence by 1.6% (95% CI 1.2%-1.9%) among various Indian subpopulations over the period 2014-2023, if SSB consumption continued to increase linearly in accordance with secular trends.
[5] However, acceleration in SSB consumption trends consistent with industry marketing models would be expected to increase the impact efficacy of taxation, averting 4.2% of prevalent overweight/obesity (95% CI 2.5-10.0%) and 2.5% (95% CI 1.0-2.8%) of incident type 2 diabetes from 2014-2023.
[6] Given current consumption and BMI distributions, our results suggest the largest relative effect would be expected among young rural men, refuting our a priori hypothesis that urban populations would be isolated beneficiaries of SSB taxation.
[7] Key limitations of this estimation approach include the assumption that consumer expenditure behavior from prior years, captured in price elasticities, will reflect future behavior among consumers, and potential underreporting of consumption in dietary recall data used to inform our calculations.
[8] CONCLUSION Sustained SSB taxation at a high tax rate could mitigate rising obesity and type 2 diabetes in India among both urban and rural subpopulations.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "However, acceleration in SSB consumption trends consistent with industry marketing models would be expected to increase the impact efficacy of taxation, averting 4.2% of prevalent overweight/obesity (95% CI 2.5-10.0%) and 2.5% (95% CI 1.0-2.8%) of incident type 2 diabetes from 2014-2023.". 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: Taxation of sugar-sweetened beverages had no effect on the incidence rate of type II diabetes in India.

Document title: Averting Obesity and Type 2 Diabetes in India through Sugar-Sweetened Beverage Taxation: An Economic-Epidemiologic Modeling Study

Abstract sentences:
[0] BACKGROUND Taxing sugar-sweetened beverages (SSBs) has been proposed in high-income countries to reduce obesity and type 2 diabetes.
[1] We sought to estimate the potential health effects of such a fiscal strategy in the middle-income country of India, where there is heterogeneity in SSB consumption, patterns of substitution between SSBs and other beverages after tax increases, and vast differences in chronic disease risk within the population.
[2] METHODS AND FINDINGS Using consumption and price variations data from a nationally representative survey of 100,855 Indian households, we first calculated how changes in SSB price alter per capita consumption of SSBs and substitution with other beverages.
[3] We then incorporated SSB sales trends, body mass index (BMI), and diabetes incidence data stratified by age, sex, income, and urban/rural residence into a validated microsimulation of caloric consumption, glycemic load, overweight/obesity prevalence, and type 2 diabetes incidence among Indian subpopulations facing a 20% SSB excise tax.
[4] The 20% SSB tax was anticipated to reduce overweight and obesity prevalence by 3.0% (95% CI 1.6%-5.9%) and type 2 diabetes incidence by 1.6% (95% CI 1.2%-1.9%) among various Indian subpopulations over the period 2014-2023, if SSB consumption continued to increase linearly in accordance with secular trends.
[5] However, acceleration in SSB consumption trends consistent with industry marketing models would be expected to increase the impact efficacy of taxation, averting 4.2% of prevalent overweight/obesity (95% CI 2.5-10.0%) and 2.5% (95% CI 1.0-2.8%) of incident type 2 diabetes from 2014-2023.
[6] Given current consumption and BMI distributions, our results suggest the largest relative effect would be expected among young rural men, refuting our a priori hypothesis that urban populations would be isolated beneficiaries of SSB taxation.
[7] Key limitations of this estimation approach include the assumption that consumer expenditure behavior from prior years, captured in price elasticities, will reflect future behavior among consumers, and potential underreporting of consumption in dietary recall data used to inform our calculations.
[8] CONCLUSION Sustained SSB taxation at a high tax rate could mitigate rising obesity and type 2 diabetes in India among both urban and rural subpopulations.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [8]
Explanation: Evidence states: "CONCLUSION Sustained SSB taxation at a high tax rate could mitigate rising obesity and type 2 diabetes in India among both urban and rural subpopulations.". 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: Teaching hospitals do not provide better care than non-teaching hospitals.

Document title: Patient Outcomes with Teaching Versus Nonteaching Healthcare: A Systematic Review

Abstract sentences:
[0] Background  Extensive debate exists in the healthcare community over whether outcomes of medical care at teaching hospitals and other healthcare units are better or worse than those at the respective nonteaching ones.
[1] Thus, our goal was to systematically evaluate the evidence pertaining to this question.
[2] Methods and Findings  We reviewed all studies that compared teaching versus nonteaching healthcare structures for mortality or any other patient outcome, regardless of health condition.
[3] Studies were retrieved from PubMed, contact with experts, and literature cross-referencing.
[4] Data were extracted on setting, patients, data sources, author affiliations, definition of compared groups, types of diagnoses considered, adjusting covariates, and estimates of effect for mortality and for each other outcome.
[5] Overall, 132 eligible studies were identified, including 93 on mortality and 61 on other eligible outcomes (22 addressed both).
[6] Synthesis of the available adjusted estimates on mortality yielded a summary relative risk of 0.96 (95% confidence interval [CI], 0.93–1.00) for teaching versus nonteaching healthcare structures and 1.04 (95% CI, 0.99–1.10) for minor teaching versus nonteaching ones.
[7] There was considerable heterogeneity between studies (I2 = 72% for the main analysis).
[8] Results were similar in studies using clinical and those using administrative databases.
[9] No differences were seen in the 14 studies fully adjusting for volume/experience, severity, and comorbidity (relative risk 1.01).
[10] Smaller studies did not differ in their results from larger studies.
[11] Differences were seen for some diagnoses (e.g., significantly better survival for breast cancer and cerebrovascular accidents in teaching hospitals and significantly better survival from cholecystectomy in nonteaching hospitals), but these were small in magnitude.
[12] Other outcomes were diverse, but typically teaching healthcare structures did not do better than nonteaching ones.
[13] Conclusions  The available data are limited by their nonrandomized design, but overall they do not suggest that a healthcare facility's teaching status on its own markedly improves or worsens patient outcomes.
[14] Differences for specific diseases cannot be excluded, but are likely to be small.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Synthesis of the available adjusted estimates on mortality yielded a summary relative risk of 0.96 (95% confidence interval [CI], 0.93–1.00) for teaching versus nonteaching healthcare structures and 1.04 (95% CI, 0.99–1.10) for minor teaching versus nonteaching ones.". 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: Teaching hospitals do not provide better care than non-teaching hospitals.

Document title: Patient Outcomes with Teaching Versus Nonteaching Healthcare: A Systematic Review

Abstract sentences:
[0] Background  Extensive debate exists in the healthcare community over whether outcomes of medical care at teaching hospitals and other healthcare units are better or worse than those at the respective nonteaching ones.
[1] Thus, our goal was to systematically evaluate the evidence pertaining to this question.
[2] Methods and Findings  We reviewed all studies that compared teaching versus nonteaching healthcare structures for mortality or any other patient outcome, regardless of health condition.
[3] Studies were retrieved from PubMed, contact with experts, and literature cross-referencing.
[4] Data were extracted on setting, patients, data sources, author affiliations, definition of compared groups, types of diagnoses considered, adjusting covariates, and estimates of effect for mortality and for each other outcome.
[5] Overall, 132 eligible studies were identified, including 93 on mortality and 61 on other eligible outcomes (22 addressed both).
[6] Synthesis of the available adjusted estimates on mortality yielded a summary relative risk of 0.96 (95% confidence interval [CI], 0.93–1.00) for teaching versus nonteaching healthcare structures and 1.04 (95% CI, 0.99–1.10) for minor teaching versus nonteaching ones.
[7] There was considerable heterogeneity between studies (I2 = 72% for the main analysis).
[8] Results were similar in studies using clinical and those using administrative databases.
[9] No differences were seen in the 14 studies fully adjusting for volume/experience, severity, and comorbidity (relative risk 1.01).
[10] Smaller studies did not differ in their results from larger studies.
[11] Differences were seen for some diagnoses (e.g., significantly better survival for breast cancer and cerebrovascular accidents in teaching hospitals and significantly better survival from cholecystectomy in nonteaching hospitals), but these were small in magnitude.
[12] Other outcomes were diverse, but typically teaching healthcare structures did not do better than nonteaching ones.
[13] Conclusions  The available data are limited by their nonrandomized design, but overall they do not suggest that a healthcare facility's teaching status on its own markedly improves or worsens patient outcomes.
[14] Differences for specific diseases cannot be excluded, but are likely to be small.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [12]
Explanation: Evidence states: "Other outcomes were diverse, but typically teaching healthcare structures did not do better than nonteaching ones.". 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: Teaching hospitals do not provide better care than non-teaching hospitals.

Document title: Patient Outcomes with Teaching Versus Nonteaching Healthcare: A Systematic Review

Abstract sentences:
[0] Background  Extensive debate exists in the healthcare community over whether outcomes of medical care at teaching hospitals and other healthcare units are better or worse than those at the respective nonteaching ones.
[1] Thus, our goal was to systematically evaluate the evidence pertaining to this question.
[2] Methods and Findings  We reviewed all studies that compared teaching versus nonteaching healthcare structures for mortality or any other patient outcome, regardless of health condition.
[3] Studies were retrieved from PubMed, contact with experts, and literature cross-referencing.
[4] Data were extracted on setting, patients, data sources, author affiliations, definition of compared groups, types of diagnoses considered, adjusting covariates, and estimates of effect for mortality and for each other outcome.
[5] Overall, 132 eligible studies were identified, including 93 on mortality and 61 on other eligible outcomes (22 addressed both).
[6] Synthesis of the available adjusted estimates on mortality yielded a summary relative risk of 0.96 (95% confidence interval [CI], 0.93–1.00) for teaching versus nonteaching healthcare structures and 1.04 (95% CI, 0.99–1.10) for minor teaching versus nonteaching ones.
[7] There was considerable heterogeneity between studies (I2 = 72% for the main analysis).
[8] Results were similar in studies using clinical and those using administrative databases.
[9] No differences were seen in the 14 studies fully adjusting for volume/experience, severity, and comorbidity (relative risk 1.01).
[10] Smaller studies did not differ in their results from larger studies.
[11] Differences were seen for some diagnoses (e.g., significantly better survival for breast cancer and cerebrovascular accidents in teaching hospitals and significantly better survival from cholecystectomy in nonteaching hospitals), but these were small in magnitude.
[12] Other outcomes were diverse, but typically teaching healthcare structures did not do better than nonteaching ones.
[13] Conclusions  The available data are limited by their nonrandomized design, but overall they do not suggest that a healthcare facility's teaching status on its own markedly improves or worsens patient outcomes.
[14] Differences for specific diseases cannot be excluded, but are likely to be small.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [13]
Explanation: Evidence states: "Conclusions  The available data are limited by their nonrandomized design, but overall they do not suggest that a healthcare facility's teaching status on its own markedly improves or worsens patient outcomes.". 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: Tetraspanin-3 is a causative factor in the development of acute myelogenous leukemia

Document title: Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia.

Abstract sentences:
[0] Acute Myelogenous Leukemia (AML) is an aggressive cancer that strikes both adults and children and is frequently resistant to therapy.
[1] Thus, identifying signals needed for AML propagation is a critical step toward developing new approaches for treating this disease.
[2] Here, we show that Tetraspanin 3 is a target of the RNA binding protein Musashi 2, which plays a key role in AML.
[3] We generated Tspan3 knockout mice that were born without overt defects.
[4] However, Tspan3 deletion impaired leukemia stem cell self-renewal and disease propagation and markedly improved survival in mouse models of AML.
[5] Additionally, Tspan3 inhibition blocked growth of AML patient samples, suggesting that Tspan3 is also important in human disease.
[6] As part of the mechanism, we show that Tspan3 deficiency disabled responses to CXCL12/SDF-1 and led to defects in AML localization within the niche.
[7] These identify Tspan3 as an important regulator of aggressive leukemias and highlight a role for Tspan3 in oncogenesis.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "However, Tspan3 deletion impaired leukemia stem cell self-renewal and disease propagation and markedly improved survival in mouse models of AML.". 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: Tetraspanin-3 is a causative factor in the development of acute myelogenous leukemia

Document title: Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia.

Abstract sentences:
[0] Acute Myelogenous Leukemia (AML) is an aggressive cancer that strikes both adults and children and is frequently resistant to therapy.
[1] Thus, identifying signals needed for AML propagation is a critical step toward developing new approaches for treating this disease.
[2] Here, we show that Tetraspanin 3 is a target of the RNA binding protein Musashi 2, which plays a key role in AML.
[3] We generated Tspan3 knockout mice that were born without overt defects.
[4] However, Tspan3 deletion impaired leukemia stem cell self-renewal and disease propagation and markedly improved survival in mouse models of AML.
[5] Additionally, Tspan3 inhibition blocked growth of AML patient samples, suggesting that Tspan3 is also important in human disease.
[6] As part of the mechanism, we show that Tspan3 deficiency disabled responses to CXCL12/SDF-1 and led to defects in AML localization within the niche.
[7] These identify Tspan3 as an important regulator of aggressive leukemias and highlight a role for Tspan3 in oncogenesis.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Additionally, Tspan3 inhibition blocked growth of AML patient samples, suggesting that Tspan3 is also important in human disease.". 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: Tetraspanin-3 is a causative factor in the development of acute myelogenous leukemia

Document title: Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia.

Abstract sentences:
[0] Acute Myelogenous Leukemia (AML) is an aggressive cancer that strikes both adults and children and is frequently resistant to therapy.
[1] Thus, identifying signals needed for AML propagation is a critical step toward developing new approaches for treating this disease.
[2] Here, we show that Tetraspanin 3 is a target of the RNA binding protein Musashi 2, which plays a key role in AML.
[3] We generated Tspan3 knockout mice that were born without overt defects.
[4] However, Tspan3 deletion impaired leukemia stem cell self-renewal and disease propagation and markedly improved survival in mouse models of AML.
[5] Additionally, Tspan3 inhibition blocked growth of AML patient samples, suggesting that Tspan3 is also important in human disease.
[6] As part of the mechanism, we show that Tspan3 deficiency disabled responses to CXCL12/SDF-1 and led to defects in AML localization within the niche.
[7] These identify Tspan3 as an important regulator of aggressive leukemias and highlight a role for Tspan3 in oncogenesis.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "These identify Tspan3 as an important regulator of aggressive leukemias and highlight a role for Tspan3 in oncogenesis.". 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 DdrB protein from Deinococcus radiodurans is an alternative SSB.

Document title: The structure of DdrB from Deinococcus: a new fold for single-stranded DNA binding proteins

Abstract sentences:
[0] Deinococcus spp. are renowned for their amazing ability to recover rapidly from severe genomic fragmentation as a result of exposure to extreme levels of ionizing radiation or desiccation.
[1] Despite having been originally characterized over 50 years ago, the mechanism underlying this remarkable repair process is still poorly understood.
[2] Here, we report the 2.8 A structure of DdrB, a single-stranded DNA (ssDNA) binding protein unique to Deinococcus spp.
[3] that is crucial for recovery following DNA damage.
[4] DdrB forms a pentameric ring capable of binding single-stranded but not double-stranded DNA.
[5] Unexpectedly, the crystal structure reveals that DdrB comprises a novel fold that is structurally and topologically distinct from all other single-stranded binding (SSB) proteins characterized to date.
[6] The need for a unique ssDNA binding function in response to severe damage, suggests a distinct role for DdrB which may encompass not only standard SSB protein function in protection of ssDNA, but also more specialized roles in protein recruitment or DNA architecture maintenance.
[7] Possible mechanisms of DdrB action in damage recovery are discussed.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Unexpectedly, the crystal structure reveals that DdrB comprises a novel fold that is structurally and topologically distinct from all other single-stranded binding (SSB) proteins characterized to date.". 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 PPR MDA5 has two N-terminal CARD domains.

Document title: Immune signaling by RIG-I-like receptors.

Abstract sentences:
[0] The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a major role in pathogen sensing of RNA virus infection to initiate and modulate antiviral immunity.
[1] The RLRs detect viral RNA ligands or processed self RNA in the cytoplasm to trigger innate immunity and inflammation and to impart gene expression that serves to control infection.
[2] Importantly, RLRs cooperate in signaling crosstalk networks with Toll-like receptors and other factors to impart innate immunity and to modulate the adaptive immune response.
[3] RLR regulation occurs at a variety of levels ranging from autoregulation to ligand and cofactor interactions and posttranslational modifications.
[4] Abberant RLR signaling or dysregulation of RLR expression is now implicated in the development of autoimmune diseases.
[5] Understanding the processes of RLR signaling and response will provide insights to guide RLR-targeted therapeutics for antiviral and immune-modifying applications.

[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 PRR MDA5 has a central DExD/H RNA helices domain.

Document title: Immune signaling by RIG-I-like receptors.

Abstract sentences:
[0] The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a major role in pathogen sensing of RNA virus infection to initiate and modulate antiviral immunity.
[1] The RLRs detect viral RNA ligands or processed self RNA in the cytoplasm to trigger innate immunity and inflammation and to impart gene expression that serves to control infection.
[2] Importantly, RLRs cooperate in signaling crosstalk networks with Toll-like receptors and other factors to impart innate immunity and to modulate the adaptive immune response.
[3] RLR regulation occurs at a variety of levels ranging from autoregulation to ligand and cofactor interactions and posttranslational modifications.
[4] Abberant RLR signaling or dysregulation of RLR expression is now implicated in the development of autoimmune diseases.
[5] Understanding the processes of RLR signaling and response will provide insights to guide RLR-targeted therapeutics for antiviral and immune-modifying applications.

[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 PRR MDA5 is a sensor of RNA virus infection.

Document title: Immune signaling by RIG-I-like receptors.

Abstract sentences:
[0] The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a major role in pathogen sensing of RNA virus infection to initiate and modulate antiviral immunity.
[1] The RLRs detect viral RNA ligands or processed self RNA in the cytoplasm to trigger innate immunity and inflammation and to impart gene expression that serves to control infection.
[2] Importantly, RLRs cooperate in signaling crosstalk networks with Toll-like receptors and other factors to impart innate immunity and to modulate the adaptive immune response.
[3] RLR regulation occurs at a variety of levels ranging from autoregulation to ligand and cofactor interactions and posttranslational modifications.
[4] Abberant RLR signaling or dysregulation of RLR expression is now implicated in the development of autoimmune diseases.
[5] Understanding the processes of RLR signaling and response will provide insights to guide RLR-targeted therapeutics for antiviral and immune-modifying applications.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a major role in pathogen sensing of RNA virus infection to initiate and modulate antiviral immunity.". 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 US health care system can save up to $750 million if 7% of patients waiting for kidney transplants participate in the optimized national kidney paired donation program.

Document title: Kidney paired donation and optimizing the use of live donor organs.

Abstract sentences:
[0] CONTEXT Blood type and crossmatch incompatibility will exclude at least one third of patients in need from receiving a live donor kidney transplant.
[1] Kidney paired donation (KPD) offers incompatible donor/recipient pairs the opportunity to match for compatible transplants.
[2] Despite its increasing popularity, very few transplants have resulted from KPD.
[3] OBJECTIVE To determine the potential impact of improved matching schemes on the number and quality of transplants achievable with KPD.
[4] DESIGN, SETTING, AND POPULATION We developed a model that simulates pools of incompatible donor/recipient pairs.
[5] We designed a mathematically verifiable optimized matching algorithm and compared it with the scheme currently used in some centers and regions.
[6] Simulated patients from the general community with characteristics drawn from distributions describing end-stage renal disease patients eligible for renal transplantation and their willing and eligible live donors.
[7] MAIN OUTCOME MEASURES Number of kidneys matched, HLA mismatch of matched kidneys, and number of grafts surviving 5 years after transplantation.
[8] RESULTS A national optimized matching algorithm would result in more transplants (47.7% vs 42.0%, P<.001), better HLA concordance (3.0 vs 4.5 mismatched antigens; P<.001), more grafts surviving at 5 years (34.9% vs 28.7%; P<.001), and a reduction in the number of pairs required to travel (2.9% vs 18.4%; P<.001) when compared with an extension of the currently used first-accept scheme to a national level.
[9] Furthermore, highly sensitized patients would benefit 6-fold from a national optimized scheme (2.3% vs 14.1% successfully matched; P<.001).
[10] Even if only 7% of patients awaiting kidney transplantation participated in an optimized national KPD program, the health care system could save as much as $750 million.
[11] CONCLUSIONS The combination of a national KPD program and a mathematically optimized matching algorithm yields more matches with lower HLA disparity.
[12] Optimized matching affords patients the flexibility of customizing their matching priorities and the security of knowing that the greatest number of high-quality matches will be found and distributed equitably.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "Even if only 7% of patients awaiting kidney transplantation participated in an optimized national KPD program, the health care system could save as much as $750 million.". 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 YAP1 and TEAD complex tanslocates into the nucleus where it interacts with transcription factors and DNA-binding proteins that modulate target gene transcription.

Document title: Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation

Abstract sentences:
[0] The Hippo pathway controls organ size and tissue homeostasis, with deregulation leading to cancer.
[1] The core Hippo components in mammals are composed of the upstream serine/threonine kinases Mst1/2, MAPK4Ks and Lats1/2.
[2] Inactivation of these upstream kinases leads to dephosphorylation, stabilization, nuclear translocation and thus activation of the major functional transducers of the Hippo pathway, YAP and its paralogue TAZ.
[3] YAP/TAZ are transcription co-activators that regulate gene expression primarily through interaction with the TEA domain DNA-binding family of transcription factors (TEAD).
[4] The current paradigm for regulation of this pathway centres on phosphorylation-dependent nucleocytoplasmic shuttling of YAP/TAZ through a complex network of upstream components.
[5] However, unlike other transcription factors, such as SMAD, NF-κB, NFAT and STAT, the regulation of TEAD nucleocytoplasmic shuttling has been largely overlooked.
[6] In the present study, we show that environmental stress promotes TEAD cytoplasmic translocation via p38 MAPK in a Hippo-independent manner.
[7] Importantly, stress-induced TEAD inhibition predominates YAP-activating signals and selectively suppresses YAP-driven cancer cell growth.
[8] Our data reveal a mechanism governing TEAD nucleocytoplasmic shuttling and show that TEAD localization is a critical determinant of Hippo signalling output.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "YAP/TAZ are transcription co-activators that regulate gene expression primarily through interaction with the TEA domain DNA-binding family of transcription factors (TEAD).". 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 amount of publicly available DNA data doubles every 10 years.

Document title: The EMBL nucleotide sequence database.

Abstract sentences:
[0] The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl. html ) constitutes Europe's primary nucleotide sequence resource.
[1] DNA and RNA sequences are directly submitted from researchers and genome sequencing groups and collected from the scientific literature and patent applications (Fig. 1).
[2] In collaboration with DDBJ and GenBank the database is produced, maintained and distributed at the European Bioinformatics Institute.
[3] Database releases are produced quarterly and are distributed on CD-ROM.
[4] EBI's network services allow access to the most up-to-date data collection via Internet and World Wide Web interface, providing database searching and sequence similarity facilities plus access to a large number of additional databases.

[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 arm density of TatAd complexes is due to structural rearrangements within Class1 TatAd complexes such as the 'charge zipper mechanism'.

Document title: Folding and Self-Assembly of the TatA Translocation Pore Based on a Charge Zipper Mechanism

Abstract sentences:
[0] We propose a concept for the folding and self-assembly of the pore-forming TatA complex from the Twin-arginine translocase and of other membrane proteins based on electrostatic "charge zippers.
[1] "
[2] Each subunit of TatA consists of a transmembrane segment, an amphiphilic helix (APH), and a C-terminal densely charged region (DCR).
[3] The sequence of charges in the DCR is complementary to the charge pattern on the APH, suggesting that the protein can be "zipped up" by a ladder of seven salt bridges.
[4] The length of the resulting hairpin matches the lipid bilayer thickness, hence a transmembrane pore could self-assemble via intra- and intermolecular salt bridges.
[5] The steric feasibility was rationalized by molecular dynamics simulations, and experimental evidence was obtained by monitoring the monomer-oligomer equilibrium of specific charge mutants.
[6] Similar "charge zippers" are proposed for other membrane-associated proteins, e.g., the biofilm-inducing peptide TisB, the human antimicrobial peptide dermcidin, and the pestiviral E(RNS) protein.

[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 availability of safe places to study is effective at decreasing homelessness.

Document title: Mental health problems of homeless children and families: longitudinal study.

Abstract sentences:
[0] OBJECTIVE To establish the mental health needs of homeless children and families before and after rehousing.
[1] DESIGN Cross sectional, longitudinal study.
[2] SETTING City of Birmingham.
[3] SUBJECTS 58 rehoused families with 103 children aged 2-16 years and 21 comparison families of low socioeconomic status in stable housing, with 54 children.
[4] MAIN OUTCOME MEASURES Children's mental health problems and level of communication; mothers' mental health problems and social support one year after rehousing.
[5] RESULTS Mental health problems remained significantly higher in rehoused mothers and their children than in the comparison group (mothers 26% v 5%, P = 0.04; children 39% v 11%, P = 0.0003).
[6] Homeless mothers continued to have significantly less social support at follow up.
[7] Mothers with a history of abuse and poor social integration were more likely to have children with persistent mental health problems.
[8] CONCLUSIONS Homeless families have a high level of complex needs that cannot be met by conventional health services and arrangements.
[9] Local strategies for rapid rehousing into permanent accommodation, effective social support and health care for parents and children, and protection from violence and intimidation should be developed and implemented.

[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 availability of safe places to study is not effective at decreasing homelessness.

Document title: Mental health problems of homeless children and families: longitudinal study.

Abstract sentences:
[0] OBJECTIVE To establish the mental health needs of homeless children and families before and after rehousing.
[1] DESIGN Cross sectional, longitudinal study.
[2] SETTING City of Birmingham.
[3] SUBJECTS 58 rehoused families with 103 children aged 2-16 years and 21 comparison families of low socioeconomic status in stable housing, with 54 children.
[4] MAIN OUTCOME MEASURES Children's mental health problems and level of communication; mothers' mental health problems and social support one year after rehousing.
[5] RESULTS Mental health problems remained significantly higher in rehoused mothers and their children than in the comparison group (mothers 26% v 5%, P = 0.04; children 39% v 11%, P = 0.0003).
[6] Homeless mothers continued to have significantly less social support at follow up.
[7] Mothers with a history of abuse and poor social integration were more likely to have children with persistent mental health problems.
[8] CONCLUSIONS Homeless families have a high level of complex needs that cannot be met by conventional health services and arrangements.
[9] Local strategies for rapid rehousing into permanent accommodation, effective social support and health care for parents and children, and protection from violence and intimidation should be developed and implemented.

[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 benefits of colchicine were achieved with effective widespread use of secondary prevention strategies such as high-dose statins.

Document title: Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis.

Abstract sentences:
[0] CONTEXT Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events.
[1] Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear.
[2] OBJECTIVE To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors.
[3] DESIGN, SETTING, AND PATIENTS Outpatients with coronary artery disease, cerebrovascular disease, or peripheral arterial disease or with multiple risk factors for atherothrombosis were enrolled in the global Reduction of Atherothrombosis for Continued Health (REACH) Registry and were followed up for as long as 4 years.
[4] Patients from 3647 centers in 29 countries were enrolled between 2003 and 2004 and followed up until 2008.
[5] Final database lock was in April 2009.
[6] MAIN OUTCOME MEASURES Rates of cardiovascular death, myocardial infarction, and stroke.
[7] RESULTS A total of 45,227 patients with baseline data were included in this 4-year analysis.
[8] During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a myocardial infarction and stroke on the same day.
[9] Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n = 21,890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n = 15,264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n = 8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P < .001 for all comparisons).
[10] In addition, in multivariable modeling, the presence of diabetes (hazard ratio [HR], 1.44; 95% CI, 1.36-1.53; P < .001), an ischemic event in the previous year (HR, 1.71; 95% CI, 1.57-1.85; P < .001), and polyvascular disease (HR, 1.99; 95% CI, 1.78-2.24; P < .001) each were associated with a significantly higher risk of the primary end point.
[11] CONCLUSION Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis.

[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 binding orientation of the ML-SA1 activator at hTRPML2 is different from the binding orientation of the ML-SA1 activator at hTRPML1.

Document title: Human TRPML1 channel structures in open and closed conformations

Abstract sentences:
[0] Transient receptor potential mucolipin 1 (TRPML1) is a Ca2+-releasing cation channel that mediates the calcium signalling and homeostasis of lysosomes.
[1] Mutations in TRPML1 lead to mucolipidosis type IV, a severe lysosomal storage disorder.
[2] Here we report two electron cryo-microscopy structures of full-length human TRPML1: a 3.72-Å apo structure at pH 7.0 in the closed state, and a 3.49-Å agonist-bound structure at pH 6.0 in an open state.
[3] Several aromatic and hydrophobic residues in pore helix 1, helices S5 and S6, and helix S6 of a neighbouring subunit, form a hydrophobic cavity to house the agonist, suggesting a distinct agonist-binding site from that found in TRPV1, a TRP channel from a different subfamily.
[4] The opening of TRPML1 is associated with distinct dilations of its lower gate together with a slight structural movement of pore helix 1.
[5] Our work reveals the regulatory mechanism of TRPML channels, facilitates better understanding of TRP channel activation, and provides insights into the molecular basis of mucolipidosis type IV pathogenesis.

[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 center of the granuloma in an immune cell induces a pro-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: [4]
Explanation: Evidence states: "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.". 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 combination of H3K4me3 and H3K79me2 is found in quiescent hair follicle stem cells.

Document title: Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage.

Abstract sentences:
[0] Using mouse skin, where bountiful reservoirs of synchronized hair follicle stem cells (HF-SCs) fuel cycles of regeneration, we explore how adult SCs remodel chromatin in response to activating cues.
[1] By profiling global mRNA and chromatin changes in quiescent and activated HF-SCs and their committed, transit-amplifying (TA) progeny, we show that polycomb-group (PcG)-mediated H3K27-trimethylation features prominently in HF-lineage progression by mechanisms distinct from embryonic-SCs.
[2] In HF-SCs, PcG represses nonskin lineages and HF differentiation.
[3] In TA progeny, nonskin regulators remain PcG-repressed, HF-SC regulators acquire H3K27me3-marks, and HF-lineage regulators lose them.
[4] Interestingly, genes poised in embryonic stem cells, active in HF-SCs, and PcG-repressed in TA progeny encode not only key transcription factors, but also signaling regulators.
[5] We document their importance in balancing HF-SC quiescence, underscoring the power of chromatin mapping in dissecting SC behavior.
[6] Our findings explain how HF-SCs cycle through quiescent and activated states without losing stemness and define roles for PcG-mediated repression in governing a fate switch irreversibly.

[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 composition of myosin-II isoform switches from the polarizable B isoform to the more homogenous A isoform during hematopoietic differentiation.

Document title: Contractile forces sustain and polarize hematopoiesis from stem and progenitor cells.

Abstract sentences:
[0] Self-renewal and differentiation of stem cells depend on asymmetric division and polarized motility processes that in other cell types are modulated by nonmuscle myosin-II (MII) forces and matrix mechanics.
[1] Here, mass spectrometry-calibrated intracellular flow cytometry of human hematopoiesis reveals MIIB to be a major isoform that is strongly polarized in hematopoietic stem cells and progenitors (HSC/Ps) and thereby downregulated in differentiated cells via asymmetric division.
[2] MIIA is constitutive and activated by dephosphorylation during cytokine-triggered differentiation of cells grown on stiff, endosteum-like matrix, but not soft, marrow-like matrix.
[3] In vivo, MIIB is required for generation of blood, while MIIA is required for sustained HSC/P engraftment.
[4] Reversible inhibition of both isoforms in culture with blebbistatin enriches for long-term hematopoietic multilineage reconstituting cells by 5-fold or more as assessed in vivo.
[5] Megakaryocytes also become more polyploid, producing 4-fold more platelets.
[6] MII is thus a multifunctional node in polarized division and niche sensing.

[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 deregulated and prolonged activation of monocytes has deleterious effects in inflammatory diseases.

Document title: Myeloid-specific Krüppel-like factor 2 inactivation increases macrophage and neutrophil adhesion and promotes atherosclerosis.

Abstract sentences:
[0] RATIONALE Hemizygous deficiency of the transcription factor Krüppel-like factor 2 (KLF2) has been shown previously to augment atherosclerosis in hypercholesterolemic mice.
[1] However, the cell type responsible for the increased atherosclerosis due to KLF2 deficiency has not been identified.
[2] This study examined the consequence of myeloid cell-specific KLF2 inactivation in atherosclerosis.
[3] METHODS AND RESULTS Cell-specific knockout mice were generated by Cre/loxP recombination.
[4] Macrophages isolated from myeloid-specific Klf2 knockout (myeKlf2(-/-)) mice were similar to myeKlf2(+/+) macrophages in response to activation, polarization, and lipid accumulation.
[5] However, in comparison to myeKlf2(+/+) macrophages, myeKlf2(-/-) macrophages adhered more robustly to endothelial cells.
[6] Neutrophils from myeKlf2(-/-) mice also adhered more robustly to endothelial cells, and fewer myeKlf2(-/-) neutrophils survived in culture over a 24-hour period in comparison with myeKlf2(+/+) neutrophils.
[7] When myeKlf2(-/-) mice were mated to Ldlr(-/-) mice and then fed a high fat and high cholesterol diet, significant increase in atherosclerosis was observed in the myeKlf2(-/-)Ldlr(-/-) mice compared with myeKlf2(+/+)Ldlr(-/-) littermates.
[8] The increased atherosclerosis in myeKlf2(-/-)Ldlr(-/-) mice was associated with elevated presence of neutrophils and macrophages, with corresponding increase of myeloperoxidase as well as chlorinated and nitrosylated tyrosine epitopes in their lesion areas compared with myeKlf2(+/+)Ldlr(-/-) mice.
[9] CONCLUSIONS This study documents a role for myeloid KLF2 expression in modulating atherosclerosis.
[10] The increased neutrophil accumulation and atherosclerosis progression with myeloid-specific KLF2 deficiency also underscores the importance of neutrophils in promoting vascular oxidative stress and atherosclerosis.
[11] Collectively, these results suggest that elevating KLF2 expression may be a novel strategy for prevention and treatment of atherosclerosis.

[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 extracellular domain of TMEM27 is cleaved in human beta cells.

Document title: Tmem27: a cleaved and shed plasma membrane protein that stimulates pancreatic beta cell proliferation.

Abstract sentences:
[0] The signals and molecular mechanisms that regulate the replication of terminally differentiated beta cells are unknown.
[1] Here, we report the identification and characterization of transmembrane protein 27 (Tmem27, collectrin) in pancreatic beta cells.
[2] Expression of Tmem27 is reduced in Tcf1(-/-) mice and is increased in islets of mouse models with hypertrophy of the endocrine pancreas.
[3] Tmem27 forms dimers and its extracellular domain is glycosylated, cleaved and shed from the plasma membrane of beta cells.
[4] This cleavage process is beta cell specific and does not occur in other cell types.
[5] Overexpression of full-length Tmem27, but not the truncated or soluble protein, leads to increased thymidine incorporation, whereas silencing of Tmem27 using RNAi results in a reduction of cell replication.
[6] Furthermore, transgenic mice with increased expression of Tmem27 in pancreatic beta cells exhibit increased beta cell mass.
[7] Our results identify a pancreatic beta cell transmembrane protein that regulates cell growth of pancreatic islets.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Tmem27 forms dimers and its extracellular domain is glycosylated, cleaved and shed from the plasma membrane of beta cells.". 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 genomic aberrations found in matasteses are very similar to those found in the primary tumor.

Document title: Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers

Abstract sentences:
[0] Human tumors show a high level of genetic heterogeneity, but the processes that influence the timing and route of metastatic dissemination of the subclones are unknown.
[1] Here we have used whole-exome sequencing of 103 matched benign, malignant and metastatic skin tumors from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumor, supporting parallel rather than linear evolution as the predominant model of metastasis.
[2] Shared mutations between primary carcinomas and their matched metastases have the distinct A-to-T signature of the initiating carcinogen dimethylbenzanthracene, but non-shared mutations are primarily G-to-T, a signature associated with oxidative stress.
[3] The existence of carcinomas that either did or did not metastasize in the same host animal suggests that there are tumor-intrinsic factors that influence metastatic seeding.
[4] We also demonstrate the importance of germline polymorphisms in determining allele-specific mutations, and we identify somatic genetic alterations that are specifically related to initiation of carcinogenesis by Hras or Kras mutations.
[5] Mouse tumors that mimic the genetic heterogeneity of human cancers can aid our understanding of the clonal evolution of metastasis and provide a realistic model for the testing of novel therapies.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Shared mutations between primary carcinomas and their matched metastases have the distinct A-to-T signature of the initiating carcinogen dimethylbenzanthracene, but non-shared mutations are primarily G-to-T, a signature associated with oxidative stress.". 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 locus rs647161 is associated with colorectal carcinoma.

Document title: Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer

Abstract sentences:
[0] To identify new genetic factors for colorectal cancer (CRC), we conducted a                 genome-wide association study in east Asians.
[1] By analyzing genome-wide data in 2,098                 cases and 5,749 controls, we selected 64 promising SNPs for replication in an                 independent set of samples, including up to 5,358 cases and 5,922 controls.
[2] We                 identified four SNPs with association P values of 8.58 ×                     10(-7) to 3.77 × 10(-10)                 in the combined analysis of all east Asian samples.
[3] Three of the four were                 replicated in a study conducted in 26,060 individuals of European descent, with                 combined P values of 1.22 × 10(-10) for                 rs647161 (5q31.1), 6.64 × 10(-9) for rs2423279                 (20p12.3) and 3.06 × 10(-8) for rs10774214                 (12p13.32 near the CCND2 gene), derived from meta-analysis of data from both                 east Asian and European-ancestry populations.
[4] This study identified three new CRC                 susceptibility loci and provides additional insight into the genetics and biology of                 CRC.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Three of the four were                 replicated in a study conducted in 26,060 individuals of European descent, with                 combined P values of 1.22 × 10(-10) for                 rs647161 (5q31.1), 6.64 × 10(-9) for rs2423279                 (20p12.3) and 3.06 × 10(-8) for rs10774214                 (12p13.32 near the CCND2 gene), derived from meta-analysis of data from both                 east Asian and European-ancestry populations.". 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 loss of the TET protein functions may have dire biological consequences, such as myeloid cancers.

Document title: Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells.

Abstract sentences:
[0] TET family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA.
[1] Here, we show that Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem cells (ESCs) and are induced concomitantly with 5hmC during reprogramming of fibroblasts to induced pluripotent stem cells.
[2] ESCs depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1 and display hyperactive Nodal signaling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro.
[3] In Fgf4- and heparin-supplemented culture conditions, Tet1-depleted ESCs activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in midgestation embryo chimeras.
[4] Consistent with these findings, Tet1-depleted ESCs form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm, and ectopic appearance of trophoblastic giant cells.
[5] Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs.

[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 minor G allele of FOXO3 is related to more severe symptoms of Crohn's Disease.

Document title: Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway

Abstract sentences:
[0] The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals.
[1] This variability critically determines the impact a disease has on a patient's life but is very poorly understood.
[2] Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis.
[3] We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn's disease and rheumatoid arthritis and with increased risk of severe malaria.
[4] Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10.
[5] Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn's disease and rheumatoid arthritis and with increased risk of severe malaria.". 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 myocardial lineage develops from cardiac progenitors of mesodermal 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: SUPPORTS
Rationale sentence ids: [0, 3, 4]
Explanation: Evidence states: "The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells. 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. When plated in monolayer cultures, these KDRlow/C-KITneg cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes.". 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 one-child policy has been successful in lowering population growth.

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: 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 relationship between a breast cancer patient's capacity to metabolize tamoxifen and treatment outcome is dependent on 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: SUPPORTS
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 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 dependent on 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: SUPPORTS
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 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 dependent on 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: SUPPORTS
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 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 repair of Cas9-induced double strand breaks in human DNA is error-prone.

Document title: Kinetics and Fidelity of the Repair of Cas9-Induced Double-Strand DNA Breaks

Abstract sentences:
[0] The RNA-guided DNA endonuclease Cas9 is a powerful tool for genome editing.
[1] Little is known about the kinetics and fidelity of the double-strand break (DSB) repair process that follows a Cas9 cutting event in living cells.
[2] Here, we developed a strategy to measure the kinetics of DSB repair for single loci in human cells.
[3] Quantitative modeling of repaired DNA in time series after Cas9 activation reveals variable and often slow repair rates, with half-life times up to ∼10 hr.
[4] Furthermore, repair of the DSBs tends to be error prone.
[5] Both classical and microhomology-mediated end joining pathways contribute to the erroneous repair.
[6] Estimation of their individual rate constants indicates that the balance between these two pathways changes over time and can be altered by additional ionizing radiation.
[7] Our approach provides quantitative insights into DSB repair kinetics and fidelity in single loci and indicates that Cas9-induced DSBs are repaired in an unusual manner.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Furthermore, repair of the DSBs tends to be error prone.". 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 increases with placental weight of pregnancies, and this association is strongest for premenopausal breast cancer.

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: SUPPORTS
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 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 increases with placental weight of pregnancies, and this association is strongest for premenopausal breast cancer.

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: SUPPORTS
Rationale sentence ids: [12]
Explanation: Evidence states: "CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer.". 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 male prisoners harming themselves is ten times that of female 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: CONTRADICTS
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 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 male prisoners harming themselves is ten times that of female 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: CONTRADICTS
Rationale sentence ids: [8]
Explanation: Evidence states: "Self-harm rates were more than ten times higher in female prisoners than in male inmates.". 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 severity of cardiac involvement in amyloidosis can be described by the degree of transmurality of late gadolinium enhancement in MRI.

Document title: Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis

Abstract sentences:
[0] BACKGROUND The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement.
[1] Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown.
[2] METHODS AND RESULTS Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance.
[3] Subjects were followed up for a mean of 24±13 months.
[4] LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only).
[5] These were compared with extracellular volume measured with T1 mapping.
[6] PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium).
[7] LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR).
[8] Sixty-seven patients (27%) died.
[9] Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05).
[10] CONCLUSIONS There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis.
[11] Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis.
[12] The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR).". 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 severity of cardiac involvement in amyloidosis can be described by the degree of transmurality of late gadolinium enhancement in MRI.

Document title: Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis

Abstract sentences:
[0] BACKGROUND The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement.
[1] Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown.
[2] METHODS AND RESULTS Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance.
[3] Subjects were followed up for a mean of 24±13 months.
[4] LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only).
[5] These were compared with extracellular volume measured with T1 mapping.
[6] PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium).
[7] LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR).
[8] Sixty-seven patients (27%) died.
[9] Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05).
[10] CONCLUSIONS There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis.
[11] Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis.
[12] The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [11]
Explanation: Evidence states: "Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis.". 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 single flash-evoked ERG b-wave is generated by activity of ON-bipolar cells.

Document title: Specific deficit of the ON response in visual transmission by targeted disruption of the mGIuR6 gene

Abstract sentences:
[0] Taking advantage of the restricted expression of metabotropic glutamate receptor subtype 6 (mGluR6) in retinal ON bipolar cells, we generated knockout mice lacking mGluR6 expression.
[1] The homozygous mutant mice showed a loss of ON responses but unchanged OFF responses to light.
[2] The mutant mice displayed no obvious changes in retinal cell organization nor in the projection of optic fibers to the brain.
[3] Furthermore, the mGluR6-deficient mice showed visual behavioral responses to light stimulation as examined by shuttle box avoidance behavior experiments using light exposure as a conditioned stimulus.
[4] The results demonstrate that mGluR6 is essential in synaptic transmission to the ON bipolar cell and that the OFF response provides an important means for transmitting visual information.

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