[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: Increased diastolic blood pressure (DBP) is associated with abdominal aortic aneurysm.

Document title: Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people

Abstract sentences:
[0] BACKGROUND The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared.
[1] In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease.
[2] METHODS We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments.
[3] We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years.
[4] This study is registered at ClinicalTrials.gov, number NCT01164371.
[5] FINDINGS During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations.
[6] In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures.
[7] The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect.
[8] Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]).
[9] Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure.
[10] Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]).
[11] People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2).
[12] Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years.
[13] INTERPRETATION The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study.
[14] Despite modern treatments, the lifetime burden of hypertension is substantial.
[15] These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them.
[16] FUNDING Medical Research Council, National Institute for Health Research, and Wellcome Trust.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure.". 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: Increased flux of microbial products provokes immune responses.

Document title: Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis.

Abstract sentences:
[0] Mice lacking junctional adhesion molecule A (JAM-A, encoded by F11r) exhibit enhanced intestinal epithelial permeability, bacterial translocation, and elevated colonic lymphocyte numbers, yet do not develop colitis.
[1] To investigate the contribution of adaptive immune compensation in response to increased intestinal epithelial permeability, we examined the susceptibility of F11r(-/-)Rag1(-/-) mice to acute colitis.
[2] Although negligible contributions of adaptive immunity in F11r(+/+)Rag1(-/-) mice were observed, F11r(-/-)Rag1(-/-) mice exhibited increased microflora-dependent colitis.
[3] Elimination of T cell subsets and cytokine analyses revealed a protective role for TGF-β-producing CD4(+) T cells in F11r(-/-) mice.
[4] Additionally, loss of JAM-A resulted in elevated mucosal and serum IgA that was dependent upon CD4(+) T cells and TGF-β.
[5] Absence of IgA in F11r(+/+)Igha(-/-) mice did not affect disease, whereas F11r(-/-)Igha(-/-) mice displayed markedly increased susceptibility to acute injury-induced colitis.
[6] These data establish a role for adaptive immune-mediated protection from acute colitis under conditions of intestinal epithelial barrier compromise.

[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: Increased flux of microbial products suppresses immune responses.

Document title: Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis.

Abstract sentences:
[0] Mice lacking junctional adhesion molecule A (JAM-A, encoded by F11r) exhibit enhanced intestinal epithelial permeability, bacterial translocation, and elevated colonic lymphocyte numbers, yet do not develop colitis.
[1] To investigate the contribution of adaptive immune compensation in response to increased intestinal epithelial permeability, we examined the susceptibility of F11r(-/-)Rag1(-/-) mice to acute colitis.
[2] Although negligible contributions of adaptive immunity in F11r(+/+)Rag1(-/-) mice were observed, F11r(-/-)Rag1(-/-) mice exhibited increased microflora-dependent colitis.
[3] Elimination of T cell subsets and cytokine analyses revealed a protective role for TGF-β-producing CD4(+) T cells in F11r(-/-) mice.
[4] Additionally, loss of JAM-A resulted in elevated mucosal and serum IgA that was dependent upon CD4(+) T cells and TGF-β.
[5] Absence of IgA in F11r(+/+)Igha(-/-) mice did not affect disease, whereas F11r(-/-)Igha(-/-) mice displayed markedly increased susceptibility to acute injury-induced colitis.
[6] These data establish a role for adaptive immune-mediated protection from acute colitis under conditions of intestinal epithelial barrier compromise.

[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: Increased lipolysis leads to higher P38 phosphorylation in adipose tissue.

Document title: Activation of AMPKα2 in adipocytes is essential for nicotine-induced insulin resistance in vivo

Abstract sentences:
[0] Cigarette smoking promotes body weight reduction in humans while paradoxically also promoting insulin resistance (IR) and hyperinsulinemia.
[1] However, the mechanisms behind these effects are unclear.
[2] Here we show that nicotine, a major constituent of cigarette smoke, selectively activates AMP-activated protein kinase α2 (AMPKα2) in adipocytes, which in turn phosphorylates MAP kinase phosphatase-1 (MKP1) at serine 334, initiating its proteasome-dependent degradation.
[3] The nicotine-dependent reduction of MKP1 induces the aberrant activation of both p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, leading to increased phosphorylation of insulin receptor substrate 1 (IRS1) at serine 307.
[4] Phosphorylation of IRS1 leads to its degradation, protein kinase B inhibition, and the loss of insulin-mediated inhibition of lipolysis.
[5] Consequently, nicotine increases lipolysis, which results in body weight reduction, but this increase also elevates the levels of circulating free fatty acids and thus causes IR in insulin-sensitive tissues.
[6] These results establish AMPKα2 as an essential mediator of nicotine-induced whole-body IR in spite of reductions in adiposity.

[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: Increased microtubule acetylation exacerbates LRRK2 Roc-COR domain mutation induced locomotor deficits.

Document title: Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations

Abstract sentences:
[0] Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease.
[1] LRRK2 is a multifunctional protein affecting many cellular processes and has been described to bind microtubules.
[2] Defective microtubule-based axonal transport is hypothesized to contribute to Parkinson's disease, but whether LRRK2 mutations affect this process to mediate pathogenesis is not known.
[3] Here we find that LRRK2 containing pathogenic Roc-COR domain mutations (R1441C, Y1699C) preferentially associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila, causing locomotor deficits in vivo.
[4] In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase αTAT1 prevents association of mutant LRRK2 with microtubules, and the deacetylase inhibitor trichostatin A (TSA) restores axonal transport.
[5] In vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal transport and locomotor behavior.
[6] Thus, this study reveals a pathogenic mechanism and a potential intervention for Parkinson's disease.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase αTAT1 prevents association of mutant LRRK2 with microtubules, and the deacetylase inhibitor trichostatin A (TSA) restores axonal transport.". 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: Increased microtubule acetylation repairs interference of axonal transport caused by LRRK2 Roc-COR domain mutations.

Document title: Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations

Abstract sentences:
[0] Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease.
[1] LRRK2 is a multifunctional protein affecting many cellular processes and has been described to bind microtubules.
[2] Defective microtubule-based axonal transport is hypothesized to contribute to Parkinson's disease, but whether LRRK2 mutations affect this process to mediate pathogenesis is not known.
[3] Here we find that LRRK2 containing pathogenic Roc-COR domain mutations (R1441C, Y1699C) preferentially associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila, causing locomotor deficits in vivo.
[4] In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase αTAT1 prevents association of mutant LRRK2 with microtubules, and the deacetylase inhibitor trichostatin A (TSA) restores axonal transport.
[5] In vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal transport and locomotor behavior.
[6] Thus, this study reveals a pathogenic mechanism and a potential intervention for Parkinson's disease.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase αTAT1 prevents association of mutant LRRK2 with microtubules, and the deacetylase inhibitor trichostatin A (TSA) restores axonal transport.". 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: Increased microtubule acetylation repairs interference of axonal transport caused by LRRK2 Roc-COR domain mutations.

Document title: Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations

Abstract sentences:
[0] Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease.
[1] LRRK2 is a multifunctional protein affecting many cellular processes and has been described to bind microtubules.
[2] Defective microtubule-based axonal transport is hypothesized to contribute to Parkinson's disease, but whether LRRK2 mutations affect this process to mediate pathogenesis is not known.
[3] Here we find that LRRK2 containing pathogenic Roc-COR domain mutations (R1441C, Y1699C) preferentially associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila, causing locomotor deficits in vivo.
[4] In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase αTAT1 prevents association of mutant LRRK2 with microtubules, and the deacetylase inhibitor trichostatin A (TSA) restores axonal transport.
[5] In vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal transport and locomotor behavior.
[6] Thus, this study reveals a pathogenic mechanism and a potential intervention for Parkinson's disease.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "In vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal transport and locomotor behavior.". 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: Increased microtubule acetylation worsens interference of axonal transport caused by LRRK2 Roc-COR domain mutations.

Document title: Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations

Abstract sentences:
[0] Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease.
[1] LRRK2 is a multifunctional protein affecting many cellular processes and has been described to bind microtubules.
[2] Defective microtubule-based axonal transport is hypothesized to contribute to Parkinson's disease, but whether LRRK2 mutations affect this process to mediate pathogenesis is not known.
[3] Here we find that LRRK2 containing pathogenic Roc-COR domain mutations (R1441C, Y1699C) preferentially associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila, causing locomotor deficits in vivo.
[4] In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase αTAT1 prevents association of mutant LRRK2 with microtubules, and the deacetylase inhibitor trichostatin A (TSA) restores axonal transport.
[5] In vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal transport and locomotor behavior.
[6] Thus, this study reveals a pathogenic mechanism and a potential intervention for Parkinson's disease.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase αTAT1 prevents association of mutant LRRK2 with microtubules, and the deacetylase inhibitor trichostatin A (TSA) restores axonal transport.". 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: Increased microtubule acetylation worsens interference of axonal transport caused by LRRK2 Roc-COR domain mutations.

Document title: Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations

Abstract sentences:
[0] Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease.
[1] LRRK2 is a multifunctional protein affecting many cellular processes and has been described to bind microtubules.
[2] Defective microtubule-based axonal transport is hypothesized to contribute to Parkinson's disease, but whether LRRK2 mutations affect this process to mediate pathogenesis is not known.
[3] Here we find that LRRK2 containing pathogenic Roc-COR domain mutations (R1441C, Y1699C) preferentially associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila, causing locomotor deficits in vivo.
[4] In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase αTAT1 prevents association of mutant LRRK2 with microtubules, and the deacetylase inhibitor trichostatin A (TSA) restores axonal transport.
[5] In vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal transport and locomotor behavior.
[6] Thus, this study reveals a pathogenic mechanism and a potential intervention for Parkinson's disease.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "In vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal transport and locomotor behavior.". 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: Increased mobility of retrotransposons does not lead to mutation and higher tumorigenesis rates.

Document title: The DNA Methylome of Human Peripheral Blood Mononuclear Cells

Abstract sentences:
[0] DNA methylation plays an important role in biological processes in human health and disease.
[1] Recent technological advances allow unbiased whole-genome DNA methylation (methylome) analysis to be carried out on human cells.
[2] Using whole-genome bisulfite sequencing at 24.7-fold coverage (12.3-fold per strand), we report a comprehensive (92.62%) methylome and analysis of the unique sequences in human peripheral blood mononuclear cells (PBMC) from the same Asian individual whose genome was deciphered in the YH project.
[3] PBMC constitute an important source for clinical blood tests world-wide.
[4] We found that 68.4% of CpG sites and <0.2% of non-CpG sites were methylated, demonstrating that non-CpG cytosine methylation is minor in human PBMC.
[5] Analysis of the PBMC methylome revealed a rich epigenomic landscape for 20 distinct genomic features, including regulatory, protein-coding, non-coding, RNA-coding, and repeat sequences.
[6] Integration of our methylome data with the YH genome sequence enabled a first comprehensive assessment of allele-specific methylation (ASM) between the two haploid methylomes of any individual and allowed the identification of 599 haploid differentially methylated regions (hDMRs) covering 287 genes.
[7] Of these, 76 genes had hDMRs within 2 kb of their transcriptional start sites of which >80% displayed allele-specific expression (ASE).
[8] These data demonstrate that ASM is a recurrent phenomenon and is highly correlated with ASE in human PBMCs.
[9] Together with recently reported similar studies, our study provides a comprehensive resource for future epigenomic research and confirms new sequencing technology as a paradigm for large-scale epigenomics studies.

[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: Increased mobility of retrotransposons is assosciated with mutation and higher tumorigenesis rates.

Document title: The DNA Methylome of Human Peripheral Blood Mononuclear Cells

Abstract sentences:
[0] DNA methylation plays an important role in biological processes in human health and disease.
[1] Recent technological advances allow unbiased whole-genome DNA methylation (methylome) analysis to be carried out on human cells.
[2] Using whole-genome bisulfite sequencing at 24.7-fold coverage (12.3-fold per strand), we report a comprehensive (92.62%) methylome and analysis of the unique sequences in human peripheral blood mononuclear cells (PBMC) from the same Asian individual whose genome was deciphered in the YH project.
[3] PBMC constitute an important source for clinical blood tests world-wide.
[4] We found that 68.4% of CpG sites and <0.2% of non-CpG sites were methylated, demonstrating that non-CpG cytosine methylation is minor in human PBMC.
[5] Analysis of the PBMC methylome revealed a rich epigenomic landscape for 20 distinct genomic features, including regulatory, protein-coding, non-coding, RNA-coding, and repeat sequences.
[6] Integration of our methylome data with the YH genome sequence enabled a first comprehensive assessment of allele-specific methylation (ASM) between the two haploid methylomes of any individual and allowed the identification of 599 haploid differentially methylated regions (hDMRs) covering 287 genes.
[7] Of these, 76 genes had hDMRs within 2 kb of their transcriptional start sites of which >80% displayed allele-specific expression (ASE).
[8] These data demonstrate that ASM is a recurrent phenomenon and is highly correlated with ASE in human PBMCs.
[9] Together with recently reported similar studies, our study provides a comprehensive resource for future epigenomic research and confirms new sequencing technology as a paradigm for large-scale epigenomics studies.

[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: Increased purity of cytoplasmic membranes isolated from overexpressors is indicated by stronger spots for OmpF in 2D BN-PAGE gels.

Document title: Identification of a Multicomponent Complex Required for Outer Membrane Biogenesis in Escherichia coli

Abstract sentences:
[0] Gram-negative bacteria have an outer membrane (OM) that functions as a barrier to protect the cell from toxic compounds such as antibiotics and detergents.
[1] The OM is a highly asymmetric bilayer composed of phospholipids, glycolipids, and proteins.
[2] Assembly of this essential organelle occurs outside the cytoplasm in an environment that lacks obvious energy sources such as ATP, and the mechanisms involved are poorly understood.
[3] We describe the identification of a multiprotein complex required for the assembly of proteins in the OM of Escherichia coli.
[4] We also demonstrate genetic interactions between genes encoding components of this protein assembly complex and imp, which encodes a protein involved in the assembly of lipopolysaccharides (LPS) in the OM.
[5] These genetic interactions suggest a role for YfgL, one of the lipoprotein components of the protein assembly complex, in a homeostatic control mechanism that coordinates the overall OM assembly process.

[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: Increased vessel density along with a reduction in fibrosis improves the efficacy of chemotherapy treatments.

Document title: Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer

Abstract sentences:
[0] OBJECTIVE Pancreatic ductal adenocarcinoma (PDA) is characterised by stromal desmoplasia and vascular dysfunction, which critically impair drug delivery.
[1] This study examines the role of an abundant extracellular matrix component, the megadalton glycosaminoglycan hyaluronan (HA), as a novel therapeutic target in PDA.
[2] METHODS Using a genetically engineered mouse model of PDA, the authors enzymatically depleted HA by a clinically formulated PEGylated human recombinant PH20 hyaluronidase (PEGPH20) and examined tumour perfusion, vascular permeability and drug delivery.
[3] The preclinical utility of PEGPH20 in combination with gemcitabine was assessed by short-term and survival studies.
[4] RESULTS PEGPH20 rapidly and sustainably depleted HA, inducing the re-expansion of PDA blood vessels and increasing the intratumoral delivery of two chemotherapeutic agents, doxorubicin and gemcitabine.
[5] Moreover, PEGPH20 triggered fenestrations and interendothelial junctional gaps in PDA tumour endothelia and promoted a tumour-specific increase in macromolecular permeability.
[6] Finally, combination therapy with PEGPH20 and gemcitabine led to inhibition of PDA tumour growth and prolonged survival over gemcitabine monotherapy, suggesting immediate clinical utility.
[7] CONCLUSIONS The authors demonstrate that HA impedes the intratumoral vasculature in PDA and propose that its enzymatic depletion be explored as a means to improve drug delivery and response in patients with pancreatic cancer.

[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: Individuals with Alzheimers who participate in six months of physical activity improve cognitive function for up to 18 months.

Document title: Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial.

Abstract sentences:
[0] CONTEXT Many observational studies have shown that physical activity reduces the risk of cognitive decline; however, evidence from randomized trials is lacking.
[1] OBJECTIVE To determine whether physical activity reduces the rate of cognitive decline among older adults at risk.
[2] DESIGN AND SETTING Randomized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth, Western Australia.
[3] Assessors of cognitive function were blinded to group membership.
[4] PARTICIPANTS We recruited volunteers who reported memory problems but did not meet criteria for dementia.
[5] Three hundred eleven individuals aged 50 years or older were screened for eligibility, 89 were not eligible, and 52 refused to participate.
[6] A total of 170 participants were randomized and 138 participants completed the 18-month assessment.
[7] INTERVENTION Participants were randomly allocated to an education and usual care group or to a 24-week home-based program of physical activity.
[8] MAIN OUTCOME MEASURE Change in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores (possible range, 0-70) over 18 months.
[9] RESULTS In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention.
[10] The absolute difference of the outcome measure between the intervention and control groups was -1.3 points (95% confidence interval,-2.38 to -0.22) at the end of the intervention.
[11] At 18 months, participants in the intervention group improved 0.73 points (95% confidence interval, -1.27 to 0.03) on the ADAS-Cog, and those in the usual care group improved 0.04 points (95% confidence interval, -0.46 to 0.88).
[12] Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well, whereas word list total immediate recall, digit symbol coding, verbal fluency, Beck depression score, and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly.
[13] CONCLUSIONS In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period.
[14] TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12605000136606.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "RESULTS In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention.". 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: Individuals with Alzheimers who participate in six months of physical activity improve cognitive function for up to 18 months.

Document title: Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial.

Abstract sentences:
[0] CONTEXT Many observational studies have shown that physical activity reduces the risk of cognitive decline; however, evidence from randomized trials is lacking.
[1] OBJECTIVE To determine whether physical activity reduces the rate of cognitive decline among older adults at risk.
[2] DESIGN AND SETTING Randomized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth, Western Australia.
[3] Assessors of cognitive function were blinded to group membership.
[4] PARTICIPANTS We recruited volunteers who reported memory problems but did not meet criteria for dementia.
[5] Three hundred eleven individuals aged 50 years or older were screened for eligibility, 89 were not eligible, and 52 refused to participate.
[6] A total of 170 participants were randomized and 138 participants completed the 18-month assessment.
[7] INTERVENTION Participants were randomly allocated to an education and usual care group or to a 24-week home-based program of physical activity.
[8] MAIN OUTCOME MEASURE Change in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores (possible range, 0-70) over 18 months.
[9] RESULTS In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention.
[10] The absolute difference of the outcome measure between the intervention and control groups was -1.3 points (95% confidence interval,-2.38 to -0.22) at the end of the intervention.
[11] At 18 months, participants in the intervention group improved 0.73 points (95% confidence interval, -1.27 to 0.03) on the ADAS-Cog, and those in the usual care group improved 0.04 points (95% confidence interval, -0.46 to 0.88).
[12] Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well, whereas word list total immediate recall, digit symbol coding, verbal fluency, Beck depression score, and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly.
[13] CONCLUSIONS In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period.
[14] TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12605000136606.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [13]
Explanation: Evidence states: "CONCLUSIONS In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period.". 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: Individuals with low serum vitamin D concentrations have decreased risk of multiple sclerosis.

Document title: Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study.

Abstract sentences:
[0] OBJECTIVE To examine whether past high sun exposure is associated with a reduced risk of multiple sclerosis.
[1] DESIGN Population based case-control study.
[2] SETTING Tasmania, latitudes 41-3 degrees S.   PARTICIPANTS 136 cases with multiple sclerosis and 272 controls randomly drawn from the community and matched on sex and year of birth.
[3] MAIN OUTCOME MEASURE Multiple sclerosis defined by both clinical and magnetic resonance imaging criteria.
[4] RESULTS Higher sun exposure when aged 6-15 years (average 2-3 hours or more a day in summer during weekends and holidays) was associated with a decreased risk of multiple sclerosis (adjusted odds ratio 0.31, 95% confidence interval 0.16 to 0.59).
[5] Higher exposure in winter seemed more important than higher exposure in summer.
[6] Greater actinic damage was also independently associated with a decreased risk of multiple sclerosis (0.32, 0.11 to 0.88 for grades 4-6 disease).
[7] A dose-response relation was observed between multiple sclerosis and decreasing sun exposure when aged 6-15 years and with actinic damage.
[8] CONCLUSION Higher sun exposure during childhood and early adolescence is associated with a reduced risk of multiple sclerosis.
[9] Insufficient ultraviolet radiation may therefore influence the development of multiple sclerosis.

[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: Induced hepatic stem cells possess the potential to differentiate into cholangiocytic cells.

Document title: Reprogramming fibroblasts into bipotential hepatic stem cells by defined factors.

Abstract sentences:
[0] Recent studies have demonstrated direct reprogramming of fibroblasts into a range of somatic cell types, but to date stem or progenitor cells have only been reprogrammed for the blood and neuronal lineages.
[1] We previously reported generation of induced hepatocyte-like (iHep) cells by transduction of Gata4, Hnf1α, and Foxa3 in p19 Arf null mouse embryonic fibroblasts (MEFs).
[2] Here, we show that Hnf1β and Foxa3, liver organogenesis transcription factors, are sufficient to reprogram MEFs into induced hepatic stem cells (iHepSCs).
[3] iHepSCs can be stably expanded in vitro and possess the potential of bidirectional differentiation into both hepatocytic and cholangiocytic lineages.
[4] In the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice, repopulating iHepSCs become hepatocyte-like cells.
[5] They also engraft as cholangiocytes into bile ducts of mice with DDC-induced bile ductular injury.
[6] Lineage conversion into bipotential expandable iHepSCs provides a strategy to enable efficient derivation of both hepatocytes and cholangiocytes for use in disease modeling and tissue engineering.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "iHepSCs can be stably expanded in vitro and possess the potential of bidirectional differentiation into both hepatocytic and cholangiocytic lineages.". 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: Induced hepatic stem cells possess the potential to differentiate into cholangiocytic cells.

Document title: Reprogramming fibroblasts into bipotential hepatic stem cells by defined factors.

Abstract sentences:
[0] Recent studies have demonstrated direct reprogramming of fibroblasts into a range of somatic cell types, but to date stem or progenitor cells have only been reprogrammed for the blood and neuronal lineages.
[1] We previously reported generation of induced hepatocyte-like (iHep) cells by transduction of Gata4, Hnf1α, and Foxa3 in p19 Arf null mouse embryonic fibroblasts (MEFs).
[2] Here, we show that Hnf1β and Foxa3, liver organogenesis transcription factors, are sufficient to reprogram MEFs into induced hepatic stem cells (iHepSCs).
[3] iHepSCs can be stably expanded in vitro and possess the potential of bidirectional differentiation into both hepatocytic and cholangiocytic lineages.
[4] In the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice, repopulating iHepSCs become hepatocyte-like cells.
[5] They also engraft as cholangiocytes into bile ducts of mice with DDC-induced bile ductular injury.
[6] Lineage conversion into bipotential expandable iHepSCs provides a strategy to enable efficient derivation of both hepatocytes and cholangiocytes for use in disease modeling and tissue engineering.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Lineage conversion into bipotential expandable iHepSCs provides a strategy to enable efficient derivation of both hepatocytes and cholangiocytes for use in disease modeling and tissue engineering.". 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: Induced hepatic stem cells possess the potential to differentiate into hepatocytic cells.

Document title: Reprogramming fibroblasts into bipotential hepatic stem cells by defined factors.

Abstract sentences:
[0] Recent studies have demonstrated direct reprogramming of fibroblasts into a range of somatic cell types, but to date stem or progenitor cells have only been reprogrammed for the blood and neuronal lineages.
[1] We previously reported generation of induced hepatocyte-like (iHep) cells by transduction of Gata4, Hnf1α, and Foxa3 in p19 Arf null mouse embryonic fibroblasts (MEFs).
[2] Here, we show that Hnf1β and Foxa3, liver organogenesis transcription factors, are sufficient to reprogram MEFs into induced hepatic stem cells (iHepSCs).
[3] iHepSCs can be stably expanded in vitro and possess the potential of bidirectional differentiation into both hepatocytic and cholangiocytic lineages.
[4] In the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice, repopulating iHepSCs become hepatocyte-like cells.
[5] They also engraft as cholangiocytes into bile ducts of mice with DDC-induced bile ductular injury.
[6] Lineage conversion into bipotential expandable iHepSCs provides a strategy to enable efficient derivation of both hepatocytes and cholangiocytes for use in disease modeling and tissue engineering.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "iHepSCs can be stably expanded in vitro and possess the potential of bidirectional differentiation into both hepatocytic and cholangiocytic lineages.". 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: Induction of urokinase receptor signaling in podocytes causes foot process effacement and proteinuria.

Document title: Modification of kidney barrier function by the urokinase receptor

Abstract sentences:
[0] Podocyte dysfunction, represented by foot process effacement and proteinuria, is often the starting point for progressive kidney disease.
[1] Therapies aimed at the cellular level of the disease are currently not available.
[2] Here we show that induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via a mechanism that includes lipid-dependent activation of αvβ3 integrin.
[3] Mice lacking uPAR (Plaur−/−) are protected from lipopolysaccharide (LPS)-mediated proteinuria but develop disease after expression of a constitutively active β3 integrin.
[4] Gene transfer studies reveal a prerequisite for uPAR expression in podocytes, but not in endothelial cells, for the development of LPS-mediated proteinuria.
[5] Mechanistically, uPAR is required to activate αvβ3 integrin in podocytes, promoting cell motility and activation of the small GTPases Cdc42 and Rac1.
[6] Blockade of αvβ3 integrin reduces podocyte motility in vitro and lowers proteinuria in mice.
[7] Our findings show a physiological role for uPAR signaling in the regulation of kidney permeability.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Here we show that induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via a mechanism that includes lipid-dependent activation of αvβ3 integrin.". 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: Inhibiting HDAC6 increases survival of mice with ARID1A mutated tumors.

Document title: ARID1A-mutated ovarian cancers depend on HDAC6 activity

Abstract sentences:
[0] ARID1A, encoding a subunit of the SWI/SNF chromatin-remodelling complex, is the most frequently mutated epigenetic regulator across all human cancers.
[1] ARID1A and TP53 mutations are typically mutually exclusive.
[2] Therapeutic approaches that correlate with this genetic characteristic remain to be explored.
[3] Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers.
[4] Inhibition of HDAC6 activity using a clinically applicable small-molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated tumours.
[5] This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumours.
[6] The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A.
[7] HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells.
[8] HDAC6 directly deacetylates Lys120 of p53, a pro-apoptotic post-translational modification.
[9] Thus, ARID1A mutation inactivates the apoptosis-promoting function of p53 by upregulating HDAC6.
[10] Together, these results indicate that pharmacological inhibition of HDAC6 is a therapeutic strategy for ARID1A-mutated cancers.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Inhibition of HDAC6 activity using a clinically applicable small-molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated tumours.". 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: Inhibiting focal adhesion formation enables cells to convert mechanical strain into eventual scarring.

Document title: Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling

Abstract sentences:
[0] Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood.
[1] One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK).
[2] Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading.
[3] Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation.
[4] We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders.
[5] Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis.
[6] Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment.
[7] These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation.". 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: Inhibiting focal adhesion formation enables cells to convert mechanical strain into eventual scarring.

Document title: Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling

Abstract sentences:
[0] Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood.
[1] One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK).
[2] Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading.
[3] Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation.
[4] We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders.
[5] Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis.
[6] Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment.
[7] These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis.". 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: Inhibiting focal adhesion formation enables cells to convert mechanical strain into eventual scarring.

Document title: Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling

Abstract sentences:
[0] Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood.
[1] One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK).
[2] Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading.
[3] Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation.
[4] We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders.
[5] Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis.
[6] Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment.
[7] These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment.". 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: Inhibiting focal adhesion formation enables cells to convert mechanical strain into eventual scarring.

Document title: Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling

Abstract sentences:
[0] Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood.
[1] One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK).
[2] Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading.
[3] Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation.
[4] We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders.
[5] Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis.
[6] Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment.
[7] These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.". 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: Inhibiting focal adhesion formation increases the rate at which cells convert mechanical strain into inflammation and fibrosis.

Document title: Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling

Abstract sentences:
[0] Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood.
[1] One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK).
[2] Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading.
[3] Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation.
[4] We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders.
[5] Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis.
[6] Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment.
[7] These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation.". 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: Inhibiting focal adhesion formation increases the rate at which cells convert mechanical strain into inflammation and fibrosis.

Document title: Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling

Abstract sentences:
[0] Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood.
[1] One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK).
[2] Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading.
[3] Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation.
[4] We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders.
[5] Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis.
[6] Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment.
[7] These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.". 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: Inhibiting glucose-6-phospate dehydrogenase improves lipogenesis by deactivating LKB1-AMPK signaling.

Document title: 6-phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumor growth by inhibiting LKB1-AMPK signaling

Abstract sentences:
[0] The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear.
[1] We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth.
[2] 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis.
[3] Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling.
[4] Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [1, 2]
Explanation: Evidence states: "We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis.". 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: Input from  mental and physical health care professionals 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: Inside the body, falciparum parasites reproduce asexually.

Document title: Malaria biology and disease pathogenesis: insights for new treatments

Abstract sentences:
[0] Plasmodium falciparum malaria, an infectious disease caused by a parasitic protozoan, claims the lives of nearly a million children each year in Africa alone and is a top public health concern.
[1] Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia.
[2] Renewed initiatives to eliminate malaria will benefit from an expanded repertoire of antimalarials, including new drugs that kill circulating P. falciparum gametocytes, thereby preventing transmission.
[3] Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs.
[4] There is also a need for new therapies to reduce the high mortality of severe malaria.
[5] An understanding of the pathophysiology of severe disease may identify rational targets for drugs that improve survival.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia.". 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: Inside the body, falciparum parasites reproduce asexually.

Document title: Malaria biology and disease pathogenesis: insights for new treatments

Abstract sentences:
[0] Plasmodium falciparum malaria, an infectious disease caused by a parasitic protozoan, claims the lives of nearly a million children each year in Africa alone and is a top public health concern.
[1] Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia.
[2] Renewed initiatives to eliminate malaria will benefit from an expanded repertoire of antimalarials, including new drugs that kill circulating P. falciparum gametocytes, thereby preventing transmission.
[3] Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs.
[4] There is also a need for new therapies to reduce the high mortality of severe malaria.
[5] An understanding of the pathophysiology of severe disease may identify rational targets for drugs that improve survival.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs.". 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: Insulin decreases risk of severe kidney failure.

Document title: Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care

Abstract sentences:
[0] OBJECTIVE To assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones).
[1] DESIGN Open cohort study in primary care.
[2] SETTING 1243 practices contributing data to the QResearch database in England.
[3] PARTICIPANTS 469,688 patients with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015.
[4] EXPOSURES Hypoglycaemic agents (glitazones, gliptins, metformin, sulphonylureas, insulin, and other) alone and in combination.
[5] MAIN OUTCOME MEASURES First recorded diagnoses of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia recorded on patients' primary care, mortality, or hospital records.
[6] Cox models estimated hazard ratios for diabetes treatments adjusting for potential confounders.
[7] RESULTS 21,308 (4.5%) and 32,533 (6.9%) patients received prescriptions for glitazones and gliptins during follow-up, respectively.
[8] Compared with non-use, glitazones were associated with a decreased risk of blindness (adjusted hazard ratio 0.71, 95% confidence interval 0.57 to 0.89; rate 14.4 per 10,000 person years of exposure) and an increased risk of hypoglycaemia (1.22, 1.10 to 1.37; 65.1); gliptins were associated with a decreased risk of hypoglycaemia (0.86, 0.77 to 0.96; 45.8).
[9] Although the numbers of patients prescribed gliptin monotherapy or glitazones monotherapy were relatively low, there were significantly increased risks of severe kidney failure compared with metformin monotherapy (adjusted hazard ratio 2.55, 95% confidence interval 1.13 to 5.74).
[10] We found significantly lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins (0.78, 0.62 to 0.97) or glitazones (0.60, 0.45 to 0.80) compared with metformin monotherapy.
[11] Patients prescribed triple therapy with metformin, sulphonylureas, and either gliptins (adjusted hazard ratio 5.07, 95% confidence interval 4.28 to 6.00) or glitazones (6.32, 5.35 to 7.45) had significantly higher risks of hypoglycaemia than those prescribed metformin monotherapy, but these risks were similar to those involving dual therapy with metformin and sulphonylureas (6.03, 5.47 to 6.63).
[12] Patients prescribed triple therapy with metformin, sulphonylureas, and glitazones had a significantly reduced risk of blindness compared with metformin monotherapy (0.67, 0.48 to 0.94).
[13] CONCLUSIONS We have found lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins or glitazones compared with metformin alone.
[14] Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and either gliptins or glitazones was associated with an increased risk of hypoglycaemia, which was similar to the risk for dual therapy with metformin and sulphonylureas.
[15] Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and glitazones was associated with a reduced risk of blindness.
[16] These results, while subject to residual confounding, could have implications for the prescribing of hypoglycaemic drugs.

[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: Insulin effects appetite via ventral tegmental neurons.

Document title: Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis.

Abstract sentences:
[0] Dopaminergic midbrain neurons integrate signals on food palatability and food-associated reward into the complex control of energy homeostasis.
[1] To define the role of insulin receptor (IR) signaling in this circuitry, we inactivated IR signaling in tyrosine hydroxylase (Th)-expressing cells of mice (IR(ΔTh)).
[2] IR inactivation in Th-expressing cells of mice resulted in increased body weight, increased fat mass, and hyperphagia.
[3] While insulin acutely stimulated firing frequency in 50% of dopaminergic VTA/SN neurons, this response was abolished in IR(ΔTh) mice.
[4] Moreover, these mice exhibited an altered response to cocaine under food-restricted conditions.
[5] Taken together, these data provide in vivo evidence for a critical role of insulin signaling in catecholaminergic neurons to control food intake and energy homeostasis.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3, 5]
Explanation: Evidence states: "While insulin acutely stimulated firing frequency in 50% of dopaminergic VTA/SN neurons, this response was abolished in IR(ΔTh) mice. Taken together, these data provide in vivo evidence for a critical role of insulin signaling in catecholaminergic neurons to control food intake and energy homeostasis.". 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: Intake of folic acid (FA) and vitamin B6 (VB6) increases levels of homocysteine.

Document title: Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.

Abstract sentences:
[0] CONTEXT Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6.
[1] However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available.
[2] OBJECTIVE To examine intakes of folate and vitamin B6 in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD.
[3] DESIGN Prospective cohort study.
[4] SETTING AND PATIENTS In 1980, a total of 80082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B6.
[5] MAIN OUTCOME MEASURE Nonfatal MI and fatal CHD confirmed by World Health Organization criteria.
[6] RESULTS During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD.
[7] After controlling for cardiovascular risk factors, including smoking and hypertension and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence interval [CI], 0.55-0.87) for folate (median intake, 696 microg/d vs 158 microg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B6 (median intake, 4.6 mg/d vs 1.1 mg/d).
[8] Controlling for the same variables, the RR was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B6 intake compared with the opposite extreme.
[9] Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95% CI, 0.65-0.90), the major source of folate and vitamin B6, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B6.
[10] In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI, 0.13-0.58).
[11] CONCLUSION These results suggest that intake of folate and vitamin B6 above the current recommended dietary allowance may be important in the primary prevention of CHD among women.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [0]
Explanation: Evidence states: "CONTEXT Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6.". 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: Intake of folic acid (FA) and vitamin B6 (VB6) reduces levels of homocysteine.

Document title: Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.

Abstract sentences:
[0] CONTEXT Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6.
[1] However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available.
[2] OBJECTIVE To examine intakes of folate and vitamin B6 in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD.
[3] DESIGN Prospective cohort study.
[4] SETTING AND PATIENTS In 1980, a total of 80082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B6.
[5] MAIN OUTCOME MEASURE Nonfatal MI and fatal CHD confirmed by World Health Organization criteria.
[6] RESULTS During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD.
[7] After controlling for cardiovascular risk factors, including smoking and hypertension and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence interval [CI], 0.55-0.87) for folate (median intake, 696 microg/d vs 158 microg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B6 (median intake, 4.6 mg/d vs 1.1 mg/d).
[8] Controlling for the same variables, the RR was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B6 intake compared with the opposite extreme.
[9] Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95% CI, 0.65-0.90), the major source of folate and vitamin B6, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B6.
[10] In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI, 0.13-0.58).
[11] CONCLUSION These results suggest that intake of folate and vitamin B6 above the current recommended dietary allowance may be important in the primary prevention of CHD among women.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "CONTEXT Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6.". 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: Integrated care is ineffective at tackling multiple comorbidities.

Document title: Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial

Abstract sentences:
[0] OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life.
[1] DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people   SETTING Fourteen primary care clinics in Seattle, Washington.   PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10.
[2] INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a "treat to target" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression.
[3] The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia.
[4] MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance).
[5] RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%).
[6] Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group.
[7] There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10).
[8] CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life.
[9] Trial registration Clinical Trials NCT00468676.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group.". 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: Integrated care is ineffective at tackling multiple comorbidities.

Document title: Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial

Abstract sentences:
[0] OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life.
[1] DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people   SETTING Fourteen primary care clinics in Seattle, Washington.   PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10.
[2] INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a "treat to target" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression.
[3] The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia.
[4] MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance).
[5] RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%).
[6] Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group.
[7] There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10).
[8] CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life.
[9] Trial registration Clinical Trials NCT00468676.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10).". 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: Integrated care is ineffective at tackling multiple comorbidities.

Document title: Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial

Abstract sentences:
[0] OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life.
[1] DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people   SETTING Fourteen primary care clinics in Seattle, Washington.   PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10.
[2] INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a "treat to target" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression.
[3] The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia.
[4] MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance).
[5] RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%).
[6] Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group.
[7] There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10).
[8] CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life.
[9] Trial registration Clinical Trials NCT00468676.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [8]
Explanation: Evidence states: "CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life.". 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: Integrated care is successful at tackling multiple comorbidities.

Document title: Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial

Abstract sentences:
[0] OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life.
[1] DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people   SETTING Fourteen primary care clinics in Seattle, Washington.   PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10.
[2] INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a "treat to target" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression.
[3] The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia.
[4] MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance).
[5] RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%).
[6] Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group.
[7] There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10).
[8] CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life.
[9] Trial registration Clinical Trials NCT00468676.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group.". 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: Integrated care is successful at tackling multiple comorbidities.

Document title: Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial

Abstract sentences:
[0] OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life.
[1] DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people   SETTING Fourteen primary care clinics in Seattle, Washington.   PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10.
[2] INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a "treat to target" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression.
[3] The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia.
[4] MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance).
[5] RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%).
[6] Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group.
[7] There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10).
[8] CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life.
[9] Trial registration Clinical Trials NCT00468676.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10).". 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: Integrated care is successful at tackling multiple comorbidities.

Document title: Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial

Abstract sentences:
[0] OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life.
[1] DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people   SETTING Fourteen primary care clinics in Seattle, Washington.   PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10.
[2] INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a "treat to target" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression.
[3] The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia.
[4] MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance).
[5] RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%).
[6] Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group.
[7] There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10).
[8] CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life.
[9] Trial registration Clinical Trials NCT00468676.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life.". 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: Integrating classroom-based collaborative learning with Web-based collaborative learning offers the best class performance.

Document title: Computer assisted learning in undergraduate medical education.

Abstract sentences:
[0] It is becoming “a truth universally acknowledged” that the education of undergraduate medical students will be enhanced through the use of computer assisted learning.
[1] Access to the wide range of online options illustrated in the figure must surely make learning more exciting, effective, and likely to be retained.
[2] This assumption is potentially but by no means inevitably correct.
[3] ### Box 1: Why fund computer assisted learning?
[4] Computer assisted learning is inevitable —Individual lecturers and departments are already beginning to introduce a wide range of computer based applications, sometimes in a haphazard way.
[5] Planned and coordinated development is better than indiscriminate expansion  It is convenient and flexible —Courses supported by computer assisted learning applications may require fewer face to face lectures and seminars and place fewer geographical and temporal constraints on staff and students.
[6] Students at peripheral hospitals or primary care centres may benefit in particular  Unique presentational benefits —Computer presentation is particularly suited to subjects that are visually intensive, detail oriented, and difficult to conceptualise, such as complex biochemical processes or microscopic images.1 Furthermore, “virtual” cases may reduce the need to use animal or human tissue in learning  Personalised learning —Each learner can progress at his or her preferred pace.
[7] They can repeat, interrupt, and resume at will, which may have particular advantages for weaker students  Economies of scale —Once an application has been set up, the incremental cost of offering it to additional students is relatively small  Competitive advantage —Potential applicants may use the quality of information technology to discriminate between medical schools.
[8] A “leading edge” virtual campus is likely to attract good students  Achieves the ultimate goal of higher education —The goal is to link people into learning communities.
[9] Computer applications, especially the internet and world wide web, are an extremely efficient way of doing this2  Expands pedagogical horizons —The most controversial argument for … RETURN TO TEXT

[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: Interferon stimulated genes (ISGs) Irf1, Irg1, Ifi27, and Rsad2 encourage West Nile virus replication in cortical neurons.

Document title: Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive stranded RNA viruses

Abstract sentences:
[0] Although susceptibility of neurons in the brain to microbial infection is a major determinant of clinical outcome, little is known about the molecular factors governing this vulnerability.
[1] Here we show that two types of neurons from distinct brain regions showed differential permissivity to replication of several positive-stranded RNA viruses.
[2] Granule cell neurons of the cerebellum and cortical neurons from the cerebral cortex have unique innate immune programs that confer differential susceptibility to viral infection ex vivo and in vivo.
[3] By transducing cortical neurons with genes that were expressed more highly in granule cell neurons, we identified three interferon-stimulated genes (ISGs; Ifi27, Irg1 and Rsad2 (also known as Viperin)) that mediated the antiviral effects against different neurotropic viruses.
[4] Moreover, we found that the epigenetic state and microRNA (miRNA)-mediated regulation of ISGs correlates with enhanced antiviral response in granule cell neurons.
[5] Thus, neurons from evolutionarily distinct brain regions have unique innate immune signatures, which probably contribute to their relative permissiveness to infection.

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