[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: Cold exposure increases BAT recruitment.

Document title: Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis

Abstract sentences:
[0] Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown.
[1] Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice.
[2] In two genetic mouse knockout models (apolipoprotein E(-/-) [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition.
[3] Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability.
[4] Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions.
[5] Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development.
[6] These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.

[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: Cold exposure reduces BAT recruitment.

Document title: Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis

Abstract sentences:
[0] Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown.
[1] Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice.
[2] In two genetic mouse knockout models (apolipoprotein E(-/-) [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition.
[3] Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability.
[4] Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions.
[5] Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development.
[6] These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.

[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: Combination nicotine replacement therapies with varenicline or bupropion lead to significantly higher long-term abstinence rates at 52 weeks than varenicline monotherapy.

Document title: Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial.

Abstract sentences:
[0] IMPORTANCE Combining pharmacotherapies for tobacco-dependence treatment may increase smoking abstinence.
[1] OBJECTIVE To determine efficacy and safety of varenicline and bupropion sustained-release (SR; combination therapy) compared with varenicline (monotherapy) in cigarette smokers.
[2] DESIGN, SETTING, AND PARTICIPANTS Randomized, blinded, placebo-controlled multicenter clinical trial with a 12-week treatment period and follow-up through week 52 conducted between October 2009 and April 2013 at 3 midwestern clinical research sites.
[3] Five hundred six adult (≥18 years) cigarette smokers were randomly assigned and 315 (62%) completed the study.
[4] INTERVENTIONS Twelve weeks of varenicline and bupropion SR or varenicline and placebo.
[5] MAIN OUTCOMES AND MEASURES Primary outcome was abstinence rates at week 12, defined as prolonged (no smoking from 2 weeks after the target quit date) abstinence and 7-day point-prevalence (no smoking past 7 days) abstinence.
[6] Secondary outcomes were prolonged and point-prevalence smoking abstinence rates at weeks 26 and 52.
[7] Outcomes were biochemically confirmed.
[8] RESULTS At 12 weeks, 53.0% of the combination therapy group achieved prolonged smoking abstinence and 56.2% achieved 7-day point-prevalence smoking abstinence compared with 43.2% and 48.6% in varenicline monotherapy (odds ratio [OR], 1.49; 95% CI, 1.05-2.12; P = .03 and OR, 1.36; 95% CI, 0.95-1.93; P = .09, respectively).
[9] At 26 weeks, 36.6% of the combination therapy group achieved prolonged and 38.2% achieved 7-day point-prevalence smoking abstinence compared with 27.6% and 31.9% in varenicline monotherapy (OR, 1.52; 95% CI, 1.04-2.22; P = .03 and OR, 1.32; 95% CI, 0.91-1.91; P = .14, respectively).
[10] At 52 weeks, 30.9% of the combination therapy group achieved prolonged and 36.6% achieved 7-day point-prevalence smoking abstinence compared with 24.5% and 29.2% in varenicline monotherapy (OR, 1.39; 95% CI, 0.93-2.07; P = .11 and OR, 1.40; 95% CI, 0.96-2.05; P = .08, respectively).
[11] Participants receiving combination therapy reported more anxiety (7.2% vs 3.1%; P = .04) and depressive symptoms (3.6% vs 0.8%; P = .03).
[12] CONCLUSIONS AND RELEVANCE Among cigarette smokers, combined use of varenicline and bupropion, compared with varenicline alone, increased prolonged abstinence but not 7-day point prevalence at 12 and 26 weeks.
[13] Neither outcome was significantly different at 52 weeks.
[14] Further research is required to determine the role of combination therapy in smoking cessation.
[15] TRIAL REGISTRATION clinicaltrials.gov Identifier: http://clinicaltrials.gov/show/NCT00935818.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10]
Explanation: Evidence states: "At 52 weeks, 30.9% of the combination therapy group achieved prolonged and 36.6% achieved 7-day point-prevalence smoking abstinence compared with 24.5% and 29.2% in varenicline monotherapy (OR, 1.39; 95% CI, 0.93-2.07; P = .11 and OR, 1.40; 95% CI, 0.96-2.05; P = .08, respectively).". 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: Combination nicotine replacement therapies with varenicline or bupropion lead to significantly higher long-term abstinence rates at 52 weeks than varenicline monotherapy.

Document title: Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial.

Abstract sentences:
[0] IMPORTANCE Combining pharmacotherapies for tobacco-dependence treatment may increase smoking abstinence.
[1] OBJECTIVE To determine efficacy and safety of varenicline and bupropion sustained-release (SR; combination therapy) compared with varenicline (monotherapy) in cigarette smokers.
[2] DESIGN, SETTING, AND PARTICIPANTS Randomized, blinded, placebo-controlled multicenter clinical trial with a 12-week treatment period and follow-up through week 52 conducted between October 2009 and April 2013 at 3 midwestern clinical research sites.
[3] Five hundred six adult (≥18 years) cigarette smokers were randomly assigned and 315 (62%) completed the study.
[4] INTERVENTIONS Twelve weeks of varenicline and bupropion SR or varenicline and placebo.
[5] MAIN OUTCOMES AND MEASURES Primary outcome was abstinence rates at week 12, defined as prolonged (no smoking from 2 weeks after the target quit date) abstinence and 7-day point-prevalence (no smoking past 7 days) abstinence.
[6] Secondary outcomes were prolonged and point-prevalence smoking abstinence rates at weeks 26 and 52.
[7] Outcomes were biochemically confirmed.
[8] RESULTS At 12 weeks, 53.0% of the combination therapy group achieved prolonged smoking abstinence and 56.2% achieved 7-day point-prevalence smoking abstinence compared with 43.2% and 48.6% in varenicline monotherapy (odds ratio [OR], 1.49; 95% CI, 1.05-2.12; P = .03 and OR, 1.36; 95% CI, 0.95-1.93; P = .09, respectively).
[9] At 26 weeks, 36.6% of the combination therapy group achieved prolonged and 38.2% achieved 7-day point-prevalence smoking abstinence compared with 27.6% and 31.9% in varenicline monotherapy (OR, 1.52; 95% CI, 1.04-2.22; P = .03 and OR, 1.32; 95% CI, 0.91-1.91; P = .14, respectively).
[10] At 52 weeks, 30.9% of the combination therapy group achieved prolonged and 36.6% achieved 7-day point-prevalence smoking abstinence compared with 24.5% and 29.2% in varenicline monotherapy (OR, 1.39; 95% CI, 0.93-2.07; P = .11 and OR, 1.40; 95% CI, 0.96-2.05; P = .08, respectively).
[11] Participants receiving combination therapy reported more anxiety (7.2% vs 3.1%; P = .04) and depressive symptoms (3.6% vs 0.8%; P = .03).
[12] CONCLUSIONS AND RELEVANCE Among cigarette smokers, combined use of varenicline and bupropion, compared with varenicline alone, increased prolonged abstinence but not 7-day point prevalence at 12 and 26 weeks.
[13] Neither outcome was significantly different at 52 weeks.
[14] Further research is required to determine the role of combination therapy in smoking cessation.
[15] TRIAL REGISTRATION clinicaltrials.gov Identifier: http://clinicaltrials.gov/show/NCT00935818.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [13]
Explanation: Evidence states: "Neither outcome was significantly different at 52 weeks.". 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: Combining phosphatidylinositide 3-kinase and MEK 1/2 inhibitors is effective at treating KRAS mutant tumors.

Document title: Effective Use of PI3K and MEK Inhibitors to Treat Mutant K-Ras G12D and PIK3CA H1047R Murine Lung Cancers

Abstract sentences:
[0] Somatic mutations that activate phosphoinositide 3-kinase (PI3K) have been identified in the p110-alpha catalytic subunit (encoded by PIK3CA).
[1] They are most frequently observed in two hotspots: the helical domain (E545K and E542K) and the kinase domain (H1047R).
[2] Although the p110-alpha mutants are transforming in vitro, their oncogenic potential has not been assessed in genetically engineered mouse models.
[3] Furthermore, clinical trials with PI3K inhibitors have recently been initiated, and it is unknown if their efficacy will be restricted to specific, genetically defined malignancies.
[4] In this study, we engineered a mouse model of lung adenocarcinomas initiated and maintained by expression of p110-alpha H1047R.
[5] Treatment of these tumors with NVP-BEZ235, a dual pan-PI3K and mammalian target of rapamycin (mTOR) inhibitor in clinical development, led to marked tumor regression as shown by positron emission tomography-computed tomography, magnetic resonance imaging and microscopic examination.
[6] In contrast, mouse lung cancers driven by mutant Kras did not substantially respond to single-agent NVP-BEZ235.
[7] However, when NVP-BEZ235 was combined with a mitogen-activated protein kinase kinase (MEK) inhibitor, ARRY-142886, there was marked synergy in shrinking these Kras-mutant cancers.
[8] These in vivo studies suggest that inhibitors of the PI3K-mTOR pathway may be active in cancers with PIK3CA mutations and, when combined with MEK inhibitors, may effectively treat KRAS mutated lung cancers.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "However, when NVP-BEZ235 was combined with a mitogen-activated protein kinase kinase (MEK) inhibitor, ARRY-142886, there was marked synergy in shrinking these Kras-mutant cancers.". 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: Combining phosphatidylinositide 3-kinase and MEK 1/2 inhibitors is effective at treating KRAS mutant tumors.

Document title: Effective Use of PI3K and MEK Inhibitors to Treat Mutant K-Ras G12D and PIK3CA H1047R Murine Lung Cancers

Abstract sentences:
[0] Somatic mutations that activate phosphoinositide 3-kinase (PI3K) have been identified in the p110-alpha catalytic subunit (encoded by PIK3CA).
[1] They are most frequently observed in two hotspots: the helical domain (E545K and E542K) and the kinase domain (H1047R).
[2] Although the p110-alpha mutants are transforming in vitro, their oncogenic potential has not been assessed in genetically engineered mouse models.
[3] Furthermore, clinical trials with PI3K inhibitors have recently been initiated, and it is unknown if their efficacy will be restricted to specific, genetically defined malignancies.
[4] In this study, we engineered a mouse model of lung adenocarcinomas initiated and maintained by expression of p110-alpha H1047R.
[5] Treatment of these tumors with NVP-BEZ235, a dual pan-PI3K and mammalian target of rapamycin (mTOR) inhibitor in clinical development, led to marked tumor regression as shown by positron emission tomography-computed tomography, magnetic resonance imaging and microscopic examination.
[6] In contrast, mouse lung cancers driven by mutant Kras did not substantially respond to single-agent NVP-BEZ235.
[7] However, when NVP-BEZ235 was combined with a mitogen-activated protein kinase kinase (MEK) inhibitor, ARRY-142886, there was marked synergy in shrinking these Kras-mutant cancers.
[8] These in vivo studies suggest that inhibitors of the PI3K-mTOR pathway may be active in cancers with PIK3CA mutations and, when combined with MEK inhibitors, may effectively treat KRAS mutated lung cancers.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "These in vivo studies suggest that inhibitors of the PI3K-mTOR pathway may be active in cancers with PIK3CA mutations and, when combined with MEK inhibitors, may effectively treat KRAS mutated lung cancers.". 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: Combining phosphatidylinositide 3-kinase and MEK 1/2 inhibitors is effective at treating KRAS mutant tumors.

Document title: NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations.

Abstract sentences:
[0] Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is a common event in human cancer, either through inactivation of the tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 or activating mutations of p110-alpha.
[1] These hotspot mutations result in oncogenic activity of the enzyme and contribute to therapeutic resistance to the anti-HER2 antibody trastuzumab.
[2] The PI3K pathway is, therefore, an attractive target for cancer therapy.
[3] We have studied NVP-BEZ235, a dual inhibitor of the PI3K and the downstream mammalian target of rapamycin (mTOR).
[4] NVP-BEZ235 inhibited the activation of the downstream effectors Akt, S6 ribosomal protein, and 4EBP1 in breast cancer cells.
[5] The antiproliferative activity of NVP-BEZ235 was superior to the allosteric selective mTOR complex inhibitor everolimus in a panel of 21 cancer cell lines of different origin and mutation status.
[6] The described Akt activation due to mTOR inhibition was prevented by higher doses of NVP-BEZ235.
[7] NVP-BEZ235 reversed the hyperactivation of the PI3K/mTOR pathway caused by the oncogenic mutations of p110-alpha, E545K, and H1047R, and inhibited the proliferation of HER2-amplified BT474 cells exogenously expressing these mutations that render them resistant to trastuzumab.
[8] In trastuzumab-resistant BT474 H1047R breast cancer xenografts, NVP-BEZ235 inhibited PI3K signaling and had potent antitumor activity.
[9] In treated animals, there was complete inhibition of PI3K signaling in the skin at pharmacologically active doses, suggesting that skin may serve as surrogate tissue for pharmacodynamic studies.
[10] In summary, NVP-BEZ235 inhibits the PI3K/mTOR axis and results in antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated p110-alpha.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "In summary, NVP-BEZ235 inhibits the PI3K/mTOR axis and results in antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated p110-alpha.". 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: Commelina yellow mottle virus' (ComYMV) genome consists of 7489 baise pairs.

Document title: Properties of Commelina yellow mottle virus's complete DNA sequence, genomic discontinuities and transcript suggest that it is a pararetrovirus.

Abstract sentences:
[0] The non-enveloped bacilliform viruses are the second group of plant viruses known to possess a genome consisting of circular double-stranded DNA.
[1] We have characterized the viral transcript and determined the complete sequence of the genome of Commelina mellow mottle virus (CoYMV), a member of this group.
[2] Analysis of the viral transcript indicates that the virus encodes a single terminally-redundant genome-length plus 120 nucleotide transcript.
[3] A fraction of the transcripts is polyadenylated, although the majority of the transcript is not polyadenylated.
[4] Analysis of the genome sequence indicates that the genome is 7489 bp in size and that the transcribed strand contains three open reading frames capable of encoding proteins of 23, 15 and 216 kd.
[5] The function of the 25 and 15 kd proteins is unknown.
[6] Similarities between the 216 kd polypeptide and the cauliflower mosaic virus coat protein and protease/reverse transcriptase polyprotein suggest that the 216 kd polypeptide is a polyprotein that is proteolytically processed to yield the virion coat protein, a protease, and replicase (reverse transcriptase and ribonuclease H).
[7] Each strand of the CoYMV genome is interrupted by site-specific discontinuities.
[8] The locations of the 5'-ends of these discontinuities, and the presence and location of a region on the CoYMV transcript capable of annealing with the 3'-end of cytosolic initiator methionine tRNA are consistent with replication by reverse transcription.
[9] We have demonstrated that a construct containing 1.3 CoYMV genomes is infective when introduced into Commelina diffusa, the host for CoYMV, using Agrobacterium-mediated infection.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Analysis of the genome sequence indicates that the genome is 7489 bp in size and that the transcribed strand contains three open reading frames capable of encoding proteins of 23, 15 and 216 kd.". 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: Crossover hot spots are not found within gene promoters in Saccharomyces cerevisiae.

Document title: Mapping Meiotic Single-Strand DNA Reveals a New Landscape of DNA Double-Strand Breaks in Saccharomyces cerevisiae

Abstract sentences:
[0] DNA double-strand breaks (DSBs), which are formed by the Spo11 protein, initiate meiotic recombination.
[1] Previous DSB-mapping studies have used rad50S or sae2Δ mutants, which are defective in break processing, to accumulate Spo11-linked DSBs, and report large (≥ 50 kb) “DSB-hot” regions that are separated by “DSB-cold” domains of similar size.
[2] Substantial recombination occurs in some DSB-cold regions, suggesting that DSB patterns are not normal in rad50S or sae2Δ mutants.
[3] We therefore developed a novel method to map genome-wide, single-strand DNA (ssDNA)–associated DSBs that accumulate in processing-capable, repair-defective dmc1Δ and dmc1Δ rad51Δ mutants.
[4] DSBs were observed at known hot spots, but also in most previously identified “DSB-cold” regions, including near centromeres and telomeres.
[5] Although approximately 40% of the genome is DSB-cold in rad50S mutants, analysis of meiotic ssDNA from dmc1Δ shows that most of these regions have substantial DSB activity.
[6] Southern blot assays of DSBs in selected regions in dmc1Δ, rad50S, and wild-type cells confirm these findings.
[7] Thus, DSBs are distributed much more uniformly than was previously believed.
[8] Comparisons of DSB signals in dmc1, dmc1 rad51, and dmc1 spo11 mutant strains identify Dmc1 as a critical strand-exchange activity genome-wide, and confirm previous conclusions that Spo11-induced lesions initiate all meiotic recombination.

[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: Crosstalk between dendritic cells (DCs) and innate lymphoid cells (ILCs) is important in the regulation of intestinal homeostasis.

Document title: The Transcription Factor T-bet Regulates Intestinal Inflammation Mediated by Interleukin-7 Receptor+ Innate Lymphoid Cells

Abstract sentences:
[0] Mice lacking the transcription factor T-bet in the innate immune system develop microbiota-dependent colitis.
[1] Here, we show that interleukin-17A (IL-17A)-producing IL-7Rα(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice.
[2] TNF-α produced by CD103(-)CD11b(+) dendritic cells synergized with IL-23 to drive IL-17A production by ILCs, demonstrating a previously unrecognized layer of cellular crosstalk between dendritic cells and ILCs.
[3] We have identified Helicobacter typhlonius as a key disease trigger driving excess TNF-α production and promoting colitis in TRUC mice.
[4] Crucially, T-bet also suppressed the expression of IL-7R, a key molecule involved in controlling intestinal ILC homeostasis.
[5] The importance of IL-7R signaling in TRUC disease was highlighted by the dramatic reduction in intestinal ILCs and attenuated colitis following IL-7R blockade.
[6] Taken together, these data demonstrate the mechanism by which T-bet regulates the complex interplay between mucosal dendritic cells, ILCs, and the intestinal microbiota.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2, 4]
Explanation: Evidence states: "TNF-α produced by CD103(-)CD11b(+) dendritic cells synergized with IL-23 to drive IL-17A production by ILCs, demonstrating a previously unrecognized layer of cellular crosstalk between dendritic cells and ILCs. Crucially, T-bet also suppressed the expression of IL-7R, a key molecule involved in controlling intestinal ILC 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: Crosstalk between dendritic cells (DCs) and innate lymphoid cells (ILCs) is important in the regulation of intestinal homeostasis.

Document title: The Transcription Factor T-bet Regulates Intestinal Inflammation Mediated by Interleukin-7 Receptor+ Innate Lymphoid Cells

Abstract sentences:
[0] Mice lacking the transcription factor T-bet in the innate immune system develop microbiota-dependent colitis.
[1] Here, we show that interleukin-17A (IL-17A)-producing IL-7Rα(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice.
[2] TNF-α produced by CD103(-)CD11b(+) dendritic cells synergized with IL-23 to drive IL-17A production by ILCs, demonstrating a previously unrecognized layer of cellular crosstalk between dendritic cells and ILCs.
[3] We have identified Helicobacter typhlonius as a key disease trigger driving excess TNF-α production and promoting colitis in TRUC mice.
[4] Crucially, T-bet also suppressed the expression of IL-7R, a key molecule involved in controlling intestinal ILC homeostasis.
[5] The importance of IL-7R signaling in TRUC disease was highlighted by the dramatic reduction in intestinal ILCs and attenuated colitis following IL-7R blockade.
[6] Taken together, these data demonstrate the mechanism by which T-bet regulates the complex interplay between mucosal dendritic cells, ILCs, and the intestinal microbiota.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5, 6]
Explanation: Evidence states: "The importance of IL-7R signaling in TRUC disease was highlighted by the dramatic reduction in intestinal ILCs and attenuated colitis following IL-7R blockade. Taken together, these data demonstrate the mechanism by which T-bet regulates the complex interplay between mucosal dendritic cells, ILCs, and the intestinal microbiota.". 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: Cytochrome c is released from the mitochondrial intermembrane space to cytosol during apoptosis.

Document title: At the gates of death.

Abstract sentences:
[0] Apoptosis that proceeds via the mitochondrial pathway involves mitochondrial outer membrane permeabilization (MOMP), responsible for the release of cytochrome c and other proteins of the mitochondrial intermembrane space.
[1] This essential step is controlled and mediated by proteins of the Bcl-2 family.
[2] The proapoptotic proteins Bax and Bak are required for MOMP, while the antiapoptotic Bcl-2 proteins, including Bcl-2, Bcl-xL, Mcl-1, and others, prevent MOMP.
[3] Different proapoptotic BH3-only proteins act to interfere with the function of the antiapoptotic Bcl-2 members and/or activate Bax and Bak.
[4] Here, we discuss an emerging view, proposed by Certo et al. in this issue of Cancer Cell, on how these interactions result in MOMP and apoptosis.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "Apoptosis that proceeds via the mitochondrial pathway involves mitochondrial outer membrane permeabilization (MOMP), responsible for the release of cytochrome c and other proteins of the mitochondrial intermembrane space.". 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: Cytosolic proteins bind to iron-responsive elements on mRNAs coding for DMT1. Cytosolic proteins bind to iron-responsive elements on mRNAs coding for proteins involved in iron uptake.

Document title: Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice

Abstract sentences:
[0] Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.
[1] We have previously identified iron-responsive element-binding protein 2 (IRP2) as an important COPD susceptibility gene and have shown that IRP2 protein is increased in the lungs of individuals with COPD.
[2] Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.
[3] By integrating RNA immunoprecipitation followed by sequencing (RIP-seq), RNA sequencing (RNA-seq), and gene expression and functional enrichment clustering analysis, we identified Irp2 as a regulator of mitochondrial function in the lungs of mice.
[4] Irp2 increased mitochondrial iron loading and levels of cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.
[5] Frataxin-deficient mice, which had higher mitochondrial iron loading, showed impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas mice deficient in the synthesis of cytochrome c oxidase, which have reduced COX, were protected from CS-induced pulmonary inflammation and impairment of MCC.
[6] Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.
[7] Mitochondrial iron chelation also alleviated CS-induced impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD.

[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: DMRT1 is a sex-determining gene that is epigenetically regulated by the MHM region.

Document title: Somatic sex identity is cell-autonomous in the chicken

Abstract sentences:
[0] In the mammalian model of sex determination, embryos are considered to be sexually indifferent until the transient action of a sex-determining gene initiates gonadal differentiation.
[1] Although this model is thought to apply to all vertebrates, this has yet to be established.
[2] Here we have examined three lateral gynandromorph chickens (a rare, naturally occurring phenomenon in which one side of the animal appears male and the other female) to investigate the sex-determining mechanism in birds.
[3] These studies demonstrated that gynandromorph birds are genuine male:female chimaeras, and indicated that male and female avian somatic cells may have an inherent sex identity.
[4] To test this hypothesis, we transplanted presumptive mesoderm between embryos of reciprocal sexes to generate embryos containing male:female chimaeric gonads.
[5] In contrast to the outcome for mammalian mixed-sex chimaeras, in chicken mixed-sex chimaeras the donor cells were excluded from the functional structures of the host gonad.
[6] In an example where female tissue was transplanted into a male host, donor cells contributing to the developing testis retained a female identity and expressed a marker of female function.
[7] Our study demonstrates that avian somatic cells possess an inherent sex identity and that, in birds, sexual differentiation is substantively cell autonomous.

[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: De novo assembly of sequence data has more specific contigs than unassembled sequence data.

Document title: A culture-independent sequence-based metagenomics approach to the investigation of an outbreak of Shiga-toxigenic Escherichia coli O104:H4.

Abstract sentences:
[0] IMPORTANCE Identification of the bacterium responsible for an outbreak can aid in disease management.
[1] However, traditional culture-based diagnosis can be difficult, particularly if no specific diagnostic test is available for an outbreak strain.
[2] OBJECTIVE To explore the potential of metagenomics, which is the direct sequencing of DNA extracted from microbiologically complex samples, as an open-ended clinical discovery platform capable of identifying and characterizing bacterial strains from an outbreak without laboratory culture.
[3] DESIGN, SETTING, AND PATIENTS In a retrospective investigation, 45 samples were selected from fecal specimens obtained from patients with diarrhea during the 2011 outbreak of Shiga-toxigenic Escherichia coli (STEC) O104:H4 in Germany.
[4] Samples were subjected to high-throughput sequencing (August-September 2012), followed by a 3-phase analysis (November 2012-February 2013).
[5] In phase 1, a de novo assembly approach was developed to obtain a draft genome of the outbreak strain.
[6] In phase 2, the depth of coverage of the outbreak strain genome was determined in each sample.
[7] In phase 3, sequences from each sample were compared with sequences from known bacteria to identify pathogens other than the outbreak strain.
[8] MAIN OUTCOMES AND MEASURES The recovery of genome sequence data for the purposes of identification and characterization of the outbreak strain and other pathogens from fecal samples.
[9] RESULTS During phase 1, a draft genome of the STEC outbreak strain was obtained.
[10] During phase 2, the outbreak strain genome was recovered from 10 samples at greater than 10-fold coverage and from 26 samples at greater than 1-fold coverage.
[11] Sequences from the Shiga-toxin genes were detected in 27 of 40 STEC-positive samples (67%).
[12] In phase 3, sequences from Clostridium difficile, Campylobacter jejuni, Campylobacter concisus, and Salmonella enterica were recovered.
[13] CONCLUSIONS AND RELEVANCE These results suggest the potential of metagenomics as a culture-independent approach for the identification of bacterial pathogens during an outbreak of diarrheal disease.
[14] Challenges include improving diagnostic sensitivity, speeding up and simplifying workflows, and reducing costs.

[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: Deamination of cytidine to uridine on the minus strand of viral DNA results in catastrophic G-to-A mutations in the viral genome.

Document title: Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts

Abstract sentences:
[0] Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products.
[1] The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lymphocytes.
[2] When produced in the presence of APOBEC3G, vif-defective virus is non-infectious.
[3] APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA.
[4] APOBEC family members also have potent DNA mutator activity through dC deamination; however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown.
[5] Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA.
[6] We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3, 5]
Explanation: Evidence states: "APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA. Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA.". 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: Deleting Raptor reduces G-CSF levels.

Document title: Oncogenic mTOR signaling recruits myeloid-derived suppressor cells to promote tumor initiation

Abstract sentences:
[0] Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression.
[1] MDSC regulation is widely variable even among patients harbouring the same type of malignancy, and the mechanisms governing such heterogeneity are largely unknown.
[2] Here, integrating human tumour genomics and syngeneic mammary tumour models, we demonstrate that mTOR signalling in cancer cells dictates a mammary tumour's ability to stimulate MDSC accumulation through regulating G-CSF.
[3] Inhibiting this pathway or its activators (for example, FGFR) impairs tumour progression, which is partially rescued by restoring MDSCs or G-CSF.
[4] Tumour-initiating cells (TICs) exhibit elevated G-CSF.
[5] MDSCs reciprocally increase TIC frequency through activating Notch in tumour cells, forming a feedforward loop.
[6] Analyses of primary breast cancers and patient-derived xenografts corroborate these mechanisms in patients.
[7] These findings establish a non-canonical oncogenic role of mTOR signalling in recruiting pro-tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend on a distinct immune microenvironment.

[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: Deletion of αvβ8 does not result in a spontaneous inflammatory phenotype.

Document title: Integrin αvβ8-Mediated TGF-β Activation by Effector Regulatory T Cells Is Essential for Suppression of T-Cell-Mediated Inflammation

Abstract sentences:
[0] Regulatory T (Treg) cells play a pivotal role in suppressing self-harmful T cell responses, but how Treg cells mediate suppression to maintain immune homeostasis and limit responses during inflammation is unclear.
[1] Here we show that effector Treg cells express high amounts of the integrin αvβ8, which enables them to activate latent transforming growth factor-β (TGF-β).
[2] Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis.
[3] However, Treg cells lacking expression of integrin αvβ8 were unable to suppress pathogenic T cell responses during active inflammation.
[4] Thus, our results identify a mechanism by which Treg cells suppress exuberant immune responses, highlighting a key role for effector Treg-cell-mediated activation of latent TGF-β in suppression of self-harmful T cell responses during active inflammation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune 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: Dexamethasone decreases risk of postoperative bleeding.

Document title: Dexamethasone and risk of nausea and vomiting and postoperative bleeding after tonsillectomy in children: a randomized trial.

Abstract sentences:
[0] CONTEXT Dexamethasone is widely used to prevent postoperative nausea and vomiting (PONV) in pediatric tonsillectomy.
[1] OBJECTIVE To assess whether dexamethasone dose-dependently reduces the risk of PONV at 24 hours after tonsillectomy.
[2] DESIGN, SETTING, AND PATIENTS Randomized placebo-controlled trial conducted among 215 children undergoing elective tonsillectomy at a major public teaching hospital in Switzerland from February 2005 to December 2007.
[3] INTERVENTIONS Children were randomly assigned to receive dexamethasone (0.05, 0.15, or 0.5 mg/kg) or placebo intravenously after induction of anesthesia.
[4] Acetaminophen-codeine and ibuprofen were given as postoperative analgesia.
[5] Follow-up continued until the 10th postoperative day.
[6] MAIN OUTCOME MEASURES The primary end point was prevention of PONV at 24 hours; secondary end points were decrease in the need for ibuprofen at 24 hours and evaluation of adverse effects.
[7] RESULTS At 24 hours, 24 of 54 participants who received placebo (44%; 95% confidence interval [CI], 31%-59%) had experienced PONV compared with 20 of 53 (38%; 95% CI, 25%-52%), 13 of 54 (24%; 95% CI, 13%-38%), and 6 of 52 (12%; 95% CI, 4%-23%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P<.001 for linear trend).
[8] Children who received dexamethasone received significantly less ibuprofen.
[9] There were 26 postoperative bleeding episodes in 22 children.
[10] Two of 53 (4%; 95% CI, 0.5%-13%)
[11] children who received placebo had bleeding compared with 6 of 53 (11%; 95% CI, 4%-23%), 2 of 51 (4%; 95% CI, 0.5%-13%), and 12 of 50 (24%; 95% CI, 13%-38%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P = .003).
[12] Dexamethasone, 0.5 mg/kg, was associated with the highest bleeding risk (adjusted relative risk, 6.80; 95% CI, 1.77-16.5).
[13] Eight children had to undergo emergency reoperation because of bleeding, all of whom had received dexamethasone.
[14] The trial was stopped early for safety reasons.
[15] CONCLUSION In this study of children undergoing tonsillectomy, dexamethasone decreased the risk of PONV dose dependently but was associated with an increased risk of postoperative bleeding.
[16] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00403806.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10, 11]
Explanation: Evidence states: "Two of 53 (4%; 95% CI, 0.5%-13%) children who received placebo had bleeding compared with 6 of 53 (11%; 95% CI, 4%-23%), 2 of 51 (4%; 95% CI, 0.5%-13%), and 12 of 50 (24%; 95% CI, 13%-38%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P = .003).". 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: Dexamethasone decreases risk of postoperative bleeding.

Document title: Dexamethasone and risk of nausea and vomiting and postoperative bleeding after tonsillectomy in children: a randomized trial.

Abstract sentences:
[0] CONTEXT Dexamethasone is widely used to prevent postoperative nausea and vomiting (PONV) in pediatric tonsillectomy.
[1] OBJECTIVE To assess whether dexamethasone dose-dependently reduces the risk of PONV at 24 hours after tonsillectomy.
[2] DESIGN, SETTING, AND PATIENTS Randomized placebo-controlled trial conducted among 215 children undergoing elective tonsillectomy at a major public teaching hospital in Switzerland from February 2005 to December 2007.
[3] INTERVENTIONS Children were randomly assigned to receive dexamethasone (0.05, 0.15, or 0.5 mg/kg) or placebo intravenously after induction of anesthesia.
[4] Acetaminophen-codeine and ibuprofen were given as postoperative analgesia.
[5] Follow-up continued until the 10th postoperative day.
[6] MAIN OUTCOME MEASURES The primary end point was prevention of PONV at 24 hours; secondary end points were decrease in the need for ibuprofen at 24 hours and evaluation of adverse effects.
[7] RESULTS At 24 hours, 24 of 54 participants who received placebo (44%; 95% confidence interval [CI], 31%-59%) had experienced PONV compared with 20 of 53 (38%; 95% CI, 25%-52%), 13 of 54 (24%; 95% CI, 13%-38%), and 6 of 52 (12%; 95% CI, 4%-23%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P<.001 for linear trend).
[8] Children who received dexamethasone received significantly less ibuprofen.
[9] There were 26 postoperative bleeding episodes in 22 children.
[10] Two of 53 (4%; 95% CI, 0.5%-13%)
[11] children who received placebo had bleeding compared with 6 of 53 (11%; 95% CI, 4%-23%), 2 of 51 (4%; 95% CI, 0.5%-13%), and 12 of 50 (24%; 95% CI, 13%-38%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P = .003).
[12] Dexamethasone, 0.5 mg/kg, was associated with the highest bleeding risk (adjusted relative risk, 6.80; 95% CI, 1.77-16.5).
[13] Eight children had to undergo emergency reoperation because of bleeding, all of whom had received dexamethasone.
[14] The trial was stopped early for safety reasons.
[15] CONCLUSION In this study of children undergoing tonsillectomy, dexamethasone decreased the risk of PONV dose dependently but was associated with an increased risk of postoperative bleeding.
[16] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00403806.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [12]
Explanation: Evidence states: "Dexamethasone, 0.5 mg/kg, was associated with the highest bleeding risk (adjusted relative risk, 6.80; 95% CI, 1.77-16.5).". 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: Dexamethasone decreases risk of postoperative bleeding.

Document title: Dexamethasone and risk of nausea and vomiting and postoperative bleeding after tonsillectomy in children: a randomized trial.

Abstract sentences:
[0] CONTEXT Dexamethasone is widely used to prevent postoperative nausea and vomiting (PONV) in pediatric tonsillectomy.
[1] OBJECTIVE To assess whether dexamethasone dose-dependently reduces the risk of PONV at 24 hours after tonsillectomy.
[2] DESIGN, SETTING, AND PATIENTS Randomized placebo-controlled trial conducted among 215 children undergoing elective tonsillectomy at a major public teaching hospital in Switzerland from February 2005 to December 2007.
[3] INTERVENTIONS Children were randomly assigned to receive dexamethasone (0.05, 0.15, or 0.5 mg/kg) or placebo intravenously after induction of anesthesia.
[4] Acetaminophen-codeine and ibuprofen were given as postoperative analgesia.
[5] Follow-up continued until the 10th postoperative day.
[6] MAIN OUTCOME MEASURES The primary end point was prevention of PONV at 24 hours; secondary end points were decrease in the need for ibuprofen at 24 hours and evaluation of adverse effects.
[7] RESULTS At 24 hours, 24 of 54 participants who received placebo (44%; 95% confidence interval [CI], 31%-59%) had experienced PONV compared with 20 of 53 (38%; 95% CI, 25%-52%), 13 of 54 (24%; 95% CI, 13%-38%), and 6 of 52 (12%; 95% CI, 4%-23%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P<.001 for linear trend).
[8] Children who received dexamethasone received significantly less ibuprofen.
[9] There were 26 postoperative bleeding episodes in 22 children.
[10] Two of 53 (4%; 95% CI, 0.5%-13%)
[11] children who received placebo had bleeding compared with 6 of 53 (11%; 95% CI, 4%-23%), 2 of 51 (4%; 95% CI, 0.5%-13%), and 12 of 50 (24%; 95% CI, 13%-38%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P = .003).
[12] Dexamethasone, 0.5 mg/kg, was associated with the highest bleeding risk (adjusted relative risk, 6.80; 95% CI, 1.77-16.5).
[13] Eight children had to undergo emergency reoperation because of bleeding, all of whom had received dexamethasone.
[14] The trial was stopped early for safety reasons.
[15] CONCLUSION In this study of children undergoing tonsillectomy, dexamethasone decreased the risk of PONV dose dependently but was associated with an increased risk of postoperative bleeding.
[16] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00403806.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [15]
Explanation: Evidence states: "CONCLUSION In this study of children undergoing tonsillectomy, dexamethasone decreased the risk of PONV dose dependently but was associated with an increased risk of postoperative bleeding.". 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: Diabetic patients with acute coronary syndrome experience increased short-term and long-term risk for bleeding events.

Document title: Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry.

Abstract sentences:
[0] BACKGROUND Although unstable coronary artery disease is the most common reason for admission to a coronary care unit, the long-term prognosis of patients with this diagnosis is unknown.
[1] This is particularly true for patients with diabetes mellitus, who are known to have a high morbidity and mortality after an acute myocardial infarction.
[2] METHODS AND RESULTS Prospectively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non-Q-wave myocardial infarction.
[3] Overall, 1718 of 8013 registry patients (21%) had diabetes.
[4] Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients (23% versus 20%, P:<0.001) but had similar rates of catheterization and angioplasty.
[5] Diabetes independently predicted mortality (relative risk [RR], 1.57; 95% CI, 1.38 to 1.81; P:<0.001), as well as cardiovascular death, new myocardial infarction, stroke, and new congestive heart failure.
[6] Moreover, compared with their nondiabetic counterparts, women had a significantly higher risk than men (RR, 1.98; 95% CI, 1.60 to 2.44; and RR, 1.28; 95% CI, 1.06 to 1.56, respectively).
[7] Interestingly, diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease.
[8] CONCLUSIONS Hospitalization for unstable angina or non-Q-wave myocardial infarction predicts a high 2-year morbidity and mortality; this is especially evident for patients with diabetes.
[9] Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Diabetes independently predicted mortality (relative risk [RR], 1.57; 95% CI, 1.38 to 1.81; P:<0.001), as well as cardiovascular death, new myocardial infarction, stroke, and new congestive heart failure.". 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: Discrimination between the initiator and elongation tRNAs depends on the translation initiation factor IF3.

Document title: Large-Scale Movements of IF3 and tRNA during Bacterial Translation Initiation

Abstract sentences:
[0] In bacterial translational initiation, three initiation factors (IFs 1-3) enable the selection of initiator tRNA and the start codon in the P site of the 30S ribosomal subunit.
[1] Here, we report 11 single-particle cryo-electron microscopy (cryoEM) reconstructions of the complex of bacterial 30S subunit with initiator tRNA, mRNA, and IFs 1-3, representing different steps along the initiation pathway.
[2] IF1 provides key anchoring points for IF2 and IF3, thereby enhancing their activities.
[3] IF2 positions a domain in an extended conformation appropriate for capturing the formylmethionyl moiety charged on tRNA.
[4] IF3 and tRNA undergo large conformational changes to facilitate the accommodation of the formylmethionyl-tRNA (fMet-tRNA(fMet)) into the P site for start codon recognition.

[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: Downregulation and mislocalization of Scribble prevents cell transformation and mammary tumorigenesis.

Document title: Deregulation of Scribble Promotes Mammary Tumorigenesis and Reveals a Role for Cell Polarity in Carcinoma

Abstract sentences:
[0] Loss of cell polarity proteins such as Scribble induces neoplasia in Drosophila by promoting uncontrolled proliferation.
[1] In mammals, the role that polarity proteins play during tumorigenesis is not well understood.
[2] Here, we demonstrate that depletion of Scribble in mammary epithelia disrupts cell polarity, blocks three-dimensional morphogenesis, inhibits apoptosis, and induces dysplasia in vivo that progress to tumors after long latency.
[3] Loss of Scribble cooperates with oncogenes such as c-myc to transform epithelial cells and induce tumors in vivo by blocking activation of an apoptosis pathway.
[4] Like depletion, mislocalization of Scribble from cell-cell junction was sufficient to promote cell transformation.
[5] Interestingly, spontaneous mammary tumors in mice and humans possess both downregulated and mislocalized Scribble.
[6] Thus, we demonstrate that scribble inhibits breast cancer formation and that deregulation of polarity pathways promotes dysplastic and neoplastic growth in mammals by disrupting morphogenesis and inhibiting cell death.

[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: During the primary early antibody response activated B cells migrate toward the inner-and outer paracortical areas where oxysterol accumulation is generated by stromal cells.

Document title: Finding the right niche: B-cell migration in the early phases of T-dependent antibody responses.

Abstract sentences:
[0] Humoral immune responses depend on B cells encountering antigen, interacting with helper T cells, proliferating and differentiating into low-affinity plasma cells or, after organizing into a germinal center (GC), high-affinity plasma cells and memory B cells.
[1] Remarkably, each of these events occurs in association with distinct stromal cells in separate subcompartments of the lymphoid tissue.
[2] B cells must migrate from niche to niche in a rapid and highly regulated manner to successfully mount a response.
[3] The chemokine, CXCL13, plays a central role in guiding B cells to follicles whereas T-zone chemokines guide activated B cells to the T zone.
[4] Sphingosine-1-phosphate (S1P) promotes cell egress from the tissue, as well as marginal-zone B-cell positioning in the spleen.
[5] Recent studies have identified a role for the orphan receptor, EBV-induced molecule 2 (EBI2; GPR183), in guiding activated B cells to inter and outer follicular niche(s) and down-regulation of this receptor is essential for organizing cells into GCs.
[6] In this review, we discuss current understanding of the roles played by chemokines, S1P and EBI2 in the migration events that underlie humoral immune responses.

[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: Enhanced early production of inflammatory chemokines improves viral control in the lung.

Document title: Memory CD4+ T cells induce innate responses independently of pathogen

Abstract sentences:
[0] Inflammation induced by recognition of pathogen-associated molecular patterns markedly affects subsequent adaptive responses.
[1] We asked whether the adaptive immune system can also affect the character and magnitude of innate inflammatory responses.
[2] We found that the response of memory, but not naive, CD4+ T cells enhances production of multiple innate inflammatory cytokines and chemokines (IICs) in the lung and that, during influenza infection, this leads to early control of virus.
[3] Memory CD4+ T cell–induced IICs and viral control require cognate antigen recognition and are optimal when memory cells are either T helper type 1 (TH1) or TH17 polarized but are independent of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production and do not require activation of conserved pathogen recognition pathways.
[4] This represents a previously undescribed mechanism by which memory CD4+ T cells induce an early innate response that enhances immune protection against pathogens.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "We found that the response of memory, but not naive, CD4+ T cells enhances production of multiple innate inflammatory cytokines and chemokines (IICs) in the lung and that, during influenza infection, this leads to early control of virus.". 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: Epidemiological disease burden from noncommunicable diseases is more prevalent in low economic settings.

Document title: Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Abstract sentences:
[0] BACKGROUND The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease.
[1] By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context.
[2] METHODS We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015.
[3] This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence.
[4] We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources.
[5] We used statistical models to pool data, adjust for bias, and incorporate covariates.
[6] We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value.
[7] Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk.
[8] We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates.
[9] We characterised risk exposure in relation to a Socio-demographic Index (SDI).
[10] FINDINGS Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%.
[11] Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period.
[12] All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs.
[13] In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]).
[14] From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines.
[15] Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use.
[16] Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI.
[17] In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015.
[18] Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa.
[19] INTERPRETATION Declines in some key environmental risks have contributed to declines in critical infectious diseases.
[20] Some risks appear to be invariant to SDI.
[21] Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention.
[22] Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining.
[23] Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden.
[24] FUNDING Bill & Melinda Gates Foundation.

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


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

Claim: Epigenetic modulating agents (EMAs) modulate antitumor immune response in a cancer model system.

Document title: Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer

Abstract sentences:
[0] Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis]) with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer immune therapy.
[1] Herein, pharmacologic and isoform specificity of HDACis are investigated to guide their addition to a DNMTi, thus devising a new, low-dose, sequential regimen that imparts a robust anti-tumor effect for non-small-cell lung cancer (NSCLC).
[2] Using in-vitro-treated NSCLC cell lines, we elucidate an interferon α/β-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA (dsRNA) induction.
[3] This is accompanied by suppression of MYC signaling and an increase in the T cell chemoattractant CCL5.
[4] Use of this combination treatment schema in mouse models of NSCLC reverses tumor immune evasion and modulates T cell exhaustion state towards memory and effector T cell phenotypes.
[5] Key correlative science metrics emerge for an upcoming clinical trial, testing enhancement of immune checkpoint therapy for NSCLC.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Use of this combination treatment schema in mouse models of NSCLC reverses tumor immune evasion and modulates T cell exhaustion state towards memory and effector T cell phenotypes.". 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: Errors in peripheral IV drug administration are most common during bolus administration and multiple-step medicine preparations.

Document title: Ethnographic study of incidence and severity of intravenous drug errors.

Abstract sentences:
[0] OBJECTIVES To determine the incidence and clinical importance of errors in the preparation and administration of intravenous drugs and the stages of the process in which errors occur.
[1] DESIGN Prospective ethnographic study using disguised observation.
[2] PARTICIPANTS Nurses who prepared and administered intravenous drugs.
[3] SETTING 10 wards in a teaching and non-teaching hospital in the United Kingdom.
[4] MAIN OUTCOME MEASURES Number, type, and clinical importance of errors.
[5] RESULTS 249 errors were identified.
[6] At least one error occurred in 212 out of 430 intravenous drug doses (49%, 95% confidence interval 45% to 54%).
[7] Three doses (1%) had potentially severe errors, 126 (29%) potentially moderate errors, and 83 (19%) potentially minor errors.
[8] Most errors occurred when giving bolus doses or making up drugs that required multiple step preparation.
[9] CONCLUSIONS The rate of intravenous drug errors was high.
[10] Although most errors would cause only short term adverse effects, a few could have been serious.
[11] A combination of reducing the amount of preparation on the ward, training, and technology to administer slow bolus doses would probably have the greatest effect on error rates.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "Most errors occurred when giving bolus doses or making up drugs that required multiple step preparation.". 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: Errors in peripheral IV drug administration are most common during bolus administration and multiple-step medicine preparations.

Document title: Ethnographic study of incidence and severity of intravenous drug errors.

Abstract sentences:
[0] OBJECTIVES To determine the incidence and clinical importance of errors in the preparation and administration of intravenous drugs and the stages of the process in which errors occur.
[1] DESIGN Prospective ethnographic study using disguised observation.
[2] PARTICIPANTS Nurses who prepared and administered intravenous drugs.
[3] SETTING 10 wards in a teaching and non-teaching hospital in the United Kingdom.
[4] MAIN OUTCOME MEASURES Number, type, and clinical importance of errors.
[5] RESULTS 249 errors were identified.
[6] At least one error occurred in 212 out of 430 intravenous drug doses (49%, 95% confidence interval 45% to 54%).
[7] Three doses (1%) had potentially severe errors, 126 (29%) potentially moderate errors, and 83 (19%) potentially minor errors.
[8] Most errors occurred when giving bolus doses or making up drugs that required multiple step preparation.
[9] CONCLUSIONS The rate of intravenous drug errors was high.
[10] Although most errors would cause only short term adverse effects, a few could have been serious.
[11] A combination of reducing the amount of preparation on the ward, training, and technology to administer slow bolus doses would probably have the greatest effect on error rates.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [11]
Explanation: Evidence states: "A combination of reducing the amount of preparation on the ward, training, and technology to administer slow bolus doses would probably have the greatest effect on error rates.". 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: Ethanol stress decreases the expression of IBP in bacteria.

Document title: Regulatory and metabolic rewiring during laboratory evolution of ethanol tolerance in E. coli

Abstract sentences:
[0] Understanding the genetic basis of adaptation is a central problem in biology.
[1] However, revealing the underlying molecular mechanisms has been challenging as changes in fitness may result from perturbations to many pathways, any of which may contribute relatively little.
[2] We have developed a combined experimental/computational framework to address this problem and used it to understand the genetic basis of ethanol tolerance in Escherichia coli.
[3] We used fitness profiling to measure the consequences of single-locus perturbations in the context of ethanol exposure.
[4] A module-level computational analysis was then used to reveal the organization of the contributing loci into cellular processes and regulatory pathways (e.g. osmoregulation and cell-wall biogenesis) whose modifications significantly affect ethanol tolerance.
[5] Strikingly, we discovered that a dominant component of adaptation involves metabolic rewiring that boosts intracellular ethanol degradation and assimilation.
[6] Through phenotypic and metabolomic analysis of laboratory-evolved ethanol-tolerant strains, we investigated naturally accessible pathways of ethanol tolerance.
[7] Remarkably, these laboratory-evolved strains, by and large, follow the same adaptive paths as inferred from our coarse-grained search of the fitness landscape.

[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: Exposure to fine particulate air pollution is relate to anxiety prevalence.

Document title: The relation between past exposure to fine particulate air pollution and prevalent anxiety: observational cohort study

Abstract sentences:
[0] OBJECTIVE To determine whether higher past exposure to particulate air pollution is associated with prevalent high symptoms of anxiety.
[1] DESIGN Observational cohort study.
[2] SETTING Nurses' Health Study.
[3] PARTICIPANTS 71,271 women enrolled in the Nurses' Health Study residing throughout the contiguous United States who had valid estimates on exposure to particulate matter for at least one exposure period of interest and data on anxiety symptoms.
[4] MAIN OUTCOME MEASURES Meaningfully high symptoms of anxiety, defined as a score of 6 points or greater on the phobic anxiety subscale of the Crown-Crisp index, administered in 2004.
[5] RESULTS The 71,271 eligible women were aged between 57 and 85 years (mean 70 years) at the time of assessment of anxiety symptoms, with a prevalence of high anxiety symptoms of 15%.
[6] Exposure to particulate matter was characterized using estimated average exposure to particulate matter <2.5 μm in diameter (PM2.5) and 2.5 to 10 μm in diameter (PM2.5-10) in the one month, three months, six months, one year, and 15 years prior to assessment of anxiety symptoms, and residential distance to the nearest major road two years prior to assessment.
[7] Significantly increased odds of high anxiety symptoms were observed with higher exposure to PM2.5 for multiple averaging periods (for example, odds ratio per 10 µg/m(3) increase in prior one month average PM2.5: 1.12, 95% confidence interval 1.06 to 1.19; in prior 12 month average PM2.5: 1.15, 1.06 to 1.26).
[8] Models including multiple exposure windows suggested short term averaging periods were more relevant than long term averaging periods.
[9] There was no association between anxiety and exposure to PM2.5-10.
[10] Residential proximity to major roads was not related to anxiety symptoms in a dose dependent manner.
[11] CONCLUSIONS Exposure to fine particulate matter (PM2.5) was associated with high symptoms of anxiety, with more recent exposures potentially more relevant than more distant exposures.
[12] Research evaluating whether reductions in exposure to ambient PM2.5 would reduce the population level burden of clinically relevant symptoms of anxiety is warranted.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "Significantly increased odds of high anxiety symptoms were observed with higher exposure to PM2.5 for multiple averaging periods (for example, odds ratio per 10 µg/m(3) increase in prior one month average PM2.5: 1.12, 95% confidence interval 1.06 to 1.19; in prior 12 month average PM2.5: 1.15, 1.06 to 1.26).". 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: Exposure to fine particulate air pollution is relate to anxiety prevalence.

Document title: The relation between past exposure to fine particulate air pollution and prevalent anxiety: observational cohort study

Abstract sentences:
[0] OBJECTIVE To determine whether higher past exposure to particulate air pollution is associated with prevalent high symptoms of anxiety.
[1] DESIGN Observational cohort study.
[2] SETTING Nurses' Health Study.
[3] PARTICIPANTS 71,271 women enrolled in the Nurses' Health Study residing throughout the contiguous United States who had valid estimates on exposure to particulate matter for at least one exposure period of interest and data on anxiety symptoms.
[4] MAIN OUTCOME MEASURES Meaningfully high symptoms of anxiety, defined as a score of 6 points or greater on the phobic anxiety subscale of the Crown-Crisp index, administered in 2004.
[5] RESULTS The 71,271 eligible women were aged between 57 and 85 years (mean 70 years) at the time of assessment of anxiety symptoms, with a prevalence of high anxiety symptoms of 15%.
[6] Exposure to particulate matter was characterized using estimated average exposure to particulate matter <2.5 μm in diameter (PM2.5) and 2.5 to 10 μm in diameter (PM2.5-10) in the one month, three months, six months, one year, and 15 years prior to assessment of anxiety symptoms, and residential distance to the nearest major road two years prior to assessment.
[7] Significantly increased odds of high anxiety symptoms were observed with higher exposure to PM2.5 for multiple averaging periods (for example, odds ratio per 10 µg/m(3) increase in prior one month average PM2.5: 1.12, 95% confidence interval 1.06 to 1.19; in prior 12 month average PM2.5: 1.15, 1.06 to 1.26).
[8] Models including multiple exposure windows suggested short term averaging periods were more relevant than long term averaging periods.
[9] There was no association between anxiety and exposure to PM2.5-10.
[10] Residential proximity to major roads was not related to anxiety symptoms in a dose dependent manner.
[11] CONCLUSIONS Exposure to fine particulate matter (PM2.5) was associated with high symptoms of anxiety, with more recent exposures potentially more relevant than more distant exposures.
[12] Research evaluating whether reductions in exposure to ambient PM2.5 would reduce the population level burden of clinically relevant symptoms of anxiety is warranted.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [11]
Explanation: Evidence states: "CONCLUSIONS Exposure to fine particulate matter (PM2.5) was associated with high symptoms of anxiety, with more recent exposures potentially more relevant than more distant exposures.". 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: Febrile seizures increase the threshold for development of epilepsy.

Document title: Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits

Abstract sentences:
[0] Febrile (fever-induced) seizures affect 3–5% of infants and young children.
[1] Despite the high incidence of febrile seizures, their contribution to the development of epilepsy later in life has remained controversial.
[2] Combining a new rat model of complex febrile seizures and patch clamp techniques, we determined that hyperthermia-induced seizures in the immature rat cause a selective presynaptic increase in inhibitory synaptic transmission in the hippocampus that lasts into adulthood.
[3] The long-lasting nature of these potent alterations in synaptic communication after febrile seizures does not support the prevalent view of the 'benign' nature of early-life febrile convulsions.

[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: Febrile seizures reduce the threshold for development of epilepsy.

Document title: Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits

Abstract sentences:
[0] Febrile (fever-induced) seizures affect 3–5% of infants and young children.
[1] Despite the high incidence of febrile seizures, their contribution to the development of epilepsy later in life has remained controversial.
[2] Combining a new rat model of complex febrile seizures and patch clamp techniques, we determined that hyperthermia-induced seizures in the immature rat cause a selective presynaptic increase in inhibitory synaptic transmission in the hippocampus that lasts into adulthood.
[3] The long-lasting nature of these potent alterations in synaptic communication after febrile seizures does not support the prevalent view of the 'benign' nature of early-life febrile convulsions.

[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: Female carriers of the Apolipoprotein E4 (APOE4) allele have increased risk for dementia.

Document title: Reproductive period and risk of dementia in postmenopausal women.

Abstract sentences:
[0] CONTEXT Exogenous estrogen use may lower risk of dementia in postmenopausal women.
[1] A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied.
[2] OBJECTIVE To determine whether a longer reproductive period, as an indicator of longer exposure to endogenous estrogens, is associated with lower risk of dementia and Alzheimer disease (AD) in women who have natural menopause.
[3] DESIGN AND SETTING The Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands.
[4] PARTICIPANTS A total of 3601 women aged 55 years or older who did not have dementia at baseline (1990-1993) and had information on age at menarche, age at menopause, and type of menopause.
[5] Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for development of dementia.
[6] MAIN OUTCOME MEASURES Incidence of dementia, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria, and AD, based on National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria, compared by quartiles of reproductive period among women with natural menopause.
[7] RESULTS During 21 046 person-years of follow-up (median follow-up, 6.3 years), 199 women developed dementia, including 159 who developed AD.
[8] After adjusting for age, dementia was not clearly associated with length of reproductive period.
[9] However, after adjusting for multiple covariates, women with natural menopause and more reproductive years had an increased risk of dementia (adjusted rate ratio [RR] for women with >39 reproductive years [highest quartile] compared with <34 reproductive years [lowest quartile], 1.78; 95% confidence interval [CI], 1.12-2.84).
[10] The adjusted RR per year of increase was 1.04 (95% CI, 1.01-1.08).
[11] For risk of AD, the adjusted RRs were 1.51 (95% CI, 0.91-2.50) and 1.03 (95% CI, 1.00-1.07), respectively.
[12] Risk of dementia associated with a longer reproductive period was most pronounced in APOE epsilon4 carriers (adjusted RR for >39 reproductive years compared with <34 reproductive years, 4.20 [95% CI, 1.97-8.92] for dementia and 3.42 [95% CI, 1.51-7.75] for AD), whereas in noncarriers, no clear association with dementia or AD was observed.
[13] CONCLUSION Our findings do not support the hypothesis that a longer reproductive period reduces risk of dementia in women who have natural menopause.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [12]
Explanation: Evidence states: "Risk of dementia associated with a longer reproductive period was most pronounced in APOE epsilon4 carriers (adjusted RR for >39 reproductive years compared with <34 reproductive years, 4.20 [95% CI, 1.97-8.92] for dementia and 3.42 [95% CI, 1.51-7.75] for AD), whereas in noncarriers, no clear association with dementia or AD was observed.". 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: Flexible molecules experience greater steric hindrance in the tumor microenviroment than rigid molecules.

Document title: Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo

Abstract sentences:
[0] A solid tumor is an organ composed of cancer and host cells embedded in an extracellular matrix and nourished by blood vessels.
[1] A prerequisite to understanding tumor pathophysiology is the ability to distinguish and monitor each component in dynamic studies.
[2] Standard fluorophores hamper simultaneous intravital imaging of these components.
[3] Here, we used multiphoton microscopy techniques and transgenic mice that expressed green fluorescent protein, and combined them with the use of quantum dot preparations.
[4] We show that these fluorescent semiconductor nanocrystals can be customized to concurrently image and differentiate tumor vessels from both the perivascular cells and the matrix.
[5] Moreover, we used them to measure the ability of particles of different sizes to access the tumor.
[6] Finally, we successfully monitored the recruitment of quantum dot–labeled bone marrow–derived precursor cells to the tumor vasculature.
[7] These examples show the versatility of quantum dots for studying tumor pathophysiology and creating avenues for treatment.

[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: FoxO3a activation in neuronal death is mediated by reactive oxygen species (ROS).

Document title: Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase.

Abstract sentences:
[0] The Sir2 deacetylase modulates organismal life-span in various species.
[1] However, the molecular mechanisms by which Sir2 increases longevity are largely unknown.
[2] We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity.
[3] SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells.
[4] SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death.
[5] Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.". 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: Free histones are degraded by a Rad53-dependent mechanism once DNA has been replicated.

Document title: Histone levels are regulated by phosphorylation and ubiquitylation dependent proteolysis

Abstract sentences:
[0] Histone levels are tightly regulated to prevent harmful effects such as genomic instability and hypersensitivity to DNA-damaging agents due to the accumulation of these highly basic proteins when DNA replication slows down or stops.
[1] Although chromosomal histones are stable, excess (non-chromatin bound) histones are rapidly degraded in a Rad53 (radiation sensitive 53) kinase-dependent manner in Saccharomyces cerevisiae.
[2] Here we demonstrate that excess histones associate with Rad53 in vivo and seem to undergo modifications such as tyrosine phosphorylation and polyubiquitylation, before their proteolysis by the proteasome.
[3] We have identified the Tyr 99 residue of histone H3 as being critical for the efficient ubiquitylation and degradation of this histone.
[4] We have also identified the ubiquitin conjugating enzymes (E2) Ubc4 and Ubc5, as well as the ubiquitin ligase (E3) Tom1 (temperature dependent organization in mitotic nucleus 1), as enzymes involved in the ubiquitylation of excess histones.
[5] Regulated histone proteolysis has major implications for the maintenance of epigenetic marks on chromatin, genomic stability and the packaging of sperm DNA.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Although chromosomal histones are stable, excess (non-chromatin bound) histones are rapidly degraded in a Rad53 (radiation sensitive 53) kinase-dependent manner in Saccharomyces cerevisiae.". 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: Free histones are degraded by a Rad53-dependent mechanism once DNA has been replicated.

Document title: Histone levels are regulated by phosphorylation and ubiquitylation dependent proteolysis

Abstract sentences:
[0] Histone levels are tightly regulated to prevent harmful effects such as genomic instability and hypersensitivity to DNA-damaging agents due to the accumulation of these highly basic proteins when DNA replication slows down or stops.
[1] Although chromosomal histones are stable, excess (non-chromatin bound) histones are rapidly degraded in a Rad53 (radiation sensitive 53) kinase-dependent manner in Saccharomyces cerevisiae.
[2] Here we demonstrate that excess histones associate with Rad53 in vivo and seem to undergo modifications such as tyrosine phosphorylation and polyubiquitylation, before their proteolysis by the proteasome.
[3] We have identified the Tyr 99 residue of histone H3 as being critical for the efficient ubiquitylation and degradation of this histone.
[4] We have also identified the ubiquitin conjugating enzymes (E2) Ubc4 and Ubc5, as well as the ubiquitin ligase (E3) Tom1 (temperature dependent organization in mitotic nucleus 1), as enzymes involved in the ubiquitylation of excess histones.
[5] Regulated histone proteolysis has major implications for the maintenance of epigenetic marks on chromatin, genomic stability and the packaging of sperm DNA.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Here we demonstrate that excess histones associate with Rad53 in vivo and seem to undergo modifications such as tyrosine phosphorylation and polyubiquitylation, before their proteolysis by the proteasome.". 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: Functional consequences of genomic alterations due to Myelodysplastic syndrome (MDS) are poorly understood due to the lack of an animal model.

Document title: Establishment of human iPSC-based models for the study and targeting of glioma initiating cells

Abstract sentences:
[0] Glioma tumour-initiating cells (GTICs) can originate upon the transformation of neural progenitor cells (NPCs).
[1] Studies on GTICs have focused on primary tumours from which GTICs could be isolated and the use of human embryonic material.
[2] Recently, the somatic genomic landscape of human gliomas has been reported.
[3] RTK (receptor tyrosine kinase) and p53 signalling were found dysregulated in ∼90% and 86% of all primary tumours analysed, respectively.
[4] Here we report on the use of human-induced pluripotent stem cells (hiPSCs) for modelling gliomagenesis.
[5] Dysregulation of RTK and p53 signalling in hiPSC-derived NPCs (iNPCs) recapitulates GTIC properties in vitro.
[6] In vivo transplantation of transformed iNPCs leads to highly aggressive tumours containing undifferentiated stem cells and their differentiated derivatives.
[7] Metabolic modulation compromises GTIC viability.
[8] Last, screening of 101 anti-cancer compounds identifies three molecules specifically targeting transformed iNPCs and primary GTICs.
[9] Together, our results highlight the potential of hiPSCs for studying human tumourigenesis.

[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: Fz/PCP-dependent Pk localizes to the anterior membrane of neuroectoderm cells during zebrafish neuralation

Document title: Planar cell polarity signalling couples cell division and morphogenesis during neurulation

Abstract sentences:
[0] Environmental and genetic aberrations lead to neural tube closure defects (NTDs) in 1 out of every 1,000 births.
[1] Mouse and frog models for these birth defects have indicated that Van Gogh-like 2 (Vangl2, also known as Strabismus) and other components of planar cell polarity (PCP) signalling might control neurulation by promoting the convergence of neural progenitors to the midline.
[2] Here we show a novel role for PCP signalling during neurulation in zebrafish.
[3] We demonstrate that non-canonical Wnt/PCP signalling polarizes neural progenitors along the anteroposterior axis.
[4] This polarity is transiently lost during cell division in the neural keel but is re-established as daughter cells reintegrate into the neuroepithelium.
[5] Loss of zebrafish Vangl2 (in trilobite mutants) abolishes the polarization of neural keel cells, disrupts re-intercalation of daughter cells into the neuroepithelium, and results in ectopic neural progenitor accumulations and NTDs.
[6] Remarkably, blocking cell division leads to rescue of trilobite neural tube morphogenesis despite persistent defects in convergence and extension.
[7] These results reveal a function for PCP signalling in coupling cell division and morphogenesis at neurulation and indicate a previously unrecognized mechanism that might underlie NTDs.

[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: Fz/PCP-dependent Pk localizes to the anterior membrane of notochord cells during zebrafish neuralation.

Document title: Planar cell polarity signalling couples cell division and morphogenesis during neurulation

Abstract sentences:
[0] Environmental and genetic aberrations lead to neural tube closure defects (NTDs) in 1 out of every 1,000 births.
[1] Mouse and frog models for these birth defects have indicated that Van Gogh-like 2 (Vangl2, also known as Strabismus) and other components of planar cell polarity (PCP) signalling might control neurulation by promoting the convergence of neural progenitors to the midline.
[2] Here we show a novel role for PCP signalling during neurulation in zebrafish.
[3] We demonstrate that non-canonical Wnt/PCP signalling polarizes neural progenitors along the anteroposterior axis.
[4] This polarity is transiently lost during cell division in the neural keel but is re-established as daughter cells reintegrate into the neuroepithelium.
[5] Loss of zebrafish Vangl2 (in trilobite mutants) abolishes the polarization of neural keel cells, disrupts re-intercalation of daughter cells into the neuroepithelium, and results in ectopic neural progenitor accumulations and NTDs.
[6] Remarkably, blocking cell division leads to rescue of trilobite neural tube morphogenesis despite persistent defects in convergence and extension.
[7] These results reveal a function for PCP signalling in coupling cell division and morphogenesis at neurulation and indicate a previously unrecognized mechanism that might underlie NTDs.

[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: GATA-3 is important for hematopoietic stem cell (HSC) function.

Document title: GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry.

Abstract sentences:
[0] Maintaining hematopoietic stem cell (HSC) quiescence is a critical property for the life-long generation of blood cells.
[1] Approximately 75% of cells in a highly enriched long-term repopulating HSC (LT-HSC) pool (Lin(-)Sca1(+)c-Kit(hi)CD150(+)CD48(-)) are quiescent, with only a small percentage of the LT-HSCs in cycle.
[2] Transcription factor GATA-3 is known to be vital for the development of T cells at multiple stages in the thymus and for Th2 differentiation in the peripheral organs.
[3] Although it is well documented that GATA-3 is expressed in HSCs, a role for GATA-3 in any prethymic progenitor cell has not been established.
[4] In the present study, we show that Gata3-null mutant mice generate fewer LT-HSCs and that fewer Gata3-null LT-HSCs are in cycle.
[5] Furthermore, Gata3 mutant hematopoietic progenitor cells fail to be recruited into an increased cycling state after 5-fluorouracil-induced myelosuppression.
[6] Therefore, GATA-3 is required for the maintenance of a normal number of LT-HSCs and for their entry into the cell cycle.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4, 5, 6]
Explanation: Evidence states: "In the present study, we show that Gata3-null mutant mice generate fewer LT-HSCs and that fewer Gata3-null LT-HSCs are in cycle. Furthermore, Gata3 mutant hematopoietic progenitor cells fail to be recruited into an increased cycling state after 5-fluorouracil-induced myelosuppression. Therefore, GATA-3 is required for the maintenance of a normal number of LT-HSCs and for their entry into the cell cycle.". 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: Gene expression does not vary appreciably across genetically identical cells.

Document title: Nature, Nurture, or Chance: Stochastic Gene Expression and Its Consequences

Abstract sentences:
[0] Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to cell-to-cell variations in mRNA and protein levels.
[1] This variation appears in organisms ranging from microbes to metazoans, and its characteristics depend both on the biophysical parameters governing gene expression and on gene network structure.
[2] Stochastic gene expression has important consequences for cellular function, being beneficial in some contexts and harmful in others.
[3] These situations include the stress response, metabolism, development, the cell cycle, circadian rhythms, and aging.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [0]
Explanation: Evidence states: "Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to cell-to-cell variations in mRNA and protein levels.". This contradicts the claim.