[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: Medications to treat obesity are highly effective.

Document title: Long term pharmacotherapy for obesity and overweight: updated meta-analysis.

Abstract sentences:
[0] OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.
[1] DESIGN Updated meta-analysis of randomised trials.
[2] DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles.
[3] All data sources were searched from December 2002 (end date of last search) to December 2006.
[4] STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer.
[5] RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365).
[6] Of these, 14 trials were new and 16 had previously been identified.
[7] Attrition rates averaged 30-40%.
[8] Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg).
[9] Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds.
[10] Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.
[11] Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
[12] CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [8]
Explanation: Evidence states: "Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg).". 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: Medications to treat obesity are highly effective.

Document title: Long term pharmacotherapy for obesity and overweight: updated meta-analysis.

Abstract sentences:
[0] OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.
[1] DESIGN Updated meta-analysis of randomised trials.
[2] DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles.
[3] All data sources were searched from December 2002 (end date of last search) to December 2006.
[4] STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer.
[5] RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365).
[6] Of these, 14 trials were new and 16 had previously been identified.
[7] Attrition rates averaged 30-40%.
[8] Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg).
[9] Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds.
[10] Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.
[11] Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
[12] CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [12]
Explanation: Evidence states: "CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.". 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: Medications to treat obesity do not have side effects.

Document title: Long term pharmacotherapy for obesity and overweight: updated meta-analysis.

Abstract sentences:
[0] OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.
[1] DESIGN Updated meta-analysis of randomised trials.
[2] DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles.
[3] All data sources were searched from December 2002 (end date of last search) to December 2006.
[4] STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer.
[5] RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365).
[6] Of these, 14 trials were new and 16 had previously been identified.
[7] Attrition rates averaged 30-40%.
[8] Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg).
[9] Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds.
[10] Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.
[11] Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
[12] CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10]
Explanation: Evidence states: "Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.". 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: Medications to treat obesity do not have side effects.

Document title: Long term pharmacotherapy for obesity and overweight: updated meta-analysis.

Abstract sentences:
[0] OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.
[1] DESIGN Updated meta-analysis of randomised trials.
[2] DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles.
[3] All data sources were searched from December 2002 (end date of last search) to December 2006.
[4] STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer.
[5] RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365).
[6] Of these, 14 trials were new and 16 had previously been identified.
[7] Attrition rates averaged 30-40%.
[8] Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg).
[9] Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds.
[10] Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.
[11] Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
[12] CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [11]
Explanation: Evidence states: "Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.". 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: Medications to treat obesity do not have side effects.

Document title: Long term pharmacotherapy for obesity and overweight: updated meta-analysis.

Abstract sentences:
[0] OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.
[1] DESIGN Updated meta-analysis of randomised trials.
[2] DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles.
[3] All data sources were searched from December 2002 (end date of last search) to December 2006.
[4] STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer.
[5] RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365).
[6] Of these, 14 trials were new and 16 had previously been identified.
[7] Attrition rates averaged 30-40%.
[8] Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg).
[9] Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds.
[10] Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.
[11] Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
[12] CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [12]
Explanation: Evidence states: "CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.". 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: Medications to treat obesity have unwanted side effects.

Document title: Long term pharmacotherapy for obesity and overweight: updated meta-analysis.

Abstract sentences:
[0] OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.
[1] DESIGN Updated meta-analysis of randomised trials.
[2] DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles.
[3] All data sources were searched from December 2002 (end date of last search) to December 2006.
[4] STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer.
[5] RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365).
[6] Of these, 14 trials were new and 16 had previously been identified.
[7] Attrition rates averaged 30-40%.
[8] Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg).
[9] Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds.
[10] Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.
[11] Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
[12] CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.". 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: Medications to treat obesity have unwanted side effects.

Document title: Long term pharmacotherapy for obesity and overweight: updated meta-analysis.

Abstract sentences:
[0] OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.
[1] DESIGN Updated meta-analysis of randomised trials.
[2] DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles.
[3] All data sources were searched from December 2002 (end date of last search) to December 2006.
[4] STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer.
[5] RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365).
[6] Of these, 14 trials were new and 16 had previously been identified.
[7] Attrition rates averaged 30-40%.
[8] Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg).
[9] Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds.
[10] Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.
[11] Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
[12] CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [11]
Explanation: Evidence states: "Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.". 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: Medications to treat obesity have unwanted side effects.

Document title: Long term pharmacotherapy for obesity and overweight: updated meta-analysis.

Abstract sentences:
[0] OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.
[1] DESIGN Updated meta-analysis of randomised trials.
[2] DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles.
[3] All data sources were searched from December 2002 (end date of last search) to December 2006.
[4] STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer.
[5] RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365).
[6] Of these, 14 trials were new and 16 had previously been identified.
[7] Attrition rates averaged 30-40%.
[8] Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg).
[9] Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds.
[10] Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein.
[11] Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
[12] CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [12]
Explanation: Evidence states: "CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.". 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: Men are more susceptible to death due to pneumonia when compared to women.

Document title: Gender-dependent differences in outcome after the treatment of infection in hospitalized patients.

Abstract sentences:
[0] CONTEXT While it is established that management strategies and outcomes differ by gender for many diseases, its effect on infection has not been adequately studied.
[1] OBJECTIVE To investigate the role of gender among hospitalized patients treated for infection.
[2] DESIGN Observational cohort study conducted during a 26-month period from December 1996 through January 1999.
[3] SETTING University-affiliated hospital.
[4] PARTICIPANTS A total of 892 patients in the surgical units of the hospital with 1470 consecutive infectious episodes (782 in men and 688 in women).
[5] MAIN OUTCOME MEASURES Mortality during hospitalization by gender for infection episodes overall and for specific infectious sites, including lung, peritoneum, bloodstream, catheter, urine, surgical site, and skin/soft tissue.
[6] RESULTS Among all infections, there was no significant difference in mortality based on gender (men, 11.1% vs women, 14.2%; P = .07).
[7] After logistic regression analysis, factors independently associated with mortality included higher APACHE (Acute Physiology and Chronic Health Evaluation) II score, older age, malignancy, blood transfusion, and diagnosis of infection more than 7 days after admission, but not gender (female odds ratio [OR] for death, 1.32; 95% confidence interval [CI], 0.90-1.94; P = .16).
[8] Mortality was higher in women for lung (men, 18% vs women, 34%; P = .002) and soft tissue (men, 2% vs women, 10%; P < or = .05) infection; for other infectious sites, mortality did not differ by gender.
[9] Factors associated with mortality due to pneumonia by logistic regression included higher APACHE II score, malignancy, diabetes mellitus, diagnosis of infection more than 7 days after admission, older age, transplantation, and female gender (OR for death, 2.25; 95% CI, 1.17-4.32; P = .02).
[10] CONCLUSIONS Although gender may not be predictive of mortality among all infections, women appear to be at increased risk for death from hospital-acquired pneumonia, even after controlling for other comorbidities.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10]
Explanation: Evidence states: "CONCLUSIONS Although gender may not be predictive of mortality among all infections, women appear to be at increased risk for death from hospital-acquired pneumonia, even after controlling for other comorbidities.". 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: Metastatic colorectal cancer treated with a single agent fluoropyrimidines resulted in similar efficacy and better quality of life when compared with oxaliplatin-based chemotherapy in elderly patients.

Document title: Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial

Abstract sentences:
[0] BACKGROUND Elderly and frail patients with cancer, although often treated with chemotherapy, are under-represented in clinical trials.
[1] We designed FOCUS2 to investigate reduced-dose chemotherapy options and to seek objective predictors of outcome in frail patients with advanced colorectal cancer.
[2] METHODS We undertook an open, 2 × 2 factorial trial in 61 UK centres for patients with previously untreated advanced colorectal cancer who were considered unfit for full-dose chemotherapy.
[3] After comprehensive health assessment (CHA), patients were randomly assigned by minimisation to: 48-h intravenous fluorouracil with levofolinate (group A); oxaliplatin and fluorouracil (group B); capecitabine (group C); or oxaliplatin and capecitabine (group D).
[4] Treatment allocation was not masked.
[5] Starting doses were 80% of standard doses, with discretionary escalation to full dose after 6 weeks.
[6] The two primary outcome measures were: addition of oxaliplatin ([A vs B] + [C vs D]), assessed with progression-free survival (PFS); and substitution of fluorouracil with capecitabine ([A vs C] + [B vs D]), assessed by change from baseline to 12 weeks in global quality of life (QoL).
[7] Analysis was by intention to treat.
[8] Baseline clinical and CHA data were modelled against outcomes with a novel composite measure, overall treatment utility (OTU).
[9] This study is registered, number ISRCTN21221452.
[10] FINDINGS 459 patients were randomly assigned (115 to each of groups A-C, 114 to group D).
[11] Factorial comparison of addition of oxaliplatin versus no addition suggested some improvement in PFS, but the finding was not significant (median 5·8 months [IQR 3·3-7·5] vs 4·5 months [2·8-6·4]; hazard ratio 0·84, 95% CI 0·69-1·01, p=0·07).
[12] Replacement of fluorouracil with capecitabine did not improve global QoL: 69 of 124 (56%) patients receiving fluorouracil reported improvement in global QoL compared with 69 of 123 (56%) receiving capecitabine.
[13] The risk of having any grade 3 or worse toxic effect was not significantly increased with oxaliplatin (83/219 [38%] vs 70/221 [32%]; p=0·17), but was higher with capecitabine than with fluorouracil (88/222 [40%] vs 65/218 [30%]; p=0·03).
[14] In multivariable analysis, fewer baseline symptoms (odds ratio 1·32, 95% CI 1·14-1·52), less widespread disease (1·51, 1·05-2·19), and use of oxaliplatin (0·57, 0·39-0·82) were predictive of better OTU.
[15] INTERPRETATION FOCUS2 shows that with an appropriate design, including reduced starting doses of chemotherapy, frail and elderly patients can participate in a randomised controlled trial.
[16] On balance, a combination including oxaliplatin was preferable to single-agent fluoropyrimidines, although the primary endpoint of PFS was not met.
[17] Capecitabine did not improve QoL compared with fluorouracil.
[18] Comprehensive baseline assessment holds promise as an objective predictor of treatment benefit.
[19] FUNDING Cancer Research UK and the Medical Research Council.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [16]
Explanation: Evidence states: "On balance, a combination including oxaliplatin was preferable to single-agent fluoropyrimidines, although the primary endpoint of PFS was not met.". 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: Mice are incapable of producing neutralizing antibodies in reponse to the Chikungunya virus (CHIKV) produced in mosquitos.

Document title: A chikungunya fever vaccine utilizing an insect-specific virus platform

Abstract sentences:
[0] Traditionally, vaccine development involves tradeoffs between immunogenicity and safety.
[1] Live-attenuated vaccines typically offer rapid and durable immunity but have reduced safety when compared to inactivated vaccines.
[2] In contrast, the inability of inactivated vaccines to replicate enhances safety at the expense of immunogenicity, often necessitating multiple doses and boosters.
[3] To overcome these tradeoffs, we developed the insect-specific alphavirus, Eilat virus (EILV), as a vaccine platform.
[4] To address the chikungunya fever (CHIKF) pandemic, we used an EILV cDNA clone to design a chimeric virus containing the chikungunya virus (CHIKV) structural proteins.
[5] The recombinant EILV/CHIKV was structurally identical at 10 Å to wild-type CHIKV, as determined by single-particle cryo-electron microscopy, and it mimicked the early stages of CHIKV replication in vertebrate cells from attachment and entry to viral RNA delivery.
[6] Yet the recombinant virus remained completely defective for productive replication, providing a high degree of safety.
[7] A single dose of EILV/CHIKV produced in mosquito cells elicited rapid (within 4 d) and long-lasting (>290 d) neutralizing antibodies that provided complete protection in two different mouse models.
[8] In nonhuman primates, EILV/CHIKV elicited rapid and robust immunity that protected against viremia and telemetrically monitored fever.
[9] Our EILV platform represents the first structurally native application of an insect-specific virus in preclinical vaccine development and highlights the potential application of such viruses in vaccinology.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "A single dose of EILV/CHIKV produced in mosquito cells elicited rapid (within 4 d) and long-lasting (>290 d) neutralizing antibodies that provided complete protection in two different mouse models.". 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: Mice defective for deoxyribonucleic acid (DNA) polymerase I (polI) fail to reveal increased sensitivity to ionizing radiation (IR).

Document title: Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo.

Abstract sentences:
[0] DNA polymerases mu (pol mu), lambda (pol lambda), and terminal deoxynucleotidyltransferase (TdT) are enzymes of the pol X family that share homology in sequence and functional domain organization.
[1] We showed previously that pol mu participates in light chain but surprisingly not heavy chain gene rearrangement.
[2] We show here that immunoglobulin heavy chain junctions from pol lambda-deficient animals have shorter length with normal N-additions, thus indicating that pol lambda is recruited during heavy chain rearrangement at a step that precedes the action of TdT. In contrast to previous in vitro studies, analysis of animals with combined inactivation of these enzymes revealed no overlapping or compensatory activities for V(D)J recombination between pol mu, pol lambda, and TdT. This complex usage of polymerases with distinct catalytic specificities may correspond to the specific function that the third hypervariable region assumes for each immunoglobulin chain, with pol lambda maintaining a large heavy chain junctional heterogeneity and pol mu ensuring a restricted light chain junctional variability.

[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: Mice defective for deoxyribonucleic acid (DNA) polymerase m (polm) fail to reveal increased sensitivity to ionizing radiation (IR).

Document title: Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo.

Abstract sentences:
[0] DNA polymerases mu (pol mu), lambda (pol lambda), and terminal deoxynucleotidyltransferase (TdT) are enzymes of the pol X family that share homology in sequence and functional domain organization.
[1] We showed previously that pol mu participates in light chain but surprisingly not heavy chain gene rearrangement.
[2] We show here that immunoglobulin heavy chain junctions from pol lambda-deficient animals have shorter length with normal N-additions, thus indicating that pol lambda is recruited during heavy chain rearrangement at a step that precedes the action of TdT. In contrast to previous in vitro studies, analysis of animals with combined inactivation of these enzymes revealed no overlapping or compensatory activities for V(D)J recombination between pol mu, pol lambda, and TdT. This complex usage of polymerases with distinct catalytic specificities may correspond to the specific function that the third hypervariable region assumes for each immunoglobulin chain, with pol lambda maintaining a large heavy chain junctional heterogeneity and pol mu ensuring a restricted light chain junctional variability.

[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: Mice defective for deoxyribonucleic acid (DNA) polymerase m (polm) reveal increased sensitivity to ionizing radiation (IR).

Document title: Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo.

Abstract sentences:
[0] DNA polymerases mu (pol mu), lambda (pol lambda), and terminal deoxynucleotidyltransferase (TdT) are enzymes of the pol X family that share homology in sequence and functional domain organization.
[1] We showed previously that pol mu participates in light chain but surprisingly not heavy chain gene rearrangement.
[2] We show here that immunoglobulin heavy chain junctions from pol lambda-deficient animals have shorter length with normal N-additions, thus indicating that pol lambda is recruited during heavy chain rearrangement at a step that precedes the action of TdT. In contrast to previous in vitro studies, analysis of animals with combined inactivation of these enzymes revealed no overlapping or compensatory activities for V(D)J recombination between pol mu, pol lambda, and TdT. This complex usage of polymerases with distinct catalytic specificities may correspond to the specific function that the third hypervariable region assumes for each immunoglobulin chain, with pol lambda maintaining a large heavy chain junctional heterogeneity and pol mu ensuring a restricted light chain junctional variability.

[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: Mice lacking Sirt1 in Sf1-expressing neurons are immune to diet-induced obesity and insulin resistance.

Document title: SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance.

Abstract sentences:
[0] Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions.
[1] Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance.
[2] Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure.
[3] Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle.
[4] Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin.
[5] Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity.
[6] Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [2, 3]
Explanation: Evidence states: "Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure. Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle.". 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: Mice lacking Sirt1 in Sf1-expressing neurons are immune to diet-induced obesity and insulin resistance.

Document title: SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance.

Abstract sentences:
[0] Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions.
[1] Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance.
[2] Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure.
[3] Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle.
[4] Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin.
[5] Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity.
[6] Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity.". 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: Mice lacking Sirt1 in Sf1-expressing neurons have increased susceptibility to diet-induced obesity and insulin resistance.

Document title: SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance.

Abstract sentences:
[0] Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions.
[1] Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance.
[2] Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure.
[3] Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle.
[4] Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin.
[5] Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity.
[6] Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2, 3]
Explanation: Evidence states: "Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure. Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle.". 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: Mice lacking Sirt1 in Sf1-expressing neurons have increased susceptibility to diet-induced obesity and insulin resistance.

Document title: SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance.

Abstract sentences:
[0] Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions.
[1] Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance.
[2] Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure.
[3] Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle.
[4] Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin.
[5] Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity.
[6] Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity.". 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: Mice that lack Interferon-γ or its receptor are highly susceptible to experimental autoimmune myocarditis.

Document title: the Development of Autoimmune Myocarditis in Mice by an

Abstract sentences:
[0] BACKGROUND Interleukin (IL)-12 exerts a potent proinflammatory effect by stimulating T-helper (Th) 1 responses.
[1] This effect is believed to be mediated primarily through the activation of STAT4 and subsequent production of interferon (IFN)-gamma.
[2] Methods and Results- We examined the role of IL-12 receptor (IL-12R) signaling in the development of murine experimental autoimmune myocarditis (EAM) induced by cardiac myosin immunization.
[3] Both IL-12Rbeta1-deficient mice and STAT4-deficient mice were resistant to the induction of myocarditis.
[4] Treatment with exogenous IL-12 exacerbated disease.
[5] We questioned whether IFN-gamma is required for the disease-promoting activity of IL-12.
[6] On the contrary, we found that IFN-gamma suppresses EAM.
[7] Lack of IFN-gamma due to either depletion with an antibody or a genetic deficiency exacerbated myocarditis.
[8] Spleens from IFN-gamma-deficient mice immunized with cardiac myosin showed increased cellularity; greater numbers of CD3+, CD4+, CD8+, and IL-2-producing cells; and heightened ability to produce cytokines on stimulation in vitro.
[9] Treatment of mice with recombinant IFN-gamma suppressed the development of myocarditis.
[10] CONCLUSIONS IL-12/IL-12R/STAT4 signaling promotes the development of EAM.
[11] In contrast, IFN-gamma plays a protective role.
[12] The disease-limiting effects of IFN-gamma might be explained by its ability to control the expansion of activated T lymphocytes.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "Lack of IFN-gamma due to either depletion with an antibody or a genetic deficiency exacerbated myocarditis.". 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: Mice that lack Interferon-γ or its receptor are highly susceptible to experimental autoimmune myocarditis.

Document title: the Development of Autoimmune Myocarditis in Mice by an

Abstract sentences:
[0] BACKGROUND Interleukin (IL)-12 exerts a potent proinflammatory effect by stimulating T-helper (Th) 1 responses.
[1] This effect is believed to be mediated primarily through the activation of STAT4 and subsequent production of interferon (IFN)-gamma.
[2] Methods and Results- We examined the role of IL-12 receptor (IL-12R) signaling in the development of murine experimental autoimmune myocarditis (EAM) induced by cardiac myosin immunization.
[3] Both IL-12Rbeta1-deficient mice and STAT4-deficient mice were resistant to the induction of myocarditis.
[4] Treatment with exogenous IL-12 exacerbated disease.
[5] We questioned whether IFN-gamma is required for the disease-promoting activity of IL-12.
[6] On the contrary, we found that IFN-gamma suppresses EAM.
[7] Lack of IFN-gamma due to either depletion with an antibody or a genetic deficiency exacerbated myocarditis.
[8] Spleens from IFN-gamma-deficient mice immunized with cardiac myosin showed increased cellularity; greater numbers of CD3+, CD4+, CD8+, and IL-2-producing cells; and heightened ability to produce cytokines on stimulation in vitro.
[9] Treatment of mice with recombinant IFN-gamma suppressed the development of myocarditis.
[10] CONCLUSIONS IL-12/IL-12R/STAT4 signaling promotes the development of EAM.
[11] In contrast, IFN-gamma plays a protective role.
[12] The disease-limiting effects of IFN-gamma might be explained by its ability to control the expansion of activated T lymphocytes.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [11]
Explanation: Evidence states: "In contrast, IFN-gamma plays a protective role.". 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: Mice that lack Interferon-γ or its receptor are highly susceptible to experimental autoimmune myocarditis.

Document title: Lethal autoimmune myocarditis in interferon-gamma receptor-deficient mice: enhanced disease severity by impaired inducible nitric oxide synthase induction.

Abstract sentences:
[0] BACKGROUND Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases.
[1] Little is known about its role in inflammatory heart disease.
[2] METHODS AND RESULTS We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality.
[3] Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease.
[4] The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts.
[5] Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis.
[6] CONCLUSIONS Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "METHODS AND RESULTS We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality.". 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: Mice that lack Interferon-γ or its receptor are highly susceptible to experimental autoimmune myocarditis.

Document title: Lethal autoimmune myocarditis in interferon-gamma receptor-deficient mice: enhanced disease severity by impaired inducible nitric oxide synthase induction.

Abstract sentences:
[0] BACKGROUND Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases.
[1] Little is known about its role in inflammatory heart disease.
[2] METHODS AND RESULTS We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality.
[3] Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease.
[4] The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts.
[5] Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis.
[6] CONCLUSIONS Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease.". This supports the claim.


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

Claim: Mice that lack Interferon-γ or its receptor are highly susceptible to experimental autoimmune myocarditis.

Document title: Lethal autoimmune myocarditis in interferon-gamma receptor-deficient mice: enhanced disease severity by impaired inducible nitric oxide synthase induction.

Abstract sentences:
[0] BACKGROUND Interferon-gamma (IFN-gamma) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases.
[1] Little is known about its role in inflammatory heart disease.
[2] METHODS AND RESULTS We showed that IFN-gamma receptor-deficient mice (IFN-gammaR(-/-)) on a BALB/c background immunized with a peptide derived from cardiac alpha-myosin heavy chain develop severe myocarditis with high mortality.
[3] Although myocarditis subsided in wild-type mice after 3 weeks, IFN-gammaR(-/-) mice showed persistent disease.
[4] The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-gammaR(-/-) hearts.
[5] Treatment of wild-type mice with the nitric oxide synthetase inhibitor N:-nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis.
[6] CONCLUSIONS Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "CONCLUSIONS Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.". 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: Mice without IFN-γ or its receptor are highly susceptible to EAM induced with α-MyHC/CFA.

Document title: the Development of Autoimmune Myocarditis in Mice by an

Abstract sentences:
[0] BACKGROUND Interleukin (IL)-12 exerts a potent proinflammatory effect by stimulating T-helper (Th) 1 responses.
[1] This effect is believed to be mediated primarily through the activation of STAT4 and subsequent production of interferon (IFN)-gamma.
[2] Methods and Results- We examined the role of IL-12 receptor (IL-12R) signaling in the development of murine experimental autoimmune myocarditis (EAM) induced by cardiac myosin immunization.
[3] Both IL-12Rbeta1-deficient mice and STAT4-deficient mice were resistant to the induction of myocarditis.
[4] Treatment with exogenous IL-12 exacerbated disease.
[5] We questioned whether IFN-gamma is required for the disease-promoting activity of IL-12.
[6] On the contrary, we found that IFN-gamma suppresses EAM.
[7] Lack of IFN-gamma due to either depletion with an antibody or a genetic deficiency exacerbated myocarditis.
[8] Spleens from IFN-gamma-deficient mice immunized with cardiac myosin showed increased cellularity; greater numbers of CD3+, CD4+, CD8+, and IL-2-producing cells; and heightened ability to produce cytokines on stimulation in vitro.
[9] Treatment of mice with recombinant IFN-gamma suppressed the development of myocarditis.
[10] CONCLUSIONS IL-12/IL-12R/STAT4 signaling promotes the development of EAM.
[11] In contrast, IFN-gamma plays a protective role.
[12] The disease-limiting effects of IFN-gamma might be explained by its ability to control the expansion of activated T lymphocytes.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "Lack of IFN-gamma due to either depletion with an antibody or a genetic deficiency exacerbated myocarditis.". 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: Mice without IFN-γ or its receptor are highly susceptible to EAM induced with α-MyHC/CFA.

Document title: the Development of Autoimmune Myocarditis in Mice by an

Abstract sentences:
[0] BACKGROUND Interleukin (IL)-12 exerts a potent proinflammatory effect by stimulating T-helper (Th) 1 responses.
[1] This effect is believed to be mediated primarily through the activation of STAT4 and subsequent production of interferon (IFN)-gamma.
[2] Methods and Results- We examined the role of IL-12 receptor (IL-12R) signaling in the development of murine experimental autoimmune myocarditis (EAM) induced by cardiac myosin immunization.
[3] Both IL-12Rbeta1-deficient mice and STAT4-deficient mice were resistant to the induction of myocarditis.
[4] Treatment with exogenous IL-12 exacerbated disease.
[5] We questioned whether IFN-gamma is required for the disease-promoting activity of IL-12.
[6] On the contrary, we found that IFN-gamma suppresses EAM.
[7] Lack of IFN-gamma due to either depletion with an antibody or a genetic deficiency exacerbated myocarditis.
[8] Spleens from IFN-gamma-deficient mice immunized with cardiac myosin showed increased cellularity; greater numbers of CD3+, CD4+, CD8+, and IL-2-producing cells; and heightened ability to produce cytokines on stimulation in vitro.
[9] Treatment of mice with recombinant IFN-gamma suppressed the development of myocarditis.
[10] CONCLUSIONS IL-12/IL-12R/STAT4 signaling promotes the development of EAM.
[11] In contrast, IFN-gamma plays a protective role.
[12] The disease-limiting effects of IFN-gamma might be explained by its ability to control the expansion of activated T lymphocytes.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [11]
Explanation: Evidence states: "In contrast, IFN-gamma plays a protective role.". 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: Microcin J25 encourages nucleoside triphosphate (NTP) binding.

Document title: Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel.

Abstract sentences:
[0] The antibacterial peptide microcin J25 (MccJ25) inhibits transcription by bacterial RNA polymerase (RNAP).
[1] Biochemical results indicate that inhibition of transcription occurs at the level of NTP uptake or NTP binding by RNAP.
[2] Genetic results indicate that inhibition of transcription requires an extensive determinant, comprising more than 50 amino acid residues, within the RNAP secondary channel (also known as the "NTP-uptake channel" or "pore").
[3] Biophysical results indicate that inhibition of transcription involves binding of MccJ25 within the RNAP secondary channel.
[4] Molecular modeling indicates that binding of MccJ25 within the RNAP secondary channel obstructs the RNAP secondary channel.
[5] We conclude that MccJ25 inhibits transcription by binding within and obstructing the RNAP secondary channel--acting essentially as a "cork in a bottle.
[6] "
[7] Obstruction of the RNAP secondary channel represents an attractive target for drug discovery.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Biochemical results indicate that inhibition of transcription occurs at the level of NTP uptake or NTP binding by RNAP.". 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: Microcin J25 inhibits nucleoside triphosphate (NTP) binding.

Document title: Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel.

Abstract sentences:
[0] The antibacterial peptide microcin J25 (MccJ25) inhibits transcription by bacterial RNA polymerase (RNAP).
[1] Biochemical results indicate that inhibition of transcription occurs at the level of NTP uptake or NTP binding by RNAP.
[2] Genetic results indicate that inhibition of transcription requires an extensive determinant, comprising more than 50 amino acid residues, within the RNAP secondary channel (also known as the "NTP-uptake channel" or "pore").
[3] Biophysical results indicate that inhibition of transcription involves binding of MccJ25 within the RNAP secondary channel.
[4] Molecular modeling indicates that binding of MccJ25 within the RNAP secondary channel obstructs the RNAP secondary channel.
[5] We conclude that MccJ25 inhibits transcription by binding within and obstructing the RNAP secondary channel--acting essentially as a "cork in a bottle.
[6] "
[7] Obstruction of the RNAP secondary channel represents an attractive target for drug discovery.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Biochemical results indicate that inhibition of transcription occurs at the level of NTP uptake or NTP binding by RNAP.". 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: Microglia are an innate immune cell type of the central nervous system.

Document title: Sublime Microglia: Expanding Roles for the Guardians of the CNS

Abstract sentences:
[0] Recent findings challenge the concept that microglia solely function in disease states in the central nervous system (CNS).
[1] Rather than simply reacting to CNS injury, infection, or pathology, emerging lines of evidence indicate that microglia sculpt the structure of the CNS, refine neuronal circuitry and network connectivity, and contribute to plasticity.
[2] These physiological functions of microglia in the normal CNS begin during development and persist into maturity.
[3] Here, we develop a conceptual framework for functions of microglia beyond neuroinflammation and discuss the rich repertoire of signaling and communication motifs in microglia that are critical both in pathology and for the normal physiology of the CNS.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "These physiological functions of microglia in the normal CNS begin during development and persist into maturity.". 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: Microglia are an innate immune cell type of the central nervous system.

Document title: Sublime Microglia: Expanding Roles for the Guardians of the CNS

Abstract sentences:
[0] Recent findings challenge the concept that microglia solely function in disease states in the central nervous system (CNS).
[1] Rather than simply reacting to CNS injury, infection, or pathology, emerging lines of evidence indicate that microglia sculpt the structure of the CNS, refine neuronal circuitry and network connectivity, and contribute to plasticity.
[2] These physiological functions of microglia in the normal CNS begin during development and persist into maturity.
[3] Here, we develop a conceptual framework for functions of microglia beyond neuroinflammation and discuss the rich repertoire of signaling and communication motifs in microglia that are critical both in pathology and for the normal physiology of the CNS.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Here, we develop a conceptual framework for functions of microglia beyond neuroinflammation and discuss the rich repertoire of signaling and communication motifs in microglia that are critical both in pathology and for the normal physiology of the CNS.". 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: Microglia are an innate immune cell type of the peripheral nervous system.

Document title: Sublime Microglia: Expanding Roles for the Guardians of the CNS

Abstract sentences:
[0] Recent findings challenge the concept that microglia solely function in disease states in the central nervous system (CNS).
[1] Rather than simply reacting to CNS injury, infection, or pathology, emerging lines of evidence indicate that microglia sculpt the structure of the CNS, refine neuronal circuitry and network connectivity, and contribute to plasticity.
[2] These physiological functions of microglia in the normal CNS begin during development and persist into maturity.
[3] Here, we develop a conceptual framework for functions of microglia beyond neuroinflammation and discuss the rich repertoire of signaling and communication motifs in microglia that are critical both in pathology and for the normal physiology of the CNS.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [2]
Explanation: Evidence states: "These physiological functions of microglia in the normal CNS begin during development and persist into maturity.". 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: Microglia are an innate immune cell type of the peripheral nervous system.

Document title: Sublime Microglia: Expanding Roles for the Guardians of the CNS

Abstract sentences:
[0] Recent findings challenge the concept that microglia solely function in disease states in the central nervous system (CNS).
[1] Rather than simply reacting to CNS injury, infection, or pathology, emerging lines of evidence indicate that microglia sculpt the structure of the CNS, refine neuronal circuitry and network connectivity, and contribute to plasticity.
[2] These physiological functions of microglia in the normal CNS begin during development and persist into maturity.
[3] Here, we develop a conceptual framework for functions of microglia beyond neuroinflammation and discuss the rich repertoire of signaling and communication motifs in microglia that are critical both in pathology and for the normal physiology of the CNS.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Here, we develop a conceptual framework for functions of microglia beyond neuroinflammation and discuss the rich repertoire of signaling and communication motifs in microglia that are critical both in pathology and for the normal physiology of the CNS.". 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: Migraine with aura is associated with ischemic stroke.

Document title: Migraine and cardiovascular disease: systematic review and meta-analysis.

Abstract sentences:
[0] OBJECTIVE To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease.
[1] DESIGN Systematic review and meta-analysis.
[2] DATA SOURCES Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009.
[3] Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease.
[4] Review methods Two investigators independently assessed eligibility of identified studies in a two step approach.
[5] Disagreements were resolved by consensus.
[6] Studies were grouped according to a priori categories on migraine and cardiovascular disease.
[7] DATA EXTRACTION Two investigators extracted data.
[8] Pooled relative risks and 95% confidence intervals were calculated.
[9] RESULTS Studies were heterogeneous for participant characteristics and definition of cardiovascular disease.
[10] Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29).
[11] Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02).
[12] Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11).
[13] Age less than 45 years, smoking, and oral contraceptive use further increased the risk.
[14] Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34).
[15] Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk.
[16] CONCLUSION Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura.
[17] Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives.
[18] We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease.
[19] Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [11]
Explanation: Evidence states: "Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02).". 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: Migraine with aura is associated with ischemic stroke.

Document title: Migraine and cardiovascular disease: systematic review and meta-analysis.

Abstract sentences:
[0] OBJECTIVE To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease.
[1] DESIGN Systematic review and meta-analysis.
[2] DATA SOURCES Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009.
[3] Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease.
[4] Review methods Two investigators independently assessed eligibility of identified studies in a two step approach.
[5] Disagreements were resolved by consensus.
[6] Studies were grouped according to a priori categories on migraine and cardiovascular disease.
[7] DATA EXTRACTION Two investigators extracted data.
[8] Pooled relative risks and 95% confidence intervals were calculated.
[9] RESULTS Studies were heterogeneous for participant characteristics and definition of cardiovascular disease.
[10] Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29).
[11] Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02).
[12] Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11).
[13] Age less than 45 years, smoking, and oral contraceptive use further increased the risk.
[14] Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34).
[15] Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk.
[16] CONCLUSION Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura.
[17] Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives.
[18] We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease.
[19] Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [16]
Explanation: Evidence states: "CONCLUSION Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura.". 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: Misunderstandings between doctors and patients can lead to non-adherence.

Document title: Misunderstandings in prescribing decisions in general practice: qualitative study.

Abstract sentences:
[0] OBJECTIVES To identify and describe misunderstandings between patients and doctors associated with prescribing decisions in general practice.
[1] DESIGN Qualitative study.
[2] SETTING 20 general practices in the West Midlands and south east England.
[3] PARTICIPANTS 20 general practitioners and 35 consulting patients.
[4] MAIN OUTCOME MEASURES Misunderstandings between patients and doctors that have potential or actual adverse consequences for taking medicine.
[5] RESULTS 14 categories of misunderstanding were identified relating to patient information unknown to the doctor, doctor information unknown to the patient, conflicting information, disagreement about attribution of side effects, failure of communication about doctor's decision, and relationship factors.
[6] All the misunderstandings were associated with lack of patients' participation in the consultation in terms of the voicing of expectations and preferences or the voicing of responses to doctors' decisions and actions.
[7] They were all associated with potential or actual adverse outcomes such as non-adherence to treatment.
[8] Many were based on inaccurate guesses and assumptions.
[9] In particular doctors seemed unaware of the relevance of patients' ideas about medicines for successful prescribing.
[10] CONCLUSIONS Patients' participation in the consultation and the adverse consequences of lack of participation are important.
[11] The authors are developing an educational intervention that builds on these findings.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6, 7]
Explanation: Evidence states: "All the misunderstandings were associated with lack of patients' participation in the consultation in terms of the voicing of expectations and preferences or the voicing of responses to doctors' decisions and actions. They were all associated with potential or actual adverse outcomes such as non-adherence to treatment.". 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: Mitochondria play a major role in apoptosis.

Document title: Mitochondria: Dynamic Organelles in Disease, Aging, and Development

Abstract sentences:
[0] Mitochondria are the primary energy-generating system in most eukaryotic cells.
[1] Additionally, they participate in intermediary metabolism, calcium signaling, and apoptosis.
[2] Given these well-established functions, it might be expected that mitochondrial dysfunction would give rise to a simple and predictable set of defects in all tissues.
[3] However, mitochondrial dysfunction has pleiotropic effects in multicellular organisms.
[4] Clearly, much about the basic biology of mitochondria remains to be understood.
[5] Here we discuss recent work that suggests that the dynamics (fusion and fission) of these organelles is important in development and disease.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Additionally, they participate in intermediary metabolism, calcium signaling, and apoptosis.". 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: Mitochondria play a major role in energy production.

Document title: Mitochondria: Dynamic Organelles in Disease, Aging, and Development

Abstract sentences:
[0] Mitochondria are the primary energy-generating system in most eukaryotic cells.
[1] Additionally, they participate in intermediary metabolism, calcium signaling, and apoptosis.
[2] Given these well-established functions, it might be expected that mitochondrial dysfunction would give rise to a simple and predictable set of defects in all tissues.
[3] However, mitochondrial dysfunction has pleiotropic effects in multicellular organisms.
[4] Clearly, much about the basic biology of mitochondria remains to be understood.
[5] Here we discuss recent work that suggests that the dynamics (fusion and fission) of these organelles is important in development and disease.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "Mitochondria are the primary energy-generating system in most eukaryotic cells.". This supports the claim.


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

Claim: Mitochondria play a trivial role in calcium homeostasis.

Document title: Mitochondria: Dynamic Organelles in Disease, Aging, and Development

Abstract sentences:
[0] Mitochondria are the primary energy-generating system in most eukaryotic cells.
[1] Additionally, they participate in intermediary metabolism, calcium signaling, and apoptosis.
[2] Given these well-established functions, it might be expected that mitochondrial dysfunction would give rise to a simple and predictable set of defects in all tissues.
[3] However, mitochondrial dysfunction has pleiotropic effects in multicellular organisms.
[4] Clearly, much about the basic biology of mitochondria remains to be understood.
[5] Here we discuss recent work that suggests that the dynamics (fusion and fission) of these organelles is important in development and disease.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Additionally, they participate in intermediary metabolism, calcium signaling, and apoptosis.". 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: Moderate consumption of candy and chocolate reduces the risk of cardiovascular disease (CVD).

Document title: Life is sweet: candy consumption and longevity.

Abstract sentences:
[0] Our attitude towards candy—“if it tastes that good, it can't be healthy”—betrays society's puritanical stance towards pleasure.
[1] Candy has been blamed for various ills, including hyperactivity in children; however, clinical trials have not supported this.1  Candy—sugar confectionery and chocolate—is not a recent invention: the ancient Arabs, Chinese, and Egyptians candied fruits and nuts in honey, and the Aztecs made a chocolate drink from the bean of the cacao tree.
[2] Today, Americans gratify themselves with, on average, 5.4 kg of sugar candy and 6.5 kg of chocolate per person annually.2  Since candy has existed for centuries, we surmised that it cannot be totally unhealthy.
[3] We decided to investigate whether candy consumption was associated with longevity.
[4] Subjects were from the Harvard alumni health study, an ongoing study of men entering Harvard University as undergraduates between 1916 and 1950.
[5] We included 7841 men, free of cardiovascular disease and cancer, who responded to a health survey …

[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: Monoclonal antibody targeting of N-cadherin encourages castration resistance.

Document title: Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance

Abstract sentences:
[0] The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology.
[1] Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC.
[2] Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis.
[3] Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro.
[4] In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression.
[5] N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion.
[6] These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance.
[7] Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion.". 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: Monoclonal antibody targeting of N-cadherin encourages metastasis.

Document title: Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance

Abstract sentences:
[0] The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology.
[1] Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC.
[2] Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis.
[3] Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro.
[4] In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression.
[5] N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion.
[6] These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance.
[7] Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression.". 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: Monoclonal antibody targeting of N-cadherin encourages metastasis.

Document title: Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance

Abstract sentences:
[0] The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology.
[1] Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC.
[2] Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis.
[3] Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro.
[4] In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression.
[5] N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion.
[6] These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance.
[7] Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.". 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: Monoclonal antibody targeting of N-cadherin inhibits castration resistance.

Document title: Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance

Abstract sentences:
[0] The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology.
[1] Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC.
[2] Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis.
[3] Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro.
[4] In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression.
[5] N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion.
[6] These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance.
[7] Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion.". 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: Monoclonal antibody targeting of N-cadherin inhibits growth.

Document title: Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance

Abstract sentences:
[0] The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology.
[1] Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC.
[2] Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis.
[3] Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro.
[4] In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression.
[5] N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion.
[6] These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance.
[7] Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro.". 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: Most termination events in Okazaki fragments are dictated by initiation patterns.

Document title: Quantitative, genome-wide analysis of eukaryotic replication initiation and termination.

Abstract sentences:
[0] Many fundamental aspects of DNA replication, such as the exact locations where DNA synthesis is initiated and terminated, how frequently origins are used, and how fork progression is influenced by transcription, are poorly understood.
[1] Via the deep sequencing of Okazaki fragments, we comprehensively document replication fork directionality throughout the S. cerevisiae genome, which permits the systematic analysis of initiation, origin efficiency, fork progression, and termination.
[2] We show that leading-strand initiation preferentially occurs within a nucleosome-free region at replication origins.
[3] Using a strain in which late origins can be induced to fire early, we show that replication termination is a largely passive phenomenon that does not rely on cis-acting sequences or replication fork pausing.
[4] The replication profile is predominantly determined by the kinetics of origin firing, allowing us to reconstruct chromosome-wide timing profiles from an asynchronous culture.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "The replication profile is predominantly determined by the kinetics of origin firing, allowing us to reconstruct chromosome-wide timing profiles from an asynchronous culture.". 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: Mouse models can be generated using "artificial spermatids."

Document title: Generation of Genetically Modified Mice by Oocyte Injection of Androgenetic Haploid Embryonic Stem Cells

Abstract sentences:
[0] Haploid cells are amenable for genetic analysis.
[1] Recent success in the derivation of mouse haploid embryonic stem cells (haESCs) via parthenogenesis has enabled genetic screening in mammalian cells.
[2] However, successful generation of live animals from these haESCs, which is needed to extend the genetic analysis to the organism level, has not been achieved.
[3] Here, we report the derivation of haESCs from androgenetic blastocysts.
[4] These cells, designated as AG-haESCs, partially maintain paternal imprints, express classical ESC pluripotency markers, and contribute to various tissues, including the germline, upon injection into diploid blastocysts.
[5] Strikingly, live mice can be obtained upon injection of AG-haESCs into MII oocytes, and these mice bear haESC-carried genetic traits and develop into fertile adults.
[6] Furthermore, gene targeting via homologous recombination is feasible in the AG-haESCs.
[7] Our results demonstrate that AG-haESCs can be used as a genetically tractable fertilization agent for the production of live animals via injection into oocytes.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Strikingly, live mice can be obtained upon injection of AG-haESCs into MII oocytes, and these mice bear haESC-carried genetic traits and develop into fertile adults.". 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: Mutant mice lacking SVCT2 have severely reduced ascorbic acid levels in both brain and adrenals.

Document title: Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival

Abstract sentences:
[0] The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy, presumably because it is a cofactor for hydroxylases required for post-translational modifications that stabilize collagen.
[1] We have created mice deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of a rat ascorbic-acid transporter, Svct2 (ref.
[2] 4).
[3] Cultured embryonic fibroblasts from homozygous Slc23a1−/− mice had less than 5% of normal ascorbic-acid uptake.
[4] Ascorbic-acid levels were undetectable or markedly reduced in the blood and tissues of Slc23a1−/− mice.
[5] Prenatal supplementation of pregnant females did not elevate blood ascorbic acid in Slc23a1−/− fetuses, suggesting Slc23a1 is important in placental ascorbic-acid transport.
[6] Slc23a1−/− mice died within a few minutes of birth with respiratory failure and intraparenchymal brain hemorrhage.
[7] Lungs showed no postnatal expansion but had normal surfactant protein B levels.
[8] Brain hemorrhage was unlikely to be simply a form of scurvy since Slc23a1−/− mice showed no hemorrhage in any other tissues and their skin had normal skin 4-hydroxyproline levels despite low ascorbic-acid content.
[9] We conclude that Slc23a1 is required for transport of ascorbic acid into many tissues and across the placenta.
[10] Deficiency of the transporter is lethal in newborn mice, thereby revealing a previously unrecognized requirement for ascorbic acid in the perinatal period.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4, 6]
Explanation: Evidence states: "Ascorbic-acid levels were undetectable or markedly reduced in the blood and tissues of Slc23a1−/− mice. Slc23a1−/− mice died within a few minutes of birth with respiratory failure and intraparenchymal brain hemorrhage.". 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: Mutant mice lacking SVCT2 have severely reduced ascorbic acid levels in both brain and adrenals.

Document title: Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival

Abstract sentences:
[0] The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy, presumably because it is a cofactor for hydroxylases required for post-translational modifications that stabilize collagen.
[1] We have created mice deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of a rat ascorbic-acid transporter, Svct2 (ref.
[2] 4).
[3] Cultured embryonic fibroblasts from homozygous Slc23a1−/− mice had less than 5% of normal ascorbic-acid uptake.
[4] Ascorbic-acid levels were undetectable or markedly reduced in the blood and tissues of Slc23a1−/− mice.
[5] Prenatal supplementation of pregnant females did not elevate blood ascorbic acid in Slc23a1−/− fetuses, suggesting Slc23a1 is important in placental ascorbic-acid transport.
[6] Slc23a1−/− mice died within a few minutes of birth with respiratory failure and intraparenchymal brain hemorrhage.
[7] Lungs showed no postnatal expansion but had normal surfactant protein B levels.
[8] Brain hemorrhage was unlikely to be simply a form of scurvy since Slc23a1−/− mice showed no hemorrhage in any other tissues and their skin had normal skin 4-hydroxyproline levels despite low ascorbic-acid content.
[9] We conclude that Slc23a1 is required for transport of ascorbic acid into many tissues and across the placenta.
[10] Deficiency of the transporter is lethal in newborn mice, thereby revealing a previously unrecognized requirement for ascorbic acid in the perinatal period.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "Brain hemorrhage was unlikely to be simply a form of scurvy since Slc23a1−/− mice showed no hemorrhage in any other tissues and their skin had normal skin 4-hydroxyproline levels despite low ascorbic-acid content.". This supports the claim.