[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: Suboptimal nutrition is a leading cause of premature death

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [13]
Explanation: Evidence states: "In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]).". 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: Suboptimal nutrition is a leading cause of premature death

Document title: The state of US health, 1990-2010: burden of diseases, injuries, and risk factors.

Abstract sentences:
[0] IMPORTANCE Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy.
[1] OBJECTIVES To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries.
[2] DESIGN We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries.
[3] Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age.
[4] Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health.
[5] Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs.
[6] Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs.
[7] Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages.
[8] RESULTS US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years.
[9] The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury.
[10] Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls.
[11] The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders.
[12] As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs.
[13] The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use.
[14] Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th.
[15] CONCLUSIONS AND RELEVANCE From 1990 to 2010, the United States made substantial progress in improving health.
[16] Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable.
[17] However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [13]
Explanation: Evidence states: "The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use.". 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: Sudden death can occur in patients with complex ventricular arrhythmias.

Document title: Myocardial muscarinic receptor upregulation and normal response to isoproterenol in denervated hearts by familial amyloid polyneuropathy.

Abstract sentences:
[0] BACKGROUND Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy.
[1] The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia.
[2] Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated.
[3] METHODS AND RESULTS Twenty-one patients were studied (age, 39+/-11 years; normal coronary arteries; left ventricular ejection fraction 68+/-9%).
[4] To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with (11)C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used.
[5] Cardiac beta-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step).
[6] The mean muscarinic receptor density was higher in patients than in control subjects (B'(max), 35.5+/-8.9 versus 26.1+/-6.7 pmol/mL, P=0.003), without change in receptor affinity.
[7] The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (DeltaHR after atropine, 11+/-21% versus 62+/-17%; P<0.001), consistent with parasympathetic denervation.
[8] Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects.
[9] CONCLUSIONS Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac beta-receptor responsiveness to catecholamines.

[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: Sudden death can occur in patients with orthostatic hypertension without cardiac conduction abnormalities.

Document title: Myocardial muscarinic receptor upregulation and normal response to isoproterenol in denervated hearts by familial amyloid polyneuropathy.

Abstract sentences:
[0] BACKGROUND Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy.
[1] The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia.
[2] Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated.
[3] METHODS AND RESULTS Twenty-one patients were studied (age, 39+/-11 years; normal coronary arteries; left ventricular ejection fraction 68+/-9%).
[4] To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with (11)C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used.
[5] Cardiac beta-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step).
[6] The mean muscarinic receptor density was higher in patients than in control subjects (B'(max), 35.5+/-8.9 versus 26.1+/-6.7 pmol/mL, P=0.003), without change in receptor affinity.
[7] The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (DeltaHR after atropine, 11+/-21% versus 62+/-17%; P<0.001), consistent with parasympathetic denervation.
[8] Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects.
[9] CONCLUSIONS Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac beta-receptor responsiveness to catecholamines.

[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: Surfactin producing cells and exopolymer producing cells cooperate to generate "Van Gogh" bundles that have sliding abilities on specialized media.

Document title: From Cell Differentiation to Cell Collectives: Bacillus subtilis Uses Division of Labor to Migrate

Abstract sentences:
[0] The organization of cells, emerging from cell-cell interactions, can give rise to collective properties.
[1] These properties are adaptive when together cells can face environmental challenges that they separately cannot.
[2] One particular challenge that is important for microorganisms is migration.
[3] In this study, we show how flagellum-independent migration is driven by the division of labor of two cell types that appear during Bacillus subtilis sliding motility.
[4] Cell collectives organize themselves into bundles (called "van Gogh bundles") of tightly aligned cell chains that form filamentous loops at the colony edge.
[5] We show, by time-course microscopy, that these loops migrate by pushing themselves away from the colony.
[6] The formation of van Gogh bundles depends critically on the synergistic interaction of surfactin-producing and matrix-producing cells.
[7] We propose that surfactin-producing cells reduce the friction between cells and their substrate, thereby facilitating matrix-producing cells to form bundles.
[8] The folding properties of these bundles determine the rate of colony expansion.
[9] Our study illustrates how the simple organization of cells within a community can yield a strong ecological advantage.
[10] This is a key factor underlying the diverse origins of multicellularity.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "The formation of van Gogh bundles depends critically on the synergistic interaction of surfactin-producing and matrix-producing 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: Surfactin producing cells and exopolymer producing cells cooperate to generate "Van Gogh" bundles that have sliding abilities on specialized media.

Document title: From Cell Differentiation to Cell Collectives: Bacillus subtilis Uses Division of Labor to Migrate

Abstract sentences:
[0] The organization of cells, emerging from cell-cell interactions, can give rise to collective properties.
[1] These properties are adaptive when together cells can face environmental challenges that they separately cannot.
[2] One particular challenge that is important for microorganisms is migration.
[3] In this study, we show how flagellum-independent migration is driven by the division of labor of two cell types that appear during Bacillus subtilis sliding motility.
[4] Cell collectives organize themselves into bundles (called "van Gogh bundles") of tightly aligned cell chains that form filamentous loops at the colony edge.
[5] We show, by time-course microscopy, that these loops migrate by pushing themselves away from the colony.
[6] The formation of van Gogh bundles depends critically on the synergistic interaction of surfactin-producing and matrix-producing cells.
[7] We propose that surfactin-producing cells reduce the friction between cells and their substrate, thereby facilitating matrix-producing cells to form bundles.
[8] The folding properties of these bundles determine the rate of colony expansion.
[9] Our study illustrates how the simple organization of cells within a community can yield a strong ecological advantage.
[10] This is a key factor underlying the diverse origins of multicellularity.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "We propose that surfactin-producing cells reduce the friction between cells and their substrate, thereby facilitating matrix-producing cells to form bundles.". 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: Surgical treatment is not superior to non-surgical in treating adults with displaced fractures of the proximal humerus.

Document title: Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial.

Abstract sentences:
[0] IMPORTANCE The need for surgery for the majority of patients with displaced proximal humeral fractures is unclear, but its use is increasing.
[1] OBJECTIVE To evaluate the clinical effectiveness of surgical vs nonsurgical treatment for adults with displaced fractures of the proximal humerus involving the surgical neck.
[2] DESIGN, SETTING, AND PARTICIPANTS A pragmatic, multicenter, parallel-group, randomized clinical trial, the Proximal Fracture of the Humerus Evaluation by Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older (mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%] were white) who presented at the orthopedic departments of 32 acute UK National Health Service hospitals between September 2008 and April 2011 within 3 weeks after sustaining a displaced fracture of the proximal humerus involving the surgical neck.
[3] Patients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data.
[4] The data for 231 patients (114 in surgical group and 117 in nonsurgical group) were included in the primary analysis.
[5] INTERVENTIONS Fracture fixation or humeral head replacement were performed by surgeons experienced in these techniques.
[6] Nonsurgical treatment was sling immobilization.
[7] Standardized outpatient and community-based rehabilitation was provided to both groups.
[8] MAIN OUTCOMES AND MEASURES Primary outcome was the Oxford Shoulder Score (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year period, with assessment and data collection at 6, 12, and 24 months.
[9] Sample size was based on a minimal clinically important difference of 5 points for the Oxford Shoulder Score.
[10] Secondary outcomes were the Short-Form 12 (SF-12), complications, subsequent therapy, and mortality.
[11] RESULTS There was no significant mean treatment group difference in the Oxford Shoulder Score averaged over 2 years (39.07 points for the surgical group vs 38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at individual time points.
[12] There were also no significant between-group differences over 2 years in the mean SF-12 physical component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39 points];
[13] P = .18); the mean SF-12 mental component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to surgery or shoulder fracture (30 patients in surgical group vs 23 patients in nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11 patients in both groups), and increased or new shoulder-related therapy (7 patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27).
[14] Ten medical complications (2 cardiovascular events, 2 respiratory events, 2 gastrointestinal events, and 4 others) occurred in the surgical group during the postoperative hospital stay.
[15] CONCLUSIONS AND RELEVANCE Among patients with displaced proximal humeral fractures involving the surgical neck, there was no significant difference between surgical treatment compared with nonsurgical treatment in patient-reported clinical outcomes over 2 years following fracture occurrence.
[16] These results do not support the trend of increased surgery for patients with displaced fractures of the proximal humerus.
[17] TRIAL REGISTRATION isrctn.com Identifier: ISRCTN50850043.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [11]
Explanation: Evidence states: "RESULTS There was no significant mean treatment group difference in the Oxford Shoulder Score averaged over 2 years (39.07 points for the surgical group vs 38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at individual time points.". 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: Surgical treatment is not superior to non-surgical in treating adults with displaced fractures of the proximal humerus.

Document title: Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial.

Abstract sentences:
[0] IMPORTANCE The need for surgery for the majority of patients with displaced proximal humeral fractures is unclear, but its use is increasing.
[1] OBJECTIVE To evaluate the clinical effectiveness of surgical vs nonsurgical treatment for adults with displaced fractures of the proximal humerus involving the surgical neck.
[2] DESIGN, SETTING, AND PARTICIPANTS A pragmatic, multicenter, parallel-group, randomized clinical trial, the Proximal Fracture of the Humerus Evaluation by Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older (mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%] were white) who presented at the orthopedic departments of 32 acute UK National Health Service hospitals between September 2008 and April 2011 within 3 weeks after sustaining a displaced fracture of the proximal humerus involving the surgical neck.
[3] Patients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data.
[4] The data for 231 patients (114 in surgical group and 117 in nonsurgical group) were included in the primary analysis.
[5] INTERVENTIONS Fracture fixation or humeral head replacement were performed by surgeons experienced in these techniques.
[6] Nonsurgical treatment was sling immobilization.
[7] Standardized outpatient and community-based rehabilitation was provided to both groups.
[8] MAIN OUTCOMES AND MEASURES Primary outcome was the Oxford Shoulder Score (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year period, with assessment and data collection at 6, 12, and 24 months.
[9] Sample size was based on a minimal clinically important difference of 5 points for the Oxford Shoulder Score.
[10] Secondary outcomes were the Short-Form 12 (SF-12), complications, subsequent therapy, and mortality.
[11] RESULTS There was no significant mean treatment group difference in the Oxford Shoulder Score averaged over 2 years (39.07 points for the surgical group vs 38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at individual time points.
[12] There were also no significant between-group differences over 2 years in the mean SF-12 physical component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39 points];
[13] P = .18); the mean SF-12 mental component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to surgery or shoulder fracture (30 patients in surgical group vs 23 patients in nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11 patients in both groups), and increased or new shoulder-related therapy (7 patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27).
[14] Ten medical complications (2 cardiovascular events, 2 respiratory events, 2 gastrointestinal events, and 4 others) occurred in the surgical group during the postoperative hospital stay.
[15] CONCLUSIONS AND RELEVANCE Among patients with displaced proximal humeral fractures involving the surgical neck, there was no significant difference between surgical treatment compared with nonsurgical treatment in patient-reported clinical outcomes over 2 years following fracture occurrence.
[16] These results do not support the trend of increased surgery for patients with displaced fractures of the proximal humerus.
[17] TRIAL REGISTRATION isrctn.com Identifier: ISRCTN50850043.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [12]
Explanation: Evidence states: "There were also no significant between-group differences over 2 years in the mean SF-12 physical component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39 points];". 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: Surgical treatment is not superior to non-surgical in treating adults with displaced fractures of the proximal humerus.

Document title: Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial.

Abstract sentences:
[0] IMPORTANCE The need for surgery for the majority of patients with displaced proximal humeral fractures is unclear, but its use is increasing.
[1] OBJECTIVE To evaluate the clinical effectiveness of surgical vs nonsurgical treatment for adults with displaced fractures of the proximal humerus involving the surgical neck.
[2] DESIGN, SETTING, AND PARTICIPANTS A pragmatic, multicenter, parallel-group, randomized clinical trial, the Proximal Fracture of the Humerus Evaluation by Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older (mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%] were white) who presented at the orthopedic departments of 32 acute UK National Health Service hospitals between September 2008 and April 2011 within 3 weeks after sustaining a displaced fracture of the proximal humerus involving the surgical neck.
[3] Patients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data.
[4] The data for 231 patients (114 in surgical group and 117 in nonsurgical group) were included in the primary analysis.
[5] INTERVENTIONS Fracture fixation or humeral head replacement were performed by surgeons experienced in these techniques.
[6] Nonsurgical treatment was sling immobilization.
[7] Standardized outpatient and community-based rehabilitation was provided to both groups.
[8] MAIN OUTCOMES AND MEASURES Primary outcome was the Oxford Shoulder Score (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year period, with assessment and data collection at 6, 12, and 24 months.
[9] Sample size was based on a minimal clinically important difference of 5 points for the Oxford Shoulder Score.
[10] Secondary outcomes were the Short-Form 12 (SF-12), complications, subsequent therapy, and mortality.
[11] RESULTS There was no significant mean treatment group difference in the Oxford Shoulder Score averaged over 2 years (39.07 points for the surgical group vs 38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at individual time points.
[12] There were also no significant between-group differences over 2 years in the mean SF-12 physical component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39 points];
[13] P = .18); the mean SF-12 mental component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to surgery or shoulder fracture (30 patients in surgical group vs 23 patients in nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11 patients in both groups), and increased or new shoulder-related therapy (7 patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27).
[14] Ten medical complications (2 cardiovascular events, 2 respiratory events, 2 gastrointestinal events, and 4 others) occurred in the surgical group during the postoperative hospital stay.
[15] CONCLUSIONS AND RELEVANCE Among patients with displaced proximal humeral fractures involving the surgical neck, there was no significant difference between surgical treatment compared with nonsurgical treatment in patient-reported clinical outcomes over 2 years following fracture occurrence.
[16] These results do not support the trend of increased surgery for patients with displaced fractures of the proximal humerus.
[17] TRIAL REGISTRATION isrctn.com Identifier: ISRCTN50850043.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [13]
Explanation: Evidence states: "P = .18); the mean SF-12 mental component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to surgery or shoulder fracture (30 patients in surgical group vs 23 patients in nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11 patients in both groups), and increased or new shoulder-related therapy (7 patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27).". 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: Surgical treatment is not superior to non-surgical in treating adults with displaced fractures of the proximal humerus.

Document title: Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial.

Abstract sentences:
[0] IMPORTANCE The need for surgery for the majority of patients with displaced proximal humeral fractures is unclear, but its use is increasing.
[1] OBJECTIVE To evaluate the clinical effectiveness of surgical vs nonsurgical treatment for adults with displaced fractures of the proximal humerus involving the surgical neck.
[2] DESIGN, SETTING, AND PARTICIPANTS A pragmatic, multicenter, parallel-group, randomized clinical trial, the Proximal Fracture of the Humerus Evaluation by Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older (mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%] were white) who presented at the orthopedic departments of 32 acute UK National Health Service hospitals between September 2008 and April 2011 within 3 weeks after sustaining a displaced fracture of the proximal humerus involving the surgical neck.
[3] Patients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data.
[4] The data for 231 patients (114 in surgical group and 117 in nonsurgical group) were included in the primary analysis.
[5] INTERVENTIONS Fracture fixation or humeral head replacement were performed by surgeons experienced in these techniques.
[6] Nonsurgical treatment was sling immobilization.
[7] Standardized outpatient and community-based rehabilitation was provided to both groups.
[8] MAIN OUTCOMES AND MEASURES Primary outcome was the Oxford Shoulder Score (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year period, with assessment and data collection at 6, 12, and 24 months.
[9] Sample size was based on a minimal clinically important difference of 5 points for the Oxford Shoulder Score.
[10] Secondary outcomes were the Short-Form 12 (SF-12), complications, subsequent therapy, and mortality.
[11] RESULTS There was no significant mean treatment group difference in the Oxford Shoulder Score averaged over 2 years (39.07 points for the surgical group vs 38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at individual time points.
[12] There were also no significant between-group differences over 2 years in the mean SF-12 physical component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39 points];
[13] P = .18); the mean SF-12 mental component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to surgery or shoulder fracture (30 patients in surgical group vs 23 patients in nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11 patients in both groups), and increased or new shoulder-related therapy (7 patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27).
[14] Ten medical complications (2 cardiovascular events, 2 respiratory events, 2 gastrointestinal events, and 4 others) occurred in the surgical group during the postoperative hospital stay.
[15] CONCLUSIONS AND RELEVANCE Among patients with displaced proximal humeral fractures involving the surgical neck, there was no significant difference between surgical treatment compared with nonsurgical treatment in patient-reported clinical outcomes over 2 years following fracture occurrence.
[16] These results do not support the trend of increased surgery for patients with displaced fractures of the proximal humerus.
[17] TRIAL REGISTRATION isrctn.com Identifier: ISRCTN50850043.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [15]
Explanation: Evidence states: "CONCLUSIONS AND RELEVANCE Among patients with displaced proximal humeral fractures involving the surgical neck, there was no significant difference between surgical treatment compared with nonsurgical treatment in patient-reported clinical outcomes over 2 years following fracture occurrence.". 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: Sweet taste receptors on the tongue are deactivated by between 1 and 10 mM glucose.

Document title: Detection of sweet and umami taste in the absence of taste receptor T1r3.

Abstract sentences:
[0] The tastes of sugars (sweet) and glutamate (umami) are thought to be detected by T1r receptors expressed in taste cells.
[1] Molecular genetics and heterologous expression implicate T1r2 plus T1r3 as a sweet-responsive receptor,and T1r1 plus T1r3,as well as a truncated form of the type 4 metabotropic glutamate receptor (taste-mGluR4),as umami-responsive receptors.
[2] Here,we show that mice lacking T1r3 showed no preference for artificial sweeteners and had diminished but not abolished behavioral and nerve responses to sugars and umami compounds.
[3] These results indicate that T1r3-independent sweet- and umami-responsive receptors and/or pathways exist in taste cells.

[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: Sympathetic nerve activity is elevated throughout normal pregnancy.

Document title: Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans.

Abstract sentences:
[0] BACKGROUND Direct recordings from peripheral sympathetic nerves have shown an increased sympathetic drive in pregnancy-induced hypertension (PIH) and preeclampsia (PE).
[1] It is unknown whether sympathetic drive is altered in normal pregnancy, when arterial blood pressure can be normal or relatively low.
[2] The aim of this study was to measure and compare peripheral sympathetic discharge, its vasoconstrictor effect and its baroreceptor control, during pregnancy and postpartum in women with normal pregnancy (NP) and PIH and in normotensive nonpregnant (NN) women.
[3] METHODS AND RESULTS Twenty-one women with NP, 18 women with PIH, and 21 NN women had muscle sympathetic nerve activity assessed from multiunit discharges (MSNA) and from single units with defined vasoconstrictor properties (s-MSNA).
[4] The s-MSNA in NP (38+/-6.6 impulses/100 beats) was greater (P<0.05) than in NN women (19+/-1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women (P<0.001) (146+/-23.5 impulses/100 beats).
[5] MSNA followed a similar trend.
[6] Cardiac baroreceptor reflex sensitivity (BRS) was impaired in NP and PIH women relative to NN.
[7] After delivery, sympathetic activity decreased to values similar to those obtained in NN, and there was an increase in BRS.
[8] In women with NP, the decrease in sympathetic output occurred despite an insignificant change in blood pressure.
[9] CONCLUSIONS Central sympathetic output was increased in women with normal pregnancy and was even greater in the hypertensive pregnant group.
[10] The findings suggest that the moderate sympathetic hyperactivity during the latter months of normal pregnancy may help to return the arterial pressure to nonpregnant levels, although when the increase in activity is excessive, hypertension may ensue.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "The s-MSNA in NP (38+/-6.6 impulses/100 beats) was greater (P<0.05) than in NN women (19+/-1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women (P<0.001) (146+/-23.5 impulses/100 beats).". 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: Sympathetic nerve activity is elevated throughout normal pregnancy.

Document title: Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans.

Abstract sentences:
[0] BACKGROUND Direct recordings from peripheral sympathetic nerves have shown an increased sympathetic drive in pregnancy-induced hypertension (PIH) and preeclampsia (PE).
[1] It is unknown whether sympathetic drive is altered in normal pregnancy, when arterial blood pressure can be normal or relatively low.
[2] The aim of this study was to measure and compare peripheral sympathetic discharge, its vasoconstrictor effect and its baroreceptor control, during pregnancy and postpartum in women with normal pregnancy (NP) and PIH and in normotensive nonpregnant (NN) women.
[3] METHODS AND RESULTS Twenty-one women with NP, 18 women with PIH, and 21 NN women had muscle sympathetic nerve activity assessed from multiunit discharges (MSNA) and from single units with defined vasoconstrictor properties (s-MSNA).
[4] The s-MSNA in NP (38+/-6.6 impulses/100 beats) was greater (P<0.05) than in NN women (19+/-1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women (P<0.001) (146+/-23.5 impulses/100 beats).
[5] MSNA followed a similar trend.
[6] Cardiac baroreceptor reflex sensitivity (BRS) was impaired in NP and PIH women relative to NN.
[7] After delivery, sympathetic activity decreased to values similar to those obtained in NN, and there was an increase in BRS.
[8] In women with NP, the decrease in sympathetic output occurred despite an insignificant change in blood pressure.
[9] CONCLUSIONS Central sympathetic output was increased in women with normal pregnancy and was even greater in the hypertensive pregnant group.
[10] The findings suggest that the moderate sympathetic hyperactivity during the latter months of normal pregnancy may help to return the arterial pressure to nonpregnant levels, although when the increase in activity is excessive, hypertension may ensue.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "The findings suggest that the moderate sympathetic hyperactivity during the latter months of normal pregnancy may help to return the arterial pressure to nonpregnant levels, although when the increase in activity is excessive, hypertension may ensue.". 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: Sympathetic nerve activity is elevated throughout normal pregnancy.

Document title: Sympathetic baroreflex gain in normotensive pregnant women.

Abstract sentences:
[0] Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting.
[1] We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls.
[2] Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)).
[3] Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls.
[4] Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy.
[5] Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03).
[6] Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2).
[7] However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02).
[8] Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting.". 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: Sympathetic nerve activity is elevated throughout normal pregnancy.

Document title: Sympathetic baroreflex gain in normotensive pregnant women.

Abstract sentences:
[0] Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting.
[1] We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls.
[2] Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)).
[3] Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls.
[4] Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy.
[5] Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03).
[6] Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2).
[7] However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02).
[8] Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls.". 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: Sympathetic nerve activity is elevated throughout normal pregnancy.

Document title: Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women.

Abstract sentences:
[0] Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation.
[1] We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls.
[2] Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001).
[3] Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls.
[4] Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04).
[5] However, neurovascular transduction during peak cold pressor-induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006).
[6] Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation.
[7] These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls.". 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: Sympathetic nerve activity is elevated throughout normal pregnancy.

Document title: Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women.

Abstract sentences:
[0] Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation.
[1] We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls.
[2] Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001).
[3] Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls.
[4] Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04).
[5] However, neurovascular transduction during peak cold pressor-induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006).
[6] Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation.
[7] These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04).". 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: Sympathetic nerve activity is reduced throughout normal pregnancy.

Document title: Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans.

Abstract sentences:
[0] BACKGROUND Direct recordings from peripheral sympathetic nerves have shown an increased sympathetic drive in pregnancy-induced hypertension (PIH) and preeclampsia (PE).
[1] It is unknown whether sympathetic drive is altered in normal pregnancy, when arterial blood pressure can be normal or relatively low.
[2] The aim of this study was to measure and compare peripheral sympathetic discharge, its vasoconstrictor effect and its baroreceptor control, during pregnancy and postpartum in women with normal pregnancy (NP) and PIH and in normotensive nonpregnant (NN) women.
[3] METHODS AND RESULTS Twenty-one women with NP, 18 women with PIH, and 21 NN women had muscle sympathetic nerve activity assessed from multiunit discharges (MSNA) and from single units with defined vasoconstrictor properties (s-MSNA).
[4] The s-MSNA in NP (38+/-6.6 impulses/100 beats) was greater (P<0.05) than in NN women (19+/-1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women (P<0.001) (146+/-23.5 impulses/100 beats).
[5] MSNA followed a similar trend.
[6] Cardiac baroreceptor reflex sensitivity (BRS) was impaired in NP and PIH women relative to NN.
[7] After delivery, sympathetic activity decreased to values similar to those obtained in NN, and there was an increase in BRS.
[8] In women with NP, the decrease in sympathetic output occurred despite an insignificant change in blood pressure.
[9] CONCLUSIONS Central sympathetic output was increased in women with normal pregnancy and was even greater in the hypertensive pregnant group.
[10] The findings suggest that the moderate sympathetic hyperactivity during the latter months of normal pregnancy may help to return the arterial pressure to nonpregnant levels, although when the increase in activity is excessive, hypertension may ensue.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "The s-MSNA in NP (38+/-6.6 impulses/100 beats) was greater (P<0.05) than in NN women (19+/-1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women (P<0.001) (146+/-23.5 impulses/100 beats).". 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: Sympathetic nerve activity is reduced throughout normal pregnancy.

Document title: Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans.

Abstract sentences:
[0] BACKGROUND Direct recordings from peripheral sympathetic nerves have shown an increased sympathetic drive in pregnancy-induced hypertension (PIH) and preeclampsia (PE).
[1] It is unknown whether sympathetic drive is altered in normal pregnancy, when arterial blood pressure can be normal or relatively low.
[2] The aim of this study was to measure and compare peripheral sympathetic discharge, its vasoconstrictor effect and its baroreceptor control, during pregnancy and postpartum in women with normal pregnancy (NP) and PIH and in normotensive nonpregnant (NN) women.
[3] METHODS AND RESULTS Twenty-one women with NP, 18 women with PIH, and 21 NN women had muscle sympathetic nerve activity assessed from multiunit discharges (MSNA) and from single units with defined vasoconstrictor properties (s-MSNA).
[4] The s-MSNA in NP (38+/-6.6 impulses/100 beats) was greater (P<0.05) than in NN women (19+/-1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women (P<0.001) (146+/-23.5 impulses/100 beats).
[5] MSNA followed a similar trend.
[6] Cardiac baroreceptor reflex sensitivity (BRS) was impaired in NP and PIH women relative to NN.
[7] After delivery, sympathetic activity decreased to values similar to those obtained in NN, and there was an increase in BRS.
[8] In women with NP, the decrease in sympathetic output occurred despite an insignificant change in blood pressure.
[9] CONCLUSIONS Central sympathetic output was increased in women with normal pregnancy and was even greater in the hypertensive pregnant group.
[10] The findings suggest that the moderate sympathetic hyperactivity during the latter months of normal pregnancy may help to return the arterial pressure to nonpregnant levels, although when the increase in activity is excessive, hypertension may ensue.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10]
Explanation: Evidence states: "The findings suggest that the moderate sympathetic hyperactivity during the latter months of normal pregnancy may help to return the arterial pressure to nonpregnant levels, although when the increase in activity is excessive, hypertension may ensue.". 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: Sympathetic nerve activity is reduced throughout normal pregnancy.

Document title: Sympathetic baroreflex gain in normotensive pregnant women.

Abstract sentences:
[0] Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting.
[1] We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls.
[2] Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)).
[3] Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls.
[4] Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy.
[5] Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03).
[6] Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2).
[7] However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02).
[8] Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [0]
Explanation: Evidence states: "Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting.". 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: Sympathetic nerve activity is reduced throughout normal pregnancy.

Document title: Sympathetic baroreflex gain in normotensive pregnant women.

Abstract sentences:
[0] Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting.
[1] We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls.
[2] Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)).
[3] Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls.
[4] Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy.
[5] Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03).
[6] Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2).
[7] However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02).
[8] Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls.". 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: Sympathetic nerve activity is reduced throughout normal pregnancy.

Document title: Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women.

Abstract sentences:
[0] Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation.
[1] We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls.
[2] Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001).
[3] Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls.
[4] Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04).
[5] However, neurovascular transduction during peak cold pressor-induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006).
[6] Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation.
[7] These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls.". 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: Sympathetic nerve activity is reduced throughout normal pregnancy.

Document title: Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women.

Abstract sentences:
[0] Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation.
[1] We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls.
[2] Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001).
[3] Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls.
[4] Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04).
[5] However, neurovascular transduction during peak cold pressor-induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006).
[6] Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation.
[7] These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04).". 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: Systemic immunosuppressive (IS) therapy does not enhance the chance of cancer mortality in patients with inflammatory eye disease (IED)

Document title: Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study.

Abstract sentences:
[0] CONTEXT Whether immunosuppressive treatment adversely affects survival is unclear.
[1] OBJECTIVE To assess whether immunosuppressive drugs increase mortality.
[2] DESIGN Retrospective cohort study evaluating overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases.
[3] Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage.
[4] The cohort's mortality risk was compared with US vital statistics using standardised mortality ratios.
[5] Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis.
[6] SETTING Five tertiary ocular inflammation clinics.
[7] Patients 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up.
[8] Exposures Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors.
[9] MAIN OUTCOME MEASURES Overall mortality, cancer mortality.
[10] RESULTS Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/100 person years), 230 (24.6%) from cancer.
[11] For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population.
[12] Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs.
[13] In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased.
[14] Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01).
[15] CONCLUSIONS Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality.
[16] Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [12]
Explanation: Evidence states: "Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs.". This supports the claim.


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

Claim: Systemic immunosuppressive (IS) therapy does not enhance the chance of cancer mortality in patients with inflammatory eye disease (IED)

Document title: Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study.

Abstract sentences:
[0] CONTEXT Whether immunosuppressive treatment adversely affects survival is unclear.
[1] OBJECTIVE To assess whether immunosuppressive drugs increase mortality.
[2] DESIGN Retrospective cohort study evaluating overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases.
[3] Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage.
[4] The cohort's mortality risk was compared with US vital statistics using standardised mortality ratios.
[5] Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis.
[6] SETTING Five tertiary ocular inflammation clinics.
[7] Patients 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up.
[8] Exposures Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors.
[9] MAIN OUTCOME MEASURES Overall mortality, cancer mortality.
[10] RESULTS Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/100 person years), 230 (24.6%) from cancer.
[11] For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population.
[12] Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs.
[13] In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased.
[14] Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01).
[15] CONCLUSIONS Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality.
[16] Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [15]
Explanation: Evidence states: "CONCLUSIONS Most commonly used immunosuppressive drugs do not seem to increase overall or cancer 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: Systemic immunosuppressive (IS) therapy increases the chance of cancer mortality in patients with inflammatory eye disease (IED)

Document title: Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study.

Abstract sentences:
[0] CONTEXT Whether immunosuppressive treatment adversely affects survival is unclear.
[1] OBJECTIVE To assess whether immunosuppressive drugs increase mortality.
[2] DESIGN Retrospective cohort study evaluating overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases.
[3] Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage.
[4] The cohort's mortality risk was compared with US vital statistics using standardised mortality ratios.
[5] Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis.
[6] SETTING Five tertiary ocular inflammation clinics.
[7] Patients 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up.
[8] Exposures Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors.
[9] MAIN OUTCOME MEASURES Overall mortality, cancer mortality.
[10] RESULTS Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/100 person years), 230 (24.6%) from cancer.
[11] For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population.
[12] Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs.
[13] In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased.
[14] Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01).
[15] CONCLUSIONS Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality.
[16] Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [12]
Explanation: Evidence states: "Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs.". 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: Systemic immunosuppressive (IS) therapy increases the chance of cancer mortality in patients with inflammatory eye disease (IED)

Document title: Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study.

Abstract sentences:
[0] CONTEXT Whether immunosuppressive treatment adversely affects survival is unclear.
[1] OBJECTIVE To assess whether immunosuppressive drugs increase mortality.
[2] DESIGN Retrospective cohort study evaluating overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases.
[3] Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage.
[4] The cohort's mortality risk was compared with US vital statistics using standardised mortality ratios.
[5] Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis.
[6] SETTING Five tertiary ocular inflammation clinics.
[7] Patients 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up.
[8] Exposures Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors.
[9] MAIN OUTCOME MEASURES Overall mortality, cancer mortality.
[10] RESULTS Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/100 person years), 230 (24.6%) from cancer.
[11] For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population.
[12] Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs.
[13] In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased.
[14] Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01).
[15] CONCLUSIONS Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality.
[16] Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [15]
Explanation: Evidence states: "CONCLUSIONS Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality.". 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: Systemic lupus erythematosus is a risk factor for cardiovascular disease.

Document title: Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study

Abstract sentences:
[0] Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors.
[1] Design Prospective open cohort study.
[2] Setting General practices in England providing data for the QResearch database.
[3] Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores.
[4] 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort.
[5] Patients were free of cardiovascular disease and not prescribed statins at baseline.
[6] Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years.
[7] Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs).
[8] We also considered erectile dysfunction diagnosis or treatment in men.
[9] Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status.
[10] Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records.
[11] Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation.
[12] All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant.
[13] The models had good calibration and high levels of explained variation and discrimination.
[14] In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination).
[15] The corresponding values for men were 54.8%, 2.26, and 0.86.
[16] Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms.
[17] Conclusion Updated QRISK3 risk prediction models were developed and validated.
[18] The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs).". 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: T cell receptor /CD3 microdomains are required to induce the immunologic synapse.

Document title: Full activation of the T cell receptor requires both clustering and conformational changes at CD3.

Abstract sentences:
[0] T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits.
[1] The mechanism by which TCRalphabeta ligand binding confers conformational changes to CD3 is unknown.
[2] By using well-defined ligands, we showed that induction of the conformational change requires both multivalent engagement and the mobility restriction of the TCR-CD3 imposed by the plasma membrane.
[3] The conformational change is elicited by cooperative rearrangements of two TCR-CD3 complexes and does not require accompanying changes in the structure of the TCRalphabeta ectodomains.
[4] This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation.
[5] Thus, our permissive geometry model provides a molecular mechanism that rationalizes how the information of ligand binding to TCRalphabeta is transmitted to the CD3 subunits and to the intracellular signaling machinery.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits.". 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: T cell receptor /CD3 microdomains are required to induce the immunologic synapse.

Document title: Full activation of the T cell receptor requires both clustering and conformational changes at CD3.

Abstract sentences:
[0] T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits.
[1] The mechanism by which TCRalphabeta ligand binding confers conformational changes to CD3 is unknown.
[2] By using well-defined ligands, we showed that induction of the conformational change requires both multivalent engagement and the mobility restriction of the TCR-CD3 imposed by the plasma membrane.
[3] The conformational change is elicited by cooperative rearrangements of two TCR-CD3 complexes and does not require accompanying changes in the structure of the TCRalphabeta ectodomains.
[4] This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation.
[5] Thus, our permissive geometry model provides a molecular mechanism that rationalizes how the information of ligand binding to TCRalphabeta is transmitted to the CD3 subunits and to the intracellular signaling machinery.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation.". 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: TMEM27 is a marker for beta cells.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Here, we report the identification and characterization of transmembrane protein 27 (Tmem27, collectrin) in pancreatic beta cells.". This supports the claim.


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

Claim: TMEM27 is a marker for beta cells.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "This cleavage process is beta cell specific and does not occur in other cell types.". 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: TMEM27 is a marker for beta cells.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Furthermore, transgenic mice with increased expression of Tmem27 in pancreatic beta cells exhibit increased beta cell mass.". 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: TNFAIP3 is a glioblastoma tumor enhancer.

Document title: Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth

Abstract sentences:
[0] Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioblastoma stem cells (GSCs).
[1] GSCs are regulated by molecular pathways distinct from the bulk tumor that may be useful therapeutic targets.
[2] We determined that A20 (TNFAIP3), a regulator of cell survival and the NF-kappaB pathway, is overexpressed in GSCs relative to non-stem glioblastoma cells at both the mRNA and protein levels.
[3] To determine the functional significance of A20 in GSCs, we targeted A20 expression with lentiviral-mediated delivery of short hairpin RNA (shRNA).
[4] Inhibiting A20 expression decreased GSC growth and survival through mechanisms associated with decreased cell-cycle progression and decreased phosphorylation of p65/RelA. Elevated levels of A20 in GSCs contributed to apoptotic resistance: GSCs were less susceptible to TNFalpha-induced cell death than matched non-stem glioma cells, but A20 knockdown sensitized GSCs to TNFalpha-mediated apoptosis.
[5] The decreased survival of GSCs upon A20 knockdown contributed to the reduced ability of these cells to self-renew in primary and secondary neurosphere formation assays.
[6] The tumorigenic potential of GSCs was decreased with A20 targeting, resulting in increased survival of mice bearing human glioma xenografts.
[7] In silico analysis of a glioma patient genomic database indicates that A20 overexpression and amplification is inversely correlated with survival.
[8] Together these data indicate that A20 contributes to glioma maintenance through effects on the glioma stem cell subpopulation.
[9] Although inactivating mutations in A20 in lymphoma suggest A20 can act as a tumor suppressor, similar point mutations have not been identified through glioma genomic sequencing: in fact, our data suggest A20 may function as a tumor enhancer in glioma through promotion of GSC survival.
[10] A20 anticancer therapies should therefore be viewed with caution as effects will likely differ depending on the tumor type.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Inhibiting A20 expression decreased GSC growth and survival through mechanisms associated with decreased cell-cycle progression and decreased phosphorylation of p65/RelA. Elevated levels of A20 in GSCs contributed to apoptotic resistance: GSCs were less susceptible to TNFalpha-induced cell death than matched non-stem glioma cells, but A20 knockdown sensitized GSCs to TNFalpha-mediated apoptosis.". This supports the claim.