[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: Obesity decreases life quality.

Document title: Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies.

Abstract sentences:
[0] BACKGROUND The main associations of body-mass index (BMI) with overall and cause-specific mortality can best be assessed by long-term prospective follow-up of large numbers of people.
[1] The Prospective Studies Collaboration aimed to investigate these associations by sharing data from many studies.
[2] METHODS Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospective studies with 894 576 participants, mostly in western Europe and North America (61% [n=541 452] male, mean recruitment age 46 [SD 11] years, median recruitment year 1979 [IQR 1975-85], mean BMI 25 [SD 4] kg/m(2)).
[3] The analyses were adjusted for age, sex, smoking status, and study.
[4] To limit reverse causality, the first 5 years of follow-up were excluded, leaving 66 552 deaths of known cause during a mean of 8 (SD 6) further years of follow-up (mean age at death 67 [SD 10] years): 30 416 vascular; 2070 diabetic, renal or hepatic; 22 592 neoplastic; 3770 respiratory; 7704 other.
[5] FINDINGS In both sexes, mortality was lowest at about 22.5-25 kg/m(2).
[6] Above this range, positive associations were recorded for several specific causes and inverse associations for none, the absolute excess risks for higher BMI and smoking were roughly additive, and each 5 kg/m(2) higher BMI was on average associated with about 30% higher overall mortality (hazard ratio per 5 kg/m(2) [HR] 1.29 [95% CI 1.27-1.32]): 40% for vascular mortality (HR 1.41 [1.37-1.45]); 60-120% for diabetic, renal, and hepatic mortality (HRs 2.16 [1.89-2.46], 1.59 [1.27-1.99], and 1.82 [1.59-2.09], respectively); 10% for neoplastic mortality (HR 1.10 [1.06-1.15]); and 20% for respiratory and for all other mortality (HRs 1.20 [1.07-1.34] and 1.20 [1.16-1.25], respectively).
[7] Below the range 22.5-25 kg/m(2), BMI was associated inversely with overall mortality, mainly because of strong inverse associations with respiratory disease and lung cancer.
[8] These inverse associations were much stronger for smokers than for non-smokers, despite cigarette consumption per smoker varying little with BMI.
[9] INTERPRETATION Although other anthropometric measures (eg, waist circumference, waist-to-hip ratio) could well add extra information to BMI, and BMI to them, BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22.5-25 kg/m(2).
[10] The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal.
[11] At 30-35 kg/m(2), median survival is reduced by 2-4 years; at 40-45 kg/m(2), it is reduced by 8-10 years (which is comparable with the effects of smoking).
[12] The definite excess mortality below 22.5 kg/m(2) is due mainly to smoking-related diseases, and is not fully explained.

[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: Obesity is determined solely by environmental factors.

Document title: Genetics of obesity in adult adoptees and their biological siblings.

Abstract sentences:
[0] An adoption study of genetic effects on obesity in adulthood was carried out in which adoptees separated from their natural parents very early in life were compared with their biological full and half siblings reared by their natural parents.
[1] The adoptees represented four groups who by sampling from a larger population were categorised as either thin, medium weight, overweight, or obese.
[2] Weight and height were obtained for 115 full siblings of 57 adoptees and for 850 half siblings of 341 adoptees.
[3] In full siblings body mass index (kg/m2) significantly increased with weight of the adoptees.
[4] Body mass index of the half siblings showed a steady but weaker increase across the four weight groups of adoptees.
[5] There were no significant interactions with sex of the adoptees, sex of the siblings, or (for the half siblings) sex of the common parent.
[6] In contrast with the findings in half siblings and (previously) the natural parents there was a striking, significant increase in body mass index between full siblings of overweight and obese adoptees.
[7] The degree of fatness in adults living in the same environment appears to be influenced by genetic factors independent of sex, which may include polygenic as well as major gene effects on obesity.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3, 4]
Explanation: Evidence states: "In full siblings body mass index (kg/m2) significantly increased with weight of the adoptees. Body mass index of the half siblings showed a steady but weaker increase across the four weight groups of adoptees.". 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: Obesity is determined solely by environmental factors.

Document title: Genetics of obesity in adult adoptees and their biological siblings.

Abstract sentences:
[0] An adoption study of genetic effects on obesity in adulthood was carried out in which adoptees separated from their natural parents very early in life were compared with their biological full and half siblings reared by their natural parents.
[1] The adoptees represented four groups who by sampling from a larger population were categorised as either thin, medium weight, overweight, or obese.
[2] Weight and height were obtained for 115 full siblings of 57 adoptees and for 850 half siblings of 341 adoptees.
[3] In full siblings body mass index (kg/m2) significantly increased with weight of the adoptees.
[4] Body mass index of the half siblings showed a steady but weaker increase across the four weight groups of adoptees.
[5] There were no significant interactions with sex of the adoptees, sex of the siblings, or (for the half siblings) sex of the common parent.
[6] In contrast with the findings in half siblings and (previously) the natural parents there was a striking, significant increase in body mass index between full siblings of overweight and obese adoptees.
[7] The degree of fatness in adults living in the same environment appears to be influenced by genetic factors independent of sex, which may include polygenic as well as major gene effects on obesity.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [6]
Explanation: Evidence states: "In contrast with the findings in half siblings and (previously) the natural parents there was a striking, significant increase in body mass index between full siblings of overweight and obese adoptees.". 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: Obesity is determined solely by environmental factors.

Document title: Genetics of obesity in adult adoptees and their biological siblings.

Abstract sentences:
[0] An adoption study of genetic effects on obesity in adulthood was carried out in which adoptees separated from their natural parents very early in life were compared with their biological full and half siblings reared by their natural parents.
[1] The adoptees represented four groups who by sampling from a larger population were categorised as either thin, medium weight, overweight, or obese.
[2] Weight and height were obtained for 115 full siblings of 57 adoptees and for 850 half siblings of 341 adoptees.
[3] In full siblings body mass index (kg/m2) significantly increased with weight of the adoptees.
[4] Body mass index of the half siblings showed a steady but weaker increase across the four weight groups of adoptees.
[5] There were no significant interactions with sex of the adoptees, sex of the siblings, or (for the half siblings) sex of the common parent.
[6] In contrast with the findings in half siblings and (previously) the natural parents there was a striking, significant increase in body mass index between full siblings of overweight and obese adoptees.
[7] The degree of fatness in adults living in the same environment appears to be influenced by genetic factors independent of sex, which may include polygenic as well as major gene effects on obesity.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "The degree of fatness in adults living in the same environment appears to be influenced by genetic factors independent of sex, which may include polygenic as well as major gene effects on obesity.". 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: Obesity is determined solely by environmental factors.

Document title: Familial obesity and leanness.

Abstract sentences:
[0] Using the Princeton School District Family Study cohort, our specific aim was to estimate the prevalence of suspected familial ponderosity and leanness, to provide empirical risk estimates for the proportion of probands' first-degree relatives who were similarly affected, and to estimate the contributions of diseases, drugs and caloric intake to relative obesity and leanness.
[1] We studied 379 probands, 125 whites and 52 blacks from a random recall group, 147 whites and 55 blacks from a hyperlipidemic recall group.
[2] Suspected familial obesity and leanness were arbitrarily identified in those kindreds with at least two first-degree relatives in the same Quetelet index decile as the proband, top or bottom respectively.
[3] Suspected familial obesity was observed in 2.4 percent and 6 percent respectively of random and hyperlipidemic recall group whites.
[4] Suspected familial leanness was identified in 2.4 percent and 1.4 percent of random and hyperlipidemic recall whites and in 3.8 percent of randomly recalled blacks.
[5] Approximately twice as many as expected white first-degree relatives of top Quetelet index decile probands themselves had top decile Quetelet indices; approximately three times as many as expected first-degree relatives of bottom decile Quetelet index probands themselves had bottom decile Quetelet indices.
[6] Nineteen percent and 31 percent of top decile Quetelet index white probands from random and hyperlipidemic recall groups came from families where at least two other first-degree relatives were similarly obese; 18 percent and 20 percent of white random and hyperlipidemic recall group probands with bottom decile Quetelet indices had suspected familial leanness.
[7] Nearly all subjects with familial obesity or leanness had no overt metabolic or pharmacological explanations for their body habitus.
[8] Within-family clustering of hypertension was common in kindreds with suspected familial obesity and was absent in kindreds with suspected familial leanness.
[9] Marked within-family clustering of both obesity and leanness is useful diagnostically; therapeutic intervention to reduce obesity, to be most effective, should be family-wide in the many kindreds which share familial obesity.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Suspected familial obesity was observed in 2.4 percent and 6 percent respectively of random and hyperlipidemic recall group whites.". 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: Obesity is determined solely by environmental factors.

Document title: Familial obesity and leanness.

Abstract sentences:
[0] Using the Princeton School District Family Study cohort, our specific aim was to estimate the prevalence of suspected familial ponderosity and leanness, to provide empirical risk estimates for the proportion of probands' first-degree relatives who were similarly affected, and to estimate the contributions of diseases, drugs and caloric intake to relative obesity and leanness.
[1] We studied 379 probands, 125 whites and 52 blacks from a random recall group, 147 whites and 55 blacks from a hyperlipidemic recall group.
[2] Suspected familial obesity and leanness were arbitrarily identified in those kindreds with at least two first-degree relatives in the same Quetelet index decile as the proband, top or bottom respectively.
[3] Suspected familial obesity was observed in 2.4 percent and 6 percent respectively of random and hyperlipidemic recall group whites.
[4] Suspected familial leanness was identified in 2.4 percent and 1.4 percent of random and hyperlipidemic recall whites and in 3.8 percent of randomly recalled blacks.
[5] Approximately twice as many as expected white first-degree relatives of top Quetelet index decile probands themselves had top decile Quetelet indices; approximately three times as many as expected first-degree relatives of bottom decile Quetelet index probands themselves had bottom decile Quetelet indices.
[6] Nineteen percent and 31 percent of top decile Quetelet index white probands from random and hyperlipidemic recall groups came from families where at least two other first-degree relatives were similarly obese; 18 percent and 20 percent of white random and hyperlipidemic recall group probands with bottom decile Quetelet indices had suspected familial leanness.
[7] Nearly all subjects with familial obesity or leanness had no overt metabolic or pharmacological explanations for their body habitus.
[8] Within-family clustering of hypertension was common in kindreds with suspected familial obesity and was absent in kindreds with suspected familial leanness.
[9] Marked within-family clustering of both obesity and leanness is useful diagnostically; therapeutic intervention to reduce obesity, to be most effective, should be family-wide in the many kindreds which share familial obesity.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "Nearly all subjects with familial obesity or leanness had no overt metabolic or pharmacological explanations for their body habitus.". 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: Obesity is determined solely by environmental factors.

Document title: The body-mass index of twins who have been reared apart.

Abstract sentences:
[0] To assess the relative importance of genetic and environmental effects on the body-mass index (weight in kilograms divided by the square of the height in meters), we studied samples of identical and fraternal twins, reared apart or reared together.
[1] The samples consisted of 93 pairs of identical twins reared apart, 154 pairs of identical twins reared together, 218 pairs of fraternal twins reared apart, and 208 pairs of fraternal twins reared together.
[2] The intrapair correlation coefficients of the values for body-mass index of identical twins reared apart were 0.70 for men and 0.66 for women.
[3] These are the most direct estimates of the relative importance of genetic influences (heritability) on the body-mass index, and they were only slightly lower than those for twins reared together in this and earlier studies.
[4] Similar estimates were derived from maximum-likelihood model-fitting analyses--0.74 for men and 0.69 for women.
[5] Nonadditive genetic variance made a significant contribution to the estimates of heritability, particularly among men.
[6] Of the potential environmental influences, only those unique to the individual and not those shared by family members were important, contributing about 30 percent of the variance.
[7] Sharing the same childhood environment did not contribute to the similarity of the body-mass index of twins later in life.
[8] We conclude that genetic influences on body-mass index are substantial, whereas the childhood environment has little or no influence.
[9] These findings corroborate and extend the results of earlier studies of twins and adoptees.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [8]
Explanation: Evidence states: "We conclude that genetic influences on body-mass index are substantial, whereas the childhood environment has little or no influence.". 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: Obesity is determined solely by environmental factors.

Document title: An adoption study of human obesity.

Abstract sentences:
[0] We examined the contributions of genetic factors and the family environment to human fatness in a sample of 540 adult Danish adoptees who were selected from a population of 3580 and divided into four weight classes: thin, median weight, overweight, and obese.
[1] There was a strong relation between the weight class of the adoptees and the body-mass index of their biologic parents - for the mothers, P less than 0.0001; for the fathers, P less than 0.02.
[2] There was no relation between the weight class of the adoptees and the body-mass index of their adoptive parents.
[3] Cumulative distributions of the body-mass index of parents showed similar results; there was a strong relation between the body-mass index of biologic parents and adoptee weight class and no relation between the index of adoptive parents and adoptee weight class.
[4] Furthermore, the relation between biologic parents and adoptees was not confined to the obesity weight class, but was present across the whole range of body fatness - from very thin to very fat.
[5] We conclude that genetic influences have an important role in determining human fatness in adults, whereas the family environment alone has no apparent effect.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [1]
Explanation: Evidence states: "There was a strong relation between the weight class of the adoptees and the body-mass index of their biologic parents - for the mothers, P less than 0.0001; for the fathers, P less than 0.02.". 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: Obesity is determined solely by environmental factors.

Document title: An adoption study of human obesity.

Abstract sentences:
[0] We examined the contributions of genetic factors and the family environment to human fatness in a sample of 540 adult Danish adoptees who were selected from a population of 3580 and divided into four weight classes: thin, median weight, overweight, and obese.
[1] There was a strong relation between the weight class of the adoptees and the body-mass index of their biologic parents - for the mothers, P less than 0.0001; for the fathers, P less than 0.02.
[2] There was no relation between the weight class of the adoptees and the body-mass index of their adoptive parents.
[3] Cumulative distributions of the body-mass index of parents showed similar results; there was a strong relation between the body-mass index of biologic parents and adoptee weight class and no relation between the index of adoptive parents and adoptee weight class.
[4] Furthermore, the relation between biologic parents and adoptees was not confined to the obesity weight class, but was present across the whole range of body fatness - from very thin to very fat.
[5] We conclude that genetic influences have an important role in determining human fatness in adults, whereas the family environment alone has no apparent effect.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Cumulative distributions of the body-mass index of parents showed similar results; there was a strong relation between the body-mass index of biologic parents and adoptee weight class and no relation between the index of adoptive parents and adoptee weight class.". 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: Obesity is determined solely by environmental factors.

Document title: An adoption study of human obesity.

Abstract sentences:
[0] We examined the contributions of genetic factors and the family environment to human fatness in a sample of 540 adult Danish adoptees who were selected from a population of 3580 and divided into four weight classes: thin, median weight, overweight, and obese.
[1] There was a strong relation between the weight class of the adoptees and the body-mass index of their biologic parents - for the mothers, P less than 0.0001; for the fathers, P less than 0.02.
[2] There was no relation between the weight class of the adoptees and the body-mass index of their adoptive parents.
[3] Cumulative distributions of the body-mass index of parents showed similar results; there was a strong relation between the body-mass index of biologic parents and adoptee weight class and no relation between the index of adoptive parents and adoptee weight class.
[4] Furthermore, the relation between biologic parents and adoptees was not confined to the obesity weight class, but was present across the whole range of body fatness - from very thin to very fat.
[5] We conclude that genetic influences have an important role in determining human fatness in adults, whereas the family environment alone has no apparent effect.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "We conclude that genetic influences have an important role in determining human fatness in adults, whereas the family environment alone has no apparent effect.". 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: Obesity is determined solely by environmental factors.

Document title: Genetic analysis of human obesity in an Italian sample.

Abstract sentences:
[0] An analysis of the genetic factors in obesity has been carried out on a sample of nuclear families from Aosta (N. Italy).
[1] The families consisted of the parents and sibs of all elementary school children considered to be obese during a preliminary screening and a similar sample of non-obese children and their nuclear families.
[2] The numbers of such families were 67 and 112, respectively.
[3] Several tests were applied in order to examine the genetic contribution to obesity, and in particular to investigate the presence of a dominant major gene.
[4] Our conclusions are that genetic factors are certainly present.
[5] Several analyses suggest the presence of a dominant major gene with weak effect.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Our conclusions are that genetic factors are certainly present.". 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: Obesity is determined solely by environmental factors.

Document title: Genetic analysis of human obesity in an Italian sample.

Abstract sentences:
[0] An analysis of the genetic factors in obesity has been carried out on a sample of nuclear families from Aosta (N. Italy).
[1] The families consisted of the parents and sibs of all elementary school children considered to be obese during a preliminary screening and a similar sample of non-obese children and their nuclear families.
[2] The numbers of such families were 67 and 112, respectively.
[3] Several tests were applied in order to examine the genetic contribution to obesity, and in particular to investigate the presence of a dominant major gene.
[4] Our conclusions are that genetic factors are certainly present.
[5] Several analyses suggest the presence of a dominant major gene with weak effect.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Several analyses suggest the presence of a dominant major gene with weak effect.". 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: Occupancy of ribosomes by IncRNAs do not make functional peptides.

Document title: Ribosome Profiling Provides Evidence that Large Noncoding RNAs Do Not Encode Proteins

Abstract sentences:
[0] Large noncoding RNAs are emerging as an important component in cellular regulation.
[1] Considerable evidence indicates that these transcripts act directly as functional RNAs rather than through an encoded protein product.
[2] However, a recent study of ribosome occupancy reported that many large intergenic ncRNAs (lincRNAs) are bound by ribosomes, raising the possibility that they are translated into proteins.
[3] Here, we show that classical noncoding RNAs and 5' UTRs show the same ribosome occupancy as lincRNAs, demonstrating that ribosome occupancy alone is not sufficient to classify transcripts as coding or noncoding.
[4] Instead, we define a metric based on the known property of translation whereby translating ribosomes are released upon encountering a bona fide stop codon.
[5] We show that this metric accurately discriminates between protein-coding transcripts and all classes of known noncoding transcripts, including lincRNAs.
[6] Taken together, these results argue that the large majority of lincRNAs do not function through encoded proteins.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Here, we show that classical noncoding RNAs and 5' UTRs show the same ribosome occupancy as lincRNAs, demonstrating that ribosome occupancy alone is not sufficient to classify transcripts as coding or noncoding.". 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: Occupancy of ribosomes by IncRNAs mirror 5 0-UTRs

Document title: Ribosome Profiling Provides Evidence that Large Noncoding RNAs Do Not Encode Proteins

Abstract sentences:
[0] Large noncoding RNAs are emerging as an important component in cellular regulation.
[1] Considerable evidence indicates that these transcripts act directly as functional RNAs rather than through an encoded protein product.
[2] However, a recent study of ribosome occupancy reported that many large intergenic ncRNAs (lincRNAs) are bound by ribosomes, raising the possibility that they are translated into proteins.
[3] Here, we show that classical noncoding RNAs and 5' UTRs show the same ribosome occupancy as lincRNAs, demonstrating that ribosome occupancy alone is not sufficient to classify transcripts as coding or noncoding.
[4] Instead, we define a metric based on the known property of translation whereby translating ribosomes are released upon encountering a bona fide stop codon.
[5] We show that this metric accurately discriminates between protein-coding transcripts and all classes of known noncoding transcripts, including lincRNAs.
[6] Taken together, these results argue that the large majority of lincRNAs do not function through encoded proteins.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Here, we show that classical noncoding RNAs and 5' UTRs show the same ribosome occupancy as lincRNAs, demonstrating that ribosome occupancy alone is not sufficient to classify transcripts as coding or noncoding.". 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: Omnivores produce less trimethylamine N-oxide from dietary I-carnitine than vegetarians.

Document title: Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

Abstract sentences:
[0] Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO).
[1] We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice.
[2] Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism.
[3] The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status.
[4] Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels.
[5] Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed.
[6] In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport.
[7] Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism.". 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: Only a minority of cells survive development after differentiation into stress-resistant spores.

Document title: Exploitative and Hierarchical Antagonism in a Cooperative Bacterium

Abstract sentences:
[0] Social organisms that cooperate with some members of their own species, such as close relatives, may fail to cooperate with other genotypes of the same species.
[1] Such noncooperation may take the form of outright antagonism or social exploitation.
[2] Myxococcus xanthus is a highly social prokaryote that cooperatively develops into spore-bearing, multicellular fruiting bodies in response to starvation.
[3] Here we have characterized the nature of social interactions among nine developmentally proficient strains of M. xanthus isolated from spatially distant locations.
[4] Strains were competed against one another in all possible pairwise combinations during starvation-induced development.
[5] In most pairings, at least one competitor exhibited strong antagonism toward its partner and a majority of mixes showed bidirectional antagonism that decreased total spore production, even to the point of driving whole populations to extinction.
[6] Differential response to mixing was the primary determinant of competitive superiority rather than the sporulation efficiencies of unmixed populations.
[7] In some competitive pairings, the dominant partner sporulated more efficiently in mixed populations than in clonal isolation.
[8] This finding represents a novel form of exploitation in bacteria carried out by socially competent genotypes and is the first documentation of social exploitation among natural bacterial isolates.
[9] Patterns of antagonistic superiority among these strains form a highly linear dominance hierarchy.
[10] At least some competition pairs construct chimeric, rather than segregated, fruiting bodies.
[11] The cooperative prokaryote M. xanthus has diverged into a large number of distinct social types that cooperate with clone-mates but exhibit intense antagonism toward distinct social types of the same species.
[12] Most lengthy migration events in nature may thus result in strong antagonism between migratory and resident populations, and this antagonism may have large effects on local population sizes and dynamics.
[13] Intense mutual antagonism appears to be more prevalent in this prokaryotic social species than has been observed in the eukaryotic social slime mold Dictyostelium discoideum, which also exhibits multicellular development.
[14] The finding of several cases of facultative social exploitation among these natural isolates suggests that such exploitation may occur frequently in nature in many prokaryotes with cooperative traits.

[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: PD-1 triggering on monocytes reduces IL-10 production by monocytes.

Document title: Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection

Abstract sentences:
[0] Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection.
[1] Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection.
[2] Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections.
[3] Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10.
[4] Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction.
[5] We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction.". 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: PD-1 triggering on monocytes reduces IL-10 production by monocytes.

Document title: Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection

Abstract sentences:
[0] Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection.
[1] Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection.
[2] Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections.
[3] Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10.
[4] Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction.
[5] We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.". 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: PDPN promotes efficient motility along stromal surfaces by activating the C-type lectin receptor to rearrange the actin cytoskeleton in dendritic cells.

Document title: Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2

Abstract sentences:
[0] To initiate adaptive immunity, dendritic cells (DCs) move from parenchymal tissues to lymphoid organs by migrating along stromal scaffolds that display the glycoprotein podoplanin (PDPN).
[1] PDPN is expressed by lymphatic endothelial and fibroblastic reticular cells and promotes blood-lymph separation during development by activating the C-type lectin receptor, CLEC-2, on platelets.
[2] Here, we describe a role for CLEC-2 in the morphodynamic behavior and motility of DCs.
[3] CLEC-2 deficiency in DCs impaired their entry into lymphatics and trafficking to and within lymph nodes, thereby reducing T cell priming.
[4] CLEC-2 engagement of PDPN was necessary for DCs to spread and migrate along stromal surfaces and sufficient to induce membrane protrusions.
[5] CLEC-2 activation triggered cell spreading via downregulation of RhoA activity and myosin light-chain phosphorylation and triggered F-actin-rich protrusions via Vav signaling and Rac1 activation.
[6] Thus, activation of CLEC-2 by PDPN rearranges the actin cytoskeleton in DCs to promote efficient motility along stromal surfaces.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Thus, activation of CLEC-2 by PDPN rearranges the actin cytoskeleton in DCs to promote efficient motility along stromal surfaces.". 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: PGE 2 promotes intestinal tumor growth by altering the expression of tumor suppressing and DNA repair genes.

Document title: Prostaglandin E2 promotes intestinal tumor growth via DNA methylation

Abstract sentences:
[0] Although aberrant DNA methylation is considered to be one of the key ways by which tumor-suppressor and DNA-repair genes are silenced during tumor initiation and progression, the mechanisms underlying DNA methylation alterations in cancer remain unclear.
[1] Here we show that prostaglandin E(2) (PGE(2)) silences certain tumor-suppressor and DNA-repair genes through DNA methylation to promote tumor growth.
[2] These findings uncover a previously unrecognized role for PGE(2) in the promotion of tumor progression.

[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: PKG-la plays an essential role in expression of pain hypersensitivity in PGK-la knockout mice.

Document title: Presynaptically Localized Cyclic GMP-Dependent Protein Kinase 1 Is a Key Determinant of Spinal Synaptic Potentiation and Pain Hypersensitivity

Abstract sentences:
[0] Synaptic long-term potentiation (LTP) at spinal neurons directly communicating pain-specific inputs from the periphery to the brain has been proposed to serve as a trigger for pain hypersensitivity in pathological states.
[1] Previous studies have functionally implicated the NMDA receptor-NO pathway and the downstream second messenger, cGMP, in these processes.
[2] Because cGMP can broadly influence diverse ion-channels, kinases, and phosphodiesterases, pre- as well as post-synaptically, the precise identity of cGMP targets mediating spinal LTP, their mechanisms of action, and their locus in the spinal circuitry are still unclear.
[3] Here, we found that Protein Kinase G1 (PKG-I) localized presynaptically in nociceptor terminals plays an essential role in the expression of spinal LTP.
[4] Using the Cre-lox P system, we generated nociceptor-specific knockout mice lacking PKG-I specifically in presynaptic terminals of nociceptors in the spinal cord, but not in post-synaptic neurons or elsewhere (SNS-PKG-I(-/-) mice).
[5] Patch clamp recordings showed that activity-induced LTP at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) was completely abolished in SNS-PKG-I(-/-) mice, although basal synaptic transmission was not affected.
[6] Analyses of synaptic failure rates and paired-pulse ratios indicated a role for presynaptic PKG-I in regulating the probability of neurotransmitter release.
[7] Inositol 1,4,5-triphosphate receptor 1 and myosin light chain kinase were recruited as key phosphorylation targets of presynaptic PKG-I in nociceptive neurons.
[8] Finally, behavioural analyses in vivo showed marked defects in SNS-PKG-I(-/-) mice in several models of activity-induced nociceptive hypersensitivity, and pharmacological studies identified a clear contribution of PKG-I expressed in spinal terminals of nociceptors.
[9] Our results thus indicate that presynaptic mechanisms involving an increase in release probability from nociceptors are operational in the expression of synaptic LTP on spinal-PAG projection neurons and that PKG-I localized in presynaptic nociceptor terminals plays an essential role in this process to regulate pain sensitivity.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Here, we found that Protein Kinase G1 (PKG-I) localized presynaptically in nociceptor terminals plays an essential role in the expression of spinal LTP.". 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: PKG-la plays an essential role in expression of pain hypersensitivity in PGK-la knockout mice.

Document title: Presynaptically Localized Cyclic GMP-Dependent Protein Kinase 1 Is a Key Determinant of Spinal Synaptic Potentiation and Pain Hypersensitivity

Abstract sentences:
[0] Synaptic long-term potentiation (LTP) at spinal neurons directly communicating pain-specific inputs from the periphery to the brain has been proposed to serve as a trigger for pain hypersensitivity in pathological states.
[1] Previous studies have functionally implicated the NMDA receptor-NO pathway and the downstream second messenger, cGMP, in these processes.
[2] Because cGMP can broadly influence diverse ion-channels, kinases, and phosphodiesterases, pre- as well as post-synaptically, the precise identity of cGMP targets mediating spinal LTP, their mechanisms of action, and their locus in the spinal circuitry are still unclear.
[3] Here, we found that Protein Kinase G1 (PKG-I) localized presynaptically in nociceptor terminals plays an essential role in the expression of spinal LTP.
[4] Using the Cre-lox P system, we generated nociceptor-specific knockout mice lacking PKG-I specifically in presynaptic terminals of nociceptors in the spinal cord, but not in post-synaptic neurons or elsewhere (SNS-PKG-I(-/-) mice).
[5] Patch clamp recordings showed that activity-induced LTP at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) was completely abolished in SNS-PKG-I(-/-) mice, although basal synaptic transmission was not affected.
[6] Analyses of synaptic failure rates and paired-pulse ratios indicated a role for presynaptic PKG-I in regulating the probability of neurotransmitter release.
[7] Inositol 1,4,5-triphosphate receptor 1 and myosin light chain kinase were recruited as key phosphorylation targets of presynaptic PKG-I in nociceptive neurons.
[8] Finally, behavioural analyses in vivo showed marked defects in SNS-PKG-I(-/-) mice in several models of activity-induced nociceptive hypersensitivity, and pharmacological studies identified a clear contribution of PKG-I expressed in spinal terminals of nociceptors.
[9] Our results thus indicate that presynaptic mechanisms involving an increase in release probability from nociceptors are operational in the expression of synaptic LTP on spinal-PAG projection neurons and that PKG-I localized in presynaptic nociceptor terminals plays an essential role in this process to regulate pain sensitivity.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "Our results thus indicate that presynaptic mechanisms involving an increase in release probability from nociceptors are operational in the expression of synaptic LTP on spinal-PAG projection neurons and that PKG-I localized in presynaptic nociceptor terminals plays an essential role in this process to regulate pain sensitivity.". This supports the claim.


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

Claim: PPAR-RXRs are inhibited by PPAR ligands.

Document title: Unique response pathways are established by allosteric interactions among nuclear hormone receptors

Abstract sentences:
[0] Heterodimerization is a common paradigm among eukaryotic transcription factors.
[1] The 9-cis retinoic acid receptor (RXR) serves as a common heterodimerization partner for several nuclear receptors, including the thyroid hormone receptor (T3R) and retinoic acid receptor (RAR).
[2] This raises the question as to whether these complexes possess dual hormonal responsiveness.
[3] We devised a strategy to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner.
[4] We find that the intrinsic binding properties of RXR are masked in T3R-RXR and RAR-RXR heterodimers.
[5] In contrast, RXR is active as a non-DNA-binding cofactor with the NGFI-B/Nurr1 orphan receptors.
[6] Heterodimerization of RXR with constitutively active NGFI-B/Nurr1 creates a novel hormone-dependent complex.
[7] These findings suggest that allosteric interactions among heterodimers create complexes with unique properties.
[8] We suggest that allostery is a critical feature underlying the generation of diversity in hormone response networks.

[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: PPAR-RXRs can be activated by PPAR ligands.

Document title: Unique response pathways are established by allosteric interactions among nuclear hormone receptors

Abstract sentences:
[0] Heterodimerization is a common paradigm among eukaryotic transcription factors.
[1] The 9-cis retinoic acid receptor (RXR) serves as a common heterodimerization partner for several nuclear receptors, including the thyroid hormone receptor (T3R) and retinoic acid receptor (RAR).
[2] This raises the question as to whether these complexes possess dual hormonal responsiveness.
[3] We devised a strategy to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner.
[4] We find that the intrinsic binding properties of RXR are masked in T3R-RXR and RAR-RXR heterodimers.
[5] In contrast, RXR is active as a non-DNA-binding cofactor with the NGFI-B/Nurr1 orphan receptors.
[6] Heterodimerization of RXR with constitutively active NGFI-B/Nurr1 creates a novel hormone-dependent complex.
[7] These findings suggest that allosteric interactions among heterodimers create complexes with unique properties.
[8] We suggest that allostery is a critical feature underlying the generation of diversity in hormone response networks.

[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: Participating in six months of physical activity improves cognitive functioning.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "RESULTS In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention.". This supports the claim.


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

Claim: Participating in six months of physical activity improves cognitive functioning.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "The absolute difference of the outcome measure between the intervention and control groups was -1.3 points (95% confidence interval,-2.38 to -0.22) at the end of the intervention.". 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: Participating in six months of physical activity improves cognitive functioning.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [13]
Explanation: Evidence states: "CONCLUSIONS In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period.". This supports the claim.


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

Claim: Patients in stable partnerships have a faster progression from HIV to AIDS.

Document title: Stable partnership and progression to AIDS or death in HIV infected patients receiving highly active antiretroviral therapy: Swiss HIV cohort study.

Abstract sentences:
[0] OBJECTIVES To explore the association between a stable partnership and clinical outcome in HIV infected patients receiving highly active antiretroviral therapy (HAART).
[1] DESIGN Prospective cohort study of adults with HIV (Swiss HIV cohort study).
[2] SETTING Seven outpatient clinics throughout Switzerland.
[3] PARTICIPANTS The 3736 patients in the cohort who started HAART before 2002 (median age 36 years, 29% female, median follow up 3.6 years).
[4] MAIN OUTCOME MEASURES Time to AIDS or death (primary endpoint), death alone, increases in CD4 cell count of at least 50 and 100 above baseline, optimal viral suppression (a viral load below 400 copies/ml), and viral rebound.
[5] RESULTS During follow up 2985 (80%) participants reported a stable partnership on at least one occasion.
[6] When starting HAART, 52% (545/1042) of participants reported a stable partnership; after five years of follow up 46% (190/412) of participants reported a stable partnership.
[7] In an analysis stratified by previous antiretroviral therapy and clinical stage when starting HAART (US Centers for Disease Control and Prevention group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was 0.79 (95% confidence interval 0.63 to 0.98) for participants with a stable partnership compared with those without.
[8] Adjusted hazards ratios for other endpoints were 0.59 (0.44 to 0.79) for progression to death, 1.15 (1.06 to 1.24) for an increase in CD4 cells of 100 counts/microl or more, and 1.06 (0.98 to 1.14) for optimal viral suppression.
[9] CONCLUSIONS A stable partnership is associated with a slower rate of progression to AIDS or death in HIV infected patients receiving HAART.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "In an analysis stratified by previous antiretroviral therapy and clinical stage when starting HAART (US Centers for Disease Control and Prevention group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was 0.79 (95% confidence interval 0.63 to 0.98) for participants with a stable partnership compared with those without.". 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: Patients in stable partnerships have a faster progression from HIV to AIDS.

Document title: Stable partnership and progression to AIDS or death in HIV infected patients receiving highly active antiretroviral therapy: Swiss HIV cohort study.

Abstract sentences:
[0] OBJECTIVES To explore the association between a stable partnership and clinical outcome in HIV infected patients receiving highly active antiretroviral therapy (HAART).
[1] DESIGN Prospective cohort study of adults with HIV (Swiss HIV cohort study).
[2] SETTING Seven outpatient clinics throughout Switzerland.
[3] PARTICIPANTS The 3736 patients in the cohort who started HAART before 2002 (median age 36 years, 29% female, median follow up 3.6 years).
[4] MAIN OUTCOME MEASURES Time to AIDS or death (primary endpoint), death alone, increases in CD4 cell count of at least 50 and 100 above baseline, optimal viral suppression (a viral load below 400 copies/ml), and viral rebound.
[5] RESULTS During follow up 2985 (80%) participants reported a stable partnership on at least one occasion.
[6] When starting HAART, 52% (545/1042) of participants reported a stable partnership; after five years of follow up 46% (190/412) of participants reported a stable partnership.
[7] In an analysis stratified by previous antiretroviral therapy and clinical stage when starting HAART (US Centers for Disease Control and Prevention group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was 0.79 (95% confidence interval 0.63 to 0.98) for participants with a stable partnership compared with those without.
[8] Adjusted hazards ratios for other endpoints were 0.59 (0.44 to 0.79) for progression to death, 1.15 (1.06 to 1.24) for an increase in CD4 cells of 100 counts/microl or more, and 1.06 (0.98 to 1.14) for optimal viral suppression.
[9] CONCLUSIONS A stable partnership is associated with a slower rate of progression to AIDS or death in HIV infected patients receiving HAART.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [9]
Explanation: Evidence states: "CONCLUSIONS A stable partnership is associated with a slower rate of progression to AIDS or death in HIV infected patients receiving HAART.". 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: Peroxynitrite is required for nitration of TCR/CD8.

Document title: Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer

Abstract sentences:
[0] Antigen-specific CD8+ T-cell tolerance, induced by myeloid-derived suppressor cells (MDSCs), is one of the main mechanisms of tumor escape.
[1] Using in vivo models, we show here that MDSCs directly disrupt the binding of specific peptide–major histocompatibility complex (pMHC) dimers to CD8-expressing T cells through nitration of tyrosines in a T-cell receptor (TCR)-CD8 complex.
[2] This process makes CD8-expressing T cells unable to bind pMHC and to respond to the specific peptide, although they retain their ability to respond to nonspecific stimulation.
[3] Nitration of TCR-CD8 is induced by MDSCs through hyperproduction of reactive oxygen species and peroxynitrite during direct cell-cell contact.
[4] Molecular modeling suggests specific sites of nitration that might affect the conformational flexibility of TCR-CD8 and its interaction with pMHC.
[5] These data identify a previously unknown mechanism of T-cell tolerance in cancer that is also pertinent to many pathological conditions associated with accumulation of MDSCs.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Nitration of TCR-CD8 is induced by MDSCs through hyperproduction of reactive oxygen species and peroxynitrite during direct cell-cell contact.". 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: Pleiotropic coupling of GLP-1R to intracellular effectors promotes distinct profiles of cellular signaling.

Document title: The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism

Abstract sentences:
[0] Ligand-directed signal bias offers opportunities for sculpting molecular events, with the promise of better, safer therapeutics.
[1] Critical to the exploitation of signal bias is an understanding of the molecular events coupling ligand binding to intracellular signaling.
[2] Activation of class B G protein-coupled receptors is driven by interaction of the peptide N terminus with the receptor core.
[3] To understand how this drives signaling, we have used advanced analytical methods that enable separation of effects on pathway-specific signaling from those that modify agonist affinity and mapped the functional consequence of receptor modification onto three-dimensional models of a receptor-ligand complex.
[4] This yields molecular insights into the initiation of receptor activation and the mechanistic basis for biased agonism.
[5] Our data reveal that peptide agonists can engage different elements of the receptor extracellular face to achieve effector coupling and biased signaling providing a foundation for rational design of biased agonists.

[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: Podocytes are motile and migrate in the presence of injury.

Document title: Tracking the fate of glomerular epithelial cells in vivo using serial multiphoton imaging in novel mouse models with fluorescent lineage tags

Abstract sentences:
[0] Podocytes are critical in the maintenance of a healthy glomerular filter; however, they have been difficult to study in the intact kidney because of technical limitations.
[1] Here we report the development of serial multiphoton microscopy (MPM) of the same glomeruli over several days to visualize the motility of podocytes and parietal epithelial cells (PECs) in vivo.
[2] In podocin-GFP mice, podocytes formed sporadic multicellular clusters after unilateral ureteral ligation and migrated into the parietal Bowman's capsule.
[3] The tracking of single cells in podocin-confetti mice featuring cell-specific expression of CFP, GFP, YFP or RFP revealed the simultaneous migration of multiple podocytes.
[4] In phosphoenolpyruvate carboxykinase (PEPCK)-GFP mice, serial MPM found PEC-to-podocyte migration and nanotubule connections.
[5] Our data support a highly dynamic rather than a static nature of the glomerular environment and cellular composition.
[6] Future application of this new approach should advance our understanding of the mechanisms of glomerular injury and regeneration.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "In podocin-GFP mice, podocytes formed sporadic multicellular clusters after unilateral ureteral ligation and migrated into the parietal Bowman's capsule.". 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: Polymeal nutrition reduces cardiovascular mortality.

Document title: The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%.

Abstract sentences:
[0] OBJECTIVE Although the Polypill concept (proposed in 2003) is promising in terms of benefits for cardiovascular risk management, the potential costs and adverse effects are its main pitfalls.
[1] The objective of this study was to identify a tastier and safer alternative to the Polypill: the Polymeal.
[2] METHODS Data on the ingredients of the Polymeal were taken from the literature.
[3] The evidence based recipe included wine, fish, dark chocolate, fruits, vegetables, garlic, and almonds.
[4] Data from the Framingham heart study and the Framingham offspring study were used to build life tables to model the benefits of the Polymeal in the general population from age 50, assuming multiplicative correlations.
[5] RESULTS Combining the ingredients of the Polymeal would reduce cardiovascular disease events by 76%.
[6] For men, taking the Polymeal daily represented an increase in total life expectancy of 6.6 years, an increase in life expectancy free from cardiovascular disease of 9.0 years, and a decrease in life expectancy with cardiovascular disease of 2.4 years.
[7] The corresponding differences for women were 4.8, 8.1, and 3.3 years.
[8] CONCLUSION The Polymeal promises to be an effective, non-pharmacological, safe, cheap, and tasty alternative to reduce cardiovascular morbidity and increase life expectancy in the general population.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "For men, taking the Polymeal daily represented an increase in total life expectancy of 6.6 years, an increase in life expectancy free from cardiovascular disease of 9.0 years, and a decrease in life expectancy with cardiovascular disease of 2.4 years.". 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: Polymeal nutrition reduces cardiovascular mortality.

Document title: The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%.

Abstract sentences:
[0] OBJECTIVE Although the Polypill concept (proposed in 2003) is promising in terms of benefits for cardiovascular risk management, the potential costs and adverse effects are its main pitfalls.
[1] The objective of this study was to identify a tastier and safer alternative to the Polypill: the Polymeal.
[2] METHODS Data on the ingredients of the Polymeal were taken from the literature.
[3] The evidence based recipe included wine, fish, dark chocolate, fruits, vegetables, garlic, and almonds.
[4] Data from the Framingham heart study and the Framingham offspring study were used to build life tables to model the benefits of the Polymeal in the general population from age 50, assuming multiplicative correlations.
[5] RESULTS Combining the ingredients of the Polymeal would reduce cardiovascular disease events by 76%.
[6] For men, taking the Polymeal daily represented an increase in total life expectancy of 6.6 years, an increase in life expectancy free from cardiovascular disease of 9.0 years, and a decrease in life expectancy with cardiovascular disease of 2.4 years.
[7] The corresponding differences for women were 4.8, 8.1, and 3.3 years.
[8] CONCLUSION The Polymeal promises to be an effective, non-pharmacological, safe, cheap, and tasty alternative to reduce cardiovascular morbidity and increase life expectancy in the general population.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "CONCLUSION The Polymeal promises to be an effective, non-pharmacological, safe, cheap, and tasty alternative to reduce cardiovascular morbidity and increase life expectancy in the general population.". 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: Pretreatment with the Arp2/3 inhibitor CK-666 affects lamelliopodia formation.

Document title: Arp2/3 complex inhibition radically alters lamellipodial actin architecture, suspended cell shape, and the cell spreading process

Abstract sentences:
[0] Recent studies have investigated the dendritic actin cytoskeleton of the cell edge's lamellipodial (LP) region by experimentally decreasing the activity of the actin filament nucleator and branch former, the Arp2/3 complex.
[1] Here we extend these studies via pharmacological inhibition of the Arp2/3 complex in sea urchin coelomocytes, cells that possess an unusually broad LP region and display correspondingly exaggerated centripetal flow.
[2] Using light and electron microscopy, we demonstrate that Arp2/3 complex inhibition via the drug CK666 dramatically altered LP actin architecture, slowed centripetal flow, drove a lamellipodial-to-filopodial shape change in suspended cells, and induced a novel actin structural organization during cell spreading.
[3] A general feature of the CK666 phenotype in coelomocytes was transverse actin arcs, and arc generation was arrested by a formin inhibitor.
[4] We also demonstrate that CK666 treatment produces actin arcs in other cells with broad LP regions, namely fish keratocytes and Drosophila S2 cells.
[5] We hypothesize that the actin arcs made visible by Arp2/3 complex inhibition in coelomocytes may represent an exaggerated manifestation of the elongate mother filaments that could possibly serve as the scaffold for the production of the dendritic actin network.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Using light and electron microscopy, we demonstrate that Arp2/3 complex inhibition via the drug CK666 dramatically altered LP actin architecture, slowed centripetal flow, drove a lamellipodial-to-filopodial shape change in suspended cells, and induced a novel actin structural organization during cell spreading.". 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: Primary cervical cancer screening with HPV detection has higher longitudinal sensitivity than conventional cytology to detect cervical intraepithelial neoplasia grade 2.

Document title: Human papillomavirus and Papanicolaou tests to screen for cervical cancer.

Abstract sentences:
[0] BACKGROUND Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown.
[1] METHODS In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group).
[2] Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy.
[3] A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group.
[4] Comprehensive registry data were used to follow the women for a mean of 4.1 years.
[5] The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated.
[6] RESULTS At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions.
[7] At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions.
[8] Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy.
[9] CONCLUSIONS The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.
[10] (ClinicalTrials.gov number, NCT00479375 [ClinicalTrials.gov].).

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "BACKGROUND Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown.". 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: Primary cervical cancer screening with HPV detection has higher longitudinal sensitivity than conventional cytology to detect cervical intraepithelial neoplasia grade 2.

Document title: Human papillomavirus and Papanicolaou tests to screen for cervical cancer.

Abstract sentences:
[0] BACKGROUND Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown.
[1] METHODS In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group).
[2] Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy.
[3] A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group.
[4] Comprehensive registry data were used to follow the women for a mean of 4.1 years.
[5] The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated.
[6] RESULTS At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions.
[7] At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions.
[8] Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy.
[9] CONCLUSIONS The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.
[10] (ClinicalTrials.gov number, NCT00479375 [ClinicalTrials.gov].).

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "CONCLUSIONS The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.". 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: Primary cervical cancer screening with HPV detection has higher longitudinal sensitivity than conventional cytology to detect cervical intraepithelial neoplasia grade 2.

Document title: Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial.

Abstract sentences:
[0] BACKGROUND Human papillomavirus (HPV) testing is known to be more sensitive, but less specific than cytology for detecting cervical intraepithelial neoplasia (CIN).
[1] We assessed the efficacy of cervical-cancer screening policies that are based on HPV testing.
[2] METHODS Between March, 2004, and December, 2004, in two separate recruitment phases, women aged 25-60 years were randomly assigned to conventional cytology or to HPV testing in combination with liquid-based cytology (first phase) or alone (second phase).
[3] Randomisation was done by computer in two screening centres and by sequential opening of numbered sealed envelopes in the remaining seven centres.
[4] During phase one, women who were HPV-positive and aged 35-60 years were referred to colposcopy, whereas women aged 25-34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive.
[5] During phase two, women in the HPV group were referred for colposcopy if the HPV test was positive.
[6] Two rounds of screening occurred in each phase, and all women had cytology testing only at the second round.
[7] The primary endpoint was the detection of grade 2 and 3 CIN, and of invasive cervical cancers during the first and second screening rounds.
[8] Analysis was done by intention to screen.
[9] This trial is registered, number ISRCTN81678807.
[10] FINDINGS In total for both phases, 47,001 women were randomly assigned to the cytology group and 47,369 to HPV testing.
[11] 33,851 women from the cytology group and 32,998 from the HPV-testing group had a second round of screening.
[12] We also retrieved the histological diagnoses from screening done elsewhere.
[13] The detection of invasive cervical cancers was similar for the two groups in the first round of screening (nine in the cytology group vs seven in the HPV group, p=0.62); no cases were detected in the HPV group during round two, compared with nine in the cytology group (p=0.004).
[14] Overall, in the two rounds of screening, 18 invasive cancers were detected in the cytology group versus seven in the HPV group (p=0.028).
[15] Among women aged 35-60 years, at round one the relative detection (HPV vs cytology) was 2.00 (95% CI 1.44-2.77) for CIN2, 2.08 (1.47-2.95) for CIN3, and 2.03 (1.60-2.57) for CIN2 and 3 together.
[16] At round two the relative detection was 0.54 (0.23-1.28) for CIN2, 0.48 (0.21-1.11) for CIN3, and 0.51 (0.28-0.93) for CIN2 and 3 together.
[17] Among women aged 25-34 years, there was significant heterogeneity between phases in the relative detection of CIN3.
[18] At round one the relative detection was 0.93 (0.52-1.64) in phase one and 3.91 (2.02-7.57) in phase two.
[19] At round two the relative detection was 1.34 (0.46-3.84) in phase one and 0.20 (0.04-0.93) in phase two.
[20] Pooling both phases, the detection ratio of CIN2 for women aged 25-34 years was 4.09 (2.24-7.48) at round one and 0.64 (0.23-1.27) at round two.
[21] INTERPRETATION HPV-based screening is more effective than cytology in preventing invasive cervical cancer, by detecting persistent high-grade lesions earlier and providing a longer low-risk period.
[22] However, in younger women, HPV screening leads to over-diagnosis of regressive CIN2.
[23] FUNDING European Union, Italian Ministry of Health, Regional Health Administrations of Piemonte, Tuscany, Veneto and Emilia-Romagna, and Public Health Agency of Lazio.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "BACKGROUND Human papillomavirus (HPV) testing is known to be more sensitive, but less specific than cytology for detecting cervical intraepithelial neoplasia (CIN).". 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: Primary cervical cancer screening with HPV detection has higher longitudinal sensitivity than conventional cytology to detect cervical intraepithelial neoplasia grade 2.

Document title: Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial.

Abstract sentences:
[0] BACKGROUND Human papillomavirus (HPV) testing is known to be more sensitive, but less specific than cytology for detecting cervical intraepithelial neoplasia (CIN).
[1] We assessed the efficacy of cervical-cancer screening policies that are based on HPV testing.
[2] METHODS Between March, 2004, and December, 2004, in two separate recruitment phases, women aged 25-60 years were randomly assigned to conventional cytology or to HPV testing in combination with liquid-based cytology (first phase) or alone (second phase).
[3] Randomisation was done by computer in two screening centres and by sequential opening of numbered sealed envelopes in the remaining seven centres.
[4] During phase one, women who were HPV-positive and aged 35-60 years were referred to colposcopy, whereas women aged 25-34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive.
[5] During phase two, women in the HPV group were referred for colposcopy if the HPV test was positive.
[6] Two rounds of screening occurred in each phase, and all women had cytology testing only at the second round.
[7] The primary endpoint was the detection of grade 2 and 3 CIN, and of invasive cervical cancers during the first and second screening rounds.
[8] Analysis was done by intention to screen.
[9] This trial is registered, number ISRCTN81678807.
[10] FINDINGS In total for both phases, 47,001 women were randomly assigned to the cytology group and 47,369 to HPV testing.
[11] 33,851 women from the cytology group and 32,998 from the HPV-testing group had a second round of screening.
[12] We also retrieved the histological diagnoses from screening done elsewhere.
[13] The detection of invasive cervical cancers was similar for the two groups in the first round of screening (nine in the cytology group vs seven in the HPV group, p=0.62); no cases were detected in the HPV group during round two, compared with nine in the cytology group (p=0.004).
[14] Overall, in the two rounds of screening, 18 invasive cancers were detected in the cytology group versus seven in the HPV group (p=0.028).
[15] Among women aged 35-60 years, at round one the relative detection (HPV vs cytology) was 2.00 (95% CI 1.44-2.77) for CIN2, 2.08 (1.47-2.95) for CIN3, and 2.03 (1.60-2.57) for CIN2 and 3 together.
[16] At round two the relative detection was 0.54 (0.23-1.28) for CIN2, 0.48 (0.21-1.11) for CIN3, and 0.51 (0.28-0.93) for CIN2 and 3 together.
[17] Among women aged 25-34 years, there was significant heterogeneity between phases in the relative detection of CIN3.
[18] At round one the relative detection was 0.93 (0.52-1.64) in phase one and 3.91 (2.02-7.57) in phase two.
[19] At round two the relative detection was 1.34 (0.46-3.84) in phase one and 0.20 (0.04-0.93) in phase two.
[20] Pooling both phases, the detection ratio of CIN2 for women aged 25-34 years was 4.09 (2.24-7.48) at round one and 0.64 (0.23-1.27) at round two.
[21] INTERPRETATION HPV-based screening is more effective than cytology in preventing invasive cervical cancer, by detecting persistent high-grade lesions earlier and providing a longer low-risk period.
[22] However, in younger women, HPV screening leads to over-diagnosis of regressive CIN2.
[23] FUNDING European Union, Italian Ministry of Health, Regional Health Administrations of Piemonte, Tuscany, Veneto and Emilia-Romagna, and Public Health Agency of Lazio.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [15]
Explanation: Evidence states: "Among women aged 35-60 years, at round one the relative detection (HPV vs cytology) was 2.00 (95% CI 1.44-2.77) for CIN2, 2.08 (1.47-2.95) for CIN3, and 2.03 (1.60-2.57) for CIN2 and 3 together.". 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: Primary cervical cancer screening with HPV detection has higher longitudinal sensitivity than conventional cytology to detect cervical intraepithelial neoplasia grade 2.

Document title: Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial.

Abstract sentences:
[0] BACKGROUND Human papillomavirus (HPV) testing is known to be more sensitive, but less specific than cytology for detecting cervical intraepithelial neoplasia (CIN).
[1] We assessed the efficacy of cervical-cancer screening policies that are based on HPV testing.
[2] METHODS Between March, 2004, and December, 2004, in two separate recruitment phases, women aged 25-60 years were randomly assigned to conventional cytology or to HPV testing in combination with liquid-based cytology (first phase) or alone (second phase).
[3] Randomisation was done by computer in two screening centres and by sequential opening of numbered sealed envelopes in the remaining seven centres.
[4] During phase one, women who were HPV-positive and aged 35-60 years were referred to colposcopy, whereas women aged 25-34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive.
[5] During phase two, women in the HPV group were referred for colposcopy if the HPV test was positive.
[6] Two rounds of screening occurred in each phase, and all women had cytology testing only at the second round.
[7] The primary endpoint was the detection of grade 2 and 3 CIN, and of invasive cervical cancers during the first and second screening rounds.
[8] Analysis was done by intention to screen.
[9] This trial is registered, number ISRCTN81678807.
[10] FINDINGS In total for both phases, 47,001 women were randomly assigned to the cytology group and 47,369 to HPV testing.
[11] 33,851 women from the cytology group and 32,998 from the HPV-testing group had a second round of screening.
[12] We also retrieved the histological diagnoses from screening done elsewhere.
[13] The detection of invasive cervical cancers was similar for the two groups in the first round of screening (nine in the cytology group vs seven in the HPV group, p=0.62); no cases were detected in the HPV group during round two, compared with nine in the cytology group (p=0.004).
[14] Overall, in the two rounds of screening, 18 invasive cancers were detected in the cytology group versus seven in the HPV group (p=0.028).
[15] Among women aged 35-60 years, at round one the relative detection (HPV vs cytology) was 2.00 (95% CI 1.44-2.77) for CIN2, 2.08 (1.47-2.95) for CIN3, and 2.03 (1.60-2.57) for CIN2 and 3 together.
[16] At round two the relative detection was 0.54 (0.23-1.28) for CIN2, 0.48 (0.21-1.11) for CIN3, and 0.51 (0.28-0.93) for CIN2 and 3 together.
[17] Among women aged 25-34 years, there was significant heterogeneity between phases in the relative detection of CIN3.
[18] At round one the relative detection was 0.93 (0.52-1.64) in phase one and 3.91 (2.02-7.57) in phase two.
[19] At round two the relative detection was 1.34 (0.46-3.84) in phase one and 0.20 (0.04-0.93) in phase two.
[20] Pooling both phases, the detection ratio of CIN2 for women aged 25-34 years was 4.09 (2.24-7.48) at round one and 0.64 (0.23-1.27) at round two.
[21] INTERPRETATION HPV-based screening is more effective than cytology in preventing invasive cervical cancer, by detecting persistent high-grade lesions earlier and providing a longer low-risk period.
[22] However, in younger women, HPV screening leads to over-diagnosis of regressive CIN2.
[23] FUNDING European Union, Italian Ministry of Health, Regional Health Administrations of Piemonte, Tuscany, Veneto and Emilia-Romagna, and Public Health Agency of Lazio.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [21]
Explanation: Evidence states: "INTERPRETATION HPV-based screening is more effective than cytology in preventing invasive cervical cancer, by detecting persistent high-grade lesions earlier and providing a longer low-risk period.". This supports the claim.


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

Claim: Primary cervical cancer screening with HPV detection has higher longitudinal sensitivity than conventional cytology to detect cervical intraepithelial neoplasia grade 2.

Document title: Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer.

Abstract sentences:
[0] More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods.
[1] A summary is given from recent meta-analyses and systematic reviews on 3 possible clinical applications of human papillomavirus (HPV) testing: triage of women with equivocal or low-grade cytologic abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer.
[2] Consistent evidence is available indicating that HPV-triage with the Hybrid Capture(®) 2 assay (Qiagen Gaithersburg, Inc., MD, USA [previously Digene Corp.] (HC2) is more accurate (higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results.
[3] Several other tests show at least similar accuracy but mRNA testing with the APTIMA(®) (Gen-Probe Inc., San Diego, CA, USA) test is similarly sensitive but more specific compared to HC2.
[4] In triage of low-grade squamous intraepithelial lesions (LSIL), HC2 is more sensitive but its specificity is substantially lower compared to repeat cytology.
[5] The APTIMA(®) test is more specific than HC2 without showing a loss in sensitivity.
[6] Identification of DNA of HPV types 16 and/or 18, or RNA from the five most carcinogenic HPV types allow selecting women at highest risk for CIN3+ but the sensitivity and negative predictive value of these markers are lower than full-range high-risk HPV (hrHPV) testing.
[7] After conservative treatment of cervical pre-cancer, HPV testing picks up more quickly, with higher sensitivity and not lower specificity, residual or recurrent high-grade CIN than follow-up cytology.
[8] Primary screening for hrHPV generally detects more CIN2, CIN3 or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASC-US) or LSIL, but is less specific.
[9] Combined HPV and cytology screening provides a further small gain in sensitivity at the expense of a considerable loss in specificity if positive by either test is referred to colposcopy, in comparison with HPV testing only.
[10] Randomised trials and follow-up of cohort studies consistently demonstrate a significantly lower cumulative incidence of CIN3+ and even of cancer, in women aged 30 years or older, who were at enrollment hrHPV DNA negative compared to those who were cytologically negative.
[11] The difference in cumulative risk of CIN3+ or cancer for double negative (cytology & HPV) versus only HPV-negative women is small.
[12] HC2, GP5+/6+ PCR (polymerase chain reaction), cobas(®) 4800 PCR (Roche Molecular Systems Inc., Alameda, CA, USA) and Real Time PCR (Abbott Molecular, Des Plaines, IL, USA) can be considered as clinically validated for use in primary screening.
[13] The loss in specificity associated with primary HPV-based screening can be compensated by appropriate algorithms involving reflex cytology and/or HPV genotyping for HPV16 or 18.
[14] There exists a substantial evidence base to support that HPV testing is advantageous both in triage of women with equivocal abnormal cytology, in surveillance after treatment of CIN lesions and in primary screening of women aged 30 years or older.
[15] However, the possible advantages offered by HPV-based screening require a well organised program with good compliance with screening and triage policies.
[16] This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "Primary screening for hrHPV generally detects more CIN2, CIN3 or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASC-US) or LSIL, but is less specific.". This supports the claim.