[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: 0-dimensional biomaterials show inductive properties.

Document title: New opportunities: the use of nanotechnologies to manipulate and track stem cells.

Abstract sentences:
[0] Nanotechnologies are emerging platforms that could be useful in measuring, understanding, and manipulating stem cells.
[1] Examples include magnetic nanoparticles and quantum dots for stem cell labeling and in vivo tracking; nanoparticles, carbon nanotubes, and polyplexes for the intracellular delivery of genes/oligonucleotides and protein/peptides; and engineered nanometer-scale scaffolds for stem cell differentiation and transplantation.
[2] This review examines the use of nanotechnologies for stem cell tracking, differentiation, and transplantation.
[3] We further discuss their utility and the potential concerns regarding their cytotoxicity.

[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: 1,000 genomes project enables mapping of genetic sequence variation consisting of rare variants with larger penetrance effects than common variants.

Document title: Rare Variants Create Synthetic Genome-Wide Associations

Abstract sentences:
[0] Genome-wide association studies (GWAS) have now identified at least 2,000 common variants that appear associated with common diseases or related traits (http://www.genome.gov/gwastudies), hundreds of which have been convincingly replicated.
[1] It is generally thought that the associated markers reflect the effect of a nearby common (minor allele frequency >0.05) causal site, which is associated with the marker, leading to extensive resequencing efforts to find causal sites.
[2] We propose as an alternative explanation that variants much less common than the associated one may create "synthetic associations" by occurring, stochastically, more often in association with one of the alleles at the common site versus the other allele.
[3] Although synthetic associations are an obvious theoretical possibility, they have never been systematically explored as a possible explanation for GWAS findings.
[4] Here, we use simple computer simulations to show the conditions under which such synthetic associations will arise and how they may be recognized.
[5] We show that they are not only possible, but inevitable, and that under simple but reasonable genetic models, they are likely to account for or contribute to many of the recently identified signals reported in genome-wide association studies.
[6] We also illustrate the behavior of synthetic associations in real datasets by showing that rare causal mutations responsible for both hearing loss and sickle cell anemia create genome-wide significant synthetic associations, in the latter case extending over a 2.5-Mb interval encompassing scores of "blocks" of associated variants.
[7] In conclusion, uncommon or rare genetic variants can easily create synthetic associations that are credited to common variants, and this possibility requires careful consideration in the interpretation and follow up of GWAS signals.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2, 5]
Explanation: Evidence states: "We propose as an alternative explanation that variants much less common than the associated one may create "synthetic associations" by occurring, stochastically, more often in association with one of the alleles at the common site versus the other allele. We show that they are not only possible, but inevitable, and that under simple but reasonable genetic models, they are likely to account for or contribute to many of the recently identified signals reported in genome-wide association studies.". 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: 1,000 genomes project enables mapping of genetic sequence variation consisting of rare variants with larger penetrance effects than common variants.

Document title: Rare Variants Create Synthetic Genome-Wide Associations

Abstract sentences:
[0] Genome-wide association studies (GWAS) have now identified at least 2,000 common variants that appear associated with common diseases or related traits (http://www.genome.gov/gwastudies), hundreds of which have been convincingly replicated.
[1] It is generally thought that the associated markers reflect the effect of a nearby common (minor allele frequency >0.05) causal site, which is associated with the marker, leading to extensive resequencing efforts to find causal sites.
[2] We propose as an alternative explanation that variants much less common than the associated one may create "synthetic associations" by occurring, stochastically, more often in association with one of the alleles at the common site versus the other allele.
[3] Although synthetic associations are an obvious theoretical possibility, they have never been systematically explored as a possible explanation for GWAS findings.
[4] Here, we use simple computer simulations to show the conditions under which such synthetic associations will arise and how they may be recognized.
[5] We show that they are not only possible, but inevitable, and that under simple but reasonable genetic models, they are likely to account for or contribute to many of the recently identified signals reported in genome-wide association studies.
[6] We also illustrate the behavior of synthetic associations in real datasets by showing that rare causal mutations responsible for both hearing loss and sickle cell anemia create genome-wide significant synthetic associations, in the latter case extending over a 2.5-Mb interval encompassing scores of "blocks" of associated variants.
[7] In conclusion, uncommon or rare genetic variants can easily create synthetic associations that are credited to common variants, and this possibility requires careful consideration in the interpretation and follow up of GWAS signals.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "In conclusion, uncommon or rare genetic variants can easily create synthetic associations that are credited to common variants, and this possibility requires careful consideration in the interpretation and follow up of GWAS signals.". 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: 1/2000 in UK have abnormal PrP positivity.

Document title: Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey

Abstract sentences:
[0] OBJECTIVES To carry out a further survey of archived appendix samples to understand better the differences between existing estimates of the prevalence of subclinical infection with prions after the bovine spongiform encephalopathy epizootic and to see whether a broader birth cohort was affected, and to understand better the implications for the management of blood and blood products and for the handling of surgical instruments.
[1] DESIGN Irreversibly unlinked and anonymised large scale survey of archived appendix samples.
[2] SETTING Archived appendix samples from the pathology departments of 41 UK hospitals participating in the earlier survey, and additional hospitals in regions with lower levels of participation in that survey.
[3] SAMPLE 32,441 archived appendix samples fixed in formalin and embedded in paraffin and tested for the presence of abnormal prion protein (PrP).
[4] RESULTS Of the 32,441 appendix samples 16 were positive for abnormal PrP, indicating an overall prevalence of 493 per million population (95% confidence interval 282 to 801 per million).
[5] The prevalence in those born in 1941-60 (733 per million, 269 to 1596 per million) did not differ significantly from those born between 1961 and 1985 (412 per million, 198 to 758 per million) and was similar in both sexes and across the three broad geographical areas sampled.
[6] Genetic testing of the positive specimens for the genotype at PRNP codon 129 revealed a high proportion that were valine homozygous compared with the frequency in the normal population, and in stark contrast with confirmed clinical cases of vCJD, all of which were methionine homozygous at PRNP codon 129.
[7] CONCLUSIONS This study corroborates previous studies and suggests a high prevalence of infection with abnormal PrP, indicating vCJD carrier status in the population compared with the 177 vCJD cases to date.
[8] These findings have important implications for the management of blood and blood products and for the handling of surgical instruments.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "RESULTS Of the 32,441 appendix samples 16 were positive for abnormal PrP, indicating an overall prevalence of 493 per million population (95% confidence interval 282 to 801 per million).". This supports the claim.


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

Claim: 5% of perinatal mortality is due to low birth weight.

Document title: Estimates of global prevalence of childhood underweight in 1990 and 2015.

Abstract sentences:
[0] CONTEXT One key target of the United Nations Millennium Development goals is to reduce the prevalence of underweight among children younger than 5 years by half between 1990 and 2015.
[1] OBJECTIVE To estimate trends in childhood underweight by geographic regions of the world.
[2] DESIGN, SETTING, AND PARTICIPANTS Time series study of prevalence of underweight, defined as weight 2 SDs below the mean weight for age of the National Center for Health Statistics and World Health Organization (WHO) reference population.
[3] National prevalence rates derived from the WHO Global Database on Child Growth and Malnutrition, which includes data on approximately 31 million children younger than 5 years who participated in 419 national nutritional surveys in 139 countries from 1965 through 2002.
[4] MAIN OUTCOME MEASURES Linear mixed-effects modeling was used to estimate prevalence rates and numbers of underweight children by region in 1990 and 2015 and to calculate the changes (ie, increase or decrease) to these values between 1990 and 2015.
[5] RESULTS Worldwide, underweight prevalence was projected to decline from 26.5% in 1990 to 17.6% in 2015, a change of -34% (95% confidence interval [CI], -43% to -23%).
[6] In developed countries, the prevalence was estimated to decrease from 1.6% to 0.9%, a change of -41% (95% CI, -92% to 343%).
[7] In developing regions, the prevalence was forecasted to decline from 30.2% to 19.3%, a change of -36% (95% CI, -45% to -26%).
[8] In Africa, the prevalence of underweight was forecasted to increase from 24.0% to 26.8%, a change of 12% (95% CI, 8%-16%).
[9] In Asia, the prevalence was estimated to decrease from 35.1% to 18.5%, a change of -47% (95% CI, -58% to -34%).
[10] Worldwide, the number of underweight children was projected to decline from 163.8 million in 1990 to 113.4 million in 2015, a change of -31% (95% CI, -40% to -20%).
[11] Numbers are projected to decrease in all subregions except the subregions of sub-Saharan, Eastern, Middle, and Western Africa, which are expected to experience substantial increases in the number of underweight children.
[12] CONCLUSIONS An overall improvement in the global situation is anticipated; however, neither the world as a whole, nor the developing regions, are expected to achieve the Millennium Development goals.
[13] This is largely due to the deteriorating situation in Africa where all subregions, except Northern Africa, are expected to fail to meet the goal.

[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: A deficiency of vitamin B12 increases blood levels of homocysteine.

Document title: Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering.

Abstract sentences:
[0] BACKGROUND Homocysteine is a risk factor for coronary artery disease (CAD), although a causal relation remains to be proven.
[1] The importance of determining direct causality rests in the fact that plasma homocysteine can be safely and inexpensively reduced by 25% with folic acid.
[2] This reduction is maximally achieved by doses of 0.4 mg/d.
[3] High-dose folic acid (5 mg/d) improves endothelial function in CAD, although the mechanism is controversial.
[4] It has been proposed that improvement occurs through reduction in total (tHcy) or free (non-protein bound) homocysteine (fHcy).
[5] We investigated the effects of folic acid on endothelial function before a change in homocysteine in patients with CAD.
[6] METHODS AND RESULTS A randomized, placebo-controlled study of folic acid (5 mg/d) for 6 weeks was undertaken in 33 patients.
[7] Endothelial function, assessed by flow-mediated dilatation (FMD), was measured before, at 2 and 4 hours after the first dose of folic acid, and after 6 weeks of treatment.
[8] Plasma folate increased markedly by 1 hour (200 compared with 25.8 nmol/L; P<0.001).
[9] FMD improved at 2 hours (83 compared with 47 microm; P<0.001) and was largely complete by 4 hours (101 compared with 51 microm; P<0.001).
[10] tHcy did not significantly differ acutely (4-hour tHcy, 9.56 compared with 9.79 micromol/L; P=NS).
[11] fHcy did not differ at 3 hours but was slightly reduced at 4 hours (1.55 compared with 1.78 micromol/L; P=0.02).
[12] FMD improvement did not correlate with reductions in either fHcy or tHcy at any time.
[13] CONCLUSIONS These data suggest that folic acid improves endothelial function in CAD acutely by a mechanism largely independent of homocysteine.

[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: A high microerythrocyte count raises vulnerability to severe anemia in homozygous alpha (+)- thalassemia trait subjects.

Document title: Increased Microerythrocyte Count in Homozygous α+-Thalassaemia Contributes to Protection against Severe Malarial Anaemia

Abstract sentences:
[0] BACKGROUND The heritable haemoglobinopathy alpha(+)-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb).
[1] Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count.
[2] Alpha(+)-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration < 50 g/l), but does not influence parasite count.
[3] We tested the hypothesis that the erythrocyte indices associated with alpha(+)-thalassaemia homozygosity provide a haematological benefit during acute malaria.
[4] METHODS AND FINDINGS Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by alpha(+)-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease.
[5] We observed a reduction in median erythrocyte count of approximately 1.5 x 10(12)/l in all children with acute falciparum malaria relative to values in community children (p < 0.001).
[6] We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count.
[7] This model predicted that children homozygous for alpha(+)-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 x 10(12)/l as a result of the reduced mean cell Hb in homozygous alpha(+)-thalassaemia.
[8] In addition, children homozygous for alpha(+)-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA.
[9] We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09).
[10] CONCLUSIONS The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA.
[11] A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum.
[12] This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia.
[13] Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [1, 9]
Explanation: Evidence states: "Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count. We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09).". 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: A high microerythrocyte count raises vulnerability to severe anemia in homozygous alpha (+)- thalassemia trait subjects.

Document title: Increased Microerythrocyte Count in Homozygous α+-Thalassaemia Contributes to Protection against Severe Malarial Anaemia

Abstract sentences:
[0] BACKGROUND The heritable haemoglobinopathy alpha(+)-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb).
[1] Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count.
[2] Alpha(+)-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration < 50 g/l), but does not influence parasite count.
[3] We tested the hypothesis that the erythrocyte indices associated with alpha(+)-thalassaemia homozygosity provide a haematological benefit during acute malaria.
[4] METHODS AND FINDINGS Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by alpha(+)-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease.
[5] We observed a reduction in median erythrocyte count of approximately 1.5 x 10(12)/l in all children with acute falciparum malaria relative to values in community children (p < 0.001).
[6] We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count.
[7] This model predicted that children homozygous for alpha(+)-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 x 10(12)/l as a result of the reduced mean cell Hb in homozygous alpha(+)-thalassaemia.
[8] In addition, children homozygous for alpha(+)-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA.
[9] We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24-1.12, p = 0.09).
[10] CONCLUSIONS The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA.
[11] A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum.
[12] This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia.
[13] Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10]
Explanation: Evidence states: "CONCLUSIONS The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA.". 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: A total of 1,000 people in the UK are asymptomatic carriers of vCJD infection.

Document title: Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey

Abstract sentences:
[0] OBJECTIVES To carry out a further survey of archived appendix samples to understand better the differences between existing estimates of the prevalence of subclinical infection with prions after the bovine spongiform encephalopathy epizootic and to see whether a broader birth cohort was affected, and to understand better the implications for the management of blood and blood products and for the handling of surgical instruments.
[1] DESIGN Irreversibly unlinked and anonymised large scale survey of archived appendix samples.
[2] SETTING Archived appendix samples from the pathology departments of 41 UK hospitals participating in the earlier survey, and additional hospitals in regions with lower levels of participation in that survey.
[3] SAMPLE 32,441 archived appendix samples fixed in formalin and embedded in paraffin and tested for the presence of abnormal prion protein (PrP).
[4] RESULTS Of the 32,441 appendix samples 16 were positive for abnormal PrP, indicating an overall prevalence of 493 per million population (95% confidence interval 282 to 801 per million).
[5] The prevalence in those born in 1941-60 (733 per million, 269 to 1596 per million) did not differ significantly from those born between 1961 and 1985 (412 per million, 198 to 758 per million) and was similar in both sexes and across the three broad geographical areas sampled.
[6] Genetic testing of the positive specimens for the genotype at PRNP codon 129 revealed a high proportion that were valine homozygous compared with the frequency in the normal population, and in stark contrast with confirmed clinical cases of vCJD, all of which were methionine homozygous at PRNP codon 129.
[7] CONCLUSIONS This study corroborates previous studies and suggests a high prevalence of infection with abnormal PrP, indicating vCJD carrier status in the population compared with the 177 vCJD cases to date.
[8] These findings have important implications for the management of blood and blood products and for the handling of surgical instruments.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "RESULTS Of the 32,441 appendix samples 16 were positive for abnormal PrP, indicating an overall prevalence of 493 per million population (95% confidence interval 282 to 801 per million).". 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: ADAR1 binds to Dicer to cleave pre-miRNA.

Document title: ADAR1 Forms a Complex with Dicer to Promote MicroRNA Processing and RNA-Induced Gene Silencing

Abstract sentences:
[0] Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosine residues to inosine specifically in double-stranded RNAs.
[1] In this study, we investigated the interaction of the RNA editing mechanism with the RNA interference (RNAi) machinery and found that ADAR1 forms a complex with Dicer through direct protein-protein interaction.
[2] Most importantly, ADAR1 increases the maximum rate (Vmax) of pre-microRNA (miRNA) cleavage by Dicer and facilitates loading of miRNA onto RNA-induced silencing complexes, identifying a new role of ADAR1 in miRNA processing and RNAi mechanisms.
[3] ADAR1 differentiates its functions in RNA editing and RNAi by the formation of either ADAR1/ADAR1 homodimer or Dicer/ADAR1 heterodimer complexes, respectively.
[4] As expected, the expression of miRNAs is globally inhibited in ADAR1(-/-) mouse embryos, which, in turn, alters the expression of their target genes and might contribute to their embryonic lethal phenotype.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "In this study, we investigated the interaction of the RNA editing mechanism with the RNA interference (RNAi) machinery and found that ADAR1 forms a complex with Dicer through direct protein-protein interaction.". 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: ADAR1 binds to Dicer to cleave pre-miRNA.

Document title: ADAR1 Forms a Complex with Dicer to Promote MicroRNA Processing and RNA-Induced Gene Silencing

Abstract sentences:
[0] Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosine residues to inosine specifically in double-stranded RNAs.
[1] In this study, we investigated the interaction of the RNA editing mechanism with the RNA interference (RNAi) machinery and found that ADAR1 forms a complex with Dicer through direct protein-protein interaction.
[2] Most importantly, ADAR1 increases the maximum rate (Vmax) of pre-microRNA (miRNA) cleavage by Dicer and facilitates loading of miRNA onto RNA-induced silencing complexes, identifying a new role of ADAR1 in miRNA processing and RNAi mechanisms.
[3] ADAR1 differentiates its functions in RNA editing and RNAi by the formation of either ADAR1/ADAR1 homodimer or Dicer/ADAR1 heterodimer complexes, respectively.
[4] As expected, the expression of miRNAs is globally inhibited in ADAR1(-/-) mouse embryos, which, in turn, alters the expression of their target genes and might contribute to their embryonic lethal phenotype.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Most importantly, ADAR1 increases the maximum rate (Vmax) of pre-microRNA (miRNA) cleavage by Dicer and facilitates loading of miRNA onto RNA-induced silencing complexes, identifying a new role of ADAR1 in miRNA processing and RNAi mechanisms.". 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: AIRE is expressed in some skin tumors.

Document title: Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes

Abstract sentences:
[0] Expression of the intermediate filament protein keratin 17 (K17) is robustly upregulated in inflammatory skin diseases and in many tumors originating in stratified and pseudostratified epithelia.
[1] We report that autoimmune regulator (Aire), a transcriptional regulator, is inducibly expressed in human and mouse tumor keratinocytes in a K17-dependent manner and is required for timely onset of Gli2-induced skin tumorigenesis in mice.
[2] The induction of Aire mRNA in keratinocytes depends on a functional interaction between K17 and the heterogeneous nuclear ribonucleoprotein hnRNP K. Further, K17 colocalizes with Aire protein in the nucleus of tumor-prone keratinocytes, and each factor is bound to a specific promoter region featuring an NF-κB consensus sequence in a relevant subset of K17- and Aire-dependent proinflammatory genes.
[3] These findings provide radically new insight into keratin intermediate filament and Aire function, along with a molecular basis for the K17-dependent amplification of inflammatory and immune responses in diseased epithelia.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "We report that autoimmune regulator (Aire), a transcriptional regulator, is inducibly expressed in human and mouse tumor keratinocytes in a K17-dependent manner and is required for timely onset of Gli2-induced skin tumorigenesis in mice.". 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: ALDH1 expression is associated with better breast cancer outcomes.

Document title: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.

Abstract sentences:
[0] Application of stem cell biology to breast cancer research has been limited by the lack of simple methods for identification and isolation of normal and malignant stem cells.
[1] Utilizing in vitro and in vivo experimental systems, we show that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties.
[2] These cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model.
[3] In breast carcinomas, high ALDH activity identifies the tumorigenic cell fraction, capable of self-renewal and of generating tumors that recapitulate the heterogeneity of the parental tumor.
[4] In a series of 577 breast carcinomas, expression of ALDH1 detected by immunostaining correlated with poor prognosis.
[5] These findings offer an important new tool for the study of normal and malignant breast stem cells and facilitate the clinical application of stem cell concepts.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "In a series of 577 breast carcinomas, expression of ALDH1 detected by immunostaining correlated with poor prognosis.". 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: ALDH1 expression is associated with poorer prognosis in breast cancer.

Document title: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.

Abstract sentences:
[0] Application of stem cell biology to breast cancer research has been limited by the lack of simple methods for identification and isolation of normal and malignant stem cells.
[1] Utilizing in vitro and in vivo experimental systems, we show that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties.
[2] These cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model.
[3] In breast carcinomas, high ALDH activity identifies the tumorigenic cell fraction, capable of self-renewal and of generating tumors that recapitulate the heterogeneity of the parental tumor.
[4] In a series of 577 breast carcinomas, expression of ALDH1 detected by immunostaining correlated with poor prognosis.
[5] These findings offer an important new tool for the study of normal and malignant breast stem cells and facilitate the clinical application of stem cell concepts.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "In a series of 577 breast carcinomas, expression of ALDH1 detected by immunostaining correlated with poor prognosis.". 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: AMP-activated protein kinase (AMPK) activation increases inflammation-related fibrosis in the lungs.

Document title: Metformin reverses established lung fibrosis in a bleomycin model

Abstract sentences:
[0] Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in a number of organs, including the lungs1.
[1] Cellular metabolism regulates tissue repair and remodelling responses to injury2-4.
[2] AMPK is a critical sensor of cellular bioenergetics and controls the switch from anabolic to catabolic metabolism5.
[3] However, the role of AMPK in fibrosis is not well understood.
[4] Here, we demonstrate that in humans with idiopathic pulmonary fibrosis (IPF) and in an experimental mouse model of lung fibrosis, AMPK activity is lower in fibrotic regions associated with metabolically active and apoptosis-resistant myofibroblasts.
[5] Pharmacological activation of AMPK in myofibroblasts from lungs of humans with IPF display lower fibrotic activity, along with enhanced mitochondrial biogenesis and normalization of sensitivity to apoptosis.
[6] In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner.
[7] These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes, and support a role for metformin (or other AMPK activators) to reverse established fibrosis by facilitating deactivation and apoptosis of myofibroblasts.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Pharmacological activation of AMPK in myofibroblasts from lungs of humans with IPF display lower fibrotic activity, along with enhanced mitochondrial biogenesis and normalization of sensitivity to apoptosis.". This contradicts the claim.


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

Claim: AMP-activated protein kinase (AMPK) activation increases inflammation-related fibrosis in the lungs.

Document title: Metformin reverses established lung fibrosis in a bleomycin model

Abstract sentences:
[0] Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in a number of organs, including the lungs1.
[1] Cellular metabolism regulates tissue repair and remodelling responses to injury2-4.
[2] AMPK is a critical sensor of cellular bioenergetics and controls the switch from anabolic to catabolic metabolism5.
[3] However, the role of AMPK in fibrosis is not well understood.
[4] Here, we demonstrate that in humans with idiopathic pulmonary fibrosis (IPF) and in an experimental mouse model of lung fibrosis, AMPK activity is lower in fibrotic regions associated with metabolically active and apoptosis-resistant myofibroblasts.
[5] Pharmacological activation of AMPK in myofibroblasts from lungs of humans with IPF display lower fibrotic activity, along with enhanced mitochondrial biogenesis and normalization of sensitivity to apoptosis.
[6] In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner.
[7] These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes, and support a role for metformin (or other AMPK activators) to reverse established fibrosis by facilitating deactivation and apoptosis of myofibroblasts.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [6]
Explanation: Evidence states: "In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner.". 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: AMP-activated protein kinase (AMPK) activation increases inflammation-related fibrosis in the lungs.

Document title: Metformin reverses established lung fibrosis in a bleomycin model

Abstract sentences:
[0] Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in a number of organs, including the lungs1.
[1] Cellular metabolism regulates tissue repair and remodelling responses to injury2-4.
[2] AMPK is a critical sensor of cellular bioenergetics and controls the switch from anabolic to catabolic metabolism5.
[3] However, the role of AMPK in fibrosis is not well understood.
[4] Here, we demonstrate that in humans with idiopathic pulmonary fibrosis (IPF) and in an experimental mouse model of lung fibrosis, AMPK activity is lower in fibrotic regions associated with metabolically active and apoptosis-resistant myofibroblasts.
[5] Pharmacological activation of AMPK in myofibroblasts from lungs of humans with IPF display lower fibrotic activity, along with enhanced mitochondrial biogenesis and normalization of sensitivity to apoptosis.
[6] In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner.
[7] These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes, and support a role for metformin (or other AMPK activators) to reverse established fibrosis by facilitating deactivation and apoptosis of myofibroblasts.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes, and support a role for metformin (or other AMPK activators) to reverse established fibrosis by facilitating deactivation and apoptosis of myofibroblasts.". 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: APOE4 expression in iPSC-derived neurons increases AlphaBeta production and tau phosphorylation causing GABA neuron degeneration.

Document title: Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector

Abstract sentences:
[0] Efforts to develop drugs for Alzheimer's disease (AD) have shown promise in animal studies, only to fail in human trials, suggesting a pressing need to study AD in human model systems.
[1] Using human neurons derived from induced pluripotent stem cells that expressed apolipoprotein E4 (ApoE4), a variant of the APOE gene product and the major genetic risk factor for AD, we demonstrated that ApoE4-expressing neurons had higher levels of tau phosphorylation, unrelated to their increased production of amyloid-β (Aβ) peptides, and that they displayed GABAergic neuron degeneration.
[2] ApoE4 increased Aβ production in human, but not in mouse, neurons.
[3] Converting ApoE4 to ApoE3 by gene editing rescued these phenotypes, indicating the specific effects of ApoE4.
[4] Neurons that lacked APOE behaved similarly to those expressing ApoE3, and the introduction of ApoE4 expression recapitulated the pathological phenotypes, suggesting a gain of toxic effects from ApoE4.
[5] Treatment of ApoE4-expressing neurons with a small-molecule structure corrector ameliorated the detrimental effects, thus showing that correcting the pathogenic conformation of ApoE4 is a viable therapeutic approach for ApoE4-related AD.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Using human neurons derived from induced pluripotent stem cells that expressed apolipoprotein E4 (ApoE4), a variant of the APOE gene product and the major genetic risk factor for AD, we demonstrated that ApoE4-expressing neurons had higher levels of tau phosphorylation, unrelated to their increased production of amyloid-β (Aβ) peptides, and that they displayed GABAergic neuron degeneration.". 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: APOE4 expression in iPSC-derived neurons increases AlphaBeta production and tau phosphorylation, delaying GABA neuron degeneration.

Document title: Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector

Abstract sentences:
[0] Efforts to develop drugs for Alzheimer's disease (AD) have shown promise in animal studies, only to fail in human trials, suggesting a pressing need to study AD in human model systems.
[1] Using human neurons derived from induced pluripotent stem cells that expressed apolipoprotein E4 (ApoE4), a variant of the APOE gene product and the major genetic risk factor for AD, we demonstrated that ApoE4-expressing neurons had higher levels of tau phosphorylation, unrelated to their increased production of amyloid-β (Aβ) peptides, and that they displayed GABAergic neuron degeneration.
[2] ApoE4 increased Aβ production in human, but not in mouse, neurons.
[3] Converting ApoE4 to ApoE3 by gene editing rescued these phenotypes, indicating the specific effects of ApoE4.
[4] Neurons that lacked APOE behaved similarly to those expressing ApoE3, and the introduction of ApoE4 expression recapitulated the pathological phenotypes, suggesting a gain of toxic effects from ApoE4.
[5] Treatment of ApoE4-expressing neurons with a small-molecule structure corrector ameliorated the detrimental effects, thus showing that correcting the pathogenic conformation of ApoE4 is a viable therapeutic approach for ApoE4-related AD.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Using human neurons derived from induced pluripotent stem cells that expressed apolipoprotein E4 (ApoE4), a variant of the APOE gene product and the major genetic risk factor for AD, we demonstrated that ApoE4-expressing neurons had higher levels of tau phosphorylation, unrelated to their increased production of amyloid-β (Aβ) peptides, and that they displayed GABAergic neuron degeneration.". 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: Activation of PPM1D suppresses p53 function.

Document title: Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas

Abstract sentences:
[0] Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect.
[1] To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic gliomas.
[2] We also performed targeted mutational analysis of an additional 24 such tumors and genome-wide methylation profiling of 45 gliomas.
[3] This study led to the discovery of tumor-specific mutations in PPM1D, encoding wild-type p53-induced protein phosphatase 1D (WIP1), in 37.5% of the BSGs that harbored hallmark H3F3A mutations encoding p.
[4] Lys27Met substitutions.
[5] PPM1D mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53 activation in vitro.
[6] PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2.
[7] These results define PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5, 6]
Explanation: Evidence states: "PPM1D mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53 activation in vitro. PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2.". 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: Activation of PPM1D suppresses p53 function.

Document title: Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer

Abstract sentences:
[0] Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease.
[1] However, there are considerable challenges with respect to study design, data analysis and replication.
[2] Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case–control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer.
[3] PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10−5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10−4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10−9).
[4] Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain.
[5] Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms.
[6] Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect.
[7] Our results have implications for the detection and management of breast and ovarian cancer risk.
[8] More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms.". 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: Activator-inhibitor pairs are provided dorsally by Admpchordin.

Document title: Regulation of ADMP and BMP2/4/7 at Opposite Embryonic Poles Generates a Self-Regulating Morphogenetic Field

Abstract sentences:
[0] Embryos have the ability to self-regulate and regenerate normal structures after being sectioned in half.
[1] How is such a morphogenetic field established?
[2] We discovered that quadruple knockdown of ADMP and BMP2/4/7 in Xenopus embryos eliminates self-regulation, causing ubiquitous neural induction throughout the ectoderm.
[3] ADMP transcription in the Spemann organizer is activated at low BMP levels.
[4] When ventral BMP2/4/7 signals are depleted, Admp expression increases, allowing for self-regulation.
[5] ADMP has BMP-like activity and signals via the ALK-2 receptor.
[6] It is unable to signal dorsally because of inhibition by Chordin.
[7] The ventral BMP antagonists Sizzled and Bambi further refine the pattern.
[8] By transplanting dorsal or ventral wild-type grafts into ADMP/BMP2/4/7-depleted hosts, we demonstrate that both poles serve as signaling centers that can induce histotypic differentiation over considerable distances.
[9] We conclude that dorsal and ventral BMP signals and their extracellular antagonists expressed under opposing transcriptional regulation provide a molecular mechanism for embryonic self-regulation.

[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: Active H. pylori urease has a polymeric structure that compromises two subunits, UreA and UreB.

Document title: Structure of the proton-gated urea channel from the gastric pathogen Helicobacter pylori

Abstract sentences:
[0] Half the world's population is chronically infected with Helicobacter pylori, causing gastritis, gastric ulcers and an increased incidence of gastric adenocarcinoma.
[1] Its proton-gated inner-membrane urea channel, HpUreI, is essential for survival in the acidic environment of the stomach.
[2] The channel is closed at neutral pH and opens at acidic pH to allow the rapid access of urea to cytoplasmic urease.
[3] Urease produces NH(3) and CO(2), neutralizing entering protons and thus buffering the periplasm to a pH of roughly 6.1 even in gastric juice at a pH below 2.0.
[4] Here we report the structure of HpUreI, revealing six protomers assembled in a hexameric ring surrounding a central bilayer plug of ordered lipids.
[5] Each protomer encloses a channel formed by a twisted bundle of six transmembrane helices.
[6] The bundle defines a previously unobserved fold comprising a two-helix hairpin motif repeated three times around the central axis of the channel, without the inverted repeat of mammalian-type urea transporters.
[7] Both the channel and the protomer interface contain residues conserved in the AmiS/UreI superfamily, suggesting the preservation of channel architecture and oligomeric state in this superfamily.
[8] Predominantly aromatic or aliphatic side chains line the entire channel and define two consecutive constriction sites in the middle of the channel.
[9] Mutation of Trp 153 in the cytoplasmic constriction site to Ala or Phe decreases the selectivity for urea in comparison with thiourea, suggesting that solute interaction with Trp 153 contributes specificity.
[10] The previously unobserved hexameric channel structure described here provides a new model for the permeation of urea and other small amide solutes in prokaryotes and archaea.

[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: Albendazole is used to treat lymphatic filariasis.

Document title: “Rapid-Impact Interventions”: How a Policy of Integrated Control for Africa's Neglected Tropical Diseases Could Benefit the Poor

Abstract sentences:
[0] Over the past two decades there have been significant achievements in the control of a handful of important human tropical infections [1].
[1] These achievements include the substantive reductions in the prevalence and incidence of the so-called neglected diseases such as lymphatic filariasis, onchocerciasis, guinea worm, leprosy, and trachoma (Box 1) [2].
[2] Each of these neglected diseases is a poverty-promoting and often stigmatizing condition occurring primarily in rural areas of low-income countries (Box 2) [3].
[3] They are ancient afflictions, described in the Bible and other ancient texts, which have burdened humanity for millennia [3].
[4] But now, as a result of aggressive regional vertical interventions, there is a possibility that some neglected tropical infections could be eventually controlled to the point of elimination in some areas of endemicity [2–8].
[5] In the case of guinea worm infection, disease eradication might also soon be possible [9].
[6] Box 2.
[7] Common Features of the Neglected Tropical Diseases          Ancient afflictions that have burdened humanity for centuries      Poverty-promoting conditions      Associated with stigma      Rural areas of low-income countries and fragile states      No commercial markets for products that target these diseases      Interventions, when applied, have a history of success

[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: Alizarin forms hydrogen bonds with residues involved in PGAM1 substrate binding.

Document title: Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation

Abstract sentences:
[0] How oncogenic signalling coordinates glycolysis and anabolic biosynthesis in cancer cells remains unclear.
[1] We recently reported that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) regulates anabolic biosynthesis by controlling intracellular levels of its substrate 3-phosphoglycerate and product 2-phosphoglycerate.
[2] Here we report a novel mechanism in which Y26 phosphorylation enhances PGAM1 activation through release of inhibitory E19 that blocks the active site, stabilising cofactor 2,3-bisphosphoglycerate binding and H11 phosphorylation.
[3] We also report the crystal structure of H11-phosphorylated PGAM1 and find that phospho-H11 activates PGAM1 at least in part by promoting substrate 3-phosphoglycerate binding.
[4] Moreover, Y26 phosphorylation of PGAM1 is common in human cancer cells and contributes to regulation of 3-phosphoglycerate and 2-phosphoglycerate levels, promoting cancer cell proliferation and tumour growth.
[5] As PGAM1 is a negative transcriptional target of TP53, and is therefore commonly upregulated in human cancers, these findings suggest that Y26 phosphorylation represents an additional acute mechanism underlying phosphoglycerate mutase 1 upregulation.

[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: All hematopoietic stem cells segregate their chromosomes randomly.

Document title: Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU

Abstract sentences:
[0] Stem cells are proposed to segregate chromosomes asymmetrically during self-renewing divisions so that older (‘immortal’) DNA strands are retained in daughter stem cells whereas newly synthesized strands segregate to differentiating cells.
[1] Stem cells are also proposed to retain DNA labels, such as 5-bromo-2-deoxyuridine (BrdU), either because they segregate chromosomes asymmetrically or because they divide slowly.
[2] However, the purity of stem cells among BrdU-label-retaining cells has not been documented in any tissue, and the ‘immortal strand hypothesis’ has not been tested in a system with definitive stem cell markers.
[3] Here we tested these hypotheses in haematopoietic stem cells (HSCs), which can be highly purified using well characterized markers.
[4] We administered BrdU to newborn mice, mice treated with cyclophosphamide and granulocyte colony-stimulating factor, and normal adult mice for 4 to 10 days, followed by 70 days without BrdU. In each case, less than 6% of HSCs retained BrdU and less than 0.5% of all BrdU-retaining haematopoietic cells were HSCs, revealing that BrdU has poor specificity and poor sensitivity as an HSC marker.
[5] Sequential administration of 5-chloro-2-deoxyuridine and 5-iodo-2-deoxyuridine indicated that all HSCs segregate their chromosomes randomly.
[6] Division of individual HSCs in culture revealed no asymmetric segregation of the label.
[7] Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Sequential administration of 5-chloro-2-deoxyuridine and 5-iodo-2-deoxyuridine indicated that all HSCs segregate their chromosomes randomly.". 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: Angiotensin converting enzyme inhibitors are associated with increased risk for functional renal insufficiency.

Document title: Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association.

Abstract sentences:
[0] Angiotensin converting enzyme (ACE) inhibitors are now one of the most frequently used classes of antihypertensive drugs.
[1] Beyond their utility in the management of hypertension, their use has been extended to the long-term management of patients with congestive heart failure (CHF), as well as diabetic and nondiabetic nephropathies.
[2] Although ACE inhibitor therapy usually improves renal blood flow (RBF) and sodium excretion rates in CHF and reduces the rate of progressive renal injury in chronic renal disease, its use can also be associated with a syndrome of “functional renal insufficiency” and/or hyperkalemia.
[3] This form of acute renal failure (ARF) most commonly develops shortly after initiation of ACE inhibitor therapy but can be observed after months or years of therapy, even in the absence of prior ill effects.
[4] ARF is most likely to occur when renal perfusion pressure cannot be sustained because of substantial decreases in mean arterial pressure (MAP) or when glomerular filtration rate (GFR) is highly angiotensin II (Ang II) dependent.
[5] Conditions that predict an adverse hemodynamic effect of ACE inhibitors in patients with CHF are preexisting hypotension and low cardiac filling pressures.
[6] The GFR is especially dependent on Ang II during extracellular fluid (ECF) volume depletion, high-grade bilateral renal artery stenosis, or stenosis of a dominant or single kidney, as in a renal transplant recipient.
[7] Understanding the pathophysiological mechanisms and the common risk factors for ACE inhibitor–induced functional ARF is critical, because preventive strategies for ARF exist, and if effectively used, they may permit use of these compounds in a less restricted fashion.
[8] Under normal physiological conditions, renal autoregulation adjusts renal vascular resistance, so that RBF and GFR remain constant over a wide range of MAPs.1 The intrinsic renal autoregulation mechanism is adjusted by Ang II and the sympathetic nervous system.
[9] When renal perfusion pressure falls (as in …

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Although ACE inhibitor therapy usually improves renal blood flow (RBF) and sodium excretion rates in CHF and reduces the rate of progressive renal injury in chronic renal disease, its use can also be associated with a syndrome of “functional renal insufficiency” and/or hyperkalemia.". 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: Angiotensin converting enzyme inhibitors are associated with increased risk for functional renal insufficiency.

Document title: Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association.

Abstract sentences:
[0] Angiotensin converting enzyme (ACE) inhibitors are now one of the most frequently used classes of antihypertensive drugs.
[1] Beyond their utility in the management of hypertension, their use has been extended to the long-term management of patients with congestive heart failure (CHF), as well as diabetic and nondiabetic nephropathies.
[2] Although ACE inhibitor therapy usually improves renal blood flow (RBF) and sodium excretion rates in CHF and reduces the rate of progressive renal injury in chronic renal disease, its use can also be associated with a syndrome of “functional renal insufficiency” and/or hyperkalemia.
[3] This form of acute renal failure (ARF) most commonly develops shortly after initiation of ACE inhibitor therapy but can be observed after months or years of therapy, even in the absence of prior ill effects.
[4] ARF is most likely to occur when renal perfusion pressure cannot be sustained because of substantial decreases in mean arterial pressure (MAP) or when glomerular filtration rate (GFR) is highly angiotensin II (Ang II) dependent.
[5] Conditions that predict an adverse hemodynamic effect of ACE inhibitors in patients with CHF are preexisting hypotension and low cardiac filling pressures.
[6] The GFR is especially dependent on Ang II during extracellular fluid (ECF) volume depletion, high-grade bilateral renal artery stenosis, or stenosis of a dominant or single kidney, as in a renal transplant recipient.
[7] Understanding the pathophysiological mechanisms and the common risk factors for ACE inhibitor–induced functional ARF is critical, because preventive strategies for ARF exist, and if effectively used, they may permit use of these compounds in a less restricted fashion.
[8] Under normal physiological conditions, renal autoregulation adjusts renal vascular resistance, so that RBF and GFR remain constant over a wide range of MAPs.1 The intrinsic renal autoregulation mechanism is adjusted by Ang II and the sympathetic nervous system.
[9] When renal perfusion pressure falls (as in …

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "Understanding the pathophysiological mechanisms and the common risk factors for ACE inhibitor–induced functional ARF is critical, because preventive strategies for ARF exist, and if effectively used, they may permit use of these compounds in a less restricted fashion.". 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: Anthrax spores can be disposed of easily after they are dispersed.

Document title: Secondary aerosolization of viable Bacillus anthracis spores in a contaminated US Senate Office.

Abstract sentences:
[0] CONTEXT Bioterrorist attacks involving letters and mail-handling systems in Washington, DC, resulted in Bacillus anthracis (anthrax) spore contamination in the Hart Senate Office Building and other facilities in the US Capitol's vicinity.
[1] OBJECTIVE To provide information about the nature and extent of indoor secondary aerosolization of B anthracis spores.
[2] DESIGN Stationary and personal air samples, surface dust, and swab samples were collected under semiquiescent (minimal activities) and then simulated active office conditions to estimate secondary aerosolization of B anthracis spores.
[3] Nominal size characteristics, airborne concentrations, and surface contamination of B anthracis particles (colony-forming units) were evaluated.
[4] RESULTS Viable B anthracis spores reaerosolized under semiquiescent conditions, with a marked increase in reaerosolization during simulated active office conditions.
[5] Increases were observed for B anthracis collected on open sheep blood agar plates (P<.001) and personal air monitors (P =.01) during active office conditions.
[6] More than 80% of the B anthracis particles collected on stationary monitors were within an alveolar respirable size range of 0.95 to 3.5 micro m.   CONCLUSIONS Bacillus anthracis spores used in a recent terrorist incident reaerosolized under common office activities.
[7] These findings have important implications for appropriate respiratory protection, remediation, and reoccupancy of contaminated office environments.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [6]
Explanation: Evidence states: "More than 80% of the B anthracis particles collected on stationary monitors were within an alveolar respirable size range of 0.95 to 3.5 micro m.   CONCLUSIONS Bacillus anthracis spores used in a recent terrorist incident reaerosolized under common office activities.". 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: Antibiotic induced alterations in the gut microbiome reduce resistance against Clostridium difficile

Document title: Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

Abstract sentences:
[0] Antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile.
[1] Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection.
[2] Levels of secondary bile acids, glucose, free fatty acids and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome.
[3] In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including the primary bile acid taurocholate for germination, and carbon sources such as mannitol, fructose, sorbitol, raffinose and stachyose for growth.
[4] Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favours C. difficile germination and growth.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "Antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile.". 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: Antibiotic induced alterations in the gut microbiome reduce resistance against Clostridium difficile

Document title: Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

Abstract sentences:
[0] Antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile.
[1] Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection.
[2] Levels of secondary bile acids, glucose, free fatty acids and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome.
[3] In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including the primary bile acid taurocholate for germination, and carbon sources such as mannitol, fructose, sorbitol, raffinose and stachyose for growth.
[4] Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favours C. difficile germination and growth.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favours C. difficile germination and growth.". 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: Antiretroviral therapy reduces rates of tuberculosis across a broad range of CD4 strata.

Document title: Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis

Abstract sentences:
[0] BACKGROUND Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa.
[1] In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide.
[2] Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis.
[3] We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection.
[4] METHODS AND FINDINGS PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched.
[5] Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries.
[6] For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count.
[7] Eleven studies met the inclusion criteria.
[8] Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44).
[9] There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20).
[10] CONCLUSIONS Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata.
[11] Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic.
[12] REVIEW REGISTRATION International Prospective Register of Systematic Reviews CRD42011001209 Please see later in the article for the Editors' Summary.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44).". 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: Antiretroviral therapy reduces rates of tuberculosis across a broad range of CD4 strata.

Document title: Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis

Abstract sentences:
[0] BACKGROUND Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa.
[1] In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide.
[2] Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis.
[3] We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection.
[4] METHODS AND FINDINGS PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched.
[5] Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries.
[6] For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count.
[7] Eleven studies met the inclusion criteria.
[8] Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44).
[9] There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20).
[10] CONCLUSIONS Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata.
[11] Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic.
[12] REVIEW REGISTRATION International Prospective Register of Systematic Reviews CRD42011001209 Please see later in the article for the Editors' Summary.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "CONCLUSIONS Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata.". 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: Arginine 90 in p150n is important for interaction with EB1.

Document title: Structural basis for the activation of microtubule assembly by the EB1 and p150Glued complex.

Abstract sentences:
[0] Plus-end tracking proteins, such as EB1 and the dynein/dynactin complex, regulate microtubule dynamics.
[1] These proteins are thought to stabilize microtubules by forming a plus-end complex at microtubule growing ends with ill-defined mechanisms.
[2] Here we report the crystal structure of two plus-end complex components, the carboxy-terminal dimerization domain of EB1 and the microtubule binding (CAP-Gly) domain of the dynactin subunit p150Glued.
[3] Each molecule of the EB1 dimer contains two helices forming a conserved four-helix bundle, while also providing p150Glued binding sites in its flexible tail region.
[4] Combining crystallography, NMR, and mutational analyses, our studies reveal the critical interacting elements of both EB1 and p150Glued, whose mutation alters microtubule polymerization activity.
[5] Moreover, removal of the key flexible tail from EB1 activates microtubule assembly by EB1 alone, suggesting that the flexible tail negatively regulates EB1 activity.
[6] We, therefore, propose that EB1 possesses an auto-inhibited conformation, which is relieved by p150Glued as an allosteric activator.

[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: Arterioles have a larger lumen diameter than venules.

Document title: Scaffold-based three-dimensional human fibroblast culture provides a structural matrix that supports angiogenesis in infarcted heart tissue.

Abstract sentences:
[0] BACKGROUND We have developed techniques to implant angiogenic patches onto the epicardium over regions of infarcted cardiac tissue to stimulate revascularization of the damaged tissue.
[1] These experiments used a scaffold-based 3D human dermal fibroblast culture (3DFC) as an epicardial patch.
[2] The 3DFC contains viable cells that secrete angiogenic growth factors and has previously been shown to stimulate angiogenic activity.
[3] The hypothesis tested was that a viable 3DFC cardiac patch would stimulate an angiogenic response within an area of infarcted cardiac tissue.
[4] METHODS AND RESULTS A coronary occlusion of a branch of the left anterior descending coronary artery was performed by thermal ligation in severe combined immunodeficient mice.
[5] 3DFCs with or without viable cells were sized to the damaged area, implanted in replicate mice onto the epicardium at the site of tissue injury, and compared with animals that received infarct surgery but no implant.
[6] Fourteen and 30 days after surgery, hearts were exposed and photographed, and tissue samples were prepared for histology and cytochemistry.
[7] Fourteen and 30 days after surgery, the damaged myocardium receiving viable 3DFC exhibited a significantly greater angiogenic response (including arterioles, venules, and capillaries) than nonviable and untreated control groups.
[8] CONCLUSIONS In this animal model, viable 3DFC stimulates angiogenesis within a region of cardiac infarction and can augment a repair response in damaged tissue.
[9] Therefore, a potential use for 3DFC is the repair of myocardial tissue damaged by infarction.

[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: Articles published in open access format are less likely to be cited than traditional journals.

Document title: Open Access Increases Citation Rate

Abstract sentences:
[0] PLoS Biology publishes today a research article by Gunther Eysenbach that is not about biology.
[1] It is about citations.
[2] It provides robust evidence that open-access articles (OA articles) are more immediately recognized and cited than non-OA articles.
[3] As such, it adds objective support to the belief we have always held that open-access publication speeds up scientific dialog between researchers and, consequently, should be extended to the whole scientific literature as quickly as possible.
[4] It is therefore fitting that we publish such a paper.
[5] We have long argued that papers freely available in a journal will be more often read and cited than those behind a subscription barrier.
[6] However, solid evidence to support or refute such a claim has been surprisingly hard to find.
[7] Since most open-access journals are new, comparisons of the effects of open access with established subscription-based journals are easily confounded by age and reputation.
[8] In the current study, Eysenbach compared citations compiled by Thomson Scientific (formerly Thomson ISI) to individual articles published between June 2004 and December 2004 in the same journal—namely, Proceedings of the National Academy of Sciences (PNAS), which announced its open-access option for authors on June 8 of that year, with an associated publication charge of US$1,000.
[9] Non-OA articles in PNAS are subject to a six-month “toll-access” delay before the article becomes publicly available.
[10] The results of this natural experiment are clear: in the 4 to 16 months following publication, OA articles gained a significant citation advantage over non-OA articles during the same period.
[11] They are twice as likely to be cited 4 to 10 months after publication and almost three times as likely between 10 and 16 months.
[12] Given that PNAS delays open access for only six months, the disparity between OA and non-OA articles in journals where the delay is longer or where articles remain “toll-access” is likely to be even greater.
[13] Eysenbach also looked at the impact of self-archiving non-OA articles.
[14] One route to open access, it is argued, is for authors to archive their published articles on their own Web sites or in institutional repositories, although this does not include an explicit business model to cover the cost of peer-review and publishing.
[15] The analysis revealed that self-archived articles are also cited less often than OA articles from the same journal.
[16] Yes, you're right; we do have a strong and vested interest in publishing results that so obviously endorse our existence.
[17] Moreover, the author of the article is also an editor of an open-access journal.
[18] But sometimes a potential conflict of interest can actually help to ensure rigor.
[19] In this case, we have an acute interest in ensuring that the article meets the same, if not higher, standards as any other research article we publish.
[20] Not only must the conclusions provide a significant advance for the field, but the study must be technically sound, with appropriate evidence to support those conclusions.
[21] As with all our research articles, we consulted throughout the evaluation process with an academic editor with appropriate expertise—in this case, Carol Tenopir, professor of information sciences at the University of Tennessee (Knoxville, Tennessee, United States).
[22] The article was reviewed by two experts in bibliometric analyses and information science, and an experienced research biologist with expertise in statistics.
[23] They all enthusiastically supported publication, although one understandably questioned the suitability of PLoS Biology as the publication venue.
[24] We have no intention of making PLoS Biology a regular home for bibliometric studies (even when about open access).
[25] What makes this study worth publishing in PLoS Biology is not only the relative strength of evidence supporting the claim but also the extent to which many (especially other publishers) have anticipated such an analysis.
[26] As far as we are aware, no other study has compared OA and non-OA articles from the same journal and controlled for so many potentially confounding factors.
[27] Eysenbach's multivariate analysis took into account the number of days since publication, number of authors, article type, country of the corresponding author, funding type, subject area, submission track ( PNAS has three different ways that authors can submit a paper), and the previous citation record of the first and last authors.
[28] He even administered a supplementary questionnaire to assess whether authors choosing the OA option in PNAS chose to do so for only their most important research (they didn't).
[29] As Ian Rowlands from the Centre for Publishing at University College London—and one of the reviewers who agreed to be identified in this article—said at the start of his review:          “Many (most) of the papers and presentations I have read/seen on this topic have completely failed to address the kinds of confounding issues that are so convincingly tackled here.
[30] For that reason alone, this paper deserves to be published and alerted to the widest possible audience.
[31] ”          In addition to providing evidence for the immediate advantage of open access, Eysenbach's analysis also highlights several potential challenges to its long-term future.
[32] Although a limited dataset, the citation history of the first and last authors differed between those who chose the open-access option and those who did not.
[33] In the group that chose open access, last authors tended to have a “stronger” previous citation record, whereas this situation was reversed among the group that declined the open-access option—here, it was the first authors who tended to be stronger.
[34] This may reflect varying attitudes of authors at different stages of their career, a stronger influence from the leader of a particular group, or an age- or career-related difference in the ability to pay the publication charge (e.g., [ 1]).
[35] Indeed, access to appropriate funds may also be a reason why a lower proportion of authors from European countries tended to choose the open-access option.
[36] In many of these countries, funds for page charges—and, by extension, open-access publication fees—are often not included within research grants.
[37] PNAS was one of the first journals to offer an open-access option to its authors.
[38] However, such hybrid journals are increasing: Blackwell, Springer, and Oxford University Press now provide this option as well.
[39] This means that similar experiments can be replicated.
[40] Moreover, although the evidence from the current analysis argues most strongly for a time advantage in citation for OA articles, a study over longer periods will reveal whether this translates into a sustained increase in the number of citations.
[41] In the meantime, open-access advocates should be emboldened by tangible evidence for what has seemed obvious all along.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [2]
Explanation: Evidence states: "It provides robust evidence that open-access articles (OA articles) are more immediately recognized and cited than non-OA articles.". 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: Articles published in open access format are less likely to be cited than traditional journals.

Document title: Open Access Increases Citation Rate

Abstract sentences:
[0] PLoS Biology publishes today a research article by Gunther Eysenbach that is not about biology.
[1] It is about citations.
[2] It provides robust evidence that open-access articles (OA articles) are more immediately recognized and cited than non-OA articles.
[3] As such, it adds objective support to the belief we have always held that open-access publication speeds up scientific dialog between researchers and, consequently, should be extended to the whole scientific literature as quickly as possible.
[4] It is therefore fitting that we publish such a paper.
[5] We have long argued that papers freely available in a journal will be more often read and cited than those behind a subscription barrier.
[6] However, solid evidence to support or refute such a claim has been surprisingly hard to find.
[7] Since most open-access journals are new, comparisons of the effects of open access with established subscription-based journals are easily confounded by age and reputation.
[8] In the current study, Eysenbach compared citations compiled by Thomson Scientific (formerly Thomson ISI) to individual articles published between June 2004 and December 2004 in the same journal—namely, Proceedings of the National Academy of Sciences (PNAS), which announced its open-access option for authors on June 8 of that year, with an associated publication charge of US$1,000.
[9] Non-OA articles in PNAS are subject to a six-month “toll-access” delay before the article becomes publicly available.
[10] The results of this natural experiment are clear: in the 4 to 16 months following publication, OA articles gained a significant citation advantage over non-OA articles during the same period.
[11] They are twice as likely to be cited 4 to 10 months after publication and almost three times as likely between 10 and 16 months.
[12] Given that PNAS delays open access for only six months, the disparity between OA and non-OA articles in journals where the delay is longer or where articles remain “toll-access” is likely to be even greater.
[13] Eysenbach also looked at the impact of self-archiving non-OA articles.
[14] One route to open access, it is argued, is for authors to archive their published articles on their own Web sites or in institutional repositories, although this does not include an explicit business model to cover the cost of peer-review and publishing.
[15] The analysis revealed that self-archived articles are also cited less often than OA articles from the same journal.
[16] Yes, you're right; we do have a strong and vested interest in publishing results that so obviously endorse our existence.
[17] Moreover, the author of the article is also an editor of an open-access journal.
[18] But sometimes a potential conflict of interest can actually help to ensure rigor.
[19] In this case, we have an acute interest in ensuring that the article meets the same, if not higher, standards as any other research article we publish.
[20] Not only must the conclusions provide a significant advance for the field, but the study must be technically sound, with appropriate evidence to support those conclusions.
[21] As with all our research articles, we consulted throughout the evaluation process with an academic editor with appropriate expertise—in this case, Carol Tenopir, professor of information sciences at the University of Tennessee (Knoxville, Tennessee, United States).
[22] The article was reviewed by two experts in bibliometric analyses and information science, and an experienced research biologist with expertise in statistics.
[23] They all enthusiastically supported publication, although one understandably questioned the suitability of PLoS Biology as the publication venue.
[24] We have no intention of making PLoS Biology a regular home for bibliometric studies (even when about open access).
[25] What makes this study worth publishing in PLoS Biology is not only the relative strength of evidence supporting the claim but also the extent to which many (especially other publishers) have anticipated such an analysis.
[26] As far as we are aware, no other study has compared OA and non-OA articles from the same journal and controlled for so many potentially confounding factors.
[27] Eysenbach's multivariate analysis took into account the number of days since publication, number of authors, article type, country of the corresponding author, funding type, subject area, submission track ( PNAS has three different ways that authors can submit a paper), and the previous citation record of the first and last authors.
[28] He even administered a supplementary questionnaire to assess whether authors choosing the OA option in PNAS chose to do so for only their most important research (they didn't).
[29] As Ian Rowlands from the Centre for Publishing at University College London—and one of the reviewers who agreed to be identified in this article—said at the start of his review:          “Many (most) of the papers and presentations I have read/seen on this topic have completely failed to address the kinds of confounding issues that are so convincingly tackled here.
[30] For that reason alone, this paper deserves to be published and alerted to the widest possible audience.
[31] ”          In addition to providing evidence for the immediate advantage of open access, Eysenbach's analysis also highlights several potential challenges to its long-term future.
[32] Although a limited dataset, the citation history of the first and last authors differed between those who chose the open-access option and those who did not.
[33] In the group that chose open access, last authors tended to have a “stronger” previous citation record, whereas this situation was reversed among the group that declined the open-access option—here, it was the first authors who tended to be stronger.
[34] This may reflect varying attitudes of authors at different stages of their career, a stronger influence from the leader of a particular group, or an age- or career-related difference in the ability to pay the publication charge (e.g., [ 1]).
[35] Indeed, access to appropriate funds may also be a reason why a lower proportion of authors from European countries tended to choose the open-access option.
[36] In many of these countries, funds for page charges—and, by extension, open-access publication fees—are often not included within research grants.
[37] PNAS was one of the first journals to offer an open-access option to its authors.
[38] However, such hybrid journals are increasing: Blackwell, Springer, and Oxford University Press now provide this option as well.
[39] This means that similar experiments can be replicated.
[40] Moreover, although the evidence from the current analysis argues most strongly for a time advantage in citation for OA articles, a study over longer periods will reveal whether this translates into a sustained increase in the number of citations.
[41] In the meantime, open-access advocates should be emboldened by tangible evidence for what has seemed obvious all along.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10]
Explanation: Evidence states: "The results of this natural experiment are clear: in the 4 to 16 months following publication, OA articles gained a significant citation advantage over non-OA articles during the same period.". This contradicts the claim.