[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: There is no known interaction between Pioneer factor OCT3/4 and major chromatin remodeling factors.

Document title: An Oct4-Centered Protein Interaction Network in Embryonic Stem Cells

Abstract sentences:
[0] Transcription factors, such as Oct4, are critical for establishing and maintaining pluripotent cell identity.
[1] Whereas the genomic locations of several pluripotency transcription factors have been reported, the spectrum of their interaction partners is underexplored.
[2] Here, we use an improved affinity protocol to purify Oct4-interacting proteins from mouse embryonic stem cells (ESCs).
[3] Subsequent purification of Oct4 partners Sall4, Tcfcp2l1, Dax1, and Esrrb resulted in an Oct4 interactome of 166 proteins, including transcription factors and chromatin-modifying complexes with documented roles in self-renewal, but also many factors not previously associated with the ESC network.
[4] We find that Esrrb associated with the basal transcription machinery and also detect interactions between transcription factors and components of the TGF-beta, Notch, and Wnt signaling pathways.
[5] Acute depletion of Oct4 reduced binding of Tcfcp2l1, Dax1, and Esrrb to several target genes.
[6] In conclusion, our purification protocol allowed us to bring greater definition to the circuitry controlling pluripotent cell identity.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Subsequent purification of Oct4 partners Sall4, Tcfcp2l1, Dax1, and Esrrb resulted in an Oct4 interactome of 166 proteins, including transcription factors and chromatin-modifying complexes with documented roles in self-renewal, but also many factors not previously associated with the ESC network.". 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: There is no relation between Erythromycin use and hypertrophic pyloric stenosis.

Document title: Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort study

Abstract sentences:
[0] OBJECTIVE To assess the association between use of macrolide antibiotics in mothers and infants from pregnancy onset until 120 days after birth and infantile hypertrophic pyloric stenosis (IHPS).
[1] DESIGN Nationwide register based cohort study.
[2] SETTING Denmark, 1996-2011.
[3] PARTICIPANTS 999,378 liveborn singletons and linked individual level information on macrolide prescriptions (maternal use during pregnancy, n=30,091; maternal use after birth, n=21,557; use in infants, n=6591), surgery for IHPS, and potential confounders.
[4] MAIN OUTCOME MEASURES Surgery for IHPS by three categories of macrolide use: in mothers during pregnancy, in mothers after birth, and in infants after birth.
[5] RESULTS 880 infants developed IHPS (0.9 cases per 1000 births).
[6] Compared with infants with no use of macrolides, the adjusted rate ratio for IHPS in infants with use of macrolides during days 0 to 13 after birth was 29.8 (95% confidence interval 16.4 to 54.1) and during days 14 to 120 was 3.24 (1.20 to 8.74); the corresponding absolute risk differences were 24.4 (95% confidence interval 13.0 to 44.1) and 0.65 (0.06 to 2.21) cases per 1000 infants exposed to macrolides, respectively.
[7] The rate ratio for maternal use of macrolides for days 0 to 13 after birth was 3.49 (1.92 to 6.34) and for days 14 to 120 was 0.70 (0.26 to 1.90); the corresponding absolute risk differences were 2.15 (0.82 to 4.64) and -0.11 (-0.26 to 0.31).
[8] The rate ratios for maternal use of macrolides during pregnancy were 1.02 (0.65 to 1.59) for weeks 0 to 27 and 1.77 (0.95 to 3.31) for weeks 28 to birth; the corresponding absolute risk differences were 0.01 (-0.31 to 0.50) and 0.67 (-0.06 to 2.02).
[9] CONCLUSIONS Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk.
[10] Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS.
[11] A possible association was also found with use during late pregnancy.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [9]
Explanation: Evidence states: "CONCLUSIONS Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk.". 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: There is no relation between Erythromycin use and hypertrophic pyloric stenosis.

Document title: Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort study

Abstract sentences:
[0] OBJECTIVE To assess the association between use of macrolide antibiotics in mothers and infants from pregnancy onset until 120 days after birth and infantile hypertrophic pyloric stenosis (IHPS).
[1] DESIGN Nationwide register based cohort study.
[2] SETTING Denmark, 1996-2011.
[3] PARTICIPANTS 999,378 liveborn singletons and linked individual level information on macrolide prescriptions (maternal use during pregnancy, n=30,091; maternal use after birth, n=21,557; use in infants, n=6591), surgery for IHPS, and potential confounders.
[4] MAIN OUTCOME MEASURES Surgery for IHPS by three categories of macrolide use: in mothers during pregnancy, in mothers after birth, and in infants after birth.
[5] RESULTS 880 infants developed IHPS (0.9 cases per 1000 births).
[6] Compared with infants with no use of macrolides, the adjusted rate ratio for IHPS in infants with use of macrolides during days 0 to 13 after birth was 29.8 (95% confidence interval 16.4 to 54.1) and during days 14 to 120 was 3.24 (1.20 to 8.74); the corresponding absolute risk differences were 24.4 (95% confidence interval 13.0 to 44.1) and 0.65 (0.06 to 2.21) cases per 1000 infants exposed to macrolides, respectively.
[7] The rate ratio for maternal use of macrolides for days 0 to 13 after birth was 3.49 (1.92 to 6.34) and for days 14 to 120 was 0.70 (0.26 to 1.90); the corresponding absolute risk differences were 2.15 (0.82 to 4.64) and -0.11 (-0.26 to 0.31).
[8] The rate ratios for maternal use of macrolides during pregnancy were 1.02 (0.65 to 1.59) for weeks 0 to 27 and 1.77 (0.95 to 3.31) for weeks 28 to birth; the corresponding absolute risk differences were 0.01 (-0.31 to 0.50) and 0.67 (-0.06 to 2.02).
[9] CONCLUSIONS Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk.
[10] Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS.
[11] A possible association was also found with use during late pregnancy.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [10]
Explanation: Evidence states: "Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS.". 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: There was an estimated 30 million cases of pneumonia in young children worldwide in 2010.

Document title: Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis

Abstract sentences:
[0] BACKGROUND The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown.
[1] We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010.
[2] METHODS We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies.
[3] We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year.
[4] We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies.
[5] FINDINGS We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3-13·9 million) episodes of severe and 3·0 million (2·1-4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide.
[6] Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies.
[7] On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265,000 (95% CI 160,000-450,000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries.
[8] Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals.
[9] INTERPRETATION Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children.
[10] Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection.
[11] Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities.
[12] FUNDING WHO.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "FINDINGS We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3-13·9 million) episodes of severe and 3·0 million (2·1-4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide.". 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: Thiopurine active metabolites can be catabolized through dephosphorylation of thioguanine nucleotides.

Document title: Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL

Abstract sentences:
[0] Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors.
[1] Despite intensive chemotherapy, 20% of pediatric patients and over 50% of adult patients with ALL do not achieve a complete remission or relapse after intensified chemotherapy, making disease relapse and resistance to therapy the most substantial challenge in the treatment of this disease.
[2] Using whole-exome sequencing, we identify mutations in the cytosolic 5'-nucleotidase II gene (NT5C2), which encodes a 5'-nucleotidase enzyme that is responsible for the inactivation of nucleoside-analog chemotherapy drugs, in 20/103 (19%) relapse T cell ALLs and 1/35 (3%) relapse B-precursor ALLs.
[3] NT5C2 mutant proteins show increased nucleotidase activity in vitro and conferred resistance to chemotherapy with 6-mercaptopurine and 6-thioguanine when expressed in ALL lymphoblasts.
[4] These results support a prominent role for activating mutations in NT5C2 and increased nucleoside-analog metabolism in disease progression and chemotherapy resistance in ALL.

[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: Tirasemtiv has no effect on cardiac muscle.

Document title: Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases

Abstract sentences:
[0] Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission.
[1] We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease.
[2] Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium.
[3] As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates.
[4] Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis.
[5] Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.

[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: Tirasemtiv targets cardiac muscle.

Document title: Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases

Abstract sentences:
[0] Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission.
[1] We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease.
[2] Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium.
[3] As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates.
[4] Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis.
[5] Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.

[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: Tirasemtiv targets fast-twitch muscle.

Document title: Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases

Abstract sentences:
[0] Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission.
[1] We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease.
[2] Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium.
[3] As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates.
[4] Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis.
[5] Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease.". This supports the claim.


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

Claim: Tirasemtiv targets fast-twitch muscle.

Document title: Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases

Abstract sentences:
[0] Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission.
[1] We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease.
[2] Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium.
[3] As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates.
[4] Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis.
[5] Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium.". 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: Toll-like receptor (TLR) signaling is involved in the pathogenesis of human MDS.

Document title: The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype.

Abstract sentences:
[0] Despite genetic heterogeneity, myelodysplastic syndromes (MDSs) share features of cytological dysplasia and ineffective hematopoiesis.
[1] We report that a hallmark of MDSs is activation of the NLRP3 inflammasome, which drives clonal expansion and pyroptotic cell death.
[2] Independent of genotype, MDS hematopoietic stem and progenitor cells (HSPCs) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct activation of caspase-1, generation of interleukin-1β (IL-1β) and IL-18, and pyroptotic cell death.
[3] Mechanistically, pyroptosis is triggered by the alarmin S100A9 that is found in excess in MDS HSPCs and bone marrow plasma.
[4] Further, like somatic gene mutations, S100A9-induced signaling activates NADPH oxidase (NOX), increasing levels of reactive oxygen species (ROS) that initiate cation influx, cell swelling, and β-catenin activation.
[5] Notably, knockdown of NLRP3 or caspase-1, neutralization of S100A9, and pharmacologic inhibition of NLRP3 or NOX suppress pyroptosis, ROS generation, and nuclear β-catenin in MDSs and are sufficient to restore effective hematopoiesis.
[6] Thus, alarmins and founder gene mutations in MDSs license a common redox-sensitive inflammasome circuit, which suggests new avenues for therapeutic intervention.

[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: Tonic signaling from the scFv induces constitutive stimulation.

Document title: 4-1BB Costimulation Ameliorates T Cell Exhaustion Induced by Tonic Signaling of Chimeric Antigen Receptors

Abstract sentences:
[0] Chimeric antigen receptors (CARs) targeting CD19 have mediated dramatic antitumor responses in hematologic malignancies, but tumor regression has rarely occurred using CARs targeting other antigens.
[1] It remains unknown whether the impressive effects of CD19 CARs relate to greater susceptibility of hematologic malignancies to CAR therapies, or superior functionality of the CD19 CAR itself.
[2] We show that tonic CAR CD3-ζ phosphorylation, triggered by antigen-independent clustering of CAR single-chain variable fragments, can induce early exhaustion of CAR T cells that limits antitumor efficacy.
[3] Such activation is present to varying degrees in all CARs studied, except the highly effective CD19 CAR.
[4] We further determine that CD28 costimulation augments, whereas 4-1BB costimulation reduces, exhaustion induced by persistent CAR signaling.
[5] Our results provide biological explanations for the antitumor effects of CD19 CARs and for the observations that CD19 CAR T cells incorporating the 4-1BB costimulatory domain are more persistent than those incorporating CD28 in clinical trials.

[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: Tonic signaling from the scFv is amplified by MyD88/CD40.

Document title: 4-1BB Costimulation Ameliorates T Cell Exhaustion Induced by Tonic Signaling of Chimeric Antigen Receptors

Abstract sentences:
[0] Chimeric antigen receptors (CARs) targeting CD19 have mediated dramatic antitumor responses in hematologic malignancies, but tumor regression has rarely occurred using CARs targeting other antigens.
[1] It remains unknown whether the impressive effects of CD19 CARs relate to greater susceptibility of hematologic malignancies to CAR therapies, or superior functionality of the CD19 CAR itself.
[2] We show that tonic CAR CD3-ζ phosphorylation, triggered by antigen-independent clustering of CAR single-chain variable fragments, can induce early exhaustion of CAR T cells that limits antitumor efficacy.
[3] Such activation is present to varying degrees in all CARs studied, except the highly effective CD19 CAR.
[4] We further determine that CD28 costimulation augments, whereas 4-1BB costimulation reduces, exhaustion induced by persistent CAR signaling.
[5] Our results provide biological explanations for the antitumor effects of CD19 CARs and for the observations that CD19 CAR T cells incorporating the 4-1BB costimulatory domain are more persistent than those incorporating CD28 in clinical trials.

[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: Tonic signaling from the scFv prevents constitutive stimulation.

Document title: 4-1BB Costimulation Ameliorates T Cell Exhaustion Induced by Tonic Signaling of Chimeric Antigen Receptors

Abstract sentences:
[0] Chimeric antigen receptors (CARs) targeting CD19 have mediated dramatic antitumor responses in hematologic malignancies, but tumor regression has rarely occurred using CARs targeting other antigens.
[1] It remains unknown whether the impressive effects of CD19 CARs relate to greater susceptibility of hematologic malignancies to CAR therapies, or superior functionality of the CD19 CAR itself.
[2] We show that tonic CAR CD3-ζ phosphorylation, triggered by antigen-independent clustering of CAR single-chain variable fragments, can induce early exhaustion of CAR T cells that limits antitumor efficacy.
[3] Such activation is present to varying degrees in all CARs studied, except the highly effective CD19 CAR.
[4] We further determine that CD28 costimulation augments, whereas 4-1BB costimulation reduces, exhaustion induced by persistent CAR signaling.
[5] Our results provide biological explanations for the antitumor effects of CD19 CARs and for the observations that CD19 CAR T cells incorporating the 4-1BB costimulatory domain are more persistent than those incorporating CD28 in clinical trials.

[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: Traditional reviews are biased in their interpretations.

Document title: Systematic reviews from astronomy to zoology: myths and misconceptions.

Abstract sentences:
[0] Systematic literature reviews are widely used as an aid to evidence based decision making.
[1] For example, reviews of randomised controlled trials are regularly used to answer questions about the effectiveness of healthcare interventions.
[2] The high profile of systematic reviews as a cornerstone of evidence based medicine, however, has led to several misconceptions about their purpose and methods.
[3] Among these is the belief that systematic reviews are applicable only to randomised controlled trials and that they are incapable of dealing with other forms of evidence, such as from non-randomised studies or qualitative research.
[4] The systematic literature review is a method of locating, appraising, and synthesising evidence.
[5] The value of regularly updated systematic reviews in the assessment of effectiveness of healthcare interventions was dramatically illustrated by Antman and colleagues, who showed that review articles failed to mention advances in treatment identified by an updated systematic review.1  It is nearly a quarter of a century since Gene Glass coined the term “meta-analysis” to refer to the quantitative synthesis of the results of primary studies.2 The importance of making explicit efforts to limit bias in the review of literature, however, has been emphasised by social scientists at least since the 1960s.3 In recent years systematic reviews have found an important role in health services research, and the growing interest in evidence based approaches to decision making makes it likely that their use will increase.
[6] Not everybody accepts that systematic reviews are necessary or desirable, and as one moves further away from the clinical applications of systematic reviews cynicism about their utility grows.
[7] Several arguments are commonly used to reject a wider role for systematic reviews, and these arguments are often based on major misconceptions about the history, purpose, methods, and uses of systematic reviews.
[8] I have examined eight common myths about …

[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: Trans-acting factors, such as lncRNAs, influence mRNA translation.

Document title: LincRNA-p21 suppresses target mRNA translation.

Abstract sentences:
[0] Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription.
[1] Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation.
[2] Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability.
[3] Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation.
[4] With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins.
[5] We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels.
[6] Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation.". 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: Trans-acting factors, such as lncRNAs, influence mRNA translation.

Document title: LincRNA-p21 suppresses target mRNA translation.

Abstract sentences:
[0] Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription.
[1] Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation.
[2] Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability.
[3] Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation.
[4] With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins.
[5] We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels.
[6] Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation.". 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: Trans-acting factors, such as lncRNAs, influence mRNA translation.

Document title: LincRNA-p21 suppresses target mRNA translation.

Abstract sentences:
[0] Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription.
[1] Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation.
[2] Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability.
[3] Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation.
[4] With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins.
[5] We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels.
[6] Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins.". 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: Trans-acting factors, such as lncRNAs, influence mRNA translation.

Document title: LincRNA-p21 suppresses target mRNA translation.

Abstract sentences:
[0] Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription.
[1] Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation.
[2] Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability.
[3] Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation.
[4] With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins.
[5] We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels.
[6] Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels.". 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: Trans-acting factors, such as lncRNAs, influence mRNA translation.

Document title: LincRNA-p21 suppresses target mRNA translation.

Abstract sentences:
[0] Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription.
[1] Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation.
[2] Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability.
[3] Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation.
[4] With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins.
[5] We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels.
[6] Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation.". 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: Transcription factor EB induces transcription of pro-inflammatory cytokines in macrophages infected with Staphylococcus aureus.

Document title: Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes.

Abstract sentences:
[0] Animal host defense against infection requires the expression of defense genes at the right place and the right time.
[1] Understanding such tight control of host defense requires the elucidation of the transcription factors involved.
[2] By using an unbiased approach in the model Caenorhabditis elegans, we discovered that HLH-30 (known as TFEB in mammals) is a key transcription factor for host defense.
[3] HLH-30 was activated shortly after Staphylococcus aureus infection, and drove the expression of close to 80% of the host response, including antimicrobial and autophagy genes that were essential for host tolerance of infection.
[4] TFEB was also rapidly activated in murine macrophages upon S. aureus infection and was required for proper transcriptional induction of several proinflammatory cytokines and chemokines.
[5] Thus, our data suggest that TFEB is a previously unappreciated, evolutionarily ancient transcription factor in the host response to infection.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "TFEB was also rapidly activated in murine macrophages upon S. aureus infection and was required for proper transcriptional induction of several proinflammatory cytokines and chemokines.". 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: Transcription rates in S. cerevisiae range between 0.7 and 2 kb/min.

Document title: Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo.

Abstract sentences:
[0] A number of proteins and drugs have been implicated in the process of transcriptional elongation by RNA polymerase (Pol) II, but the factors that govern the elongation rate (nucleotide additions per min) and processivity (nucleotide additions per initiation event) in vivo are poorly understood.
[1] Here, we show that a mutation in the Rpb2 subunit of Pol II reduces both the elongation rate and processivity in vivo.
[2] In contrast, none of the putative elongation factors tested affect the elongation rate, although mutations in the THO complex and in Spt4 significantly reduce processivity.
[3] The drugs 6-azauracil and mycophenolic acid reduce both the elongation rate and processivity, and this processivity defect is aggravated by mutations in Spt4, TFIIS, and CTDK-1.
[4] Our results suggest that, in vivo, a reduced rate of Pol II elongation leads to premature dissociation along the chromatin template and that Pol II processivity can be uncoupled from elongation rate.

[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: Transcription rates in S. cerevisiae range between 7 and 12 kb/min.

Document title: Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo.

Abstract sentences:
[0] A number of proteins and drugs have been implicated in the process of transcriptional elongation by RNA polymerase (Pol) II, but the factors that govern the elongation rate (nucleotide additions per min) and processivity (nucleotide additions per initiation event) in vivo are poorly understood.
[1] Here, we show that a mutation in the Rpb2 subunit of Pol II reduces both the elongation rate and processivity in vivo.
[2] In contrast, none of the putative elongation factors tested affect the elongation rate, although mutations in the THO complex and in Spt4 significantly reduce processivity.
[3] The drugs 6-azauracil and mycophenolic acid reduce both the elongation rate and processivity, and this processivity defect is aggravated by mutations in Spt4, TFIIS, and CTDK-1.
[4] Our results suggest that, in vivo, a reduced rate of Pol II elongation leads to premature dissociation along the chromatin template and that Pol II processivity can be uncoupled from elongation rate.

[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: Transplanted human glial progenitor cells can mature in their host animal.

Document title: Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice.

Abstract sentences:
[0] Human astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution.
[1] To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice.
[2] Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes.
[3] The engrafted human glia were gap-junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca2+ signals 3-fold faster than their hosts.
[4] Long-term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning.
[5] Mice allografted with murine GPCs showed no enhancement of either LTP or learning.
[6] These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes.". 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: Treatment with a protein named FN impairs regenerative abilities of aged muscles.

Document title: Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice

Abstract sentences:
[0] Age-related changes in the niche have long been postulated to impair the function of somatic stem cells.
[1] Here we demonstrate that the aged stem cell niche in skeletal muscle contains substantially reduced levels of fibronectin (FN), leading to detrimental consequences for the function and maintenance of muscle stem cells (MuSCs).
[2] Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers.
[3] By using an extracellular matrix (ECM) library screen and pathway profiling, we characterize FN as a preferred adhesion substrate for MuSCs and demonstrate that integrin-mediated signaling through focal adhesion kinase and the p38 mitogen-activated protein kinase pathway is strongly de-regulated in MuSCs from aged mice because of insufficient attachment to the niche.
[4] Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration.
[5] Taken together, we identify the loss of stem cell adhesion to FN in the niche ECM as a previously unknown aging mechanism.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers.". 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: Treatment with a protein named FN impairs regenerative abilities of aged muscles.

Document title: Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice

Abstract sentences:
[0] Age-related changes in the niche have long been postulated to impair the function of somatic stem cells.
[1] Here we demonstrate that the aged stem cell niche in skeletal muscle contains substantially reduced levels of fibronectin (FN), leading to detrimental consequences for the function and maintenance of muscle stem cells (MuSCs).
[2] Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers.
[3] By using an extracellular matrix (ECM) library screen and pathway profiling, we characterize FN as a preferred adhesion substrate for MuSCs and demonstrate that integrin-mediated signaling through focal adhesion kinase and the p38 mitogen-activated protein kinase pathway is strongly de-regulated in MuSCs from aged mice because of insufficient attachment to the niche.
[4] Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration.
[5] Taken together, we identify the loss of stem cell adhesion to FN in the niche ECM as a previously unknown aging mechanism.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration.". 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: Treatment with a protein named FN restores regenerative abilities of aged muscles.

Document title: Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice

Abstract sentences:
[0] Age-related changes in the niche have long been postulated to impair the function of somatic stem cells.
[1] Here we demonstrate that the aged stem cell niche in skeletal muscle contains substantially reduced levels of fibronectin (FN), leading to detrimental consequences for the function and maintenance of muscle stem cells (MuSCs).
[2] Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers.
[3] By using an extracellular matrix (ECM) library screen and pathway profiling, we characterize FN as a preferred adhesion substrate for MuSCs and demonstrate that integrin-mediated signaling through focal adhesion kinase and the p38 mitogen-activated protein kinase pathway is strongly de-regulated in MuSCs from aged mice because of insufficient attachment to the niche.
[4] Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration.
[5] Taken together, we identify the loss of stem cell adhesion to FN in the niche ECM as a previously unknown aging mechanism.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers.". 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: Treatment with a protein named FN restores regenerative abilities of aged muscles.

Document title: Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice

Abstract sentences:
[0] Age-related changes in the niche have long been postulated to impair the function of somatic stem cells.
[1] Here we demonstrate that the aged stem cell niche in skeletal muscle contains substantially reduced levels of fibronectin (FN), leading to detrimental consequences for the function and maintenance of muscle stem cells (MuSCs).
[2] Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers.
[3] By using an extracellular matrix (ECM) library screen and pathway profiling, we characterize FN as a preferred adhesion substrate for MuSCs and demonstrate that integrin-mediated signaling through focal adhesion kinase and the p38 mitogen-activated protein kinase pathway is strongly de-regulated in MuSCs from aged mice because of insufficient attachment to the niche.
[4] Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration.
[5] Taken together, we identify the loss of stem cell adhesion to FN in the niche ECM as a previously unknown aging mechanism.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration.". 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: Treatment with the EC uptake inhibitor AM404 resulted in a dose-dependent decrease in the expression of immobility.

Document title: Functional role of high-affinity anandamide transport, as revealed by selective inhibition.

Abstract sentences:
[0] Anandamide, an endogenous ligand for central cannabinoid receptors, is released from neurons on depolarization and rapidly inactivated.
[1] Anandamide inactivation is not completely understood, but it may occur by transport into cells or by enzymatic hydrolysis.
[2] The compound N-(4-hydroxyphenyl)arachidonylamide (AM404) was shown to inhibit high-affinity anandamide accumulation in rat neurons and astrocytes in vitro, an indication that this accumulation resulted from carrier-mediated transport.
[3] Although AM404 did not activate cannabinoid receptors or inhibit anandamide hydrolysis, it enhanced receptor-mediated anandamide responses in vitro and in vivo.
[4] The data indicate that carrier-mediated transport may be essential for termination of the biological effects of anandamide, and may represent a potential drug target.

[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: Tuberculosis incidence occurs at higher rates in more sparsely populated areas in the UK.

Document title: Ecological analysis of ethnic differences in relation between tuberculosis and poverty.

Abstract sentences:
[0] OBJECTIVE To examine the effect of ethnicity on the relation between tuberculosis and deprivation.
[1] DESIGN Retrospective ecological study comparing incidence of tuberculosis in white and south Asian residents of the 39 electoral wards in Birmingham with ethnic specific indices of deprivation.
[2] SETTING Birmingham, 1989-93.
[3] SUBJECTS 1516 notified cases of tuberculosis.
[4] MAIN OUTCOME MEASURES Rates of tuberculosis and measures of deprivation.
[5] RESULTS Univariate analysis showed significant associations of tuberculosis rates for the whole population with several indices of deprivation (P<0.01) and with the proportion of the population of south Asian origin (P<0.01).
[6] All deprivation covariates were positively associated with each other but on multiple regression, higher level of overcrowding was independently associated with tuberculosis rates.
[7] For the white population, overcrowding was associated with tuberculosis rates independently of other variables (P=0.0036).
[8] No relation with deprivation was found for the south Asian population in either single or multivariable analyses.
[9] CONCLUSIONS Poverty is significantly associated with tuberculosis in the white population, but no such relation exists for those of Asian ethnicity.
[10] These findings suggest that causal factors, and therefore potential interventions, will also differ by ethnic group.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [6]
Explanation: Evidence states: "All deprivation covariates were positively associated with each other but on multiple regression, higher level of overcrowding was independently associated with tuberculosis rates.". 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: Tuberculosis incidence occurs at higher rates in more sparsely populated areas in the UK.

Document title: Ecological analysis of ethnic differences in relation between tuberculosis and poverty.

Abstract sentences:
[0] OBJECTIVE To examine the effect of ethnicity on the relation between tuberculosis and deprivation.
[1] DESIGN Retrospective ecological study comparing incidence of tuberculosis in white and south Asian residents of the 39 electoral wards in Birmingham with ethnic specific indices of deprivation.
[2] SETTING Birmingham, 1989-93.
[3] SUBJECTS 1516 notified cases of tuberculosis.
[4] MAIN OUTCOME MEASURES Rates of tuberculosis and measures of deprivation.
[5] RESULTS Univariate analysis showed significant associations of tuberculosis rates for the whole population with several indices of deprivation (P<0.01) and with the proportion of the population of south Asian origin (P<0.01).
[6] All deprivation covariates were positively associated with each other but on multiple regression, higher level of overcrowding was independently associated with tuberculosis rates.
[7] For the white population, overcrowding was associated with tuberculosis rates independently of other variables (P=0.0036).
[8] No relation with deprivation was found for the south Asian population in either single or multivariable analyses.
[9] CONCLUSIONS Poverty is significantly associated with tuberculosis in the white population, but no such relation exists for those of Asian ethnicity.
[10] These findings suggest that causal factors, and therefore potential interventions, will also differ by ethnic group.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [7]
Explanation: Evidence states: "For the white population, overcrowding was associated with tuberculosis rates independently of other variables (P=0.0036).". 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: Tuberculosis incidence occurs at higher rates in more sparsely populated areas in the UK.

Document title: Tuberculosis mortality in England and Wales during 1982-1992: its association with poverty, ethnicity and AIDS.

Abstract sentences:
[0] This paper seeks to establish the strength of association between contemporary tuberculosis (TB) in England and Wales and several potential aetiological factors.
[1] It presents an ecological analysis of standardised annual TB mortality rates for the 403 local authority districts between 1982 and 1992, disaggregated by age and sex.
[2] Social, demographic and ethnicity measures from the 1981 and 1991 censuses and standardised annual AIDS-related mortality rates for young men are used to calculate Poisson regression models.
[3] A strong association was found between all TB mortality groups and overcrowding at the household level.
[4] For women, no other measures improved the explanatory power of the models.
[5] In multiple regressions, both poverty and AIDS-related mortality explained additional variation in the model for younger men.
[6] The link between ethnicity and tuberculosis notifications was not reflected in this analysis of mortality.
[7] For all groups no evidence of a positive relationship with ethnicity was found, once overcrowding had been accounted for.
[8] The significance of household as opposed to district level crowding suggests that prolonged contact is required for disease transmission.
[9] Regression analysis indicates that it is the overcrowding and poverty among ethnic populations that is significant for their tuberculosis mortality.
[10] The fact that the relationship between AIDS and TB is confined to the group most typical of AIDS patients provides evidence that AIDS has little influence on the level of tuberculosis mortality in the wider population.
[11] Explanations for the observed relationship include preferential certification, migration for treatment and shortcomings in health care provision.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "A strong association was found between all TB mortality groups and overcrowding at the household level.". 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: Tuberculosis incidence occurs at higher rates in more sparsely populated areas in the UK.

Document title: Tuberculosis mortality in England and Wales during 1982-1992: its association with poverty, ethnicity and AIDS.

Abstract sentences:
[0] This paper seeks to establish the strength of association between contemporary tuberculosis (TB) in England and Wales and several potential aetiological factors.
[1] It presents an ecological analysis of standardised annual TB mortality rates for the 403 local authority districts between 1982 and 1992, disaggregated by age and sex.
[2] Social, demographic and ethnicity measures from the 1981 and 1991 censuses and standardised annual AIDS-related mortality rates for young men are used to calculate Poisson regression models.
[3] A strong association was found between all TB mortality groups and overcrowding at the household level.
[4] For women, no other measures improved the explanatory power of the models.
[5] In multiple regressions, both poverty and AIDS-related mortality explained additional variation in the model for younger men.
[6] The link between ethnicity and tuberculosis notifications was not reflected in this analysis of mortality.
[7] For all groups no evidence of a positive relationship with ethnicity was found, once overcrowding had been accounted for.
[8] The significance of household as opposed to district level crowding suggests that prolonged contact is required for disease transmission.
[9] Regression analysis indicates that it is the overcrowding and poverty among ethnic populations that is significant for their tuberculosis mortality.
[10] The fact that the relationship between AIDS and TB is confined to the group most typical of AIDS patients provides evidence that AIDS has little influence on the level of tuberculosis mortality in the wider population.
[11] Explanations for the observed relationship include preferential certification, migration for treatment and shortcomings in health care provision.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [9]
Explanation: Evidence states: "Regression analysis indicates that it is the overcrowding and poverty among ethnic populations that is significant for their tuberculosis mortality.". This contradicts the claim.


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

Claim: Tuberculosis-induced granulomas express different immune system protein signatures than the surrounding tissue.

Document title: Inflammatory signaling in human Tuberculosis granulomas is spatially organized

Abstract sentences:
[0] Granulomas are the pathological hallmark of tuberculosis (TB).
[1] However, their function and mechanisms of formation remain poorly understood.
[2] To understand the role of granulomas in TB, we analyzed the proteomes of granulomas from subjects with tuberculosis in an unbiased manner.
[3] Using laser-capture microdissection, mass spectrometry and confocal microscopy, we generated detailed molecular maps of human granulomas.
[4] We found that the centers of granulomas have a pro-inflammatory environment that is characterized by the presence of antimicrobial peptides, reactive oxygen species and pro-inflammatory eicosanoids.
[5] Conversely, the tissue surrounding the caseum has a comparatively anti-inflammatory signature.
[6] These findings are consistent across a set of six human subjects and in rabbits.
[7] Although the balance between systemic pro- and anti-inflammatory signals is crucial to TB disease outcome, here we find that these signals are physically segregated within each granuloma.
[8] From the protein and lipid snapshots of human and rabbit lesions analyzed here, we hypothesize that the pathologic response to TB is shaped by the precise anatomical localization of these inflammatory pathways during the development of the granuloma.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4, 5]
Explanation: Evidence states: "We found that the centers of granulomas have a pro-inflammatory environment that is characterized by the presence of antimicrobial peptides, reactive oxygen species and pro-inflammatory eicosanoids. Conversely, the tissue surrounding the caseum has a comparatively anti-inflammatory signature.". 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: Tuberculosis-induced granulomas express different immune system protein signatures than the surrounding tissue.

Document title: Inflammatory signaling in human Tuberculosis granulomas is spatially organized

Abstract sentences:
[0] Granulomas are the pathological hallmark of tuberculosis (TB).
[1] However, their function and mechanisms of formation remain poorly understood.
[2] To understand the role of granulomas in TB, we analyzed the proteomes of granulomas from subjects with tuberculosis in an unbiased manner.
[3] Using laser-capture microdissection, mass spectrometry and confocal microscopy, we generated detailed molecular maps of human granulomas.
[4] We found that the centers of granulomas have a pro-inflammatory environment that is characterized by the presence of antimicrobial peptides, reactive oxygen species and pro-inflammatory eicosanoids.
[5] Conversely, the tissue surrounding the caseum has a comparatively anti-inflammatory signature.
[6] These findings are consistent across a set of six human subjects and in rabbits.
[7] Although the balance between systemic pro- and anti-inflammatory signals is crucial to TB disease outcome, here we find that these signals are physically segregated within each granuloma.
[8] From the protein and lipid snapshots of human and rabbit lesions analyzed here, we hypothesize that the pathologic response to TB is shaped by the precise anatomical localization of these inflammatory pathways during the development of the granuloma.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "Although the balance between systemic pro- and anti-inflammatory signals is crucial to TB disease outcome, here we find that these signals are physically segregated within each granuloma.". 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: Tumor development occurs in conjunction with suppression of pro-inflammatory cytokines.

Document title: Paraneoplastic thrombocytosis: the secrets of tumor self-promotion.

Abstract sentences:
[0] Paraneoplastic thrombocytosis is associated with many solid tumors and often correlates with reduced survival.
[1] Recent studies suggest that a pathogenic feed back loop may be operative between platelets and tumor cells, with reciprocal interactions between tumor growth/metastasis and thrombocytosis/platelet activation.
[2] Specific molecular pathways have been identified in which tumors can stimulate platelet production and activation; activated platelets can, in turn, promote tumor growth and metastasis.
[3] Taken together, these findings provide exciting new potential targets for therapeutic intervention.

[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: Tumor development occurs in conjunction with upregulation of pro-inflammatory cytokines.

Document title: Paraneoplastic thrombocytosis: the secrets of tumor self-promotion.

Abstract sentences:
[0] Paraneoplastic thrombocytosis is associated with many solid tumors and often correlates with reduced survival.
[1] Recent studies suggest that a pathogenic feed back loop may be operative between platelets and tumor cells, with reciprocal interactions between tumor growth/metastasis and thrombocytosis/platelet activation.
[2] Specific molecular pathways have been identified in which tumors can stimulate platelet production and activation; activated platelets can, in turn, promote tumor growth and metastasis.
[3] Taken together, these findings provide exciting new potential targets for therapeutic intervention.

[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: Two variants of chromosome 6q21 are associated with radiation therapy-induced second malignancies in pediatric Hodgkin lymphoma patients.

Document title: Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin's lymphoma

Abstract sentences:
[0] Survivors of pediatric Hodgkin's lymphoma are at risk for radiation therapy–induced second malignant neoplasms (SMNs).
[1] We identified two variants at chromosome 6q21 associated with SMNs in survivors of Hodgkin's lymphoma treated with radiation therapy as children but not as adults.
[2] The variants comprise a risk locus associated with decreased basal expression of PRDM1 (encoding PR domain containing 1, with ZNF domain) and impaired induction of the PRDM1 protein after radiation exposure.
[3] These data suggest a new gene-exposure interaction that may implicate PRDM1 in the etiology of radiation therapy-induced SMNs.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "We identified two variants at chromosome 6q21 associated with SMNs in survivors of Hodgkin's lymphoma treated with radiation therapy as children but not as adults.". This supports the claim.


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

Claim: Type 1 Diabetes is associated with subtle perturbations in T reg development.

Document title: Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes

Abstract sentences:
[0] Genome-wide association studies are now identifying disease-associated chromosome regions.
[1] However, even after convincing replication, the localization of the causal variant(s) requires comprehensive resequencing, extensive genotyping and statistical analyses in large sample sets leading to targeted functional studies.
[2] Here, we have localized the type 1 diabetes (T1D) association in the interleukin 2 receptor alpha (IL2RA) gene region to two independent groups of SNPs, spanning overlapping regions of 14 and 40 kb, encompassing IL2RA intron 1 and the 5′ regions of IL2RA and RBM17 (odds ratio = 2.04, 95% confidence interval = 1.70–2.45; P = 1.92 × 10−28; control frequency = 0.635).
[3] Furthermore, we have associated IL2RA T1D susceptibility genotypes with lower circulating levels of the biomarker, soluble IL-2RA (P = 6.28 × 10−28), suggesting that an inherited lower immune responsiveness predisposes to T1D.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Here, we have localized the type 1 diabetes (T1D) association in the interleukin 2 receptor alpha (IL2RA) gene region to two independent groups of SNPs, spanning overlapping regions of 14 and 40 kb, encompassing IL2RA intron 1 and the 5′ regions of IL2RA and RBM17 (odds ratio = 2.04, 95% confidence interval = 1.70–2.45; P = 1.92 × 10−28; control frequency = 0.635).". 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: Type 1 Diabetes is associated with subtle perturbations in T reg development.

Document title: Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes

Abstract sentences:
[0] Genome-wide association studies are now identifying disease-associated chromosome regions.
[1] However, even after convincing replication, the localization of the causal variant(s) requires comprehensive resequencing, extensive genotyping and statistical analyses in large sample sets leading to targeted functional studies.
[2] Here, we have localized the type 1 diabetes (T1D) association in the interleukin 2 receptor alpha (IL2RA) gene region to two independent groups of SNPs, spanning overlapping regions of 14 and 40 kb, encompassing IL2RA intron 1 and the 5′ regions of IL2RA and RBM17 (odds ratio = 2.04, 95% confidence interval = 1.70–2.45; P = 1.92 × 10−28; control frequency = 0.635).
[3] Furthermore, we have associated IL2RA T1D susceptibility genotypes with lower circulating levels of the biomarker, soluble IL-2RA (P = 6.28 × 10−28), suggesting that an inherited lower immune responsiveness predisposes to T1D.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Furthermore, we have associated IL2RA T1D susceptibility genotypes with lower circulating levels of the biomarker, soluble IL-2RA (P = 6.28 × 10−28), suggesting that an inherited lower immune responsiveness predisposes to T1D.". 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: Type 1 Diabetes is associated with subtle perturbations in T reg development.

Document title: Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function.

Abstract sentences:
[0] Numerous reports have demonstrated that CD4(+)CD25(+) regulatory T cells (Tregs) from individuals with a range of human autoimmune diseases, including type 1 diabetes, are deficient in their ability to control autologous proinflammatory responses when compared with nondiseased, control individuals.
[1] Treg dysfunction could be a primary, causal event or may result from perturbations in the immune system during disease development.
[2] Polymorphisms in genes associated with Treg function, such as IL2RA, confer a higher risk of autoimmune disease.
[3] Although this suggests a primary role for defective Tregs in autoimmunity, a link between IL2RA gene polymorphisms and Treg function has not been examined.
[4] We addressed this by examining the impact of an IL2RA haplotype associated with type 1 diabetes on Treg fitness and suppressive function.
[5] Studies were conducted using healthy human subjects to avoid any confounding effects of disease.
[6] We demonstrated that the presence of an autoimmune disease-associated IL2RA haplotype correlates with diminished IL-2 responsiveness in Ag-experienced CD4(+) T cells, as measured by phosphorylation of STAT5a, and is associated with lower levels of FOXP3 expression by Tregs and a reduction in their ability to suppress proliferation of autologous effector T cells.
[7] These data offer a rationale that contributes to the molecular and cellular mechanisms through which polymorphisms in the IL-2RA gene affect immune regulation, and consequently upon susceptibility to autoimmune and inflammatory diseases.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "Numerous reports have demonstrated that CD4(+)CD25(+) regulatory T cells (Tregs) from individuals with a range of human autoimmune diseases, including type 1 diabetes, are deficient in their ability to control autologous proinflammatory responses when compared with nondiseased, control individuals.". 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: Ultrasound guidance significantly reduces the number of needle insertion attempts necessary for a given procedure.

Document title: Ultrasound imaging for lumbar punctures and epidural catheterisations: systematic review and meta-analysis.

Abstract sentences:
[0] OBJECTIVE To determine whether ultrasound imaging can reduce the risk of failed lumbar punctures or epidural catheterisations, when compared with standard palpation methods, and whether ultrasound imaging can reduce traumatic procedures, insertion attempts, and needle redirections.
[1] DESIGN Systematic review and meta-analysis of randomised controlled trials.
[2] DATA SOURCES Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 2012, without restriction by language or publication status.
[3] REVIEW METHODS Randomised trials that compared ultrasound imaging with standard methods (no imaging) in the performance of a lumbar puncture or epidural catheterisation were identified.
[4] RESULTS 14 studies with a total of 1334 patients were included (674 patients assigned to the ultrasound group, 660 to the control group).
[5] Five studies evaluated lumbar punctures and nine evaluated epidural catheterisations.
[6] Six of 624 procedures conducted in the ultrasound group failed; 44 of 610 procedures in the control group failed.
[7] Ultrasound imaging reduced the risk of failed procedures (risk ratio 0.21 (95% confidence interval 0.10 to 0.43), P<0.001).
[8] Risk reduction was similar when subgroup analysis was performed for lumbar punctures (risk ratio 0.19 (0.07 to 0.56), P=0.002) or epidural catheterisations (0.23 (0.09 to 0.60), P=0.003).
[9] Ultrasound imaging also significantly reduced the risk of traumatic procedures (risk ratio 0.27 (0.11 to 0.67), P=0.005), the number of insertion attempts (mean difference -0.44 (-0.64 to -0.24), P<0.001), and the number of needle redirections (mean difference -1.00 (-1.24 to -0.75), P<0.001).
[10] CONCLUSIONS Ultrasound imaging can reduce the risk of failed or traumatic lumbar punctures and epidural catheterisations, as well as the number of needle insertions and redirections.
[11] Ultrasound may be a useful adjunct for these procedures.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "Ultrasound imaging also significantly reduced the risk of traumatic procedures (risk ratio 0.27 (0.11 to 0.67), P=0.005), the number of insertion attempts (mean difference -0.44 (-0.64 to -0.24), P<0.001), and the number of needle redirections (mean difference -1.00 (-1.24 to -0.75), P<0.001).". 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: Ultrasound guidance significantly reduces the number of needle insertion attempts necessary for a given procedure.

Document title: Ultrasound imaging for lumbar punctures and epidural catheterisations: systematic review and meta-analysis.

Abstract sentences:
[0] OBJECTIVE To determine whether ultrasound imaging can reduce the risk of failed lumbar punctures or epidural catheterisations, when compared with standard palpation methods, and whether ultrasound imaging can reduce traumatic procedures, insertion attempts, and needle redirections.
[1] DESIGN Systematic review and meta-analysis of randomised controlled trials.
[2] DATA SOURCES Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 2012, without restriction by language or publication status.
[3] REVIEW METHODS Randomised trials that compared ultrasound imaging with standard methods (no imaging) in the performance of a lumbar puncture or epidural catheterisation were identified.
[4] RESULTS 14 studies with a total of 1334 patients were included (674 patients assigned to the ultrasound group, 660 to the control group).
[5] Five studies evaluated lumbar punctures and nine evaluated epidural catheterisations.
[6] Six of 624 procedures conducted in the ultrasound group failed; 44 of 610 procedures in the control group failed.
[7] Ultrasound imaging reduced the risk of failed procedures (risk ratio 0.21 (95% confidence interval 0.10 to 0.43), P<0.001).
[8] Risk reduction was similar when subgroup analysis was performed for lumbar punctures (risk ratio 0.19 (0.07 to 0.56), P=0.002) or epidural catheterisations (0.23 (0.09 to 0.60), P=0.003).
[9] Ultrasound imaging also significantly reduced the risk of traumatic procedures (risk ratio 0.27 (0.11 to 0.67), P=0.005), the number of insertion attempts (mean difference -0.44 (-0.64 to -0.24), P<0.001), and the number of needle redirections (mean difference -1.00 (-1.24 to -0.75), P<0.001).
[10] CONCLUSIONS Ultrasound imaging can reduce the risk of failed or traumatic lumbar punctures and epidural catheterisations, as well as the number of needle insertions and redirections.
[11] Ultrasound may be a useful adjunct for these procedures.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "CONCLUSIONS Ultrasound imaging can reduce the risk of failed or traumatic lumbar punctures and epidural catheterisations, as well as the number of needle insertions and redirections.". 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: Ultrasound guidance significantly reduces the number of traumatic procedures when attempting needle insertion.

Document title: Ultrasound imaging for lumbar punctures and epidural catheterisations: systematic review and meta-analysis.

Abstract sentences:
[0] OBJECTIVE To determine whether ultrasound imaging can reduce the risk of failed lumbar punctures or epidural catheterisations, when compared with standard palpation methods, and whether ultrasound imaging can reduce traumatic procedures, insertion attempts, and needle redirections.
[1] DESIGN Systematic review and meta-analysis of randomised controlled trials.
[2] DATA SOURCES Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 2012, without restriction by language or publication status.
[3] REVIEW METHODS Randomised trials that compared ultrasound imaging with standard methods (no imaging) in the performance of a lumbar puncture or epidural catheterisation were identified.
[4] RESULTS 14 studies with a total of 1334 patients were included (674 patients assigned to the ultrasound group, 660 to the control group).
[5] Five studies evaluated lumbar punctures and nine evaluated epidural catheterisations.
[6] Six of 624 procedures conducted in the ultrasound group failed; 44 of 610 procedures in the control group failed.
[7] Ultrasound imaging reduced the risk of failed procedures (risk ratio 0.21 (95% confidence interval 0.10 to 0.43), P<0.001).
[8] Risk reduction was similar when subgroup analysis was performed for lumbar punctures (risk ratio 0.19 (0.07 to 0.56), P=0.002) or epidural catheterisations (0.23 (0.09 to 0.60), P=0.003).
[9] Ultrasound imaging also significantly reduced the risk of traumatic procedures (risk ratio 0.27 (0.11 to 0.67), P=0.005), the number of insertion attempts (mean difference -0.44 (-0.64 to -0.24), P<0.001), and the number of needle redirections (mean difference -1.00 (-1.24 to -0.75), P<0.001).
[10] CONCLUSIONS Ultrasound imaging can reduce the risk of failed or traumatic lumbar punctures and epidural catheterisations, as well as the number of needle insertions and redirections.
[11] Ultrasound may be a useful adjunct for these procedures.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7, 8, 9]
Explanation: Evidence states: "Ultrasound imaging reduced the risk of failed procedures (risk ratio 0.21 (95% confidence interval 0.10 to 0.43), P<0.001). Risk reduction was similar when subgroup analysis was performed for lumbar punctures (risk ratio 0.19 (0.07 to 0.56), P=0.002) or epidural catheterisations (0.23 (0.09 to 0.60), P=0.003). Ultrasound imaging also significantly reduced the risk of traumatic procedures (risk ratio 0.27 (0.11 to 0.67), P=0.005), the number of insertion attempts (mean difference -0.44 (-0.64 to -0.24), P<0.001), and the number of needle redirections (mean difference -1.00 (-1.24 to -0.75), P<0.001).". 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: Ultrasound guidance significantly reduces the number of traumatic procedures when attempting needle insertion.

Document title: Ultrasound imaging for lumbar punctures and epidural catheterisations: systematic review and meta-analysis.

Abstract sentences:
[0] OBJECTIVE To determine whether ultrasound imaging can reduce the risk of failed lumbar punctures or epidural catheterisations, when compared with standard palpation methods, and whether ultrasound imaging can reduce traumatic procedures, insertion attempts, and needle redirections.
[1] DESIGN Systematic review and meta-analysis of randomised controlled trials.
[2] DATA SOURCES Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 2012, without restriction by language or publication status.
[3] REVIEW METHODS Randomised trials that compared ultrasound imaging with standard methods (no imaging) in the performance of a lumbar puncture or epidural catheterisation were identified.
[4] RESULTS 14 studies with a total of 1334 patients were included (674 patients assigned to the ultrasound group, 660 to the control group).
[5] Five studies evaluated lumbar punctures and nine evaluated epidural catheterisations.
[6] Six of 624 procedures conducted in the ultrasound group failed; 44 of 610 procedures in the control group failed.
[7] Ultrasound imaging reduced the risk of failed procedures (risk ratio 0.21 (95% confidence interval 0.10 to 0.43), P<0.001).
[8] Risk reduction was similar when subgroup analysis was performed for lumbar punctures (risk ratio 0.19 (0.07 to 0.56), P=0.002) or epidural catheterisations (0.23 (0.09 to 0.60), P=0.003).
[9] Ultrasound imaging also significantly reduced the risk of traumatic procedures (risk ratio 0.27 (0.11 to 0.67), P=0.005), the number of insertion attempts (mean difference -0.44 (-0.64 to -0.24), P<0.001), and the number of needle redirections (mean difference -1.00 (-1.24 to -0.75), P<0.001).
[10] CONCLUSIONS Ultrasound imaging can reduce the risk of failed or traumatic lumbar punctures and epidural catheterisations, as well as the number of needle insertions and redirections.
[11] Ultrasound may be a useful adjunct for these procedures.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "CONCLUSIONS Ultrasound imaging can reduce the risk of failed or traumatic lumbar punctures and epidural catheterisations, as well as the number of needle insertions and redirections.". 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: Understanding epigenetic regulation of replication is essential for the reational design of episomally replicating vectors.

Document title: Global Reorganization of Replication Domains During Embryonic Stem Cell Differentiation

Abstract sentences:
[0] DNA replication in mammals is regulated via the coordinate firing of clusters of replicons that duplicate megabase-sized chromosome segments at specific times during S-phase.
[1] Cytogenetic studies show that these "replicon clusters" coalesce as subchromosomal units that persist through multiple cell generations, but the molecular boundaries of such units have remained elusive.
[2] Moreover, the extent to which changes in replication timing occur during differentiation and their relationship to transcription changes has not been rigorously investigated.
[3] We have constructed high-resolution replication-timing profiles in mouse embryonic stem cells (mESCs) before and after differentiation to neural precursor cells.
[4] We demonstrate that chromosomes can be segmented into multimegabase domains of coordinate replication, which we call "replication domains," separated by transition regions whose replication kinetics are consistent with large originless segments.
[5] The molecular boundaries of replication domains are remarkably well conserved between distantly related ESC lines and induced pluripotent stem cells.
[6] Unexpectedly, ESC differentiation was accompanied by the consolidation of smaller differentially replicating domains into larger coordinately replicated units whose replication time was more aligned to isochore GC content and the density of LINE-1 transposable elements, but not gene density.
[7] Replication-timing changes were coordinated with transcription changes for weak promoters more than strong promoters, and were accompanied by rearrangements in subnuclear position.
[8] We conclude that replication profiles are cell-type specific, and changes in these profiles reveal chromosome segments that undergo large changes in organization during differentiation.
[9] Moreover, smaller replication domains and a higher density of timing transition regions that interrupt isochore replication timing define a novel characteristic of the pluripotent state.

[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: Up-regulation of the p53 pathway and related molecular events speeds cancer progression.

Document title: Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors

Abstract sentences:
[0] Cells from organisms with renewable tissues can permanently withdraw from the cell cycle in response to diverse stress, including dysfunctional telomeres, DNA damage, strong mitogenic signals, and disrupted chromatin.
[1] This response, termed cellular senescence, is controlled by the p53 and RB tumor suppressor proteins and constitutes a potent anticancer mechanism.
[2] Nonetheless, senescent cells acquire phenotypic changes that may contribute to aging and certain age-related diseases, including late-life cancer.
[3] Thus, the senescence response may be antagonistically pleiotropic, promoting early-life survival by curtailing the development of cancer but eventually limiting longevity as dysfunctional senescent cells accumulate.

[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: Upon developing tyrosine-kinase inhibitor resistance, new mutations in epidermal growth factor receptors emerge and cause treatment failure.

Document title: Acquired EGFR C797S mutation mediates resistance to AZD9291 in non–small cell lung cancer harboring EGFR T790M

Abstract sentences:
[0] Here we studied cell-free plasma DNA (cfDNA) collected from subjects with advanced lung cancer whose tumors had developed resistance to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) AZD9291.
[1] We first performed next-generation sequencing of cfDNA from seven subjects and detected an acquired EGFR C797S mutation in one; expression of this mutant EGFR construct in a cell line rendered it resistant to AZD9291.
[2] We then performed droplet digital PCR on serial cfDNA specimens collected from 15 AZD9291-treated subjects.
[3] All were positive for the T790M mutation before treatment, but upon developing AZD9291 resistance three molecular subtypes emerged: six cases acquired the C797S mutation, five cases maintained the T790M mutation but did not acquire the C797S mutation and four cases lost the T790M mutation despite the presence of the underlying EGFR activating mutation.
[4] Our findings provide insight into the diversity of mechanisms through which tumors acquire resistance to AZD9291 and highlight the need for therapies that are able to overcome resistance mediated by the EGFR C797S mutation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "We first performed next-generation sequencing of cfDNA from seven subjects and detected an acquired EGFR C797S mutation in one; expression of this mutant EGFR construct in a cell line rendered it resistant to AZD9291.". 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: Upon developing tyrosine-kinase inhibitor resistance, new mutations in epidermal growth factor receptors emerge and cause treatment failure.

Document title: Acquired EGFR C797S mutation mediates resistance to AZD9291 in non–small cell lung cancer harboring EGFR T790M

Abstract sentences:
[0] Here we studied cell-free plasma DNA (cfDNA) collected from subjects with advanced lung cancer whose tumors had developed resistance to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) AZD9291.
[1] We first performed next-generation sequencing of cfDNA from seven subjects and detected an acquired EGFR C797S mutation in one; expression of this mutant EGFR construct in a cell line rendered it resistant to AZD9291.
[2] We then performed droplet digital PCR on serial cfDNA specimens collected from 15 AZD9291-treated subjects.
[3] All were positive for the T790M mutation before treatment, but upon developing AZD9291 resistance three molecular subtypes emerged: six cases acquired the C797S mutation, five cases maintained the T790M mutation but did not acquire the C797S mutation and four cases lost the T790M mutation despite the presence of the underlying EGFR activating mutation.
[4] Our findings provide insight into the diversity of mechanisms through which tumors acquire resistance to AZD9291 and highlight the need for therapies that are able to overcome resistance mediated by the EGFR C797S mutation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "All were positive for the T790M mutation before treatment, but upon developing AZD9291 resistance three molecular subtypes emerged: six cases acquired the C797S mutation, five cases maintained the T790M mutation but did not acquire the C797S mutation and four cases lost the T790M mutation despite the presence of the underlying EGFR activating mutation.". 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: Upon viral challenge, influenza-specific memory CD4+ T cells greatly diminish the early production of inflammatory chemokines in the lung.

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

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

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [2]
Explanation: Evidence states: "We found that the response of memory, but not naive, CD4+ T cells enhances production of multiple innate inflammatory cytokines and chemokines (IICs) in the lung and that, during influenza infection, this leads to early control of virus.". This 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: Upon viral challenge, influenza-specific memory CD4+ T cells greatly enhance the early production of inflammatory chemokines in the lung.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "We found that the response of memory, but not naive, CD4+ T cells enhances production of multiple innate inflammatory cytokines and chemokines (IICs) in the lung and that, during influenza infection, this leads to early control of virus.". This supports the claim.


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

Claim: Upregulation of PD1 causes the downmodulation of Satb1.

Document title: SATB1 Expression Governs Epigenetic Repression of PD‐1 in Tumor‐Reactive T Cells

Abstract sentences:
[0] &NA; Despite the importance of programmed cell death‐1 (PD‐1) in inhibiting T cell effector activity, the mechanisms regulating its expression remain poorly defined.
[1] We found that the chromatin organizer special AT‐rich sequence‐binding protein‐1 (Satb1) restrains PD‐1 expression induced upon T cell activation by recruiting a nucleosome remodeling deacetylase (NuRD) complex to Pdcd1 regulatory regions.
[2] Satb1 deficienct T cells exhibited a 40‐fold increase in PD‐1 expression.
[3] Tumor‐derived transforming growth factor &bgr; (Tgf‐&bgr;) decreased Satb1 expression through binding of Smad proteins to the Satb1 promoter.
[4] Smad proteins also competed with the Satb1‐NuRD complex for binding to Pdcd1 enhancers, releasing Pdcd1 expression from Satb1‐mediated repression, Satb1‐deficient tumor‐reactive T cells lost effector activity more rapidly than wild‐type lymphocytes at tumor beds expressing PD‐1 ligand (CD274), and these differences were abrogated by sustained CD274 blockade.
[5] Our findings suggest that Satb1 functions to prevent premature T cell exhaustion by regulating Pdcd1 expression upon T cell activation.
[6] Dysregulation of this pathway in tumor‐infiltrating T cells results in diminished anti‐tumor immunity.
[7] Graphical Abstract Figure.
[8] No caption available.
[9] HighlightsT cell activation increased the expression of Satb1 in mature CD8+ and CD4+ T cellsRecruitment of the NuRD repression complex by Satb1 inhibits expression of Pdcd1In tumors, TGF‐&bgr; inhibits Satb1 expression in T cells, increasing Pdcd1 expressionSatb1−/− T cells express high amounts of PD‐1 and have decreased anti‐tumor activity &NA; Stephen et al. show that the chromatin organizer Satb1 controls expression levels of PD‐1 upon T cell activation through the recruitment of a de‐acetylase complex to regulatory regions of the Pdcd1 gene.
[10] Tumor‐derived TGF‐&bgr; dysregulates this pathway, unleashing PD‐1 expression in tumor‐infiltrating T cells and decreasing anti‐tumor immunity.

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