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

Claim: TNFAIP3 is a glioblastoma tumor enhancer.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "Although inactivating mutations in A20 in lymphoma suggest A20 can act as a tumor suppressor, similar point mutations have not been identified through glioma genomic sequencing: in fact, our data suggest A20 may function as a tumor enhancer in glioma through promotion of GSC survival.". This supports the claim.


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

Claim: TNFAIP3 is a glioblastoma tumor suppressor.

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

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

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Inhibiting A20 expression decreased GSC growth and survival through mechanisms associated with decreased cell-cycle progression and decreased phosphorylation of p65/RelA. Elevated levels of A20 in GSCs contributed to apoptotic resistance: GSCs were less susceptible to TNFalpha-induced cell death than matched non-stem glioma cells, but A20 knockdown sensitized GSCs to TNFalpha-mediated apoptosis.". This 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: TNFAIP3 is a glioblastoma tumor suppressor.

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

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

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [9]
Explanation: Evidence states: "Although inactivating mutations in A20 in lymphoma suggest A20 can act as a tumor suppressor, similar point mutations have not been identified through glioma genomic sequencing: in fact, our data suggest A20 may function as a tumor enhancer in glioma through promotion of GSC survival.". 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: TNFAIP3 is a tumor enhancer in glioblastoma.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "The tumorigenic potential of GSCs was decreased with A20 targeting, resulting in increased survival of mice bearing human glioma xenografts.". This supports the claim.


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

Claim: TNFAIP3 is a tumor enhancer in glioblastoma.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "Although inactivating mutations in A20 in lymphoma suggest A20 can act as a tumor suppressor, similar point mutations have not been identified through glioma genomic sequencing: in fact, our data suggest A20 may function as a tumor enhancer in glioma through promotion of GSC survival.". 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: TRAP+ osteoclasts regulate mature osteoblast maintenance.

Document title: PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis

Abstract sentences:
[0] Osteogenesis during bone modeling and remodeling is coupled with angiogenesis.
[1] A recent study showed that a specific vessel subtype, strongly positive for CD31 and endomucin (CD31hiEmcnhi), couples angiogenesis and osteogenesis.
[2] Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31hiEmcnhi vessel formation during bone modeling and remodeling.
[3] Mice with depletion of PDGF-BB in the tartrate-resistant acid phosphatase–positive cell lineage show significantly lower trabecular and cortical bone mass, serum and bone marrow PDGF-BB concentrations, and fewer CD31hiEmcnhi vessels compared to wild-type mice.
[4] In the ovariectomy (OVX)-induced osteoporotic mouse model, serum and bone marrow levels of PDGF-BB and numbers of CD31hiEmcnhi vessels are significantly lower compared to sham-operated controls.
[5] Treatment with exogenous PDGF-BB or inhibition of cathepsin K to increase the number of preosteoclasts, and thus the endogenous levels of PDGF-BB, increases CD31hiEmcnhi vessel number and stimulates bone formation in OVX mice.
[6] Thus, pharmacotherapies that increase PDGF-BB secretion from preosteoclasts offer a new therapeutic target for treating osteoporosis by promoting angiogenesis and thus bone formation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Mice with depletion of PDGF-BB in the tartrate-resistant acid phosphatase–positive cell lineage show significantly lower trabecular and cortical bone mass, serum and bone marrow PDGF-BB concentrations, and fewer CD31hiEmcnhi vessels compared to wild-type mice.". This supports the claim.


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

Claim: Taking 400mg of α-tocopheryl acetate does not prevent prostate cancer.

Document title: Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial.

Abstract sentences:
[0] CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements.
[1] A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship.
[2] No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.
[3] OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.
[4] DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007.
[5] A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.
[6] INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.
[7] MAIN OUTCOME MEASURES Prostate and total cancer.
[8] RESULTS During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers.
[9] Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41).
[10] There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80).
[11] Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers.
[12] Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results.
[13] Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.
[14] CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer.
[15] These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men.
[16] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41).". 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: Taking 400mg of α-tocopheryl acetate does not prevent prostate cancer.

Document title: Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial.

Abstract sentences:
[0] CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements.
[1] A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship.
[2] No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.
[3] OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.
[4] DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007.
[5] A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.
[6] INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.
[7] MAIN OUTCOME MEASURES Prostate and total cancer.
[8] RESULTS During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers.
[9] Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41).
[10] There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80).
[11] Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers.
[12] Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results.
[13] Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.
[14] CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer.
[15] These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men.
[16] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [14]
Explanation: Evidence states: "CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer.". 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: Taking 400mg of α-tocopheryl acetate in combination with vitamin C reduces the risk of prostate cancer.

Document title: Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial.

Abstract sentences:
[0] CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements.
[1] A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship.
[2] No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.
[3] OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.
[4] DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007.
[5] A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.
[6] INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.
[7] MAIN OUTCOME MEASURES Prostate and total cancer.
[8] RESULTS During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers.
[9] Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41).
[10] There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80).
[11] Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers.
[12] Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results.
[13] Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.
[14] CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer.
[15] These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men.
[16] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [9, 10]
Explanation: Evidence states: "Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80).". 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: Taking 400mg of α-tocopheryl acetate in combination with vitamin C reduces the risk of prostate cancer.

Document title: Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial.

Abstract sentences:
[0] CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements.
[1] A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship.
[2] No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.
[3] OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.
[4] DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007.
[5] A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.
[6] INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.
[7] MAIN OUTCOME MEASURES Prostate and total cancer.
[8] RESULTS During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers.
[9] Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41).
[10] There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80).
[11] Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers.
[12] Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results.
[13] Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.
[14] CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer.
[15] These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men.
[16] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [14]
Explanation: Evidence states: "CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer.". 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: Taking anti-depresents is associated with a decrease in the Aβ level in the brain of experimental animals.

Document title: An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice

Abstract sentences:
[0] Serotonin signaling suppresses generation of amyloid-β (Aβ) in vitro and in animal models of Alzheimer’s disease (AD).
[1] We show that in an aged transgenic AD mouse model (APP/PS1 plaque-bearing mice), the antidepressant citalopram, a selective serotonin reuptake inhibitor, decreased Aβ in brain interstitial fluid in a dose-dependent manner.
[2] Growth of individual amyloid plaques was assessed in plaque-bearing mice that were chronically administered citalopram.
[3] Citalopram arrested the growth of preexisting plaques and reduced the appearance of new plaques by 78%.
[4] In healthy human volunteers, citalopram’s effects on Aβ production and Aβ concentrations in cerebrospinal fluid (CSF) were measured prospectively using stable isotope labeling kinetics, with CSF sampling during acute dosing of citalopram.
[5] Aβ production in CSF was slowed by 37% in the citalopram group compared to placebo.
[6] This change was associated with a 38% decrease in total CSF Aβ concentrations in the drug-treated group.
[7] The ability to safely decrease Aβ concentrations is potentially important as a preventive strategy for AD.
[8] This study demonstrates key target engagement for future AD prevention trials.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Aβ production in CSF was slowed by 37% in the citalopram group compared to placebo.". 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: Taxation of sugar-sweetened beverages reduced the incidence rate of type II diabetes in India.

Document title: Averting Obesity and Type 2 Diabetes in India through Sugar-Sweetened Beverage Taxation: An Economic-Epidemiologic Modeling Study

Abstract sentences:
[0] BACKGROUND Taxing sugar-sweetened beverages (SSBs) has been proposed in high-income countries to reduce obesity and type 2 diabetes.
[1] We sought to estimate the potential health effects of such a fiscal strategy in the middle-income country of India, where there is heterogeneity in SSB consumption, patterns of substitution between SSBs and other beverages after tax increases, and vast differences in chronic disease risk within the population.
[2] METHODS AND FINDINGS Using consumption and price variations data from a nationally representative survey of 100,855 Indian households, we first calculated how changes in SSB price alter per capita consumption of SSBs and substitution with other beverages.
[3] We then incorporated SSB sales trends, body mass index (BMI), and diabetes incidence data stratified by age, sex, income, and urban/rural residence into a validated microsimulation of caloric consumption, glycemic load, overweight/obesity prevalence, and type 2 diabetes incidence among Indian subpopulations facing a 20% SSB excise tax.
[4] The 20% SSB tax was anticipated to reduce overweight and obesity prevalence by 3.0% (95% CI 1.6%-5.9%) and type 2 diabetes incidence by 1.6% (95% CI 1.2%-1.9%) among various Indian subpopulations over the period 2014-2023, if SSB consumption continued to increase linearly in accordance with secular trends.
[5] However, acceleration in SSB consumption trends consistent with industry marketing models would be expected to increase the impact efficacy of taxation, averting 4.2% of prevalent overweight/obesity (95% CI 2.5-10.0%) and 2.5% (95% CI 1.0-2.8%) of incident type 2 diabetes from 2014-2023.
[6] Given current consumption and BMI distributions, our results suggest the largest relative effect would be expected among young rural men, refuting our a priori hypothesis that urban populations would be isolated beneficiaries of SSB taxation.
[7] Key limitations of this estimation approach include the assumption that consumer expenditure behavior from prior years, captured in price elasticities, will reflect future behavior among consumers, and potential underreporting of consumption in dietary recall data used to inform our calculations.
[8] CONCLUSION Sustained SSB taxation at a high tax rate could mitigate rising obesity and type 2 diabetes in India among both urban and rural subpopulations.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "The 20% SSB tax was anticipated to reduce overweight and obesity prevalence by 3.0% (95% CI 1.6%-5.9%) and type 2 diabetes incidence by 1.6% (95% CI 1.2%-1.9%) among various Indian subpopulations over the period 2014-2023, if SSB consumption continued to increase linearly in accordance with secular trends.". 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: Taxation of sugar-sweetened beverages reduced the incidence rate of type II diabetes in India.

Document title: Averting Obesity and Type 2 Diabetes in India through Sugar-Sweetened Beverage Taxation: An Economic-Epidemiologic Modeling Study

Abstract sentences:
[0] BACKGROUND Taxing sugar-sweetened beverages (SSBs) has been proposed in high-income countries to reduce obesity and type 2 diabetes.
[1] We sought to estimate the potential health effects of such a fiscal strategy in the middle-income country of India, where there is heterogeneity in SSB consumption, patterns of substitution between SSBs and other beverages after tax increases, and vast differences in chronic disease risk within the population.
[2] METHODS AND FINDINGS Using consumption and price variations data from a nationally representative survey of 100,855 Indian households, we first calculated how changes in SSB price alter per capita consumption of SSBs and substitution with other beverages.
[3] We then incorporated SSB sales trends, body mass index (BMI), and diabetes incidence data stratified by age, sex, income, and urban/rural residence into a validated microsimulation of caloric consumption, glycemic load, overweight/obesity prevalence, and type 2 diabetes incidence among Indian subpopulations facing a 20% SSB excise tax.
[4] The 20% SSB tax was anticipated to reduce overweight and obesity prevalence by 3.0% (95% CI 1.6%-5.9%) and type 2 diabetes incidence by 1.6% (95% CI 1.2%-1.9%) among various Indian subpopulations over the period 2014-2023, if SSB consumption continued to increase linearly in accordance with secular trends.
[5] However, acceleration in SSB consumption trends consistent with industry marketing models would be expected to increase the impact efficacy of taxation, averting 4.2% of prevalent overweight/obesity (95% CI 2.5-10.0%) and 2.5% (95% CI 1.0-2.8%) of incident type 2 diabetes from 2014-2023.
[6] Given current consumption and BMI distributions, our results suggest the largest relative effect would be expected among young rural men, refuting our a priori hypothesis that urban populations would be isolated beneficiaries of SSB taxation.
[7] Key limitations of this estimation approach include the assumption that consumer expenditure behavior from prior years, captured in price elasticities, will reflect future behavior among consumers, and potential underreporting of consumption in dietary recall data used to inform our calculations.
[8] CONCLUSION Sustained SSB taxation at a high tax rate could mitigate rising obesity and type 2 diabetes in India among both urban and rural subpopulations.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "However, acceleration in SSB consumption trends consistent with industry marketing models would be expected to increase the impact efficacy of taxation, averting 4.2% of prevalent overweight/obesity (95% CI 2.5-10.0%) and 2.5% (95% CI 1.0-2.8%) of incident type 2 diabetes from 2014-2023.". 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: Taxation of sugar-sweetened beverages reduced the incidence rate of type II diabetes in India.

Document title: Averting Obesity and Type 2 Diabetes in India through Sugar-Sweetened Beverage Taxation: An Economic-Epidemiologic Modeling Study

Abstract sentences:
[0] BACKGROUND Taxing sugar-sweetened beverages (SSBs) has been proposed in high-income countries to reduce obesity and type 2 diabetes.
[1] We sought to estimate the potential health effects of such a fiscal strategy in the middle-income country of India, where there is heterogeneity in SSB consumption, patterns of substitution between SSBs and other beverages after tax increases, and vast differences in chronic disease risk within the population.
[2] METHODS AND FINDINGS Using consumption and price variations data from a nationally representative survey of 100,855 Indian households, we first calculated how changes in SSB price alter per capita consumption of SSBs and substitution with other beverages.
[3] We then incorporated SSB sales trends, body mass index (BMI), and diabetes incidence data stratified by age, sex, income, and urban/rural residence into a validated microsimulation of caloric consumption, glycemic load, overweight/obesity prevalence, and type 2 diabetes incidence among Indian subpopulations facing a 20% SSB excise tax.
[4] The 20% SSB tax was anticipated to reduce overweight and obesity prevalence by 3.0% (95% CI 1.6%-5.9%) and type 2 diabetes incidence by 1.6% (95% CI 1.2%-1.9%) among various Indian subpopulations over the period 2014-2023, if SSB consumption continued to increase linearly in accordance with secular trends.
[5] However, acceleration in SSB consumption trends consistent with industry marketing models would be expected to increase the impact efficacy of taxation, averting 4.2% of prevalent overweight/obesity (95% CI 2.5-10.0%) and 2.5% (95% CI 1.0-2.8%) of incident type 2 diabetes from 2014-2023.
[6] Given current consumption and BMI distributions, our results suggest the largest relative effect would be expected among young rural men, refuting our a priori hypothesis that urban populations would be isolated beneficiaries of SSB taxation.
[7] Key limitations of this estimation approach include the assumption that consumer expenditure behavior from prior years, captured in price elasticities, will reflect future behavior among consumers, and potential underreporting of consumption in dietary recall data used to inform our calculations.
[8] CONCLUSION Sustained SSB taxation at a high tax rate could mitigate rising obesity and type 2 diabetes in India among both urban and rural subpopulations.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "CONCLUSION Sustained SSB taxation at a high tax rate could mitigate rising obesity and type 2 diabetes in India among both urban and rural subpopulations.". 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: Ten percent (10%) of kidney cancers in the UK are attributable to excess weight.

Document title: Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults

Abstract sentences:
[0] BACKGROUND High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken.
[1] We aimed to investigate the links between BMI and the most common site-specific cancers.
[2] METHODS With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders.
[3] We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects.
[4] FINDINGS 5·24 million individuals were included; 166,955 developed cancers of interest.
[5] BMI was associated with 17 of 22 cancers, but effects varied substantially by site.
[6] Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001).
[7] BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics.
[8] We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94).
[9] By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount.
[10] Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight.
[11] We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI.
[12] INTERPRETATION BMI is associated with cancer risk, with substantial population-level effects.
[13] The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups.
[14] FUNDING National Institute for Health Research, Wellcome Trust, and Medical Research Council.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight.". 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: The C-type lectin receptor (CLEC-2) rearranges the actin cytoskeleton in dendritic cells to promote efficient motility along stromal surfaces.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "CLEC-2 activation triggered cell spreading via downregulation of RhoA activity and myosin light-chain phosphorylation and triggered F-actin-rich protrusions via Vav signaling and Rac1 activation.". 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: The C-type lectin receptor (CLEC-2) rearranges the actin cytoskeleton in dendritic cells to promote efficient motility along stromal surfaces.

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

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

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Thus, activation of CLEC-2 by PDPN rearranges the actin cytoskeleton in DCs to promote efficient motility along stromal surfaces.". This supports the claim.


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

Claim: The DESMOND program caused substantial weight loss in most participants.

Document title: Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care

Abstract sentences:
[0] OBJECTIVE To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years.
[1] DESIGN Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level.
[2] SETTING 207 general practices in 13 primary care sites in the United Kingdom.
[3] PARTICIPANTS 731 of the 824 participants included in the original trial were eligible for follow-up.
[4] Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants.
[5] INTERVENTION A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care.
[6] MAIN OUTCOME MEASURES The primary outcome was glycated haemoglobin (HbA(1c)) levels.
[7] The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years.
[8] RESULTS HbA(1c) levels at three years had decreased in both groups.
[9] After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17).
[10] The groups did not differ for the other biomedical and lifestyle outcomes and drug use.
[11] The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01).
[12] Depression scores and quality of life did not differ at three years.
[13] CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs.
[14] TRIAL REGISTRATION Current Controlled Trials ISRCTN17844016.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [13]
Explanation: Evidence states: "CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs.". 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: The DESMOND program demonstrates no significant impact on biochemical outcomes.

Document title: Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care

Abstract sentences:
[0] OBJECTIVE To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years.
[1] DESIGN Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level.
[2] SETTING 207 general practices in 13 primary care sites in the United Kingdom.
[3] PARTICIPANTS 731 of the 824 participants included in the original trial were eligible for follow-up.
[4] Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants.
[5] INTERVENTION A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care.
[6] MAIN OUTCOME MEASURES The primary outcome was glycated haemoglobin (HbA(1c)) levels.
[7] The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years.
[8] RESULTS HbA(1c) levels at three years had decreased in both groups.
[9] After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17).
[10] The groups did not differ for the other biomedical and lifestyle outcomes and drug use.
[11] The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01).
[12] Depression scores and quality of life did not differ at three years.
[13] CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs.
[14] TRIAL REGISTRATION Current Controlled Trials ISRCTN17844016.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [9]
Explanation: Evidence states: "After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17).". 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: The DESMOND program demonstrates no significant impact on biochemical outcomes.

Document title: Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care

Abstract sentences:
[0] OBJECTIVE To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years.
[1] DESIGN Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level.
[2] SETTING 207 general practices in 13 primary care sites in the United Kingdom.
[3] PARTICIPANTS 731 of the 824 participants included in the original trial were eligible for follow-up.
[4] Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants.
[5] INTERVENTION A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care.
[6] MAIN OUTCOME MEASURES The primary outcome was glycated haemoglobin (HbA(1c)) levels.
[7] The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years.
[8] RESULTS HbA(1c) levels at three years had decreased in both groups.
[9] After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17).
[10] The groups did not differ for the other biomedical and lifestyle outcomes and drug use.
[11] The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01).
[12] Depression scores and quality of life did not differ at three years.
[13] CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs.
[14] TRIAL REGISTRATION Current Controlled Trials ISRCTN17844016.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "The groups did not differ for the other biomedical and lifestyle outcomes and drug use.". This supports the claim.


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

Claim: The DESMOND program demonstrates no significant impact on biochemical outcomes.

Document title: Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care

Abstract sentences:
[0] OBJECTIVE To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years.
[1] DESIGN Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level.
[2] SETTING 207 general practices in 13 primary care sites in the United Kingdom.
[3] PARTICIPANTS 731 of the 824 participants included in the original trial were eligible for follow-up.
[4] Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants.
[5] INTERVENTION A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care.
[6] MAIN OUTCOME MEASURES The primary outcome was glycated haemoglobin (HbA(1c)) levels.
[7] The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years.
[8] RESULTS HbA(1c) levels at three years had decreased in both groups.
[9] After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17).
[10] The groups did not differ for the other biomedical and lifestyle outcomes and drug use.
[11] The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01).
[12] Depression scores and quality of life did not differ at three years.
[13] CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs.
[14] TRIAL REGISTRATION Current Controlled Trials ISRCTN17844016.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [13]
Explanation: Evidence states: "CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs.". 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: The DESMOND program demonstrates no significant impact on lifestyles outcomes.

Document title: Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care

Abstract sentences:
[0] OBJECTIVE To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years.
[1] DESIGN Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level.
[2] SETTING 207 general practices in 13 primary care sites in the United Kingdom.
[3] PARTICIPANTS 731 of the 824 participants included in the original trial were eligible for follow-up.
[4] Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants.
[5] INTERVENTION A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care.
[6] MAIN OUTCOME MEASURES The primary outcome was glycated haemoglobin (HbA(1c)) levels.
[7] The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years.
[8] RESULTS HbA(1c) levels at three years had decreased in both groups.
[9] After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17).
[10] The groups did not differ for the other biomedical and lifestyle outcomes and drug use.
[11] The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01).
[12] Depression scores and quality of life did not differ at three years.
[13] CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs.
[14] TRIAL REGISTRATION Current Controlled Trials ISRCTN17844016.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [13]
Explanation: Evidence states: "CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs.". 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: The DESMOND program demonstrates no significant impact on weight loss.

Document title: Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care

Abstract sentences:
[0] OBJECTIVE To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years.
[1] DESIGN Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level.
[2] SETTING 207 general practices in 13 primary care sites in the United Kingdom.
[3] PARTICIPANTS 731 of the 824 participants included in the original trial were eligible for follow-up.
[4] Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants.
[5] INTERVENTION A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care.
[6] MAIN OUTCOME MEASURES The primary outcome was glycated haemoglobin (HbA(1c)) levels.
[7] The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years.
[8] RESULTS HbA(1c) levels at three years had decreased in both groups.
[9] After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17).
[10] The groups did not differ for the other biomedical and lifestyle outcomes and drug use.
[11] The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01).
[12] Depression scores and quality of life did not differ at three years.
[13] CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs.
[14] TRIAL REGISTRATION Current Controlled Trials ISRCTN17844016.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [13]
Explanation: Evidence states: "CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs.". 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: The DEXI promoter region is bound by multiple transcription factors in a murine haematopoietic progenitor cell line.

Document title: Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators.

Abstract sentences:
[0] Combinatorial transcription factor (TF) interactions control cellular phenotypes and, therefore, underpin stem cell formation, maintenance, and differentiation.
[1] Here, we report the genome-wide binding patterns and combinatorial interactions for ten key regulators of blood stem/progenitor cells (SCL/TAL1, LYL1, LMO2, GATA2, RUNX1, MEIS1, PU.1, ERG, FLI-1, and GFI1B), thus providing the most comprehensive TF data set for any adult stem/progenitor cell type to date.
[2] Genome-wide computational analysis of complex binding patterns, followed by functional validation, revealed the following: first, a previously unrecognized combinatorial interaction between a heptad of TFs (SCL, LYL1, LMO2, GATA2, RUNX1, ERG, and FLI-1).
[3] Second, we implicate direct protein-protein interactions between four key regulators (RUNX1, GATA2, SCL, and ERG) in stabilizing complex binding to DNA.
[4] Third, Runx1(+/-)::Gata2(+/-) compound heterozygous mice are not viable with severe hematopoietic defects at midgestation.
[5] Taken together, this study demonstrates the power of genome-wide analysis in generating novel functional insights into the transcriptional control of stem and progenitor cells.

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


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

Claim: The DdrB protein from Deinococcus radiodurans functions as a pentamer.

Document title: The structure of DdrB from Deinococcus: a new fold for single-stranded DNA binding proteins

Abstract sentences:
[0] Deinococcus spp. are renowned for their amazing ability to recover rapidly from severe genomic fragmentation as a result of exposure to extreme levels of ionizing radiation or desiccation.
[1] Despite having been originally characterized over 50 years ago, the mechanism underlying this remarkable repair process is still poorly understood.
[2] Here, we report the 2.8 A structure of DdrB, a single-stranded DNA (ssDNA) binding protein unique to Deinococcus spp.
[3] that is crucial for recovery following DNA damage.
[4] DdrB forms a pentameric ring capable of binding single-stranded but not double-stranded DNA.
[5] Unexpectedly, the crystal structure reveals that DdrB comprises a novel fold that is structurally and topologically distinct from all other single-stranded binding (SSB) proteins characterized to date.
[6] The need for a unique ssDNA binding function in response to severe damage, suggests a distinct role for DdrB which may encompass not only standard SSB protein function in protection of ssDNA, but also more specialized roles in protein recruitment or DNA architecture maintenance.
[7] Possible mechanisms of DdrB action in damage recovery are discussed.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "DdrB forms a pentameric ring capable of binding single-stranded but not double-stranded DNA.". 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: The G34R/V mutation creates a hypomethylated phenotype at the H3K36 histone.

Document title: ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression

Abstract sentences:
[0] Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin.
[1] H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation.
[2] In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription.
[3] However, much less is known about the role of H3K36me3 in transcription regulation in mammals.
[4] This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies.
[5] Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation.
[6] Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11.
[7] Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3.
[8] Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage.
[9] ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis.
[10] Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice.
[11] Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.

[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: The G34R/V mutation does not create a hypomethylated phenotype at the H3K36 histone.

Document title: ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression

Abstract sentences:
[0] Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin.
[1] H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation.
[2] In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription.
[3] However, much less is known about the role of H3K36me3 in transcription regulation in mammals.
[4] This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies.
[5] Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation.
[6] Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11.
[7] Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3.
[8] Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage.
[9] ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis.
[10] Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice.
[11] Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.

[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: The H2A-H2B eviction defect is compensated for by other histone chaperone(s).

Document title: FACT Disrupts Nucleosome Structure by Binding H2A-H2B with Conserved Peptide Motifs.

Abstract sentences:
[0] FACT, a heterodimer of Spt16 and Pob3, is an essential histone chaperone.
[1] We show that the H2A-H2B binding activity that is central to FACT function resides in short acidic regions near the C termini of each subunit.
[2] Mutations throughout these regions affect binding and cause correlated phenotypes that range from mild to lethal, with the largest individual contributions unexpectedly coming from an aromatic residue and a nearby carboxylate residue within each domain.
[3] Spt16 and Pob3 bind overlapping sites on H2A-H2B, and Spt16-Pob3 heterodimers simultaneously bind two H2A-H2B dimers, the same stoichiometry as the components of a nucleosome.
[4] An Spt16:H2A-H2B crystal structure explains the biochemical and genetic data, provides a model for Pob3 binding, and implies a mechanism for FACT reorganization that we confirm biochemically.
[5] Moreover, unexpected similarity to binding of ANP32E and Swr1 with H2A.Z-H2B reveals that diverse H2A-H2B chaperones use common mechanisms of histone binding and regulating nucleosome functions.

[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: The HSV-2 infection is typically asymptomatic.

Document title: Persistence of HIV-1 Receptor-Positive Cells after HSV-2 Reactivation: A Potential Mechanism for Increased HIV-1 Acquisition

Abstract sentences:
[0] To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition, we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy.
[1] CD4(+) and CD8(+) T cells and a mixed population of plasmacytoid and myeloid dendritic cells (DCs), including cells expressing the C-type lectin receptor DC-SIGN, persisted at sites of HSV-2 reactivation for months after healing, even with daily antiviral therapy.
[2] The CD4(+) T cells that persisted reacted to HSV-2 antigen, were enriched for expression of the chemokine receptor CCR5, and were contiguous to DCs expressing the interleukin-3 receptor CD123 or DC-SIGN.
[3] Ex vivo infection with a CCR5-tropic strain of HIV-1 revealed greater concentrations of integrated HIV-1 DNA in cells derived from healed genital lesion biopsies than in cells from control skin biopsies.
[4] The persistence and enrichment of HIV receptor-positive inflammatory cells in the genitalia help explain the inability of anti-HSV-2 therapy to reduce HIV acquisition.

[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: The M2-phenotype in brown adipose tissue macrophages increases brown adipose tissue thermogenic activity.

Document title: Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis

Abstract sentences:
[0] All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments.
[1] In the prevailing model of thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue and white adipose tissue.
[2] Acting via the β(3)-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes, whereas it stimulates the expression of thermogenic genes, such as PPAR-γ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes.
[3] However, the precise nature of all the cell types involved in this efferent loop is not well established.
[4] Here we report in mice an unexpected requirement for the interleukin-4 (IL-4)-stimulated program of alternative macrophage activation in adaptive thermogenesis.
[5] Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue.
[6] Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner.
[7] Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue.". 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: The M2-phenotype in brown adipose tissue macrophages increases brown adipose tissue thermogenic activity.

Document title: Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis

Abstract sentences:
[0] All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments.
[1] In the prevailing model of thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue and white adipose tissue.
[2] Acting via the β(3)-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes, whereas it stimulates the expression of thermogenic genes, such as PPAR-γ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes.
[3] However, the precise nature of all the cell types involved in this efferent loop is not well established.
[4] Here we report in mice an unexpected requirement for the interleukin-4 (IL-4)-stimulated program of alternative macrophage activation in adaptive thermogenesis.
[5] Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue.
[6] Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner.
[7] Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner.". 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: The NF-κB essential modulator gene induces intestinal inflammation by promoting receptor-interacting protein (RIP) kinase 1 kinase activity-mediated epithelial cell death.

Document title: NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions

Abstract sentences:
[0] Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD).
[1] IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon.
[2] Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions.
[3] Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency.
[4] Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency.". 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: The NF-κB essential modulator gene induces intestinal inflammation by promoting receptor-interacting protein (RIP) kinase 1 kinase activity-mediated epithelial cell death.

Document title: NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions

Abstract sentences:
[0] Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD).
[1] IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon.
[2] Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions.
[3] Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency.
[4] Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.". 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: The NF-κB essential modulator gene prevents intestinal inflammation by inhibiting receptor-interacting protein (RIP) kinase 1 kinase activity-mediated epithelial cell death.

Document title: NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions

Abstract sentences:
[0] Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD).
[1] IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon.
[2] Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions.
[3] Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency.
[4] Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency.". 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: The NF-κB essential modulator gene prevents intestinal inflammation by inhibiting receptor-interacting protein (RIP) kinase 1 kinase activity-mediated epithelial cell death.

Document title: NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions

Abstract sentences:
[0] Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD).
[1] IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon.
[2] Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions.
[3] Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency.
[4] Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.". 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: The PDPN gene deactivates the C-type lectin receptor (CLEC-2).

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

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

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [1]
Explanation: Evidence states: "PDPN is expressed by lymphatic endothelial and fibroblastic reticular cells and promotes blood-lymph separation during development by activating the C-type lectin receptor, CLEC-2, on platelets.". 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: The PDPN gene deactivates the C-type lectin receptor (CLEC-2).

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

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

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Thus, activation of CLEC-2 by PDPN rearranges the actin cytoskeleton in DCs to promote efficient motility along stromal surfaces.". This 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: The PPR MDA5 has twenty N-terminal CARD domains.

Document title: Immune signaling by RIG-I-like receptors.

Abstract sentences:
[0] The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a major role in pathogen sensing of RNA virus infection to initiate and modulate antiviral immunity.
[1] The RLRs detect viral RNA ligands or processed self RNA in the cytoplasm to trigger innate immunity and inflammation and to impart gene expression that serves to control infection.
[2] Importantly, RLRs cooperate in signaling crosstalk networks with Toll-like receptors and other factors to impart innate immunity and to modulate the adaptive immune response.
[3] RLR regulation occurs at a variety of levels ranging from autoregulation to ligand and cofactor interactions and posttranslational modifications.
[4] Abberant RLR signaling or dysregulation of RLR expression is now implicated in the development of autoimmune diseases.
[5] Understanding the processes of RLR signaling and response will provide insights to guide RLR-targeted therapeutics for antiviral and immune-modifying applications.

[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: The PRDM1 gene is a key determinant of primordial germ cells.

Document title: The Germ Cell Determinant Blimp1 Is Not Required for Derivation of Pluripotent Stem Cells

Abstract sentences:
[0] Blimp1 (Prdm1), the key determinant of primordial germ cells (PGCs), plays a combinatorial role with Prdm14 during PGC specification from postimplantation epiblast cells.
[1] They together initiate epigenetic reprogramming in early germ cells toward an underlying pluripotent state, which is equivalent to embryonic stem cells (ESCs).
[2] Whereas Prdm14 alone can promote reprogramming and is important for the propagation of the pluripotent state, it is not known whether Blimp1 is similarly involved.
[3] By using a genetic approach, we demonstrate that Blimp1 is dispensable for the derivation and maintenance of ESCs and postimplantation epiblast stem cells (epiSCs).
[4] Notably, Blimp1 is also dispensable for reprogramming epiSCs to ESCs.
[5] Thus, although Blimp1 is obligatory for PGC specification, it is not required for the reversion of epiSCs to ESCs and for their maintenance thereafter.
[6] This study suggests that reprogramming, including that of somatic cells to ESCs, may not entail an obligatory route through a Blimp1-positive PGC-like state.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "Blimp1 (Prdm1), the key determinant of primordial germ cells (PGCs), plays a combinatorial role with Prdm14 during PGC specification from postimplantation epiblast cells.". This supports the claim.


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

Claim: The PRDM1 gene, when combined with the PRDM14 gene, plays an important role during primordial germ cell specification.

Document title: The Germ Cell Determinant Blimp1 Is Not Required for Derivation of Pluripotent Stem Cells

Abstract sentences:
[0] Blimp1 (Prdm1), the key determinant of primordial germ cells (PGCs), plays a combinatorial role with Prdm14 during PGC specification from postimplantation epiblast cells.
[1] They together initiate epigenetic reprogramming in early germ cells toward an underlying pluripotent state, which is equivalent to embryonic stem cells (ESCs).
[2] Whereas Prdm14 alone can promote reprogramming and is important for the propagation of the pluripotent state, it is not known whether Blimp1 is similarly involved.
[3] By using a genetic approach, we demonstrate that Blimp1 is dispensable for the derivation and maintenance of ESCs and postimplantation epiblast stem cells (epiSCs).
[4] Notably, Blimp1 is also dispensable for reprogramming epiSCs to ESCs.
[5] Thus, although Blimp1 is obligatory for PGC specification, it is not required for the reversion of epiSCs to ESCs and for their maintenance thereafter.
[6] This study suggests that reprogramming, including that of somatic cells to ESCs, may not entail an obligatory route through a Blimp1-positive PGC-like state.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "Blimp1 (Prdm1), the key determinant of primordial germ cells (PGCs), plays a combinatorial role with Prdm14 during PGC specification from postimplantation epiblast cells.". This supports the claim.