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

Claim: Active Ly49Q prevents neutrophil polarization.

Document title: The Ly49Q receptor plays a crucial role in neutrophil polarization and migration by regulating raft trafficking.

Abstract sentences:
[0] Neutrophils rapidly undergo polarization and directional movement to infiltrate the sites of infection and inflammation.
[1] Here, we show that an inhibitory MHC I receptor, Ly49Q, was crucial for the swift polarization of and tissue infiltration by neutrophils.
[2] During the steady state, Ly49Q inhibited neutrophil adhesion by preventing focal-complex formation, likely by inhibiting Src and PI3 kinases.
[3] However, in the presence of inflammatory stimuli, Ly49Q mediated rapid neutrophil polarization and tissue infiltration in an ITIM-domain-dependent manner.
[4] These opposite functions appeared to be mediated by distinct use of effector phosphatase SHP-1 and SHP-2.
[5] Ly49Q-dependent polarization and migration were affected by Ly49Q regulation of membrane raft functions.
[6] We propose that Ly49Q is pivotal in switching neutrophils to their polarized morphology and rapid migration upon inflammation, through its spatiotemporal regulation of membrane rafts and raft-associated signaling molecules.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [6]
Explanation: Evidence states: "We propose that Ly49Q is pivotal in switching neutrophils to their polarized morphology and rapid migration upon inflammation, through its spatiotemporal regulation of membrane rafts and raft-associated signaling molecules.". 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: Active caspase-11 participate in regulating phagosome-lysosome fusion.

Document title: Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with lysosomes by modulating actin polymerization.

Abstract sentences:
[0] Inflammasomes are multiprotein complexes that include members of the NLR (nucleotide-binding domain leucine-rich repeat containing) family and caspase-1.
[1] Once bacterial molecules are sensed within the macrophage, the inflammasome is assembled, mediating the activation of caspase-1.
[2] Caspase-11 mediates caspase-1 activation in response to lipopolysaccharide and bacterial toxins, and yet its role during bacterial infection is unknown.
[3] Here, we demonstrated that caspase-11 was dispensable for caspase-1 activation in response to Legionella, Salmonella, Francisella, and Listeria.
[4] We also determined that active mouse caspase-11 was required for restriction of L. pneumophila infection.
[5] Similarly, human caspase-4 and caspase-5, homologs of mouse caspase-11, cooperated to restrict L. pneumophila infection in human macrophages.
[6] Caspase-11 promoted the fusion of the L. pneumophila vacuole with lysosomes by modulating actin polymerization through cofilin.
[7] However, caspase-11 was dispensable for the fusion of lysosomes with phagosomes containing nonpathogenic bacteria, uncovering a fundamental difference in the trafficking of phagosomes according to their cargo.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "However, caspase-11 was dispensable for the fusion of lysosomes with phagosomes containing nonpathogenic bacteria, uncovering a fundamental difference in the trafficking of phagosomes according to their cargo.". 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: Active caspase-11 protein promotes pyroptosis.

Document title: Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with lysosomes by modulating actin polymerization.

Abstract sentences:
[0] Inflammasomes are multiprotein complexes that include members of the NLR (nucleotide-binding domain leucine-rich repeat containing) family and caspase-1.
[1] Once bacterial molecules are sensed within the macrophage, the inflammasome is assembled, mediating the activation of caspase-1.
[2] Caspase-11 mediates caspase-1 activation in response to lipopolysaccharide and bacterial toxins, and yet its role during bacterial infection is unknown.
[3] Here, we demonstrated that caspase-11 was dispensable for caspase-1 activation in response to Legionella, Salmonella, Francisella, and Listeria.
[4] We also determined that active mouse caspase-11 was required for restriction of L. pneumophila infection.
[5] Similarly, human caspase-4 and caspase-5, homologs of mouse caspase-11, cooperated to restrict L. pneumophila infection in human macrophages.
[6] Caspase-11 promoted the fusion of the L. pneumophila vacuole with lysosomes by modulating actin polymerization through cofilin.
[7] However, caspase-11 was dispensable for the fusion of lysosomes with phagosomes containing nonpathogenic bacteria, uncovering a fundamental difference in the trafficking of phagosomes according to their cargo.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Here, we demonstrated that caspase-11 was dispensable for caspase-1 activation in response to Legionella, Salmonella, Francisella, and Listeria.". 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: Active caspase-11 protein promotes pyroptosis.

Document title: Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with lysosomes by modulating actin polymerization.

Abstract sentences:
[0] Inflammasomes are multiprotein complexes that include members of the NLR (nucleotide-binding domain leucine-rich repeat containing) family and caspase-1.
[1] Once bacterial molecules are sensed within the macrophage, the inflammasome is assembled, mediating the activation of caspase-1.
[2] Caspase-11 mediates caspase-1 activation in response to lipopolysaccharide and bacterial toxins, and yet its role during bacterial infection is unknown.
[3] Here, we demonstrated that caspase-11 was dispensable for caspase-1 activation in response to Legionella, Salmonella, Francisella, and Listeria.
[4] We also determined that active mouse caspase-11 was required for restriction of L. pneumophila infection.
[5] Similarly, human caspase-4 and caspase-5, homologs of mouse caspase-11, cooperated to restrict L. pneumophila infection in human macrophages.
[6] Caspase-11 promoted the fusion of the L. pneumophila vacuole with lysosomes by modulating actin polymerization through cofilin.
[7] However, caspase-11 was dispensable for the fusion of lysosomes with phagosomes containing nonpathogenic bacteria, uncovering a fundamental difference in the trafficking of phagosomes according to their cargo.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "We also determined that active mouse caspase-11 was required for restriction of L. pneumophila infection.". 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: Acute ablation of KRAS causes severe growth impairment.

Document title: Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression.

Abstract sentences:
[0] Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers.
[1] We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent phosphatidylinositol 3-kinase (PI3K) inhibition caused synergistic cell death.
[2] Additional combinations that enhanced ERK inhibitor action were also identified.
[3] Unexpectedly, long-term treatment of sensitive cell lines caused senescence, mediated in part by MYC degradation and p16 reactivation.
[4] Enhanced basal PI3K-AKT-mTOR signaling was associated with de novo resistance to ERK inhibitor, as were other protein kinases identified by kinome-wide siRNA screening and a genetic gain-of-function screen.
[5] Our findings reveal distinct consequences of inhibiting this kinase cascade at the level of ERK.

[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: Acute ablation of Snail in the embryonic cortex affects the proliferation and number of embryonic cortical precursors.

Document title: Control of Apoptosis by Asymmetric Cell Division

Abstract sentences:
[0] Asymmetric cell division and apoptosis (programmed cell death) are two fundamental processes that are important for the development and function of multicellular organisms.
[1] We have found that the processes of asymmetric cell division and apoptosis can be functionally linked.
[2] Specifically, we show that asymmetric cell division in the nematode Caenorhabditis elegans is mediated by a pathway involving three genes, dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail, that directly control the enzymatic machinery responsible for apoptosis.
[3] Interestingly, the MIDA1-like protein GlsA of the alga Volvox carteri, as well as the Snail-related proteins Snail, Escargot, and Worniu of Drosophila melanogaster, have previously been implicated in asymmetric cell division.
[4] Therefore, C. elegans dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail may be components of a pathway involved in asymmetric cell division that is conserved throughout the plant and animal kingdoms.
[5] Furthermore, based on our results, we propose that this pathway directly controls the apoptotic fate in C. elegans, and possibly other animals as well.

[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: Addition of BMP4, activin A, CHIR99021, and SU504 to reprogramming fibroblasts generates, expands and maintains cardiovascular progenitor cells (CPCs)

Document title: Expandable Cardiovascular Progenitor Cells Reprogrammed from Fibroblasts.

Abstract sentences:
[0] Stem cell-based approaches to cardiac regeneration are increasingly viable strategies for treating heart failure.
[1] Generating abundant and functional autologous cells for transplantation in such a setting, however, remains a significant challenge.
[2] Here, we isolated a cell population with extensive proliferation capacity and restricted cardiovascular differentiation potentials during cardiac transdifferentiation of mouse fibroblasts.
[3] These induced expandable cardiovascular progenitor cells (ieCPCs) proliferated extensively for more than 18 passages in chemically defined conditions, with 10(5) starting fibroblasts robustly producing 10(16) ieCPCs.
[4] ieCPCs expressed cardiac signature genes and readily differentiated into functional cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) in vitro, even after long-term expansion.
[5] When transplanted into mouse hearts following myocardial infarction, ieCPCs spontaneously differentiated into CMs, ECs, and SMCs and improved cardiac function for up to 12 weeks after transplantation.
[6] Thus, ieCPCs are a powerful system to study cardiovascular specification and provide strategies for regenerative medicine in the heart.

[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: Adult tissue-resident macrophages are seeded before birth.

Document title: Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis.

Abstract sentences:
[0] Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense.
[1] Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential.
[2] However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined.
[3] Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression.
[4] We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes.
[5] Furthermore, we have established that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly6C(-) cells and that the abundance of Ly6C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes.". 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: Adult tissue-resident macrophages are seeded before birth.

Document title: Origin and functions of tissue macrophages.

Abstract sentences:
[0] Macrophages are distributed in tissues throughout the body and contribute to both homeostasis and disease.
[1] Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes.
[2] Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are functionally interchangeable or have unique roles at steady state.
[3] This new understanding also prompts reconsideration of the function of circulating monocytes.
[4] Classical Ly6c(hi) monocytes patrol the extravascular space in resting organs, and Ly6c(lo) nonclassical monocytes patrol the vasculature.
[5] Inflammation triggers monocytes to differentiate into macrophages, but whether resident and newly recruited macrophages possess similar functions during inflammation is unclear.
[6] Here, we define the tools used for identifying the complex origin of tissue macrophages and discuss the relative contributions of tissue niche versus ontological origin to the regulation of macrophage functions during steady state and inflammation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes.". 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: Adult tissue-resident macrophages are seeded before birth.

Document title: Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis.

Abstract sentences:
[0] Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense.
[1] Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential.
[2] However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined.
[3] Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression.
[4] We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes.
[5] Furthermore, we have established that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly6C(-) cells and that the abundance of Ly6C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes.". 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: Adult tissue-resident macrophages are seeded before birth.

Document title: Origin and functions of tissue macrophages.

Abstract sentences:
[0] Macrophages are distributed in tissues throughout the body and contribute to both homeostasis and disease.
[1] Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes.
[2] Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are functionally interchangeable or have unique roles at steady state.
[3] This new understanding also prompts reconsideration of the function of circulating monocytes.
[4] Classical Ly6c(hi) monocytes patrol the extravascular space in resting organs, and Ly6c(lo) nonclassical monocytes patrol the vasculature.
[5] Inflammation triggers monocytes to differentiate into macrophages, but whether resident and newly recruited macrophages possess similar functions during inflammation is unclear.
[6] Here, we define the tools used for identifying the complex origin of tissue macrophages and discuss the relative contributions of tissue niche versus ontological origin to the regulation of macrophage functions during steady state and inflammation.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [1]
Explanation: Evidence states: "Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes.". 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: Adult tissue-resident macrophages possess a self-renewing capacity.

Document title: Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis.

Abstract sentences:
[0] Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense.
[1] Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential.
[2] However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined.
[3] Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression.
[4] We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes.
[5] Furthermore, we have established that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly6C(-) cells and that the abundance of Ly6C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes.". 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: Adult tissue-resident macrophages stem from the embryonal yolk sac and fetal liver.

Document title: Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis.

Abstract sentences:
[0] Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense.
[1] Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential.
[2] However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined.
[3] Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX(3)CR1 promoter-driven Cre recombinase expression.
[4] We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes.
[5] Furthermore, we have established that short-lived Ly6C(+) monocytes constitute obligatory steady-state precursors of blood-resident Ly6C(-) cells and that the abundance of Ly6C(+) blood monocytes dynamically controls the circulation lifespan of their progeny.

[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: Adult tissue-resident macrophages stem from the embryonal yolk sac and fetal liver.

Document title: Origin and functions of tissue macrophages.

Abstract sentences:
[0] Macrophages are distributed in tissues throughout the body and contribute to both homeostasis and disease.
[1] Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes.
[2] Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are functionally interchangeable or have unique roles at steady state.
[3] This new understanding also prompts reconsideration of the function of circulating monocytes.
[4] Classical Ly6c(hi) monocytes patrol the extravascular space in resting organs, and Ly6c(lo) nonclassical monocytes patrol the vasculature.
[5] Inflammation triggers monocytes to differentiate into macrophages, but whether resident and newly recruited macrophages possess similar functions during inflammation is unclear.
[6] Here, we define the tools used for identifying the complex origin of tissue macrophages and discuss the relative contributions of tissue niche versus ontological origin to the regulation of macrophage functions during steady state and inflammation.

[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: Aged patients are less susceptible to ischaemia/reperfusion injury.

Document title: Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function

Abstract sentences:
[0] Chaperone-mediated autophagy (CMA), a selective mechanism for degradation of cytosolic proteins in lysosomes, contributes to the removal of altered proteins as part of the cellular quality-control systems.
[1] We have previously found that CMA activity declines in aged organisms and have proposed that this failure in cellular clearance could contribute to the accumulation of altered proteins, the abnormal cellular homeostasis and, eventually, the functional loss characteristic of aged organisms.
[2] To determine whether these negative features of aging can be prevented by maintaining efficient autophagic activity until late in life, in this work we have corrected the CMA defect in aged rodents.
[3] We have generated a double transgenic mouse model in which the amount of the lysosomal receptor for CMA, previously shown to decrease in abundance with age, can be modulated.
[4] We have analyzed in this model the consequences of preventing the age-dependent decrease in receptor abundance in aged rodents at the cellular and organ levels.
[5] We show here that CMA activity is maintained until advanced ages if the decrease in the receptor abundance is prevented and that preservation of autophagic activity is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function.

[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: Aged patients are more susceptible to ischaemia/reperfusion injury.

Document title: Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function

Abstract sentences:
[0] Chaperone-mediated autophagy (CMA), a selective mechanism for degradation of cytosolic proteins in lysosomes, contributes to the removal of altered proteins as part of the cellular quality-control systems.
[1] We have previously found that CMA activity declines in aged organisms and have proposed that this failure in cellular clearance could contribute to the accumulation of altered proteins, the abnormal cellular homeostasis and, eventually, the functional loss characteristic of aged organisms.
[2] To determine whether these negative features of aging can be prevented by maintaining efficient autophagic activity until late in life, in this work we have corrected the CMA defect in aged rodents.
[3] We have generated a double transgenic mouse model in which the amount of the lysosomal receptor for CMA, previously shown to decrease in abundance with age, can be modulated.
[4] We have analyzed in this model the consequences of preventing the age-dependent decrease in receptor abundance in aged rodents at the cellular and organ levels.
[5] We show here that CMA activity is maintained until advanced ages if the decrease in the receptor abundance is prevented and that preservation of autophagic activity is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function.

[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: Aggravated inflammation is dependent on NLRP3 inflammasome activation.

Document title: Gout-associated uric acid crystals activate the NALP3 inflammasome

Abstract sentences:
[0] Development of the acute and chronic inflammatory responses known as gout and pseudogout are associated with the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and periarticular tissues.
[1] Although MSU crystals were first identified as the aetiological agent of gout in the eighteenth century and more recently as a ‘danger signal’ released from dying cells, little is known about the molecular mechanisms underlying MSU- or CPPD-induced inflammation.
[2] Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1β and IL-18.
[3] Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1β activation.
[4] Moreover, an impaired neutrophil influx is found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL-1β receptor (IL-1R).
[5] These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2]
Explanation: Evidence states: "Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1β and IL-18.". 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: Aggravated inflammation is dependent on NLRP3 inflammasome activation.

Document title: Gout-associated uric acid crystals activate the NALP3 inflammasome

Abstract sentences:
[0] Development of the acute and chronic inflammatory responses known as gout and pseudogout are associated with the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and periarticular tissues.
[1] Although MSU crystals were first identified as the aetiological agent of gout in the eighteenth century and more recently as a ‘danger signal’ released from dying cells, little is known about the molecular mechanisms underlying MSU- or CPPD-induced inflammation.
[2] Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1β and IL-18.
[3] Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1β activation.
[4] Moreover, an impaired neutrophil influx is found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL-1β receptor (IL-1R).
[5] These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1β 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: Albendazole is used to treat soil-transmitted helminths.

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

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

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


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

Claim: Algerian physicians constitue the largest component of sub-Saharan Africa-trained physicians in the United States.

Document title: Physician Emigration from Sub-Saharan Africa to the United States: Analysis of the 2011 AMA Physician Masterfile

Abstract sentences:
[0] BACKGROUND The large-scale emigration of physicians from sub-Saharan Africa (SSA) to high-income nations is a serious development concern.
[1] Our objective was to determine current emigration trends of SSA physicians found in the physician workforce of the United States.
[2] METHODS AND FINDINGS We analyzed physician data from the World Health Organization (WHO) Global Health Workforce Statistics along with graduation and residency data from the 2011 American Medical Association Physician Masterfile (AMA-PM) on physicians trained or born in SSA countries who currently practice in the US.
[3] We estimated emigration proportions, year of US entry, years of practice before emigration, and length of time in the US.
[4] According to the 2011 AMA-PM, 10,819 physicians were born or trained in 28 SSA countries.
[5] Sixty-eight percent (n = 7,370) were SSA-trained, 20% (n = 2,126) were US-trained, and 12% (n = 1,323) were trained outside both SSA and the US.
[6] We estimated active physicians (age ≤ 70 years) to represent 96% (n = 10,377) of the total.
[7] Migration trends among SSA-trained physicians increased from 2002 to 2011 for all but one principal source country; the exception was South Africa whose physician migration to the US decreased by 8% (-156).
[8] The increase in last-decade migration was >50% in Nigeria (+1,113) and Ghana (+243), >100% in Ethiopia (+274), and >200% (+244) in Sudan.
[9] Liberia was the most affected by migration to the US with 77% (n = 175) of its estimated physicians in the 2011 AMA-PM.
[10] On average, SSA-trained physicians have been in the US for 18 years.
[11] They practiced for 6.5 years before US entry, and nearly half emigrated during the implementation years (1984-1999) of the structural adjustment programs.
[12] CONCLUSION Physician emigration from SSA to the US is increasing for most SSA source countries.
[13] Unless far-reaching policies are implemented by the US and SSA countries, the current emigration trends will persist, and the US will remain a leading destination for SSA physicians emigrating from the continent of greatest need.
[14] Please see later in the article for the Editors' Summary.

[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: Alirocumab treatment reduces apo(a) fractional clearance rate.

Document title: Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans

Abstract sentences:
[0] BACKGROUND Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB).
[1] Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism.
[2] In particular, it is not known whether inhibition of PCSK9 has any effects on very low-density lipoprotein or intermediate-density lipoprotein (IDL) metabolism.
[3] Inhibition of PCSK9 also results in reductions of plasma lipoprotein (a) levels.
[4] The regulation of plasma Lp(a) levels, including the role of LDL receptors in the clearance of Lp(a), is poorly defined, and no mechanistic studies of the Lp(a) lowering by alirocumab in humans have been published to date.
[5] METHODS Eighteen (10 F, 8 mol/L) participants completed a placebo-controlled, 2-period study.
[6] They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart.
[7] At the end of each period, fractional clearance rates (FCRs) and production rates (PRs) of apoB and apo(a) were determined.
[8] In 10 participants, postprandial triglycerides and apoB48 levels were measured.
[9] RESULTS Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%.
[10] The fall in LDL-apoB was caused by an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR.
[11] The latter was due to a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL.
[12] The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR.
[13] Alirocumab had no effects on FCRs or PRs of very low-density lipoproteins-apoB and very low-density lipoproteins triglycerides or on postprandial plasma triglycerides or apoB48 concentrations.
[14] CONCLUSIONS Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs and decreasing LDL-apoB PR.
[15] These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.
[16] The increase in apo(a) FCR during alirocumab treatment suggests that increased LDL receptors may also play a role in the reduction of plasma Lp(a).
[17] CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
[18] Unique identifier: NCT01959971.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [9, 10]
Explanation: Evidence states: "RESULTS Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%. The fall in LDL-apoB was caused by an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR.". 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: Alirocumab treatment reduces apo(a) fractional clearance rate.

Document title: Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans

Abstract sentences:
[0] BACKGROUND Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB).
[1] Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism.
[2] In particular, it is not known whether inhibition of PCSK9 has any effects on very low-density lipoprotein or intermediate-density lipoprotein (IDL) metabolism.
[3] Inhibition of PCSK9 also results in reductions of plasma lipoprotein (a) levels.
[4] The regulation of plasma Lp(a) levels, including the role of LDL receptors in the clearance of Lp(a), is poorly defined, and no mechanistic studies of the Lp(a) lowering by alirocumab in humans have been published to date.
[5] METHODS Eighteen (10 F, 8 mol/L) participants completed a placebo-controlled, 2-period study.
[6] They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart.
[7] At the end of each period, fractional clearance rates (FCRs) and production rates (PRs) of apoB and apo(a) were determined.
[8] In 10 participants, postprandial triglycerides and apoB48 levels were measured.
[9] RESULTS Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%.
[10] The fall in LDL-apoB was caused by an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR.
[11] The latter was due to a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL.
[12] The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR.
[13] Alirocumab had no effects on FCRs or PRs of very low-density lipoproteins-apoB and very low-density lipoproteins triglycerides or on postprandial plasma triglycerides or apoB48 concentrations.
[14] CONCLUSIONS Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs and decreasing LDL-apoB PR.
[15] These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.
[16] The increase in apo(a) FCR during alirocumab treatment suggests that increased LDL receptors may also play a role in the reduction of plasma Lp(a).
[17] CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
[18] Unique identifier: NCT01959971.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [12]
Explanation: Evidence states: "The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR.". 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: Alirocumab treatment reduces apo(a) fractional clearance rate.

Document title: Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans

Abstract sentences:
[0] BACKGROUND Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB).
[1] Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism.
[2] In particular, it is not known whether inhibition of PCSK9 has any effects on very low-density lipoprotein or intermediate-density lipoprotein (IDL) metabolism.
[3] Inhibition of PCSK9 also results in reductions of plasma lipoprotein (a) levels.
[4] The regulation of plasma Lp(a) levels, including the role of LDL receptors in the clearance of Lp(a), is poorly defined, and no mechanistic studies of the Lp(a) lowering by alirocumab in humans have been published to date.
[5] METHODS Eighteen (10 F, 8 mol/L) participants completed a placebo-controlled, 2-period study.
[6] They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart.
[7] At the end of each period, fractional clearance rates (FCRs) and production rates (PRs) of apoB and apo(a) were determined.
[8] In 10 participants, postprandial triglycerides and apoB48 levels were measured.
[9] RESULTS Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%.
[10] The fall in LDL-apoB was caused by an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR.
[11] The latter was due to a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL.
[12] The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR.
[13] Alirocumab had no effects on FCRs or PRs of very low-density lipoproteins-apoB and very low-density lipoproteins triglycerides or on postprandial plasma triglycerides or apoB48 concentrations.
[14] CONCLUSIONS Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs and decreasing LDL-apoB PR.
[15] These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.
[16] The increase in apo(a) FCR during alirocumab treatment suggests that increased LDL receptors may also play a role in the reduction of plasma Lp(a).
[17] CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
[18] Unique identifier: NCT01959971.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [14]
Explanation: Evidence states: "CONCLUSIONS Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs and decreasing LDL-apoB PR.". 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: Alirocumab treatment reduces apo(a) fractional clearance rate.

Document title: Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans

Abstract sentences:
[0] BACKGROUND Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB).
[1] Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism.
[2] In particular, it is not known whether inhibition of PCSK9 has any effects on very low-density lipoprotein or intermediate-density lipoprotein (IDL) metabolism.
[3] Inhibition of PCSK9 also results in reductions of plasma lipoprotein (a) levels.
[4] The regulation of plasma Lp(a) levels, including the role of LDL receptors in the clearance of Lp(a), is poorly defined, and no mechanistic studies of the Lp(a) lowering by alirocumab in humans have been published to date.
[5] METHODS Eighteen (10 F, 8 mol/L) participants completed a placebo-controlled, 2-period study.
[6] They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart.
[7] At the end of each period, fractional clearance rates (FCRs) and production rates (PRs) of apoB and apo(a) were determined.
[8] In 10 participants, postprandial triglycerides and apoB48 levels were measured.
[9] RESULTS Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%.
[10] The fall in LDL-apoB was caused by an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR.
[11] The latter was due to a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL.
[12] The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR.
[13] Alirocumab had no effects on FCRs or PRs of very low-density lipoproteins-apoB and very low-density lipoproteins triglycerides or on postprandial plasma triglycerides or apoB48 concentrations.
[14] CONCLUSIONS Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs and decreasing LDL-apoB PR.
[15] These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.
[16] The increase in apo(a) FCR during alirocumab treatment suggests that increased LDL receptors may also play a role in the reduction of plasma Lp(a).
[17] CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
[18] Unique identifier: NCT01959971.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [16]
Explanation: Evidence states: "The increase in apo(a) FCR during alirocumab treatment suggests that increased LDL receptors may also play a role in the reduction of plasma Lp(a).". 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: Allogeneic mechanical circulatory support is not as effective as autologous mechanical circulatory support for treating acute myocardial infarction.

Document title: Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.

Abstract sentences:
[0] CONTEXT Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM).
[1] Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared.
[2] OBJECTIVE To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM.
[3] DESIGN, SETTING, AND PATIENTS A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up.
[4] INTERVENTION Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites.
[5] MAIN OUTCOME MEASURES Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs).
[6] Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index.
[7] RESULTS Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%.
[8] The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46).
[9] At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10).
[10] Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max.
[11] Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF.
[12] Allogeneic MSCs reduced LV end-diastolic volumes.
[13] Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF.
[14] Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions.
[15] CONCLUSIONS In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions.
[16] In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling.
[17] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01087996.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [8]
Explanation: Evidence states: "The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46).". 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: Allogeneic mechanical circulatory support is not as effective as autologous mechanical circulatory support for treating acute myocardial infarction.

Document title: Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.

Abstract sentences:
[0] CONTEXT Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM).
[1] Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared.
[2] OBJECTIVE To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM.
[3] DESIGN, SETTING, AND PATIENTS A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up.
[4] INTERVENTION Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites.
[5] MAIN OUTCOME MEASURES Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs).
[6] Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index.
[7] RESULTS Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%.
[8] The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46).
[9] At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10).
[10] Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max.
[11] Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF.
[12] Allogeneic MSCs reduced LV end-diastolic volumes.
[13] Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF.
[14] Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions.
[15] CONCLUSIONS In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions.
[16] In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling.
[17] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01087996.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [9]
Explanation: Evidence states: "At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10).". 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: Allogeneic mechanical circulatory support is not as effective as autologous mechanical circulatory support for treating acute myocardial infarction.

Document title: Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.

Abstract sentences:
[0] CONTEXT Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM).
[1] Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared.
[2] OBJECTIVE To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM.
[3] DESIGN, SETTING, AND PATIENTS A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up.
[4] INTERVENTION Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites.
[5] MAIN OUTCOME MEASURES Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs).
[6] Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index.
[7] RESULTS Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%.
[8] The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46).
[9] At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10).
[10] Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max.
[11] Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF.
[12] Allogeneic MSCs reduced LV end-diastolic volumes.
[13] Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF.
[14] Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions.
[15] CONCLUSIONS In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions.
[16] In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling.
[17] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01087996.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [11]
Explanation: Evidence states: "Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF.". 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: Allogeneic mechanical circulatory support is not as effective as autologous mechanical circulatory support for treating acute myocardial infarction.

Document title: Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.

Abstract sentences:
[0] CONTEXT Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM).
[1] Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared.
[2] OBJECTIVE To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM.
[3] DESIGN, SETTING, AND PATIENTS A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up.
[4] INTERVENTION Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites.
[5] MAIN OUTCOME MEASURES Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs).
[6] Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index.
[7] RESULTS Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%.
[8] The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46).
[9] At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10).
[10] Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max.
[11] Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF.
[12] Allogeneic MSCs reduced LV end-diastolic volumes.
[13] Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF.
[14] Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions.
[15] CONCLUSIONS In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions.
[16] In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling.
[17] TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01087996.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [15]
Explanation: Evidence states: "CONCLUSIONS In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions.". 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: Alteration of origin firing causes changes in termination zones of Okazaki fragments.

Document title: Quantitative, genome-wide analysis of eukaryotic replication initiation and termination.

Abstract sentences:
[0] Many fundamental aspects of DNA replication, such as the exact locations where DNA synthesis is initiated and terminated, how frequently origins are used, and how fork progression is influenced by transcription, are poorly understood.
[1] Via the deep sequencing of Okazaki fragments, we comprehensively document replication fork directionality throughout the S. cerevisiae genome, which permits the systematic analysis of initiation, origin efficiency, fork progression, and termination.
[2] We show that leading-strand initiation preferentially occurs within a nucleosome-free region at replication origins.
[3] Using a strain in which late origins can be induced to fire early, we show that replication termination is a largely passive phenomenon that does not rely on cis-acting sequences or replication fork pausing.
[4] The replication profile is predominantly determined by the kinetics of origin firing, allowing us to reconstruct chromosome-wide timing profiles from an asynchronous culture.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Using a strain in which late origins can be induced to fire early, we show that replication termination is a largely passive phenomenon that does not rely on cis-acting sequences or replication fork pausing.". 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: Ambulatory blood pressure monitoring is inaccurate at diagnosing hypertension.

Document title: Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: systematic review

Abstract sentences:
[0] OBJECTIVE To determine the relative accuracy of clinic measurements and home blood pressure monitoring compared with ambulatory blood pressure monitoring as a reference standard for the diagnosis of hypertension.
[1] DESIGN Systematic review with meta-analysis with hierarchical summary receiver operating characteristic models.
[2] Methodological quality was appraised, including evidence of validation of blood pressure measurement equipment.
[3] DATA SOURCES Medline (from 1966), Embase (from 1980), Cochrane Database of Systematic Reviews, DARE, Medion, ARIF, and TRIP up to May 2010.
[4] Eligibility criteria for selecting studies Eligible studies examined diagnosis of hypertension in adults of all ages using home and/or clinic blood pressure measurement compared with those made using ambulatory monitoring that clearly defined thresholds to diagnose hypertension.
[5] RESULTS The 20 eligible studies used various thresholds for the diagnosis of hypertension, and only seven studies (clinic) and three studies (home) could be directly compared with ambulatory monitoring.
[6] Compared with ambulatory monitoring thresholds of 135/85 mm Hg, clinic measurements over 140/90 mm Hg had mean sensitivity and specificity of 74.6% (95% confidence interval 60.7% to 84.8%) and 74.6% (47.9% to 90.4%), respectively, whereas home measurements over 135/85 mm Hg had mean sensitivity and specificity of 85.7% (78.0% to 91.0%) and 62.4% (48.0% to 75.0%).
[7] CONCLUSIONS Neither clinic nor home measurement had sufficient sensitivity or specificity to be recommended as a single diagnostic test.
[8] If ambulatory monitoring is taken as the reference standard, then treatment decisions based on clinic or home blood pressure alone might result in substantial overdiagnosis.
[9] Ambulatory monitoring before the start of lifelong drug treatment might lead to more appropriate targeting of treatment, particularly around the diagnostic threshold.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Compared with ambulatory monitoring thresholds of 135/85 mm Hg, clinic measurements over 140/90 mm Hg had mean sensitivity and specificity of 74.6% (95% confidence interval 60.7% to 84.8%) and 74.6% (47.9% to 90.4%), respectively, whereas home measurements over 135/85 mm Hg had mean sensitivity and specificity of 85.7% (78.0% to 91.0%) and 62.4% (48.0% to 75.0%).". 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: Ambulatory blood pressure monitoring is inaccurate at diagnosing hypertension.

Document title: Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: systematic review

Abstract sentences:
[0] OBJECTIVE To determine the relative accuracy of clinic measurements and home blood pressure monitoring compared with ambulatory blood pressure monitoring as a reference standard for the diagnosis of hypertension.
[1] DESIGN Systematic review with meta-analysis with hierarchical summary receiver operating characteristic models.
[2] Methodological quality was appraised, including evidence of validation of blood pressure measurement equipment.
[3] DATA SOURCES Medline (from 1966), Embase (from 1980), Cochrane Database of Systematic Reviews, DARE, Medion, ARIF, and TRIP up to May 2010.
[4] Eligibility criteria for selecting studies Eligible studies examined diagnosis of hypertension in adults of all ages using home and/or clinic blood pressure measurement compared with those made using ambulatory monitoring that clearly defined thresholds to diagnose hypertension.
[5] RESULTS The 20 eligible studies used various thresholds for the diagnosis of hypertension, and only seven studies (clinic) and three studies (home) could be directly compared with ambulatory monitoring.
[6] Compared with ambulatory monitoring thresholds of 135/85 mm Hg, clinic measurements over 140/90 mm Hg had mean sensitivity and specificity of 74.6% (95% confidence interval 60.7% to 84.8%) and 74.6% (47.9% to 90.4%), respectively, whereas home measurements over 135/85 mm Hg had mean sensitivity and specificity of 85.7% (78.0% to 91.0%) and 62.4% (48.0% to 75.0%).
[7] CONCLUSIONS Neither clinic nor home measurement had sufficient sensitivity or specificity to be recommended as a single diagnostic test.
[8] If ambulatory monitoring is taken as the reference standard, then treatment decisions based on clinic or home blood pressure alone might result in substantial overdiagnosis.
[9] Ambulatory monitoring before the start of lifelong drug treatment might lead to more appropriate targeting of treatment, particularly around the diagnostic threshold.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [8]
Explanation: Evidence states: "If ambulatory monitoring is taken as the reference standard, then treatment decisions based on clinic or home blood pressure alone might result in substantial overdiagnosis.". 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: Ambulatory blood pressure monitoring is inaccurate at diagnosing hypertension.

Document title: Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: systematic review

Abstract sentences:
[0] OBJECTIVE To determine the relative accuracy of clinic measurements and home blood pressure monitoring compared with ambulatory blood pressure monitoring as a reference standard for the diagnosis of hypertension.
[1] DESIGN Systematic review with meta-analysis with hierarchical summary receiver operating characteristic models.
[2] Methodological quality was appraised, including evidence of validation of blood pressure measurement equipment.
[3] DATA SOURCES Medline (from 1966), Embase (from 1980), Cochrane Database of Systematic Reviews, DARE, Medion, ARIF, and TRIP up to May 2010.
[4] Eligibility criteria for selecting studies Eligible studies examined diagnosis of hypertension in adults of all ages using home and/or clinic blood pressure measurement compared with those made using ambulatory monitoring that clearly defined thresholds to diagnose hypertension.
[5] RESULTS The 20 eligible studies used various thresholds for the diagnosis of hypertension, and only seven studies (clinic) and three studies (home) could be directly compared with ambulatory monitoring.
[6] Compared with ambulatory monitoring thresholds of 135/85 mm Hg, clinic measurements over 140/90 mm Hg had mean sensitivity and specificity of 74.6% (95% confidence interval 60.7% to 84.8%) and 74.6% (47.9% to 90.4%), respectively, whereas home measurements over 135/85 mm Hg had mean sensitivity and specificity of 85.7% (78.0% to 91.0%) and 62.4% (48.0% to 75.0%).
[7] CONCLUSIONS Neither clinic nor home measurement had sufficient sensitivity or specificity to be recommended as a single diagnostic test.
[8] If ambulatory monitoring is taken as the reference standard, then treatment decisions based on clinic or home blood pressure alone might result in substantial overdiagnosis.
[9] Ambulatory monitoring before the start of lifelong drug treatment might lead to more appropriate targeting of treatment, particularly around the diagnostic threshold.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [9]
Explanation: Evidence states: "Ambulatory monitoring before the start of lifelong drug treatment might lead to more appropriate targeting of treatment, particularly around the diagnostic threshold.". 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: Ambulatory blood pressure monitoring is inaccurate at diagnosing hypertension.

Document title: Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study.

Abstract sentences:
[0] BACKGROUND The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension.
[1] We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension.
[2] METHODS We did a Markov model-based probabilistic cost-effectiveness analysis.
[3] We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population.
[4] We compared three diagnostic strategies-further blood pressure measurement in the clinic, at home, and with an ambulatory monitor-in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness.
[5] FINDINGS Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages.
[6] It was cost-saving for all groups (from -£56 [95% CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to 0·022 [0·012 to 0·035] for men aged 70 years).
[7] This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive.
[8] INTERPRETATION Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs.
[9] Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment.
[10] Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs.
[11] FUNDING National Institute for Health Research and the National Institute for Health and Clinical Excellence.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [0]
Explanation: Evidence states: "BACKGROUND The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension.". 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: Ambulatory blood pressure monitoring is inaccurate at diagnosing hypertension.

Document title: Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study.

Abstract sentences:
[0] BACKGROUND The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension.
[1] We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension.
[2] METHODS We did a Markov model-based probabilistic cost-effectiveness analysis.
[3] We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population.
[4] We compared three diagnostic strategies-further blood pressure measurement in the clinic, at home, and with an ambulatory monitor-in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness.
[5] FINDINGS Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages.
[6] It was cost-saving for all groups (from -£56 [95% CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to 0·022 [0·012 to 0·035] for men aged 70 years).
[7] This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive.
[8] INTERPRETATION Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs.
[9] Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment.
[10] Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs.
[11] FUNDING National Institute for Health Research and the National Institute for Health and Clinical Excellence.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [8]
Explanation: Evidence states: "INTERPRETATION Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs.". 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: Amitriptyline is an effective treatment for chronic tension-type headaches.

Document title: Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial.

Abstract sentences:
[0] CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice.
[1] Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects.
[2] OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches.
[3] DESIGN AND SETTING Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio.
[4] PARTICIPANTS Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo).
[5] INTERVENTIONS Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53).
[6] MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating >/=5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group.
[7] RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity.
[8] Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001).
[9] On other measures the combined therapy and its 2 component therapies produced similar outcomes.
[10] CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches.
[11] Combined therapy may improve outcome relative to monotherapy.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity.". 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: Amitriptyline is an effective treatment for chronic tension-type headaches.

Document title: Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial.

Abstract sentences:
[0] CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice.
[1] Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects.
[2] OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches.
[3] DESIGN AND SETTING Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio.
[4] PARTICIPANTS Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo).
[5] INTERVENTIONS Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53).
[6] MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating >/=5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group.
[7] RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity.
[8] Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001).
[9] On other measures the combined therapy and its 2 component therapies produced similar outcomes.
[10] CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches.
[11] Combined therapy may improve outcome relative to monotherapy.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [8]
Explanation: Evidence states: "Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001).". This supports the claim.


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

Claim: Amitriptyline is an effective treatment for chronic tension-type headaches.

Document title: Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial.

Abstract sentences:
[0] CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice.
[1] Behavioral and pharmacological therapies each appear modestly effective, but data are lacking on their separate and combined effects.
[2] OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for chronic tension-type headaches.
[3] DESIGN AND SETTING Randomized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio.
[4] PARTICIPANTS Two hundred three adults (mean age, 37 years; 76% women) with diagnosis of chronic tension-type headaches (mean, 26 headache d/mo).
[5] INTERVENTIONS Participants were randomly assigned to receive tricyclic antidepressant (amitriptyline hydrochloride, up to 100 mg/d, or nortriptyline hydrochloride, up to 75 mg/d) medication (n = 53), placebo (n = 48), stress management (eg, relaxation, cognitive coping) therapy (3 sessions and 2 telephone contacts) plus placebo (n = 49), or stress management therapy plus antidepressant medication (n = 53).
[6] MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings (0-10 scale) recorded by participants in a daily diary 4 times per day; number of days per month with at least moderate pain (pain rating >/=5), analgesic medication use, and Headache Disability Inventory scores, compared by intervention group.
[7] RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity, analgesic medication use, and headache-related disability than placebo, but antidepressant medication yielded more rapid improvements in headache activity.
[8] Combined therapy was more likely to produce clinically significant (>/=50%) reductions in headache index scores (64% of participants) than antidepressant medication (38% of participants; P =.006), stress management therapy (35%; P =.003), or placebo (29%; P =.001).
[9] On other measures the combined therapy and its 2 component therapies produced similar outcomes.
[10] CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches.
[11] Combined therapy may improve outcome relative to monotherapy.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [10]
Explanation: Evidence states: "CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches.". 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: Amitriptyline is an effective treatment for chronic tension-type headaches.

Document title: Amitriptyline is effective in chronic but not in episodic tension-type headache: pathogenetic implications.

Abstract sentences:
[0] The tricyclic antidepressant, amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine.
[1] However, its efficacy in episodic tension-type headache has not yet been clarified.
[2] We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension-type headache in an open-label study.
[3] Amitriptyline significantly reduced (P < 0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache.
[4] Further placebo-controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension-type headache.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "The tricyclic antidepressant, amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine.". 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: Amitriptyline is an effective treatment for chronic tension-type headaches.

Document title: Amitriptyline is effective in chronic but not in episodic tension-type headache: pathogenetic implications.

Abstract sentences:
[0] The tricyclic antidepressant, amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine.
[1] However, its efficacy in episodic tension-type headache has not yet been clarified.
[2] We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension-type headache in an open-label study.
[3] Amitriptyline significantly reduced (P < 0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache.
[4] Further placebo-controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension-type headache.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Amitriptyline significantly reduced (P < 0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache.". 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: Amitriptyline is an effective treatment for chronic tension-type headaches.

Document title: Efficacy and tolerability of amitriptylinoxide in the treatment of chronic tension-type headache: a multi-centre controlled study.

Abstract sentences:
[0] Amitriptyline is the medication of first choice in the treatment of chronic tension-type headache.
[1] In 197 patients with chronic tension-type headache (87M and 110F with a mean age of 38 +/-
[2] 13 (18-68)) efficacy and tolerability of 60-90 mg amitriptylinoxide (AO) were compared with 50-75 mg amitriptyline (AM) and placebo (PL) in a double-blind, parallel-group trial consisting of a four weeks' baseline phase and 12 weeks of treatment.
[3] The primary study endpoint was a reduction of at least 50% of the product of headache duration and frequency and a reduction of at least 50% in headache intensity.
[4] Statistics used were Fisher's exact test and analysis of variance.
[5] No significant difference emerged between AO, AM and PL with respect to the primary study endpoint.
[6] Treatment response occurred in 30.3% of the AO, 22.4% of the AM and 21.9% of the PL group.
[7] A reduction in headache duration and frequency of at least 50% was found in 39.4% on AO, in 25.4% on AM and in 26.6% on PL (PAO-PL = .1384, PAM-PL = 1.000, PAO-AM = .0973).
[8] A reduction in headache intensity of at least 50% was found in 31.8% on AO, in 26.9% on AM and in 26.6% on PL (PAO-PL = .5657, PAM-PL = 1.000, PAO-AM = .5715).
[9] Trend analysis with respect to a significant reduction of headache intensity (p < 0.05) and the product of headache duration and frequency revealed a superior effect of AO.(ABSTRACT TRUNCATED AT 250 WORDS)

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [0]
Explanation: Evidence states: "Amitriptyline is the medication of first choice in the treatment of chronic tension-type headache.". 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: Amitriptyline is an effective treatment for chronic tension-type headaches.

Document title: Efficacy and tolerability of amitriptylinoxide in the treatment of chronic tension-type headache: a multi-centre controlled study.

Abstract sentences:
[0] Amitriptyline is the medication of first choice in the treatment of chronic tension-type headache.
[1] In 197 patients with chronic tension-type headache (87M and 110F with a mean age of 38 +/-
[2] 13 (18-68)) efficacy and tolerability of 60-90 mg amitriptylinoxide (AO) were compared with 50-75 mg amitriptyline (AM) and placebo (PL) in a double-blind, parallel-group trial consisting of a four weeks' baseline phase and 12 weeks of treatment.
[3] The primary study endpoint was a reduction of at least 50% of the product of headache duration and frequency and a reduction of at least 50% in headache intensity.
[4] Statistics used were Fisher's exact test and analysis of variance.
[5] No significant difference emerged between AO, AM and PL with respect to the primary study endpoint.
[6] Treatment response occurred in 30.3% of the AO, 22.4% of the AM and 21.9% of the PL group.
[7] A reduction in headache duration and frequency of at least 50% was found in 39.4% on AO, in 25.4% on AM and in 26.6% on PL (PAO-PL = .1384, PAM-PL = 1.000, PAO-AM = .0973).
[8] A reduction in headache intensity of at least 50% was found in 31.8% on AO, in 26.9% on AM and in 26.6% on PL (PAO-PL = .5657, PAM-PL = 1.000, PAO-AM = .5715).
[9] Trend analysis with respect to a significant reduction of headache intensity (p < 0.05) and the product of headache duration and frequency revealed a superior effect of AO.(ABSTRACT TRUNCATED AT 250 WORDS)

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [3]
Explanation: Evidence states: "The primary study endpoint was a reduction of at least 50% of the product of headache duration and frequency and a reduction of at least 50% in headache intensity.". 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: Amitriptyline is an effective treatment for chronic tension-type headaches.

Document title: Efficacy and tolerability of amitriptylinoxide in the treatment of chronic tension-type headache: a multi-centre controlled study.

Abstract sentences:
[0] Amitriptyline is the medication of first choice in the treatment of chronic tension-type headache.
[1] In 197 patients with chronic tension-type headache (87M and 110F with a mean age of 38 +/-
[2] 13 (18-68)) efficacy and tolerability of 60-90 mg amitriptylinoxide (AO) were compared with 50-75 mg amitriptyline (AM) and placebo (PL) in a double-blind, parallel-group trial consisting of a four weeks' baseline phase and 12 weeks of treatment.
[3] The primary study endpoint was a reduction of at least 50% of the product of headache duration and frequency and a reduction of at least 50% in headache intensity.
[4] Statistics used were Fisher's exact test and analysis of variance.
[5] No significant difference emerged between AO, AM and PL with respect to the primary study endpoint.
[6] Treatment response occurred in 30.3% of the AO, 22.4% of the AM and 21.9% of the PL group.
[7] A reduction in headache duration and frequency of at least 50% was found in 39.4% on AO, in 25.4% on AM and in 26.6% on PL (PAO-PL = .1384, PAM-PL = 1.000, PAO-AM = .0973).
[8] A reduction in headache intensity of at least 50% was found in 31.8% on AO, in 26.9% on AM and in 26.6% on PL (PAO-PL = .5657, PAM-PL = 1.000, PAO-AM = .5715).
[9] Trend analysis with respect to a significant reduction of headache intensity (p < 0.05) and the product of headache duration and frequency revealed a superior effect of AO.(ABSTRACT TRUNCATED AT 250 WORDS)

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [7]
Explanation: Evidence states: "A reduction in headache duration and frequency of at least 50% was found in 39.4% on AO, in 25.4% on AM and in 26.6% on PL (PAO-PL = .1384, PAM-PL = 1.000, PAO-AM = .0973).". This supports the claim.