abstract: Protective effect of @entity917 ( @entity2596 ), an angiotensin II (AII)-receptor blocker ( @entity11882 ), against @entity16 is reported to depend on the dosing time in @entity101 @entity1 . Dosing-time-dependent effect of @entity2596 on survival of @entity64 -prone spontaneously @entity101 @entity35 (SHRSP) under a 12-h lighting cycle was examined. @entity2596 (4 mg/kg per day) and @entity15632 (OM) (1 mg/kg per day), another @entity11882 with a slower dissociation from the AII receptor, were given once daily at 2, 8, 14, or 20 @entity3917 ( @entity3917 ). Dosing-time-dependent differences in plasma drug concentrations and effect on blood pressure (BP) were also evaluated. Survival of SHRSP showed a dosing-time-dependent change during @entity2596 therapy, with a peak at 2 @entity3917 and a trough at 14 @entity3917 . OM equally prolonged survival in all groups. The BP-lowering effect persisted for more than 24 h after dosing of @entity2596 at 2 @entity3917 and of OM at 2 and 14 @entity3917 , but disappeared at 5.5-h after @entity2596 dosing at 14 @entity3917 . Plasma concentrations of @entity2596 and OM were higher after dosing at 2 @entity3917 than at 14 @entity3917 . These results suggest that the chronopharmacological phenomenon of @entity2596 was partly due to the dosing-time-dependent difference in plasma concentration and subsequent duration of the antihypertensive effect. Slower dissociation of OM from AII receptors might have blunted a potential dosing-time-dependent event.

title: Chronopharmacology of angiotensin II-receptor blockers in XXXX -prone spontaneously @entity101 @entity35 .

entities_list: @entity917 :: ('MESH:C081489', 'Chemical') :: ['valsartan']

entities_list: @entity1 :: ('9606', 'Species') :: ['patients']

entities_list: @entity101 :: ('MESH:D006973', 'Disease') :: ['hypertensive']

entities_list: @entity16 :: ('MESH:D009422', 'Disease') :: ['organ damage']

entities_list: @entity15632 :: ('MESH:C097933', 'Chemical') :: ['olmesartan medoxomil']

entities_list: @entity3917 :: ('MESH:D020795', 'Disease') :: ['hours after lights on', 'HALO']

answer: @entity64 :: (MESH:D020521,Disease) :: ['stroke']


abstract: Protective effect of @entity917 ( @entity2596 ), an angiotensin II (AII)-receptor blocker ( @entity11882 ), against @entity16 is reported to depend on the dosing time in @entity101 @entity1 . Dosing-time-dependent effect of @entity2596 on survival of @entity64 -prone spontaneously @entity101 @entity35 (SHRSP) under a 12-h lighting cycle was examined. @entity2596 (4 mg/kg per day) and @entity15632 (OM) (1 mg/kg per day), another @entity11882 with a slower dissociation from the AII receptor, were given once daily at 2, 8, 14, or 20 @entity3917 ( @entity3917 ). Dosing-time-dependent differences in plasma drug concentrations and effect on blood pressure (BP) were also evaluated. Survival of SHRSP showed a dosing-time-dependent change during @entity2596 therapy, with a peak at 2 @entity3917 and a trough at 14 @entity3917 . OM equally prolonged survival in all groups. The BP-lowering effect persisted for more than 24 h after dosing of @entity2596 at 2 @entity3917 and of OM at 2 and 14 @entity3917 , but disappeared at 5.5-h after @entity2596 dosing at 14 @entity3917 . Plasma concentrations of @entity2596 and OM were higher after dosing at 2 @entity3917 than at 14 @entity3917 . These results suggest that the chronopharmacological phenomenon of @entity2596 was partly due to the dosing-time-dependent difference in plasma concentration and subsequent duration of the antihypertensive effect. Slower dissociation of OM from AII receptors might have blunted a potential dosing-time-dependent event.

title: Chronopharmacology of angiotensin II-receptor blockers in @entity64 -prone spontaneously XXXX @entity35 .

answer: @entity101 :: (MESH:D006973,Disease) :: ['hypertensive']


abstract: Protective effect of @entity917 ( @entity2596 ), an angiotensin II (AII)-receptor blocker ( @entity11882 ), against @entity16 is reported to depend on the dosing time in @entity101 @entity1 . Dosing-time-dependent effect of @entity2596 on survival of @entity64 -prone spontaneously @entity101 @entity35 (SHRSP) under a 12-h lighting cycle was examined. @entity2596 (4 mg/kg per day) and @entity15632 (OM) (1 mg/kg per day), another @entity11882 with a slower dissociation from the AII receptor, were given once daily at 2, 8, 14, or 20 @entity3917 ( @entity3917 ). Dosing-time-dependent differences in plasma drug concentrations and effect on blood pressure (BP) were also evaluated. Survival of SHRSP showed a dosing-time-dependent change during @entity2596 therapy, with a peak at 2 @entity3917 and a trough at 14 @entity3917 . OM equally prolonged survival in all groups. The BP-lowering effect persisted for more than 24 h after dosing of @entity2596 at 2 @entity3917 and of OM at 2 and 14 @entity3917 , but disappeared at 5.5-h after @entity2596 dosing at 14 @entity3917 . Plasma concentrations of @entity2596 and OM were higher after dosing at 2 @entity3917 than at 14 @entity3917 . These results suggest that the chronopharmacological phenomenon of @entity2596 was partly due to the dosing-time-dependent difference in plasma concentration and subsequent duration of the antihypertensive effect. Slower dissociation of OM from AII receptors might have blunted a potential dosing-time-dependent event.

title: Chronopharmacology of angiotensin II-receptor blockers in @entity64 -prone spontaneously @entity101 XXXX .

answer: @entity35 :: (10116,Species) :: ['rats']


abstract: OBJECTIVE: To determine the effectiveness of specialist nurse-led clinics for @entity101 and @entity407 provided for @entity6 @entity1 receiving hospital-based care. RESEARCH DESIGN AND METHODS: This study was a randomized controlled implementation trial at Hope Hospital, Salford, U.K. The subjects consisted of 1,407 subjects presenting for annual review with raised blood pressure(>or=140/80 mmHg), raised total @entity165 (>or=5.0 mmol/l), or both. Individuals with @entity6 were randomized to usual care or usual care with subsequent invitation to attend specialist nurse-led clinics. Nurses provided clinics for @entity1 , with attendance every 4-6 weeks, until targets were achieved. Lifestyle advice and titration of drug therapies were provided according to the locally agreed upon guidelines. @entity1 with both conditions were eligible for enrollment in either or both clinics. At subsequent annual review, blood pressure and total @entity165 values were obtained from the Salford electronic @entity6 register. Data relating to deaths were obtained from the national strategic tracing service. The primary outcome was the odds ratio of achieving targets in @entity101 and @entity407 , attributable to the specialist nurse-led intervention. RESULTS: Overall, specialist nurse-led clinics were associated with a significant improvement in @entity1 achieving the target after 1 year (odds ratio [OR] 1.37 [95% CI 1.11-1.69], P = 0.003). This primary analysis revealed a borderline difference in effect between the two types of clinics (test for interaction between groups: P = 0.06). Secondary analysis, consistent with the prior beliefs of the health care professionals involved, suggested that targets were achieved more frequently in @entity1 enrolled in the specialist nurse-led clinic for @entity407 (OR 1.69 [1.25-2.29], P = 0.0007) than for @entity101 (OR 1.14 [0.86-1.51], P = 0.37). Intervention (enrolled to either or both clinics) was associated with a reduction in all-cause mortality (OR 0.55 [0.32-0.92], P = 0.02). CONCLUSIONS: This study provides good evidence to support the use of specialist nurse-led clinics as an effective adjunct to hospital-based care of @entity1 with @entity6 . If the standards of care recommended in the National Service Framework for @entity6 are to be achieved, then such proven methods for delivering care must be adopted.

title: Specialist nurse-led intervention to treat and control XXXX and @entity407 in @entity6 (SPLINT): a randomized controlled trial.

entities_list: @entity407 :: ('MESH:D006949', 'Disease') :: ['hyperlipidemia']

entities_list: @entity1 :: ('9606', 'Species') :: ['participants', 'Patients', 'patients']

entities_list: @entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension']

entities_list: @entity6 :: ('MESH:D003920', 'Disease') :: ['Diabetes', 'diabetic', 'diabetes']

entities_list: @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']

answer: @entity101 :: (MESH:D006973,Disease) :: ['hypertension']


abstract: OBJECTIVE: To determine the effectiveness of specialist nurse-led clinics for @entity101 and @entity407 provided for @entity6 @entity1 receiving hospital-based care. RESEARCH DESIGN AND METHODS: This study was a randomized controlled implementation trial at Hope Hospital, Salford, U.K. The subjects consisted of 1,407 subjects presenting for annual review with raised blood pressure(>or=140/80 mmHg), raised total @entity165 (>or=5.0 mmol/l), or both. Individuals with @entity6 were randomized to usual care or usual care with subsequent invitation to attend specialist nurse-led clinics. Nurses provided clinics for @entity1 , with attendance every 4-6 weeks, until targets were achieved. Lifestyle advice and titration of drug therapies were provided according to the locally agreed upon guidelines. @entity1 with both conditions were eligible for enrollment in either or both clinics. At subsequent annual review, blood pressure and total @entity165 values were obtained from the Salford electronic @entity6 register. Data relating to deaths were obtained from the national strategic tracing service. The primary outcome was the odds ratio of achieving targets in @entity101 and @entity407 , attributable to the specialist nurse-led intervention. RESULTS: Overall, specialist nurse-led clinics were associated with a significant improvement in @entity1 achieving the target after 1 year (odds ratio [OR] 1.37 [95% CI 1.11-1.69], P = 0.003). This primary analysis revealed a borderline difference in effect between the two types of clinics (test for interaction between groups: P = 0.06). Secondary analysis, consistent with the prior beliefs of the health care professionals involved, suggested that targets were achieved more frequently in @entity1 enrolled in the specialist nurse-led clinic for @entity407 (OR 1.69 [1.25-2.29], P = 0.0007) than for @entity101 (OR 1.14 [0.86-1.51], P = 0.37). Intervention (enrolled to either or both clinics) was associated with a reduction in all-cause mortality (OR 0.55 [0.32-0.92], P = 0.02). CONCLUSIONS: This study provides good evidence to support the use of specialist nurse-led clinics as an effective adjunct to hospital-based care of @entity1 with @entity6 . If the standards of care recommended in the National Service Framework for @entity6 are to be achieved, then such proven methods for delivering care must be adopted.

title: Specialist nurse-led intervention to treat and control @entity101 and @entity407 in XXXX (SPLINT): a randomized controlled trial.

answer: @entity6 :: (MESH:D003920,Disease) :: ['diabetes']


abstract: OBJECTIVE: To determine the effectiveness of specialist nurse-led clinics for @entity101 and @entity407 provided for @entity6 @entity1 receiving hospital-based care. RESEARCH DESIGN AND METHODS: This study was a randomized controlled implementation trial at Hope Hospital, Salford, U.K. The subjects consisted of 1,407 subjects presenting for annual review with raised blood pressure(>or=140/80 mmHg), raised total @entity165 (>or=5.0 mmol/l), or both. Individuals with @entity6 were randomized to usual care or usual care with subsequent invitation to attend specialist nurse-led clinics. Nurses provided clinics for @entity1 , with attendance every 4-6 weeks, until targets were achieved. Lifestyle advice and titration of drug therapies were provided according to the locally agreed upon guidelines. @entity1 with both conditions were eligible for enrollment in either or both clinics. At subsequent annual review, blood pressure and total @entity165 values were obtained from the Salford electronic @entity6 register. Data relating to deaths were obtained from the national strategic tracing service. The primary outcome was the odds ratio of achieving targets in @entity101 and @entity407 , attributable to the specialist nurse-led intervention. RESULTS: Overall, specialist nurse-led clinics were associated with a significant improvement in @entity1 achieving the target after 1 year (odds ratio [OR] 1.37 [95% CI 1.11-1.69], P = 0.003). This primary analysis revealed a borderline difference in effect between the two types of clinics (test for interaction between groups: P = 0.06). Secondary analysis, consistent with the prior beliefs of the health care professionals involved, suggested that targets were achieved more frequently in @entity1 enrolled in the specialist nurse-led clinic for @entity407 (OR 1.69 [1.25-2.29], P = 0.0007) than for @entity101 (OR 1.14 [0.86-1.51], P = 0.37). Intervention (enrolled to either or both clinics) was associated with a reduction in all-cause mortality (OR 0.55 [0.32-0.92], P = 0.02). CONCLUSIONS: This study provides good evidence to support the use of specialist nurse-led clinics as an effective adjunct to hospital-based care of @entity1 with @entity6 . If the standards of care recommended in the National Service Framework for @entity6 are to be achieved, then such proven methods for delivering care must be adopted.

title: Specialist nurse-led intervention to treat and control @entity101 and XXXX in @entity6 (SPLINT): a randomized controlled trial.

answer: @entity407 :: (MESH:D006949,Disease) :: ['hyperlipidemia']


abstract: @entity164 2 @entity6 is a global problem, and current ineffective therapeutic strategies pave the way for novel treatments like small molecular activators targeting glucokinase ( @entity14224 ). @entity14224 activity is fundamental to beta cell and hepatocyte @entity413 metabolism, and heterozygous activating and inactivating @entity14224 mutations cause @entity1717 ( @entity1717 ) and @entity2175 ( @entity2175 ) respectively. Over 600 naturally occurring inactivating mutations have been reported, whereas only 13 activating mutations are documented to date. We report two novel @entity14224 @entity1717 mutations ( @entity72689 and @entity72690 ) at residues where @entity2175 mutations also occur ( @entity72691 and @entity36575 ). Using recombinant proteins with in vitro assays, we demonstrated that both @entity1717 mutants had a greater relative activity index than wild type (6.0 for @entity72689 , 8.4 for @entity72690 , and 1.0 for wild type). This was driven by an increased affinity for @entity413 (S(0.5), 3.3    0.1 and 3.5    0.1 mm, respectively) versus wild type (7.5    0.1 mm). Correspondingly, the @entity72691 and @entity36575 @entity2175 mutants had markedly reduced relative activity indexes (<0.1). @entity36575 had an altered affinity for @entity413 (S(0.5), 24.9    0.6 mm), whereas @entity72691 also exhibited a reduced affinity for @entity855 and decreased catalysis rate (S(0.5), 78.6    4.5 mm; @entity855 (K(m)), 1.5    0.1 mm; K(cat), 10.3    1.1s(-1)) compared with wild type ( @entity855 (K(m)), 0.4    <0.1; K(cat), 62.9    1.2). Both Thr-103 mutants showed reduced inhibition by the endogenous hepatic inhibitor glucokinase regulatory protein. Molecular modeling demonstrated that Thr-103 maps to the allosteric activator site, whereas @entity2596 -389 is located remotely to this position and all other previously reported activating mutations, highlighting a-helix 11 as a novel region regulating @entity14224 activity. Our data suggest that pharmacological manipulation of @entity14224 activity at locations distal from the allosteric activator site is possible.

title: Discovery of a novel site regulating glucokinase activity following characterization of a new mutation causing XXXX in humans.

entities_list: @entity2175 :: ('MESH:D003924', 'Disease') :: ['maturity onset diabetes of the young', 'MODY']

entities_list: @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes']

entities_list: @entity1717 :: ('MESH:D044903', 'Disease') :: ['HH', 'hyperinsulinemic hypoglycemia']

entities_list: @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']

answer: @entity1717 :: (MESH:D044903,Disease) :: ['hyperinsulinemic hypoglycemia']


abstract: PURPOSE: To assess the outcome of surgery in @entity1 with a history of contact lens wear. DESIGN: Retrospective, comparative interventional case series. METHODS: A total of 419 @entity1 underwent @entity1736 surgery during a 1-year period (2005-2006) at Moorfields Eye Hospital. Those included in this study had a diagnosis of @entity1736 and history of contact lens wear. MAIN OUTCOME MEASURES: The outcome was considered a success if the following criteria were met: 1) a margin reflex distance of between 3 and 5 mm, 2) an interlid difference of 1 mm or less, and 3) absence of redo surgery. RESULTS: Thirty @entity1 (7.2%) were identified with a history of contact lens wear and were matched against a control group of 46 @entity1 . The mean margin-reflex distance at presentation was 0.5    2.4 mm. This equated to a @entity1736 graded as mild (>= 1.5 mm) for 32% of @entity1 , moderate (0.5-1.0 mm) for 29%, and severe ( <=0.0 mm) for 39%, with similar proportions in the control group (36% mild, 39% moderate, and 25% severe). The power of the refractive correction (p < 0.005) and the age of the @entity1 (p < 0.05) were directly related to increased severity of @entity1736 at presentation. The surgical outcome of the @entity1736 correction was successful in 72% of @entity1 , which was significantly lower than in the control group (89%) (p < 0.005). CONCLUSIONS: The severity of contact lens-related @entity1736 was related to the degree of @entity1714 and the age of the @entity1 but not to the duration of contact lens wear. There was a higher level of failure and requirement for redo surgery in @entity1 with contact lens-related @entity1736 compared with matched controls.

title: Outcome following surgery for contact lens-induced XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'patient']

entities_list: @entity1736 :: ('MESH:D001763', 'Disease') :: ['ptosis', 'aponeurotic ptosis']

answer: @entity1736 :: (MESH:D001763,Disease) :: ['ptosis']


abstract: OBJECTIVES: @entity14000 ( @entity14000 ) is one of the most intractable @entity2531 , especially in elderly @entity1 . There is evidence that repetitive transcranial magnetic stimulation (rTMS) reduces @entity9 ; however, its effectiveness for @entity14000 is unknown. This study investigated the efficacy of high-frequency rTMS in @entity1 with @entity14000 . DESIGN: A total of 40 @entity1 were randomly assigned to receive 10 sessions of real or sham rTMS of the primary motor cortex. Each stimulation session consisted of a series of 300 five-second pulses with a frequency of 10 Hz and an interval of 3 seconds between each train, giving a total of 1500 pulses per session. The primary outcome was @entity158 intensity measured before stimulation from first intervention (T0) to the final stimulation (T10), @entity676 months after final stimulation (T11 and T12). Other outcomes measured included scores on the short form @entity158 questionnaire, self-rating @entity308 scale, quality of life (QOL), sleep quality, the @entity1 global impression of change, medication regulation, and reported adverse events. RESULTS: The real rTMS group demonstrated greater reduction of visual analogue scale (VAS) than the sham group at each time point except for T0 (P   =   0.399) and T1 (P   =   0.091). Mean VAS reduction in the real rTMS group was 16.89% for duration of disease longer than 6 months. These analgesic effects were associated with long-term improvement in rating-scale items related to QOL. CONCLUSION: The results suggest that rTMS is an effective and safe therapy in @entity1 with @entity14000 .

title: High-Frequency Repetitive Transcranial Magnetic Stimulation Reduces XXXX in @entity14000 .

entities_list: @entity308 :: ('MESH:D003866', 'Disease') :: ['depression']

entities_list: @entity2531 :: ('MESH:D013001', 'Disease') :: ['pain disorders']

entities_list: @entity158 :: ('MESH:D010146', 'Disease') :: ['McGill pain', 'pain']

entities_list: @entity14000 :: ('MESH:D051474', 'Disease') :: ['PHN', 'Postherpetic neuralgia']

entities_list: @entity9 :: ('MESH:D009437', 'Disease') :: ['neuropathic pain']

answer: @entity158 :: (MESH:D010146,Disease) :: ['Pain']


abstract: OBJECTIVES: @entity14000 ( @entity14000 ) is one of the most intractable @entity2531 , especially in elderly @entity1 . There is evidence that repetitive transcranial magnetic stimulation (rTMS) reduces @entity9 ; however, its effectiveness for @entity14000 is unknown. This study investigated the efficacy of high-frequency rTMS in @entity1 with @entity14000 . DESIGN: A total of 40 @entity1 were randomly assigned to receive 10 sessions of real or sham rTMS of the primary motor cortex. Each stimulation session consisted of a series of 300 five-second pulses with a frequency of 10 Hz and an interval of 3 seconds between each train, giving a total of 1500 pulses per session. The primary outcome was @entity158 intensity measured before stimulation from first intervention (T0) to the final stimulation (T10), @entity676 months after final stimulation (T11 and T12). Other outcomes measured included scores on the short form @entity158 questionnaire, self-rating @entity308 scale, quality of life (QOL), sleep quality, the @entity1 global impression of change, medication regulation, and reported adverse events. RESULTS: The real rTMS group demonstrated greater reduction of visual analogue scale (VAS) than the sham group at each time point except for T0 (P   =   0.399) and T1 (P   =   0.091). Mean VAS reduction in the real rTMS group was 16.89% for duration of disease longer than 6 months. These analgesic effects were associated with long-term improvement in rating-scale items related to QOL. CONCLUSION: The results suggest that rTMS is an effective and safe therapy in @entity1 with @entity14000 .

title: High-Frequency Repetitive Transcranial Magnetic Stimulation Reduces @entity158 in XXXX .

answer: @entity14000 :: (MESH:D051474,Disease) :: ['Postherpetic Neuralgia']


abstract: PURPOSE: This study was designed to determine whether vonapanitase (formerly PRT-201), a recombinant @entity1 elastase, treatment can fragment the protein @entity2362 in elastic fibers and cause dilation of @entity731 @entity1 peripheral arteries subjected to ex vivo balloon angioplasty. MATERIALS AND METHODS: Seven @entity1 undergoing lower limb amputation for @entity3657 or who died and donated their bodies to science donated 11 tibial arteries (5 anterior, 6 posterior) for this study. All arteries were @entity731 by visual inspection. The arteries underwent ex vivo balloon angioplasty and thereafter were cut into rings and studied on wire myographs where the rings were stretched and @entity2701 was recorded. After treatment with vonapanitase 2 mg/mL or vehicle control, myography was repeated and the rings were then subject to @entity2362 content measurement using a @entity13403 radioimmunoassay and elastic fiber visualization by histology. The wire myography data were used to derive compliance, stress-strain, and incremental elastic modulus curves. RESULTS: Vonapanitase treatment reduced @entity2362 ( @entity13403 ) content by 60% and decreased elastic fiber histologic staining. Vonapanitase-treated rings experienced less @entity2701 at any level of stretch and as a result had shifts in the compliance and stress-strain curves relative to vehicle-treated rings. Vonapanitase treatment did not alter the incremental elastic modulus curve. CONCLUSIONS: Vonapanitase treatment of @entity731 @entity1 peripheral arteries after ex vivo balloon angioplasty fragmented @entity2362 in elastic fibers, decreased @entity2701 in the rings at any level of stretch, and altered the compliance and stress-strain curves in a manner predicting @entity384 in vivo. Based on this result, local treatment of balloon angioplasty sites may increase blood vessel diameter and thereby improve the success of balloon angioplasty in @entity3657 .

title: Recombinant XXXX Elastase Alters the Compliance of Atherosclerotic Tibial Arteries After Ex Vivo Angioplasty.

entities_list: @entity1 :: ('9606', 'Species') :: ['human', 'patients']

entities_list: @entity3657 :: ('MESH:D058729', 'Disease') :: ['peripheral artery disease']

entities_list: @entity13403 :: ('MESH:D003895', 'Chemical') :: ['desmosine']

entities_list: @entity384 :: ('MESH:D002311', 'Disease') :: ['arterial dilation']

entities_list: @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerotic']

answer: @entity1 :: (9606,Species) :: ['Human']


abstract: BACKGROUND: The impact of pregnancy on mast cell (MC)-related symptoms and newborn outcome in @entity1 with @entity5310 is not well described. We report a series of 30 @entity1 who had 45 pregnancies. METHODS: @entity1 completed a specific questionnaire concerning MC mediator release symptoms graded according to their frequency to detect clinical changes occurring during pregestation and pregnancy as well as postpartum. Information about the medications received during pregnancy and labor and about newborn medical complications was also recorded. RESULTS: Worsening of MC-related symptoms during pregnancy was observed in 10 cases (22%); additionally, 1 @entity1 developed @entity272 as a manifestation of @entity262 ( @entity262 ) within the third trimester of pregnancy. Conversely, 15 cases (33%) experienced clinical improvement during pregnancy, with a complete resolution of pregestational symptoms in 7 cases. MC mediator release symptoms intrapartum were observed in 5 cases (11%) without any fatal outcome. Newborn medical complications (e.g. prematurity, low birth weight, and @entity649 ) were detected in 7 @entity1 (16%) who were all successfully managed with conservative measures. One @entity1 developed @entity20145 several years after birth. CONCLUSIONS: @entity5310 has a heterogeneous clinical behavior during pregnancy: the profile of MC-related symptoms remained unchanged in half of the cases, while in the other half pregnant @entity1 experienced either an improvement or an exacerbation of the symptoms, with the manifestation of @entity262 during pregnancy in 1 case. To prevent potential life-threatening MC-related symptoms, adequate prophylactic antimediator therapy intrapartum should be systematically administered. The absence of both maternal and @entity1 severe complications suggests that @entity1 with nonaggressive categories of @entity5310 should not be advised against pregnancy.

title: Clinical impact of pregnancy in XXXX : a study of the Spanish Network on @entity5310 (REMA) in 45 cases.

entities_list: @entity1 :: ('9606', 'Species') :: ['women', 'Patients', 'woman', 'patients', 'infants', 'infant']

entities_list: @entity20145 :: ('MESH:D034701', 'Disease') :: ['cutaneous mastocytosis']

entities_list: @entity5310 :: ('MESH:D008415', 'Disease') :: ['mastocytosis', 'Mastocytosis']

entities_list: @entity649 :: ('MESH:D012128', 'Disease') :: ['respiratory distress']

entities_list: @entity262 :: ('MESH:D034721', 'Disease') :: ['indolent systemic mastocytosis', 'ISM']

entities_list: @entity272 :: ('MESH:D012871', 'Disease') :: ['skin lesions']

answer: @entity5310 :: (MESH:D008415,Disease) :: ['mastocytosis']


abstract: BACKGROUND: The impact of pregnancy on mast cell (MC)-related symptoms and newborn outcome in @entity1 with @entity5310 is not well described. We report a series of 30 @entity1 who had 45 pregnancies. METHODS: @entity1 completed a specific questionnaire concerning MC mediator release symptoms graded according to their frequency to detect clinical changes occurring during pregestation and pregnancy as well as postpartum. Information about the medications received during pregnancy and labor and about newborn medical complications was also recorded. RESULTS: Worsening of MC-related symptoms during pregnancy was observed in 10 cases (22%); additionally, 1 @entity1 developed @entity272 as a manifestation of @entity262 ( @entity262 ) within the third trimester of pregnancy. Conversely, 15 cases (33%) experienced clinical improvement during pregnancy, with a complete resolution of pregestational symptoms in 7 cases. MC mediator release symptoms intrapartum were observed in 5 cases (11%) without any fatal outcome. Newborn medical complications (e.g. prematurity, low birth weight, and @entity649 ) were detected in 7 @entity1 (16%) who were all successfully managed with conservative measures. One @entity1 developed @entity20145 several years after birth. CONCLUSIONS: @entity5310 has a heterogeneous clinical behavior during pregnancy: the profile of MC-related symptoms remained unchanged in half of the cases, while in the other half pregnant @entity1 experienced either an improvement or an exacerbation of the symptoms, with the manifestation of @entity262 during pregnancy in 1 case. To prevent potential life-threatening MC-related symptoms, adequate prophylactic antimediator therapy intrapartum should be systematically administered. The absence of both maternal and @entity1 severe complications suggests that @entity1 with nonaggressive categories of @entity5310 should not be advised against pregnancy.

title: Clinical impact of pregnancy in @entity5310 : a study of the Spanish Network on XXXX (REMA) in 45 cases.

answer: @entity5310 :: (MESH:D008415,Disease) :: ['Mastocytosis']


abstract: BACKGROUND: Advances in the treatment of metastatic @entity14 (mCRC) in the last decade have significantly improved survival; however, simple biomarkers to predict response or @entity137 have not been identified, which are applicable to all community oncology settings worldwide. The use of inflammatory markers based on differential white-cell counts, such as the neutrophil/lymphocyte ratio (NLR), may be simple and readily available biomarkers. METHODS: Clinical information and baseline laboratory parameters were available for 349 @entity1 , from two independent cohorts, with unresectable mCRC receiving first-line palliative chemotherapy. Associations between baseline prognostic variables, including inflammatory markers such as the NLR and @entity5 response, progression and survival were investigated. RESULTS: In the training cohort, combination-agent chemotherapy (P=0.001) and NLR  <= 5 (P=0.003) were associated with improved clinical benefit. The ECOG performance status    1 (P=0.002), NLR>5 (P=0.01), hypoalbuminaemia (P=0.03) and single-agent chemotherapy (P<0.0001) were associated with increased risk of progression. The ECOG performance status >=  1 (P=0.004) and NLR>5 (P=0.002) predicted worse @entity1349 ( @entity1349 ). The NLR was confirmed to independently predict @entity1349 in the validation cohort (P<0.0001). Normalisation of the NLR after one cycle of chemotherapy in a subset of @entity1 resulted in improved progression-free survival (P=0.012). CONCLUSION: These results have highlighted NLR as a potentially useful clinical biomarker of systemic inflammatory response in predicting clinically meaningful outcomes in two independent cohorts. Results of this study have also confirmed the importance of a chronic systemic inflammatory response influencing clinical outcomes in @entity1 with mCRC.

title: Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in @entity1 with advanced XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['patients']

entities_list: @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumour']

entities_list: @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer']

entities_list: @entity1349 :: ('MESH:D011475', 'Disease') :: ['OS', 'overall survival']

answer: @entity14 :: (MESH:D015179,Disease) :: ['colorectal cancer']


abstract: BACKGROUND: Advances in the treatment of metastatic @entity14 (mCRC) in the last decade have significantly improved survival; however, simple biomarkers to predict response or @entity137 have not been identified, which are applicable to all community oncology settings worldwide. The use of inflammatory markers based on differential white-cell counts, such as the neutrophil/lymphocyte ratio (NLR), may be simple and readily available biomarkers. METHODS: Clinical information and baseline laboratory parameters were available for 349 @entity1 , from two independent cohorts, with unresectable mCRC receiving first-line palliative chemotherapy. Associations between baseline prognostic variables, including inflammatory markers such as the NLR and @entity5 response, progression and survival were investigated. RESULTS: In the training cohort, combination-agent chemotherapy (P=0.001) and NLR  <= 5 (P=0.003) were associated with improved clinical benefit. The ECOG performance status    1 (P=0.002), NLR>5 (P=0.01), hypoalbuminaemia (P=0.03) and single-agent chemotherapy (P<0.0001) were associated with increased risk of progression. The ECOG performance status >=  1 (P=0.004) and NLR>5 (P=0.002) predicted worse @entity1349 ( @entity1349 ). The NLR was confirmed to independently predict @entity1349 in the validation cohort (P<0.0001). Normalisation of the NLR after one cycle of chemotherapy in a subset of @entity1 resulted in improved progression-free survival (P=0.012). CONCLUSION: These results have highlighted NLR as a potentially useful clinical biomarker of systemic inflammatory response in predicting clinically meaningful outcomes in two independent cohorts. Results of this study have also confirmed the importance of a chronic systemic inflammatory response influencing clinical outcomes in @entity1 with mCRC.

title: Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in XXXX with advanced @entity14 .

answer: @entity1 :: (9606,Species) :: ['patients']


abstract: INTRODUCTION: @entity7502 mesh has previously been shown to be an effective treatment for failed patellar tendon repairs after total knee arthroplasty (TKA), but there have been few reports of this synthetic mesh used in complete @entity397 after TKA. METHODS: We retrospectively reviewed seven consecutive cases in six @entity1 with complete @entity121 tears after TKA who had their @entity121 tendon repaired with suture and @entity7502 mesh augmentation. All but two @entity1 had previously failed primary suture repair. @entity1 outcomes were evaluated using the Knee Society Score. Standardized anterior-posterior (AP), lateral and merchant radiographs were evaluated preoperatively and at final follow-up. RESULTS: Seven knees in six @entity1 were evaluated with a mean follow-up of 34  10 (range 24 to 49months) months. There were only four clinical successes defined as an extensor lag less than 30  . Of the functioning knees at final follow-up (n=5) the overall extensor lag in this group did significantly improve from 50  13   to 20  15   (range 5 to 40  ) (p=.01). Mean postoperative flexion at final follow-up was 115  8  . Mean Knee Society Score for function improved from 20  30 to 45  54 (p=.03) as did the mean Knee Society Score for @entity158 (44  18 vs. 74  78, p=.02). DISCUSSION: @entity7502 mesh offered limited postoperative functional results when used as an augment to the multiply operated knee that sustains a complete @entity397 after TKA, but did allow for significant improvement in postoperative @entity158 outcomes. LEVEL OF EVIDENCE: IV.

title: XXXX mesh augmentation for complete @entity397 after total knee arthroplasty.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'Patient']

entities_list: @entity7502 :: ('MESH:D011126', 'Chemical') :: ['polypropylene', 'Polypropylene']

entities_list: @entity397 :: ('MESH:D012421', 'Disease') :: ['quadriceps rupture']

entities_list: @entity121 :: ('MESH:D009135', 'Disease') :: ['quadriceps']

answer: @entity7502 :: (MESH:D011126,Chemical) :: ['Polypropylene']


abstract: INTRODUCTION: @entity7502 mesh has previously been shown to be an effective treatment for failed patellar tendon repairs after total knee arthroplasty (TKA), but there have been few reports of this synthetic mesh used in complete @entity397 after TKA. METHODS: We retrospectively reviewed seven consecutive cases in six @entity1 with complete @entity121 tears after TKA who had their @entity121 tendon repaired with suture and @entity7502 mesh augmentation. All but two @entity1 had previously failed primary suture repair. @entity1 outcomes were evaluated using the Knee Society Score. Standardized anterior-posterior (AP), lateral and merchant radiographs were evaluated preoperatively and at final follow-up. RESULTS: Seven knees in six @entity1 were evaluated with a mean follow-up of 34  10 (range 24 to 49months) months. There were only four clinical successes defined as an extensor lag less than 30  . Of the functioning knees at final follow-up (n=5) the overall extensor lag in this group did significantly improve from 50  13   to 20  15   (range 5 to 40  ) (p=.01). Mean postoperative flexion at final follow-up was 115  8  . Mean Knee Society Score for function improved from 20  30 to 45  54 (p=.03) as did the mean Knee Society Score for @entity158 (44  18 vs. 74  78, p=.02). DISCUSSION: @entity7502 mesh offered limited postoperative functional results when used as an augment to the multiply operated knee that sustains a complete @entity397 after TKA, but did allow for significant improvement in postoperative @entity158 outcomes. LEVEL OF EVIDENCE: IV.

title: @entity7502 mesh augmentation for complete XXXX after total knee arthroplasty.

answer: @entity397 :: (MESH:D012421,Disease) :: ['quadriceps rupture']


abstract: BACKGROUND: The HAROW project was founded by the Stiftung M  nnergesundheit to have a closer look at the situation of @entity1 who suffer from @entity263 , especially focusing on their situation regarding supply and services. METHODS: In the current study 504 members of support groups were asked about their health-related quality of life (QOL). Standardized questionnaires were used to ensure the validation. Both the diagnosis and initial therapy dated back at least 12 months. The EORTC QLQ-C30 as well as the prostate-specific module (PSM) were used as questionnaires. RESULTS: Various forms of therapies proved to have different impacts on QOL. @entity1 with a combined hormonal therapy and radiation therapy evaluated their QOL worse than others with different forms of therapies. @entity1 with @entity5 reported significantly better data than those in the middle of therapy or the uncured. CONCLUSION: The data even indicate that their QOL is similar to @entity1 living under normal circumstances and health situations. Particular characteristics however exist on specific scales. @entity1 attending support groups show surprisingly high values for QOL.

title: [Quality of life after XXXX in members of support groups: first results of the HAROW retro study].

entities_list: @entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'people']

entities_list: @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate cancer']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['cured tumors']

answer: @entity263 :: (MESH:D011471,Disease) :: ['prostate cancer']


abstract: This clinical guideline provides recommendations for the behavioural and psychosocial interventions (BPI) of @entity1 and adolescents with @entity1765 prepared by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). A systematic literature search was conducted to obtain an update on the efficacy of BPI for tics. Relevant studies were identified using computerised searches of the Medline and PsycINFO databases and the Cochrane Library for the years 1950-2010. The search identified no meta-analyses, yet twelve (systematic) reviews and eight randomised controlled trials provided evidence for the current review. Most evidence was found for habit reversal training (HRT) and the available but smaller evidence also supports the efficacy of exposure with response prevention (ERP). Both interventions are considered first line behavioural treatments for tics for both @entity1 and adults and should be offered to a @entity1 , taking into account his preference. Treatments that are considered second line or add-on behavioural treatments are contingency management, function based interventions and relaxation training. Neurofeedback is still experimental. Almost no research was identified that examined the efficacy of psychosocial interventions, e.g., psychoeducation and group work. Based on clinical practice, this guideline recommends behavioural treatment as first line offer to @entity1 in most cases. It should be embedded within a psychoeducational and supportive context and can be combined with drug treatment.

title: European clinical guidelines for Tourette syndrome and other XXXX . Part III: behavioural and psychosocial interventions.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'children', 'patient']

entities_list: @entity1765 :: ('MESH:D013981', 'Disease') :: ['tic disorders']

answer: @entity1765 :: (MESH:D013981,Disease) :: ['tic disorders']


abstract: IMPORTANCE: Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected @entity1 populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants. OBJECTIVE: To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in @entity943 susceptibility genes. DESIGN, SETTING, AND @entity1 : This prospective cohort study included 2022 individuals recruited for nonantiarrhythmic drug exposure phenotypes from October 5, 2012, to September 30, 2013, for the Electronic Medical Records and Genomics Network Pharmacogenomics project from 7 US academic medical centers. Variants in @entity1788 and @entity9678 , disease genes for long QT and @entity1789 , were assessed for potential pathogenicity by 3 laboratories with ion channel expertise and by comparison with the ClinVar database. Relevant phenotypes were determined from EMRs, with data available from 2002 (or earlier for some sites) through September 10, 2014. EXPOSURES: One or more variants designated as pathogenic in @entity1788 or @entity9678 . MAIN OUTCOMES AND MEASURES: @entity943 or electrocardiographic (ECG) phenotypes defined by International Classification of Diseases, Ninth Revision (ICD-9) codes, ECG data, and manual EMR review. RESULTS: Among 2022 study @entity1 (median age, 61 years [interquartile range, 56-65 years]; 1118 [55%] female; 1491 [74%] white), a total of 122 rare (minor allele frequency <0.5%) nonsynonymous and splice-site variants in 2 @entity943 susceptibility genes were identified in 223 individuals (11% of the study cohort). Forty-two variants in 63 @entity1 were designated potentially pathogenic by at least 1 laboratory or ClinVar, with low concordance across laboratories (Cohen k   =   0.26). An ICD-9 code for @entity943 was found in 11 of 63 (17%) variant carriers vs 264 of 1959 (13%) of those without variants (difference, +4%; 95% CI, -5% to +13%; P   =   .35). In the 1270 (63%) with ECGs, corrected QT intervals were not different in variant carriers vs those without (median, 429 vs 439 milliseconds; difference, -10 milliseconds; 95% CI, -16 to +3 milliseconds; P   =   .17). After manual review, 22 of 63 @entity1 (35%) with designated variants had any ECG or @entity943 phenotype, and only 2 had corrected QT interval longer than 500 milliseconds. CONCLUSIONS AND RELEVANCE: Among laboratories experienced in genetic testing for @entity943 , there was low concordance in designating @entity1788 and @entity9678 variants as pathogenic. In an unselected population, the putatively pathogenic genetic variants were not associated with an abnormal phenotype. These findings raise questions about the implications of notifying @entity1 of incidental genetic findings.

title: Association of XXXX -Related Genetic Variants With Phenotypes Documented in Electronic Medical Records.

entities_list: @entity1 :: ('9606', 'Species') :: ['participants', 'patients', 'patient', 'PARTICIPANTS']

entities_list: @entity1789 :: ('MESH:D053840', 'Disease') :: ['Brugada syndromes']

entities_list: @entity943 :: ('MESH:D001145', 'Disease') :: ['cardiac arrhythmia disorders', 'Arrhythmia', 'arrhythmia']

answer: @entity943 :: (MESH:D001145,Disease) :: ['Arrhythmia']


abstract: DNA methyltransferases-- @entity16610 , @entity15786 , and @entity15894 --produce methylation patterns that dynamically regulate chromatin remodeling and gene expression. The vertebrate retina provides an ideal model to elucidate molecular control of neurogenesis as all neuronal cell types and M  ller glia are generated in a conserved order from common pools of progenitor cells. As a prelude to exploring epigenetic regulation of @entity1 retinal development, we investigated the expression of @entity16610 , @entity15786 , and @entity15894 in the @entity19 retina from embryonic day (E) 10.5 to 10 months of age. High levels of transcripts for all three Dnmt genes were observed in early stages of retinal differentiation, with significantly reduced expression after birth. Although @entity16610 protein is abundant in retinal progenitors at E10.5, it becomes restricted to postmitotic cells by E15.5. Most cells in the postnatal retina show nuclear immunostaining of @entity16610 ; however, the photoreceptors exhibit distinctive patterns. In rods, weak expression of @entity16610 is detected in perinuclear region and in the nucleus, whereas a strong nuclear labeling is evident in cones. @entity15786 and @entity15894 show a discrete pattern in developing retina with high expression at E11.5, little or no immunostaining by E15.5, and then postnatal expression overlapping with @entity16610 in early born neurons (ganglion, amacrine and horizontal cells, and cones). Robust nuclear localization of DNMTs in cones compared to rods suggests a potential role of DNA methylation in differential remodeling of chromatin in these two specialized neurons. Our studies indicate that DNA methyltransferases contribute to the establishment and maturation of cell fates during retinal development.

title: Distinct nuclear localization patterns of DNA methyltransferases in developing and mature XXXX retina.

entities_list: @entity1 :: ('9606', 'Species') :: ['mammalian']

answer: @entity1 :: (9606,Species) :: ['mammalian']


abstract: The recovery of exocrine and endocrine testicular function was studied in six @entity1 orchidectomized for an @entity172 -producing @entity8302 . @entity247 disappeared in four @entity1 . The contralateral testis, whose volume was reduced, returned to normal size after 30 days. Sperm density returned to normal in only one of the four @entity1 in whom the preoperative sperm count was reduced. One day after unilateral orchidectomy, plasma @entity53 decreased to normal and @entity251 (T) fell about 50%. On the 10th postoperative day, plasma T [5.60 +/- 1.20 ng/ml (SD)] was normal. On day 120, T was higher than on day 10 (6.83 +/- 1.20 ng/ml). There was no significant @entity101 after a single injection of hCG (5000 IU) on day 10, and the T response was similar to that of normal @entity1 on day 120. Plasma FSH and LH were increased on the 10th postoperative day; they then decreased between 60 and 120 days after the operation but were still above the normal values on day 120. The FSH/LH ratio, which was 0.43 +/- 0.17 preoperatively returned to normal (1.60 +/- 0.25) 10 days postoperatively. In conclusion, after hemicastration for an @entity172 -secreting @entity5 , testicular hormonal secretion returns to normal within 120 days but spermatogenesis may still be impaired at this time.

title: XXXX with @entity247 : further studies--the recovery after unilateral orchidectomy.

entities_list: @entity1 :: ('9606', 'Species') :: ['men', 'patients']

entities_list: @entity172 :: ('MESH:D004967', 'Chemical') :: ['estrogen']

entities_list: @entity251 :: ('MESH:D013739', 'Chemical') :: ['testosterone']

entities_list: @entity101 :: ('MESH:D006973', 'Disease') :: ['increase of T']

entities_list: @entity53 :: ('MESH:D004958', 'Chemical') :: ['estradiol']

entities_list: @entity247 :: ('MESH:D006177', 'Disease') :: ['Gynecomastia']

entities_list: @entity8302 :: ('MESH:D007984', 'Disease') :: ['Leydig cell tumor']

answer: @entity8302 :: (MESH:D007984,Disease) :: ['Leydig cell tumor']


abstract: The recovery of exocrine and endocrine testicular function was studied in six @entity1 orchidectomized for an @entity172 -producing @entity8302 . @entity247 disappeared in four @entity1 . The contralateral testis, whose volume was reduced, returned to normal size after 30 days. Sperm density returned to normal in only one of the four @entity1 in whom the preoperative sperm count was reduced. One day after unilateral orchidectomy, plasma @entity53 decreased to normal and @entity251 (T) fell about 50%. On the 10th postoperative day, plasma T [5.60 +/- 1.20 ng/ml (SD)] was normal. On day 120, T was higher than on day 10 (6.83 +/- 1.20 ng/ml). There was no significant @entity101 after a single injection of hCG (5000 IU) on day 10, and the T response was similar to that of normal @entity1 on day 120. Plasma FSH and LH were increased on the 10th postoperative day; they then decreased between 60 and 120 days after the operation but were still above the normal values on day 120. The FSH/LH ratio, which was 0.43 +/- 0.17 preoperatively returned to normal (1.60 +/- 0.25) 10 days postoperatively. In conclusion, after hemicastration for an @entity172 -secreting @entity5 , testicular hormonal secretion returns to normal within 120 days but spermatogenesis may still be impaired at this time.

title: @entity8302 with XXXX : further studies--the recovery after unilateral orchidectomy.

answer: @entity247 :: (MESH:D006177,Disease) :: ['gynecomastia']


abstract: UNASSIGNED: @entity1 Ab-secreting cell (ASC) populations in circulation are not well studied. In addition to @entity12950 ( @entity2225 (+) @entity2731 (+) @entity3053 (lo/int) @entity12910 (+)) cell and conventional plasmablast (PB) ( @entity2225 - @entity2731 (hi) @entity3053 (hi)) cell populations, in this study, we identified a novel B cell population termed 20(+)38(hi) B cells ( @entity2225 (+) @entity2731 (hi) @entity3053 (hi)) that spontaneously secretes Ab. At steady-state, 20(+)38(hi) B cells are distinct from PBs on the basis of @entity2225 expression, amount of Ab production, frequency of mutation, and diversity of BCR repertoire. However, cytokine treatment of 20(+)38(hi) B cells induces loss of @entity2225 and acquisition of @entity13221 , suggesting that 20(+)38(hi) B cells are precursors to PBs or pre-PBs. We then evaluated similarities and differences among @entity2225 (+) @entity2731 (+) @entity3053 (lo/int) @entity12910 (+) @entity12950 cells, @entity2225 (+) @entity2731 (hi) @entity3053 (hi) 20(+)38(hi) B cells, @entity2225 (-) @entity2731 (hi) @entity3053 (hi) PBs, and @entity2225 (+) @entity2731 (+) @entity3053 (lo/int) @entity12910 (-) memory B cells. We found that @entity12950 cells differ from 20(+)38(hi) B cells and PBs in a number of ways, including Ag expression, morphological appearance, transcriptional profiling, Ab skewing, Ab repertoire, and secretory response to stimulation. In terms of gene expression, @entity12950 cells align more closely with memory B cells than with 20(+)38(hi) B cells or PBs, but differ in that memory B cells do not express Ab secretion-related genes. We found that @entity12950 cell Abs use Vh4-34, which is often associated with autoreactivity, 3- to 6-fold more often than other B cell populations. Along with selective production of IgM anti- @entity2945 , these data suggest that @entity1 @entity12950 cells might be preferentially selected for autoreactivity/natural specificity. In summary, our results indicate that @entity1 healthy adult peripheral blood at steady-state consists of three distinct ASC populations.

title: Distinctions among Circulating Antibody-Secreting Cell Populations, Including XXXX Cells, in @entity1 Adult Peripheral Blood.

entities_list: @entity2945 :: ('MESH:D010767', 'Chemical') :: ['phosphoryl choline']

answer: @entity12950 :: (931,Gene) :: ['B-1']


abstract: UNASSIGNED: @entity1 Ab-secreting cell (ASC) populations in circulation are not well studied. In addition to @entity12950 ( @entity2225 (+) @entity2731 (+) @entity3053 (lo/int) @entity12910 (+)) cell and conventional plasmablast (PB) ( @entity2225 - @entity2731 (hi) @entity3053 (hi)) cell populations, in this study, we identified a novel B cell population termed 20(+)38(hi) B cells ( @entity2225 (+) @entity2731 (hi) @entity3053 (hi)) that spontaneously secretes Ab. At steady-state, 20(+)38(hi) B cells are distinct from PBs on the basis of @entity2225 expression, amount of Ab production, frequency of mutation, and diversity of BCR repertoire. However, cytokine treatment of 20(+)38(hi) B cells induces loss of @entity2225 and acquisition of @entity13221 , suggesting that 20(+)38(hi) B cells are precursors to PBs or pre-PBs. We then evaluated similarities and differences among @entity2225 (+) @entity2731 (+) @entity3053 (lo/int) @entity12910 (+) @entity12950 cells, @entity2225 (+) @entity2731 (hi) @entity3053 (hi) 20(+)38(hi) B cells, @entity2225 (-) @entity2731 (hi) @entity3053 (hi) PBs, and @entity2225 (+) @entity2731 (+) @entity3053 (lo/int) @entity12910 (-) memory B cells. We found that @entity12950 cells differ from 20(+)38(hi) B cells and PBs in a number of ways, including Ag expression, morphological appearance, transcriptional profiling, Ab skewing, Ab repertoire, and secretory response to stimulation. In terms of gene expression, @entity12950 cells align more closely with memory B cells than with 20(+)38(hi) B cells or PBs, but differ in that memory B cells do not express Ab secretion-related genes. We found that @entity12950 cell Abs use Vh4-34, which is often associated with autoreactivity, 3- to 6-fold more often than other B cell populations. Along with selective production of IgM anti- @entity2945 , these data suggest that @entity1 @entity12950 cells might be preferentially selected for autoreactivity/natural specificity. In summary, our results indicate that @entity1 healthy adult peripheral blood at steady-state consists of three distinct ASC populations.

title: Distinctions among Circulating Antibody-Secreting Cell Populations, Including @entity12950 Cells, in XXXX Adult Peripheral Blood.

answer: @entity1 :: (9606,Species) :: ['Human']


abstract: UNASSIGNED: Inflammation may initiate and promote @entity0 development, and be associated with elevated circulating levels of @entity32 markers. A total of eight 130 initially healthy @entity1 , participated in the population-based Troms   study (1994-2008). Pre-diagnostic high-sensitivity @entity1851 (hs-CRP) was assessed. During 14.6  years of follow-up, a total of 192 @entity1 developed @entity0 . These cases were followed for additional 7.2  years. Detailed medical records were obtained. We observed an overall positive dose-response relationship between pre-diagnostic hs-CRP and @entity0 risk (hazard ratio (HR)  =  1.06, 95  % CI 1.01-1.11). Postmenopausal @entity1 with above median levels of hs-CRP (>1.2  mg/l) had a 1.42 (95  % CI 1.01-2.00) higher @entity0 risk compared to postmenopausal @entity1 with hs-CRP below median. Postmenopausal @entity1 , who were hormone replacement therapy non-users, and were in the middle tertile (0.8-1.9  mg/l), or highest tertile of hs-CRP (>1.9  mg/l), had a 2.31 (95  % CI 1.31-4.03) and 2.08 (95  % CI 1.16-3.76) higher @entity0 risk, respectively, compared with @entity1 in the lowest tertile. For each unit increase in pre-diagnostic hs-CRP levels (mg/l), we observed an 18  % increase in disease-free interval (95  % CI 0.70-0.97), and a 22  % reduction in overall mortality (95  % CI 0.62-0.98). Our study supports a positive association between pre-diagnostic hs-CRP and @entity0 risk. In contrast, increased pre-diagnostic hs-CRP was associated with improved overall mortality, but our findings are based on a small sample size, and should be interpreted with caution.

title: Pre-diagnostic high-sensitive XXXX and @entity0 risk, recurrence, and survival.

entities_list: @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation']

entities_list: @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer', 'invasive breast cancer']

entities_list: @entity1851 :: ('1401', 'Gene') :: ['C-reactive protein']

answer: @entity1851 :: (1401,Gene) :: ['C-reactive protein']


abstract: UNASSIGNED: Inflammation may initiate and promote @entity0 development, and be associated with elevated circulating levels of @entity32 markers. A total of eight 130 initially healthy @entity1 , participated in the population-based Troms   study (1994-2008). Pre-diagnostic high-sensitivity @entity1851 (hs-CRP) was assessed. During 14.6  years of follow-up, a total of 192 @entity1 developed @entity0 . These cases were followed for additional 7.2  years. Detailed medical records were obtained. We observed an overall positive dose-response relationship between pre-diagnostic hs-CRP and @entity0 risk (hazard ratio (HR)  =  1.06, 95  % CI 1.01-1.11). Postmenopausal @entity1 with above median levels of hs-CRP (>1.2  mg/l) had a 1.42 (95  % CI 1.01-2.00) higher @entity0 risk compared to postmenopausal @entity1 with hs-CRP below median. Postmenopausal @entity1 , who were hormone replacement therapy non-users, and were in the middle tertile (0.8-1.9  mg/l), or highest tertile of hs-CRP (>1.9  mg/l), had a 2.31 (95  % CI 1.31-4.03) and 2.08 (95  % CI 1.16-3.76) higher @entity0 risk, respectively, compared with @entity1 in the lowest tertile. For each unit increase in pre-diagnostic hs-CRP levels (mg/l), we observed an 18  % increase in disease-free interval (95  % CI 0.70-0.97), and a 22  % reduction in overall mortality (95  % CI 0.62-0.98). Our study supports a positive association between pre-diagnostic hs-CRP and @entity0 risk. In contrast, increased pre-diagnostic hs-CRP was associated with improved overall mortality, but our findings are based on a small sample size, and should be interpreted with caution.

title: Pre-diagnostic high-sensitive @entity1851 and XXXX risk, recurrence, and survival.

answer: @entity0 :: (MESH:D001943,Disease) :: ['breast cancer']


abstract: @entity867 in the young are rare. Only 14 such abscesses have been seen at Texas @entity1 's Hospital since 1968. Most abscesses developed in association with @entity299 (5), although @entity1244 and @entity2267 were precipitating causes in two @entity1 and one @entity1 , respectively. The latter three @entity1 ' cases are reviewed in detail. Clinical and bacteriologic findings in all @entity1 are discussed. There were signs of @entity428 in nine @entity1 (64%). All abscesses were drained; in several, repeated drainage was necessary. Anaerobic organisms were recovered in six @entity1 (43%), aerobic organisms were recovered in five (36%), and both were recovered in two (14%). In one @entity1 no growth was reported. Antimicrobial therapy was administered to all @entity1 but one, whose abscess was completely excised. Morbidity and mortality remained significant: three @entity1 (21%) died and one has a @entity1269 .

title: XXXX in the young.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'Children', 'patient']

entities_list: @entity1244 :: ('MESH:D012852', 'Disease') :: ['sinusitis']

entities_list: @entity428 :: ('MESH:D019586', 'Disease') :: ['increased intracranial pressure']

entities_list: @entity1269 :: ('MESH:D010291', 'Disease') :: ['residual hemiparesis']

entities_list: @entity2267 :: ('MESH:D008417', 'Disease') :: ['mastoiditis']

entities_list: @entity299 :: ('MESH:D006331', 'Disease') :: ['congenital heart disease']

entities_list: @entity867 :: ('MESH:D001922', 'Disease') :: ['Brain abscesses']

answer: @entity867 :: (MESH:D001922,Disease) :: ['Brain abscesses']


abstract: The effects of @entity2072 on a @entity1 electroencephalographic event related potential (ERP) were measured. Forty-eight subjects received one of three IV doses (0.2, 0.4, or 0.6 mg/kg) and placebo. Thirty-three subjects received one of three oral doses (2, 3, or 4 mg/kg). All IV and oral doses reduced amplitude of the auditory ERP @entity19689 and @entity3493 components during the oddball task. @entity19689 latency decreased. N100 amplitude was reduced only after IV administration. The changes in ERPs occurred during the period of peak cardiovascular and subjective effects. The amplitude reduction in ERP components occurring before the @entity3493 component is consistent with decrements in attention, specifically selective attention. The @entity3493 amplitude reduction after @entity2072 suggests a disruption of stimulus evaluation resources. The findings are inconsistent with the notion that stimulants affect only response selection and execution. The degree to which stimulants alter cognitive processes prior to response selection may depend on the magnitude of the cardiovascular, subjective, and probably other noncognitive effects.

title: Information processing components of the auditory event related potential are reduced by XXXX .

answer: @entity2072 :: (MESH:D003042,Chemical) :: ['cocaine']


abstract: UNASSIGNED: One of the most significant health problems in the American continent in terms of @entity1 health, and socioeconomic impact is @entity1526 , caused by the protozoan parasite @entity1527 . Infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. Likewise, @entity1526 used to be endemic from Northern Mexico to Argentina, but migrations have earned it global. The parasite has a complex life cycle, infecting different species, and invading a variety of cells - including muscle and nerve cells of the heart and gastrointestinal tract - in the @entity1 host. @entity1 @entity281 outcome is a potentially fatal @entity296 , and @entity344 . In absence of a vaccine, vector control and treatment of @entity1 are the only tools to control the disease. Unfortunately, the only drugs now available for @entity1526 , Nifurtimox and @entity5220 , are relatively toxic for adult @entity1 , and require prolonged administration. @entity5220 is the first choice for @entity1526 treatment due to its lower side effects than @entity16580 . However, different strategies are being sought to overcome @entity5220 's @entity137 including shorter or intermittent administration schedules-either alone or in combination with other drugs. In addition, a long list of compounds has shown trypanocidal activity, ranging from natural products to specially designed molecules, re-purposing drugs commercialized to treat other maladies, and homeopathy. In the present review, we will briefly summarize the upturns of current treatment of @entity1526 , discuss the increment on research and scientific publications about this topic, and give an overview of the state-of-the-art research aiming to produce an alternative medication to treat @entity1527 @entity281 .

title: Current drug therapy and pharmaceutical challenges for XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['mammalian', 'human', 'patients', 'Human']

entities_list: @entity296 :: ('MESH:D009202', 'Disease') :: ['cardiomyopathy']

entities_list: @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity']

entities_list: @entity1527 :: ('5693', 'Species') :: ['Trypanosoma cruzi', 'T. cruzi']

entities_list: @entity5220 :: ('MESH:C009999', 'Chemical') :: ['Benznidazole']

entities_list: @entity344 :: ('MESH:D005767', 'Disease') :: ['gastrointestinal tract lesions']

entities_list: @entity1526 :: ('MESH:D014355', 'Disease') :: ['Chagas disease', "Chagas' disease"]

entities_list: @entity281 :: ('MESH:D007239', 'Disease') :: ['infection']

entities_list: @entity16580 :: ('MESH:D009547', 'Chemical') :: ['Nifurtimox']

answer: @entity1526 :: (MESH:D014355,Disease) :: ['Chagas disease']


abstract: Concomitant presentation of @entity378 ( @entity378 ) and @entity706 is a rare entity. A primary malignancy such as @entity978 ( @entity978 ) may cause suppression of the cell-mediated immunity, which predisposes to a concomitant @entity378 . We report a case of an 18-year-old @entity1 , who presented with @entity221 and was found to have pallor, generalised @entity3329 , @entity828 , @entity843 and pedal @entity4 . Ultrasound of the abdomen revealed enlarged lymph nodes in the para-aortic and peripancreatic region. On chest contrast-enhanced CT, calcified mediastinal lymph nodes were seen. A surgical biopsy of a cervical lymph node was performed, which revealed @entity39 surrounded by epithelioid cells along with diffuse nodal architectural effacement by large atypical lymphoid cells. Numerous Reed Sternberg cells were also seen. Immunohistochemistry confirmed diagnosis of @entity978 . The same lymph node came out to be positive for mycobacterium @entity378 on polymerised chain reaction. The @entity1 was given antitubercular therapy concomitantly with chemotherapy for @entity978 , and improved with treatment.

title: Simultaneous occurrence of XXXX and tubercular lymphadenitis in the same cervical lymph node: a rare presentation.

entities_list: @entity3329 :: ('MESH:D008206', 'Disease') :: ['lymphadenopathy']

entities_list: @entity706 :: ('MESH:D008223', 'Disease') :: ['lymphoma']

entities_list: @entity39 :: ('MESH:D009336', 'Disease') :: ['caseous necrosis']

entities_list: @entity4 :: ('MESH:D004487', 'Disease') :: ['oedema']

entities_list: @entity828 :: ('MESH:C535727', 'Disease') :: ['hepatosplenomegaly']

entities_list: @entity378 :: ('MESH:D014376', 'Disease') :: ['TB infection', 'TB', 'tuberculosis']

entities_list: @entity978 :: ('MESH:D006689', 'Disease') :: ['HD', "Hodgkin's lymphoma", "Hodgkin's disease"]

answer: @entity978 :: (MESH:D006689,Disease) :: ['Hodgkin's disease']


abstract: UNASSIGNED: Many randomized clinical trials (RCTs) have investigated the efficacy and safety of renin-angiotensin system inhibitors (RASIs) plus @entity460 channel blockers (CCBs), compared with other two-drug combinations, but systematic assessment in this aspect is still lacking. We carried out the present meta-analysis of randomized controlled trials to evaluate the long-term effect and safety of RASIs plus CCBs. Literatures were searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials in September 2014. A fixed-effect model was used to estimate the pooled effect of trials identified. Thirty-four trials with 41   694 @entity1 were included. Compared with RASIs plus diuretics, RASIs plus CCBs @entity65 (CV) events (relative risk (RR) 0.82, 95% confidence interval (CI): 0.75, 0.91, adjusted RR (ARR) 1.7%) and withdrawals due to adverse effect (WDAE) (RR 0.87, 95% CI: 0.80, 0.94, @entity5262 .3%). Compared with CCBs plus diuretics, RASIs plus CCBs decreased WDAE (RR 0.63, 95% CI: 0.45, 0.90, @entity5262 .1%). Our meta-analysis indicates that RASIs plus CCBs provide a superior safety and prevention of CV events to RASIs plus diuretics, whereas this combination is also safer than CCBs plus diuretics. We also raise a new hypothesis. More high-quality RCTs focused on hard end points with CV, cerebrovascular and renal events are needed to confirm the hypothesis we have brought out.Journal of @entity1 @entity101 advance online publication, 7 January 2016; doi:10.1038/jhh.2015.125.

title: Combination therapy of renin-angiotensin system inhibitors plus @entity460 channel blockers versus other two-drug combinations for XXXX : a systematic review and meta-analysis.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'Human']

entities_list: @entity101 :: ('MESH:D006973', 'Disease') :: ['Hypertension']

entities_list: @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium']

entities_list: @entity65 :: ('MESH:D002318', 'Disease') :: ['decreased total cardiovascular']

answer: @entity101 :: (MESH:D006973,Disease) :: ['hypertension']


abstract: UNASSIGNED: Many randomized clinical trials (RCTs) have investigated the efficacy and safety of renin-angiotensin system inhibitors (RASIs) plus @entity460 channel blockers (CCBs), compared with other two-drug combinations, but systematic assessment in this aspect is still lacking. We carried out the present meta-analysis of randomized controlled trials to evaluate the long-term effect and safety of RASIs plus CCBs. Literatures were searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials in September 2014. A fixed-effect model was used to estimate the pooled effect of trials identified. Thirty-four trials with 41   694 @entity1 were included. Compared with RASIs plus diuretics, RASIs plus CCBs @entity65 (CV) events (relative risk (RR) 0.82, 95% confidence interval (CI): 0.75, 0.91, adjusted RR (ARR) 1.7%) and withdrawals due to adverse effect (WDAE) (RR 0.87, 95% CI: 0.80, 0.94, @entity5262 .3%). Compared with CCBs plus diuretics, RASIs plus CCBs decreased WDAE (RR 0.63, 95% CI: 0.45, 0.90, @entity5262 .1%). Our meta-analysis indicates that RASIs plus CCBs provide a superior safety and prevention of CV events to RASIs plus diuretics, whereas this combination is also safer than CCBs plus diuretics. We also raise a new hypothesis. More high-quality RCTs focused on hard end points with CV, cerebrovascular and renal events are needed to confirm the hypothesis we have brought out.Journal of @entity1 @entity101 advance online publication, 7 January 2016; doi:10.1038/jhh.2015.125.

title: Combination therapy of renin-angiotensin system inhibitors plus XXXX channel blockers versus other two-drug combinations for @entity101 : a systematic review and meta-analysis.

answer: @entity460 :: (MESH:D002118,Chemical) :: ['calcium']


abstract: OBJECTIVES: Prevention of type 2 @entity6 (T2DM) is a priority in healthcare, but there is a lack of evidence investigating how to effectively translate prevention research into a UK primary care setting. We assessed whether a structured education programme targeting lifestyle and behaviour change was effective at preventing progression to T2DM in @entity1 with @entity6 . MATERIALS AND METHODS: Forty-four general practices were randomised to receive either standard care or a 6hour group structured education programme with an annual refresher course, and regular phone contact. @entity1 were followed up for 3years. The primary outcome was progression to T2DM. RESULTS: Eight hundred and eighty @entity1 were included (36% female, mean age 64years, 16% ethnic minority group); 131 @entity1 developed T2DM. There was a non-significant 26% reduced risk of developing T2DM in the intervention arm compared to standard care (HR 0.74, 95% CI 0.48, 1.14, p=0.18). The reduction in T2DM risk when excluding those who did not attend the initial education session was also non-significant (HR 0.65, 0.41, 1.03, p=0.07). There were statistically significant improvements in HbA1c (-0.06, -0.11, -0.01), LDL @entity165 (-0.08, -0.15, -0.01), sedentary time (-26.29, -45.26, -7.32) and step count (498.15, 162.10, 834.20) when data were analysed across all time points. CONCLUSIONS: This study suggests that a relatively low resource, pragmatic @entity6 prevention programme resulted in modest benefits to biomedical, lifestyle and psychosocial outcomes, however the reduction to the risk of T2DM did not reach significance. The findings have important implications for future research and primary care.

title: A community based primary prevention programme for type 2 XXXX integrating identification and lifestyle intervention for prevention: the Let's Prevent @entity6 cluster randomised controlled trial.

entities_list: @entity1 :: ('9606', 'Species') :: ['participants', 'Participants', 'people']

entities_list: @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']

entities_list: @entity6 :: ('MESH:D003920', 'Disease') :: ['pre-diabetes', 'diabetes']

answer: @entity6 :: (MESH:D003920,Disease) :: ['diabetes']


abstract: OBJECTIVES: Prevention of type 2 @entity6 (T2DM) is a priority in healthcare, but there is a lack of evidence investigating how to effectively translate prevention research into a UK primary care setting. We assessed whether a structured education programme targeting lifestyle and behaviour change was effective at preventing progression to T2DM in @entity1 with @entity6 . MATERIALS AND METHODS: Forty-four general practices were randomised to receive either standard care or a 6hour group structured education programme with an annual refresher course, and regular phone contact. @entity1 were followed up for 3years. The primary outcome was progression to T2DM. RESULTS: Eight hundred and eighty @entity1 were included (36% female, mean age 64years, 16% ethnic minority group); 131 @entity1 developed T2DM. There was a non-significant 26% reduced risk of developing T2DM in the intervention arm compared to standard care (HR 0.74, 95% CI 0.48, 1.14, p=0.18). The reduction in T2DM risk when excluding those who did not attend the initial education session was also non-significant (HR 0.65, 0.41, 1.03, p=0.07). There were statistically significant improvements in HbA1c (-0.06, -0.11, -0.01), LDL @entity165 (-0.08, -0.15, -0.01), sedentary time (-26.29, -45.26, -7.32) and step count (498.15, 162.10, 834.20) when data were analysed across all time points. CONCLUSIONS: This study suggests that a relatively low resource, pragmatic @entity6 prevention programme resulted in modest benefits to biomedical, lifestyle and psychosocial outcomes, however the reduction to the risk of T2DM did not reach significance. The findings have important implications for future research and primary care.

title: A community based primary prevention programme for type 2 @entity6 integrating identification and lifestyle intervention for prevention: the Let's Prevent XXXX cluster randomised controlled trial.

answer: @entity6 :: (MESH:D003920,Disease) :: ['Diabetes']


abstract: BACKGROUND AND PURPOSE: The PED is a new endoluminal construct designed to exclude @entity439 from the parent cerebrovasculature. We report the very late (>1 year) @entity715 of PED constructs in 2 @entity1 . RESULTS: Two @entity1 with very large fusiform basilar trunk @entity439 underwent parent artery reconstruction with the PED. Both @entity1 were maintained on dual antiplatelet therapy throughout the first year following treatment. Follow-up conventional angiography, performed 12 months after treatment, demonstrated, in both @entity1 , @entity715 of most of the @entity439 with minimal residual flow through the construct and into the @entity439 fundus. In response to the @entity41 , @entity1397 was discontinued ( @entity117 therapy was maintained). Both @entity1 presented with symptomatic acute occlusions of the PED constructs within 14 days of @entity1397 discontinuation. DISCUSSION: @entity1 1 presented with constitutional symptoms that progressed to severe @entity10 without other neurologic signs or symptoms. Occlusion of the PED construct was confirmed with conventional angiography. MR imaging demonstrated no evidence of @entity1188 or @entity130 . The @entity10 were managed successfully with @entity134 therapy. @entity1 2 presented with a syndrome of @entity432 with @entity64 . Complete occlusion was confirmed on angiography. Emergent thrombolysis with mechanical revascularization was performed successfully; however, the @entity1 ultimately succumbed to the @entity1188 . CONCLUSIONS: It appears that flow-diverting constructs built across large circumferential @entity439 may remain thrombogenic for much longer than conventional intracranial or peripheral bare metal stents. Constructs in these @entity1 may remain susceptible to very late @entity715 , >1 year after implantation. These @entity1 likely require long-term dual antiplatelet therapy (>1 year) to provide adequate prophylaxis against @entity715 . If these types of @entity439 demonstrate persistent @entity41 months after PED reconstruction, operators should consider the placement of additional devices as an alternative to the discontinuation of 1 of the antiplatelet medications.

title: Very late @entity715 of flow-diverting constructs after the treatment of large fusiform posterior circulation XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'patient', 'Patient']

entities_list: @entity64 :: ('MESH:D020521', 'Disease') :: ['brain stem stroke']

entities_list: @entity41 :: ('MESH:D018365', 'Disease') :: ['residual filling']

entities_list: @entity1397 :: ('MESH:C055162', 'Chemical') :: ['clopidogrel']

entities_list: @entity117 :: ('MESH:D001241', 'Chemical') :: ['aspirin']

entities_list: @entity134 :: ('CHEBI:35341', 'Chemical') :: ['steroid']

entities_list: @entity439 :: ('MESH:D000783', 'Disease') :: ['aneurysms', 'aneurysm']

entities_list: @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarction']

entities_list: @entity432 :: ('MESH:D001157', 'Disease') :: ['acute basilar occlusion']

entities_list: @entity715 :: ('MESH:D013927', 'Disease') :: ['thrombosis']

entities_list: @entity10 :: ('MESH:D006261', 'Disease') :: ['headache', 'headaches']

entities_list: @entity130 :: ('MESH:D014947', 'Disease') :: ['parenchymal injury']

answer: @entity439 :: (MESH:D000783,Disease) :: ['aneurysms']


abstract: BACKGROUND AND PURPOSE: The PED is a new endoluminal construct designed to exclude @entity439 from the parent cerebrovasculature. We report the very late (>1 year) @entity715 of PED constructs in 2 @entity1 . RESULTS: Two @entity1 with very large fusiform basilar trunk @entity439 underwent parent artery reconstruction with the PED. Both @entity1 were maintained on dual antiplatelet therapy throughout the first year following treatment. Follow-up conventional angiography, performed 12 months after treatment, demonstrated, in both @entity1 , @entity715 of most of the @entity439 with minimal residual flow through the construct and into the @entity439 fundus. In response to the @entity41 , @entity1397 was discontinued ( @entity117 therapy was maintained). Both @entity1 presented with symptomatic acute occlusions of the PED constructs within 14 days of @entity1397 discontinuation. DISCUSSION: @entity1 1 presented with constitutional symptoms that progressed to severe @entity10 without other neurologic signs or symptoms. Occlusion of the PED construct was confirmed with conventional angiography. MR imaging demonstrated no evidence of @entity1188 or @entity130 . The @entity10 were managed successfully with @entity134 therapy. @entity1 2 presented with a syndrome of @entity432 with @entity64 . Complete occlusion was confirmed on angiography. Emergent thrombolysis with mechanical revascularization was performed successfully; however, the @entity1 ultimately succumbed to the @entity1188 . CONCLUSIONS: It appears that flow-diverting constructs built across large circumferential @entity439 may remain thrombogenic for much longer than conventional intracranial or peripheral bare metal stents. Constructs in these @entity1 may remain susceptible to very late @entity715 , >1 year after implantation. These @entity1 likely require long-term dual antiplatelet therapy (>1 year) to provide adequate prophylaxis against @entity715 . If these types of @entity439 demonstrate persistent @entity41 months after PED reconstruction, operators should consider the placement of additional devices as an alternative to the discontinuation of 1 of the antiplatelet medications.

title: Very late XXXX of flow-diverting constructs after the treatment of large fusiform posterior circulation @entity439 .

answer: @entity715 :: (MESH:D013927,Disease) :: ['thrombosis']


abstract: The histopathologic interpretation of proliferative nodules (PNs) in @entity8205 can present significant challenges as some PNs may exhibit atypical features that make the distinction from @entity320 . We compared histologic features, Ki-67%, PHH3, and CD117% expression levels by immunohistochemistry in 18 benign and 25 atypical PNs (from 41 @entity1 ) with that of background @entity7174 (of these 43 cases), 10 @entity7174 , and 3 dermal @entity320 arising in @entity66 . In addition, we evaluated the presence of @entity817 , @entity10158 , @entity8498 , @entity984 , and @entity8497 mutations in all groups using the SNaPshot Multiplex System. Follow-up was available on 19 @entity1 (9 benign and 10 atypical PNs) (range, 2 to 20 y; median, 8 y) and all were alive with no evidence of disease. The specific histologic features of atypical PNs, such as sharp demarcation (P<0.001), expansile growth (P<0.001), epidermal effacement (P<0.001), nuclear pleomorphism (P<0.001), and increased mitoses (P<0.001), differed significantly from those of benign PNs. Immunohistochemical results showed that Ki-67% and PHH3 scores, but not CD117% expression, were significantly higher (P<0.05) in atypical PNs. Molecular analyses showed that the PNs and background @entity8205 of the giant @entity7174 possess more frequent @entity8497 mutations and infrequent @entity817 mutations when compared with those of the remaining cases. These findings suggest that histologic features and Ki-67 and PHH3 expression levels are the strongest parameters to distinguish between benign versus atypical PNs. The immunohistochemical results suggest that atypical PNs are distinct borderline lesions residing between benign PNs and dermal @entity320 . Although numerous mutations are detected in the samples, the diagnostic use of molecular analysis in this regard is limited.

title: Proliferative nodules arising within XXXX : a histologic, immunohistochemical, and molecular analyses of 43 cases.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients']

entities_list: @entity66 :: ('MESH:D004194', 'Disease') :: ['congenital melanocytic lesions']

entities_list: @entity8205 :: ('MESH:D009508', 'Disease') :: ['congenital melanocytic nevi']

entities_list: @entity7174 :: ('MESH:D009506', 'Disease') :: ['congenital nevi']

entities_list: @entity320 :: ('MESH:D008545', 'Disease') :: ['melanomas', 'melanoma difficult']

answer: @entity8205 :: (MESH:D009508,Disease) :: ['congenital melanocytic nevi']


abstract: Prenatal selective @entity750 reuptake inhibitor (SSRI) exposure increases the risk for adverse neonatal behavioral outcomes; although it is unknown whether altered brain function is present before birth. We investigated fetal vascular and heart rate changes at 36-wk gestation in SSRI-treated @entity1 with @entity1316 (n = 29) [exposed (EXP)] and controls (n = 45) [non-EXP (NEXP)]. @entity2500 (MCA) flow parameters and heart rate characteristics were obtained during pre-SSRI dose morning and postdose afternoon sessions. Maternal mood and cord Hb and hematocrit were measured. Basal fetal heart rate (fHR) did not differ between groups or across the day. The fHR short- and long-term variations, accelerations, and duration of high variability episodes remained lower and did not change across the day in EXP, whereas all increased significantly in NEXP. In both groups, MCA flow velocity and volume flow increased significantly across the day. EXP MCA pulsatility index was significantly lower, as was MCA cross-sectional area. EXP cord Hb and hematocrit were significantly increased. Prenatal SSRI exposure reduced fetal MCA flow resistance and fHR variability, before and after an SSRI dose, controlling for maternal mood. These changes and the SSRI-related increased red cell indices suggest possible @entity7396 .

title: Third trimester fetal heart rate and Doppler middle cerebral artery blood flow velocity characteristics during prenatal selective XXXX reuptake inhibitor exposure.

entities_list: @entity2500 :: ('MESH:D020244', 'Disease') :: ['Fetal middle cerebral artery']

entities_list: @entity7396 :: ('MESH:D005311', 'Disease') :: ['fetal hypoxia']

entities_list: @entity1316 :: ('MESH:D019964', 'Disease') :: ['mood disorders']

entities_list: @entity750 :: ('MESH:D012701', 'Chemical') :: ['serotonin']

answer: @entity750 :: (MESH:D012701,Chemical) :: ['serotonin']


abstract: The number of reported cases of smooth @entity11090 (SMT) arising in @entity1 with @entity791 has been increasing since the mid-1990s. The aim of this study is to characterize the epidemiology, clinical manifestations, pathologic features, prognosis and, management of @entity9653 -related SMT (EBV-SMT) in @entity1 with @entity791 . An English language literature search identified 53 articles including 64 reported cases of EBV-SMT. The majority of these reports involved @entity1 who were young, severely immunosuppressed, and had multifocal @entity5 . The central nervous system was the most common site to be involved. Histologically, @entity5 had smooth muscle features and were immunoreactive for muscle markers and all but two @entity5 demonstrated the presence of EBV by either immunohistochemistry, in situ hybridization, and/or PCR. While mitoses and/or @entity39 were used to separate @entity2909 from @entity1822 , these features did not correlate with clinical outcome. Treatment included primarily resection, and less often radiotherapy, chemotherapy and highly active antiretroviral therapy (HAART). Overall, EBV-SMTs appear to have variable @entity146 and clinical outcome and may exhibit a more favorable prognosis compared to @entity1822 . Tumor-related death from EBV-SMT occurred in only 4 of 51 @entity1 .

title: XXXX -Related EBV-Associated Smooth Muscle Tumors: A Review of 64 Published Cases.

entities_list: @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumors']

entities_list: @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressiveness']

entities_list: @entity1822 :: ('MESH:D007890', 'Disease') :: ['leiomyosarcoma', 'conventional leiomyosarcoma']

entities_list: @entity9653 :: ('10376', 'Species') :: ['Epstein-Barr virus']

entities_list: @entity11090 :: ('MESH:D019042', 'Disease') :: ['muscle tumor']

entities_list: @entity2909 :: ('MESH:D007889', 'Disease') :: ['leiomyoma']

answer: @entity791 :: (MESH:D000163,Disease) :: ['AIDS']


abstract: Tau is the proteinaceous component of intraneuronal aggregates common to @entity179 called @entity13859 , including @entity3918 type 1. In @entity3918 type 1, the presence of @entity3668 aggregates is associated with a @entity248 -splicing of Tau. A toxic gain-of-function at the @entity10731 level is a major etiological factor responsible for the @entity248 -splicing of several transcripts in @entity3918 type 1. These are probably the consequence of a loss of @entity48973 ( @entity48973 ) function or gain of @entity6047 and ETR3-like factor 1 ( @entity6047 ) splicing function. Whether these two dysfunctions occur together or separately and whether all @entity248 -splicing events in @entity3918 type 1 brain result from one or both of these dysfunctions remains unknown. Here, we analyzed the splicing of Tau exons 2 and 10 in the brain of @entity3918 type 1 @entity1 . Two @entity3918 type 1 @entity1 showed a @entity248 -splicing of exon 10 whereas exon 2-inclusion was reduced in all @entity3918 type 1 @entity1 . In order to determine the potential factors responsible for exon 10 @entity248 -splicing, we studied the effect of the splicing factors @entity48973 ( @entity48973 ), @entity6047 and ETR3-like factor 1 ( @entity6047 ), @entity6047 and ETR3-like factor 2 ( @entity67396 ), and @entity6047 and ETR3-like factor 4 ( @entity52551 ) or a dominant-negative @entity6047 and ETR-3 like factor ( @entity29726 ) factor on Tau exon 10 splicing by ectopic expression or siRNA. Interestingly, the inclusion of Tau exon 10 is reduced by @entity6047 and ETR3-like factor 2 ( @entity67396 ) whereas it is insensitive to the loss-of-function of @entity48973 ( @entity48973 ), @entity6047 and ETR3-like factor 1 ( @entity6047 ) gain-of-function, or a dominant-negative of @entity6047 and ETR-3 like factor ( @entity29726 ) factor. Moreover, we observed an increased expression of @entity6047 and ETR3-like factor 2 ( @entity67396 ) only in the brain of @entity3918 type 1 @entity1 with a @entity248 -splicing of exon 10. Taken together, our results indicate the occurrence of a @entity248 -splicing event in @entity3918 type 1 that is induced neither by a loss of @entity48973 ( @entity48973 ) function nor by a gain of @entity6047 and ETR3-like factor 1 ( @entity6047 ) function but is rather associated to @entity6047 and ETR3-like factor 2 ( @entity67396 ) gain-of-function.

title: @entity248 -splicing of Tau exon 10 in XXXX type 1 is reproduced by overexpression of @entity67396 but not by @entity48973 silencing.

entities_list: @entity13859 :: ('MESH:D024801', 'Disease') :: ['Tauopathies']

entities_list: @entity179 :: ('MESH:D019636', 'Disease') :: ['neurodegenerative diseases']

entities_list: @entity10731 :: ('CHEBI:33697', 'Chemical') :: ['ribonucleic acid']

entities_list: @entity3918 :: ('MESH:D009223', 'Disease') :: ['myotonic dystrophy']

entities_list: @entity3668 :: ('4137', 'Gene') :: ['microtubule-associated protein Tau']

answer: @entity3918 :: (MESH:D009223,Disease) :: ['myotonic dystrophy']


abstract: Tau is the proteinaceous component of intraneuronal aggregates common to @entity179 called @entity13859 , including @entity3918 type 1. In @entity3918 type 1, the presence of @entity3668 aggregates is associated with a @entity248 -splicing of Tau. A toxic gain-of-function at the @entity10731 level is a major etiological factor responsible for the @entity248 -splicing of several transcripts in @entity3918 type 1. These are probably the consequence of a loss of @entity48973 ( @entity48973 ) function or gain of @entity6047 and ETR3-like factor 1 ( @entity6047 ) splicing function. Whether these two dysfunctions occur together or separately and whether all @entity248 -splicing events in @entity3918 type 1 brain result from one or both of these dysfunctions remains unknown. Here, we analyzed the splicing of Tau exons 2 and 10 in the brain of @entity3918 type 1 @entity1 . Two @entity3918 type 1 @entity1 showed a @entity248 -splicing of exon 10 whereas exon 2-inclusion was reduced in all @entity3918 type 1 @entity1 . In order to determine the potential factors responsible for exon 10 @entity248 -splicing, we studied the effect of the splicing factors @entity48973 ( @entity48973 ), @entity6047 and ETR3-like factor 1 ( @entity6047 ), @entity6047 and ETR3-like factor 2 ( @entity67396 ), and @entity6047 and ETR3-like factor 4 ( @entity52551 ) or a dominant-negative @entity6047 and ETR-3 like factor ( @entity29726 ) factor on Tau exon 10 splicing by ectopic expression or siRNA. Interestingly, the inclusion of Tau exon 10 is reduced by @entity6047 and ETR3-like factor 2 ( @entity67396 ) whereas it is insensitive to the loss-of-function of @entity48973 ( @entity48973 ), @entity6047 and ETR3-like factor 1 ( @entity6047 ) gain-of-function, or a dominant-negative of @entity6047 and ETR-3 like factor ( @entity29726 ) factor. Moreover, we observed an increased expression of @entity6047 and ETR3-like factor 2 ( @entity67396 ) only in the brain of @entity3918 type 1 @entity1 with a @entity248 -splicing of exon 10. Taken together, our results indicate the occurrence of a @entity248 -splicing event in @entity3918 type 1 that is induced neither by a loss of @entity48973 ( @entity48973 ) function nor by a gain of @entity6047 and ETR3-like factor 1 ( @entity6047 ) function but is rather associated to @entity6047 and ETR3-like factor 2 ( @entity67396 ) gain-of-function.

title: @entity248 -splicing of Tau exon 10 in @entity3918 type 1 is reproduced by overexpression of XXXX but not by @entity48973 silencing.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients']

answer: @entity67396 :: (10659,Gene) :: ['CELF2']


abstract: Tau is the proteinaceous component of intraneuronal aggregates common to @entity179 called @entity13859 , including @entity3918 type 1. In @entity3918 type 1, the presence of @entity3668 aggregates is associated with a @entity248 -splicing of Tau. A toxic gain-of-function at the @entity10731 level is a major etiological factor responsible for the @entity248 -splicing of several transcripts in @entity3918 type 1. These are probably the consequence of a loss of @entity48973 ( @entity48973 ) function or gain of @entity6047 and ETR3-like factor 1 ( @entity6047 ) splicing function. Whether these two dysfunctions occur together or separately and whether all @entity248 -splicing events in @entity3918 type 1 brain result from one or both of these dysfunctions remains unknown. Here, we analyzed the splicing of Tau exons 2 and 10 in the brain of @entity3918 type 1 @entity1 . Two @entity3918 type 1 @entity1 showed a @entity248 -splicing of exon 10 whereas exon 2-inclusion was reduced in all @entity3918 type 1 @entity1 . In order to determine the potential factors responsible for exon 10 @entity248 -splicing, we studied the effect of the splicing factors @entity48973 ( @entity48973 ), @entity6047 and ETR3-like factor 1 ( @entity6047 ), @entity6047 and ETR3-like factor 2 ( @entity67396 ), and @entity6047 and ETR3-like factor 4 ( @entity52551 ) or a dominant-negative @entity6047 and ETR-3 like factor ( @entity29726 ) factor on Tau exon 10 splicing by ectopic expression or siRNA. Interestingly, the inclusion of Tau exon 10 is reduced by @entity6047 and ETR3-like factor 2 ( @entity67396 ) whereas it is insensitive to the loss-of-function of @entity48973 ( @entity48973 ), @entity6047 and ETR3-like factor 1 ( @entity6047 ) gain-of-function, or a dominant-negative of @entity6047 and ETR-3 like factor ( @entity29726 ) factor. Moreover, we observed an increased expression of @entity6047 and ETR3-like factor 2 ( @entity67396 ) only in the brain of @entity3918 type 1 @entity1 with a @entity248 -splicing of exon 10. Taken together, our results indicate the occurrence of a @entity248 -splicing event in @entity3918 type 1 that is induced neither by a loss of @entity48973 ( @entity48973 ) function nor by a gain of @entity6047 and ETR3-like factor 1 ( @entity6047 ) function but is rather associated to @entity6047 and ETR3-like factor 2 ( @entity67396 ) gain-of-function.

title: XXXX -splicing of Tau exon 10 in @entity3918 type 1 is reproduced by overexpression of @entity67396 but not by @entity48973 silencing.

answer: @entity248 :: (268,Gene) :: ['Mis']


abstract: Tau is the proteinaceous component of intraneuronal aggregates common to @entity179 called @entity13859 , including @entity3918 type 1. In @entity3918 type 1, the presence of @entity3668 aggregates is associated with a @entity248 -splicing of Tau. A toxic gain-of-function at the @entity10731 level is a major etiological factor responsible for the @entity248 -splicing of several transcripts in @entity3918 type 1. These are probably the consequence of a loss of @entity48973 ( @entity48973 ) function or gain of @entity6047 and ETR3-like factor 1 ( @entity6047 ) splicing function. Whether these two dysfunctions occur together or separately and whether all @entity248 -splicing events in @entity3918 type 1 brain result from one or both of these dysfunctions remains unknown. Here, we analyzed the splicing of Tau exons 2 and 10 in the brain of @entity3918 type 1 @entity1 . Two @entity3918 type 1 @entity1 showed a @entity248 -splicing of exon 10 whereas exon 2-inclusion was reduced in all @entity3918 type 1 @entity1 . In order to determine the potential factors responsible for exon 10 @entity248 -splicing, we studied the effect of the splicing factors @entity48973 ( @entity48973 ), @entity6047 and ETR3-like factor 1 ( @entity6047 ), @entity6047 and ETR3-like factor 2 ( @entity67396 ), and @entity6047 and ETR3-like factor 4 ( @entity52551 ) or a dominant-negative @entity6047 and ETR-3 like factor ( @entity29726 ) factor on Tau exon 10 splicing by ectopic expression or siRNA. Interestingly, the inclusion of Tau exon 10 is reduced by @entity6047 and ETR3-like factor 2 ( @entity67396 ) whereas it is insensitive to the loss-of-function of @entity48973 ( @entity48973 ), @entity6047 and ETR3-like factor 1 ( @entity6047 ) gain-of-function, or a dominant-negative of @entity6047 and ETR-3 like factor ( @entity29726 ) factor. Moreover, we observed an increased expression of @entity6047 and ETR3-like factor 2 ( @entity67396 ) only in the brain of @entity3918 type 1 @entity1 with a @entity248 -splicing of exon 10. Taken together, our results indicate the occurrence of a @entity248 -splicing event in @entity3918 type 1 that is induced neither by a loss of @entity48973 ( @entity48973 ) function nor by a gain of @entity6047 and ETR3-like factor 1 ( @entity6047 ) function but is rather associated to @entity6047 and ETR3-like factor 2 ( @entity67396 ) gain-of-function.

title: @entity248 -splicing of Tau exon 10 in @entity3918 type 1 is reproduced by overexpression of @entity67396 but not by XXXX silencing.

answer: @entity48973 :: (4154,Gene) :: ['MBNL1']


abstract: INTRODUCTION: We assessed the effectiveness of mandibular advancement device (MAD) on 113 @entity1 having consulted in our specialized unit for @entity27 ( @entity27 ), from January 2005 to January 2010. METHODS: We included all adult @entity1 referred by pulmonologists for @entity27 . The data collected were gender, age, BMI, dental occlusion, presentation of retromandibulism, @entity27 index (AHI) at diagnosis, and MAD effectiveness (AHI, compliance, satisfaction, tolerance). RESULTS: One hundred and thirteen @entity1 were included, 83 @entity1 and 30 @entity1 , with an average age of 53.6 years, and average BMI of 26.9. Fifty-eight @entity1 (55.8%) used the MAD regularly, 17 (16.4%) irregularly, and 29 (27.9%) stopped using it. Fifty-seven @entity1 (54.8%) were very satisfied, 20 (19.2%) somewhat satisfied, and 27 (26%) not at all. The average AHI with MAD was 13.3 (  10.3) and the average improvement of AHI was 19 (  14.1). Twenty-seven @entity1 (28.7%) were cured, 46 (48.9%) presented with an AHI decrease greater than 50%, and for 21 (22.3%) the treatment failed. DISCUSSION: The sample of @entity1 in this study has the same characteristics as the general apneic population. Adherence and satisfaction were satisfactory. AHI results were also good but seemed low compared to other studies. This was due to more stringent criteria for cure, more in line with the overall management. No criterion for inclusion was predictive of good tolerance and no score predictive of success could be established. However, the improvement in AHI was significantly correlated to the @entity1 's BMI and its diagnostic AHI.

title: [Mandibular advancement device: a 5-year long experience in XXXX ].

entities_list: @entity1 :: ('9606', 'Species') :: ['women', 'patients', 'patient', 'men']

entities_list: @entity27 :: ('MESH:D020181', 'Disease') :: ['apnea hypopnea', 'OSAS', 'obstructive sleep apnea syndrome']

answer: @entity27 :: (MESH:D020181,Disease) :: ['obstructive sleep apnea/hypopnea syndrome']