abstract: OBJECTIVE: Indications for @entity1164 ( @entity1164 ) primary prevention are unknown in @entity1 with repaired tetralogy of Fallot (ToF). The role of microvolt T-wave alternans (MTWA) in @entity1164 risk stratification was documented. However, the prevalence of spectral MTWA and its association with @entity943 ( @entity943 ) in adults after ToF repair were not elucidated. DESIGN: Microvolt T-wave alternans, electrocardiogram (ECG), ambulatory ECG monitoring, echocardiography, and spiroergometry were evaluated in 102 adults after ToF repair. Microvolt T-wave alternans results were classified as normal: negative(-), abnormal: positive(+), and indeterminate(ind). Owing to similar prognostic significance, MTWA(+) and MTWA(ind) due to @entity1 factors were combined into nonnegative group: MTWA(abnormal). RESULTS: Microvolt T-wave alternans(abnormal) was more frequent in the studied group as compared with controls (P = .0005). The MTWA(abnormal) group had greater right ventricular end-diastolic diameter (P = .005), higher incidence of @entity338 (P = .015), lower peak @entity26 consumption (P = .01), and higher VE/VCO2 slope (P = .04) in comparison with MTWA(normal). Univariate logistic regression proved @entity338 (OR = 3.57, 95% CI 1.27-10.04), @entity943 (OR = 3.26, 95% CI 1.06-10.05), right ventricular end-diastolic enlargement (OR = 1.11, 95% CI 1.03-1.2), increase in VE/VCO2 slope (OR = 1.08, 95% CI 1.01-1.17), and decrease in peak @entity26 uptake (OR = .91, 95% CI 0.83-0.99) to increase MTWA(abnormal) prevalence. CONCLUSIONS: In adults after ToF repair, abnormal MTWA occurred more often than in controls. Probability of abnormal MTWA did not rise with prevalence of malignant @entity943 ; however, presence of abnormal MTWA was associated with @entity943 risk factors: @entity338 , @entity4266 , and consequent @entity712 . The role of MTWA in selecting @entity1 late after ToF repair at risk of @entity1164 needs further observation.

title: Microvolt T-wave Alternans in Adult XXXX with Repaired Tetralogy of Fallot.

entities_list: @entity1164 :: ('MESH:D016757', 'Disease') :: ['sudden cardiac death', 'SCD']

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

entities_list: @entity712 :: ('MESH:D006333', 'Disease') :: ['heart failure']

entities_list: @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen']

entities_list: @entity338 :: ('MESH:D011665', 'Disease') :: ['pulmonary regurgitation']

entities_list: @entity943 :: ('MESH:D001145', 'Disease') :: ['ventricular arrhythmia', 'VA']

entities_list: @entity4266 :: ('MESH:D018497', 'Disease') :: ['right ventricular enlargement']

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


abstract: OBJECTIVES: To quantify rates and variation in @entity341 ( @entity341 ) cranial computed tomography (CT) utilization in @entity1 with ventricular shunts, estimate radiation exposure, and evaluate the association between CT utilization and shunt revision. STUDY DESIGN: Retrospective longitudinal cohort study of @entity341 visits from 2003-2013 in @entity1 0-18  years old with initial shunt placement in 2003. Data were examined from 31 hospitals in the Pediatric Health Information System. Main outcomes were cranial CT performed during an @entity341 visit, estimated cumulative effective radiation dose, and shunt revision within 7  days. Multivariable regression modeled the relationship between @entity1 - and hospital-level covariates and CT utilization. RESULTS: The 1319 @entity1 with initial shunt placed in 2003 experienced 6636 @entity341 visits during the subsequent decade. A cranial CT was obtained in 49.4% of all @entity341 visits; 19.9% of @entity341 visits with CT were associated with a shunt revision. Approximately 6% of @entity1 received >= 10 CTs, accounting for 37.2% of all @entity341 visits with a CT. The mean number of CTs per @entity1 varied nearly 20-fold across hospitals; the individual hospital accounted for the most variation in CT utilization. The median (IQR) cumulative effective radiation dose was 7.2 millisieverts (3.6-14.0) overall, and 33.4 millisieverts (27.2-43.8) among @entity1 receiving >= 10 CTs. CONCLUSIONS: A CT scan was obtained in half of @entity341 visits for @entity1 with a ventricular shunt, with wide variability in utilization by hospitals. Strategies are needed to identify @entity1 at risk of @entity5033 to reduce variability in CT utilization and radiation exposure in the @entity341 .

title: Emergency Department Use of Computed Tomography for XXXX with Ventricular Shunts.

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

entities_list: @entity341 :: ('MESH:D004630', 'Disease') :: ['emergency department', 'ED']

entities_list: @entity5033 :: ('MESH:C562451', 'Disease') :: ['shunt malfunction']

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


abstract: BACKGROUND: Reports on the clinical meaningfulness of outcome measures in @entity2057 ( @entity2057 ) are rare. In this two-part study, our aim was to explore @entity1 ' and caregivers' views on the clinical relevance of the Hammersmith Functional Motor Scale Expanded- (HFMSE). METHODS: First, we used focus groups including @entity2057 @entity1 and caregivers to explore their views on the clinical relevance of the individual activities included in the HFMSE. Then we asked caregivers to comment on the clinical relevance of possible changes of HFMSE scores over time. As functional data of individual @entity1 were available, some of the questions were tailored according to their functional level on the HFMSE. RESULTS: Part 1: Sixty-three individuals participated in the focus groups. This included 30 caregivers, 25 @entity1 and 8 professionals who facilitated the discussion. The caregivers provided a comparison to activities of daily living for each of the HFMSE items. Part 2: One hundred and forty-nine caregivers agreed to complete the questionnaire: in response to a general question, 72% of the caregivers would consider taking part in a clinical trial if the treatment was expected to slow down deterioration, 88% if it would stop deterioration and 97% if the treatment was expected to produce an improvement. Caregivers were informed of the first three items that their @entity1 could not achieve on the HFMSE. In response 75% indicated a willingness to take part in a clinical trial if they could achieve at least one of these abilities, 89% if they could achieve two, and 100% if they could achieve more than 2. CONCLUSIONS: Our findings support the use of the HFMSE as a key outcome measure in @entity2057 clinical trials because the individual items and the detected changes have clear content validity and clinical meaningfulness for @entity1 and their caregivers.

title: Content validity and clinical meaningfulness of the HFMSE in XXXX .

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

entities_list: @entity2057 :: ('MESH:D009133', 'Disease') :: ['SMA', 'spinal muscular atrophy']

answer: @entity2057 :: (MESH:D009133,Disease) :: ['spinal muscular atrophy']


abstract: BACKGROUND: The use of permissive @entity551 includes a restrained volume preclinical therapy. However, in the elderly @entity1 , this approach has raised concerns because of the increased cardiovascular risk profile and a higher incidence of @entity101 under normal conditions. The aim of the study was to examine whether preclinical administration of restrictive volume therapy in the elderly @entity1 can be safe. @entity1 AND METHODS: A retrospective matched-pair analysis with the data set of the TraumaRegister DGU(  ) (TR-DGU) was performed based on data of 176 pairs of totally 67,000 @entity1 . To address elderly potentially @entity548 @entity1 without major @entity1545 the following inclusion criteria were chosen: @entity1 >= 60 years, ISS>= 16, @entity1984 head<4, preclinical blood pressure between 60 and 100mmHg and recorded preclinical volume administration. @entity1 that met the inclusion criteria (908) were divided into two groups: pre-clinical volume resuscitation  <=1000ml (=low volume) and >1000ml (high volume). @entity1 with high- and low-volume fluid replacement were matched according to the following criteria: age group, gender, date of the accident   5 years, ISS, GCS, preclinical intubation, ground-/air-transport, pre-clinical blood pressure. RESULTS: Preclinical volume resuscitation showed a difference of about 1000ml between the "low volume" and "high volume" group. The "low volume" group showed a significantly elongated prothrombin time. The amount of blood products given in the emergency department was not significantly different. The ventilation was 2 days shorter in the "low volume", although the number of @entity1 with severe @entity130 was greater in this group. The length of stay in the ICU differed by 3 days in favour of the "low volume" group. The overall mortality was almost the same in both groups. CONCLUSIONS: Based on these data it can be assumed that the lower preclinical volume administration has a positive effect on the @entity3459 status in elderly @entity1 . In spite of some limitations such as low number of matched pairs, we draw the cautious conclusion that a restrictive preclinical volume therapy is safe and also indicated in elderly @entity1 .

title: Limited volume resuscitation in XXXX elderly multiple trauma is safe and prevents early clinical dilutive coagulopathy - A matched pair analysis from TraumaRegister DGU(  ).

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

entities_list: @entity1545 :: ('MESH:D020214', 'Disease') :: ['brain injury']

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

entities_list: @entity548 :: ('MESH:D006470', 'Disease') :: ['bleeding']

entities_list: @entity3459 :: ('MESH:D025861', 'Disease') :: ['initial coagulation']

entities_list: @entity551 :: ('MESH:D007022', 'Disease') :: ['hypotension']

entities_list: @entity130 :: ('MESH:D014947', 'Disease') :: ['thoracic trauma']

answer: @entity551 :: (MESH:D007022,Disease) :: ['hypotensive']


abstract: BACKGROUND: Admission @entity413 levels correlate with clinical outcome in @entity1 with @entity6 ( @entity6 ) hospitalized in general medicine wards. OBJECTIVE: To investigate whether in-hospital @entity4854 alone, and after adjustment for age, gender and @entity407 , correlates with in- and out-of-hospital mortality. METHODS: Capillary @entity413 , serum lipids and diagnoses at discharge among @entity1 with @entity6 hospitalized in the general medical wards of our hospital were documented. Correlation with in- and out-of-hospital mortality was determined through uni- and multivariate analyses. RESULTS: Of the 4607 @entity1 included in the study 22% died while hospitalized. From a median of five capillary @entity413 tests obtained per @entity1 , average capillary @entity413 level was significantly lower in those who survived than in those who died (174    64 vs. 180    65 mg/dl, P = 0.005). Overall, blood @entity165 was higher in those who survived than in those who died (P < 0.001). Multivariate analysis, however, including age, gender, @entity407 and glycemia, showed that only age and male gender correlated with mortality. CONCLUSIONS: @entity4854 was associated with increased in- and out-of-hospital mortality on univariate analysis. However, it was not an independent risk factor when corrected for age, gender and @entity407 .

title: @entity4854 in @entity6 XXXX in General Medicine Wards: No independent correlation with In- and Out-Of-Hospital Mortality.

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

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

entities_list: @entity6 :: ('MESH:D003920', 'Disease') :: ['T2DM', 'type 2 diabetes mellitus']

entities_list: @entity4854 :: ('MESH:D006943', 'Disease') :: ['hyperglycemia', 'Hyperglycemia']

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

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

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


abstract: PURPOSE: @entity4854 during or after cardiac surgery is a common finding that is associated with poor outcome. Very few data, however, are available regarding a correlation between admission blood @entity413 and outcomes after coronary artery bypass grafting (CABG). Thus, the goal of the current study was to examine the relationship between admission blood @entity413 and outcome after emergency CABG surgery. MATERIALS AND METHODS: A retrospective analysis to evaluate whether admission @entity4854 associated with increased morbidity or mortality was performed in @entity1 after emergency CABG surgery. The records of all the @entity1 undergoing emergency CABG surgery between January 1999 and December 2010 at the University of Virginia Health System were reviewed. Postoperative in-hospital mortality and complications were considered as study end points. RESULTS: A total of 240 @entity1 met the final inclusion criteria. Overall mortality was 14.1%. The median admission blood @entity413 in @entity1 who died 7.4 (interquartile range, 5.9-10.1) mmol/L was significantly higher compared with survivors 6.1 (interquartile range, 5.4-7.2; P < .01). Furthermore, 59% of the @entity1 who died had admission blood @entity413 levels higher than 6.6 mmol/L, whereas only 35% of the @entity1 who survived had similar blood @entity413 levels (P = .01). On multivariable analysis, admission blood @entity413 was identified as an independent risk factor for @entity204 after emergency CABG (P = .01; odds ratio, 1.16; 95% confidence interval, 1.04-1.29). Admission blood @entity413 was further identified as independently associated with increased risk for a composite outcome of @entity204 , @entity177 or @entity64 (P = .01; odds ratio, 1.14; 95% confidence interval, 1.03-1.27). CONCLUSIONS: Our study shows for the first time that admission blood @entity413 is correlated with increased morbidity and mortality among @entity1 undergoing emergency CABG surgery.

title: Admission XXXX is associated with poor outcome after emergent coronary bypass grafting surgery.

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

entities_list: @entity177 :: ('MESH:D051437', 'Disease') :: ['postoperative renal failure']

answer: @entity4854 :: (MESH:D006943,Disease) :: ['hyperglycemia']


abstract: In October 2000, 71,187 @entity1 were treated for @entity3754 using @entity3753 and @entity6566 ( @entity6567 ) or @entity6567 alone in Leogane, Haiti. We documented the frequency of adverse reactions, severity and cost of treatment. Adverse reactions were classified as minor, moderate, or severe. Overall, 24% (17,421) of the treated @entity1 reported one or more adverse reactions. There were 15,916 (91%) minor and 1502 (9%) moderate adverse reaction reports. @entity1 outnumbered @entity1 2:1 in reporting moderate problems. Three @entity1 , representing roughly one in 25,000 @entity1 treated, were hospitalized with severe adverse reactions judged to be treatment-associated by physician review. The cost per @entity1 treated for adverse reactions was more than twice the cost per @entity1 treated for @entity3754 (dollar 1.60 versus dollar 0.71). Severe adverse reactions to @entity3754 treatment using @entity6567 with or without @entity3753 are uncommon. Minor and moderate reactions are more commonly reported and their management represents a challenge to @entity3754 elimination programs.

title: Frequency, severity, and costs of adverse reactions following mass treatment for XXXX using @entity6566 and @entity3753 in Leogane, Haiti, 2000.

entities_list: @entity1 :: ('9606', 'Species') :: ['women', 'patients', 'Men', 'person', 'persons']

entities_list: @entity3753 :: ('MESH:D015766', 'Chemical') :: ['albendazole']

entities_list: @entity6566 :: ('MESH:D004049', 'Chemical') :: ['diethylcarbamazine']

entities_list: @entity3754 :: ('MESH:D004605', 'Disease') :: ['lymphatic filariasis']

answer: @entity3754 :: (MESH:D004605,Disease) :: ['lymphatic filariasis']


abstract: BACKGROUND: The aim of this study was to analyse a possible synergistic effect between @entity615 and @entity146 ( @entity146 ) in relation to future @entity717 ( @entity717 ). METHOD: All 4 823 069 individuals aged 16-64 years, living in Sweden in December 2004, not pensioned in 2005 and without ongoing sickness @entity2048 at the turn of 2004/2005 formed the cohort of this register-based study. Hazard ratios (HRs) and 95% confidence intervals (CIs) for @entity717 (2006-2010) were estimated. Exposure variables were @entity615 (M54) (sickness @entity2048 or inpatient or specialized outpatient care in 2005) and @entity24962 (F40-F48) [sickness @entity2048 or inpatient or specialized outpatient care or antidepressants (N06a) in 2005]. RESULTS: HRs for @entity717 were 4.03 (95% CI 3.87-4.21) and 3.86 (95% CI 3.68-4.04) in @entity1 and @entity1 with @entity615 . HRs for @entity717 in @entity1 and @entity1 with @entity24962 were 4.98 (95% CI 4.88-5.08) and 6.05 (95% CI 5.90-6.21). In @entity1 and @entity1 with both conditions, HRs for @entity717 were 15.62 (95% CI 14.40-16.94) and 19.84 (95% CI 17.94-21.94). In @entity1 , synergy index, relative excess risk due to interaction, and attributable proportion were 1.24 (95% CI 1.13-1.36), 0.18 (95% CI 0.11-0.25), and 2.08 (95% CI 1.09-3.06). The corresponding figures for @entity1 were 1.45 (95% CI 1.29-1.62), 0.29 (95% CI 0.22-0.36), and 4.21 (95% CI 2.71-5.70). CONCLUSIONS: Co-morbidity of @entity615 and @entity24962 is associated with a higher risk of @entity717 than either individual condition, when added up, which has possible clinical implications to prevent further disability and exclusion from the labour market.

title: Synergistic effect between @entity615 and XXXX and the risk of future @entity717 : a nationwide study from Sweden.

entities_list: @entity146 :: ('MESH:D001523', 'Disease') :: ['CMDs', 'common mental disorders']

entities_list: @entity615 :: ('MESH:D001416', 'Disease') :: ['back pain']

entities_list: @entity717 :: ('MESH:D009069', 'Disease') :: ['disability pension', 'DP']

answer: @entity146 :: (MESH:D001523,Disease) :: ['common mental disorders']


abstract: There are three members in the natriuretic peptide hormone family, atrial natriuretic peptide (ANP), @entity3876 ( @entity3876 , brain natriuretic peptide), and @entity21695 ( @entity21695 ), that are involved in the regulation of blood pressure and fluid homeostasis. @entity21695 is found principally in the central nervous system and vascular endothelial cells while ANP and @entity3876 are cardiac hormones. ANP is synthesized mainly in the atria of the normal adult heart, while @entity3876 is produced by both the atria and ventricles. The mechanisms controlling ANP release have been the subject of intense research, and are now fairly well understood. The major determinant of ANP secretion is myocyte stretch. Although much less is known about the factors regulating @entity3876 release from the heart, myocyte stretch has also been reported to stimulate @entity3876 release from both atria and ventricles. However, whether wall stretch acts directly or via factors such as endothelin- , @entity842 , or @entity2178 liberated in response to distension has not been established. Recent studies show that by stimulating endothelin type A receptors endothelin plays an important physiological role as a mediator of acute-volume load-induced ANP secretion from atrial myocytes in conscious animals. In fact, endogenous paracrine/autocrine factors liberated in response to atrial wall stretch rather than direct stretch appears to be responsible for activation of ANP secretion in response to volume load, as evidenced by almost complete blockade of ANP secretion during combined inhibition of endothelin type A/B and @entity2178 receptors. Furthermore, under certain experimental conditions @entity2178 and @entity842 may also exert a significant modulatory effect on stretch-activated ANP secretion. The molecular mechanisms by which @entity2232 , @entity2178 , and @entity842 synergistically regulate stretch-activated ANP release are yet unclear.

title: Mechanisms of mechanical load-induced atrial natriuretic peptide secretion: role of endothelin, XXXX , and @entity2178 .

entities_list: @entity21695 :: ('4880', 'Gene') :: ['CNP', 'C-type natriuretic peptide']

entities_list: @entity2178 :: ('183', 'Gene') :: ['angiotensin II']

entities_list: @entity3876 :: ('4879', 'Gene') :: ['BNP', 'B-type natriuretic peptide']

entities_list: @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide']

answer: @entity842 :: (MESH:D009569,Chemical) :: ['nitric oxide']


abstract: We searched for morphological evidence to support the hypothesis that stem cells are responsible for renal tubular cell proliferation. The rationale of the study was that if proliferation relies on progenitors, mitotically active cells should be less differentiated than their neighbors. As the retention of the @entity1014 analog @entity1603 has been the only approach employed to identify stem cells in the kidney up to now we additionally characterized @entity1603 -retaining cells. @entity35 kidneys were fixed by perfusion. Cycling cells identified by mitotic figures or the expression of the @entity1975 ( @entity1975 ) were examined by light microscopy and electron microscopy as well as immunofluorescence for four differentiation markers. Newborn @entity35 were injected with @entity1603 in order to detect label-retaining cells. After a period of 8, 14 and 35 weeks the kidneys were examined for @entity1603 by immunofluorescence and the four differentiation markers mentioned above. All cycling cells showed the same degree of differentiation compared to non-cycling cells. Most of the detected label-retaining cells were differentiated. We conclude that cycling cells in tubules of the healthy kidney are differentiated and that the retention of label is not a criterion to identify stem cells in renal tubules.

title: Tubular cell proliferation in the healthy XXXX kidney.

entities_list: @entity1975 :: ('25737(Tax:10116)', 'Gene') :: ['PCNA', 'proliferating cell nuclear antigen']

entities_list: @entity1014 :: ('MESH:D013936', 'Chemical') :: ['thymidine']

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


abstract: BACKGROUND: To evaluate if @entity3025 ( @entity3025 ) contralateral to the @entity15740 can interfere with the compensatory @entity8 . METHODS: Twenty-seven @entity1 (17 males, 10 females) with @entity15740 ( @entity15740 ) (14 on the right, 13 on the left) have been treated at the Nephrology Unit of the Pediatric Department of the University of Verona from birth up to the second year of life. All these @entity1 were diagnosed as having @entity15740 by prenatal ultrasonography. Seven @entity1 (4 males and 3 females) had @entity3025 (5 monolateral, 2 bilateral), diagnosed at the end of the first month of life. After diagnosis children underwent antibiotic prophylaxis with @entity3405 compounds at low doses. Four @entity1 underwent a surgical correction of @entity3025 associated with nephrectomy within the second year of life. The remaining 3 @entity1 were treated with antibiotic prophylaxis; a progressive resolution or downgrading of reflux grade took place respectively in 1 and in 2 of them. Only 6 @entity1 with @entity15740 underwent nephrectomy. @entity8 was studied by serial echographic measurements of the @entity8 (performed at birth, at 6 months, and at 2 years of life). RESULTS: Renal length was 5.68+/-1.24 cm, 6.72+/-0.88 cm, 8.56+/-1.27 cm in @entity1 without @entity3025 , respectively at birth, 6 months and 2 years of life. Renal length was 4.65+/-0.63 cm, 6.70+/-0.64 cm, 7.07+/-1.14 cm in @entity1 with @entity3025 , respectively at birth, 6 months and 2 years of life. A statistically significant difference was observed between the two groups at birth (p<0.05) and at 2 years of life (p<0.01). CONCLUSIONS: The conclusion is that @entity3025 contralateral to the @entity15740 is associated with small kidneys and reduced renal growth both at birth and at 2 years of life.

title: @entity15740 and contralateral XXXX . @entity8 .

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

entities_list: @entity8 :: ('MESH:D007674', 'Disease') :: ['longitudinal renal lenght', 'Renal growth', 'renal hypertrophy']

entities_list: @entity3405 :: ('CHEBI:35627', 'Chemical') :: ['beta-lactam']

entities_list: @entity15740 :: ('MESH:D021782', 'Disease') :: ['MDK', 'multicystic dysplastic kidney']

entities_list: @entity3025 :: ('MESH:D014718', 'Disease') :: ['VUR', 'vesicoureteral reflux']

answer: @entity3025 :: (MESH:D014718,Disease) :: ['vesicoureteral reflux']


abstract: BACKGROUND: @entity177 ( @entity177 ), defined as need for re-intubation within 24-72  h, is multifactorial. Factors predicting @entity177 in adults generally are not useful in @entity1 . OBJECTIVE: To determine the factors associated with @entity177 and to facilitate prediction of @entity177 in mechanically ventilated @entity1 and @entity1 less than 12  years of age. MATERIAL AND  METHODS: Design Prospective cohort study. Setting PICU and NICU of a multispecialty tertiary care institute. @entity1 All consecutive newborns, @entity1 and @entity1 , who remained on the ventilator for more than 12  h, were included. @entity1 with @entity4094 , complex anatomic @entity600 , accidental extubation, tracheostomy or @entity204 before extubation were excluded. Methods The pre-extubation clinical, laboratory and ventilatory parameters were collected for 92 cases over a one and half year period. The @entity177 rate was calculated for each variable using STATA 9. All the treating physicians were blinded to the data collection procedure. MEASUREMENTS AND RESULTS: Demographics were comparable between the extubation success and @entity177 groups. @entity1576 was the main cause requiring ventilation (46.74  %, 95  % CI 0.37-0.57) as well as @entity177 (30.23  %, 95  % CI 0.08-0.23). 76.92  % (95  % CI 0.58-0.89) of @entity1 that failed extubation had alterations in respiratory effort, 38.46  % (95  % CI 0.22-0.57) each had either poor or increased respiratory effort. Poor cough reflex (p  =  0.001), thick endotracheal secretions (p  =  0.02), failed spontaneous breathing trial (SBT) (p  =  0.001) and higher rapid shallow breathing index (RSBI) (p  =  0.001) were found to be associated with @entity177 . CONCLUSIONS: Paediatric @entity177 is multifactorial. Increased or poor respiratory effort and failed SBT are potential factors in deciding re-intubation. Increased RSBI, poor cough reflex and thick.

title: Prediction of extubation failure in newborns, @entity1 and XXXX : brief report of a prospective (blinded) cohort study at a tertiary care paediatric centre in India.

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

entities_list: @entity4094 :: ('MESH:D009468', 'Disease') :: ['upper airway obstruction, neuromuscular disorders']

entities_list: @entity600 :: ('MESH:D000014', 'Disease') :: ['malformations']

entities_list: @entity177 :: ('MESH:D051437', 'Disease') :: ['EF', 'Extubation failure']

entities_list: @entity1576 :: ('MESH:D012131', 'Disease') :: ['Respiratory failure']

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


abstract: @entity61863 ( @entity61863 ), a raphidophycean flagellate, is a causative organism of red tide, and highly toxic to fish. In this study, we found that the cell-free @entity1042 extract prepared from this flagellate exhibited potent hemolytic activity against @entity95 erythrocytes. Interestingly, the hemolytic activity of the extract was absolutely light-dependent, and no hemolytic activity was detected in the dark even at very high concentration. Gel filtration chromatography of the @entity1042 extract on a column of Sephadex LH-20 revealed that the extract contained @entity11230 as well as hemolytic agents, and the substances responsible for these activities were separately eluted. These results suggest that the hemagglutinating and hemolytic activities were derived from distinct compounds. The hemolytic fraction obtained after gel filtration (F4) caused marked inhibition of the growth of @entity61863 itself and other species of phytoplanktons. Furthermore, F4 showed a potent @entity137 toward various @entity1 cultured cell lines including @entity1 @entity5 cells (HeLa cells) in a dose-dependent manner. The @entity137 was also light-dependent, and no cytotoxic effect was exhibited in any cell lines tested in the dark. After further purification procedures via preparative thin-layer chromatography and subsequent HPLC, a major hemolytic agent was obtained as highly purified form. Since the @entity1042 extracts prepared from other raphidophycean flagellates such as @entity35232 , Olisthodiscus luteus, and Fibrocapsa japonica showed light-dependent hemolytic activity toward @entity95 erythrocytes, it was suggested that the light-dependent hemolytic agents commonly exist at least in these raphidophycean flagellates.

title: Isolation and characterization of light-dependent hemolytic cytotoxin from harmful red tide phytoplankton XXXX .

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

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

entities_list: @entity61863 :: ('90936', 'Species') :: ['Chattonella marina', 'C. marina']

entities_list: @entity1042 :: ('MESH:D000432', 'Chemical') :: ['methanol']

entities_list: @entity35232 :: ('2829', 'Species') :: ['Heterosigma akashiwo']

entities_list: @entity11230 :: ('MESH:D006388', 'Chemical') :: ['hemagglutinin']

answer: @entity61863 :: (90936,Species) :: ['Chattonella marina']


abstract: The application of circulating @entity5 DNA(ctDNA) represents a non-invasive method for @entity5 detection. Its prognostic significance in @entity1 with @entity14 is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in @entity1 with @entity14 . We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and @entity1349 ( @entity1349 ) stratified by ctDNA prior to December 6, 2016. We evaluated the quality and design of these studies. A total of 22 studies were eligible for systematic review. Among them, 11 studies investigated the prognostic value of ctDNA on disease-free survival (DFS). Seven of 11 studies showed that ctDNA was an independent variable to estimate the probability of DFS by multivariate analyses. Thirteen studies assessed the relationship between ctDNA and @entity1349 ( @entity1349 ). Eight of 13 studies showed that ctDNA was an independent predictor of worse @entity1349 through the use of multivariate analyses. This analysis provides evidence that ctDNA may be a prognostic biomarker, negatively correlated with the survival of @entity1 with @entity14 .

title: Prognostic value of circulating @entity5 DNA in XXXX with colon cancer: Systematic review.

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

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

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

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


abstract: BACKGROUND: The central nervous system (CNS) is one of the most commonly involved sites in the systemic progression of primary @entity784 ( @entity784 ) such as @entity4888 ( @entity4888 ). There is no consensus on the treatment of CNS progression in CTCL, but survival of 3-6  months is suggested when @entity1499 -based chemotherapy and/or CNS irradiation is used. @entity2903 is active in earlier stages of @entity4888 and readily crosses the blood-brain barrier. There are no published data on its use in @entity4888 @entity1 with CNS involvement. METHODS: Four @entity4888 @entity1 were treated with oral @entity2903 (200  mg/m(2) per day for 5  d on a 28-day cycle) for CNS progression. Two @entity1 received @entity2903 with low-dose CNS irradiation as initial treatment, and two received @entity2903 following disease progression after @entity1499 -based chemotherapy and CNS irradiation. All @entity1 received @entity619 . RESULTS: @entity2903 was well tolerated; there were no treatment withdrawals or dose reductions caused by @entity137 . @entity1  1 had an excellent partial response in pre-irradiated disease. @entity1  2 showed disease stabilization following irradiation. @entity1  3 showed a complete response after a partial response to irradiation. @entity1  4 demonstrated continued stabilization after a partial response to irradiation. Overall survival ranged from 10 to 33  months. @entity1  3 remains alive and symptom-free at 23  months following treatment. CONCLUSIONS: @entity2903 following low-dose CNS irradiation appears to be well tolerated and effective in @entity4888 @entity1 with CNS progression. It may represent a less toxic alternative to chemotherapy containing @entity1499 or an option for second-line therapy.

title: XXXX for central nervous system involvement in @entity4888 .

entities_list: @entity4888 :: ('MESH:D009182', 'Disease') :: ['mycosis fungoides', 'MF']

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

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

entities_list: @entity784 :: ('MESH:D016399', 'Disease') :: ['CTCLs', 'cutaneous T  cell lymphomas']

entities_list: @entity619 :: ('MESH:D003907', 'Chemical') :: ['dexamethasone']

entities_list: @entity2903 :: ('MESH:C047246', 'Chemical') :: ['Temozolomide', 'temozolomide']

entities_list: @entity1499 :: ('MESH:D008727', 'Chemical') :: ['methotrexate']

answer: @entity2903 :: (MESH:C047246,Chemical) :: ['Temozolomide']


abstract: BACKGROUND: Childhood @entity5 survivors (CCS) are at high risk of developing treatment-related late effects, including @entity65 and @entity6 . Late effects can be exacerbated by low physical activity (PA) levels. Relationships between PA and cardiovascular risk factors during childhood have not been well described in CCS. PROCEDURE: PA and cardiovascular risk factors were measured cross-sectionally in 319 CCS and 208 sibling controls aged 9-18 years. Comparisons between CCS and controls and associations of outcomes with PA (dichotomized at 60   min/day or treated as continuous) were performed with linear regression. RESULTS: Among CCS, the high PA group had lower percent fat mass (24.4% vs. 29.8%, P   <   0.0001), abdominal subcutaneous fat (67.9 vs. 97.3   cm(3) , P   =   0.0004), and abdominal visceral fat (20.0 vs. 24.9   cm(3) , P   =   0.007) and greater lean body mass (41.3 vs. 39.5   kg, P   =   0.009) than the low PA group. Comparing CCS to controls, differences in waist circumference (Pinteraction    =   0.04), percent fat mass (Pinteraction    =   0.04), and abdominal subcutaneous (Pinteraction    =   0.02) and visceral (Pinteraction    =   0.004) fat between low and high PA groups were greater in CCS than controls, possibly due to greater overall adiposity in CCS. CONCLUSIONS: High PA in CCS resulted in an improved cardiovascular profile, consisting primarily of lower fat mass and greater lean mass, similar to that observed in controls. This suggests interventions directed to increase PA in CCS may reduce the risk of future @entity65 . Pediatr @entity5    2014 Wiley Periodicals, Inc.

title: Physical activity and cardiovascular risk factors in childhood XXXX survivors.

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer', 'Blood Cancer']

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

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

answer: @entity5 :: (MESH:D009369,Disease) :: ['cancer']


abstract: UNASSIGNED: @entity7171 , a well established oncogenic member of @entity12841 family, is among the most intensely investigated kinase drug targets. In contrast to hotspot mutations of @entity12841 , few mutations of @entity7171 locate in activation loop within kinase domain. We previously reported the molecular mechanism underlying hyper kinase activity of HER2 @entity68900 , a mutation located in activation loop. However, its tumorigenicity in vivo and relevant therapeutics remain to be determined. Here, we report for the first time that HER2H878Y was tumorigenic in vivo in @entity2220 transgenic @entity19 model. Induced expression of HER2H878Y in lung epithelial compartments resulted in formation of poorly differentiated @entity2220 with @entity133 ( @entity133 ) features. Strikingly, we found that these @entity5 depended on continuous expression of HER2H878Y for maintenance. Typical @entity7171 downstream signaling mediators, including PLCy1, @entity23117 and @entity1994 , were hyperactivated in @entity2 . More importantly, administration of @entity36447 , a @entity4149 kinase inhibitor (TKI), efficiently shrank HER2H878Y driven @entity5 in transgenic @entity19 model. Moreover, we found that combinational treatment with @entity36447 and @entity3470 inhibitor, @entity3446 , showed a superior @entity137 to @entity68900 mutant transformed cells and enhanced activity to elicit apoptosis and inhibit growth in situ in tumorous area. Our work therefore showed that HER2 @entity68900 mutant was a reasonable drug target. Hence, our work supported the assessment of @entity36447 / @entity3446 treatment in clinical trials.

title: @entity5 driven by gain-of-function @entity7171 XXXX mutant is highly sensitive to @entity7171 inhibitor.

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

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

entities_list: @entity2 :: ('MESH:D008175', 'Disease') :: ['HER2H878Y driven lung tumors']

entities_list: @entity133 :: ('MESH:D002282', 'Disease') :: ['bronchioloalveolar carcinoma', 'BAC']

entities_list: @entity3446 :: ('MESH:D020123', 'Chemical') :: ['Rapamycin', 'rapamycin']

entities_list: @entity2220 :: ('MESH:C538231', 'Disease') :: ['lung adenocarcinoma']

answer: @entity68900 :: (p|SUB|H|878|Y,ProteinMutation) :: ['H878Y']


abstract: Hookworm is highly endemic to Hainan Province, an island located in the South China Sea. To investigate the prevalence and intensity of infection in the area, the village of Xiulongkan was surveyed between April and July 1998. A cross-sectional study was conducted in which fecal samples of 80% of the village residents (631 individuals) were tested for the presence of helminth eggs. Hookworm was the predominant intestinal helminth in Xiulongkan, where it was determined that 60% of those tested were infected. @entity17447 was the predominant species of hookworm in this population. The prevalence of hookworm increased with age, and then leveled to a plateau for ages 41 yr and up. This observation was in contrast to infections with @entity9124 , where the highest prevalences occurred among school-aged @entity1 . @entity1 had a significantly higher prevalence of hookworm than @entity1 and this difference emerged in early adulthood. The intensity of hookworm infection also significantly increased with age, with the highest intensity infections occurring among middle-aged and elderly residents. Females were more likely to have moderate or heavy infections, whereas males were more likely to have light infections. The rates of hookworm transmission are particularly high among the middle-aged and elderly residents of Xiulongkan.

title: Epidemiology of XXXX hookworm infections in Xiulongkan Village, Hainan Province, China: high prevalence and intensity among middle-aged and elderly residents.

entities_list: @entity17447 :: ('51031', 'Species') :: ['Necator americanus']

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

entities_list: @entity9124 :: ('6252', 'Species') :: ['Ascaris lumbricoides']

answer: @entity17447 :: (51031,Species) :: ['Necator americanus']


abstract: AIM: To investigate associations between the postoperative immune response and the levels of extracellular circulating DNA (cDNA), @entity1851 ( @entity1851 ), neutrophil/lymphocyte (N/L) ratio, and regulatory T (Treg) cells in the peripheral blood and their role as potential predictors of postoperative septic complications. METHODS: This was a prospective observational study involving 115 adult @entity1 who underwent elective surgery. @entity1 were divided into three groups: with benign disease, with @entity5 , and with @entity5 and administration of @entity619 . Serum @entity1851 levels, N/L ratio, monocyte human leukocyte antigen-DR (HLA-DR) expression, proportion of Treg cells, and cDNA levels were measured at different time points before and after surgery. RESULTS: All @entity1 had increased @entity1851 levels after surgery. @entity5414 @entity1 had higher serum @entity1851 levels at baseline. Compared with the other groups, the @entity619 group had significantly higher @entity1851 levels before and after surgery, a significantly higher N/L ratio before surgery, a significantly lower rise in the N/L ratio after surgery, and a significantly lower HLA-DR expression at baseline, which remained stable after surgery. In the @entity5 group, we observed a significant postoperative decrease in the HLA-DR expression. CONCLUSIONS: Our results suggest that the immunosuppressive effect of surgery and the presence of a @entity5 may contribute to a higher risk of @entity86 . Preoperative @entity1851 levels may be a reliable predictor of @entity295 in oncological @entity1 .

title: Postoperative immunosuppression markers and the occurrence of XXXX in @entity1 with benign and @entity5 .

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

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['malignant-disease', 'malignant disease']

entities_list: @entity86 :: ('MESH:D019106', 'Disease') :: ['postoperative sepsis']

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

answer: @entity295 :: (MESH:D018805,Disease) :: ['sepsis']


abstract: OBJECTIVE: To assess the optimum duration of topical ofloxacin therapy for @entity102 media and to compare the response between @entity1 with @entity102 media (CSOM) and acute exacerbation of @entity102 media (AE). STUDY DESIGN: Prospective observational study. SETTING: Five university hospitals and 30 affiliated institutions. @entity1 : A total of 294 @entity1 who presented to the participating institutions with CSOM were enrolled. Among them, 268 @entity1 were evaluable for safety and 237 were evaluable for efficacy (64 with CSOM and 173 with AE . INTERVENTION: @entity800 otic solution was administered for as long as 4 weeks. MAIN OUTCOME MEASURES: Clinical and bacteriologic assessment was done weekly during the treatment period. The clinical response was assessed on the basis of the symptom scores. RESULTS: There were no differences between CSOM and AE @entity1 with respect to sex, age, and severity. The most common bacterial isolate from middle ear discharge was @entity794 . The clinical response rates in @entity1 with CSOM and AE were 39.1% and 61.3% after 2 weeks of treatment and 57.8% and 75.1% after 4 weeks, respectively, and the bacterial eradication rate was 91.0% at 2 weeks and 94.6% at 4 weeks. Detection of new @entity364 did not increase as the duration of therapy was prolonged. No serious adverse events were reported. CONCLUSIONS: The duration of treatment was shorter and the clinical response was higher in AE @entity1 than in CSOM @entity1 . The standard topical ofloxacin regimen for @entity102 media should consist of a 2-week course from the aspect of bacteriologic efficacy, although @entity1 showing insufficient symptomatic improvement after 2 weeks may benefit from another 1 or 2 weeks of therapy. Administration of this drug for as long as 4 weeks can increase the clinical efficacy without causing safety problems.

title: Topical @entity800 for @entity102 media and acute exacerbation of XXXX media: optimum duration of treatment.

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

entities_list: @entity794 :: ('1280', 'Species') :: ['Staphylococcus aureus']

entities_list: @entity102 :: ('MESH:D002908', 'Disease') :: ['chronic otitis', 'chronic suppurative otitis']

entities_list: @entity364 :: ('MESH:D009181', 'Disease') :: ['fungal infection']

entities_list: @entity800 :: ('MESH:D015242', 'Chemical') :: ['Ofloxacin']

answer: @entity102 :: (MESH:D002908,Disease) :: ['chronic otitis']


abstract: BACKGROUND: The objective of the study was to evaluate the gene expression of inflammatory cytokines (interleukin [IL]-1b, IL-6, IL-8, IL-10, @entity5 @entity39 factor [TNF]-a, IL-1 receptor antagonist [ra] and serum amyloid A (SAA) in endometrial tissue and circulating leukocytes in response to uterine inoculation of 105 colony forming units (CFU) @entity526 in mares. Before inoculation, mares were classified as resistant or susceptible to persistent @entity7288 based on their uterine inflammatory response to infusion of 109 killed spermatozoa and histological assessment of the endometrial quality. Endometrial biopsies were obtained 3, 12, 24 and 72 hours (h) after bacterial inoculation and blood samples were obtained during the 7 day period post bacterial inoculation. Expression levels of cytokines and SAA were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR). RESULTS: Compared to levels in a control biopsy (obtained in the subsequent estrous), resistant mares showed an up-regulation of IL-1b, IL-6, IL-8 and TNF-a at 3 h after @entity526 inoculation, while susceptible mares showed increased gene expression of IL-6 and IL-1ra. Susceptible mares had a significant lower gene expression of TNF-a,IL-6 and increased expression of IL-1ra 3 h after @entity526 inoculation compared to resistant mares. Susceptible mares showed a sustained and prolonged inflammatory response with increased gene expression levels of IL-1b, IL-8, IL-1ra and IL-1b:IL-1ra ratio throughout the entire study period (72 h), whereas levels in resistant mares returned to estrous control levels by 12 hours. Endometrial mRNA transcripts of IL-1b and IL-1ra were significantly higher in mares with heavy uterine bacterial growth compared to mares with no/mild growth.All blood parameters were unaffected by intrauterine @entity526 infusion, except for a lower gene expression of IL-10 at 168 h and an increased expression of IL-1ra at 48 h observed in susceptible mares compared to resistant mares. CONCLUSIONS: The current investigation suggests that endometrial mRNA transcripts of pro-inflammatory cytokines in response to @entity7288 are finely regulated in resistant mares, with initial high expression levels followed by normalization within a short period of time. Susceptible mares had a prolonged expression of pro-inflammatory cytokines, supporting the hypothesis that an unbalanced endometrial gene expression of inflammatory cytokines might play an important role in the pathogenesis of persistent @entity7288 .

title: Inflammatory responses to induced XXXX in mares resistant or susceptible to persistent @entity7288 .

entities_list: @entity7288 :: ('MESH:D004716', 'Disease') :: ['endometritis']

entities_list: @entity526 :: ('562', 'Species') :: ['Escherichia coli', 'E. coli']

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

answer: @entity7288 :: (MESH:D004716,Disease) :: ['infectious endometritis']


abstract: BACKGROUND: The mechanisms underlying post-extracranial to intracranial (EC-IC) bypass neurocognitive changes are poorly understood. METHODS: Data from 55 @entity1 who underwent a unilateral EC-IC bypass for @entity2998 (ICA)/middle cerebral artery (MCA) steno-occlusive disease were retrospectively evaluated. These @entity1 underwent neuropsychological examinations (NPEs), including assessment by the Wechsler Adult Intelligence Scale-Third Edition and Wechsler Memory Scale-Revised (WMS-R) before and 6  months after EC-IC bypass. Results of NPEs were converted into Z-scores from which preoperative cognitive composite scores (CSpre) and postoperative cognitive composite scores (CSpost) were obtained. The association between the change of composite score between pre- and postoperative NPEs (CSpost-pre   =   CS post - CS pre) and various variables were assessed. These latter variables included occluded artery (ICA or MCA), preexisting @entity2806 as verified in preoperative T2WI, robust bypass patency as verified by MRA performed approximately 6  months postoperatively, and postoperative transient @entity16 and/or @entity282 ( @entity6087 ), both of which were dichotomized as postoperative events. RESULTS: Postoperative MRI follow-up (median, 6  months; interquartile range, 5-8 months) confirmed successful bypasses in all @entity1 , with no additional ischemic lesions on T2WI when compared with preoperative imaging. Further, MRA showed patent bypasses in all @entity1 . A nearly statistically significant CS post-pre decrease was observed in @entity1 with postoperative events when compared with those without postoperative events (-0.158 vs. 0.039; p   =   0.069). A multiple regression model predicting CSpost-pre was performed. After controlling for occluded arteries, postoperative events were identified as an independent predictor of a decline in CSpost-pre (p   =   0.044). In the group rate analysis, three of four postoperative NPE scores (Performance IQ, @entity3297 ) were significantly improved relative to preoperative NPE scores. CONCLUSIONS: Postoperative transient @entity16 and/or @entity6087 might play a significant role in the subtle decline in cognition following an EC-IC bypass. However, this detrimental effect was small, and based on the group rate analysis, we concluded that a successful unilateral EC-IC bypass does not adversely affect postoperative cognitive function.

title: Postoperative transient @entity16 and XXXX after extracranial-intracranial bypass for internal carotid/middle cerebral atherosclerotic steno-occlusive diseases: negative effect on cognitive performance.

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

entities_list: @entity2806 :: ('MESH:D002545', 'Disease') :: ['ischemic lesion']

entities_list: @entity16 :: ('MESH:D009422', 'Disease') :: ['neurological symptoms']

entities_list: @entity2998 :: ('MESH:D002340', 'Disease') :: ['atherosclerotic internal carotid artery']

entities_list: @entity3297 :: ('MESH:D018980', 'Disease') :: ['WMS-memory, WMS-attention']

entities_list: @entity282 :: ('MESH:D010149', 'Disease') :: ['postoperative chronic subdural hematoma']

answer: @entity6087 :: (MESH:D020200,Disease) :: ['chronic subdural hematoma']


abstract: Degradation of mitotic cyclins on exit from M phase occurs by ubiquitin-mediated proteolysis. The ubiquitination of mitotic cyclins is regulated by the @entity7319 ( @entity7319 ) or cyclosome. @entity70423 , the @entity1238 homolog of the Suc1/Cks protein, is required for some step in mitotic cyclin destruction in @entity1238 egg extracts. Specifically, if p9 is removed from interphase egg extracts, these p9-depleted extracts are unable to carry out the proteolysis of cyclin B after entry into mitosis and thus remain arrested in M phase. To explore the molecular basis of this defect, we depleted p9 from extracts that had already entered M phase and thus contained an active @entity7319 . We found that ubiquitin-mediated proteolysis of cyclin B was not compromised under these circumstances, suggesting that p9 is not directly required for ubiquitination or proteolysis. Further analysis of extracts from which p9 had been removed during interphase showed that, at the beginning of mitosis, these extracts are unable to carry out the hyperphosphorylation of the @entity42406 component of the @entity7319 , which coincides with the initial activation of the @entity7319 . p9 can be found in a complex with a small fraction of the @entity42406 protein during M phase but not interphase. The phosphorylation of the @entity42406 protein (either associated with the @entity7319 or in an isolated, bacterially expressed form) by recombinant @entity2111 /cyclin B is strongly enhanced by p9. Our results indicate that p9 directly regulates the phosphorylation of the @entity7319 by @entity2111 /cyclin B. These studies indicate that the Suc1/Cks protein modulates substrate recognition by a cyclin-dependent kinase.

title: @entity70423 , a @entity1238 Suc1/Cks protein, is essential for the XXXX -dependent phosphorylation of the anaphase- promoting complex at mitosis.

entities_list: @entity7319 :: ('MESH:D030401', 'Disease') :: ['APC', 'anaphase-promoting complex']

answer: @entity2111 :: (379785(Tax:8355),Gene) :: ['Cdc2']


abstract: UNASSIGNED: The association between @entity5 and immune-mediated rheumatic conditions is controversial, especially as far as @entity2760 ( @entity2760 ) is concerned. Furthermore, no clinical feature has been shown to be suggestive of a @entity627 . With the present study, we aim to address both these issues. The study population comprised N  =  1750 @entity1 , including N  =  100 with @entity2760 , who attended our tertiary immuno-rheumatology clinic between January 1, 2005 and November 30, 2012. A @entity627 was deemed paraneoplastic if @entity5 had been diagnosed in the 2  years preceding or following its onset. The probability of a significant association between a specific @entity627 and @entity5 was evaluated by computing the odds ratio (OR): N  =  702 @entity1 with @entity571 serving as controls. Furthermore, clinical features distinguishing paraneoplastic @entity627 were searched for by univariate and multivariate analysis. @entity10632 ( @entity10632 ) [OR 3.6 (CI 95% 1.7-7.5)], @entity2760 (OR 5.1 CI 95% 2.9-8.9), @entity6017 / @entity6558 [OR 12.09 (CI 95% 2.6-55.8)] and @entity1333 [OR 3.70 (CI 95% 1.81-7.52)] are associated with @entity5 . At multivariate analysis, older age is associated with @entity5 among @entity10632 @entity1 (p  =  0.03), while in the @entity2760 group, older age, male gender, and >= 6 tender joints are independent predictors of paraneoplastic @entity2760 (p  <  0.0004). Cancer frequently either heralds or follows rheumatic manifestations, including @entity2760 . Older age, male gender and a more extensive joint involvement should be considered red flags for paraneoplastic @entity2760 .

title: Association between XXXX and @entity5 : results from a clinical practice cohort study.

entities_list: @entity627 :: ('MESH:D012216', 'Disease') :: ['rheumatic disease', 'rheumatic diseases', 'paraneoplastic rheumatic syndrome']

entities_list: @entity571 :: ('MESH:D010003', 'Disease') :: ['osteoarthritis']

entities_list: @entity6017 :: ('MESH:D003882', 'Disease') :: ['dermatomyositis']

entities_list: @entity1333 :: ('MESH:D014657', 'Disease') :: ['vasculitis']

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

entities_list: @entity2760 :: ('MESH:D011111', 'Disease') :: ['polymyalgia rheumatica', 'PMR']

entities_list: @entity10632 :: ('MESH:D012859', 'Disease') :: ["Sjogren's syndrome", 'SS']

entities_list: @entity6558 :: ('MESH:D017285', 'Disease') :: ['polymyositis']

answer: @entity627 :: (MESH:D012216,Disease) :: ['rheumatic diseases']


abstract: A previous study performed using steady state fluorescence has revealed the existence of residual structures surrounding the two @entity2340 residues in an unfolded form of @entity375 @entity21590 [Garcia, P., et al. (1995) Biochemistry 34, 397-404]. In this paper, we present a more detailed characterization of these residual structures, through the study of two single @entity2340 -containing mutants of yPGK, @entity69424 and @entity69425 . Denaturation experiments have first been performed at low temperatures to assess the nature of the interactions stabilizing these residual structures. On the other hand, the compactness and dynamics of the protein matrix were probed using @entity2340 fluorescence quenching by @entity3323 at various denaturant concentrations. Taking into consideration the changes in sample viscosity induced by addition of @entity2097 made feasible the use of this technique during the denaturation process. These different approaches have shown that the residual structures around @entity2340 308 are mainly stabilized by hydrophobic interactions and are more compact and less fluctuant than the ones surrounding @entity2340 333. Native and denatured yPGK have also been studied by time-resolved fluorescence spectroscopy. In the native protein, @entity2340 buried in the core, W333, is mainly associated with a lifetime close to 0.1 ns, whereas @entity2340 that is partially accessible to the solvent, W308, has a lifetime close to 0. 5 ns. The time-resolved @entity2340 fluorescence emission of wild-type yPGK can be accounted for quantitatively by the summed emissions of its two single @entity2340 mutants. The significance of minor long lifetime components is discussed for the two @entity2340 residues. This new assignment of fluorescent decay times has allowed for the detection of a folding intermediate in which the environment of @entity2340 333 is modified for denaturant concentrations lower than those for @entity2340 308.

title: Steady state and time-resolved fluorescence study of residual structures in an unfolded form of @entity375 XXXX .

entities_list: @entity21590 :: ('850370(Tax:4932)', 'Gene') :: ['phosphoglycerate kinase']

entities_list: @entity2340 :: ('CHEBI:27897', 'Chemical') :: ['tryptophan']

entities_list: @entity3323 :: ('MESH:D020106', 'Chemical') :: ['acrylamide']

entities_list: @entity2097 :: ('MESH:D019791', 'Chemical') :: ['guanidinium chloride']

answer: @entity21590 :: (850370(Tax:4932),Gene) :: ['phosphoglycerate kinase']


abstract: OBJECTIVE: To further understand the association between semen quality and @entity5 risk by means of well defined semen parameters. DESIGN: Retrospective cohort study. SETTING: Not applicable. @entity1 (S): A total of 20,433 @entity1 who underwent semen analysis (SA) and a sample of 20,433 fertile control subjects matched by age and birth year. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Risk of all @entity5 as well as site-specific results for @entity263 , @entity5 , and @entity320 . RESULT(S): Compared with fertile @entity1 , @entity1 with SA had an increased risk of @entity5 (hazard rate [HR] 3.3). When the characterization of @entity249 was refined using individual semen parameters, we found that oligozoospermic @entity1 had an increased risk of @entity5 compared with fertile control subjects. This association was particularly strong for @entity5 , with increased risk in @entity1 with @entity6660 based on concentration (HR 11.9) and on sperm count (HR 10.3). @entity1 in the in the lowest @entity1319 (HR 6.9) had higher risk of @entity5 compared with fertile @entity1 . @entity1 with sperm concentration and count in the 90th percentiles of the distribution (>= 178 and >= 579 * 10(6)/mL, respectively), as well as total motile count, had an increased risk of @entity320 (HRs 2.1, 2.7, and 2.0, respectively). We found no differences in @entity5 risk between azoospermic and fertile @entity1 . CONCLUSION(S): @entity1 with SA had an increased risk of @entity5 which varied by semen quality. Unlike earlier work, we did not find an association between @entity3893 and @entity5 risk.

title: Subfertility increases risk of XXXX : evidence from population-based semen samples.

entities_list: @entity249 :: ('MESH:D007246', 'Disease') :: ['infertility']

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

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'testicular cancer', 'cancer', 'increased cancer']

entities_list: @entity3893 :: ('MESH:D053713', 'Disease') :: ['azoospermia']

entities_list: @entity6660 :: ('MESH:D009845', 'Disease') :: ['oligozoospermia']

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

entities_list: @entity1319 :: ('MESH:D015835', 'Disease') :: ['quartile of motility (HR 4.1), viability (HR 6.6), morphology (HR 4.2), or total motile count']

answer: @entity5 :: (MESH:D009369,Disease) :: ['testicular cancer']


abstract: BACKGROUND: @entity1416 ( @entity1416 ) improves non-operative splenic salvage rates in adults, but its utility and safety in the pediatric population is less well defined. OBJECTIVE: Because adolescent @entity130 @entity1 are often triaged to adult @entity130 centers, we were interested in evaluating @entity1416 in this particular population. We hypothesize that angiography and embolization is a safe and effective adjunct to non-operative management in the adolescent population. METHODS: A retrospective review of all @entity1 aged 13-17 years admitted to our Level I @entity130 Center with blunt @entity130 from 1997-2005 was performed. We reviewed @entity1 demographics, operative reports, admission, and follow-up abdominal computed tomography (ACT) results, angiographic reports, and @entity1 outcomes. RESULTS: A total of 97 @entity1 were reviewed. Eighteen @entity1 underwent immediate surgery, and 79 of the remaining @entity1 had planned non-operative management. Of those participating in non-operative management, 35/79 (44%) were initially observed and 44/79 (56%) underwent initial angiography, 23/44 having embolization. @entity1 in the embolization group had an overall high grade of injury (American Association for the Surgery of @entity130 mean grade 3.3, SD 0.6). The overall splenic salvage rate was 96% (76/79) in the non-operative management group; 100% splenic salvage was seen in the observational group; 100% salvage was also seen in @entity1 with negative angiography, and 87% salvage (20/23) in the @entity1416 group. CONCLUSION: @entity1416 may be a valuable adjunct in adolescent blunt @entity130 , especially in higher grade injuries or with evidence of @entity1317 on ACT.

title: Blunt @entity130 in the adolescent XXXX population: the role of angiography and embolization.

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

entities_list: @entity1317 :: ('MESH:D057772', 'Disease') :: ['splenic vascular injury']

entities_list: @entity1416 :: ('MESH:D020762', 'Disease') :: ['Splenic artery embolization', 'SAE', 'splenic artery embolization']

entities_list: @entity130 :: ('MESH:D014947', 'Disease') :: ['splenic injury', 'Trauma', 'trauma']

answer: @entity130 :: (MESH:D014947,Disease) :: ['trauma']


abstract: @entity2333 ( @entity2333 ) counterpulsation is a useful hemodynamic assist device during complex percutaneous coronary intervention (PCI) in @entity1 with poor left ventricular function; however, the presence of an @entity1028 poses a problem, because insertion via the femoral artery may cause @entity887 and @entity1756 . A 92-year-old @entity1 with unstable @entity951 was admitted to our hospital. Coronary angiography revealed @entity432 of the proximal left anterior descending artery and severe @entity850 of the left circumflex artery (LCX). The left ventricular ejection fraction was 36%. He also had an @entity1028 with a diameter of 55 mm. Supported PCI was performed for the management of the LCX lesion. A novel 6-Fr @entity2333 catheter was inserted via the left brachial artery. The lesion was successfully dilated, and a 3.0   13 mm Cypher   stent was placed. After the PCI procedure, the @entity2333 catheter was retrieved in the catheter laboratory, and the @entity1 was discharged after 7 days. When a femoral approach is contraindicated in PCI, 6-Fr @entity2333 catheter insertion via the brachial artery is feasible and effective.

title: Supported percutaneous coronary intervention using a novel 6-Fr intra-aortic balloon pump catheter via the brachial artery in a nonagenarian @entity1 with an XXXX .

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

entities_list: @entity887 :: ('MESH:D004617', 'Disease') :: ['distal embolism']

entities_list: @entity432 :: ('MESH:D001157', 'Disease') :: ['chronic total occlusion']

entities_list: @entity2333 :: ('MESH:D001018', 'Disease') :: ['Intra-aortic balloon pump', 'IABP']

entities_list: @entity850 :: ('MESH:D003251', 'Disease') :: ['stenosis']

entities_list: @entity1028 :: ('MESH:D017544', 'Disease') :: ['infrarenal abdominal aortic aneurysm', 'abdominal aortic aneurysm']

entities_list: @entity1756 :: ('MESH:D017542', 'Disease') :: ['aneurysm rupture']

answer: @entity1028 :: (MESH:D017544,Disease) :: ['abdominal aortic aneurysm']


abstract: UNASSIGNED: @entity320 is known as an exceptionally aggressive and treatment-resistant @entity1 @entity5 . Although a great deal of progress has been made in the past decade, including the development of immunotherapy using immune checkpoint inhibitors and targeted therapy using @entity817 , MEK or KIT inhibitors, treatment for unresectable stage III, stage IV, and recurrent @entity320 is still challenging with limited response rate, severe side effects and poor prognosis, highlighting an urgent need for discovering and designing more effective approaches to conquer @entity320 . @entity320 is not only driven by malignant melanocytes, but also by the altered communication between neoplastic cells and non-malignant cell populations, including fibroblasts, endothelial and inflammatory cells, in the @entity5 stroma. Infiltrated and surrounding fibroblasts, also known as @entity5 -associated fibroblasts (CAFs), exhibit both phenotypical and physiological differences compared to normal dermal fibroblasts. They acquire properties of myofibroblasts, remodel the extracellular matrix (ECM) and architecture of the diseased tissue and secrete chemical factors, which all together promote the transformation process by encouraging @entity5 growth, @entity7499 , @entity32 and @entity3 and contribute to drug resistance. A number of in vitro and in vivo experiments have shown that stromal fibroblasts promote @entity320 cell proliferation and they have been targeted to suppress @entity5 growth effectively. Evidently, a combination therapy co-targeting @entity5 cells and stromal fibroblasts may provide promising strategies to improve therapeutic outcomes and overcome treatment resistance. A significant benefit of targeting CAFs is that the approach aims to create a @entity5 -resistant environment that inhibits growth of @entity320 carrying different genetic mutations. However, the origin of CAFs and precise mechanisms by which CAFs contribute to @entity320 and drug resistance remain poorly understood. In this review, we discuss the origin, activation and heterogeneity of @entity5 microenvironment and examine the contributions of stromal fibroblasts at different stages of @entity320 development. We also highlight the recent progression in dissecting and characterizing how local fibroblasts become reprogrammed and build a dynamic yet optimal microenvironment for @entity5 to develop and @entity3 . In addition, we review key developments in ongoing preclinical studies and clinical applications targeting CAFs and @entity5 -stroma interactions for @entity320 treatment.

title: Perspective of Targeting Cancer-Associated Fibroblasts in XXXX .

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

entities_list: @entity7499 :: ('MESH:D016510', 'Disease') :: ['angiogenesis']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors', 'CAFs in the melanoma tumor', 'cancer']

entities_list: @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis', 'metastasize']

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

answer: @entity320 :: (MESH:D008545,Disease) :: ['Melanoma']


abstract: BACKGROUND: @entity1150 ( @entity1150 ) @entity4096 is a vexing problem despite effective anticoagulation, and is characterized by vein wall @entity82 . This study tested the hypothesis that P-selectin inhibition would decrease post-thrombotic vein wall @entity82 and associated profibrotic mediators. METHODS: A @entity35 stasis model of @entity1150 was used to produce a 2-day-old @entity1150 . @entity35 then received either intravenous saline (control), rPSGL-Ig (4 mg/kg) once, or daily subcutaneous low molecular weight heparin (LMWH) (0.5 mg/kg). Inferior vena cava wall was harvested 7 days after treatment and processed for @entity715 size; leukocyte content; profibrotic mediators by enzyme-linked immunosorbent assay; collagen I and III mRNA expression by semiquantitative real-time polymerase chain reaction; and for collagen protein. RESULTS: Thrombus mass and leukocyte counts were similar between the groups. Treatment with rPSGL-Ig and LMWH resulted in less vein wall collagen (P <.05). rPSGL-Ig treatment (and a similar trend for LMWH) was associated with decreased profibrotic mediators, including less @entity10957 , @entity4647 , bFGH, and transforming growth factor-beta (P <.05). Collagen III gene expression, but not collagen I gene expression, was increased with LMWH treatment (P <.05). CONCLUSIONS: P-selectin inhibition with rPSGL-Ig or LMWH decreases post- @entity1150 vein wall @entity82 , and is associated with decreased vein wall profibrotic mediators. This effect is independent of @entity715 mass and vein wall leukocytes.

title: P-selectin inhibition decreases post-thrombotic vein wall @entity82 in a XXXX model.

entities_list: @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis']

entities_list: @entity1150 :: ('MESH:D020246', 'Disease') :: ['Post-deep vein thrombosis', 'DVT']

entities_list: @entity4096 :: ('MESH:D014689', 'Disease') :: ['venous insufficiency']

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

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


abstract: @entity409 results in complex alterations of all 3 phases of hemostasis. It is now recognized that hemostasis is @entity409 . The fall in clotting factor levels is accompanied by a parallel fall in anticoagulant proteins. High @entity2880 factor levels counteract defects in primary hemostasis. Conventional coagulation tests do not fully reflect the derangement in hemostasis and do not accurately predict the risk of @entity548 . Global coagulation assays (thrombin generation, thromboelastography) reflect the interaction between procoagulant factors, anticoagulant factors, platelets, and the fibrinolytic system and show promise for assessing @entity548 risk and guiding therapy. These assays are not yet commercially approved or validated. Prevention of @entity548 should not be aimed at correcting conventional coagulation tests. Thrombopoietin receptor agonists were shown to increase the platelet count in cirrhotic @entity1 undergoing invasive procedures but may increase the risk of @entity715 . Rebalanced hemostasis in @entity409 is precarious and may be tipped toward @entity548 or @entity715 depending on coexisting circumstantial risk factors. @entity2348 may impair hemostasis in @entity82 by triggering the release of endogenous heparinoids. There are no evidence-based guidelines for hemostatic therapy of @entity548 in @entity409 . There is currently inadequate evidence to support the use of recombinant FVIIa, prothrombin complex concentrates, or @entity927 in acute variceal or other @entity548 .

title: XXXX : a balancing act.

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

entities_list: @entity82 :: ('MESH:D005355', 'Disease') :: ['cirrhosis']

entities_list: @entity548 :: ('MESH:D006470', 'Disease') :: ['hemorrhage', 'bleeding', 'acute hemorrhage']

entities_list: @entity409 :: ('MESH:D008107', 'Disease') :: ['rebalanced in chronic liver disease', 'Liver disease', 'liver disease']

entities_list: @entity2348 :: ('MESH:D001424', 'Disease') :: ['Bacterial infection']

entities_list: @entity927 :: ('MESH:D014148', 'Chemical') :: ['tranexamic acid']

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

entities_list: @entity2880 :: ('MESH:D014842', 'Disease') :: ['von Willebrand']

answer: @entity409 :: (MESH:D008107,Disease) :: ['Coagulopathy in liver disease']


abstract: BACKGROUND: @entity1643 is one of the most common conditions managed in primary care. Restricted activity, rest, and symptomatic analgesics are the most commonly prescribed treatment for @entity1643 and @entity13549 . OBJECTIVES: To assess the effects of advice to stay active as single treatment for @entity1 with @entity1643 . SEARCH STRATEGY: Computerised searches in MEDLINE, EMBASE, Sport, The Cochrane Controlled Trials Register, Musculoskeletal Group's Trials Register and Scisearch, and scanning of reference lists from relevant articles were undertaken. Relevant studies were also traced by contacting authors. Date of the most recent searches: December 1998. SELECTION CRITERIA: We included all randomised trials or quasi-randomised trials where the study population consisted of adult @entity1 with @entity1643 or @entity13549 , in which one comparison group was advised to stay active. The main outcomes of interest were @entity158 , functional status, recovery and return to work. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed the validity of included trials and extracted data. Investigators were contacted to collect missing data or for clarification when needed. MAIN RESULTS: Four trials, with a total of 491 @entity1 , were included. Advice to stay active was compared to advice to rest in bed in all trials. Two trials were assessed to have low risk of bias and two to have moderate to high risk of bias. The results were heterogeneous. Results from one high quality trial of @entity1 with acute simple LBP found small differences in functional status [Weighted Mean Difference (on a 0-100 scale) 6.0 (95% CI: 1.5, 10.5)] and length of sick leave [WMD 3.4 days (95% CI: 1.6, 5.2)] in favour of staying active compared to advice to stay in bed for two days. The other high quality trial compared advice to stay active with advice to rest in bed for 14 days for @entity1 with @entity1930 , and found no differences between the groups. One of the high quality trials also compared advice to stay active with exercises for @entity1 with acute simple LBP, and found improvement in functional status and reduction in sick leave in favour of advice to stay active. REVIEWER'S CONCLUSIONS: The best available evidence suggests that advice to stay active alone has small beneficial effects for @entity1 with @entity1643 , and little or no effect for @entity1 with @entity13549 . There is no evidence that advice to stay active is harmful for either @entity1643 or @entity13549 . If there is no major difference between advice to stay active and advice to rest in bed, and there is potential harmful effects of prolonged bed rest, then it is reasonable to advise @entity1 with @entity1643 and @entity13549 to stay active. These conclusions are based on single trials.

title: Advice to stay active as a single treatment for @entity1643 and XXXX .

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

entities_list: @entity1643 :: ('MESH:D017116', 'Disease') :: ['Low back pain', 'low back pain', 'acute simple low back pain', 'acute low back pain']

entities_list: @entity1930 :: ('MESH:D020426', 'Disease') :: ['sciatic syndrome']

answer: @entity13549 :: (MESH:D012585,Disease) :: ['sciatica']


abstract: BACKGROUND: Toothbrushing enhances gingival fibroblast proliferation, which promotes wound healing. Optimum force and duration of toothbrushing for stimulation of fibroblast proliferation are key factors in maximizing effects of toothbrushing on periodontal wound healing. We therefore evaluated the effects of different durations and forces of toothbrushing on proliferative activity and procollagen synthesis of gingival fibroblasts. METHODS: Twelve @entity235 were used. In each @entity235 , buccal gingivae of 12 teeth were examined for 3 weeks. Nine of these 12 teeth were each assigned to 1 of 9 different combinations of brushing force (0.98, 1.96, or 2.45 N) and duration (10, 20, or 40 seconds). The remaining 3 teeth received plaque removal without brushing, via a scaler. RESULTS: Force and duration of toothbrushing affected both @entity25270 ( @entity25270 )-positive and procollagen Type I C-peptide (PIP)-positive fibroblast ratios (P < 0.05). The highest ratio of @entity25270 -positive fibroblasts was produced by brushing at 1.96 N for 20 seconds. The highest ratio of PIP-positive fibroblasts was produced by brushing at 1.96 N for 10 seconds. CONCLUSIONS: Toothbrushing at certain forces and durations enhanced the proliferative activity and procollagen synthesis of gingival fibroblasts. The toothbrushing duration that increased procollagen synthesis (10 seconds) was shorter than that which increased fibroblast proliferative activity (20 seconds).

title: Optimum force and duration of toothbrushing to enhance gingival fibroblast proliferation and procollagen type I synthesis in XXXX .

entities_list: @entity25270 :: ('477166(Tax:9615)', 'Gene') :: ['PCNA', 'proliferating cell nuclear antigen']

answer: @entity235 :: (9615,Species) :: ['dogs']


abstract: OBJECTIVES: To characterize the population pharmacokinetics of @entity7302 after intramuscular administration of its long-acting @entity47371 at various doses and at two different injection sites (deltoid and gluteal muscle). METHODS: The retrospective analysis included pooled data from 1795 subjects from six phase I trials and five phase II and III trials. A total of 18 530 pharmacokinetic samples with valid concentration timepoints were available for this analysis. Nonlinear mixed-effects modelling of the pooled data was conducted using NONMEM software. The full dataset was divided into an index dataset (model development) and a validation dataset. After validation both the index and validation datasets were combined and the final model was re-run on the full dataset. RESULTS: The concentration-time data for @entity7302 following intramuscular administration of its @entity47371 were best fitted to a one-compartment model with first-order elimination. The absorption component of the model allowed a fraction of the dose (f(2)) to enter relatively quickly into the central compartment via a zero-order process. After a lag time, the remaining fraction then entered the systemic circulation via a first-order process. Interindividual variability (IIV) in clearance (CL), central volume of distribution (V(d)) and the absorption rate constant (k(a)) were estimated at a 40%, 69% and 59% coefficient of variation (CV), respectively. The IIV on f(2) for @entity7302 absorption via the dual-input process was fitted through logit transformation, and its standard deviation (SD) was 0.064. Similarly, the interoccasion variability (IOV) on CL, V(d) and f(2) was 26% CV, 14% CV and 0.07 SD, respectively. An additive-error model with log-transformed data was used to describe the residual variability (RV), and its SD was 0.22. The final covariate model indicated that the following variables had a significant influence on k(a): sex, age, injection volume (IVOL) and injection site (INJS). Similarly, the following variables had a significant influence on f(2): sex, body mass index (BMI), needle length (NDLL), INJS and IVOL. In addition, CL was related to @entity1011 clearance (CL(CR)), whereas V(d) was related to BMI and sex. CONCLUSIONS: A dual-absorption pharmacokinetic model best described the complex pharmacokinetics of @entity7302 after intramuscular administration of its @entity47371 . These results suggest that the pharmacokinetics of @entity16864 are mostly influenced by BMI, CL(CR), INJS, IVOL and NDLL.

title: Population pharmacokinetics of intramuscular XXXX in patients with schizophrenia: a novel once-monthly, long-acting formulation of an atypical antipsychotic.

entities_list: @entity7302 :: ('MESH:C079150', 'Chemical') :: ['paliperidone']

entities_list: @entity16864 :: ('MESH:C548956', 'Chemical') :: ['paliperidone palmitate']

entities_list: @entity47371 :: ('CHEBI:25835', 'Chemical') :: ['palmitate ester']

entities_list: @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine']

answer: @entity16864 :: (MESH:C548956,Chemical) :: ['paliperidone palmitate']


abstract: PURPOSE: To evaluate the efficacy and safety of the @entity1205 - @entity900 combination in @entity1 with advanced @entity1149 ( @entity1149 ). @entity1 AND METHODS: Chemotherapy-na  ve @entity1 with histologically confirmed, measurable stage IIIB or IV @entity1149 , a World Health Organization (WHO) performance status of 0-2 and adequate bone marrow, @entity8 were eligible for the study. @entity1 received @entity1205 (100 mg/m2) as an one-hour infusion on day 1 and @entity900 (80 mg/m2) as a 30-min infusion with appropriate hydration on day 2. @entity1261 ( @entity1261 ; 150 micrograms/m2, SC) was given on days 3 to 13. Treatment was repeated every three weeks. RESULTS: Fifty-three @entity1 were enrolled (28 with stage IIIB and 25 with stage IV). One complete and 23 partial responses were observed (overall response rate (OR): 45%; 95% CI: 34.1%-61.8%). The response rate was 57% and 32% in @entity1 with stages IIIB and IV disease (P = NS). The median time to progression was 36 weeks and the median survival 48 weeks; the one-year survival was 48%. Grade 3-4 @entity1398 occurred in 23 @entity1 , 15 of whom were hospitalized for @entity221 ; two @entity1 died of @entity295 . Grade 2 @entity2359 was observed in six @entity1 and grade 3 in five @entity1 ; grade 3 @entity1295 occurred in seven @entity1 , grade 3-4 @entity33 in four @entity1 and grade 3-4 @entity294 in six @entity1 . Mild @entity56 and @entity4 were observed in five and four @entity1 , respectively. The median dose intensity was 30 mg/m2/week for @entity1205 and 24 mg/m2/week for @entity900 , corresponding to 91% and 89% of the specified protocol doses, respectively. CONCLUSIONS: The @entity1205 - @entity900 combination is an active regimen in advanced @entity1149 , but @entity1503 remains high despite the prophylactic use of @entity1261 .

title: First-line treatment of advanced @entity1149 with @entity1205 and XXXX : a multicenter phase II study.

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

entities_list: @entity8 :: ('MESH:D007674', 'Disease') :: ['renal, hepatic and cardiac function']

entities_list: @entity1261 :: ('1440', 'Gene') :: ['G-CSF', 'Granulocyte colony-stimulating factor']

entities_list: @entity221 :: ('MESH:D005334', 'Disease') :: ['neutropenic fever']

entities_list: @entity294 :: ('MESH:D003967', 'Disease') :: ['diarrhea']

entities_list: @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small-cell lung cancer']

entities_list: @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin']

entities_list: @entity33 :: ('MESH:D052016', 'Disease') :: ['mucositis']

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

entities_list: @entity1503 :: ('MESH:D006402', 'Disease') :: ['hematologic toxicity']

entities_list: @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia']

entities_list: @entity56 :: ('MESH:D004342', 'Disease') :: ['allergic reactions']

entities_list: @entity1205 :: ('MESH:C067311', 'Chemical') :: ['docetaxel']

entities_list: @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity']

answer: @entity900 :: (MESH:D002945,Chemical) :: ['cisplatin']


abstract: Interrupted aortic arch with @entity1757 in the neonate is sometimes complicated by severe @entity475 from posterior deviation of the infundibular septum. We have developed a novel approach to the treatment of this condition. The infundibular septum is penetrated from the right-ventricular side to the left-ventricular outflow tract. It is compressed with patch fixation. The lower margin of the infundibular septum is everted. Three consecutive neonates were treated. The smallest diameters of the left-ventricular outflow tract were 3,4, and 2.5 mm. All @entity1 survived the operation and were discharged from the hospital. They remained well 2 to 7 years after the repair and were in normal sinus rhythm without a @entity714 or any significant pressure gradient between the upper and lower extremities. Follow-up two-dimensional and Doppler echocardiography demonstrated no residual shunt, no left-ventricular outflow-tract pressure gradient, and no @entity337 . This technique provides effective widening of the left-ventricular outflow tract, and is more safely and easily performed than conventional methods.

title: Everting closure for interrupted aortic arch, @entity1757 , and severe XXXX .

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

entities_list: @entity714 :: ('MESH:D002037', 'Disease') :: ['left bundle branch block']

entities_list: @entity1757 :: ('MESH:D006345', 'Disease') :: ['ventricular septal defect']

entities_list: @entity475 :: ('MESH:C564793', 'Disease') :: ['subaortic stenosis']

entities_list: @entity337 :: ('MESH:D001022', 'Disease') :: ['aortic regurgitation']

answer: @entity475 :: (MESH:C564793,Disease) :: ['subaortic stenosis']


abstract: OBJECTIVE: To investigate the effects of @entity63 preconditioning (PC) and @entity855 sensitive K+ channels (KATP(+) opener @entity7976 on @entity943 and electrophysiology. METHODS: Langendorff-perfused @entity35 hearts were subjected to @entity63 PC with three cycles of 2 minutes of global @entity63 or infusion of KATP(+) opener @entity7976 with subsequent 5 minutes global @entity63 and reperfusion. The incidence of @entity943 , @entity2224 ( @entity2224 ), effective refractory period (ERP) and monophasic action potential duration (MAPD) of the left and right ventricles were compared to those from control @entity35 hearts. RESULTS: The results indicated that PC reduced the incidence of @entity943 and @entity2224 during reperfusion (P < 0.05, vs controls). PC markedly delayed the onset of @entity943 after reperfusion (P < 0.01, vs controls). PC significantly enhanced the @entity2224 values during reperfusion and shortened the ERP and the MAPD during @entity63 . @entity2224 was restored more rapidly than that in controls. KATP+ opener @entity7976 neither reduced the incidence of @entity943 and VF nor delayed @entity943 onset. @entity7976 shortened ERP and MAPD90 without enhancing the @entity2224 values, and @entity2224 returned to normal as slowly as that in controls. CONCLUSIONS: We conclude that PC protects the globally @entity63 @entity35 hearts from @entity943 . The antiarrhythmic effect of PC is likely to be related to a significant increase of @entity2224 . KATP(+) opener @entity7976 has no potential antiarrhythmic action and KATP(+) channels may not play a major role in the antiarrhythmic effects of @entity63 PC in isolated @entity35 hearts.

title: Effects of @entity63 preconditioning on @entity943 and electrophysiology in isolated XXXX hearts: it is not a role of KATP(+) channels.

entities_list: @entity943 :: ('MESH:D001145', 'Disease') :: ['total arrhythmias', 'arrhythmia', 'reperfusion arrhythmias']

entities_list: @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia', 'ischemic']

entities_list: @entity2224 :: ('MESH:D014693', 'Disease') :: ['ventricular fibrillation', 'VFT', 'ventricular fibrillation threshold']

entities_list: @entity7976 :: ('MESH:D020108', 'Chemical') :: ['nicorandil', 'Nicorandil']

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


abstract: BACKGROUND: In 1995, the two-part National Institute of @entity16 and @entity64 (NINDS) Recombinant @entity1456 @entity64 Trial found that @entity1 who were treated with @entity3479 ) within three hours after the onset of symptoms of acute @entity385 were at least 30 percent more likely than @entity1 given placebo to have minimal or no disability three months after the @entity64 . It was unknown, however, whether the benefit would be sustained for longer periods. METHODS: In the NINDS Trial, a total of 624 @entity1 with @entity64 were randomly assigned to receive either @entity1456 or placebo. We collected outcome data over a period of 12 months after the occurrence of @entity64 . The primary outcome measure was a "favorable outcome," defined as minimal or no disability as measured by the Barthel index, the modified Rankin Scale, and the Glasgow Outcome Scale. We assessed the treatment effect using a global statistic. RESULTS: Using an intention-to-treat analysis for the combined results of the two parts of the trial at 6 months and 12 months, we found that the global statistic favored the @entity1456 group (odds ratio for a favorable outcome at 6 months, 1.7; 95 percent confidence interval, 1.3 to 2.3; odds ratio at 12 months, 95 percent confidence interval, 1.7; 1.2 to 2.3). The @entity1 treated with @entity1456 were at least 30 percent more likely to have minimal or no disability at 12 months than were the placebo-treated @entity1 (absolute increase in the proportion with a favorable outcome, 11 to 13 percentage points). There was no significant difference in mortality at 12 months between the @entity1456 group and the placebo group (24 percent vs. 28 percent, P=0.29). There was no interaction between the type of @entity64 identified at base line and treatment with respect to the long-term response. The rate of recurrent @entity64 at 12 months was similar in the two groups. CONCLUSIONS: During 12 months of follow-up, the @entity1 with acute @entity385 who were treated with @entity1456 within three hours after the onset of symptoms were more likely to have minimal or no disability, than the @entity1 given placebo. These results indicate a sustained benefit of @entity1456 for such @entity1 .

title: Effects of @entity1456 for acute XXXX at one year. National Institute of @entity16 and @entity64 Recombinant @entity1456 @entity64 Study Group.

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

entities_list: @entity16 :: ('MESH:D009422', 'Disease') :: ['Neurological Disorders']

entities_list: @entity1456 :: ('100128998', 'Gene') :: ['t-PA', 'Tissue Plasminogen Activator']

entities_list: @entity3479 :: ('5327', 'Gene') :: ['tissue plasminogen activator (t-PA']

entities_list: @entity385 :: ('MESH:D002544', 'Disease') :: ['ischemic stroke']

answer: @entity385 :: (MESH:D002544,Disease) :: ['ischemic stroke']


abstract: OBJECTIVES: Lepidic growth pattern @entity2220 commonly presents as a dominant lesion (DL) with associated pulmonary nodules either in the ipsilateral or contralateral lung fields, posing a challenge in clinical decision-making. These @entity5 may be clinically upstaged compared with those who present with solitary lesions and, as a result, may be offered different therapies. The purpose of this study is to compare recurrence rates, the development of new lesions and survival in @entity1 with @entity420 with a lepidic component presenting with a DL with or without additional nodules. METHODS: We performed a 13-year retrospective chart review of @entity1 with lepidic growth pattern @entity420 . @entity1 were grouped into a uninodular group (UG) if they presented with a solitary lesion and a @entity1376 ( @entity1376 ) if they had a DL with additional nodules. Clinicopathological features, outcomes and survival between the two groups were analysed. RESULTS: A total of 149 @entity1 were identified: 62 (42%) in the UG and 87 (58%) in the @entity1376 . In addition to the DL, 217 nodules were preoperatively identified in the @entity1376 : 60 were resected concomitantly with the DL, while 157 were radiologically surveyed. Invasive @entity420 was the predominant pathological cell type in both groups. The median time of follow-up was 3 years [interquartile range (IQR) 1.9-5.1]. Local (1 vs 2%), regional (1 vs 3%) and distant recurrences (7 vs 4%) were detected, respectively, in the UG and the @entity1376 . In the UG, 20 new lesions were identified, while in the @entity1376 there were 28. Only 4 of 157 (2.5%) surveyed pre-existing lesions were found to be malignant and required further treatment. No statistically significant differences were observed in 5-year disease-free and overall survival between the UG and the @entity1376 (82.3 vs 83.8%, P = 0.254 and 86.7 vs 93.8%, P = 0.096, respectively). CONCLUSIONS: We observed that @entity1 with lepidic growth pattern @entity420 presenting with a DL with associated secondary nodules appear to behave similarly to @entity1 with a solitary lesion. Multiple nodules including those that are malignant in this specific subset of @entity1149 should not be upstaged as @entity1442 and @entity1 should be treated with the same curative intent as those presenting with uninodular disease.

title: XXXX with multiple nodules and a dominant @entity2220 have similar outcomes and survival compared with @entity1 who have a solitary @entity420

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

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

entities_list: @entity1376 :: ('MESH:C564546', 'Disease') :: ['multinodular group', 'MG']

entities_list: @entity1149 :: ('MESH:D002289', 'Disease') :: ['non-small-cell lung cancer']

entities_list: @entity420 :: ('MESH:D000230', 'Disease') :: ['adenocarcinoma']

entities_list: @entity1442 :: ('MESH:D020178', 'Disease') :: ['advanced disease']

entities_list: @entity2220 :: ('MESH:C538231', 'Disease') :: ['lung adenocarcinoma']

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


abstract: BACKGROUND: Thromboxanes are produced in excess and platelets are activated in active @entity30 . Preliminary reports have suggested that @entity18648 , a dual @entity2871 synthase inhibitor and receptor antagonist, may have therapeutic benefit in @entity1 with @entity29 . AIMS: To investigate the efficacy of @entity18648 in @entity1 with active @entity30 . @entity1 AND METHODS: This was an international, multicentre, randomized, double-blind, placebo-controlled trial of 5 mg/day oral @entity18648 for 12 weeks in 85 @entity1 with moderately active @entity30 . Sixty @entity1 were randomized to receive @entity18648 , and 25 to placebo. The @entity30 activity index (CDAI) was used to assess disease activity: remission was defined as a CDAI < 150. Changes in clinical condition, as assessed by the Harvey-Bradshaw index, global evaluation by the investigator and the @entity1 , and blood measures of @entity32 , were used as secondary outcomes. RESULTS: The @entity1 ' mean (s.d.) CDAI at recruitment was 277 (68) in the @entity18648 treated group and 265 (70) in the placebo group. At their final assessment, 20 out of 60 (35%) @entity1 who had been given @entity18648 in an intention-to-treat analysis and seven out of 25 (28%) @entity1 given placebo were in remission (no significant difference). No significant differences in Harvey- Bradshaw index or global evaluation were noted between @entity1 given @entity18648 and those given placebo. Adverse events were similar in both groups. CONCLUSION: A 5-mg dose of oral @entity18648 was not more effective than placebo in inducing remission in @entity1 with moderately active @entity30 . If @entity2871 synthesis and platelet function are to be targeted for the treatment of @entity30 , more potent agents require development and assessment.

title: Lack of efficacy of @entity18648 , a @entity2871 synthase inhibitor, in a placebo-controlled, double-blind, multi-centre clinical trial in active XXXX .

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

entities_list: @entity2871 :: ('CHEBI:26995', 'Chemical') :: ['thromboxane']

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

entities_list: @entity29 :: ('MESH:D015212', 'Disease') :: ['inflammatory bowel disease']

entities_list: @entity30 :: ('MESH:D003424', 'Disease') :: ["Crohn's disease"]

answer: @entity30 :: (MESH:D003424,Disease) :: ['Crohn's disease']


abstract: OBJECTIVES: Initial gait speed is a good predictor of @entity303 in later life. This prospective study used repeated measures analysis to identify potential gait performance trajectory patterns and to determine whether gait performance trajectory patterns were associated with incident disabling @entity303 among community-dwelling older Japanese. DESIGN: A prospective, observational, population-based follow-up study. SETTING: Japan, 2002 to  2014. @entity1 : A total of 1686 adults without @entity303 (mean [SD] age, 71.2 [5.6] years; @entity1 , 56.3%) aged 65 to 90  years participated in annual geriatric health assessments during the period from June 2002 through July 2014. The average number of follow-up assessments was 3.9, and the total number of observations was  6509. MEASUREMENTS: Gait performance was assessed by measuring gait speed and step length at usual and maximum paces. A review of municipal databases in the Japanese public long-term care insurance system revealed that 196 (11.6%) @entity1 developed disabling @entity303 through December  2014. RESULTS: We identified 3 distinct trajectory patterns (high, middle, and low) in gait speed and step length at usual and maximum paces in adults aged 65 to 90  years; these trajectory patterns showed parallel declines among @entity1 and @entity1 . After adjusting for important confounders, @entity1 in the low trajectory groups for gait speed and step length at usual pace were 3.46 (95% confidence interval 1.88-6.40) and 2.12 (1.29-3.49) times as likely to develop incident disabling @entity303 , respectively, as those in the high trajectory group. The respective values for low trajectories of gait speed and step length at maximum pace were 2.05 (1.02-4.14) and 2.80 (1.48-5.28), respectively. CONCLUSIONS: Regardless of baseline level, the 3 major trajectory patterns for gait speed and step length tended to show similar age-related changes in @entity1 and @entity1 in later life. Individuals with low trajectories for gait speed and step length had a higher @entity303 risk, which highlights the importance of interventions for improvements in gait performance, even among older adults with low gait performance.

title: Gait Performance Trajectories and Incident Disabling XXXX Among Community-Dwelling Older Japanese.

entities_list: @entity303 :: ('MESH:D003704', 'Disease') :: ['dementia']

entities_list: @entity1 :: ('9606', 'Species') :: ['participants', 'women', 'PARTICIPANTS', 'men']

answer: @entity303 :: (MESH:D003704,Disease) :: ['Dementia']