nils-herrmann/clean_scirepeval huggingface dataset:
Role of endothelin-1 in exposure to high altitude: Acute Mountain Sickness and Endothelin-1 (ACME-1) study.

The degree of pulmonary hypertension in healthy subjects exposed to acute hypobaric hypoxia at high altitude was found to be related to increased plasma endothelin (ET)-1. The aim of the present study was to investigate the effects of ET-1 antagonism on pulmonary hypertension, renal water, and sodium balance under acute and prolonged exposure to high-altitude-associated hypoxia.



In a double-blind fashion, healthy volunteers were randomly assigned to receive bosentan (62.5 mg for 1 day and 125 mg for the following 2 days; n=10) or placebo (n=10) at sea level and after rapid ascent to high altitude (4559 m). At sea level, bosentan did not induce any significant changes in hemodynamic or renal parameters. At altitude, bosentan induced a significant reduction of systolic pulmonary artery pressure (21+/-7 versus 31+/-7 mm Hg, P<0.03) and a mild increase in arterial oxygen saturation versus placebo after just 1 day of treatment. However, both urinary volume and free water clearance (H2OCl/glomerular filtration rate) were significantly reduced versus placebo after 2 days of ET-1 antagonism (1100+/-200 versus 1610+/-590 mL; -6.7+/-3.5 versus -1.8+/-4.8 mL/min, P<0.05 versus placebo for both). Sodium clearance and segmental tubular function were not significantly affected by bosentan administration.



The present results indicate that the early beneficial effect of ET-1 antagonism on pulmonary blood pressure is followed by an impairment in volume adaptation. These findings must be considered for the prevention and treatment of acute mountain sickness.
Body fat and risk of colorectal cancer among postmenopausal women

Studies of the relationship between anthropometric indices of obesity and colorectal cancer risk in women have shown only weak and inconsistent associations. Given the limitations of such indices, we used dual-energy X-ray absorptiometry (DXA)-derived measures of body fat obtained in the Women’s Health Initiative to examine the association between body fat and risk of incident colorectal cancer. We compared these risk estimates with those obtained using conventional anthropometric measurements (body mass index and waist circumference). After exclusions, the study population consisted of 11,124 postmenopausal women with DXA measurements at baseline and no history of colorectal cancer. After a median follow-up period of 12.9 years, 169 incident colorectal cancer cases were ascertained. Cox’s proportional hazards models were used to estimate hazard ratios and 95 % confidence intervals for the exposures of interest. Neither DXA-derived body fat measures nor anthropometric measures showed significant associations with risk. In view of the limited number of cases, we cannot rule out the existence of weak associations of these measures with risk of colorectal cancer.
Inverse relationship between aldosterone and large artery compliance in chronically treated heart failure patients.

The purpose of this study was to examine, in chronically treated heart failure patients vs control subjects, the influence of neurohumoral activation and aldosterone escape on arterial elastic behaviour, assessed by non-invasive mathematical lumped-parameter modelling of the compliance of the arterial system.



Radial arterial pulse waves were recorded non-invasively for 30 s with an arterial tonometer sensor array in 13 chronic heart failure patients (mean age, 59 +/- 2.5 years) in New York Heart Association class II. The patients had been taking digoxin, furosemide, captopril and aspirin for more than 3 months. Thirteen healthy subjects (mean age, 50 +/- 4.0 years) acted as controls. Compliance of the proximal (aorta and major branches, C1) and distal parts (C2) of the circulation were derived from a third order four-element modified Windkessel model which can reproduce arterial pressure waveforms, including both exponential and oscillatory sections. Active renin, angiotensin II and aldosterone levels were determined on venous blood samples in the supine position and after 30 min active standing. There was decreased proximal (C1, 1.51 +/- 0.11 ml x mmHg(-1), P<0.01) and distal (C2, 0.050 +/- 0.011 ml x mmHg(-1)) arterial compliance in the chronic heart failure patients vs controls (C1, 1.71 +/- 0.16 ml x mmHg(-1); C2, 0.054 +/- 0.006 ml x mmHg(-1)). The chronic heart failure patients were characterized by an aldosterone escape phenomenon which was inversely correlated with the proximal arterial compliance in both supine (r= - 0.795, P=0.002) and standing (r= - 0.628, P=0.029) positions.



In chronically treated heart failure patients with full angiotensin-converting enzyme-inhibition and diuretics, there is decreased compliance of the aorta and its major branches, which is inversely correlated with the aldosterone escape phenomenon.
Is the combination of chromogranin A and pancreatic polypeptide serum determinations of interest in the diagnosis and follow-up of gastro-entero-pancreatic neuroendocrine tumours?

Chromogranin A (CgA) is the principal tumour marker for gastroenteropancreatic neuroendocrine tumours (GEPNET). Combining serum CgA and pancreatic polypeptide (PP) levels may increase the sensitivity of tumour markers in the diagnosis of GEPNET.



(1) To evaluate the sensitivity of PP and CgA in GEPNET. (2) To compare changes in serum CgA and PP levels with the morphological evolution of the tumours.



Sixty-six pancreatic and 49 gastrointestinal NET, with at least one serum determination of CgA and PP at the same time were retrieved from an institutional data base. Secondly, the variations in serum CgA or PP at successive determinations were compared to Response Evaluation Criteria in Solid Tumours (RECIST) criteria in 57 patients (112 follow-up visits) with high serum CgA levels and in 21 patients (37 follow-up visits) with high serum PP levels.



Among the 115 patients included in the study group, an increase in serum CgA (normal <98 μg/L) or PP (normal <100 pmol/L) was found in respectively 79 (69%) and 36 (31%) cases. Seven patients had normal CgA and elevated PP levels. Both markers were significantly more elevated in metastatic disease (74% versus 51% for CgA and 37% versus 18% for PP). The concordance rates between serum markers and RECIST criteria were 51% for CgA and 54% for PP.



Serum PP determination identify few false-negative results of serum CgA determination in GEPNET. Our study does not validate the use of CgA or PP as surrogate markers for detecting changes in tumour burden.
Safety and efficacy of fluticasone/formoterol combination therapy in adolescent and adult patients with mild-to-moderate asthma: a randomised controlled trial

This study investigated the efficacy and safety of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol; flutiform®), administered twice daily (b.i.d.) via a single aerosol inhaler, compared with its individual components administered separately and placebo, in patients with mild-to-moderate asthma.



Patients aged ≥ 12 years were evenly randomised to 12 weeks of treatment with fluticasone/formoterol (100/10 μg b.i.d.), fluticasone (100 μg b.i.d.), formoterol (10 μg b.i.d.), or placebo, in this double-blind, parallel group, multicentre study. The three co-primary endpoints were: a) change in forced expiratory volume in the first second (FEV(1)) from morning pre-dose at baseline to pre-dose at week 12 for the comparison with formoterol; b) change in FEV(1) from morning pre-dose at baseline to 2 hours post-dose at week 12 for the comparison with fluticasone, and c) time to discontinuation due to lack of efficacy from baseline to week 12 for the comparison with placebo. Safety was assessed based on adverse events, clinical laboratory tests and vital sign evaluations.



Statistically significant differences were demonstrated for all the three co-primary endpoints. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in pre-dose FEV(1) compared with formoterol (Least Squares (LS) mean treatment difference: 0.101 L; 95% Confidence Interval (CI): 0.002, 0.199; p = 0.045) and the change in pre-dose compared with 2 hours post-dose FEV(1) versus fluticasone (LS mean treatment difference: 0.200 L; 95% CI: 0.109, 0.292; p < 0.001). The time to discontinuation due to lack of efficacy was significantly longer for patients in the combination therapy group compared with those receiving placebo (p = 0.015). Overall, the results from multiple secondary endpoints assessing lung function, asthma symptoms, and rescue medication use supported the superior efficacy of the combination product compared with fluticasone, formoterol, and placebo. The fluticasone/formoterol combination therapy had a good safety and tolerability profile over the 12 week treatment period.



Fluticasone/formoterol had a good safety and tolerability profile and showed statistically superior efficacy for the three co-primary endpoints compared to fluticasone, formoterol, and placebo, in adolescents and adults with mild-to-moderate asthma. EudraCT number: 2007-002866-36; US NCT number: NCT00393991.
Formoterol Turbuhaler as reliever medication in patients with acute asthma.

The aim of this study was to compare the efficacy and safety of formoterol versus salbutamol as reliever medication in patients presenting at an emergency dept with acute asthma. A randomised, double-blind, double-dummy, parallel group study was performed in four Australian emergency treatment centres. The study included a total of 78 adult patients (mean baseline forced expiratory volume in one second (FEV1) 1.83 L; 59% predicted) with acute asthma. Based on the expected dose equivalence of formoterol Turbuhaler 4.5 microg (delivered dose) and salbutamol pressurised metered-dose inhaler 200 microg (metered dose), patients received a total of formoterol Turbuhaler 36 microg (delivered) or salbutamol pressurised metered-dose inhaler with spacer 1,600 microg (metered), divided into two equal doses at 0 and 30 min. FEV1, peak expiratory flow and systemic beta2-agonist effects were monitored for 4 h. The primary variable was FEV1% pred at 45 min. At 45 min, mean increases in FEV1 expressed in % pred were 6.6% and 9.3%, respectively, with a small adjusted mean difference in favour of salbutamol (3.0%, 95% confidence interval -2.0-8.0). Transient increases in systemic beta2-agonist effects occurred predominantly with salbutamol, although no significant treatment differences were observed. Eight patients discontinued due to adverse events. In this study of patients presenting at emergency depts with acute asthma, formoterol Turbuhaler 36 microg was well tolerated and, as rescue therapy, had an efficacy that was not different from that of salbutamol pressurised metered-dose inhaler with spacer 1,600 microg in the number of patients studied.
BReK12: a book recommender for K-12 users

Ideally, students in K-12 grade levels can turn to book recommenders to locate books that match their interests. Existing book recommenders, however, fail to take into account the readability levels of their users, and hence their recommendations may be unsuitable for the users. To address this issue, we introduce BReK12, a recommender that targets K-12 users and prioritizes the reading level of its users in suggesting books of interest. Empirical studies conducted using the Bookcrossing dataset show that BReK12 outperforms a number of existing recommenders (developed for general users) in identifying books appealing to K-12 users.
Higher circulating adiponectin levels are associated with increased risk of atrial fibrillation in older adults.

Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner.



We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74±5 years).



During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1-76, the HR (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05 to 1.24), while that for HMW adiponectin was 1.17 (1.08 to 1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids and inflammation, did not significantly affect these estimates.



The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age.
The effectiveness of antioxidant vitamins C and E in reducing myocardial infarct size in patients subjected to percutaneous coronary angioplasty (PREVEC Trial): study protocol for a pilot randomized double-blind controlled trial

Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Oxidative stress has been involved in the ischemia-reperfusion injury in AMI. It has been suggested that reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented.Therefore, we propose that antioxidant reinforcement through vitamins C and E supplementation should protect against the ischemia-reperfusion damage, thus decreasing infarct size.The PREVEC Trial (Prevention of reperfusion damage associated with percutaneous coronary angioplasty following acute myocardial infarction) seeks to evaluate whether antioxidant vitamins C and E reduce infarct size in patients subjected to percutaneous coronary angioplasty after AMI.



This is a randomized, 1:1, double-blind, placebo-controlled clinical trial.The study takes place at two centers in Chile: University of Chile Clinical Hospital and San Borja Arriarán Clinical Hospital.The subjects will be 134 adults with acute myocardial infarction with indication for percutaneous coronary angioplasty.This intervention is being performed as a pilot study, involving high-dose vitamin C infusion plus oral administration of vitamin E (Vitamin-treatment group) or placebo (Control group) during the angioplasty procedure. Afterward, the Vitamin-treatment group receives oral doses of vitamins C and E, and the Control group receives placebo for 84 days after coronary angioplasty.Primary outcome is infarct size, assessed by cardiac magnetic resonance (CMR), measured 6 and 84 days after coronary angioplasty.Secondary outcomes are ejection fraction, measured 6 and 84 days after coronary angioplasty with CMR, and biomarkers for oxidative stress, antioxidant status, heart damage, and inflammation, which will be measured at baseline, at the onset of reperfusion, 6 to 8 hours after revascularization, and at hospital discharge.



The ischemia-reperfusion event occurring during angioplasty is known to increase myocardial infarct size. The cardioprotective benefits of high doses of vitamin C combined with vitamin E have not been fully explored. The PREVEC Trial seeks to determine the suitability of the therapeutic use of vitamins C and E against the reperfusion damage produced during angioplasty.Patient recruitment opened in February 2013. The trial is scheduled to end in March 2016.
Long-term inhaled corticosteroids in preschool children at high risk for asthma.

It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma.



We randomly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate (at a dose of 88 mug twice daily) or masked placebo for two years, followed by a one-year period without study medication. The primary outcome was the proportion of episode-free days during the observation year.



During the observation year, no significant differences were seen between the two groups in the proportion of episode-free days, the number of exacerbations, or lung function. During the treatment period, as compared with placebo use, use of the inhaled corticosteroid was associated with a greater proportion of episode-free days (P=0.006) and a lower rate of exacerbations (P<0.001) and of supplementary use of controller medication (P<0.001). In the inhaled-corticosteroid group, as compared with the placebo group, the mean increase in height was 1.1 cm less at 24 months (P<0.001), but by the end of the trial, the height increase was 0.7 cm less (P=0.008). During treatment, the inhaled corticosteroid reduced symptoms and exacerbations but slowed growth, albeit temporarily and not progressively.



In preschool children at high risk for asthma, two years of inhaled-corticosteroid therapy did not change the development of asthma symptoms or lung function during a third, treatment-free year. These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued.
Monitoring of HIV type 1 DNA load and drug resistance in peripheral blood mononuclear cells during suppressive antiretroviral therapy does not predict virologic failure.

Our objective was to determine whether monitoring HIV-1 DNA concentration or new resistance mutations in peripheral blood mononuclear cells (PBMCs) during effective antiretroviral therapy (ART) predicts virologic failure. A retrospective analysis used blood specimens and clinical data from three nevirapine containing arms of a four-arm, open-label, randomized trial comparing ART regimens in HIV-1-infected children who had failed mono- or dual-nucleoside therapy. Sensitive assays compared cell-associated HIV-1 DNA concentrations and nevirapine (NVP) and lamivudine (3TC) resistance mutations in children with plasma HIV-1 RNA <400 copies(c)/ml who did or did not experience subsequent virologic failure. Forty-six children were analyzed through the last available follow-up specimen, collected at 48 (n=16) or 96 (n=30) weeks of ART. Thirty-five (76%) had sustained viral suppression and 11 (24%) had plasma viral rebound to ≥ 400 c/ml (virologic failure detected at a median of 36 weeks). HIV-1 DNA levels at baseline, 24, 48, and 96 weeks of ART were similar in children who did vs. did not experience virologic failure (p=0.82). HIV-1 DNA levels did not increase prior to viral rebound. NVP resistance mutations were detected in 91% of subjects in the failure group vs. 3% in the suppressed group (p <0.0001). Among nine evaluable children, NVP mutations were first detected prior to virologic failure in two (22%), at viral rebound in five (56%), and after failure in two (22%) children. HIV-1 DNA concentrations did not predict virologic failure in this cohort. New drug resistance mutations were detected in the PBMCs of a minority of virologically suppressed children who subsequently failed ART.
Definition of ambulatory blood pressure targets for diagnosis and treatment of hypertension in relation to clinic blood pressure: prospective cohort study

Twenty-four hour ambulatory blood pressure thresholds have been defined for the diagnosis of mild hypertension but not for its treatment or for other blood pressure thresholds used in the diagnosis of moderate to severe hypertension. We aimed to derive age and sex related ambulatory blood pressure equivalents to clinic blood pressure thresholds for diagnosis and treatment of hypertension.



We collated 24 hour ambulatory blood pressure data, recorded with validated devices, from 11 centres across six Australian states (n=8575). We used least product regression to assess the relation between these measurements and clinic blood pressure measured by trained staff and in a smaller cohort by doctors (n=1693).



Mean age of participants was 56 years (SD 15) with mean body mass index 28.9 (5.5) and mean clinic systolic/diastolic blood pressure 142/82 mm Hg (19/12); 4626 (54%) were women. Average clinic measurements by trained staff were 6/3 mm Hg higher than daytime ambulatory blood pressure and 10/5 mm Hg higher than 24 hour blood pressure, but 9/7 mm Hg lower than clinic values measured by doctors. Daytime ambulatory equivalents derived from trained staff clinic measurements were 4/3 mm Hg less than the 140/90 mm Hg clinic threshold (lower limit of grade 1 hypertension), 2/2 mm Hg less than the 130/80 mm Hg threshold (target upper limit for patients with associated conditions), and 1/1 mm Hg less than the 125/75 mm Hg threshold. Equivalents were 1/2 mm Hg lower for women and 3/1 mm Hg lower in older people compared with the combined group.



Our study provides daytime ambulatory blood pressure thresholds that are slightly lower than equivalent clinic values. Clinic blood pressure measurements taken by doctors were considerably higher than those taken by trained staff and therefore gave inappropriate estimates of ambulatory thresholds. These results provide a framework for the diagnosis and management of hypertension using ambulatory blood pressure values.
A phase II study of vinorelbine and estramustine in patients with hormone-resistant prostate cancer.

This phase II study was designed to evaluate the efficacy of vinorelbine in combination with estramustine in patients with chemotherapy-naïve hormone-refractory prostate cancer.



Patients received vinorelbine (i.v. 25 mg/m2) on days 1 and 8 every 3 weeks and estramustine (oral, 600 mg/m2) daily. Eligible patients were required to have progressive metastatic disease following the first hormonal manipulation.



Of the 51 patients enrolled (median age = 69 years), 84% presented bone involvement and 75% had at least two organs involved at the time of study entry and 47 were evaluable for treatment efficacy. Prostate specific antigen (PSA) response (> or =50% decrease) which was the primary efficacy criterion was reported in 21 patients (41.2%) in the intent-to-treat (ITT) population and in 20 patients (48.8%) in the per protocol (PP) population. Of the 7 patients with measurable disease, 2 achieved partial response. Median progression-free survival and overall survival were 4.7 months (range: 1.9-8.6) and 14.3 months (range: 4.2-21.2), respectively. Grade 3-4 neutropenia was reported in 6.1% of patients and in 1% of cycles. The incidence of complicated neutropenia (febrile neutropenia reported in 1 patient and septic shock with severe neutropenia reported in 2 patients) was 5.8%. The most frequent grade 3-4 non-haematological events (% of patients > or =5%) included anorexia (10%), thrombosis/embolism (8%), vomiting and hypotension (6% each). There were 3 toxic deaths (5.9 %) resulting from pulmonary embolism, angina pectoris, and septic shock. The impact of combined chemotherapy on the quality-of-life (QL) of the patients was assessed between baseline and the first evaluation scheduled at 6 weeks indicated a marked reduction in pain while the rest of the symptoms remained stable. Overall, health status improved slightly over the treatment period.



This study confirmed that the combination of vinorelbine and estramustine is an active regimen in patients with hormone-resistant prostate cancer who had not been treated previously with chemotherapy. Main toxicities included complicated neutropenia even though the incidence of severe neutropenia was low. We observed a higher incidence of toxic deaths which could have been related to the regimen of estramustine used in the study.