nils-herrmann/clean_scirepeval huggingface dataset:
Common and rare variants in SCN10A modulate the risk of atrial fibrillation.

Genome-wide association studies have shown that the common single nucleotide polymorphism rs6800541 located in SCN10A, encoding the voltage-gated Nav1.8 sodium channel, is associated with PR-interval prolongation and atrial fibrillation (AF). Single nucleotide polymorphism rs6800541 is in high linkage disequilibrium with the nonsynonymous variant in SCN10A, rs6795970 (V1073A, ). We therefore sought to determine whether common and rare SCN10A variants are associated with early onset AF.



SCN10A was sequenced in 225 AF patients in whom there was no evidence of other cardiovascular disease or dysfunction (lone AF). In an association study of the rs6795970 single nucleotide polymorphism variant, we included 515 AF patients and 2 control cohorts of 730 individuals free of AF and 6161 randomly sampled individuals. Functional characterization of SCN10A variants was performed by whole-cell patch-clamping. In the lone AF cohort, 9 rare missense variants and 1 splice site donor variant were detected. Interestingly, AF patients were found to have higher G allele frequency of rs6795970, which encodes the alanine variant at position 1073 (described from here on as A1073, odds ratio =1.35 [1.16-1.54]; P=2.3×10(-5)). Both of the common variants, A1073 and P1092, induced a gain-of-channel function, whereas the rare missense variants, V94G and R1588Q, resulted in a loss-of-channel function.



The common variant A1073 is associated with increased susceptibility to AF. Both rare and common variants have effect on the function of the channel, indicating that these variants influence susceptibility to AF. Hence, our study suggests that SCN10A variations are involved in the genesis of AF.
Risk factors for intraventricular hemorrhage in very low birth weight premature infants: a retrospective case-control study.

High-grade intraventricular hemorrhage (IVH) is an important cause of severe cognitive and motor neurologic impairment in very low birth weight infants and is associated with a high mortality rate. The risk of IVH is inversely related to gestational age and birth weight. Previous studies have proposed a number of risk factors for IVH; however, lack of adequate matching for gestational age and birth weight may have confounded the results. The purpose of this study was to identify variables that affect the risk of high-grade IVH, using a retrospective and case-control clinical study.



From a cohort of 641 consecutive preterm infants with a birth weight of <1500 g, 36 infants with IVH grade 3 and/or 4 were identified. A control group of 69 infants, closely matched for gestational age and birth weight, was selected. Maternal factors, labor and delivery characteristics, and neonatal parameters were collected in both groups. Results of cranial ultrasound examinations, whether routine or performed in presence of clinical suspicion, were also collected. Univariate analysis and multivariate logistic regression analysis were performed.



High fraction of inspired oxygen in the first 24 hours, pneumothorax, fertility treatment (mostly IVF), and early sepsis were associated with an increased risk of IVH. A higher number of suctioning procedures, a higher first hematocrit, and a relatively low arterial pressure of carbon dioxide during the first 24 hours of life were associated with a lower occurrence. In the multivariate logistic regression model, early sepsis (odds ratio [OR]: 8.19; 95% confidence interval [CI]: 1.55-43.1) and fertility treatment (OR: 4.34; 95% CI: 1.42-13.3) were associated with a greater risk of high-grade IVH, whereas for every dose of antenatal steroid treatment there was a lower risk of high-grade IVH (OR: 0.52; 95% CI: 0.30-0.90) and each decrease in a mmHg unit of arterial pressure of carbon dioxide during the first 24 hours was associated with a lower risk of IVH (OR: 0.91; 95% CI: 0.83-0.98). This multivariate model had a sensitivity of 77%, a specificity of 75%, and a positive predictive value of 76%. The area under the curve derived from the receiver operator characteristic plots is 0.82.



Our results confirm that the development of IVH is associated with early sepsis and failure to give antenatal steroid treatment. We propose that fertility treatment (and especially IVF) may be a new risk factor, and more research is needed to assess its role.
A Phase I Randomized Clinical Trial of Candidate Human Immunodeficiency Virus type 1 Vaccine MVA.HIVA Administered to Gambian Infants

A vaccine to decrease transmission of human immunodeficiency virus type 1 (HIV-1) during breast-feeding would complement efforts to eliminate infant HIV-1 infection by antiretroviral therapy. Relative to adults, infants have distinct immune development, potentially high-risk of transmission when exposed to HIV-1 and rapid progression to AIDS when infected. To date, there have been only three published HIV-1 vaccine trials in infants.



We conducted a randomized phase I clinical trial PedVacc 001 assessing the feasibility, safety and immunogenicity of a single dose of candidate vaccine MVA.HIVA administered intramuscularly to 20-week-old infants born to HIV-1-negative mothers in The Gambia.



Infants were followed to 9 months of age with assessment of safety, immunogenicity and interference with Expanded Program on Immunization (EPI) vaccines. The trial is the first stage of developing more complex prime-boost vaccination strategies against breast milk transmission of HIV-1.



From March to October 2010, 48 infants (24 vaccine and 24 no-treatment) were enrolled with 100% retention. The MVA.HIVA vaccine was safe with no difference in adverse events between vaccinees and untreated infants. Two vaccine recipients (9%) and no controls had positive ex vivo interferon-γ ELISPOT assay responses. Antibody levels elicited to the EPI vaccines, which included diphtheria, tetanus, whole-cell pertussis, hepatitis B virus, Haemophilus influenzae type b and oral poliovirus, reached protective levels for the vast majority and were similar between the two arms.



A single low-dose of MVA.HIVA administered to 20-week-old infants in The Gambia was found to be safe and without interference with the induction of protective antibody levels by EPI vaccines, but did not alone induce sufficient HIV-1-specific responses. These data support the use of MVA carrying other transgenes as a boosting vector within more complex prime-boost vaccine strategies against transmission of HIV-1 and/or other infections in this age group.
Optimum BMI Cut Points to Screen Asian Americans for Type 2 Diabetes

Asian Americans manifest type 2 diabetes at low BMI levels but may not undergo diagnostic testing for diabetes if the currently recommended BMI screening cut point of ≥25 kg/m(2) is followed. We aimed to ascertain an appropriate lower BMI cut point among Asian-American adults without a prior diabetes diagnosis.



We consolidated data from 1,663 participants, ages ≥45 years, without a prior diabetes diagnosis, from population- and community-based studies, including the Mediators of Atherosclerosis in South Asians Living in America study, the North Kohala Study, the Seattle Japanese American Community Diabetes Study, and the University of California San Diego Filipino Health Study. Clinical measures included a 2-h 75-g oral glucose tolerance test, BMI, and glycosylated hemoglobin (HbA1c).



Mean age was 59.7 years, mean BMI was 25.4 kg/m(2), 58% were women, and type 2 diabetes prevalence  was 16.9%. At BMI ≥25 kg/m(2), sensitivity (63.7%), specificity (52.8%), and Youden index (0.16) values were low; limiting screening to BMI ≥25 kg/m(2) would miss 36% of Asian Americans with type 2 diabetes. For screening purposes, higher sensitivity is desirable to minimize missing cases, especially if the diagnostic test is relatively simple and inexpensive. At BMI ≥23 kg/m(2), sensitivity (84.7%) was high in the total sample and by sex and Asian-American subgroup and would miss only ∼15% of Asian Americans with diabetes.



The BMI cut point for identifying Asian Americans who should be screened for undiagnosed type 2 diabetes should be <25 kg/m(2), and ≥23 kg/m(2) may be the most practical.
Combined Alkaline Phosphatase and Phosphorus Levels as a Predictor of Mortality in Maintenance Hemodialysis Patients

Hyperphosphatemia-induced vascular calcification and higher alkaline phosphatase (ALP) levels-related high-turnover bone diseases are linked to mortality among patients with chronic kidney disease (CKD). Nonetheless, no large epidemiological study in patients with CKD has been conducted to investigate the interaction and joint effect of hyperphosphatemia and higher ALP levels on mortality.We analyzed 11,912 maintenance hemodialysis patients from January 2005 to December 2010. Unadjusted and adjusted hazard ratios (aHRs) of death were calculated for different categories of serum phosphorus and ALP using the Cox regression model. The modification effect between serum phosphorus and ALP on mortality was determined using an interaction product term.Both hypophosphatemia (<3.0 mg/dL) and hyperphosphatemia (>7.0 mg/dL) were associated with incremental risks of death (aHR: 1.25 [95% confidence intervals (CIs): 1.09-1.44], and 1.15 [95% CI: 1.01-1.31], respectively) compared to the lowest hazard ratio (HR) group (5 mg/dL ≤ phosphorus<6 mg/dL). ALP levels were linearly associated with incremental risks for death (aHR: 1.58 [95% CI: 1.41-1.76] for the category of ALP>150 U/L). In the stratified analysis, patients with combined higher ALP (>150 U/L) and hyperphosphatemia (>7.0 mg/dL) had the greatest mortality risk (aHR: 2.25 [95% CI: 1.69-2.98] compared to the lowest HR group (ALP ≤ 60 U/L and 4 mg/dL ≤ phosphorus<5 mg/dL). Although the effect of hyperphosphatemia on mortality seemed stronger in higher ALP levels, the interaction was not statistically significant (P=0.22).The association between serum phosphorus levels and mortality was not limited to higher ALP levels. Regardless of serum ALP levels, we may control serum phosphorus levels merely toward the normal range. While considering the joint effect of ALP and hyperphosphatemia on mortality, the optimal phosphorus range should be stricter.
A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy

Safe, effective and convenient antiemetic regimens that preserve benefit over repeated cycles are needed for optimal supportive care during cancer treatment. NEPA, an oral fixed-dose combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron (PALO), a distinct 5-HT3 RA, was shown to be superior to PALO in preventing chemotherapy-induced nausea and vomiting after a single cycle of highly (HEC) or moderately (MEC) emetogenic chemotherapy in recent trials. This study was designed primarily to assess the safety but also to evaluate the efficacy of NEPA over multiple cycles of HEC and MEC.



This multinational, double-blind, randomized phase III study (NCT01376297) in 413 chemotherapy-naïve patients evaluated a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) given on day 1 with oral dexamethasone (DEX). An oral 3-day aprepitant (APR) regimen + PALO + DEX was included as a control (3:1 NEPA:APR randomization). In HEC, DEX was administered on days 1-4 and in MEC on day 1. Safety was assessed primarily by adverse events (AEs), including cardiac AEs; efficacy by complete response (CR: no emesis, no rescue).



Patients completed 1961 total chemotherapy cycles (76% MEC, 24% HEC) with 75% completing ≥4 cycles. The incidence/type of AEs was comparable for both groups. Most frequent NEPA-related AEs included constipation (3.6%) and headache (1.0%); there was no indication of increasing AEs over multiple cycles. The majority of AEs were mild/moderate and there were no cardiac safety concerns based on AEs and electrocardiograms. The overall (0-120 h) CR rates in cycle 1 were 81% and 76% for NEPA and APR + PALO, respectively, and antiemetic efficacy was maintained over repeated cycles.



NEPA, a convenient single oral dose antiemetic targeting dual pathways, was safe, well tolerated and highly effective over multiple cycles of HEC/MEC.
A Community Jury on PSA screening: what do well-informed men want the government to do about prostate cancer screening—a qualitative analysis

Cancer screening policies and programmes should take account of public values and concerns. This study sought to determine the priorities, values and concerns of men who were 'fully informed' about the benefits and harms of prostate-specific antigen (PSA) screening; and empirically examine the value of a community jury in eliciting public values on PSA screening.



Community jury was convened on the Gold Coast, Queensland (Australia) to consider PSA screening benefits and harms, and whether government campaigns on PSA screening should be conducted.



27 men (volunteers) aged 50-70 with no personal history of prostate cancer and willing to attend jury 6-7 April 2013: 12 were randomly allocated to jury (11 attended).



A qualitative analysis was conducted of the jury deliberations (audio-recorded and transcribed) to elicit the jury's views and recommendations. A survey determined the impact of the jury process on participants' individual testing decisions compared with control group.



The jury concluded governments should not invest in programmes focused on PSA screening directed at the public because the PSA test did not offer sufficient reassurance or benefit and could raise unnecessary alarm. It recommended an alternative programme to support general practitioners to provide patients with better quality and more consistent information about PSA screening. After the jury, participants were less likely to be tested in the future compared with the controls, but around half said they would still consider doing so.



The jury's unanimous verdict about government programmes was notable in the light of their divergent views on whether or not they would be screened themselves in the future. Community juries provide valuable insights into the priorities and concerns of men weighing up the benefits and harms of PSA screening. It will be important to assess the degree to which the findings are generalisable to other settings.
Attributable risks for acute myocardial infarction in four countries of Latin America.

This multicenter case control study investigated, in four countries of America, the proportions of acute myocardial infarction (AMI) attributable to cholesterol, smoking, hypertension, body mass index, diabetes and family history of coronary heart disease (attributable risks, AR). AR were estimated using information from 1060 cases of AMI and 1071 controls from Argentina, 323 cases of AMI and 314 controls from Cuba, 200 cases of AMI and 200 controls from Mexico and 266 cases of AMI and 264 controls from Venezuela. AR were obtained from the prevalence of coronary risk factors in the cases and the corresponding Odds Ratio (OR) derived through appropriate multivariate models. The AR for AMI observed for hypercholesterolaemia were the following: Venezuela 27%, Mexico 3%, Cuba 30% and Argentina 36%; for diabetes: Venezuela 10%, Mexico 15%, Cuba 5% and Argentina 7% and for body mass Index: Venezuela 12%, Mexico 3%, Cuba 19% and Argentina 17%. The same risk factor may have a different attributable risk in different populations. Together, hypercholesterolaemia, hypertension, smoking, diabetes, body mass index and family history of coronary heart disease accounted for 76% of all cases of AMI in Venezuela, 70% in Mexico, 81% in Cuba and 79% in Argentina. The knowledge of attributable risks could have important implications for public health strategies, especially in those countries with limited health care resources.
Prevalence of electrocardiographic abnormalities in a middle-aged, biracial population: Coronary Artery Risk Development in Young Adults study.

Few studies to date have described the prevalence of electrocardiographic (ECG) abnormalities in a biracial middle-aged cohort.



Participants underwent measurement of traditional risk factors and 12-lead ECGs coded using both Minnesota Code and Novacode criteria. Among 2585 participants, of whom 57% were women and 44% were black (mean age 45 years), the prevalence of major and minor abnormalities was significantly higher (all P < .001) among black men and women compared to whites. These differences were primarily due to higher QRS voltage and ST/T-wave abnormalities among blacks. There was also a higher prevalence of Q waves (Minnesota Code 1-1, 1-2, 1-3) than described by previous studies. These racial differences remained after multivariate adjustment for traditional cardiovascular (CV) risk factors.



Black men and women have a significantly higher prevalence of ECG abnormalities, independent of traditional cardiovascular risk factors, than whites in a contemporary cohort of middle-aged participants.
Levosimendan in decompensated heart failure patients: efficacy in a Brazilian cohort. Results of the BELIEF study.

Levosimendan is a new inodilatory agent that enhances cardiac contractility via Ca(2+) sensitization and induces vasodilation through the activation of KATP/BKCa.



To study the efficacy and safety of levosimendan in a decompensated heart failure (DHF) Brazilian cohort, and in b-adrenergic agonist resistant patients.



The Brazilian Evaluation of Levosimendan Infusion Efficacy (BELIEF) study was prospective, multicenter, observational and included 182 high-risk DHF patients, all of which received open-label levosimendan. Primary end point was hospital discharge without additional inotropic therapy (responder). Secondary end points were changes in hemodynamics, clinical parameters, and brain natriuretic peptide (BNP).



Mortality rate was 14.8%, and 139 of 182 patients were responders. In non responders it was 62.8%. Systolic blood pressure was a predictor of response. In b-adrenergic agonist resistant group, 55.8% were responders. Overall, 54 patients experienced at least one adverse event; most of them resolved either spontaneously or after levosimendan dose reduction. A significant improvement in quality of life was verified at 2-6 months of follow-up (p<0.0001).



Our results suggest levosimendan infusion as an alternative therapy in the short term management of DHF patients. HF severity can influence the response to levosimendan treatment. Prospective studies are warranted in a Brazilian cohort including Chagas heart disease.
Brachial artery flow-mediated dilation and asymmetrical dimethylarginine in the cardiovascular risk in young Finns study.

Elevated asymmetrical dimethylarginine (ADMA) is a novel risk factor for atherosclerosis that may impair endothelial function by interfering with endothelial nitric oxide synthesis. To gain insight into the effects of ADMA on systemic endothelial function, we examined the association between ADMA and brachial artery flow-mediated dilation (FMD) in a large population of young adults.



Plasma ADMA and brachial FMD, as well as conventional cardiovascular risk factors, were measured in 2096 white adults aged 24 to 39 years. In univariate analysis, ADMA was inversely correlated with FMD (r=-0.07, P=0.003). The inverse association between ADMA and FMD remained significant in a multivariable regression model adjusted for age, sex, conventional cardiovascular risk factors, estimated glomerular filtration rate, and brachial artery baseline diameter (beta+/-SE -1.56+/-0.62%, P=0.01).



We conclude that elevated plasma ADMA concentrations are associated with decreased brachial FMD responses in healthy adults. These data provide evidence at the population level that ADMA levels are associated with endothelial function.
Evaluation of an intervention to reduce sun exposure in children: design and baseline results.

The Kidskin Study is a 5-year intervention study (1995-1999) involving 1,776 5- and 6-year-old children attending 33 primary schools in Perth, Western Australia. The aim of the study is to design, implement, and evaluate an intervention to reduce sun exposure in young children. There are three study groups: a control group, a "moderate intervention" group, and a "high intervention" group. The control schools receive the standard Western Australian health education curriculum, while the moderate and high intervention schools receive a specially designed curricular intervention. In addition, children in the high intervention group receive program materials over the summer holidays, when exposure is likely to be highest, and are offered sun-protective swimwear at low cost. The main outcome measure is the number of nevi on the back. Other outcomes include nevi on the chest (boys only), face, and arms, levels of suntanning, degree of freckling, and sun-related behaviors. At baseline, the three groups were similar with respect to nevi and freckling after adjustment for observer and month of observation. Sun exposure was slightly higher in the high intervention group. The groups were also similar with respect to most potential confounders, although they differed with respect to Southern European ethnicity and parental education.
Functional Assessment Taxonomy Relevant to Low-Back Impairments

A taxonomy of functional assessment constructs was developed to help the Social Security Administration refine the measurements of work disability. This report addresses content validity of the new taxonomy by examining the relevance of its constructs to a specific disability, and by examining the relationship between these constructs and constructs in other taxonomies. Seven experts linked the new taxonomy to consequences of low-back impairments. The selected constructs were compared to those reported independently by patients (Harper AC, Harper DA, Lambert L, Andrews HB, Lo SK, Ross FM, Straker LM. Pain 1992; 50(2): 189–195). The International Classification of Impairments, Disabilities and Handicaps served to bridge the two exercises. The findings reveal that it is feasible to use the taxonomy to define the impact of a specific disability and consequently link it to a set of standard measurements. Low-back impairments may be best assessed through measures of physical functional limitations, vocational impact, and interpersonal and emotional behavior. The study did not yield cognitive and intellectual measures that were relevant to this impairment.