Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional effects of naturally occurring KCNJ11 mutations causing neonatal diabetes on cloned cardiac KATP channels

ATP‐sensitive K+ (KATP) channels are hetero‐octamers of inwardly rectifying K+ channel (Kir6.2) and sulphonylurea receptor subunits (SUR1 in pancreatic β‐cells, SUR2A in heart). Heterozygous gain‐of‐function mutations in Kir6.2 cause neonatal diabetes, which may be accompanied by epilepsy and developmental delay. However, despite the importance of KATP channels in the heart, patients have no obvious cardiac problems. We examined the effects of adenine nucleotides on KATP channels containing wild‐type or mutant (Q52R, R201H) Kir6.2 plus either SUR1 or SUR2A. In the absence of Mg2+, both mutations reduced ATP inhibition of SUR1‐ and SUR2A‐containing channels to similar extents, but when Mg2+ was present ATP blocked mutant channels containing SUR1 much less than SUR2A channels. Mg‐nucleotide activation of SUR1, but not SUR2A, channels was markedly increased by the R201H mutation. Both mutations also increased resting whole‐cell KATP currents through heterozygous SUR1‐containing channels to a greater extent than for heterozygous SUR2A‐containing channels. The greater ATP inhibition of mutant Kir6.2/SUR2A than of Kir6.2/SUR1 can explain why gain‐of‐function Kir6.2 mutations manifest effects in brain and β‐cells but not in the heart.
Perceived Control and Adaptation in Elder Caregivers: Development of an Explanatory Model

Perceived control has been implicated in the adaptation and well-being of older adults and may be especially relevant to elder caregivers. However, few studies have investigated perceived control within the individual's unique personal, social, and environmental context. This study tested a model representing the hypothesis that perceived control, defined as the perception that salient or valued aspects of one's life are manageable, mediates the objective and subjective aspects of caregiving and caregiver adaptation. Sixty elderly caregivers ranging in age from sixty to eighty-four (M = 69.4) were interviewed. Perceived control had a direct relationship with life satisfaction and depression, and an indirect relationship with subjective symptoms of stress. Wishful thinking coping behavior had a negative relationship with all adaptation variables. Findings are discussed in relation to further refinement and development of a theoretical approach to caregiver research and intervention studies in light of the obtained path model.
Meta-Analysis of First-Line Therapies in Advanced Non–Small-Cell Lung Cancer Harboring EGFR-Activating Mutations

Introduction: Tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib have been compared with chemotherapy as first-line therapies for patients with advanced non–small-cell lung cancer harboring epidermal growth factor receptor–activating mutations. This meta-analysis compares gefitinib, erlotinib, afatinib, and chemotherapy. Methods: Literature search was performed using relevant keywords. Direct and indirect meta-estimates were generated using log-linear mixed-effects models, with random effects for study. Study-to-study heterogeneity was summarized using I2 statistics and predictive intervals (PIs). Results: Literature search yielded eight randomized phase 3 clinical trials comparing gefitinib, erlotinib, or afatinib with chemotherapy as first-line therapy in patients with advanced non–small-cell lung cancer during the last 5 years. Hazard ratio meta-estimates for progression-free survival were for gefitinib versus chemotherapy 0.44 (95% confidence interval [CI] 0.31–0.63; 95% PI, 0.22–0.88), erlotinib versus chemotherapy 0.25 (95% CI, 0.15–0.42; 95% PI, 0.11–0.55), afatinib versus chemotherapy 0.44 (95% CI, 0.26–0.75; 95% PI, 0.20–0.98), erlotinib versus gefitinib 0.57 (95% CI, 0.30–1.08; 95% PI, 0.24–1.36), afatinib versus gefitinib 1.01 (95% CI, 0.53–1.92; 95% PI, 0.41–2.42), and erlotinib versus afatinib 0.56 (95% CI, 0.27–1.18; 95% PI, 0.22–1.46). Results for overall response rate and disease control rate were similar. There was no evidence that gefitinib, erlotinib, or afatinib improved overall survival compared with chemotherapy. Conclusion: Gefitinib, erlotinib, and afatinib out-performed chemotherapy in terms of progression-free survival, overall response rate, and disease control rate. Differences among gefitinib, erlotinib, and afatinib were not statistically significant.
Psychometric Validation of the Anticipated Effects of Alcohol Mixed With Energy Drinks Scale

Young people are increasingly consuming alcohol mixed with energy drinks (AmEDs). As coingestion of these beverages results in greater adverse consequences than from drinking alcohol alone, we need to understand what factors contribute to and deter coingestion. Existing studies in this area have not utilized a theoretically based or empirically validated measure of outcome expectancies for drinking AmEDs. Our study modified Morean, Corbin, and Treat’s (2012) Anticipated Effects of Alcohol Scale to assess the expected effects of drinking AmEDs. We evaluated the factor structure and concurrent validity of the Anticipated Effects of Alcohol Mixed with Energy Drinks (AEAMEDS) among 549 university students, aged 18–25, who had a lifetime history of consuming alcohol (231 had consumed AmEDs in the past 90 days). Exploratory and confirmatory factor analysis supported a 4-factor structure. Consistent with hypotheses, stronger high arousal/positive expectancies and weaker low arousal/negative expectancies were associated with greater AmED use. At the bivariate level, stronger low arousal/positive expectancies were associated with greater quantities of AmED use, but this relationship disappeared when taking into account other outcome expectancies. Moreover, students expected low arousal/positive expectancies to be less intense when consuming AmEDs than alcohol alone, but ratings for all other AmED expectancies were equivalent to consuming alcohol alone. These findings contribute to our knowledge of risk and protective factors for AmED use.
Minimum schedule lengths with rate control in wireless networks

In this paper, we study the problem of joint scheduling and rate control in wireless networks, when each transmitter has a finite amount of data traffic to deliver to its corresponding receiver. Our objective is to minimize the time required to deliver the total data traffic. The scheduling decisions take into account the constraints of the physical layer through the well-known physical interference model. First, we consider a time-slotted system. We provide an optimal solution through a graph-theoretic model, where the minimum-length scheduling problem is formulated as finding a shortest path on a single source directed acyclic graph. Next, due to the complexity of the discrete time problem, we simplify it in two dimensions: (i) we map it to a continuous time problem, and (ii) we restrict the set of feasible scheduling and rate control decisions that can be employed. We finally obtain an optimal scheduling and rate control policy of this simplified problem.
Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models

Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis. A mAb that neutralizes mouse uPA significantly reduced arthritis progression in the CIA and delayed-type hypersensitivity arthritis models. In the CIA model, the impact of anti-uPA treatment was on par with the effect of blocking TNF-α by etanercept. A pharmacokinetics evaluation of the therapeutic Ab revealed target-mediated drug disposition consistent with a high turnover of endogenous uPA. The cellular expression patterns of uPA and uPAR were characterized by double immunofluorescence in the inflamed synovium from patients with rheumatoid arthritis and compared with synovium from healthy donors. The arthritic synovium showed expression of uPA and uPAR in neutrophils, macrophages, and a fraction of endothelial cells, whereas there was little or no expression in synovium from healthy donors. The data from animal models and human material provide preclinical proof-of-principle that validates uPA as a novel therapeutic target in rheumatic diseases.
Comparisons of Safety and Clinical Outcomes Between Multiple-level and Single-level Cervical Disk Replacement for Cervical Spondylosis: A Systematic Review and Meta-analysis

Study Design:This is a systematic review and meta-analysis. Objective:The aim of this study was to evaluate the efficacy and safety of multiple-level cervical disk replacement (CDR) over single-level CDR for the treatment of cervical spondylosis. Summary of Background Data:Some authors advocate for the multiple-level CDR instead of anterior decompression and fusion in cervical multiple-level spondylosis. However, whether the efficacy and safety of multi-level CDR are as favorable as that of single-level CDR remains controversial. Methods:MEDLINE, EMBASE, and Cochrane library databases were searched up to November 2015 for controlled studies that compared the clinical outcomes of single-level and multiple-level CDR for the treatment of cervical spondylosis. The following outcomes were extracted and analyzed: prevalence of heterotopic ossification and reoperation, preoperative and postoperative Neck Disability Index scores, preoperative and postoperative Visual Analog Scale scores, and success rate using the Odom grading system. Results:Ten studies involving 1402 patients were included: including 3 randomized controlled trials, 5 prospective studies, and 3 retrospective studies. No significant differences between single-level and multiple-level groups were found in terms of the prevalence of heterotopic ossification and reoperation rate, Neck Disability Index score, Visual Analog Scale score, and success rate using the Odom grading system. Conclusions:On the basis of this meta-analysis, clinical outcomes of multiple-level CDR are similar to those of single-level CDR for cervical spondylosis, which suggests the multiple-level CDR is as effective and safe as the single-level CDR. Nonetheless, more well-designed studies are needed for further evaluation.
Exit-Site Care in Austrian Peritoneal Dialysis Centers — a Nationwide Survey

Background Catheter-associated infections markedly contribute to treatment failure in peritoneal dialysis (PD) patients. There is much controversy surrounding prophylactic strategies to prevent these infections. Methods In this nationwide multicenter study we analyzed strategies to prevent catheter-associated infections as performed in Austrian PD centers in 2006. A questionnaire was sent to all 23 PD centers in Austria. Results Ten different catheter models were used in the 332 patients being treated in the 23 Austrian PD centers. Systemic antibiotics prior to catheter placement were given by 17 of the 23 PD centers (glycopeptides, n = 7; cephalosporins, n = 10). Nasal swabs were taken preoperatively by 17 PD centers; nasal Staphylococcus aureus carriers were treated prophylactically with mupirocin cream in 15 of these centers. Dressing change was routinely performed in 318 of 332 chronic PD patients (nonocclusive film dressing, n = 58; gauze dressing, n = 260). Disinfectants for chronic exit-site care included povidone iodine (n = 155), sodium hypochlorite (n = 31), povidone iodine + sodium hypochlorite together (n = 102), and octenidine dihydrochloride/phenoxyethanol (n = 17). Water+non-disinfectant soap or 0.9% sodium chloride was administered as a cleansing agent to the exit site by 27 patients. Routine S. aureus screening (nasal and/or exit-site swabs) in chronic PD patients was performed in 12 PD centers; carriers were treated with mupirocin cream in 11 of these centers. Dialysis staff members were screened for S. aureus in 8 PD centers and spouses were screened for S. aureus in 5 PD centers. The overall exit-site infection rate was 1 episode/43.9 patient-months, tunnel infection rate was 1 episode/88.9 patient-months, and peritonitis rate was 1 episode/51.0 patient-months. Patients of centers that have installed a prophylaxis protocol for treating S. aureus carriers had lower mean infection rates compared with those not using such a protocol. Conclusion Various individual prophylactic strategies are used to prevent catheter-associated infections in Austrian PD centers. Infection rates are within the range reported in the literature. There is still scope for improvement in some centers (e.g., by establishing a prophylaxis protocol).
MEF2 transcription factors are key regulators of sprouting angiogenesis

In this study, Saccilotto et al. investigated the molecular connection between proangiogenic signals and downstream gene expression during angiogenesis. By characterizing a Dll4 enhancer directing expression to endothelial cells at the angiogenic front, the authors identified MEF2 transcription factors as crucial regulators of sprouting angiogenesis directly downstream from VEGFA.
Earnings benchmarks, earnings management and future stock performance of Chinese listed companies reporting under ASBE-IFRS

Prior literature has revealed three key earnings benchmarks: earnings level; earnings change; and analysts’ expectations. The purpose of this paper is twofold. First, the authors seek to establish which earnings benchmark induces the largest extent of earnings management. Second, the authors explore the implications of earnings management on firm future performance. Both of these purposes are investigated for Chinese listed companies during China’s IFRS/ISA reporting era. ,The authors rely upon the unique regulations and incentives for Chinese listed companies in order to develop four testable hypotheses. Next, the authors employ both logistic and ordinary least squares regressions to test the hypotheses. ,The results suggest that Chinese listed firms have the highest level of income increasing discretionary accruals around the earnings level benchmark, followed by the earnings change benchmark. The authors do not find any evidence of earnings management to beat analysts’ expectation. In addition, the authors find evidence that Chinese listed firms with relatively high level of earnings management and low earnings exhibit relatively weak future stock performance. ,The findings are the first to document an earnings management benchmark hierarchy with respect to the extent of income increasing discretionary accruals, while simultaneously establishing a link between earnings management and firm future stock performance, for Chinese listed companies. The findings are valuable for regulators and investors by suggesting that management intervention in the reporting process during China’s IFRS/ISA reporting era may act to circumvent delisting regulations and cloud earnings signal for firms that beat certain earnings benchmarks.
Genetic variation and risk of DNA damage in peripheral blood lymphocytes of Iranian formaldehyde-exposed workers

Formaldehyde (FA) has given positive results for the genetic damage evaluated in human peripheral blood lymphocytes. Polymorphism plays a special role in the toxicity of chemicals. DNA damage in blood cells was evaluated in workers who were occupationally exposed to FA. This study tested the association of alcohol dehydrogenase III (ADH3) and manganese-superoxide dismutase (Mn-SOD) gene polymorphism, with DNA damage of peripheral blood lymphocytes. Gene polymorphisms were evaluated in 54 workers from melamine dinnerware workshops and 34 workers from dairy production workshops. The control and exposed population were matched based on age, smoking, work history and socioeconomic status. DNA damage was evaluated by alkaline comet assay in the peripheral blood lymphocytes. ADH3 and Mn-SOD genotypes were determined in all workers using polymerase chain reaction–restriction fragment length polymorphism method. DNA damage of lymphocyte cells was significantly higher (p < 0.001) in the exposed individuals in comparison with the control population. The examinations of the exposed group had revealed significantly higher (p < 0.01) variant of Val/Val of Mn-SOD compared to control group. In workers with ADH32–2 variant, significantly higher levels of DNA damage (p < 0.01) were observed than the control population with the same genotype. It could be concluded that enzymes involved in the metabolism of FA and oxidative stress controlling are two important effective parameters for DNA damage of peripheral blood lymphocytes in exposed people. These results are regarded as a pioneer investigation for the management of health risks assessment.
Characterization of the Heterotrimeric G-Protein Complex and Its Regulator from the Green Alga Chara braunii Expands the Evolutionary Breadth of Plant G-Protein Signaling1[C][W][OPEN]

The presence of a complete repertoire of heterotrimeric G-protein complex components and its regulator in a green alga confirms that the origin of this signaling mechanism in plants is more ancient than previously thought and is not related to the colonization of land by plants. The lack of heterotrimeric G-protein homologs in the sequenced genomes of green algae has led to the hypothesis that, in plants, this signaling mechanism coevolved with the embryophytic life cycle and the acquisition of terrestrial habitat. Given the large evolutionary gap that exists between the chlorophyte green algae and most basal land plants, the bryophytes, we evaluated the presence of this signaling complex in a charophyte green alga, Chara braunii, proposed to be the closest living relative of land plants. The C. braunii genome encodes for the entire G-protein complex, the Gα, Gβ, and Gγ subunits, and the REGULATOR OF G-PROTEIN SIGNALING (RGS) protein. The biochemical properties of these proteins and their cross-species functionality show that they are functional homologs of canonical G-proteins. The subunit-specific interactions between CbGα and CbGβ, CbGβ and CbGγ, and CbGα and CbRGS are also conserved, establishing the existence of functional G-protein complex-based signaling mechanisms in green algae.
Does government R&D stimulate or crowd out firm R&D spending? Evidence from Chinese manufacturing industries

We examine whether receiving a government R&D grant stimulates or crowds out a firm’s own R&D spending in Chinese manufacturing industries. Using a database that spans the population of large and medium size privately owned Chinese manufacturing firms for the period from 2007 to 2011, a matching estimator and a matching and difference in‐differences estimator, we find a large firm R&D promoting effect of government R&D: receiving a government R&D grant led to a 4 to 9‐million‐yuan increase in a firm’s own R&D expenditures. This is a significant effect since the average R&D expenditures ranged from 5 to 9 million yuan in the year before receiving the grant. To understand the mechanisms behind this effect, we compare the before‐ and after‐treatment performance and behaviour of the treated and the control firms. We find that the government R&D receiving firms became more profitable following their receipt of the grant. We also find that receiving a government R&D grant increases the likelihood of a firm continuing its R&D performance after receiving the initial grant.
Mechanical properties of primate vascularized vs. nonvascularized patellar tendon grafts; changes over time

Mechanical properties of patellar tendon autografts used to replace the anterior cruciate ligament (ACL) in the cynomolgus monkey were measured at four time periods up to 1 year. The ACL was replaced in each knee with the medial half of the patellar tendon: as a vascularized graft (VG) on one side and as a nonvascularized or free graft (FG) on the other. Postoperative care consisted of 4 weeks of cast immobilization at 30° flexion followed by unrestricted activity in a large cage. Both grafts showed low stiffness and maximum force at 7 weeks (24% and 16% of ACL control values, respectively), increasing to 57% of control ACL stiffness and 39% of control maximum force by 1 year. Corresponding material properties, modulus and maximum stress, also increased over time, but at 1 year were only 34% and 26% of ACL values, respectively. The results indicate that retaining vascularity does not prevent significant reduction in graft properties that occur postoperatively, nor does it accelerate the return in strength and stiffness. Tissue stiffness, which returns earlier than maximum force and joint anteroposterior (AP) force displacement data, should be routinely reported in any healing study. Finally, in studies of this kind, the large variation in the results makes sampling only one or two animals from each time period unreliable.
Impairment of airway mucociliary transport by Pseudomonas aeruginosa products. Role of oxygen radicals.

We previously showed that the supernatant of a Pseudomonas aeruginosa (PA) culture and its constituents pyocyanin and 1-hydroxyphenazine inhibit ciliary activity of dispersed tracheal epithelial cells in vitro via the generation of oxygen radicals by phagocytes. In the present study, we wished to determine if tracheal mucus velocity (TMV) is also impaired by PA supernatant and if oxygen radicals have a mediating role. In conscious sheep, TMV (measured with a radiographic method) was determined before and serially following aerosol challenge with the cell-free supernatant of a PA culture or unconditioned culture medium (control). TMV decreased from a mean (+/- SEM) baseline of 6.7 +/- 1.1 mm/min (n = 6) by 29, 35, and 25% at 0.5, 3, and 24 h after challenge, respectively (p < 0.05), and returned to baseline 1 wk later (-6%, p = NS). Control medium had no effect on TMV (maximum decrease by 15% at 0.5 h). Aerosolized catalase blunted the effect of PA supernatant on TMV. To determine if the impairment of TMV involved ciliary inhibition, tissues were mounted in a chamber and ciliary beat frequency (CBF) and surface liquid velocity (SLV) were measured with a microscopic method. PA supernatant decreased both CBF (maximum mean decrease 12%; n = 5, p < 0.05) and SLV (maximum mean decrease 78%; n = 5, p < 0.05) in a dose-dependent fashion, with a correlation between the two parameters; these effects were blocked by catalase. (ABSTRACT TRUNCATED AT 250 WORDS)
Distribution of galanin‐like immunoreactivity in the brain of Rana esculenta and Xenopus laevis

The immunocytochemical distribution of galanin‐containing perikarya and nerve terminals in the brain of Rana esculenta and Xenopus laevis was determined with antisera directed toward either porcine or rat galanin. The pattern of galanin‐like immunoreactivity appeared to be identical with antisera directed toward either target antige.
Decreased variation of inflammatory markers in gestational diabetes

Gestational diabetes is a prediabetic state. Sub‐clinical inflammation may play a role in the transition from gestational diabetes to type 2 diabetes; the role of the autonomic nervous system as a mediating system has been raised. We aimed to study the association of the sympathetic nervous system and sub‐clinical inflammation in women with gestational diabetes.