Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduction of falls and fractures after permanent pacemaker implantation in elderly patients with sinus node dysfunction

Aims Elderly patients with sinus node dysfunction (SND) are at increased risk of falls with possible injuries. However, the incidence of these adverse events and its reduction after permanent pacemaker (PPM) implantation are not known. Methods and results Eighty-seven patients (mean [SD] age 75.4 [8.3] years, 51% women) with SND and an indication for cardiac pacing were included and were examined by a standardized interview targeting fall history. The incidence and total number of falls, falls with injury, falls requiring treatment, and falls resulting in a fracture were assessed for the time period of 12 months before (retrospectively) and after PPM implantation (prospectively). Furthermore, symptoms such as syncope, dizziness, and dyspnea were evaluated before and after PPM implantation. The implantation of a PPM was associated with a reduced proportion of patients experiencing at least one fall by 71% (from 53 to 15%, P < 0.001) and a reduction of the absolute number of falls by 90% (from 127 to 13, P < 0.001) during the 12 months before vs. after PPM implant. Falls with injury (28 vs. 10%, P = 0.005), falls requiring medical attention (31 vs. 8%, P < 0.001), and falls leading to fracture (8 vs. 0%, P = 0.013) were similarly reduced. Notably, fewer patients had syncope (4 vs. 45%, P < 0.001) and dizziness after PPM implantation (12 vs. 45%, P < 0.001). Conclusion Falls, fall-related injuries, and fall-related fractures are frequent in SND patients. Permanent pacemaker implantation is associated with a significantly reduced risk of these adverse events, although no causal relationship could be established due to the study design.
Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: results from the ETOP Lungscape Project

Background Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods Clinically annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is >1% for most of the ∼150 (13 genes) mutations covered in the multiplex test. Results Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63 µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Conclusion Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance.
Moth bean germplasm screening against yellow mosaic virus, II. Developmentof moth bean high-yielding seed and fodder cultivars

Moth bean (Vigna aconitifolia (Jacq.) Marechal) susceptibility to yellow mosaic virus (YMV) purged the crop from the farming system. Therefore, genotype-by-environment interaction (GEI) and biplot studies were undertaken to develop YMV-resistant moth bean cultivars from the germplasm. The germplasm was acquired from the National Agricultural Research Centre (NARC), Islamabad and from the farm fields in two provinces, Punjab and Sindh, Pakistan. Two different groups of moth bean genotypes were screened for YMV versus seed yield (11 genotypes) and YMV versus fodder yield (10 genotypes) over three years (2006-2008) in three locations in Pakistan (D.I.Khan Agriculture Research Station (ARS), Serai Naurang ARS, and Karak ARS). In all germplasm, four moth bean lines were identified as highly resistant to YMV with maximum grain (013393-C, 013388) and fodder (DMB-118-E, DMB-118-A) yields across all years and locations. Genotype, environment, GEI, and biplot analysis revealed that two moth bean lines (013393-C and DMB-118-E) showed the lowest YMV scoring (1) and maximum grain (33.40, 29.70, and 33.98 g plant -1 ) and fodder yields (15.30, 17.40, and 15.35 t ha -1 ) compared with susceptible checks, respectively. Keeping in view the genetic potential of YMV-resistance and the high grain and fodder yields of two moth bean lines (013393-C, DMB-118-E), the Provincial Seed Council (PSC) of Khyber Pakhtunkhwa, Pakistan approved the two lines with the highest grain and fodder yields as new moth bean cultivars, naming them Dera Moth and Green Moth, respectively.
Dutch version of the Fear of Pain Questionnaire for adolescents with chronic pain

Abstract Background: Fear of pain is important in the development and maintenance of chronic pain. The Fear of Pain Questionnaire-Child version has been developed to assess pain related fear in children and adolescents. Objective: Translating the original questionnaire into Dutch, and investigating internal consistency and construct validity to enable use in the Dutch pain rehabilitation setting for treatment and research. Methods: Cross-sectional validation study: After forward and back translation of the FOPQ-C, adolescents (11–22 years old) with chronic musculoskeletal pain completed an assessment containing the Dutch Fear of Pain Questionnaire, and questionnaires about demographics, pain catastrophizing, functional disability, and pain intensity. Internal consistency and construct validity were evaluated through exploratory factor analysis (principal axis factoring with oblique rotation) and hypotheses testing using pain catastrophizing, functional disability, and pain intensity as comparative constructs. Results: Eighty-six adolescents completed the assessment. Exploratory factor analysis resulted in a two-factor structure, explaining 43% of the variance. Internal consistency was strong (Cronbach’s α = 0.92 total scale, α = 0.88 factor 1, and α = .86 factor 2). Five out of 6 hypotheses were confirmed. Conclusions: The Dutch version demonstrated good internal consistency and good construct validity in a population of adolescents with chronic musculoskeletal pain. Implications for rehabilitation The Fear of Pain Questionnaire-Child version was developed to measure fear of pain and avoidance in children and adolescents with chronic pain. Identification of fear of pain and activities that are being avoided are important during screening and assessment of the adolescent for chronic pain rehabilitation treatment. The presence of fear of pain and/or avoidance behavior is important information to shape and target multidisciplinary rehabilitation treatment.
A Functional Study of AUXILIN-LIKE1 and 2, Two Putative Clathrin Uncoating Factors in Arabidopsis[OPEN]

Two putative clathrin uncoating factors were identified via clathrin interaction studies, live imaging, overexpression, and loss-of-function analyses, shedding light on cellular trafficking in plants. Clathrin-mediated endocytosis (CME) is a cellular trafficking process in which cargoes and lipids are internalized from the plasma membrane into vesicles coated with clathrin and adaptor proteins. CME is essential for many developmental and physiological processes in plants, but its underlying mechanism is not well characterized compared with that in yeast and animal systems. Here, we searched for new factors involved in CME in Arabidopsis thaliana by performing tandem affinity purification of proteins that interact with clathrin light chain, a principal component of the clathrin coat. Among the confirmed interactors, we found two putative homologs of the clathrin-coat uncoating factor auxilin previously described in non-plant systems. Overexpression of AUXILIN-LIKE1 and AUXILIN-LIKE2 in Arabidopsis caused an arrest of seedling growth and development. This was concomitant with inhibited endocytosis due to blocking of clathrin recruitment after the initial step of adaptor protein binding to the plasma membrane. By contrast, auxilin-like1/2 loss-of-function lines did not present endocytosis-related developmental or cellular phenotypes under normal growth conditions. This work contributes to the ongoing characterization of the endocytotic machinery in plants and provides a robust tool for conditionally and specifically interfering with CME in Arabidopsis.
High-frequency urban measurements of molecular hydrogen and carbon monoxide in the United Kingdom

Abstract. High-frequency measurements of atmospheric molecular hydrogen (H2) and carbon monoxide (CO) were made at an urban site in the United Kingdom (UK) from mid-December, 2008 until early March, 2009. Very few measurements of H2 exist in the urban environment, particularly within the UK, but are an essential component in the assessment of anthropogenic emissions of H2 and to a certain extent CO. These data provide detailed information on urban time-series, diurnal cycles as well as sources and sinks of both H2 and CO at urban locations. High-frequency data were found to be strongly influenced by local meteorological conditions of wind speed and temperature. Diurnal cycles were found to follow transport frequency very closely due to the sites proximity to major carriageways, consequently a strong correlation was found between H2 and CO mole fractions. Background subtracted mean and rush hour molar H2/CO emission ratios of 0.53±0.08 and 0.57±0.06 respectively, were calculated from linear fitting of data. The scatter plot of all H2 and CO data displayed an unusual two population pattern, thought to be associated with a large industrial area 85 km to the west of the site. However, the definitive source of this two branch pattern could not be fully elucidated. H2 emissions from transport in the UK were estimated to be 188±39 Gg H2/yr, with 8.1±2.3 Tg/yr of H2 produced from vehicle emissions globally. H2 and CO deposition velocities were calculated during stable night-time inversion events when a clear decay of both species was observed. CO was found to have a much higher deposition velocity than H2, 1.3±0.8×10−3 and 2.2±1.5×10−4 m s−1 (1σ) respectively, going against the law of molecular diffusivity. The source of this unusual result was investigated, however no conclusive explanation was found for increased loss of CO over H2 during stable night time inversion events.
Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine

Androgen deprivation therapy (ADT) has been widely prescribed for patients with advanced prostate cancer (PC) to control key signaling pathways via androgen receptor (AR) and AR-collaborative transcriptional factors; however, PC gradually acquires a lethal phenotype and results in castration-resistant PC (CRPC) during ADT. Therefore, new therapeutic strategies are required in clinical practice. In addition, ARs; estrogen receptors (ERs; ERα and ERβ); and estrogen-related receptors (ERRs; ERRα, ERRβ, and ERRγ) have been reported to be involved in the development or regulation of PC. Recent investigations have revealed the role of associated molecules, such as KLF5, FOXO1, PDGFA, VEGF-A, WNT5A, TGFβ1, and micro-RNA 135a of PC, via ERs and ERRs. Selective ER modulators (SERMs) have been developed. Recently, estrogen and androgen blockade (EAB) using a combination of toremifene and ADT has been demonstrated to improve biochemical recurrence rate in treatment-naïve bone metastatic PC. In the future, the suitability of ADT alone or EAB for individuals may be evaluated by making clinical decisions on the basis of information obtained from RT-PCR, gene-panel, or liquid biopsy to create a “personalized medicine” or “precision medicine”. In this review, we summarize ER and ERR signaling pathways, molecular diagnosis, and SERMs as candidates for advanced PC treatment.
Thyroid Signaling, Insulin Resistance, and 2 Diabetes Mellitus: A Mendelian Randomization Study

Context Increasing evidence suggests an association between thyroid-stimulating hormone (TSH), free thyroxine (fT4), and deiodinases with insulin resistance and type 2 diabetes mellitus (T2D). Objective We examined whether TSH and fT4 levels and deiodinases are causally associated with insulin resistance and T2D, using Mendelian randomization. Methods We selected 20 genetic variants for TSH level and four for fT4 level (identified in a genome-wide association study (GWAS) meta-analysis of European-ancestry cohorts) as instrumental variables for TSH and fT4 levels, respectively. We used summary data from GWASs on the outcomes T2D [Diabetes, Genetics Replication and Meta-analysis (DIAGRAM), n = 12,171 cases and n = 56,862 control subjects] and glycemic traits in patients without diabetes [Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC), n = 46,186 for fasting glucose and insulin and n = 46,368 for hemoglobin A1c]. To examine whether the associations between TSH/fT4 levels and the study outcomes were causal, we combined the effects of the genetic instruments. Furthermore, we examined the associations among 16 variants in DIO1, DIO2, DIO3, and T2D and glycemic traits. Results We found no evidence for an association between the combined genetic instrumental variables for TSH and fT4 and the study outcomes. For example, we did not observe a genetically determined association between high TSH level and T2D (odds ratio, 0.91 per standard deviation TSH increase; 95% confidence interval, 0.78 to 1.07). Selected genetic variants in DIO1 (e.g., rs7527713) were associated with measures of insulin resistance. Conclusion We found no evidence for a causal association between circulatory levels of TSH and fT4 with insulin resistance and T2D, but we found suggestive evidence that DIO1 affects glucose metabolism.
Risk Factors for Renal Survival in Chinese Patients with Myeloperoxidase-ANCA-Associated GN.

BACKGROUND AND OBJECTIVES Our study explored the association of histopathologic classification of ANCA-associated GN with renal survival in Chinese patients with myeloperoxidase-ANCA-associated GN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Two hundred fifteen patients with biopsy-proven myeloperoxidase-ANCA-associated GN were included from January of 1996 to December of 2014. The biopsies included focal (n=27), mixed (n=82), crescentic (n=47), and sclerotic (n=59) classes. The long-term renal outcome and risk factors of myeloperoxidase-ANCA-associated GN for different histopathologic classes were retrospectively analyzed. RESULTS During a median follow-up time of 22 (9-51) months, 88 (40.9%) patients reached ESRD. The 5-year renal survival (overall 58.7%) was highest in the focal class (100.0%) and lowest in the sclerotic class (20.7%), with no difference between the mixed (58.9%) and crescentic (67.4%) classes. Patients in the mixed (hazard ratio, 0.34; 95% confidence interval, 0.20 to 0.57; P<0.001) and crescentic (hazard ratio, 0.31; 95% confidence interval, 0.16 to 0.59; P<0.001) classes were at lower risk for ESRD compared with patients in the sclerotic class, as were patients who received glucocorticoids plus mycophenolate mofetil (hazard ratio, 0.32; 95% confidence interval, 0.18 to 0.60; P<0.001) compared with those receiving glucocorticoids alone. In addition, patients with a serum creatinine level ≥4 mg/dl (hazard ratio, 2.93; 95% confidence interval, 1.77 to 4.85; P<0.001) or hypoalbuminemia (hazard ratio, 2.11; 95% confidence interval, 1.32 to 3.34; P=0.002) were at higher risk for ESRD. A serum creatinine level ≥4 mg/dl and a percentage of global sclerotic glomeruli ≥60% were the two independent risk factors for ESRD in the sclerotic class. CONCLUSIONS The histopathologic classification of ANCA-associated GN in combination with serum creatinine and serum albumin levels and treatment regimen is associated with renal outcome in myeloperoxidase-ANCA-associated GN. The evaluation of serum creatinine level and percentage of global sclerotic glomeruli provides additional information on the risk of renal survival in the sclerotic class of myeloperoxidase-ANCA-associated GN.
Effects of Oxandrolone on Cardiometabolic Health in Boys With Klinefelter Syndrome: A Randomized Controlled Trial

Context Klinefelter syndrome (KS) is a common condition in males, resulting in androgen deficiency and cardiometabolic diseases. These interrelated conditions may be present in prepubertal boys with KS. Objective To determine whether supplemental low-dose androgen has a beneficial effect on body composition in prepubertal boys with KS. Design, Setting, and Participants We conducted a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial in 93 boys with KS aged 4 to 12 years. Interventions Oral oxandrolone (Ox) 0.06 mg/kg/d or placebo for 2 years. Outcome Measures The primary outcome was percent body fat standard deviation score (%BF SDS) at 2 years. Secondary outcomes included additional measures of cardiometabolic health and safety. Results The %BF SDS at 2 years was significantly lower in the treatment (0.29 ± 0.76 SDS) compared with placebo group (0.81 ± 0.72 SDS) after adjusting for age and baseline %BF SDS (95% confidence interval for the difference between means -0.86 to -0.19 SDS, P = 0.009). Ox resulted in lower triglycerides (P = 0.043), but also lower high-density lipoprotein (HDL) cholesterol (P < 0.001) and a more rapid advancement in bone age (P = 0.011). Conclusions Ox has positive effects on measures of cardiometabolic health in prepubertal boys with KS; however, it does lower HDL cholesterol and advance bone age.
Rectified factor networks for biclustering of omics data

Motivation: Biclustering has become a major tool for analyzing large datasets given as matrix of samples times features and has been successfully applied in life sciences and e‐commerce for drug design and recommender systems, respectively. Factor Analysis for Bicluster Acquisition (FABIA), one of the most successful biclustering methods, is a generative model that represents each bicluster by two sparse membership vectors: one for the samples and one for the features. However, FABIA is restricted to about 20 code units because of the high computational complexity of computing the posterior. Furthermore, code units are sometimes insufficiently decorrelated and sample membership is difficult to determine. We propose to use the recently introduced unsupervised Deep Learning approach Rectified Factor Networks (RFNs) to overcome the drawbacks of existing biclustering methods. RFNs efficiently construct very sparse, non‐linear, high‐dimensional representations of the input via their posterior means. RFN learning is a generalized alternating minimization algorithm based on the posterior regularization method which enforces non‐negative and normalized posterior means. Each code unit represents a bicluster, where samples for which the code unit is active belong to the bicluster and features that have activating weights to the code unit belong to the bicluster. Results: On 400 benchmark datasets and on three gene expression datasets with known clusters, RFN outperformed 13 other biclustering methods including FABIA. On data of the 1000 Genomes Project, RFN could identify DNA segments which indicate, that interbreeding with other hominins starting already before ancestors of modern humans left Africa. Availability and implementation: https://github.com/bioinf‐jku/librfn Contact: djork‐arne.clevert@bayer.com or hochreit@bioinf.jku. at
Lifetime Marijuana and Alcohol use, and Cognitive Dysfunction in People with Human Immunodeficiency virus Infection

Background Substance use is common among people with human immunodeficiency virus (HIV) infection. Alcohol, marijuana, and HIV can have negative effects on cognition. Associations between current and lifetime marijuana and alcohol use and cognitive dysfunction in people with HIV infection were examined. Methods Some 215 HIV-infected adults with Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) substance dependence or ever injection drug use were studied. In adjusted cross-sectional regression analyses associations were assessed between current marijuana use, current heavy alcohol use, lifetime marijuana use, lifetime alcohol use, duration of heavy alcohol use (the independent variables), and 3 measures of cognitive dysfunction (dependent variables): both the (i) memory and (ii) attention domains from the Montreal Cognitive Assessment (MoCA) and the (iii) 4-item cognitive function scale (CF4) from the Medical Outcomes Study HIV Health Survey (MOS-HIV). Analyses were adjusted for demographics, primary language, depressive symptoms, anxiety, comorbidities, antiretroviral therapy, hepatitis C virus (ever), duration of HIV infection (years), HIV-viral load (log copies/mL), CD4 cell count, lifetime and recent cocaine use, and recent illicit and prescribed opioid use. Results Current marijuana use was significantly and negatively associated with the MOS-HIV CF4 score (adjusted mean difference = −0.40, P = .01). Current marijuana use was not significantly associated with either MoCA score. Lifetime marijuana use and current heavy and lifetime alcohol use and duration of heavy alcohol use were not associated with any measure of cognitive dysfunction. Conclusion Current marijuana use was associated with one measure of cognitive dysfunction, but there was not a consistent pattern of association with lifetime marijuana use or alcohol use and measures of cognitive dysfunction. Understanding the mechanism by which marijuana, with and without alcohol, are associated with worse cognition warrants larger, longer studies with more precise and diverse measurements of cognitive function.
BMP7 regulates lung fibroblast proliferation in newborn rats with bronchopulmonary dysplasia

The present study investigated the expression of bone morphogenetic protein (BMP) 7 in a newborn rat model of bronchopulmonary dysplasia (BPD) and the biological effects of BMP7 on newborn rat lung fibroblast (LF) cells. For this purpose, a total of 196 newborn rats were randomly and equally assigned to a model group and a control group. Lung tissue was collected at days 3, 7, 14 and 21 for histological analysis. The location and expression of BMP7 was examined by immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. A total of 38 full-term newborn rats on the day of birth were sacrificed and LF cells were isolated and treated with BMP7. The biological effects of BMP7 on LF cells were assessed by cell proliferation and cell cycle analysis. The findings demonstrated that abnormal alveolar development due to BPD was gradually intensified in the model group over time. Immunohistochemical staining revealed that the location of BMP7 in lung tissue was altered. Immunohistochemistry and RT-qPCR assays demonstrated a gradual decrease in BMP7 expression in the model group induced by hyperoxia. MTT assays demonstrated that BMP7 inhibited LF cells and the inhibitory effect was dose-dependent and time-dependent. Flow cytometry revealed that the inhibitory effect of BMP7 in LF cells was causing cell cycle arrest at the G1 phase. The present study demonstrated that BMP7 may serve an important role in alveolar development in a BPD model. BMP7 may be involved in abnormal alveolar development through the regulation of LF proliferation.