Miracle-dz/UniFAR-FTUs huggingface dataset:
Is There a Demand for PGD and/or PND Among Healthy BRCA1/2 Carriers at a Reproductive Age? A Contingent Valuation Survey.

Breast cancer is one of the most common neoplasms in women and 2-5% are due to high-risk penetrance genes, such as BRCA1/2. Carriers have a higher risk of developing breast and ovarian cancer at a younger age. Few options are available to avoid transferring their mutation (risk=50%): adopting, ovum/sperm donation, preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND). In France PGD and PND are allowed based on the severity and non curability of a condition, however no authorization has yet been reported. The national GENEPSO cohort gives us the opportunity to elicit preferences toward access to PGD and PND using the contingent valuation method. Eligible subjects were carriers of a BRCA1/2 mutation and unaffected by cancer. Among the 460 respondents 28% declared that, in the context of a next pregnancy, they would wish to beneficiate neither from PGD nor from PND. Among the remaining 330 respondents, 64% have given a value to PGD or PND (1952€ vs. 1808€). WTP PGD increases with income, acceptability of therapeutic ToP, knowledge of the risk of transmission and certainty of wishing to beneficiate from PGD. WTP PGD decreases when maternity project was not influenced by the test and when ToP was experienced. WTP PND was determined by WTP PGD , but also increases with income, being a male and certainty of wishing to beneficiate from PND. Debate around PGD/PND came from the fact that a mutation “only” predisposes to cancer. Our survey shows that BRCA carriers support the availability of access to PGD/PND and challenges the recommendations to be made to onco-geneticians.
Conformational diversity of dynactin sidearm and domain organization of its subunit p150

Dynactin is a principal regulator of the minus-end directed microtubule motor dynein. The sidearm of dynactin is essential for binding to microtubules and regulation of dynein activity. Although our understanding of the structure of the dynactin backbone (Arp1 rod) has greatly improved recently, structural details of the sidearm subcomplex remain elusive. Here, we report the flexible nature and diverse conformations of dynactin sidearm observed by electron microscopy. Using nanogold labeling and deletion mutant analysis, we determined the domain organization of the largest subunit p150 and discovered that its coiled-coil (CC1), dynein-binding domain, adopted either a folded or an extended form. Furthermore, the entire sidearm exhibited several characteristic forms, and the equilibrium among them depended on salt concentrations. These conformational diversities of the dynactin complex provide clues to understanding how it binds to microtubules and regulates dynein.
Infectious Esophagitis in Romanian Children: From Etiology and Risk Factors to Clinical Characteristics and Endoscopic Features

Objectives. The aim of this study is to provide information about prevalence, etiology, risk factors, clinical characteristics and endoscopic features of various types of infectious esophagitis in children. Methods. We performed a total of 520 upper gastrointestinal tract endoscopies in Pediatric Clinic II, Emergency Hospital for Children, Cluj-Napoca. Indications for endoscopy in our cohort were gastrointestinal tract symptoms such as dysphagia, heartburn, or appetite loss. Results. The prevalence of infectious esophagitis in the study population was 2.11% (11 patients). Candida albicans (C. albicans) was the most frequent cause. Our data illustrates that herpes simplex virus (HSV)-induced esophagitis is common in immunocompromised patients and should be systematically suspected in cases of severe dysphagia, heartburn, or hematemesis. In the present study, all cytomegalovirus (CMV) esophagitis patients were immunocompromised. Immunodeficiency (81.8%) and prolonged antibiotic therapy with broad-spectrum antibiotics were by far the most important risk factors involved in the pathogenicity of the disease. Dysphagia, appetite loss, heartburn, epigastralgia, and hematemesis were the main clinical manifestations. Infectious esophagitis was associated with significant mortality. In four patients, endoscopy during life showed signs of infectious esophagitis; however, the precise etiology was only established post-mortem, in the pathological anatomy laboratory department. A risk factor involved in pathogenesis of post-mortem diagnosed infectious esophagitis is the DiGeorge syndrome for CMV and HSV patients. Conclusions. The study illustrates that infectious esophagitis should be considered in immunocompromised infants with prolonged antibiotic therapy with broad-spectrum antibiotics.
The gut mycobiome: The overlooked constituent of clinical outcomes and treatment complications in patients with cancer and other immunosuppressive conditions

Extensive efforts have focused on investigating the contributions of the intestinal microbiome to health and disease, including immunomodulation [1, 2]. While the term “microbiome” technically refers to microorganisms including bacteria, fungi, viruses, protozoa, and parasites, the majority of studies focus on the bacteriome [3]. Although the bacteriome constitutes >99% of the microbiome [4] (which is potentially the reason most studies focus on the bacteriome), it is irrefutable that the commensal fungi, or the “mycobiome,” alongside the other microorganisms, coexist and interact ways that can be beneficial or detrimental to the host [5– 7]. Emerging research has focused on how the bacteriome relates to gastrointestinal (GI) disorders, cancer therapy–related toxicities, and stem-cell transplantation outcomes; including correlations with infection, graft-versus-host disease (GvHD), tumorigenesis, cancer relapse, and mortality [8–11]. Thus far, there has been a lack of dedicated research focusing on the influence of mycobiome-associated immunomodulation in patients with cancer and other states of immunosuppression. Herein, by focusing on the gut ecosystem, we discuss the role of fungi in various patient populations, the importance of bacterial-fungal dysbiosis, and offer ideas for future investigations regarding the role of mycobiome.
The biosynthesis of the molybdenum cofactors in Escherichia coli.

The biosynthesis of the molybdenum cofactor (Moco) is highly conserved among all kingdoms of life. In all molybdoenzymes containing Moco, the molybdenum atom is coordinated to a dithiolene group present in the pterin-based 6-alkyl side chain of molybdopterin (MPT). In general, the biosynthesis of Moco can be divided into four steps in in bacteria: i) the starting point is the formation of the cyclic pyranopterin monophosphate (cPMP) from 5'GTP, ii) in the second step the two sulfur atoms are inserted into cPMP leading to the formation of MPT, iii) in the third step the molybdenum atom is inserted into molybdopterin to form Moco, and iv) in the fourth step bis-Mo-MPT is formed and an additional modification of Moco is possible with the attachment of a nucleotide (CMP or GMP) to the phosphate group of MPT, forming the dinucleotide variants of Moco. This review presents an update on the well characterized Moco biosynthesis in the model organism Escherichia coli including novel discoveries from the recent years. This article is protected by copyright. All rights reserved.
Nanoporous iron oxide nanoparticle: hydrothermal fabrication, human serum albumin interaction and potential antibacterial effects

Abstract Nanoporous iron oxide (Fe3O4) nanoparticles (NIONPs) have been widely used as promising agents in biomedical applications. Herein, the NIONPs were synthesized by one-step hydrothermal method and well-characterized by FESEM and TEM investigations. Afterwards, their interaction with human serum albumin (HSA) was studied using a wide range of biophysical approaches, including intrinsic and extrinsic fluorescence, far and near UV-CD, and UV-Vis spectroscopic methods as well as molecular docking investigation. Furthermore, the antibacterial effect of NIONPs was examined on the standard strains of the following pathogenic bacteria, Staphylococcus aureus (ATCC 25923), Klebsiella penumoniae (ATCC 33883), Enterococcus faecalis (ATCC 29212) and Pseudomonas aeruginosa (ATCC 27853). The results showed the feasible fabrication of spherical-shaped NIONPs with an average diameter of around 100 nm. Intrinsic fluorescence spectroscopy data depicted that NIONPs formed a complex with HSA by a KSV value of 0.092 (µg/ml)−1. Extrinsic fluorescence, near UV-CD and UV-vis spectroscopic methods revealed that NIONPs induced some changes on the quaternary structure of HSA, whereas Tm measurement and far UV-CD spectroscopy showed some slight changes on the secondary structure of HSA even in the presence of high concentration of NIONPs. Molecular docking study disclosed that Fe3O4 nanoclusters with varying morphologies and dimensions could interact with different residues on the surface of HSA molecules. In addition, antibacterial assays exhibited a significant inhibition on both Gram-positive and Gram-negative pathogenic bacteria. In conclusion, these NPs can be used as promising antibacterial agents. Communicated by Ramaswamy H. Sarma
Double-Sided Graphene Oxide Encapsulated Silver Nanowire Transparent Electrode with Improved Chemical and Electrical Stability

Owing to their high conductivity, transparency, flexibility, and compatibility with solution processes, silver nanowire (AgNW) networks have been widely explored as a promising alternative to indium tin oxide (ITO). However, their susceptibility to corrosion and thermal instability still remain limiting factors for widespread adoption in a range of devices including solar cells, transparent heaters, and light-emitting diodes. In this study, we report a scalable and economically viable process involving electrophoretic deposition (EPD) to fabricate a highly stable hybrid transparent electrode with a sandwich-like structure, where a AgNW network is covered by graphene oxide (GO) films on both sides. The newly developed all solution process allows the conductive transparent film to be transferred to an arbitrary surface after deposition and demonstrates excellent sheet resistance (15 Ω/sq) and tunable transmittance (70–87% at 550 nm). Unlike bare AgNW networks, the hybrid electrode retains its original conductivity under long-term storage at up to 80% relative humidity. This chemical resilience is explained by the absence of silver corrosion products for the AgNW encapsulated by GO as indicated by X-ray photoelectron spectroscopy. In situ voltage ramping and resistance measurements up to 20 V indicate a novel stabilization mechanism enabled by the presence of GO which delays the failure onset and prevents abrupt divergence of the resistance to the megaohm range experienced by bare AgNW networks. The double-sided nature of the GO coating offers combined stability and performance to the AgNW network, which adds unique versatility of our electrodes to be used toward applications that require a wide range of thermal and chemical stabilities.
Altered expression of 17-β-hydroxysteroid dehydrogenase type 2 and its prognostic significance in non-small cell lung cancer

Numerous studies have reported that oestrogens may contribute to the development of non small cell lung cancer (NSCLC). Although different steroidogenic enzymes have been detected in the lung, the precise mechanism leading to an exaggerated accumulation of active oestrogens in NSCLC remains unexplained. 17 β Hydroxysteroid dehydro genase type 2 (HSD17B2) is an enzyme involved in oestrogen and androgen inactivation by converting 17 β oestradiol into oestrone, and testosterone into 4 androstenedione. Therefore, the enzyme serves an important role in regulation of the intra cellular availability of active sex steroids. This study aimed to determine the expression levels of HSD17B2 in lung cancer (LC) and adjacent histopathologically unchanged tissues obtained from 161 patients with NSCLC, and to analyse the association of HSD17B2 with clinicopathological features. For that purpose, reverse transcription quantitative PCR, western blotting and immunohistochemistry were conducted. The results revealed that the mRNA and protein expression levels of HSD17B2 were significantly decreased in LC tissues compared with matched controls (P<10 6). Conversely, strong cytoplasmic staining of HSD17B2 was detected in the unchanged respiratory epithelium and in glandular cells. Notably, a strong association was detected between reduced HSD17B2 expression and advanced tumour stage, grade and size. Furthermore, it was revealed that HSD17B2 may have potential prognostic significance in NSCLC. A log-rank test revealed the benefit of high HSD17B2 protein expression for the overall survival (OS) of patients (P=0.0017), and multivariate analysis confirmed this finding (hazard ratio=0.21; 95% confidence interval=0.07-0.63; P=0.0043). Stratified analysis in the Kaplan Meier Plotter database indicated that patients with higher HSD17B2 expression presented better OS and post-progression survival. This beneficial effect was particularly evident in patients with adenocarcinoma and during the early stages of NSCLC. Decreased expression of HSD17B2 appears to be a frequent feature in NSCLC. Retrospective analysis suggests that the HSD17B2 mRNA and protein status might be independent prognostic factors in NSCLC and should be further investigated.
Incorporating Milk Protein Isolate into an Energy-Restricted Western-Style Eating Pattern Augments Improvements in Blood Pressure and Triglycerides, but Not Body Composition Changes in Adults Classified as Overweight or Obese: A Randomized Controlled Trial

Unhealthy Western-style eating patterns (WSEP) predominate, adversely affecting health. Resistance to improving dietary patterns prompts interest to incorporate a potentially health-promoting ingredient into typical WSEP foods and beverages. We assessed the effect of incorporating isocalorically matched carbohydrates versus milk protein isolate (MPI) into a WSEP on weight loss-induced changes in cardiometabolic health and body composition. In a randomized, double-blind, parallel-design study, 44 participants (age 52 ± 1 years, body mass index (BMI) 31.4 ± 0.5 kg/m2, mean ± standard error) consumed a weight maintenance WSEP (0.8 g total protein/kg/day) for 3 weeks (baseline). After, participants consumed an energy-restricted (750 kcal/day below estimated requirement) WSEP for 16 weeks, randomly assigned to contain either an additional 0.7 g carbohydrate/kg/d (CON: n = 23, 0.8 g total protein/kg/day) or 0.7 g protein/kg/d from MPI (MPI: n = 21, 1.5 g total protein/kg/day) incorporated into foods and beverages. Compared to CON, the MPI favored reductions in average 24 h and sleeping systolic and diastolic blood pressures (BP), waking hours systolic BP, and fasting plasma triglyceride concentrations. Reductions in fasting plasma insulin, glucose, total cholesterol, and low-density lipoprotein cholesterol concentrations were not different between groups. Among all participants, whole body mass, lean mass, fat mass, and thigh muscle area, each decreased over time. For adults finding it difficult to deviate from a WSEP, replacing a portion of their carbohydrate with foods and beverages containing MPI may be an effective dietary strategy to reduce BP after weight loss.
Opioid-Prescribing Metrics in Washington State: Trends and Challenges

Context: Analyses of prescribing trends using prescription drug monitoring programs (PDMP) are impacted by changes in reporting requirements and in the scheduling of medications by the Drug Enforcement Administration. In 2014, the Drug Enforcement Administration changed the status of tramadol from an unscheduled to a scheduled medication. The addition of tramadol to the PDMP may affect the prevalence of opioid-prescribing metrics and the interpretation of prescribing trends. Objective: The objectives were to (1) examine trends in opioid prescribing in Washington State between 2012 and 2017, (2) assess the potential impact of adding tramadol to PDMP on these trends, and (3) describe challenges in defining and implementing opioid-prescribing metrics. Design: Analysis of quarterly summary statistics of opioid prescribing. Setting: Washington State. Participants: Washington State residents. Main Outcome Measures: The metrics include measures of opioid prescribing overall and by age group, chronic opioid prescribing, high-dose prescribing among those on chronic opioid therapy, prescribing of concurrent opioids and sedatives, days' supply of new opioid prescriptions, and transition from short-term to long-term use of opioids. Results: In Washington, the prevalence of any opioid prescribing, chronic opioid prescribing, high-dose opioid prescribing, and prescribing of concurrent opioids and sedatives declined between 2012 and 2017. The prevalence of opioid prescribing was higher in older than in younger age groups. The addition of tramadol to the Washington PDMP in 2014 affected the observed prevalence of all opioid metrics and of all opioid-prescribing trends. Conclusions about trends in opioid prescribing differ substantially depending on whether tramadol is included or not, particularly in 2014 and 2015. Conclusions: The development of opioid-prescribing metrics is relatively new. There is likely much benefit of standard definitions of opioid metrics at the state and national levels to track important trends and compare progress from state to state.
Intimate partner violence: A key correlate of women’s physical and mental health in informal settlements in Nairobi, Kenya

Globally, one billion people live in informal settlements, and that number is expected to triple by 2050. Studies suggests that health in informal settlements is a serious and growing concern, yet there is a paucity of research focused on health outcomes and the correlates of health in these settlements. Studies cite individual, environmental and social correlates to health in informal settlements, but they often lack empirical evidence. In particular, research suggests that high rates of violence against women (VAW) in informal settlements may be associated with detrimental effects on women’s health, but few studies have investigated this link. The purpose of this study was to fill this gap by empirically exploring associations between women’s experiences of intimate partner violence (IPV) and their physical and mental health. Data for this study were collected in August 2018 in Mathare Valley Informal Settlement in Nairobi, Kenya. A total of 550 randomly-selected women participated in surveys; however, analyses for this study were run on a subpopulation of the women (n = 361). Multivariate logistic regressions were used to investigate the link between psychological, sexual, and emotional IPV and women’s mental and physical health. Results suggest that while some socioeconomic, demographic, and environmental variables were significantly associated with women’s mental and physical health outcomes, all types of IPV emerged key correlates in this context. In particular, women’s experiences of IPV were associated with lower odds of normal-high physical health component scores (based on SF-36); higher odds of gynecological and reproductive health issues, psychological distress (based on K-10), depression, suicidality, and substance use. Findings from this study suggest that policies and interventions focused on prevention and response to VAW in informal settlements may make critical contributions to improving health for women in these rapidly growing settlements.
Draft Genome Sequence of Daldinia childiae JS-1345, an Endophytic Fungus Isolated from Stem Tissue of Korean Fir

The fungus Daldinia childiae strain JS-1345, isolated from stem tissue of Abies koreana (Korean fir), has shown strong anti-inflammatory activity. Here, we report the genome sequence of D. childiae JS-1345. The final assembly consisted of 133 scaffolds totaling 38,652,569 bp (G+C content, 44.07%). ABSTRACT The fungus Daldinia childiae strain JS-1345, isolated from stem tissue of Abies koreana (Korean fir), has shown strong anti-inflammatory activity. Here, we report the genome sequence of D. childiae JS-1345. The final assembly consisted of 133 scaffolds totaling 38,652,569 bp (G+C content, 44.07%).
Association of E-Selectin gene rs5361 polymorphism with ischemic stroke susceptibility: a systematic review and Meta-analysis

Abstract Background Over the years, a number of published studies showed that E-Selectin gene rs5361 (S128R, Ser128Arg, A561C) variants were associated with the risk of ischemic stroke (IS). However, the results of those case-control studies were still equivocal. Therefore, we performed this meta-analysis to clarify the relationship between E-Selectin gene rs5361 polymorphism and IS risk. Methods We searched the Web of Science, PubMed, VIP, CNKI (China National Knowledge Infrastructure) and Wanfang databases for obtainning the eligible studies according to the inclusion and exclusion criteria. Odds ratios (ORs) with its 95% confidence intervals (CIs) were calculated to evaluate the relationship of E-Selectin gene rs5361 polymorphism with IS susceptibility under the dominant and allelic model with fixed or random effects model. Results Totally, 13 studies with 2888 cases and 2976 controls were selected in this systematic review and meta-analysis This meta-analysis obtained that E-Selectin gene rs5361variants contributed to increase the risk of IS (C vs. A: OR = 2.23, 95%CI = 1.70-2.92, p < 0.001). We also performed a sub-analysis by ethnicity, the results indicated that rs5361 variants were related to an increased risk of IS (East Asian population: C vs. A: OR = 1.97, 95%CI =1.58-2.45, p < 0.001; African population: C vs. A: OR = 5.52, 95%CI = 3.48-8.76, p < 0.001; Caucasian population: C vs. A: OR =1.67, 95%CI =1.32-2.10, p < 0.001). Conclusions Therefore, our meta-analysis suggested that C allele, AA and AC genotypes of E-Selectin gene rs5361 variants were related to an increased risk of IS in overall populations.