Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Characterization and Phylogenetic Position of Two New Species in Rhabdoviridae Infecting the Parasitic Copepod, Salmon Louse (Lepeophtheirus salmonis)

Several new viruses have emerged during farming of salmonids in the North Atlantic causing large losses to the industry. Still the blood feeding copepod parasite, Lepeophtheirus salmonis, remains the major challenge for the industry. Histological examinations of this parasite have revealed the presence of several virus-like particles including some with morphologies similar to rhabdoviruses. This study is the first description of the genome and target tissues of two new species of rhabdoviruses associated with pathology in the salmon louse. Salmon lice were collected at different Atlantic salmon (Salmo salar) farming sites on the west coast of Norway and prepared for histology, transmission electron microscopy and Illumina sequencing of the complete RNA extracted from these lice. The nearly complete genomes, around 11 600 nucleotides encoding the five typical rhabdovirus genes N, P, M, G and L, of two new species were obtained. The genome sequences, the putative protein sequences, and predicted transcription strategies for the two viruses are presented. Phylogenetic analyses of the putative N and L proteins indicated closest similarity to the Sigmavirus/Dimarhabdoviruses cluster, however, the genomes of both new viruses are significantly diverged with no close affinity to any of the existing rhabdovirus genera. In situ hybridization, targeting the N protein genes, showed that the viruses were present in the same glandular tissues as the observed rhabdovirus-like particles. Both viruses were present in all developmental stages of the salmon louse, and associated with necrosis of glandular tissues in adult lice. As the two viruses were present in eggs and free-living planktonic stages of the salmon louse vertical, transmission of the viruses are suggested. The tissues of the lice host, Atlantic salmon, with the exception of skin at the attachment site for the salmon louse chalimi stages, were negative for these two viruses.
Space modulation on wireless fading channels

To increase the data rate for future wireless systems, a novel scheme using multiple transmit antennas for space digital modulation is proposed. In the scheme of space modulation, more than two antennas are employed to transmit and signal the information bits. The novel space modulation scheme is termed space shift keying (SSK). Numerical results are presented to examine the reception performance.
BET Proteins Exhibit Transcriptional and Functional Opposition in the Epithelial-to-Mesenchymal Transition

Transcriptional programs in embryogenesis and cancer, such as the epithelial-to-mesenchymal transition (EMT), ensure cellular plasticity, an essential feature of carcinoma progression. As effectors of signal transduction, the bromodomain and extraterminal (BET) proteins are well suited to support plasticity because they function as co-activators or co-repressors of mammalian transcriptomes. Here, using both hormone-sensitive and triple-negative breast cancer (TNBC) model systems, we systematically altered EMT transcriptional profiles by manipulating individual BET proteins and found that BRD2 positively regulates EMT, whereas BRD3 and BRD4 repress this program. Knockdown of individual BET proteins revealed independent transcriptional networks that differed from each other and from the small-molecule pan-BET inhibitor JQ1, which previously had been misleadingly asserted to be BRD4-selective. Available small-molecule pan-BET inhibitors, proposed as antiproliferative agents in cancer clinical trials, obscure these biological differences. Transcriptional profiling reveals that individual BET proteins, inhibited separately, engage in and control EMT through unique processes. Implications: The distinct and opposing functions of BET proteins in the EMT process suggests the need for more member-selective epigenetic targeting agents. Visual Overview: http://mcr.aacrjournals. org/content/molcanres/16/4/580/F1.large. jpg. Mol Cancer Res; 16(4); 580–6. ©2018 AACR. Visual Overview
Biocompatibility of braided poly(L-lactic acid) nanofiber wires applied as tissue sutures

Almost all sutures in current usage only play one role, i.e. to mechanically tie wound tissues together. Drug-loaded composite nanofibers obtained through coaxial electrospinning can initiate the development of a new type of biodegradable sutures with drug release. In this work, electrospun poly(L-lactic acid) (PLLA) nanofibers with uniaxial alignment were made into braided wires and were coated with chitosan and applied as tissue sutures. Toxicity evaluation on cells for the chitosan-coated PLLA braided wires was carried out using the MTT (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) test, and an in vivo study was conducted by implanting the braided wires into muscle tissues of rats. The inflammation responses were examined at 3, 7, 14, 21 and 28 days after implanting. Experimental results indicated that the braided PLLA nanofiber wires coated with chitosan exhibited comparable tensile and knot strengths to those of a commercial suture, could tie wounded tissues for a complete healing without any breakage, had no cellular toxicity and could promote cell growth well. The chitosan-coated PLLA sutures showed better histological compatibility than a silk suture in the in vivo study. Braided PLLA nanofiber wires fabricated using an electrospinning process followed by a braiding technique and coated with chitosan are applicable for uses within the body. Copyright © 2009 Society of Chemical Industry
Benchmark Dose Estimation for Cadmium-Induced Renal Tubular Damage among Environmental Cadmium-Exposed Women Aged 35–54 Years in Two Counties of China

Background A number of factors, including gender, age, smoking habits, and occupational exposure, affect the levels of urinary cadmium. Few studies have considered these influences when calculating the benchmark dose (BMD) of cadmium. In the present study, we aimed to calculate BMDs and their 95% lower confidence bounds (BMDLs) for cadmium-induced renal tubular effects in an age-specific population in south-central China. Methods In this study, urinary cadmium, β2-microglobulin, and N-acetyl-β-D-glucosaminidase levels were measured in morning urine samples from 490 randomly selected non-smoking women aged 35–54 years. Participants were selected using stratified cluster sampling in two counties (counties A and B) in China. Multiple regression and logistic regression analyses were used to investigate the dose-response relationship between urinary cadmium levels and tubular effects. BMDs/BMDLs corresponding to an additional risk (benchmark response) of 5% and 10% were calculated with assumed cut-off values of the 84th and 90th percentile of urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase levels of the controls. Results Urinary levels of β2-microglobulin and N-acetyl-β-D-glucosaminidase increased significantly with increasing levels of urinary cadmium. Age was not associated with urinary cadmium levels, possibly because of the narrow age range included in this study. Based on urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase, BMDs and BMDLs of urinary cadmium ranged from 2.08 to 3.80 (1.41–2.18) µg/g cr for subjects in county A and from 0.99 to 3.34 (0.74–1.91) µg/g cr for those in county B. The predetermined benchmark response of 0.05 and the 90th percentiles of urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase levels of the subjects not exposed to cadmium (i.e., the control group) served as cut-off values. Conclusions The obtained BMDs of urinary cadmium were similar to the reference point of 1 µg/g cr, as suggested by the European Food Safety Authority, indicating that cadmium exposure must be reduced to protect human health.
Risk of Embolism and Death in Infective Endocarditis: Prognostic Value of Echocardiography: A Prospective Multicenter Study

Background—The incidence of embolic events (EE) and death is still high in patients with infective endocarditis (IE), and data about predictors of these 2 major complications are conflicting. Moreover, the exact role of echocardiography in risk stratification is not well defined. Methods and Results—In a multicenter prospective European study, including 384 consecutive patients (aged 57±17 years) with definite IE according to Duke University criteria, we tested clinical, microbiological, and echocardiographic data as potential predictors of EE and 1-year mortality. Transesophageal echocardiography was performed in all patients. Embolism occurred before or after IE diagnosis (total-EE) in 131 patients (34.1%) and after initiation of antibiotic therapy (new-EE) in 28 patients (7.3%). Staphylococcus aureus and Streptococcus bovis were independently associated with total-EE, whereas vegetation length >10 mm and severe vegetation mobility were predictors of new-EE, even after adjustment for S aureus and S bovis. One-year mortality was 20.6%. In multivariable analysis, independently of the other predictors of death (age, female sex, creatinine serum >2 mg/L, moderate or severe congestive heart failure, and S aureus) and comorbidity, vegetation length >15 mm was a predictor of 1-year mortality (adjusted relative risk=1.8; 95% CI, 1.10 to 2.82; P=0.02). Conclusions—In IE, vegetation length is a strong predictor of new-EE and mortality. In combination with clinical and microbiological findings, echocardiography may identify high-risk patients who will need a more aggressive therapeutic strategy.
Novel Loci Associated With PR Interval in a Genome-Wide Association Study of 10 African American Cohorts

Background—The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results—We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (&lgr; range: 0.9–1.1), although not after genomic control correction was applied to the overall meta-analysis (&lgr;: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0×10−8), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0×10−8). Conclusions—This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.
Bovine Exome Sequence Analysis and Targeted SNP Genotyping of Recessive Fertility Defects BH1, HH2, and HH3 Reveal a Putative Causative Mutation in SMC2 for HH3

The recent discovery of bovine haplotypes with negative effects on fertility in the Brown Swiss, Holstein, and Jersey breeds has allowed producers to identify carrier animals using commercial single nucleotide polymorphism (SNP) genotyping assays. This study was devised to identify the causative mutations underlying defective bovine embryo development contained within three of these haplotypes (Brown Swiss haplotype 1 and Holstein haplotypes 2 and 3) by combining exome capture with next generation sequencing. Of the 68,476,640 sequence variations (SV) identified, only 1,311 genome-wide SNP were concordant with the haplotype status of 21 sequenced carriers. Validation genotyping of 36 candidate SNP identified only 1 variant that was concordant to Holstein haplotype 3 (HH3), while no variants located within the refined intervals for HH2 or BH1 were concordant. The variant strictly associated with HH3 is a non-synonymous SNP (T/C) within exon 24 of the Structural Maintenance of Chromosomes 2 (SMC2) on Chromosome 8 at position 95,410,507 (UMD3.1). This polymorphism changes amino acid 1135 from phenylalanine to serine and causes a non-neutral, non-tolerated, and evolutionarily unlikely substitution within the NTPase domain of the encoded protein. Because only exome capture sequencing was used, we could not rule out the possibility that the true causative mutation for HH3 might lie in a non-exonic genomic location. Given the essential role of SMC2 in DNA repair, chromosome condensation and segregation during cell division, our findings strongly support the non-synonymous SNP (T/C) in SMC2 as the likely causative mutation. The absence of concordant variations for HH2 or BH1 suggests either the underlying causative mutations lie within a non-exomic region or in exome regions not covered by the capture array.
Prevalence of Hypertrophic Cardiomyopathy in Fetuses of Mothers with Gestational Diabetes before Initiating Treatment

Abstract Objective To evaluate the prevalence of hypertrophic cardiomyopathy (HCM) in fetuses of pregnant women with gestational diabetes mellitus (GDM) in the beginning of the treatment. Methods A cross-sectional study was performed between July 1, 2013, and December 20, 2013, in a public maternity clinic in southern Brazil. The subjects were 63 fetuses of mothers with gestational diabetes, with a single pregnancy and no other associated pathologies. We diagnosed HCM through a fetal echocardiography before treatment and evaluated the maternal and fetal characteristics. Results The average age of the pregnant women was 32.32 (±6.2) years, and the average gestational age at the time of the evaluation was 30.59 (±2.27) weeks. The interventricular septum thickness showed a standard deviation of more than two in 50.8% of the fetuses (95% confidence interval [95%CI]: 38.1–63.5%). The left ventricular wall thickness showed a standard deviation of more than 2 in 13 (20.6%) fetuses (95%CI: 11.1–30.2%). The HCM was confirmed in 54% of the fetuses (95%CI: 41.3–65.1%). The fetal abdominal circumference was normal in 46 (73%) fetuses, and 50% of these fetuses had HCM. Conclusion The prevalence of hypertrophic cardiomyopathy in fetuses of pregnant women with GDM before treatment was of 54% (95%CI: 41.3–65.1%).
Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol‐containing oral contraceptive in healthy adult women

Aims This study aimed to investigate whether cabotegravir (CAB), an integrase inhibitor in development for treatment and prevention of human immunodeficiency virus‐1, influences the pharmacokinetics (PK) of a levonorgestrel (LNG) and ethinyl oestradiol (EO)–containing oral contraceptive (OC) in healthy women. Methods In this open‐label, fixed‐sequence crossover study, healthy female subjects received LNG 0.15 mg/EO 0.03 mg tablet once daily Days 1–10 alone and with oral CAB 30 mg once daily Days 11–21. At the end of each treatment period, subjects underwent predose sampling for concentrations of follicle‐stimulating hormone, luteinizing hormone, and progesterone and serial PK sampling for plasma LNG, EO, and CAB concentrations. Results Twenty women were enrolled, and 19 completed the study. One subject was withdrawn due to an adverse event unrelated to study medications. Geometric least squares mean ratios (90% confidence interval) of LNG + CAB vs. LNG alone for LNG area under the plasma concentration–time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.12 (1.07–1.18) and 1.05 (0.96–1.15), respectively. Geometric least squares mean ratio (90% confidence interval) of EO + CAB vs. EO alone for EO area under the plasma concentration–time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.02 (0.97–1.08) and 0.92 (0.83–1.03), respectively. Steady‐state CAB PK parameters were comparable to historical values. There was no apparent difference in mean luteinizing hormone, follicle‐stimulating hormone, and progesterone concentrations between periods. No clinically significant trends in laboratory values, vital signs, or electrocardiography values were observed. Conclusions Repeat doses of oral CAB had no significant effect on LNG/EO PK or pharmacodynamics, which supports CAB coadministration with LNG/EO OCs in clinical practice.
Hemodialysis Disparities in African Americans: The Deeply Integrated Concept of Race in the Social Fabric of Our Society

End‐stage renal disease (ESRD) is one of the starkest examples of racial/ethnic disparities in health. Racial/ethnic minorities are 1.5 to nearly 4 times more likely than their non‐Hispanic White counterparts to require renal replacement therapy (RRT), with African Americans suffering from the highest rates of ESRD. Despite improvements over the last 25 years, substantial racial differences are persistent in dialysis quality measures such as RRT modality options, dialysis adequacy, anemia, mineral and bone disease, vascular access, and pre‐ESRD care. This report will outline the current status of racial disparities in key ESRD quality measures and explore the impact of race. While the term race represents a social construct, its association with health is more complex. Multiple individual and community level social determinants of health are defined by the social positioning of race in the U.S., while biologic differences may reflect distinct epigenetic changes and linkages to ancestral geographic origins. Together, these factors conspire to influence dialysis outcomes among African Americans with ESRD.
Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors

Significance Monitoring human organ-on-a-chip systems presents a significant challenge, where the capability of in situ continual monitoring of organ behaviors and their responses to pharmaceutical compounds over extended periods of time is critical in understanding the dynamics of drug effects and therefore accurate prediction of human organ reactions. In this work, we report a fully integrated modular physical, biochemical, and optical sensing platform, interfaced through a fluidics-routing breadboard with a multi–organ-on-a-chip system to achieve in situ, continual, and automated sensing of microenvironment biophysical and biochemical parameters. It is anticipated that our platform technology that is conveniently compatible with existing organ-on-a-chip models will potentially enhance their performance in drug screening by providing a multitude of sensing data not previously available. Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner. We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters.
Moral dilemmas of women undergoing pregnancy termination for medical reasons in Poland

Abstract Objectives: We explored the religious views and dilemmas of Polish women making the decision to terminate a pregnancy. The article discusses the highly restrictive legislation and significant influence of the Church on the lives of Polish citizens. Methods: This study was designed to investigate the effect of religious and political beliefs, social and moral conditioning and professional support on the decision to abort a fetus. A 65-item questionnaire was administered to 60 participants at the time of their pregnancy termination. Results: Pregnancy termination was performed outside the resident county in 32% of cases. Approximately 88% of respondents declared themselves Catholic, but only 22% intended to admit to the pregnancy termination during confession. Five percent of respondents feared the reaction of the priest, while the remaining respondents did not perceive termination of pregnancy for medical reasons as a sin. Of the women who had previously opposed pregnancy termination, 27% changed their mind once they were personally involved. Conclusions: The decision to abort a pregnancy for medical reasons is sensitive to religious and social determinants, especially in the current political situation in which abortion may become prohibited in Poland. The high response rate (100%) was probably the result of the patients’ attitudes: they repeatedly emphasised they were thankful for the help and empathy of the medical personnel and for being allowed to undergo the procedure. In Poland, the majority of centres use conscience clauses to justify their refusal to terminate a pregnancy.