Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Human Prostate and Bladder Smooth Muscle Contraction, Vasoconstriction of Porcine Renal and Coronary Arteries, and Growth-Related Functions of Prostate Stromal Cells by Presumed Small Molecule Gαq/11 Inhibitor, YM-254890

Introduction: Lower urinary tract symptoms (LUTS) involve benign prostatic hyperplasia (BPH) and overactive bladder (OAB). Standard-of-care medical treatment includes α1-blockers and antimuscarinics for reduction of prostate and detrusor smooth muscle tone, respectively, and 5α-reductase inhibitors (5-ARI) to prevent prostate growth. Current medications are marked by high discontinuation rates due to unfavourable balance between efficacy and treatment-limiting side effects, ranging from dry mouth for antimuscarinics to cardiovascular dysregulation and a tendency to fall for α1-blockers, which results from hypotension, due to vasorelaxation. Agonist-induced smooth muscle contractions are caused by activation of receptor-coupled G-proteins. However, little is known about receptor- and organ-specific differences in coupling to G-proteins. With YM-254890, a small molecule inhibitor with presumed specificity for Gαq/11 became recently available. Here, we investigated effects of YM-254890 on prostate, bladder and vascular smooth muscle contraction, and on growth-related functions in prostate stromal cells. Methods: Contractions of human prostate and detrusor tissues, porcine renal and coronary arteries were induced in an organ bath. Proliferation (EdU assay), growth (colony formation), apoptosis and cell death (flow cytometry), viability (CCK-8) and actin organization (phalloidin staining) were studied in cultured human prostate stromal cells (WPMY-1). Results: Contractions by α1-adrenergic agonists, U46619, endothelin-1, and neurogenic contractions were nearly completely inhibited by YM-254890 (30 nM) in prostate tissues. Contractions by cholinergic agonists, U46619, endothelin-1, and neurogenic contractions were only partly inhibited in detrusor tissues. Contractions by α1-adrenergic agonists, U46619, endothelin-1, and neurogenic contractions were strongly, but not fully inhibited in renal arteries. Contractions by cholinergic agonists were completely, but by U46619 and endothelin-1 only strongly inhibited, and neurogenic contractions reduced by half in coronary arteries. YM-254890 had no effect on agonist-independent contractions induced by highmolar (80 mM) potassium chloride (KCl). Neurogenic detrusor contractions were fully sensitive to tetrodotoxin. In WPMY-1 cells, YM-254890 caused breakdown of actin polymerization and organization, and obvious, but clearly limited decreases of proliferation rate, colony formation and viability, and slightly increased apoptosis. Conclusion: Intracellular post-receptor signaling pathways are shared by Gαq-coupled contractile receptors in multiple smooth muscle-rich organs, but to different extent. While inhibition of Gαq/11 causes actin breakdown, anti-proliferative effects were detectable but clearly limited. Together this may aid in developing future pharmaceutical targets for LUTS and antihypertensive medication.
Performance and Configuration of Artificial Intelligence in Educational Settings. Introducing a New Reliability Concept Based on Content Analysis

Learning analytics represent a promising approach for fostering personalized learning processes. Most applications of this technology currently do not use textual data for providing information on learning, or for deriving recommendations for further development. This paper presents the results of three studies aiming to make textual information usable. In the first study, the iota concept is introduced as a new content analysis measure to evaluate inter-coder reliability. The main advantage of this new concept is that it provides a reliability estimation for every single category, allowing deeper insight into the quality of textual analysis. The second study simulates the process of content analysis, comparing the new iota concept with well-established measures (e.g., Krippendorff’s Alpha, percentage agreement). The results show that the new concept covers the true reliability of a coding scheme, and is not affected by the number of coders or categories, the sample size, or the distribution of data. Furthermore, cut-off values are derived for judging the quality of the analysis. The third study employs the new concept, as it analyzes the performance of different artificial intelligence (AI) approaches for interpreting textual data based on 90 different constructs. The texts used here were either created by apprentices, students, and pupils, or were taken from vocational textbooks. The paper shows that AI can reliably interpret textual information for learning purposes, and also provides recommendations for optimal AI configuration.
Heat Stress Affects Jejunal Immunity of Yellow-Feathered Broilers and Is Potentially Mediated by the Microbiome

In the perspective of the global climate change leading to increasing temperature, heat stress (HS) has become a severe issue in broiler production, including the indigenous yellow-feathered broilers. The present study aimed to investigate the effects of HS on jejunal immune response, microbiota structure and their correlation in yellow-feathered broilers. A total of forty female broilers (56-days-old) were randomly and equally divided into normal treatment group (NT group, 21.3 ± 1.2°C, 24 h/day) and HS group (32.5 ± 1.4°C, 8 h/day) with five replicates of each for 4 weeks feeding trial. The results showed that HS exposure increased the contents of TNF-α, IL-1β, and IL-6 in jejunal mucosa (p < 0.05). The HS exposure up-regulated the relative fold changes of NF-κB, TNF-α, IL-1β, and IL-6 (p < 0.01) while down-regulated the relative fold change of IFN-γ in jejunal mucosa (p < 0.05). Meanwhile, HS had no significant impacts on alpha diversity of jejunal microbiota such as Simpson, Chao1 richness estimator (Chao 1), abundance-based coverage estimators (ACE), and Shannon index (p > 0.10). Broilers exposed to HS reduced the jejunal microbial species number at the class and order level (p < 0.05). Moreover, HS decreased the relative abundance of Ruminococcus, Bdellovibrio, and Serratia at the genus level in jejunum (p < 0.05). At the phylum level, four species of bacteria (Bacteroidetes, Cyanobacteria, Thermi, and TM7) were significantly associated with immune-related genes expression (p < 0.05). At the genus level, ten species of bacteria were significantly correlated with the expression of immune-related genes (p < 0.05), including Caulobacteraceae, Actinomyces, Ruminococcaceae, Thermus, Bdellovibrio, Clostridiales, Sediminibacterium, Bacteroides, Sphingomonadales and Ruminococcus. In particular, the microbial with significantly different abundances, Ruminococcus and Bdellovibrio, were negatively associated with pro-inflammatory cytokines expression (p < 0.05). These findings demonstrated that HS exposure promoted the production of pro-inflammatory cytokines in yellow-feathered broilers’ jejunum. The detrimental effects of HS on jejunal immune response might be related to dysbiosis, especially the reduced levels of Ruminococcus and Bdellovibrio.
Development of an ergonomic risk assessment tool for work postures

The most widely used method for assessing work-related musculoskeletal disorders (WMSDs) is still the observational method, mainly because it is inexpensive and practical for use in a wide range of workplaces. However, there are no tools available that cover the wide range of physical risk factors at workplaces. Most of the existing observational methods have not been extensively tested for their reliability and validity during the development process. Therefore, the main objectives of this study are to (1) to develop a new observational technique called the Workplace Ergonomic Risk Assessment (WERA) method and (2) to determine the reliability and validity of the WERA method. The study was conducted in two phases: development of the WERA paper checklist from scientific evidence and literature review (Phase 1) and development of the WERA software program using Visual Basic programming (Phase 2). In the validity trials, the relationship of the main WERA body part scores to the development of pain or discomfort was statistically significant for the wrist, shoulder, and back regions. This shows that the WERA assessment provided a good indication of work related musculoskeletal disorders which may be reported as pains, aches or discomfort in the relevant body area. In the reliability trials, the results of inter-observer reliability demonstrated moderate agreement among the observers (K=0.41) from the feedback survey about the usability of WERA tool. On the other hand, all participants were agreed that the WERA tool was easy and quick to use, applicable to workplace assessment for the wide range of tasks, and valuable at work. The WERA tool has been developed for both paper checklist and software program use. It can be used to identify the physical risk factors associated with WMSDs at workplaces.
Identification and Pathogenicity Analysis of the Pathogen Causing Spotted Spleen in Muscovy Duck

Since September 2020, the clinical symptoms of Muscovy duck spleen spots have appeared in Guangdong, Guangxi, Jiangxi, Hunan, Hubei, and other provinces, resulting in a large number of Muscovy duck deaths and great economic losses. The absence of the typical clinical symptoms caused by pathogenic microorganisms makes the cause of the spotted spleen a mystery. High-throughput sequencing results suggested that Riemerella anatipestifer (R. anatipestifer) may be the pathogen. Then, R. anatipestifer was regarded as the research target for isolation, identification, and pathogenicity assessment. After biochemical test, PCR amplification, and serotype determination, it was confirmed that the isolated strain CZG-1 was serotype 15 R. anatipestifer. Typical spotted spleen symptoms were observed after CZG-1 infection. Furthermore, drug sensitivity assays showed the similar drug-resistant spectrum of R. anatipestifer serotype 15 to other serotypes; for example, all test strains were resistant to polymyxin, gentamicin, and neomycin. The CZG-1 strain has high pathogenicity, and its lethal dose of 50% (LD50) is 35.122 CFU/ml. Virulence gene determination showed that the CZG-1 strain had at least five virulence genes, bioF, TSS9-1, TSS9-2, PncA, and 0373Right. Above all, this study identified and proved that the pathogen of spotted spleen in ducks was R. anatipestifer serotype 15, which caused death of ducks without the typical symptoms of bacterial infection. The results of this study enriched the knowledge of symptom after R. anatipestifer infection, provided a reference to the identification of the pathogen of spotted spleen, and provided theoretical basis for prevention and control of spotted spleen.
Farmer Perceptions Related to Potato Production and Late Blight Management in Two Communities in the Peruvian Andes

Potato late blight (LB), caused by the oomycete, Phytophthora infestans, continues to be a major constraint of potato in the Andean region and worldwide. Farmers perception regarding potato production with particular emphasis on management practices for LB was surveyed in two communities in the Peruvian highlands using a questionnaire with 25 questions, many with multiple choice questions. In the village of Paucartambo, 84 women and 485 men of different ages participated in the survey, while in the village of Ulcumayo, there were 146 women and 396 men, also of different ages. Overall, responses were similar between the two locations, with some small but significant differences. In general, there was a very clear association between age and education, with only young men and women having secondary education. Respondents in both locations overwhelmingly chose LB as the main constraint to production and cited either personal experience or agrochemical vendors as the primary sources of information about disease management. Many cultivars (25+) are grown in both locations, with the two most important cultivars, Yungay and Huayro, being common in both locations while others differed. There was evidence of confusion around the concept of host plant resistance, as certain cultivars were cited as both relatively resistant and susceptible. Many trade names of fungicides were recalled by respondents, but most were relatively old products. Correspondence analysis indicated gender effects on LB management practices and information sources in both locations that could be taken into consideration to refine future interventions for research and capacity building, such as offering refresher training courses for extension educators, including female extension workers, to help farmers understand basic concepts to manage host resistance and fungicides properly, and improve access to resistant varieties and effective fungicides.
Mechanisms of Cardiorenal Protection With SGLT2 Inhibitors in Patients With T2DM Based on Network Pharmacology

Purpose Sodium-glucose cotransporter 2 (SGLT2) inhibitors have cardiorenal protective effects regardless of whether they are combined with type 2 diabetes mellitus, but their specific pharmacological mechanisms remain undetermined. Materials and Methods We used databases to obtain information on the disease targets of “Chronic Kidney Disease,” “Heart Failure,” and “Type 2 Diabetes Mellitus” as well as the targets of SGLT2 inhibitors. After screening the common targets, we used Cytoscape 3.8. 2 software to construct SGLT2 inhibitors' regulatory network and protein-protein interaction network. The clusterProfiler R package was used to perform gene ontology functional analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analyses on the target genes. Molecular docking was utilized to verify the relationship between SGLT2 inhibitors and core targets. Results Seven different SGLT2 inhibitors were found to have cardiorenal protective effects on 146 targets. The main mechanisms of action may be associated with lipid and atherosclerosis, MAPK signaling pathway, Rap1 signaling pathway, endocrine resistance, fluid shear stress, atherosclerosis, TNF signaling pathway, relaxin signaling pathway, neurotrophin signaling pathway, and AGEs-RAGE signaling pathway in diabetic complications were related. Docking of SGLT2 inhibitors with key targets such as GAPDH, MAPK3, MMP9, MAPK1, and NRAS revealed that these compounds bind to proteins spontaneously. Conclusion Based on pharmacological networks, this study elucidates the potential mechanisms of action of SGLT2 inhibitors from a systemic and holistic perspective. These key targets and pathways will provide new ideas for future studies on the pharmacological mechanisms of cardiorenal protection by SGLT2 inhibitors.
RNA-Seq Analysis of the Growth Hormone Transgenic Female Triploid Atlantic Salmon (Salmo salar) Hepatic Transcriptome Reveals Broad Temperature-Mediated Effects on Metabolism and Other Biological Processes

This study examined the impact of rearing temperature (10.5, 13.5 or 16.5°C) on the hepatic transcriptome of AquAdvantage Salmon (growth hormone transgenic female triploid Atlantic salmon) at an average weight of 800 g. Six stranded PE libraries were Illumina-sequenced from each temperature group, resulting in an average of over 100 M raw reads per individual fish. RNA-sequencing (RNA-seq) results showed the greatest difference in the number of differentially expressed transcripts (1750 DETs), as revealed by both DESeq2 and edgeR (q < 0.05; fold-change > |1.5|), was between the 10.5 and 16.5°C temperature groups. In contrast, 172 and 52 DETs were found in the 10.5 vs. 13.5°C and the 13.5 vs. 16.5°C comparisons, respectively. Considering the DETs between the 10.5 and 16.5°C groups, 282 enriched gene ontology (GO) terms were identified (q < 0.05), including “response to stress”, “immune system process”, “lipid metabolic process”, “oxidation-reduction process”, and “cholesterol metabolic process”, suggesting elevated temperature elicited broad effects on multiple biological systems. Pathway analysis using ClueGO showed additional impacts on amino acid and lipid metabolism. There was a significant positive correlation between RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) results for 8 of 9 metabolic-related transcripts tested. RT-qPCR results also correlated to changes in fillet tissue composition previously reported in these salmon (e.g., methionine and lysine concentrations positively correlated with hsp90ab1 transcript expression), suggesting that rearing temperature played a significant role in mediating metabolic/biosynthetic pathways of AquAdvantage Salmon. Many transcripts related to lipid/fatty acid metabolism (e.g., elovl2, fabpi, hacd2, mgll, s27a2, thrsp) were downregulated at 16.5°C compared to both other temperature groups. Additionally, enrichment of stress-, apoptosis- and catabolism-relevant GO terms at 16.5°C suggests that this temperature may not be ideal for commercial production when using freshwater recirculating aquaculture systems (RAS). This study relates phenotypic responses to transcript-specific findings and therefore aids in the determination of an optimal rearing temperature for AquAdvantage Salmon. With approval to grow and sell AquAdvantage Salmon in the United States and Canada, the novel insights provided by this research can help industry expansion by promoting optimal physiological performance and health.
Healthcare Professionals' Views on the Management of Medication Complexities in the Elderly With Mental Health Disorders: A Cross-Sectional Study

Background Many challenges in elderly pharmacotherapy are identified, including the use of Potentially Inappropriate Medications (PIMs) which may increase the odds of adverse events, especially in elderly patients with mental health disorders (e. g., behavioral, and psychological symptoms of dementia–BPSD, schizophrenia, bipolar disorder). However, information on the knowledge and practice of healthcare professionals (HCPs) about this topic is still scarce. Methods A cross-sectional study was undertaken from July-October 2019. An online questionnaire was specifically designed and validated for this study. We sought HCPs (physicians, pharmacists, and nurses) worldwide, using (a) social media, via Facebook, Twitter, and LinkedIn; and (b) email contacts of the research team (convenience sample). Either way participants were asked to share on their social media or via e-mail the questionnaires with other HCPs (snowballing sample). The survey assessed two main domains: knowledge and practice. Knowledge was evaluated by self-report (perceived knowledge by a 5-item Likert confidence scale) and using three clinical cases, scored between 0 and 30 points (each one rated from 0 to 10 points; real knowledge). Barriers in clinical practice were evaluated using a 5-item Likert scale judging practitioners' opinion. Results A total of 165 questionnaires were collected. HCPs were mainly female (n = 114; 69.1%), with a mean age of 35.3 ± 11.3 years old. Seventy-two percent (n = 118) were pharmacists, 21.1% (n = 35) were physicians, and 7.3% (n = 12) nurses. There was a weak correlation, albeit significant, between perceived and real knowledge (r = 0.199; p = 0.001). The mean score of the clinical vignettes regarding elderly patients with dementia and bipolar disorder were 4.59 ± 4.08 and 4.86 ± 2.97 points, respectively. Most HCPs were classified as having an intermediate knowledge (n = 100; 60.6%) about medication complexities in the elderly with mental disorders. Most HCPs agreed that lack of time (81.6%; n = 138), lack of education and training on elderly pharmacotherapy (72.2%; n = 122), and lack of tools adapted to daily practice (61.8%; n = 105) were the main barriers. Conclusions Most of the HCPs felt confident to manage medication complexities in elder patients with mental disorders, but only a minority obtained a good score in the knowledge assessment test. The main barriers identified included structural barriers (tools unfit for practice) and process barriers (time).
HIV-Quasipore: A Suite of HIV-1-Specific Nanopore Basecallers Designed to Enhance Viral Quasispecies Detection

Accounting for genetic variation is an essential consideration during human immunodeficiency virus type 1 (HIV-1) investigation. Nanopore sequencing preserves proviral integrity by passing long genomic fragments through ionic channels, allowing reads that span the entire genome of different viral quasispecies (vQS). However, this sequencing method has suffered from high error rates, limiting its utility. This was the inspiration behind HIV-Quasipore: an HIV-1-specific Nanopore basecaller suite designed to overcome these error rates through training with gold-standard data. It comprises three deep learning-based R9.4. 1 basecallers: fast, high accuracy (HAC), super accuracy (SUP), and two R10.3 deep learning-based basecallers: HAC and SUP. This was accomplished by sequencing the HIV-1 J-Lat 10.6 cell line using Nanopore and high-quality Sanger techniques. Training significantly reduced basecaller error rates across all models (Student’s one-sided t-test; p = 0.0) where median error rates were 0.0189, 0.0018, 0.0008, for R9.4. 1 HIV-Quasipore-fast, HAC, SUP, and 0.0007, 0.0011 for R10.3 HIV-Quasipore-HAC, and SUP, respectively. This improved quality reduces the resolution needed to accurately detect a vQS from 22.4 to 2.6% of total positional coverage for R9.4. 1 HIV-Quasipore-fast, 6.9 to 0.5% for R9.4. 1 HIV-Quasipore-HAC, 4.5 to 0.3% for R9.4. 1 HIV-Quasipore-SUP, 8.0 to 0.3% for R10.3 HIV-Quasipore-HAC, and 5.4 to 0.3% for R10.3 HIV-Quasipore-SUP. This was consistently observed across the entire J-Lat 10.6 genome and maintained across longer reads. Reads with greater than 8,000 nucleotides display a median nucleotide identity of 0.9819, 0.9982, and 0.9991, for R9.4. 1 HIV-Quasipore-fast, HAC, SUP, and 0.9993, 0.9988 for R10.3 HIV-Quasipore-HAC, and SUP, respectively. To evaluate the robustness of this tool against unseen data, HIV-Quasipore and their corresponding pretrained basecallers were used to sequence the J-Lat 9.2 cell line and a clinical isolate acquired from the Drexel Medicine CARES cohort. When sample reads were compared against their corresponding consensus sequence, all HIV-Quasipore basecallers displayed higher median alignment accuracies than their pretrained counterparts for both the J-Lat 9.2 cell line and clinical isolate. Using Nanopore sequencing can allow investigators to explore topics, such as vQS profile detection, HIV-1 integration site analysis, whole genome amplification, gene coevolution, and CRISPR-induced indel detection, among others. HIV-Quasipore basecallers can be acquired here: https://github.com/DamLabResources/HIV-Quasipore-basecallers.
Deep Learning in RNA Structure Studies

Deep learning, or artificial neural networks, is a type of machine learning algorithm that can decipher underlying relationships from large volumes of data and has been successfully applied to solve structural biology questions, such as RNA structure. RNA can fold into complex RNA structures by forming hydrogen bonds, thereby playing an essential role in biological processes. While experimental effort has enabled resolving RNA structure at the genome-wide scale, deep learning has been more recently introduced for studying RNA structure and its functionality. Here, we discuss successful applications of deep learning to solve RNA problems, including predictions of RNA structures, non-canonical G-quadruplex, RNA-protein interactions and RNA switches. Following these cases, we give a general guide to deep learning for solving RNA structure problems.