Miracle-dz/UniFAR-FTUs huggingface dataset:
A multifaceted investigation into molecular associations of chronic thromboembolic pulmonary hypertension pathogenesis

Purpose Chronic thromboembolic pulmonary hypertension is characterized by incomplete thrombus resolution following acute pulmonary embolism, leading to pulmonary hypertension and right ventricular dysfunction. Conditions such as thrombophilias, dysfibrinogenemias, and inflammatory states have been associated with chronic thromboembolic pulmonary hypertension, but molecular mechanisms underlying this disease are poorly understood. We sought to characterize the molecular and functional features associated with chronic thromboembolic pulmonary hypertension using a multifaceted approach. Methods We utilized functional assays to compare clot lysis times between chronic thromboembolic pulmonary hypertension patients and multiple controls. We then performed immunohistochemical characterization of tissue from chronic thromboembolic pulmonary hypertension, pulmonary arterial hypertension, and healthy controls, and examined RNA expression patterns of cultured lymphocytes and pulmonary arterial specimens. We then confirmed RNA expression changes using immunohistochemistry, immunofluorescence, and Western blotting in pulmonary arterial tissue. Results Clot lysis times in chronic thromboembolic pulmonary hypertension patients are similar to multiple controls. Chronic thromboembolic pulmonary hypertension endarterectomized tissue has reduced expression of both smooth muscle and endothelial cell markers. RNA expression profiles in pulmonary arteries and peripheral blood lymphocytes identified differences in RNA transcript levels related to inflammation and growth factor signaling, which we confirmed using immunohistochemistry. Gene expression data also suggested significant alterations in metabolic pathways, and immunofluorescence and Western blot experiments confirmed that unglycosylated CD36 and adiponectin expression were increased in chronic thromboembolic pulmonary hypertension versus controls. Conclusions Our data do not support impaired clot lysis underlying chronic thromboembolic pulmonary hypertension, but did demonstrate distinct molecular patterns present both in peripheral blood and in pathologic specimens of chronic thromboembolic pulmonary hypertension patients suggesting that altered metabolism may play a role in chronic thromboembolic pulmonary hypertension pathogenesis.
Expression of melanocortin 1 receptor before and after narrowband UVB phototherapy treatment in patients with stable vitiligo: A prospective study

Vitiligo is a disease characterized by skin depigmentation caused by the selective destruction of melanocytes. The melanocortin system participates as a regulator of melanogenesis and skin pigmentation. Narrowband UVB phototherapy (nb-UVB) is currently considered to be the gold standard and first choice treatment method for vitiligo vulgaris. The aim of the present study was to analyze the clinical and biochemical parameters of vitiligo, as well as to determine the expression of proopiomelanocortin (POMC), melanocortin 1 receptor (MC1R) and melanocortin 4 receptor (MC4R) genes in the skin of patients with stable vitiligo receiving nb-UVB phototherapy. Patient clinical and biochemical parameters, and the skin biopsies of 22 patients with stable vitiligo were analyzed. These biopsies were obtained before and after nb-UVB phototherapy. The genetic expression analysis of POMC, MC1R and MC4R genes was performed via RNA-Sequence analysis. A statistical evaluation of the clinical and biochemical parameters, the degree of response to treatment and the expression profiles of the melanocortin system genes were performed to identify their association with treatment response. A two-sided P≤0.05 value was considered to indicate a statistically significant difference. Alterations were observed in the expression profiles of MC1R following nb-UVB phototherapy (P≤0.05). In addition, elevated levels of triiodothyronine were associated with a poor response to nb-UVB phototherapy. In conclusion the current study revealed that nb-UVB phototherapy altered the expression profile of the MC1R gene.
Interdisciplinary Sport Research Can Better Predict Competition Performance, Identify Individual Differences, and Quantify Task Representation

Sport performance consists of interacting individual, task and environmental constraints, but research has used a monodisciplinary, rather than an interdisciplinary approach to understand performance. This study used Australian football (AF) as the exemplar sport to investigate the value of an interdisciplinary approach to understand sport performance. Through this, it was also possible to quantify individual differences and representative task design. Fifty-nine semi-professional Australian footballers participated. Based upon accessibility, combinations of these players completed physiological (3 × 1 km trial) and perceptual-cognitive-motor (small-sided game, SSG) tests, with coach rating of psychological skill (mental toughness coach, MTC). Univariate monodisciplinary models indicated that all tests predicted disposal efficiency; 3 × 1 km trial (p = 0.047), SSG (p = 0.001), and MTC (p = 0.035), but only the SSG predicted coaches' vote (p = 0.003). A multivariate interdisciplinary model indicated that SSG and MTC tests predicted disposal efficiency with a better model fit than the corresponding univariate model. The interdisciplinary model formulated an equation that could identify individual differences in disposal efficiency. In addition, the interdisciplinary model showed that the higher representative SSG test contributed a greater magnitude to the prediction of competition performance, than the lower representative MTC rating. Overall, this study demonstrates that a more comprehensive understanding of sport performance, individual differences, and representative tasks, can be obtained through an interdisciplinary approach.
GPU-Accelerated Discovery of Pathogen-Derived Molecular Mimics of a T-Cell Insulin Epitope

The strong links between (Human Leukocyte Antigen) HLA, infection and autoimmunity combine to implicate T-cells as primary triggers of autoimmune disease (AD). T-cell crossreactivity between microbially-derived peptides and self-peptides has been shown to break tolerance and trigger AD in experimental animal models. Detailed examination of the potential for T-cell crossreactivity to trigger human AD will require means of predicting which peptides might be recognised by autoimmune T-cell receptors (TCRs). Recent developments in high throughput sequencing and bioinformatics mean that it is now possible to link individual TCRs to specific pathologies for the first time. Deconvolution of TCR function requires knowledge of TCR specificity. Positional Scanning Combinatorial Peptide Libraries (PS-CPLs) can be used to predict HLA-restriction and define antigenic peptides derived from self and pathogen proteins. In silico search of the known terrestrial proteome with a prediction algorithm that ranks potential antigens in order of recognition likelihood requires complex, large-scale computations over several days that are infeasible on a personal computer. We decreased the time required for peptide searching to under 30 min using multiple blocks on graphics processing units (GPUs). This time-efficient, cost-effective hardware accelerator was used to screen bacterial and fungal human pathogens for peptide sequences predicted to activate a T-cell clone, InsB4, that was isolated from a patient with type 1 diabetes and recognised the insulin B-derived epitope HLVEALYLV in the context of disease-risk allele HLA A*0201. InsB4 was shown to kill HLA A*0201+ human insulin producing β-cells demonstrating that T-cells with this specificity might contribute to disease. The GPU-accelerated algorithm and multispecies pathogen proteomic databases were validated to discover pathogen-derived peptide sequences that acted as super-agonists for the InsB4 T-cell clone. Peptide-MHC tetramer binding and surface plasmon resonance were used to confirm that the InsB4 TCR bound to the highest-ranked peptide agonists derived from infectious bacteria and fungi. Adoption of GPU-accelerated prediction of T-cell agonists has the capacity to revolutionise our understanding of AD by identifying potential targets for autoimmune T-cells. This approach has further potential for dissecting T-cell responses to infectious disease and cancer.
Frequency-Dependent Reaction of the Triceps Surae Muscle of the Mouse During Electromyostimulation

The difference in the efficacy of altered stimulation parameters in whole-body-electromyostimulation training (WB-EMS) has hardly been examined. Higher impulse frequencies (>50 Hz) might be most adequate for strength gains because of the force frequency relationship (FFR), which describes a greater force production by increasing the applied frequency. Frequencies below this value, however, also seem to have positive influences on muscle strength increases. Therefore, the aim of this study was to analyze possible muscle length changes to different stimulation frequencies of the dissected mouse triceps surae muscle. A bending rod transducer was used to measure and compare changes in muscle lengths at different frequencies in relation to the initial length in the prepared muscle. We found significant differences between the muscle shortening at different frequencies (p < 0.001). At 20 Hz the largest muscle shortening was observed (20 Hz = 3.32 ± 2.06, 60 Hz = 0.77 ± 0.58, 85 Hz = 0.32 ± 0.29, 100 Hz = 0.31 ± 0.29). From a frequency of 60 Hz, the muscle shortening decreased progressively, at stimulation frequencies above 60 Hz the lowest shortenings were recorded. The results demonstrate a different behavior of the isolated triceps surae muscle of the mouse in an ex vivo environment. Even if there is no FFR in this investigation, the results indicate a higher metabolic demand using higher frequencies in electromyostimulation, despite the experimental execution in ex vivo design. Therefore, future studies should take this faster fatigue into account when drawing up training protocols in order to counteract possible frequency modulations.
A Novel Splicing Mutation in the FBN2 Gene in a Family With Congenital Contractural Arachnodactyly

Congenital contractural arachnodactyly (CCA) is an extremely rare monogenic disorder in humans, and the prevalence of CCA is estimated to be less than 1 in 10,000 worldwide. CCA is characterized by arachnodactyly, camptodactyly, the contracture of major joints, scoliosis, pectus deformities, and crumpled ears. Mutations in FBN2 (which encodes fibrillin-2) are responsible for causing this disease. A family with CCA was investigated in this study, and a novel variant, c.3724+3A > C (also identified as IVS28+3A > C), in FBN2 was found in nine patients from the family but was not found in seven unaffected relatives. Reverse transcription-PCR (RT-PCR) and complementary DNA (cDNA) sequencing data showed that exon 28 was skipped in the FBN2 gene. The FBN2 c.3724+3A > C variant led to an in-frame deletion during transcription, which eventually triggered CCA in the Chinese family.
Assessment of Health Research Capacity in Western Sydney Local Health District (WSLHD): A Study on Medical, Nursing and Allied Health Professionals

Background Research should inform clinical decision-making and evidence-based practice for all health professionals. To build research capacity among all health professionals, there is a need to measure the levels of research capacity and identify the gaps and needs of health-care professionals. The aim of the study was to better understand the research culture and capacity of health professionals (medical, nursing and allied health) in Western Sydney Local Health District, Sydney, Australia. Methods A research capacity and culture tool (RCCT) survey was electronically distributed to all health staff in WSLHD. Data were collected between November 2016 and January 2017. Participants were surveyed through a 10-point Likert scale that measured research capacity at the individual, team and organisational levels. Results A total of 393 health staff responded to the study: allied health practitioners (46.3%), nursing staff (35.4%) and medical practitioners (18.3%). Females made 76% of the sample, and 54% were aged between 35 and 54 years. Individual responses were different across professions, with an average median score for medical 6.3 (95% CI 5.8–6.9), allied health 5.3 (95% CI 4.9–5.7) and nursing 4.5 (95% CI 4.1–5.0) after adjustment for age and gender. Team responses for medical staff (average median score 5.9 95% CI 5.3–6.4) were higher than allied health (4.1 95% CI 3.7–4.6) and nursing (4.3 95% CI 3.8–4.8), after adjusting for age and gender. However, there were no differences between the three professions for the organisational responses. Allied health and nursing staff were less confident in obtaining research funding, submitting ethics applications, writing for publication and mentoring colleagues about research. Conclusion This study demonstrates the individual research capacity for medical, allied health and nursing professionals are different. Research capacity building needs to be individually tailored to the specific needs of each profession. This research will inform future capacity building activities and training for health professionals in a large public health organisation of Sydney, Australia.
Survival Rates of Endodontically Treated Teeth After Placement of Definitive Coronal Restoration: 8-Year Retrospective Study

Introduction Preservation of endodontically treated teeth (ETT) depends upon several patient-related and operator-related factors. The objectives of this study were to assess the effects of different types of coronal restoration and delayed placement on ETT survival. Methods Data on dates of root canal treatment (RCT), restoration type, and extraction time of tooth, when applicable, were analyzed for all patients who underwent RCT from 2010 to 2018 at our institution. Inclusion Criteria Root canal-treated teeth with complete preoperative and postoperative radiographs; ETT that were restorable and received final permanent coronal restorations; no periodontal disease or crack detected during RCT; and ETT with acceptable RCT quality. Exclusion Criteria Patients who did not attend for follow-up, those had incomplete information available about the coronal restoration, and those with periodontally compromised teeth were excluded. ETT that involved any procedural error were also excluded. The teeth were categorized according to whether they underwent definitive coronal restoration 0–14 days, 15–59 days, or 60+ days after RCT. The statistical analysis was performed using SPSS version 25 (IBM Corp., Armonk, NY). The rate of survival of ETT of 8 years was estimated, and the differences between groups were determined after applying Kaplan–Meier statistics and log-rank tests. A multivariate Cox regression test and Wilcoxon (Gehan) statistics were computed to analyze the influence of different variables. A P-value <0.05 was considered as statistically significant. Results The type of restoration, opposing dentition, presence of a post, and dentistry training (year 4 or 5 students) showed significant effects on the survival of ETT (P ≤ 0.000). ETT which received crowns was 2.05 times more likely to need extraction than those in which a composite buildup was performed (hazard ratio [HR] 2.05; confidence interval [CI] 1.84–2.29; P ≤ 0.000). All composite buildups were performed within 14 days of completion of RCT. There was a significant correlation between the time of placement of the final coronal restoration and ETT survival (P ≤ 0.000). Extraction of ETT was 25% more likely (HR 0.25; CI 0.231–0.277) when the final coronal restoration was placed 15–59 days after completion of RCT and 73% more likely (HR 0.73; CI 0.655–0.814) when placed after 60 days than when placed at 0–14 days. Conclusion Timely placement of the final coronal restoration is found to be the most critical factor affecting the long-term survival of teeth after RCT.
Epidemiology of General, Central Obesity and Associated Cardio-Metabolic Risks Among University Employees, Ethiopia: A Cross-Sectional Study

Background Evidence suggests that middle and low-income countries such as Ethiopia are facing the growing epidemic of both communicable and non-communicable diseases creating a burden on their economy and healthcare system. The increasing prevalence of non-communicable diseases is attributed to sedentarism, lifestyle changes, nutritional transition, and the presence of other cardiometabolic risk factors. Therefore this study was designed to assess the prevalence and association of overweight, obesity, and cardio-metabolic risks and to explore if there was any agreement among the anthropometric measurements among the academic employees of the University of Gondar, Ethiopia. Methods An institutional-based cross-sectional study was conducted using the WHO stepwise approach and recommendations on 381 academic staff of the university. In addition, physical measurements such as weight, height, waist and hip circumferences, and biochemical measures such as blood pressure and fasting blood glucose level (peripheral blood samples by finger puncture) were measured using standardized tools. Results The mean age of the participants was 33.5 (95% CI: 32.7, 34.2) years. The prevalence of obesity among the study participants calculated by body mass index, waist circumference (WC), waist-height ratio (WHtR), and waist-hip ratio (WHR) was 13.1%, 33.6%, 51.9%, and 58.5% respectively. The prevalence of diabetes was 4.7% among which 1.3% was not diagnosed prior to this study. About 53 (13.9%) of the study sample were found to be hypertensive (HTN) (6.3% known versus 29 7.6% newly diagnosed). Among the participants, 39.4% and 23.4% were found to be pre-hypertensive and pre-diabetic respectively. WC was significantly associated with hypertension (AOR = 5.14; 2.503, 9.72), pre-DM (AOR = 4.03; 2.974, 5.96), DM (AOR = 3.29; 1.099, 6.01). In addition, WHtR was significantly associated with Pre-HTN (AOR = 2.69; 1.49, 4.58), HTN (AOR = 2.066; 1.008, 6.31), and DM (AOR = 1.855; 0.76, 4.32). On the contrary, both WHR and general obesity measured by BMI were not significantly associated with pre-HTN, HTN, pre-DM and DM groups. Conclusion This study results revealed the variable prevalence between general obesity and the anthropometric indices (IDF cutoff) defining central obesity; WC, WHtR, and WHR among the participants. The result of this study suggests that the constructs of central obesity, not BMI has to be used to screen risks of cardio-metabolic risks among Ethiopians.
Effects of Tilmicosin Treatment on the Nasopharyngeal Microbiota of Feedlot Cattle With Respiratory Disease During the First Week of Clinical Recovery

While the nasopharyngeal (NP) microbiota is believed to be a key player in bovine respiratory health, there is limited published information about the change of NP microbiota associated with clinical recovery from bovine respiratory disease (BRD). The objective of this study was to evaluate the effect of tilmicosin treatment on the NP microbiota composition and diversity of BRD-affected calves during the first week of clinical recovery. Deep NP swabs were collected from diseased calves at the initial diagnosis of BRD, and again 7 days after the administration of a single dose of tilmicosin. As an experimental control, samples were collected from clinically healthy, pen-matched calves at the time of initial BRD diagnosis. In general, the NP microbiota from the control calves were more diverse than the NP microbiota from tilmicosin treated and BRD-affected calves. Principle coordinate analysis (PCOA) of Bray-Curtis and Jaccard dissimilarity also revealed that the overall composition of NP microbial communities in tilmicosin-treated calves closely resembled that of BRD-affected calves but differed significantly from pen-matched healthy calves. Overall, it appeared that there were only minor changes in NP microbial communities following tilmicosin treatment and, during the early phase of clinical recovery the NP microbiota in treated animals was disparate from that observed in healthy control calves. Understanding the potential impact of this prolonged recovery in mucosal microbiota would be important in optimizing the use of antimicrobials in health management programs in the feedlot industry.
Porcine Circovirus Type 2 ORF5 Protein Induces Autophagy to Promote Viral Replication via the PERK-eIF2α-ATF4 and mTOR-ERK1/2-AMPK Signaling Pathways in PK-15 Cells

Porcine circovirus type 2 (PCV2) is the primary causative agent that causing porcine circovirus-associated disease (PCVAD). The open reading frame 5 (ORF5) protein is a newly discovered non-structural protein in PCV2, which the function in viral pathogenesis remains unknown. The aim of this study was to investigate the mechanism of PCV2 ORF5 protein on autophagy and viral replication. The pEGFP-tagged ORF5 gene was ectopic expressed in PK-15 cells and an ORF5-deficient PCV2 mutant strain (PCV2ΔORF5) were used to infected PK-15 cells. This study demonstrated that the ORF5 is essential for the of PCV2-induced autophagy. The ORF5 protein triggers the phosphorylation of PERK, eIF2α and the expression of downstream transcription factor ATF4. In addition, ORF5 protein activated the AMPK-ERK1/2-mTOR signaling pathways. These findings suggest that ORF5 play essential roles in the induction of autophagy by PCV2. We further revealed that PCV2 ORF5 promotes viral replication through PERK-eIF2α-ATF4 and AMPK-ERK1/2-mTOR pathways. In conclusion, we showed that PCV2 ORF5 induces autophagy to promote virus replication in PK-15 cells. Graphical Abstract PCV2 ORF5 inducing autophagy to promote PCV2 replication.
Detection of Chromosomal and Plasmid-Mediated Quinolone Resistance Among Escherichia coli Isolated from Urinary Tract Infection Cases; Zagazig University Hospitals, Egypt

Introduction Resistance to fluoroquinolones (FQ) in uropathogenic Escherichia coli (UPEC) has emerged as a growing problem. Chromosomal mutations and plasmid-mediated quinolone resistance (PMQR) determinants have been implicated. Data concerning the prevalence of these determinants in UPEC in our hospital are quite limited. Purpose To investigate the occurrence and genetic determinants of FQ resistance in UPEC isolated from urinary tract infection (UTI) cases in Zagazig University Hospitals. Patients and Methods Following their isolation, the identification and susceptibility of UPEC isolates were performed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometer (MALDI-TOF MS). FQ resistance was detected by the disc diffusion method. Ciprofloxacin minimal inhibitory concentration (MIC) was determined using E-test. Chromosomal mutations in the gyrA gene were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and for detection of PMQR, a couple of multiplex PCR reactions were used. Results Among a total of 192 UPEC isolates, 46.9% (n=90) were FQ resistant. More than half of the isolates (57.8%) exhibited high-level ciprofloxacin resistance (MIC > 32 µg/mL). Mutations in gyrA were detected in 76.7% of isolates, with 34.4% having mutations at more than one site. PMQR determinants were detected in 80.1% of UPEC isolates, with aac(6ʹ)-Ib-cr gene being the most frequent found in 61.1% of isolates. Conclusion There is a high prevalence of both gyrA mutations and PMQR determinants among UPEC isolates in our hospital which contribute to high-level ciprofloxacin resistance, a finding that may require the revision of the antibiotics used for empirical treatment of UTI.