Miracle-dz/UniFAR-FTUs huggingface dataset:
Impaired Autophagy Induced by oxLDL/β2GPI/anti-β2GPI Complex through PI3K/AKT/mTOR and eNOS Signaling Pathways Contributes to Endothelial Cell Dysfunction

Endothelial cell dysfunction plays a fundamental role in the pathogenesis of atherosclerosis (AS), and endothelial autophagy has protective effects on the development of AS. Our previous study had shown that oxidized low-density lipoprotein/β2-glycoprotein I/anti-β2-glycoprotein I antibody (oxLDL/β2GPI/anti-β2GPI) complex could promote the expressions of inflammatory cytokines and enhance the adhesion of leukocytes to endothelial cells. In the present study, we aimed to assess the effects of oxLDL/β2GPI/anti-β2GPI complex on endothelial autophagy and explore the associated potential mechanisms. Human umbilical vein endothelial cells (HUVECs) and mouse brain endothelial cell line (bEnd.3) were used as models of the vascular endothelial cells. Autophagy was evaluated by examining the expressions of autophagic proteins using western blotting analysis, autophagosome accumulation using transmission electron microscopy, and RFP-GFP-LC3 adenoviral transfection and autophagic flux using lysosome inhibitor chloroquine. The expressions of phospho-PI3K, phospho-AKT, phospho-mTOR, and phospho-eNOS were determined by western blotting analysis. 3-Methyladenine (3-MA) and rapamycin were used to determine the role of autophagy in oxLDL/β2GPI/anti-β2GPI complex-induced endothelial cell dysfunction. We showed that oxLDL/β2GPI/anti-β2GPI complex suppressed the autophagy, evidenced by an increase in p62 protein, a decrease in LC3-II and Beclin1, and a reduction of autophagosome generation in endothelial cells. Moreover, inhibition of autophagy was associated with PI3K/AKT/mTOR and eNOS signaling pathways. Rapamycin attenuated oxLDL/β2GPI/anti-β2GPI complex-induced endothelial inflammation, oxidative stress, and apoptosis, whereas 3-MA alone induced the endothelial injury. Our results suggested that oxLDL/β2GPI/anti-β2GPI complex inhibited endothelial autophagy via PI3K/AKT/mTOR and eNOS signaling pathways and further contributed to endothelial cell dysfunction. Collectively, our findings provided a novel mechanism for vascular endothelial injury in AS patients with an antiphospholipid syndrome (APS) background.
Trends and Variation in Data Quality on the EU Clinical Trials Register: A Cross-Sectional Study

The EU Clinical Trial Register (EUCTR) is a public facing portal containing information on trials of medicinal products conducted in the European Union (EU) and European Economic Area (EEA). Today, the registry holds information on over 30,000 trials. Given its distinct regulatory purpose, and results reporting requirements, the EUCTR should be a valuable open-source hub for trial information. Past work examining the EUCTR has suggested that data quality on the registry may be lacking. Using the full EUCTR public dataset, we examined areas in which national regulators are expected to ensure data quality including the posting of registrations, updating trial completion information, and monitoring results posting in line with EU guidelines. We identified issues across all areas examined with notable research hubs like France, Spain, and The Netherlands lacking consistent and complete data on the registry. These deficiencies complicate the utility of the EUCTR for research, transparency, and accountability efforts.
PERFORMANCE AND UTILITY OF AN ORAL FLUID-BASED RAPID POINT-OF-CARE TEST FOR SARS-COV-2 ANTIBODY RESPONSE FOLLOWING COVID-19 INFECTION OR VACCINATION

Analysis of anti-SARS-CoV-2 antibodies can identify recent-onset or prior COVID-19 infection or vaccine-induced humoral immunity. We have developed a rapid point-of-care test for IgG, M, or A-class immunoglobulins that recognize the S1 domain of the SARS-CoV-2 spike protein (CovAb). The test employs a lateral-flow strip design with a recombinant SARS-CoV-2 spike protein S1 domain capture antigen to detect anti-SARS-CoV-2 antibodies in oral fluid samples. Oral fluid samples are collected with a swab that captures the gingival crevicular fluid component of oral fluid that represents a plasma transudate and that is the primary source of oral fluid monomeric antibodies. The sensitivity of the CovAb test is 97.29% and the specificity is 98.13%, and the results obtained are similar to those obtained using matched fingerstick whole blood samples and in an EUA-approved commercial serology test. Oral fluid SARS-CoV-2 antibodies could be detected in subjects more than 7 months post-symptom onset. We also demonstrate the utility of the CovAb test in characterizing adaptive immune responses to vaccination in COVID-19-naive and exposed populations after first and second vaccine doses and show that significant heterogeneity in magnitude of antibody titers achieved is seen after both doses and that prior COVID-19 exposure increases the adaptive immune response to vaccination.
Blastocystis species and Gastrointestinal Symptoms in Peruvian Adults Attended in a Public Hospital

The objective of this study was to evaluate the role of Blastocystis sp. in gastrointestinal symptoms reported by adult patients in a Peruvian hospital. A case-control 3:1 study was performed at the outpatient clinic. Direct stool examinations were done. One hundred sixty patients were included, 40 cases and 120 controls. Positivity to Blastocystis sp. was associated with dyspepsia (P <0.001), bloating (P <0.001) and abdominal pain (P = 0.03) in patients attending our hospital outpatient clinic.
Statistical analysis of ENDOR spectra

Significance Statistical modeling of experimental data is gaining increasing importance in biological science due to the availability of large datasets. Here we present a statistical analysis of electron–nuclear double resonance, a technique that delivers information on the angstrom to nanometer scale around paramagnetic centers in proteins. The described method allows for recognizing experimental artifacts and provides the most probable signal as well as its uncertainty. Application to representative high-field electron–nuclear double resonance spectra of a prototype tyrosyl radical in a protein, the β2 subunit of Escherichia coli ribonucleotide reductase, demonstrates that subtle information can be uncovered, such as a distribution of molecular orientations relevant for the biological function of this essential radical. Electron–nuclear double resonance (ENDOR) measures the hyperfine interaction of magnetic nuclei with paramagnetic centers and is hence a powerful tool for spectroscopic investigations extending from biophysics to material science. Progress in microwave technology and the recent availability of commercial electron paramagnetic resonance (EPR) spectrometers up to an electron Larmor frequency of 263 GHz now open the opportunity for a more quantitative spectral analysis. Using representative spectra of a prototype amino acid radical in a biologically relevant enzyme, the Y122• in Escherichia coli ribonucleotide reductase, we developed a statistical model for ENDOR data and conducted statistical inference on the spectra including uncertainty estimation and hypothesis testing. Our approach in conjunction with 1H/2H isotopic labeling of Y122• in the protein unambiguously established new unexpected spectral contributions. Density functional theory (DFT) calculations and ENDOR spectral simulations indicated that these features result from the beta-methylene hyperfine coupling and are caused by a distribution of molecular conformations, likely important for the biological function of this essential radical. The results demonstrate that model-based statistical analysis in combination with state-of-the-art spectroscopy accesses information hitherto beyond standard approaches.
Mental health of college students and associated factors in Hubei of China

Background Although many studies have analyzed mental health problems in college students in China, the associations of mental health with individual and family circumstances, academic performance, and social support were rarely discussed. Objectives The study aimed to determine the mental health status and its associated factors among college students in China. Methods An online survey was conducted on 300 students selected through a cluster sampling strategy in a university in Hubei, China, tapping into sociodemographic characteristics of the participants, their mental health status measured by the modified Symptom Checklist-90 (SCL-90), and social support measured by the Social Support Rating Scale. Multivariate linear regression models were established to identify predictors of the SCL-90 scores. Results Mental health disorders were found in 8% of the respondents, with obsessive compulsive, interpersonal sensitivity and depression as the top three reported problems. Compared with the national population norms of university students in 2014, our study participants had higher scores in SCL-90. There were statistically significant difference in the Global Severity index (GSI) and all nine subscales scores (p<0.05). Poorer self-rated health, higher study pressure, and lower social support were significant predictors of higher SCL-90 scores (p<0.05) after adjustment for variations in other variables. Conclusions College students in Hubei, China may experience a range of different mental health problems, which are associated with their individual, study, and social circumstances.
“I have to start learning how to live with becoming sick”: A scoping review of the lived experiences of people with Huntington's disease

Person‐centered care (PCC) is recognized as a key component of the delivery of quality healthcare and a model for healthcare systems worldwide. The experience of illness through a person's perspective is one domain defining PCC contributing to a growing interest in examining the lived experiences of illness. This scoping review sought to examine what is known from the existing literature about the lived experiences of persons gene‐positive for or living with Huntington's disease (HD) as described in their own voices and to outline prominent psychosocial themes of those experiences. Five databases were systematically searched and analyzed resulting in 19 publications for inclusion. Using a thematic analysis, five prominent psychosocial themes were identified: grappling with control, avoidance as an escape from realities, adaptation to new realities, managing emotions, and appreciation for life. Variation in themes existed across HD life stage of being undiagnosed or diagnosed with HD. The findings of this review demonstrate that individuals who are gene‐positive for or living with HD require support well beyond the disclosure of genetic testing and that it may be beneficial for healthcare providers to consider where along the life stage trajectory a person affected by HD may be to ensure the delivery of quality PCC.
Modifying TIMER to generate a slow-folding DsRed derivative for optimal use in quickly-dividing bacteria

It is now well appreciated that members of pathogenic bacterial populations exhibit heterogeneity in growth rates and metabolic activity, and it is known this can impact the ability to eliminate all members of the bacterial population during antibiotic treatment. It remains unclear which pathways promote slowed bacterial growth within host tissues, primarily because it has been difficult to identify and isolate slow growing bacteria from host tissues for downstream analyses. To overcome this limitation, we have developed a novel variant of TIMER, a slow-folding fluorescent protein, named DsRed42, to identify subsets of slowly dividing bacteria within host tissues. The original TIMER folds too slowly for fluorescence accumulation in quickly replicating bacterial species (Escherichia coli, Yersinia pseudotuberculosis), however DsRed42 accumulates red fluorescence in late stationary phase cultures of E. coli and Y. pseudotuberculosis. We show DsRed42 signal also accumulates during exposure to sources of nitric oxide (NO), suggesting DsRed42 signal detects growth-arrested bacterial cells. In a mouse model of Y. pseudotuberculosis deep tissue infection, DsRed42 signal was detected, and primarily accumulates in bacteria expressing markers of stationary phase growth. There was no significant overlap between DsRed42 signal and NO-exposed subpopulations of bacteria within host tissues, suggesting NO stress was transient, allowing bacteria to recover from this stress and resume replication. This novel DsRed42 variant represents a tool that will enable additional studies of slow-growing subpopulations of bacteria, specifically within bacterial species that quickly divide.
Is This WhatsApp Conversation Aggressive? Adolescents’ Perception of Cyber Dating Aggression

This study investigated adolescents’ understanding of cyber dating aggression in terms of frequency and aggressiveness: how prevalent they perceived cyber dating aggression among adolescents and how aggressive they perceived such behaviors to be. To do so, different WhatsApp scenarios were presented to adolescents, controlling for the typology of cyber dating aggression (verbal/emotional, controlling, or sexual) and its publicity (public or private cyber dating aggression). The moderating effect of gender and moral disengagement (MD) was also analyzed. A total of 262 adolescents (56.5% girls; mean age of 14.46 years) participated in the study and answered a computer-based questionnaire. General linear models revealed that adolescents consider cyber dating aggression to be present in most adolescent romantic relationships. Controlling online behavior was perceived as the most frequent and the least aggressive behavior. Adolescents rated private cyber aggression as more frequent and less aggressive than public cyber aggressions. Controlling for gender, girls reported that cyber dating aggression was more common and more severe than boys. Moreover, participants with high levels of MD perceived cyber dating aggressions to be less aggressive than participants with medium-low MD. This study reveals the significance of the type of cyber dating aggression, the public/private dimension, gender, and MD as variables that influence adolescent understanding of cyber dating aggression. These results have implications not only for the design of cyber dating aggression prevention programs but also for future research on cyber dating aggression.
Natural history of disease in cynomolgus monkeys exposed to Ebola virus Kikwit strain demonstrates the reliability of this non-human primate model for Ebola virus disease

Filoviruses (Family Filoviridae genera Ebolavirus and Marburgvirus) are negative-stranded RNA viruses that cause severe health effects in humans and non-human primates, including death. Except in outbreak settings, vaccines and other medical countermeasures against Ebola virus (EBOV) will require testing under the FDA Animal Rule. Multiple vaccine candidates have been evaluated using cynomolgus monkeys (CM) exposed to EBOV Kikwit strain. To the best of our knowledge, however, animal model development data supporting the use of CM in vaccine research have not been submitted to the FDA. This study describes a large CM database (122 CM, 62 female and 60 male, age 2 to 9 years) and demonstrates the consistency of the CM model through time to death models and descriptive statistics. CMs were exposed to EBOV doses of 0.1 to 100,000 PFU in 33 studies conducted at three Animal Biosafety Level 4 facilities, by three exposure routes. Time to death was modeled using Cox proportional hazards models with a frailty term that incorporated study-to-study variability. Despite significant differences attributed to exposure variables, all CMs exposed to the 100 to 1,000 pfu doses commonly used in vaccine studies died or met euthanasia criteria within 21 days of exposure, median 7 days, 93% between 5 and 12 days of exposure. Moderate clinical signs were observed 4 to 5 days after exposure and preceded death or euthanasia by approximately one day. Viremia was detected within a few days of infection. Hematology indices were indicative of viremia and the propensity for hemorrhage with progression of Ebola viremia. Changes associated with coagulation parameters and platelets were consistent with coagulation disruption. Changes in leukocyte profiles were indicative of an acute inflammatory response. Increased liver enzymes were observed shortly after exposure. Taken together, these factors suggest that the cynomolgus monkey is a reliable animal model for human disease.
Functional analysis of novel genetic variants of NKX2‐5 associated with nonsyndromic congenital heart disease

NKX2‐5, a master cardiac regulatory transcription factor was the first known genetic cause of congenital heart diseases (CHDs). To further investigate its role in CHD pathogenesis, we performed mutational screening of 285 CHD probands and 200 healthy controls. Five coding sequence variants were identified in six CHD cases (2.1%), including three in the N‐terminal region (p.A61G, p.R95L, and p.E131K) and one each in homeodomain (HD) (p.A148E) and tyrosine‐rich domain (p.P247A). Variant‐p.A148E showed tertiary structure changes and differential DNA binding affinity of mutant compared to wild type. Two N‐terminal variants—p.A61G and p.E131K along with HD variant p.A148E demonstrated significantly reduced transcriptional activity of Nppa and Actc1 promoters in dual luciferase promoter assay supported by their reduced expression in qRT‐PCR. Nonetheless, variant p.R95L affected the synergy of NKX2‐5 with serum response factor and TBX5 leading to significantly decreased Actc1 promoter activity depicting a distinctive role of this region. The aberrant expression of other target genes—Irx4, Mef2c, Bmp10, Myh6, Myh7, and Myocd is also observed in response to NKX2‐5 variants, possibly due to the defective gene regulatory network. Severely impaired downstream promoter activities and abnormal expression of target genes due to N‐terminal variants supports the emerging role of this region during cardiac‐developmental pathways.
Fukushima Daiichi Unit 1 Ex-Vessel Prediction: Core-Concrete Interaction

Abstract Lower head failure and corium-concrete interaction were predicted to occur at Fukushima Daiichi Unit 1 (1F1) by several different system-level code analyses, including MELCOR v2.1 and MAAP5. Although these codes capture a wide range of accident phenomena, they do not contain detailed models for ex-vessel core melt behavior. However, specialized codes exist for the analysis of ex-vessel melt spreading (e.g., MELTSPREAD) and long-term debris coolability (e.g., CORQUENCH). On this basis, an analysis was carried out to further evaluate ex-vessel behavior for 1F1 using MELTSPREAD and CORQUENCH. Best-estimate melt pour conditions predicted by MELCOR v2.1 and MAAP5 were used as input. MELTSPREAD was then used to predict the spatially dependent melt conditions and extent of spreading during relocation from the vessel. The results of the MELTSPREAD analysis are reported in a companion paper. This information was used as input for the long-term debris coolability analysis with CORQUENCH. For the MELCOR-based melt pour scenario, CORQUENCH predicted the melt would readily cool within 2.5 h after the pour, and the sumps would experience limited ablation (approximately 18 cm) under water-flooded conditions. For the MAAP-based melt pour scenarios, CORQUENCH predicted that the melt would cool in approximately 22.5 h, and the sumps would experience approximately 65 cm of concrete ablation under water-flooded conditions.
Interaction of Ciprofloxacin and Extract of Hibiscus sabdariffa Linn (Roselle) Calyses in Antimicrobial Assays by ‘Agar-well Cross-reaction Technique’

Aims: To evaluate the antibacterial activities of aqueous extract of Hibiscus sabdariffa Linn calyces and ciprofloxacin, separately and in combination, and introduce a simple method in the study of drug interactions. Study Design: Experimental design. Place and Duration of Study: Department of Biological Sciences, Ondo State University of Science and Technology, Okitipupa, between March 2013 and June 2015. Methodology: Antimicrobial assays using five bacterial isolates including S. aureus, Pseudomonas aeruginosa, and S. aureus NCTC 6571, by agar-well diffusion method were performed. Interaction assay of extract and ciprofloxacin by an ‘Agar-well Cross-reaction Technique’ was performed. Inferences for synergistic, additive, indifferent or antagonistic interaction were drawn from the percentage differences in the inhibition zone diameters (IZDs) produced. Results: All test bacteria were susceptible to the extract, IZDs ranging from 10 mm to 32 mm. Four test bacteria were susceptible to ciprofloxacin, IZDs ranging from 15 mm to 35 mm. Out of the twenty five interactions against S. aureus O1, there were 6 (24%) synergistic, 6 (24%) additive, 3 Original Research Article Nmema; BJAST, 15(2): 1-8, 2016; Article no.BJAST. 24793 2 (12%) indifferent, 5 (20%) antagonistic reactions, and 5 (20%) showed no activity. Out of the twenty five interactions against P. aeruginosa PA2, there were 2 (8.0%) synergistic, 2 (8.0%) additive, 1 (4%) indifferent, 9 (36%) antagonistic reactions, and 11 (44%) showed no activity. Summing up the fifty interactions for the two test isolates, 36 (72%) interactions were favorable or indifferent while 14 (28%) interactions were antagonistic. Results of Chi square test showed this to be statistically significant (P = .05). Conclusion: H. sabdariffa calyces extract posseses antibacterial properties similar to ciprofloxacin, and inhibited ciprofloxacin-resistant isolates. Concomitant use of ciprofloxacin and H. sabdariffa extract may not produce antagonistic reactions. The ‘Agar-well Cross-reaction Technique’ proved to be sensitive and effective, eliminating many of the difficulties experienced with other methods of studying drug interactions.