Bridging the Gaps: The Transformative Effect of Coronavirus Disease 2019 (COVID-19) on Preventive Measures Among Medical and Health Sciences College Students in Madinah, Saudi Arabia.

Background The global impact of coronavirus disease 2019 (COVID-19) has disrupted the activities of medical and health profession education institutions. This study aimed to determine the impact of COVID-19 on medical and health profession education students' knowledge, attitudes, and practices toward preventive measures and their commitment to precautionary measures before, during, and after the pandemic. Materials and methods A cross-sectional study was carried out from January to March 2023 using an online, structured, validated questionnaire survey to gather information from medical and health sciences students from three universities, encompassing five colleges in Madinah, Saudi Arabia. The minimum required sample size was estimated using the Epi Info software as 380. The data was analyzed using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, United States). Statistical tests including Student's t-test, chi-squared test, and analysis of variance (ANOVA) test were applied. Results The findings revealed that personal experiences with COVID-19 infection had a significant impact on students' attitudes and commitment to preventive measures (p<0.05). Among the participants, 172 students (45%) reported having contracted COVID-19. Students with clinical exposure showed a higher level of understanding and adherence to preventive measures (248 students, 68%), compared to pre-clinical students (198 students, 52%) (p<0.05). Positive attitudes were observed toward practices such as sneezing etiquette (289 students, 76%) and flu vaccination (314 students, 83%) (p<0.05). However, negative attitudes were observed toward mask-wearing (155 students, 41%) and social distancing (144 students, 38%), particularly among male students (p<0.05). Conclusion The study provided valuable insights into the impact of the COVID-19 pandemic on medical and health sciences students' knowledge, attitudes, and practices toward preventive measures and the importance of introducing COVID-19 prevention measures in the pre-clinical phase as well as mental health support to promote positive attitudes and enhance adherence to preventive measures.

AP39 through AMPK-ULK1-FUNDC1 pathway regulates mitophagy, inhibits pyroptosis, and improves doxorubicin-induced myocardial fibrosis.

Doxorubicin induces myocardial injury and fibrosis. Still, no effective interventions are available. AP39 is an H2S donor that explicitly targets mitochondria. This study investigated whether AP39 could improve doxorubicin-induced myocardial fibrosis. Doxorubicin induced significant myocardial fibrosis while suppressing mitophagy-related proteins and elevating pyroptosis-related proteins. Conversely, AP39 reverses these effects, enhancing mitophagy and inhibiting pyroptosis. In vitro experiments revealed that AP39 inhibited H9c2 cardiomyocyte pyroptosis, improved doxorubicin-induced impairment of mitophagy, reduced ROS levels, ameliorated the mitochondrial membrane potential, and upregulated AMPK-ULK1-FUNDC1 expression. In contrast, AMPK inhibitor (dorsomorphin) and ULK1 inhibitor (SBI-0206965) reversed AP39 antagonism of doxorubicin-induced FUNDC1-mediated impairment of mitophagy and secondary cardiomyocyte pyroptosis. These results suggest that mitochondria-targeted H2S can antagonize doxorubicin-induced pyroptosis and impaired mitophagy in cardiomyocytes via AMPK-ULK1-FUNDC1 and ameliorated myocardial fibrosis and remodeling.

Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease.

Clonal hematopoiesis (CH) is a risk factor for atherosclerotic cardiovascular disease, but the impact of smaller clones and the effect on inflammatory parameters is largely unknown. Using ultrasensitive single-molecule molecular inversion probe sequencing, we evaluated the association between CH and a first major adverse cardiovascular event (MACE) in patients with angiographically documented stable coronary artery disease (CAD) and no history of acute ischemic events. CH was associated with an increased rate of MACE at four years follow-up. The size of the clone predicted MACE at an optimal cut-off value of 1.07% variant allele frequency (VAF). Mutation carriers had no change in monocytes subsets or cytokine production capacity but had higher levels of circulating tissue factor, matrilysin, and proteinase-activated receptor-1. Our study identified CH driver mutations with a VAF as small as 1.07% as a residual cardiovascular risk factor and identified potential biomarkers and therapeutic targets for patients with stable CAD.

Oleuropein activates autophagy to circumvent anti-plasmodial defense.

Antimalarial drug resistance and unavailability of effective vaccine warrant for newer drugs and drug targets. Hence, anti-inflammatory activity of phyto-compound (oleuropein; OLP) was determined in antigen (LPS)-stimulated human THP-1 macrophages (macrophage model of inflammation; MMI). Reduction in the inflammation was controlled by the PI3K-Akt1 signaling to establish the "immune-homeostasis." Also, OLP treatment influenced the cell death/autophagy axis leading to the modulated inflammation for extended cell survival. The findings with MII prompted us to detect the antimalarial activity of OLP in the wild type (3D7), D10-expressing GFP-Atg18 parasite, and chloroquine-resistant (Dd2) parasite. OLP did not show the parasite inhibition in the routine in vitro culture of P. falciparum whereas OLP increased the antimalarial activity of artesunate. The molecular docking of autophagy-related proteins, investigations with MMI, and parasite inhibition assays indicated that the host activated the autophagy to survive OLP pressure. The challenge model of P. berghei infection showed to induce autophagy for circumventing anti-plasmodial defenses.

Personalised learning in higher education for health sciences: a scoping review protocol.

BACKGROUND: Personalised learning, an educational approach that tailors teaching and learning to individual needs and preferences, has gained attention in recent years, particularly in higher education. Advances in educational technology have facilitated the implementation of personalised learning in various contexts. Despite its potential benefits, the literature on personalised learning in health sciences higher education remains scattered and heterogeneous. This scoping review aims to identify and map the current literature on personalised learning in health sciences higher education and its definition, implementation strategies, benefits, and limitations. METHODS: A comprehensive search of electronic databases, PubMed, Scopus, Google Scholar, Educational Research Complete, and Journal Storage (JSTOR), will be conducted to identify relevant articles. The search will be limited to articles published in the English language between 2000 and 2023. The search strategy will be designed and adapted for each database using a combination of keywords and subject headings related to personalised learning and health sciences higher education. Eligibility criteria will be applied to screen and select articles. Data extraction and quality assessment will be performed, and thematic synthesis will be used to analyse the extracted data. DISCUSSION: The results of the scoping review will present a comprehensive and coherent overview of the literature on personalised learning in health sciences higher education. Key themes and topics related to personalised learning, its definitions, models, implementation strategies, benefits, and limitations, will be identified. The geographical and temporal distribution of research on personalised learning in health sciences higher education will also be described. This scoping review will provide a structured synthesis of the available evidence on personalised learning in health sciences higher education, highlighting potential gaps and areas for future research. The findings will contribute to ongoing scholarly and policy debates on personalised learning in higher education, informing the development of best practices, guidelines, and future research agendas.

Protocol to evaluate the antiviral effect of FDA-approved drugs against dengue virus in Huh7 cells and AG129 mice.

Finding an effective therapy against diseases caused by flaviviruses remains a challenge. Here, we present a protocol to test Food and Drug Administration-approved drugs that inhibit host nuclear protein import, promoting a reduction of dengue infection. We describe steps for analyzing the drug effect on nuclear import inhibition of cellular and viral proteins by confocal microscopy or western blotting. We then describe procedures for measuring the antiviral drug effects on virus-infected cells by flow cytometry and testing drug efficacy in dengue-infected AG129 mice by survival assays. For complete details on the use and execution of this protocol, please refer to Palacios-Rápalo et al.1.

Protocol for isolating single species of bacteria with swarming ability from human feces.

Understanding the specific movements of bacteria isolated from human feces can serve as a novel diagnostic and therapeutic tool for inflammatory bowel disease. Here, we present a protocol for a microbial swarming assay and to isolate the bacteria responsible for swarming activity. We describe steps for identifying bacteria using MALDI-TOF mass spectrometry and whole-genome sequencing. We then detail procedures for validating findings by observing the same swarming phenotype upon reperforming the swarming assay. For complete details on the use and execution of this protocol, please refer to De et al.1.

Exploring the relationship among soccer-related knowledge, attitude, practice, and self-health in Chinese campus soccer education.

China has promoted campus soccer for over a decade due to its potential health benefits. The study aimed to explore soccer knowledge (SK), soccer attitude (SA), soccer practice (SP), and health status among Chinese freshmen and sophomore undergraduates who had received campus soccer education. Of the 7419 participants, 1,069 were valid and included in the analysis. Structural equation modeling (SEM) results indicated SK is positively associated with SA (p < 0.001), but negatively with SP (p < 0.01). SA was positively linked to SP (p < 0.001). SK indirectly affected SP through SA (Z = 13.677). Random forest-tree-structured Parzen estimators (RF-TPE) with SHAP indicated SP holds primary importance with a strong negative impact on health. Additionally, differences in rankings for SK, SA, and SP were observed among gender and urban-rural groups. These results reveal current campus soccer education is suboptimal to health promotion.

Machine learning approaches for practical predicting outpatient near-future AECOPD based on nationwide electronic medical records.

In this research, we aimed to harness machine learning to predict the imminent risk of acute exacerbation in chronic obstructive pulmonary disease (AECOPD) patients. Utilizing retrospective data from electronic medical records of two Taiwanese hospitals, we identified 26 critical features. To predict 3- and 6-month AECOPD occurrences, we deployed five distinct machine learning algorithms alongside ensemble learning. The 3-month risk prediction was best realized by the XGBoost model, achieving an AUC of 0.795, whereas the XGBoost was superior for the 6-month prediction with an AUC of 0.813. We conducted an explainability analysis and found that the episode of AECOPD, mMRC score, CAT score, respiratory rate, and the use of inhaled corticosteroids were the most impactful features. Notably, our approach surpassed predictions that relied solely on CAT or mMRC scores. Accordingly, we designed an interactive prediction system that provides physicians with a practical tool to predict near-term AECOPD risk in outpatients.

Protocol for isolating murine kidney tubules and ex vivo cell death assays.

Isolating kidney tubules offers insights into their biological function without stroma, vascular cells, and immune system interference. Our murine tubule isolation protocol focuses on ex vivo cell death assays. We describe steps for solution preparation; kidney extraction, decapsulation, and slicing; and tubule isolation. We also outline assays like western blotting, lactate dehydrogenase release assay, and live-cell imaging of vital dyes during experimental acute tubular necrosis. This adaptable protocol allows the generation of outgrown primary tubular cells that maintain the features of tubular cells.

Protocol to detect senescence-associated ß-galactosidase and immunoperoxidase activity in fresh-frozen murine tissues.

Double labeling to identify different markers in the same tissue section represents a useful tool either for in situ diagnosis or characterization of molecular associations. Here, we present a protocol to detect senescence-associated ß-galactosidase (SA-ßGal) and immunoperoxidase (IPO) activity in fresh-frozen murine tissues. We describe steps for tissue collection, solution preparation, SA-ßGal staining, IPO staining, hematoxylin counterstaining, microscopic observation, and signal quantification. This protocol can be used to detect in situ proteins alongside SA-ßGal activity. For complete details on the use and execution of this protocol, please refer to Pacheco-Rivera et al.1.

Endometriosis and endometrial cancer: A propensity score-adjusted real-world data study.

Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. Our study investigated the effect of endometriosis on the risk of endometrial cancer (EC) and the prognosis of endometriosis-associated EC. In our study, 197,196 patients with endometriosis and without a previous diagnosis of EC were compared with 6,455,556 females encountering health services for examinations, with body mass index (BMI) data, and without endometriosis or EC. A propensity score generated 197,141 matched pairs. In the endometriosis cohort, 875 cases of EC were seen, whereas 558 were in the control group: the hazard ratio (HR) was 1.56 (95% CI 1.40-1.73, p < 0.001). Women with endometriosis were more likely to develop invasive endometrioid (p = 0.005) and clear cell (p < 0.001) EC. There was no difference in overall survival between endometriosis-associated EC and EC without endometriosis. Our epidemiological findings were consistent with the evidence of an association between endometriosis and EC.

Inspiring basic and applied research in genome integrity mechanisms: Dedication to Samuel H. Wilson.

This Special Issue (SI) of Environmental and Molecular Mutagenesis (EMM), entitled "Inspiring Basic and Applied Research in Genome Integrity Mechanisms," is to update the community on recent findings and advances on genome integrity mechanisms with emphasis on their importance for basic and environmental health sciences. This SI includes two research articles, one brief research communication, and four reviews that highlight cutting edge research findings and perspectives, from both established leaders and junior trainees, on DNA repair mechanisms. In particular, the authors provided an updated understanding on several distinct enzymes (e.g., DNA polymerase beta, DNA polymerase theta, DNA glycosylase NEIL2) and the associated molecular mechanisms in base excision repair, nucleotide excision repair, and microhomology-mediated end joining of double-strand breaks. In addition, genome-wide sequencing analysis or site-specific mutational signature analysis of DNA lesions from environmental mutagens (e.g., UV light and aflatoxin) provide further characterization and sequence context impact of DNA damage and mutations. This SI is dedicated to the legacy of Dr. Samuel H. Wilson from the U.S. National Institute of Environmental Health Sciences at the National Institutes of Health.

Modeling non-genetic information dynamics in cells using reservoir computing.

Virtually all cells use energy-driven, ion-specific membrane pumps to maintain large transmembrane gradients of Na+, K+, Cl-, Mg++, and Ca++, but the corresponding evolutionary benefit remains unclear. We propose that these gradients enable a dynamic and versatile biological system that acquires, analyzes, and responds to environmental information. We hypothesize that environmental signals are transmitted into the cell by ion fluxes along pre-existing gradients through gated ion-specific membrane channels. The consequent changes in cytoplasmic ion concentration can generate a local response or orchestrate global/regional cellular dynamics through wire-like ion fluxes along pre-existing and self-assembling cytoskeleton to engage the endoplasmic reticulum, mitochondria, and nucleus.

Single cell characterization of blood and expanded regulatory T cells in autoimmune polyendocrine syndrome type 1.

Immune tolerance fails in autoimmune polyendocrine syndrome type 1 (APS-1) because of AIRE mutations. We have used single cell transcriptomics to characterize regulatory T cells (Tregs) sorted directly from blood and from in vitro expanded Tregs in APS-1 patients compared to healthy controls. We revealed only CD52 and LTB (down) and TXNIP (up) as consistently differentially expressed genes in the datasets. There were furthermore no large differences of the TCR-repertoire of expanded Tregs between the cohorts, but unique patients showed a more restricted use of specific clonotypes. We also found that in vitro expanded Tregs from APS-1 patients had similar suppressive capacity as controls in co-culture assays, despite expanding faster and having more exhausted cells. Our results suggest that APS-1 patients do not have intrinsic defects in their Treg functionality, and that their Tregs can be expanded ex vivo for potential therapeutic applications.

Machine learning-assisted novel recyclable flexible triboelectric nanogenerators for intelligent motion.

In the smart era, big data analysis based on sensor units is important in intelligent motion. In this study, a dance sports and injury monitoring system (DIMS) based on a recyclable flexible triboelectric nanogenerator (RF-TENG) sensor module, a data processing hardware module, and an upper computer intelligent analysis module are developed to promote intelligent motion. The resultant RF-TENG exhibits an ultra-fast response time of 17 ms, coupled with robust stability demonstrated over 4200 operational cycles, with 6% variation in output voltage. The DIMS enables immersive training by providing visual feedback on sports status and interacting with virtual games. Combined with machine learning (K-nearest neighbor), good classification results are achieved for ground-jumping techniques. In addition, it shows some potential in sports injury prediction (i.e., ankle sprains, knee hyperextension). Overall, the sensing system designed in this study has broad prospects for future applications in intelligent motion and healthcare.

B cell somatic hypermutation following COVID-19 vaccination with Ad26.COV2.S.

The viral vector-based COVID-19 vaccine Ad26.COV2.S has been recommended by the WHO since 2021 and has been administered to over 200 million people. Prior studies have shown that Ad26.COV2.S induces durable neutralizing antibodies (NAbs) that increase in coverage of variants over time, even in the absence of boosting or infection. Here, we studied humoral responses following Ad26.COV2.S vaccination in individuals enrolled in the initial Phase 1/2a trial of Ad26.COV2.S in 2020. Through 8 months post vaccination, serum NAb responses increased to variants, including B.1.351 (Beta) and B.1.617.2 (Delta), without additional boosting or infection. The level of somatic hypermutation, measured by nucleotide changes in the VDJ region of the heavy and light antibody chains, increased in Spike-specific B cells. Highly mutated mAbs from these sequences neutralized more SARS-CoV-2 variants than less mutated comparators. These findings suggest that the increase in NAb breadth over time following Ad26.COV2.S vaccination is mediated by affinity maturation.

Multilingual education: medical interns perceptions regarding the usefulness of non-mother tongue communications skills taught during the undergraduate curriculum.

BACKGROUND: This paper investigates the perceptions of medical interns regarding the usefulness of non-mother tongue communication skills taught during the undergraduate curriculum at the University of Cape Town in South Africa. In 2003, the university decided to incorporate Afrikaans and IsiXhosa communication skills into the new MBChB curriculum in order to meet the Faculty of Health Sciences goals to promote quality and equity in healthcare, and to prepare graduating health practitioners for multilingual communities where they would be serving. Despite annual internal evaluations and reviews of the languages courses, the usefulness, if any, of the additional languages in the working clinical environment had not been determined. METHODS: Data were collected during the second year of medical internship across a five-year period through survey questionnaires, as well as focus group interviews conducted in the Western Cape, South Africa. Surveys were conducted from 2009 to 2013. RESULTS: The study shows that the usefulness of each of the probed categories was not consistent across both languages. The interns expressed a need for an overall improvement of the isiXhosa course offering, while the outcomes for the Afrikaans language were more positive across all categories except for cultural understanding. CONCLUSION: The study indicates a positive trend amongst the interns towards developing usefulness in communication skills in Afrikaans and isiXhosa to communicate with their patients.

Non-invasive PET imaging of liver fibrogenesis using a RESCA-conjugated Affibody molecule.

Non-invasive assessment of fibrogenic activity, rather than fibrotic scars, could significantly improve the management of fibrotic diseases and the development of anti-fibrotic drugs. This study explores the potential of an Affibody molecule (Z09591) labeled with the Al(18)F-restrained complexing agent (RESCA) method as a tracer for the non-invasive detection of fibrogenic cells. Z09591 was functionalized with the RESCA chelator for direct labeling with [18F]AlF. In vivo positron emission tomography/magnetic resonance imaging scans on U-87 tumor-bearing mice exhibited high selectivity of the resulting radiotracer, [18F]AlF-RESCA-Z09591, for platelet-derived growth factor receptor ß (PDGFRß), with minimal non-specific background uptake. Evaluation in a mouse model with carbon tetrachloride-induced fibrotic liver followed by a disease regression phase, revealed the radiotracer's high affinity and specificity for fibrogenic cells in fibrotic livers (standardized uptake value [SUV] 0.43 ± 0.05), with uptake decreasing during recovery (SUV 0.29 ± 0.03) (p < 0.0001). [18F]AlF-RESCA-Z09591 accurately detects PDGFRß, offering non-invasive assessment of fibrogenic cells and promising applications in precise liver fibrogenesis diagnosis, potentially contributing significantly to anti-fibrotic drug development.

Effects of long-term closed and socially isolating spaceflight analog environment on default mode network connectivity as indicated by fMRI.

Long-term manned spaceflight and extraterrestrial planet settlement become the focus of space powers. However, the potential influence of closed and socially isolating spaceflight on the brain function remains unclear. A 180-day controlled ecological life support system integrated experiment was conducted, establishing a spaceflight analog environment to explore the effect of long-term socially isolating living. Three crewmembers were enrolled and underwent resting-state fMRI scanning before and after the experiment. We performed both seed-based and network-based analyses to investigate the functional connectivity (FC) changes of the default mode network (DMN), considering its key role in multiple higher-order cognitive functions. Compared with normal controls, the leader of crewmembers exhibited significantly reduced within-DMN and between-DMN FC after the experiment, while two others exhibited opposite trends. Moreover, individual differences of FC changes were further supported by evidence from behavioral analyses. The findings may shed new light on the development of psychological protection for space exploration.