Miracle-dz/UniFAR-FTUs huggingface dataset:
The rOSCE: A remote clinical examination during COVID lockdown and beyond

This article was migrated. The article was marked as recommended. The COVID-19 pandemic has created a challenge for all medical educators. There is a clear need to train the next generation of doctors whilst ensuring that patient safety is preserved. The OSCE has long been used as the gold standard for assessing clinical competency in undergraduates ( Khan et al., 2013a). However, social distancing rules have meant that we have had to reconsider our traditional assessment methods. We held a remote eight-station summative OSCE (rOSCE) for three final year resit students using Microsoft Teams. Apart from clinical examinations and practical procedures which are assessed elsewhere in our programme, the content was similar to our standard OSCE. Staff and student training ensured familiarity with the assessment modality. The rOSCE was found to be a feasible tool with high face validity. The rOSCE is a remote assessment tool that can offer an alternative to the traditional face to face OSCEs for use in high stakes examinations. Although further research is needed, we believe that the rOSCE is scalable to larger cohorts of students and is adaptable to the needs of most undergraduate clinical competency assessments.
Selective Glucocorticoid Receptor Modulator: A Novel Class of Anti-inflammatory Compounds

Background: Glucocorticoids exert a wide range of physiological effects. They effectively control various inflammatory and autoimmune diseases and play an important role in organ transplantation. Glucocorticoids are associated with unfavorable side effects that restrict their utilization. The most undesirable side effects are related to the transactivation of target genes. On the other hand, the transrepression of the genes is also responsible for the anti-inflammatory and immunomodulator of glucocorticoids. Principal Findings: The separation between these two processes through alteration in glucocorticoid receptor resulting in a compound with similar GCs benefit activity with fewer side effects. This review will discuss the molecular mechanism and summarizes the most common compounds and their beneficial effect in preclinical experiments. Conclusion: Several compounds that possess this feature are tested in preclinical experiments with promising results. These compounds are expected to be a better alternative to GCs drugs in the management of different diseases with a high degree of effectiveness.
Socially Accountable Medical Education: Our Story Might Not Be Yours

Socially Accountable Medical Education is a global educational movement transforming the development and delivery of medical schools in higher education. It is described as an upstream policy approach that seeks to align medical education and local community healthcare needs. To better understand social accountability as a policy initiative, we conducted a narrative review to identify key themes in the literature around frameworks of implementation. Our findings illustrate that social accountability has been mostly defined to date in terms of outcomes and related-actions and that there is a lack of focus on critical social constructs, such as power and place, that can reorient processes and inequities within health systems and educational institutions. We conclude that while socially accountable medical education is a promising paradigm shift in higher education, we call for a more complexified, contextualized, and nuanced approach.
Insights into the etiology and physiopathology of MODY5/HNF1B pancreatic phenotype with a mouse model of the human disease

Maturity‐onset diabetes of the young type 5 (MODY5) is due to heterozygous mutations or deletion of HNF1B. No mouse models are currently available to recapitulate the human MODY5 disease. Here, we investigate the pancreatic phenotype of a unique MODY5 mouse model generated by heterozygous insertion of a human HNF1B splicing mutation at the intron‐2 splice donor site in the mouse genome. This Hnf1bsp2/+ model generated with targeted mutation of Hnf1b mimicking the c.544+1G>T (T) mutation identified in humans, results in alternative transcripts and a 38% decrease of native Hnf1b transcript levels. As a clinical feature of MODY5 patients, the hypomorphic mouse model Hnf1bsp2/+ displays glucose intolerance. Whereas Hnf1bsp2/+ isolated islets showed no altered insulin secretion, we found a 65% decrease in pancreatic insulin content associated with a 30% decrease in total large islet volume and a 20% decrease in total β‐cell volume. These defects were associated with a 30% decrease in expression of the pro‐endocrine gene Neurog3 that we previously identified as a direct target of Hnf1b, showing a developmental etiology. As another clinical feature of MODY5 patients, the Hnf1bsp2/+ pancreases display exocrine dysfunction with hypoplasia. We observed chronic pancreatitis with loss of acinar cells, acinar‐to‐ductal metaplasia, and lipomatosis, with upregulation of signaling pathways and impaired acinar cell regeneration. This was associated with ductal cell deficiency characterized by shortened primary cilia. Importantly, the Hnf1bsp2/+ mouse model reproduces the pancreatic features of the human MODY5/HNF1B disease, providing a unique in vivo tool for molecular studies of the endocrine and exocrine defects and to advance basic and translational research. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Soil CO2 concentration and efflux as affected by heavy traffic in forest in northeast France

An experimental site was set up in northeast France on a Luvisol (ruptic) soil to examine the duration of physical, chemical and biological disturbances in the soil following mechanized forest harvesting. Soil carbon dioxide (CO2) efflux (SE) and concentration ([CO2]) in the silt loam layer (0–50 cm) were measured from March 2008 to March 2010 in the trafficked (T) and control (C) plots of this site. This study aimed to validate these two measurements as indicators for long‐term soil monitoring following disturbance by heavy traffic in 2007. Throughout the sampling period, SE in the T‐treatment was significantly reduced relative to that in the C‐treatment. The response of [CO2] to traffic depended on the season; it decreased during summer and increased during winter and spring. The combination of the two measurements indicated an increase in the frequency and duration of anoxic conditions resulting from poor gas diffusion after heavy forest traffic. The relationships between soil climatic properties (temperature, water content and water table level) on one hand and SE or [CO2] on the other, demonstrated a strong control of SE by soil biological activity and a double control of [CO2] by gas production/consumption and gas transfer. Our findings suggest that [CO2] and SE are sensitive to soil degradation by forest harvesting and that the impact of soil compaction provides complementary information on the processes involved in regulating CO2 production and efflux. However, their use as simple indicators is questionable as the impact varied with time and was probably dependent on the soil type.
Assessment of the Membranous Labyrinth in Infants Using a Heavily T2-weighted 3D FLAIR Sequence without Contrast Agent Administration

BACKGROUND AND PURPOSE: Imaging is fundamental to assessing the acoustic pathway in infants with congenital deafness. We describe our depiction of the membranous labyrinth in infants using the heavily T2-weighted 3D FLAIR sequence without a contrast agent. MATERIALS AND METHODS: We retrospectively reviewed 10 infants (20 ears) (median term equivalent age: 2 weeks; IQR: 1–5 weeks) who had undergone brain MR imaging including a noncontrast heavily T2-weighted 3D FLAIR scan of the temporal bone. For each ear, 3 observers analyzed, in consensus, the saccule, the utricle, and the 3 ampullae, assessing the visibility (score 0, not appreciable; score 1, visible without well-defined boundaries; score 2, visible with well-defined boundaries) and morphology (“expected” or “unexpected” compared with adults). The heavily T2-weighted 3D FLAIR sequence was scored for overall quality (score 0, inadequate; score 1, adequate but with the presence of image degradation; score 2, adequate). RESULTS: Six (60%) MR examinations were considered adequate (score 1 or 2). The saccule was visible in 10 ears (83.3%) with an expected morphology in 9 ears (90%). In 1 ear of an infant with congenital deafness, the saccule showed an unexpected morphology. The utricle was visible as expected in 12 ears (100%). The lateral ampulla was visible in 5 ears (41.6%), the superior ampulla was visible in 6 ears (50.0%), and the posterior ampulla was visible in 6 ears (50.0%), always with expected morphology (100%). CONCLUSIONS: MR imaging can depict the membranous labyrinth in infants using heavily T2-weighted 3D FLAIR without an injected contrast agent, but the sequence acquisition time reduces its feasibility in infants undergoing MR studies during natural sleep.
Impact of ENaC downregulation in transgenic mice on the outcomes of acute lung injury induced by bleomycin

What is the central question of this study? How does the downregulation of ENaC, the major driving force for alveolar fluid clearance, impact acute lung injury outcomes induced by bleomycin, featuring alveolar damage, as observed during ARDS exudative phase? What is the main finding and its importance? ENaC downregulation in αENaC(−/−)Tg+ mice did not elicit a substantial worsening impact on the main bleomycin outcomes. In ARDS patients, both ENaC alteration and alveolar damage are observed. Thus, novel therapeutic avenues, favouring alveolar integrity restauration, in addition to lung oedema resolution capacity, mainly driven by ENaC, would be essential.
Development, Implementation and First Evaluation of an Online Portal to Promote the Mental Health of University Students (me@JGU)

Background: University students encounter various stressors such as exam preparation, workload and economic concerns. Having to deal with a multitude of stressors can lead to mental health problems and have a negative impact on academic outcomes in students attending university. This paper describes the development and usability evaluation of an open and easily accessible online portal (me@JGU) designed to help students build skills they need to cope with common stressors and manage their own mental health. Methods: We developed a website that addresses the most common stressors among university students and offers strategies for dealing with difficult situations. Initial evaluation results were collected using website statistics and a short anonymous survey regarding the attractiveness and usability of the website. Results: Over an eight-month period, there were 5739 visitors, a total of 16,495 page views and 3748 downloads. The survey results indicate that me@JGU covers relevant topics and that the students like the layout. Conclusions: Online interventions promoting mental health of university populations are easily accessible and cost effective for large populations. They may prevent study difficulties, inform students about mental health and offer possible solutions. In addition, at-risk students can receive information about other relevant resources, and feel encouraged to access support and treatment.
11C- and 18F-Radiotracers for In Vivo Imaging of the Dopamine System: Past, Present and Future

The applications of positron emission tomography (PET) imaging to study brain biochemistry, and in particular the aspects of dopamine neurotransmission, have grown significantly over the 40 years since the first successful in vivo imaging studies in humans. In vivo PET imaging of dopaminergic functions of the central nervous system (CNS) including dopamine synthesis, vesicular storage, synaptic release and receptor binding, and reuptake processes, are now routinely used for studies in neurology, psychiatry, drug abuse and addiction, and drug development. Underlying these advances in PET imaging has been the development of the unique radiotracers labeled with positron-emitting radionuclides such as carbon-11 and fluorine-18. This review focuses on a selection of the more accepted and utilized PET radiotracers currently available, with a look at their past, present and future.
A Comprehensive Review of Detection Methods for SARS-CoV-2

Recently, the outbreak of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, in China and its subsequent spread across the world has caused numerous infections and deaths and disrupted normal social activity. Presently, various techniques are used for the diagnosis of SARS-CoV-2 infection, with various advantages and weaknesses to each. In this paper, we summarize promising methods, such as reverse transcription-polymerase chain reaction (RT-PCR), serological testing, point-of-care testing, smartphone surveillance of infectious diseases, nanotechnology-based approaches, biosensors, amplicon-based metagenomic sequencing, smartphone, and wastewater-based epidemiology (WBE) that can also be utilized for the detection of SARS-CoV-2. In addition, we discuss principles, advantages, and disadvantages of these detection methods, and highlight the potential methods for the development of additional techniques and products for early and fast detection of SARS-CoV-2.
Holin-Dependent Secretion of the Large Clostridial Toxin TpeL by Clostridium perfringens

Little is known about the mechanism by which LCTs are secreted. Since LCTs are major virulence factors in clostridial pathogens, we wanted to define the mechanism by which an LCT in C. perfringens, TpeL, is secreted by a protein (TpeE) lacking homology to previously described secretion-associated holins. ABSTRACT Large clostridial toxins (LCTs) are secreted virulence factors found in several species, including Clostridioides difficile, Clostridium perfringens, Paeniclostridium sordellii, and Clostridium novyi. LCTs are large toxins that lack a secretion signal sequence, and studies by others have shown that the LCTs of C. difficile, TcdA and TcdB, require a holin-like protein, TcdE, for secretion. The TcdE gene is located on the pathogenicity locus (PaLoc) of C. difficile, and holin-encoding genes are also present in the LCT-encoded PaLocs from P. sordellii and C. perfringens. However, the holin (TpeE) associated with the C. perfringens LCT TpeL has no homology and a different membrane topology than TcdE. In addition, TpeE has a membrane topology identical to that of the TatA protein, which is the core of the twin-arginine translocation (Tat) secretion system. To determine if TpeE was necessary and sufficient to secrete TpeL, the genes from a type C strain of C. perfringens were expressed in a type A strain of C. perfringens, HN13, and secretion was measured using Western blot methods. We found that TpeE was required for TpeL secretion and that secretion was not due to cell lysis. Mutant forms of TpeE lacking an amphipathic helix and a charged C-terminal domain failed to secrete TpeL, and mutations that deleted conserved LCT domains in TpeL indicated that only the full-length protein could be secreted. In summary, we have identified a novel family of holin-like proteins that can function, in some cases, as a system of protein secretion for proteins that need to fold in the cytoplasm. IMPORTANCE Little is known about the mechanism by which LCTs are secreted. Since LCTs are major virulence factors in clostridial pathogens, we wanted to define the mechanism by which an LCT in C. perfringens, TpeL, is secreted by a protein (TpeE) lacking homology to previously described secretion-associated holins. We discovered that TpeE is a member of a widely dispersed class of holin proteins, and TpeE is necessary for the secretion of TpeL. TpeE bears a high degree of similarity in membrane topology to TatA proteins, which form the pore through which Tat secretion substrates pass through the cytoplasmic membrane. Thus, the TpeE-TpeL secretion system may be a model for understanding not only holin-dependent secretion but also how TatA proteins function in the secretion process.
Global Plant Virus Disease Pandemics and Epidemics

The world’s staple food crops, and other food crops that optimize human nutrition, suffer from global virus disease pandemics and epidemics that greatly diminish their yields and/or produce quality. This situation is becoming increasingly serious because of the human population’s growing food requirements and increasing difficulties in managing virus diseases effectively arising from global warming. This review provides historical and recent information about virus disease pandemics and major epidemics that originated within different world regions, spread to other continents, and now have very wide distributions. Because they threaten food security, all are cause for considerable concern for humanity. The pandemic disease examples described are six (maize lethal necrosis, rice tungro, sweet potato virus, banana bunchy top, citrus tristeza, plum pox). The major epidemic disease examples described are seven (wheat yellow dwarf, wheat streak mosaic, potato tuber necrotic ringspot, faba bean necrotic yellows, pepino mosaic, tomato brown rugose fruit, and cucumber green mottle mosaic). Most examples involve long-distance virus dispersal, albeit inadvertent, by international trade in seed or planting material. With every example, the factors responsible for its development, geographical distribution and global importance are explained. Finally, an overall explanation is given of how to manage global virus disease pandemics and epidemics effectively.
Accurate Blood Pressure Estimation During Activities of Daily Living: A Wearable Cuffless Solution

The objective is to develop a cuffless method that accurately estimates blood pressure (BP) during activities of daily living. User-specific nonlinear autoregressive models with exogenous inputs (NARX) are implemented using artificial neural networks to estimate the BP waveforms from electrocardiography and photoplethysmography signals. To broaden the range of BP in the training data, subjects followed a short procedure consisting of sitting, standing, walking, Valsalva maneuvers, and static handgrip exercises. The procedure was performed before and after a six-hour testing phase wherein five participants went about their normal daily living activities. Data were further collected at a four-month time point for two participants and again at six months for one of the two. The performance of three different NARX models was compared with three pulse arrival time (PAT) models. The NARX models demonstrate superior accuracy and correlation with “ground truth” systolic and diastolic BP measures compared to the PAT models and a clear advantage in estimating the large range of BP. Preliminary results show that the NARX models can accurately estimate BP even months apart from the training. Preliminary testing suggests that it is robust against variabilities due to sensor placement. This establishes a method for cuffless BP estimation during activities of daily living that can be used for continuous monitoring and acute hypotension and hypertension detection.
Improvement of Gait Dysfunction after Applying a Hinged Ankle–Foot Orthosis in a Hemiplegic Cerebral Palsy Patient with Disrupted Medial Lemniscus: A Case Report

We describe the successful application of hinged ankle−foot orthoses (AFOs) in a cerebral palsied (CP) patient with gait instability due to a disrupted medial lemniscus (ML). The patient was a 27-month-old male CP child with gait instability who presented with reduced knee flexion and ankle dorsiflexion, with severe genu recurvatum on his right lower extremity during gait. The patient had no motor weakness or spasticity. Conventional magnetic resonance imaging (MRI) revealed no definite abnormal lesion. However, diffusion tensor tractography (DTT) showed disruption of the left ML, consistent with right hemiplegic symptoms. The integrity of the major motor-related neural tracts, including the corticospinal and corticoreticulospinal tracts, was preserved. We considered that the patient’s abnormal gait pattern was related to the disrupted ML state. We applied hinged AFOs, which immediately resulted in a significantly stabilized gait. The angles of knee flexion and ankle dorsiflexion increased. Our findings indicate that the application of hinged AFOs could be a useful therapeutic option for CP patients with gait instability related to ML disruption. In addition, we showed that DTT is a useful tool for identifying the causative brain pathology in CP patients, especially when conventional brain MRIs show no specific lesion.
De Novo Mutation and Rapid Protein (Co-)evolution during Meiotic Adaptation in Arabidopsis arenosa

Abstract A sudden shift in environment or cellular context necessitates rapid adaptation. A dramatic example is genome duplication, which leads to polyploidy. In such situations, the waiting time for new mutations might be prohibitive; theoretical and empirical studies suggest that rapid adaptation will largely rely on standing variation already present in source populations. Here, we investigate the evolution of meiosis proteins in Arabidopsis arenosa, some of which were previously implicated in adaptation to polyploidy, and in a diploid, habitat. A striking and unexplained feature of prior results was the large number of amino acid changes in multiple interacting proteins, especially in the relatively young tetraploid. Here, we investigate whether selection on meiosis genes is found in other lineages, how the polyploid may have accumulated so many differences, and whether derived variants were selected from standing variation. We use a range-wide sample of 145 resequenced genomes of diploid and tetraploid A. arenosa, with new genome assemblies. We confirmed signals of positive selection in the polyploid and diploid lineages they were previously reported in and find additional meiosis genes with evidence of selection. We show that the polyploid lineage stands out both qualitatively and quantitatively. Compared with diploids, meiosis proteins in the polyploid have more amino acid changes and a higher proportion affecting more strongly conserved sites. We find evidence that in tetraploids, positive selection may have commonly acted on de novo mutations. Several tests provide hints that coevolution, and in some cases, multinucleotide mutations, might contribute to rapid accumulation of changes in meiotic proteins.
A Full Set of In Vitro Assays in Chitosan/Tween 80 Microspheres Loaded with Magnetite Nanoparticles

Microspheres have been proposed for different medical applications, such as the delivery of therapeutic proteins. The first step, before evaluating the functionality of a protein delivery system, is to evaluate their biological safety. In this work, we developed chitosan/Tween 80 microspheres loaded with magnetite nanoparticles and evaluated cell damage. The formation and physical–chemical properties of the microspheres were determined by FT-IR, Raman, thermogravimetric analysis (TGA), energy-dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS), and SEM. Cell damage was evaluated by a full set of in vitro assays using a non-cancerous cell line, human erythrocytes, and human lymphocytes. At the same time, to know if these microspheres can load proteins over their surface, bovine serum albumin (BSA) immobilization was measured. Results showed 7 nm magnetite nanoparticles loaded into chitosan/Tween 80 microspheres with average sizes of 1.431 µm. At concentrations from 1 to 100 µg/mL, there was no evidence of changes in mitochondrial metabolism, cell morphology, membrane rupture, cell cycle, nor sister chromatid exchange formation. For each microgram of microspheres 1.8 µg of BSA was immobilized. The result provides the fundamental understanding of the in vitro biological behavior, and safety, of developed microspheres. Additionally, this set of assays can be helpful for researchers to evaluate different nano and microparticles.