Miracle-dz/UniFAR-FTUs huggingface dataset:
Examining the psychological and financial impact of travel restrictions on citizens and permanent residents stranded abroad during the COVID-19 pandemic: international cross-sectional study

Objectives This study aimed to evaluate the psychological and financial distress reported by citizens and permanent residents stranded abroad due to international travel restrictions introduced in response to the COVID-19 pandemic. Design An international cross-sectional study. Setting A primary analysis of data collected between July and September 2021 through an online survey targeting individuals stranded abroad and unable to return to their country of residence due to international travel restrictions. Respondents A total of 1054 individuals aged 18–84 years. Data analysis Multivariable logistic regression models were used to explore the relationship between higher levels of depression, anxiety and stress and participant variables. Outcome measures The survey answered questions regarding COVID-19 travel restriction-related impacts: personal stress, anxiety and depression (using the validated 21-item Depression, Anxiety and Stress Scale (DASS-21) tool), as well as impacts on housing and financial security and demographic data. Results A total of 75.4% of respondents reported wanting to return to the Oceania region (75.4%), with 45% stranded in Europe. 64.2% reported financial distress while stranded abroad. 64.4% (x̄=9.43, SD=5.81) reported moderate-to-extremely severe (based on the DASS-21 classification) levels of depression, 41.7% for anxiety (x̄=5.46, SD=4.74), and 58.1% for stress (x̄=10.64, SD=5.26). Multivariable analysis indicated that financial stress, an employment change, being <30 years, having a high perceived risk of contracting COVID-19 abroad and being stranded for >2 months were significantly related to scores of moderate-to-extremely severe depression, anxiety and stress. Conclusion The study is among the first to explore the psychological and financial distress-related impacts associated with being stranded abroad due to COVID-19 travel restrictions. It highlights a range of unintended consequences that arise from pandemic-related travel restrictions, identifies the health and social needs of a particularly vulnerable population, and provides clues as to the types of support that may be adopted to best support them.
Complex Disease Genes Identification Using a Heterogeneous Network Embedding Approach

Finding the causal relation between a gene and a disease using experimental approaches is a time-consuming and expensive task. However, computational approaches are cost-efficient methods for identifying candidate genes. This article proposes a new heterogeneous biological network embedding approach, named NetEM, to identify disease-associated genes. To evaluate NetEM, we examine six complex diseases, including peroxisomal disorders, sarcoma, grave's disease, lysosomal storage diseases, blood coagulation disorders, and cardiomyopathy hypertrophic. Our experiments indicate that NetEM outperforms three well-known state-of-the-art algorithms: Cardigan, DIAMOnD and GeneWanderer, in identifying disease genes. We examine TCGA data of Invasive Lobular Breast Cancer and CPTAC data of human glioblastoma as other case studies to evaluate NetEM using real data. This evaluation also indicates the validity of the method. The source codes of NetEM and data are available in the supplementary of this article.
Physical exercise training in the syllabus of Bachelor of Science in nursing degrees: an environmental scan

Background: Scientific evidence regarding the effectiveness of physical activity (PA) in the prevention and treatment of chronic diseases is increasing. Healthcare systems are trying to increase exercise prescription treatments. However, it is not clear if health professionals are sufficiently trained. Aim: to analyze the contents related to PA and exercise in the prevention and treatment of chronic diseases in the syllabus of the Bachelor of Science in Nursing at all Spanish universities. Methods: A systematic environmental scan that included a web page search of curricular guide programs of all Spanish universities offering the Bachelor of Science in Nursing was undertaken for the 2017–2018 academic course. The assessment of the European Credit Transfer System (ECTS) about physical activity and/or exercise health-related benefits in the prevention or treatment of chronic diseases was performed by two experts in a peer-review process. ECTS of Practicum and Bachelor thesis were not included in the analysis. Results: In the mean, the Bachelor of Science in Nursing dedicated 5.82% (5.01% mandatory and 0.82% voluntary) of a total of 240 ECTS (ranging from 0 to 45 ECTS). The majority of contents were related to PA promotion; in contrast, contents related to exercise prescription are neglectable. Five Spanish universities do not offer any academic teaching to physical activity on prescription. Conclusions: A great disparity between universities was identified. In general, acquired knowledge seems scarce for PA promotion and exercise prescription in primary healthcare staff. Nurses would need additional physical activity on prescription training to improve PA promotion and exercise prescription knowledge as a coadjutant non-pharmacological treatment for non-communicable chronic diseases in Primary Healthcare settings.
Nonalcoholic fatty liver disease and osteoporosis: A potential association with therapeutic implications

Nonalcoholic fatty liver disease (NAFLD) and osteoporosis are two highly prevalent metabolic diseases. Increasing experimental evidence supports a pathophysiological link between NAFLD and osteoporosis. A key feature could be chronic, low‐grade inflammation, which characterizes NAFLD and possibly affects bone metabolism. In this context, several factors, including but not limited to receptor activator of nuclear factor kappa‐B ligand, osteoprotegerin, osteopontin and osteocalcin, may serve as mediators. In the clinical setting, most but not all epidemiological evidence indicates that NAFLD is associated with lower bone mineral density or osteoporosis in adults. Although an association between NAFLD and osteoporosis has not yet been established, and thus remains speculative, pharmacological considerations already exist. Some of the current and emerging pharmacological options for NAFLD have shown possible anti‐osteoporotic properties (eg, vitamin E, obeticholic acid, semaglutide), while others (eg, pioglitazone, canagliflozin) have been associated with increased risk of fractures and may be avoided in patients with NAFLD and concomitant osteoporosis, especially those at high fracture risk. Conversely, some anti‐osteoporotic medications (denosumab) might benefit NAFLD, while others (raloxifene) might adversely affect it and, consequently, may be avoided in patients with osteoporosis and NAFLD. If an association between NAFLD and osteoporosis is established, a medication that could target both diseases would be a great advancement. This review summarizes the main experimental and clinical evidence on the potential association between NAFLD and osteoporosis and focuses on treatment considerations derived from this potential association.
Pathophysiology and mechanism of long COVID: a comprehensive review

Abstract Background After almost 2 years of fighting against SARS-CoV-2 pandemic, the number of patients enduring persistent symptoms long after acute infection is a matter of concern. This set of symptoms was referred to as “long COVID”, and it was defined more recently as “Post COVID-19 condition” by the World health Organization (WHO). Although studies have revealed that long COVID can manifest whatever the severity of inaugural illness, the underlying pathophysiology is still enigmatic. Aim To conduct a comprehensive review to address the putative pathophysiology underlying the persisting symptoms of long COVID. Method We searched 11 bibliographic databases (Cochrane Library, JBI EBP Database, Medline, Embase, PsycInfo, CINHAL, Ovid Nursing Database, Journals@Ovid, SciLit, EuropePMC, and CoronaCentral). We selected studies that put forward hypotheses on the pathophysiology, as well as those that encompassed long COVID patients in their research investigation. Results A total of 98 articles were included in the systematic review, 54 of which exclusively addressed hypotheses on pathophysiology, while 44 involved COVID patients. Studies that included patients displayed heterogeneity with respect to the severity of initial illness, timing of analysis, or presence of a control group. Although long COVID likely results from long-term organ damage due to acute-phase infection, specific mechanisms following the initial illness could contribute to the later symptoms possibly affecting many organs. As such, autonomic nervous system damage could account for many symptoms without clear evidence of organ damage. Immune dysregulation, auto-immunity, endothelial dysfunction, occult viral persistence, as well as coagulation activation are the main underlying pathophysiological mechanisms so far. Conclusion Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. Apart from long-term organ damage, many hints suggest that specific mechanisms following acute illness could be involved in long COVID symptoms. KEY MESSAGES Long-COVID is a multisystem disease that develops regardless of the initial disease severity. Its clinical spectrum comprises a wide range of symptoms. The mechanisms underlying its pathophysiology are still unclear. Although organ damage from the acute infection phase likely accounts for symptoms, specific long-lasting inflammatory mechanisms have been proposed, as well. Existing studies involving Long-COVID patients are highly heterogeneous, as they include patients with various COVID-19 severity levels and different time frame analysis, as well.
Learned Motor Patterns Are Replayed in Human Motor Cortex during Sleep

Consolidation of memory is believed to involve offline replay of neural activity. While amply demonstrated in rodents, evidence for replay in humans, particularly regarding motor memory, is less compelling. To determine whether replay occurs after motor learning, we sought to record from motor cortex during a novel motor task and subsequent overnight sleep. A 36-year-old man with tetraplegia secondary to cervical spinal cord injury enrolled in the ongoing BrainGate brain–computer interface pilot clinical trial had two 96-channel intracortical microelectrode arrays placed chronically into left precentral gyrus. Single- and multi-unit activity was recorded while he played a color/sound sequence matching memory game. Intended movements were decoded from motor cortical neuronal activity by a real-time steady-state Kalman filter that allowed the participant to control a neurally driven cursor on the screen. Intracortical neural activity from precentral gyrus and 2-lead scalp EEG were recorded overnight as he slept. When decoded using the same steady-state Kalman filter parameters, intracortical neural signals recorded overnight replayed the target sequence from the memory game at intervals throughout at a frequency significantly greater than expected by chance. Replay events occurred at speeds ranging from 1 to 4 times as fast as initial task execution and were most frequently observed during slow-wave sleep. These results demonstrate that recent visuomotor skill acquisition in humans may be accompanied by replay of the corresponding motor cortex neural activity during sleep. SIGNIFICANCE STATEMENT Within cortex, the acquisition of information is often followed by the offline recapitulation of specific sequences of neural firing. Replay of recent activity is enriched during sleep and may support the consolidation of learning and memory. Using an intracortical brain–computer interface, we recorded and decoded activity from motor cortex as a human research participant performed a novel motor task. By decoding neural activity throughout subsequent sleep, we find that neural sequences underlying the recently practiced motor task are repeated throughout the night, providing direct evidence of replay in human motor cortex during sleep. This approach, using an optimized brain–computer interface decoder to characterize neural activity during sleep, provides a framework for future studies exploring replay, learning, and memory.
Landscape genetics reveals contrasting patterns of connectivity in two newt species (Lissotriton montandoni and L. vulgaris)

Ecologically distinct species may respond to landscape changes in different ways. In addition to basic ecological data, the extent of the geographic range has been successfully used as an indicator of species sensitivity to anthropogenic landscapes, with widespread species usually found to be less sensitive compared to range‐restricted species. In this study, we investigate connectivity patterns of two closely related but ecologically distinct newt species – the range‐restricted, Lissotriton montandoni and the widespread, L. vulgaris – using genomic data, a highly replicated setting (six geographic regions per species), and tools from landscape genetics. Our results show the importance of forest for connectivity in both species, but at the same time suggest differential use of forested habitat, with L. montandoni and L. vulgaris showing the highest connectivity at forest‐core and forest‐edges, respectively. Anthropogenic landscapes (i.e., higher crop‐ or urban‐cover) increased resistance in both species, but the effect was one to three orders of magnitude stronger in L. montandoni than in L. vulgaris. This result is consistent with a view of L. vulgaris as an ecological generalist. Even so, currently, the negative impact of anthropogenic landscapes is mainly seen in connectivity among L. vulgaris populations, which show significantly stronger isolation and lower effective sizes relative to L. montandoni. Overall, this study emphasizes how habitat destruction is compromising genetic connectivity not only in endemic, range‐restricted species of conservation concern but also in widespread generalist species, despite their comparatively lower sensitivity to anthropogenic landscape changes.
Koncepce úspěchuschopnosti a její pojetí strategie

Success-ability based conception represents approach viewing the behavior of the company from the point of success, strategy, competitiveness and competition. Each of these elements has specific delimitation in given conception and its integral role. Such approach can be understood not only as an alternative, but also as completing approach to the delimitation of company strategy. It integrates classic approaches with new requirements, thus enabling their better utilization in contemporary environment. Its basic characteristics can be summarized into following points: • specific terminology - key term is just success-ability as such, marking the ability to reach under factual conditions objectives set in advance in required level with required level of development; • complex understanding of the success of the company in relation to all key stakeholders - three main dimensions are defined, which must be taken into consideration within the fra- mework of the evaluation of company success-ability; • specific understanding of competition and competitive environment, including not only com- petitive relations, but also the effects of environment and its mutual links - the conceptions operates with competitive space in which just mentioned links can represent key elements; • differentiation of various types of competitive advantages and competitiveness which it forms - the conception has its own classification of competitive advantages, enabling the involve- ment of factors which the company utilizes in a very complex way; • specific approach to the implementation level based on clearly key role of the management not only in the moment of the formulation, but also during the implementation itself - the cha- racteristic feature of this conception is just the cohesion of formulation and implementation of the strategy; • approach analyzing the company in compliance with the logics of the conception of success- -ability, enabling the competitive advantages of companies, method of their development, possibility to control and influence their development and the importance of advantages from the view of competitors and customers - the use of specific break-down of competitive advan- tages and specific approach to competitive environment demands so as traditional tools of strategic analyses would be completed with approaches, coming -out from the principles of the success-ability conception.
Structural insights into ClpP protease side exit pore‐opening by a pH drop coupled with substrate hydrolysis

The ClpP serine peptidase is a tetradecameric degradation molecular machine involved in many physiological processes. It becomes a competent ATP‐dependent protease when coupled with Clp‐ATPases. Small chemical compounds, acyldepsipeptides (ADEPs), are known to cause the dysregulation and activation of ClpP without ATPases and have potential as novel antibiotics. Previously, structural studies of ClpP from various species revealed its structural details, conformational changes, and activation mechanism. Although product release through side exit pores has been proposed, the detailed driving force for product release remains elusive. Herein, we report crystal structures of ClpP from Bacillus subtilis (BsClpP) in unforeseen ADEP‐bound states. Cryo‐electron microscopy structures of BsClpP revealed various conformational states under different pH conditions. To understand the conformational change required for product release, we investigated the relationship between substrate hydrolysis and the pH‐lowering process. The production of hydrolyzed peptides from acidic and basic substrates by proteinase K and BsClpP lowered the pH values. Our data, together with those of previous findings, provide insight into the molecular mechanism of product release by the ClpP self‐compartmentalizing protease.
Idebenone regulates sirt1/Nrf2/TNF-α pathway with inhibition of oxidative stress, inflammation, and apoptosis in testicular torsion/detorsion in juvenile rats

Testicular torsion is an emergency, mainly in newborn and adolescent males, resulting in testicular ischemia. The current study aimed to evaluate the effect of Idebenone (IDE) on testicular torsion/detorsion (T/D) in juvenile rats. Thirty-two rats were randomized into: (1) the sham group: rats received sham operations with no other interventions; (2) the IDE group: rats received idebenone (100 mg/kg, i. p) without T/D; (3) the T/D group: rats underwent torsion for 2 h and detorsion for 4 h; and (4) the IDE+ T/D group: rats received IDE 1 h before T/D. Testicular malondialdehyde (MDA), total nitrite/nitrate (NOx), total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α), caspase-3, sirtuin type 1 (Sirt1), serum interleukin-1β (IL-1β), total cholesterol, and testosterone were measured. Histological changes, nuclear factor (erythroid-derived 2)-like-2 factors (Nrf2), and proliferating cell nuclear antigen (PCNA) immuno-expressions were assessed. T/D displayed an increase in MDA, NOx, TNF-α, caspase-3, IL-1β, and total cholesterol with a significant decrease in TAC, Sirt1, and testosterone and strong positive Nrf2 and negative PCNA immuno-expressions. IDE could improve all oxidative, inflammatory, and apoptotic indicators. Therefore, IDE significantly reduced testicular ischemia-reperfusion injury in the juvenile rat testicular T/D model by limiting oxidative stress, inflammation, and apoptosis via the Sirt1/Nrf2/TNF-α pathway. Graphical Abstract
First-in-Humans PET Imaging of Tissue Factor in Patients with Primary and Metastatic Cancers Using 18F-labeled Active-Site Inhibited Factor VII (18F-ASIS): Potential as Companion Diagnostic

Visual Abstract Tissue factor (TF) expression in cancers correlates with poor prognosis. Recently, the first TF-targeted therapy was approved by the U.S. Food and Drug Administration for cervical cancer. To unfold the potential of TF-targeted therapies, correct stratification and selection of patients eligible for treatments may become important for optimization of patient outcomes. TF-targeted PET imaging based on 18F-radiolabeled active-site inhibited versions of the TF natural ligand coagulation factor VII (18F-ASIS) has in preclinical models convincingly demonstrated its use for noninvasive quantitative measurements of TF expression in tumor tissue. 18F-ASIS PET imaging thus has the potential to act as a diagnostic companion for TF-targeted therapies in the clinical setting. Methods: In this first-in-humans trial, we included 10 cancer patients (4 pancreatic, 3 breast, 2 lung, and 1 cervical cancer) for 18F-ASIS PET imaging. The mean and SD of administered 18F-ASIS activity was 157 ± 35 MBq (range, 93–198 MBq). PET/CT was performed after 1, 2, and 4 h. The primary objectives were to establish the safety, biodistribution, pharmacokinetics, and dosimetry of 18F-ASIS. Secondary objectives included quantitative measurements of SUVs in tumor tissue with PET and evaluation of the correlation (Pearson correlation) between tumor SUVmax and ex vivo TF expression in tumor tissue. Results: Administration of 18F-ASIS was safe, and no adverse events were observed. No clinically significant changes in vital signs, electrocardiograms, or blood parameters were observed after injection of 18F-ASIS. Mean 18F-ASIS plasma half-life was 3.2 ± 0.6 h, and the radiotracer was predominantly excreted in the urine. For injection activity of 200 MBq of 18F-ASIS, effective whole-body dose was 4 mSv and no prohibitive organ-specific absorbed doses were found. Heterogeneous radiotracer uptake was observed across patients and within tumors. We found a trend of a positive correlation between tumor SUVmax and ex vivo TF expression (r = 0.84, P = 0.08, n = 5). Conclusion: 18F-ASIS can be safely administered to cancer patients for PET imaging of TF expression in tumors. The trial marks the first test of a TF-targeted PET radiotracer in humans (first-in-class). The findings represent important first steps toward clinical implementation of 18F-ASIS PET imaging of TF expression.
Spelling out the roles of individual nucleoporins in nuclear export of mRNA

ABSTRACT The Nuclear Pore Complex (NPC) represents a critical passage through the nuclear envelope for nuclear import and export that impacts nearly every cellular process at some level. Recent technological advances in the form of Auxin Inducible Degron (AID) strategies and Single-Point Edge-Excitation sub-Diffraction (SPEED) microscopy have enabled us to provide new insight into the distinct functions and roles of nuclear basket nucleoporins (Nups) upon nuclear docking and export for mRNAs. In this paper, we provide a review of our recent findings as well as an assessment of new techniques, updated models, and future perspectives in the studies of mRNA’s nuclear export.