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During the period of remote learning caused by the COVID-19 pandemic, honors programs were forced to innovate new digital possibilities for fulfilling the objectives of an honors education. Learning experiences offered during study abroad programs were among the most difficult to provide in a virtual format. The honors program at Eastern Michigan University has developed the Virtual International Experience (VIE) in response to this need. Even as the 2022-2023 academic year marked a transition back to traditional in-person classes, the VIE offers unique tools for learning skills of cultural analysis and cross-cultural communication, particularly as these occur in remote contexts, something that is becoming increasingly relevant. As three students who participated in the VIE and the professor who created it, the authors have taken this second shift in instructional format as an opportunity to consider the advantages of tools acquired during remote learning while also reaffirming the irreplaceable value of traditional study abroad programs.

BACKGROUND: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19. METHODS: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728). FINDINGS: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group. INTERPRETATION: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19. FUNDING: Biophytis.

Background. To treat patients with hypocoagulation, an objective assessment of the hemostasis system is mandatory. Owren prothrombin time method is rare in Ukrainian hospitals. Objective: in this review, we describe Quick and Owren prothrombin time methods, advantages and limitations of each of them in the treatment of patients with liver failure or anticoagulant users. Materials and methods. Advanced literature search was completed in PubMed, linked with MEDLINE database in English and Google Scholar in Ukrainian. Results. Thirty-four articles met search criteria and were included in the literature review. Conclusions. We can’t compare Quick and Owren prothrombin time methods in seconds and percentages because of different dilution methods. Quick prothrombin time method is more widespread due to the lower costs. Owren prothrombin time method has advantages in patients with hepatobiliar disorders, anticoagulant users and for optimization of the diagnosis of chronic liver failure according to the MELD score for liver transplantation.

Objective: to evaluate the efficacy of a single or double administration of a preparation of high molecular weight hyaluronic acid (HLA) with chondroitin sulfate (CS) in post-traumatic knee osteoarthritis (OA). Material and methods. The study included 91 patients with stage III post-traumatic knee OA. All patients received intra-articular (i/a) injection of high molecular weight HLA with CS; 36 patients received the drug once (group 1) and 55 twice (group 2) with an average interval of 7±2 days. Before the start of treatment and 2 weeks, 1, 3, 6 and 12 months after i/a injection of HLA, pain intensity at rest and during movement was assessed using a visual analogue scale (VAS) and function was assessed using KOOS questionnaire (Knee injury and Osteoarthritis Outcome Score). Results and discussion. In general, patients receiving single and double i/a injections of HLA, pain during movement at baseline, and after 2 weeks, 1, 3, 6 and 12 months was 6.7±1.1; 4.0±0.7; 4.3±0.8; 4.6±1.0; 4.5±1.1 and 5.3±0.4 cm; pain at rest – 2.7±0.6; 1.5±0.2; 1.8±0.2; 2.1±0.5; 2.2±0.3 and 2.6±0.2 cm, and KOOS score was 35.9±13.6; 43.5±13.6; 49.2±17.6; 57.0±12.5; 51.5±11.7 and 40.3±10.2, respectively. In group 1, pain during movement at the same time line reached 6.7±1.2; 4.0±0.7; 4.3±1.1; 4.6±.08; 4.5±0.6 and 5.3±1.3 cm; pain at rest – 2.7±0.5; 1.5±0.3; 1.8±0.4; 2.1±0.4; 2.2±0.6 and 2.6±0.6 cm; KOOS score – 37.2±8.7; 39.1±10.1; 43.0±12.3; 47.0±13.6; 49.5±14.7 and 35.7±12.4, respectively.In the 2nd group, pain during movement was 6.1±1.5; 3.3±0.7; 3.6±0.6; 3.4±0.5; 3.7±0.4 and 4.4±0.3 cm; pain at rest was 2.6±0.3; 1.9±0.2; 1.1±0.2; 0.9±0.1; 0.7±0.1 and 1.7±0.3 cm; KOOS score was 34.7±9.4; 47.1±11.1; 59.3±11.5; 61.4±12.7; 57.2±14.3 and 45.7±12.4, respectively. Conclusion. In patients with stage III knee OA, double injections of HLA with HS were more effective. The maximum pain reduction and functional improvement were observed in the first 3 months after local injection therapy.

Abstract Background Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death. Methods Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6–29) and 28-day all-cause mortality (Days 1–29). Results One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (

Background and Aim of Study: War has an extremely negative effect on people’s psyches. This is especially true for student youth. They have to build personal lives and continue their studies in these difficult and traumatic conditions. The aim of the study: to identify the peculiarities of the dynamics of psychological trauma, and the manifestations of depression, anxiety and stress among students in wartime. Material and Methods: The study involved university students from Ukraine and European Union countries in 2022-2024. Respondents aged 20-50 years were divided into 4 groups. Group 1 consisted of 107 students, including 64 (59.8%) males and 43 (40.2%) females, living in areas where there was no hostilities or shelling (November 2022). Group 2 consisted of 103 students, including 52 (50.5%) males and 51 (49.5%) females, living in the area of active hostilities (November 2022). Group 3 consisted of 112 students, including 41 (36.6%) males and 71 (63.4%) females, living in areas where there was no hostilities or shelling (March 2024). Group 4 consisted of 115 students, including 30 (26.1%) males and 85 (73.9%) females, living in the area of active hostilities (March 2024). The study involved the development of the author’s questionnaire and the adapted psychological test on the DASS-21, which is available on the Google Forms platform. The technique was found to have adequate internal consistency. Cronbach’s alpha was 0.807. Results: Longitudinal studies have shown that university students in wartime are characterised by a tendency to increase psychogenics related to martial law, communication and safety. A closer look at the dynamics of psychopathological symptoms revealed a trend towards increased depression and anxiety, as well as a stabilisation of acute stress indicators in all groups. This indicates a serious deterioration in the mental health of the students and a further chronicisation of their neurotic disorders. Conclusions: The negative impact of the war in Ukraine on the mental health of student youth requires the active implementation of psychological support measures and psychoprophylaxis in accordance with individual psychodiagnostic findings.

Instantaneous frequency measurement devices are designated for very fast measurements of the current frequency value of microwave signals, even if they are very short in the time domain. Fast measurements of frequency temporary values may be based on the evaluation of the phase difference of signal propagating through the microwave transmission lines with unequal, but known, lengths. This paper presents the principle of determination of temporary values of the microwave signal frequency using the digitalized signals and the binary value of them eventually. In the purpose of increase the frequency discrimination resolution, additional tracks with lines with a larger length are proposed. For the system with elements with analytical model transmission characteristics it is typical that bands of ambiguity of frequency measurement occurs. To tackle this problem in addition to 4 x 4 Butler matrix implementation the method of using combination sine and cosine signals is proposed.

The article presents the main provisions of the theory of functional modeling in relation to solving an important and relevant problem for the methodology of information security managing – the development of mathematical models characterizing the dynamic capabilities of malware to implement destructive effects on critical information infrastructure objects. As a result of the analysis of the models that pose a threat to information security through the use of malicious codes, such as the "chain of cyber intrusions", the "unified chain of cyber intrusions", the basic and advanced models of Diamond intrusion analysis, the ATT&CK model, an up-to-date version of the functional model in the IDEF0 notation of the process of malware destructive impact on the operating environment of a special-purpose automated control system was built. The process of malware exposure is decomposed into individual stages, tactics, and techniques. The purpose of the research was to develop a variant of the malware impact on a special-purpose automated control system as a method of violating the state of information security and its processes of the system under consideration. The obtained results are a tool for the formalized presentation of the described processes in terms of the Markov processes and the development of analytical models, appropriate temporal and probabilistic characteristics for quantitative assessment of the intruder's ability to implement threats to the information security state in special-purpose automated control systems, through the malware impact.

Background and Aim of Study: The full-scale military aggression against Ukraine in February 2022 had an extremely negative impact on the psyche of its residents. This is especially felt by young people who should continue studying at universities in these difficult conditions. The aim of the study: To identify the specifics of psychotraumatic impact in the conditions of war and martial law on university students and cadets, to detail their level of stress, anxiety and depression. Materials and Methods: The study was conducted in November 2022 based on KNUIA, Ukraine. Respondents aged 20-27 were divided into 3 groups: 1) 115 cadets: 85.22% men and 14.78% women, who are outside of permanent deployment; 2) 107 students: 59.81% men and 40.19% women, who are forcibly displaced persons in Ukraine and abroad; 3) 103 students: 50.49% men and 49.51% women, located in Kharkiv and Kharkiv region. A Google-form questionnaire was used to study the level and nature of psychotraumatization. Data collection on the level of stress and its content was carried out using the DASS-21 tool. Results: Among the group 3 respondents, the psychotraumatic impact is characterized by high tension and the specific weight of vital psychogenia. Severe and extremely severe manifestations of anxiety in group 3 students were 2-3 times higher than the similar indicators of groups 1, 2 respondents. Manifestations of depression among women are the highest in group 3 respondents. Stress was more expressed among men in all groups. Group 3 respondents had the highest stress indicators among men. Conclusions: The negative impact of the war in Ukraine on the student youth' mental health requires the active implementation of psychological assistance and psychoprophylaxis measures in accordance with the individual results of psychodiagnostics.

Summary: Under stress, protein synthesis is attenuated to preserve energy and mitigate challenges to protein homeostasis. Here, we describe, with high temporal resolution, the dynamic landscape of changes in the abundance of proteins synthesized upon stress from transient mitochondrial inner membrane depolarization. This nascent proteome was altered when global translation was attenuated by stress and began to normalize as translation was recovering. This transition was associated with a transient desynchronization of cytosolic and mitochondrial translation and recovery of cytosolic and mitochondrial ribosomal proteins. Further, the elongation factor EEF1A1 was downregulated upon mitochondrial stress, and its silencing mimicked the stress-induced nascent proteome remodeling, including alterations in the nascent respiratory chain proteins. Unexpectedly, the stress-induced alterations in the nascent proteome were independent of physiological protein abundance and turnover. In summary, we provide insights into the physiological and pathological consequences of mitochondrial function and dysfunction.

BackgroundCavernous angiomas (CAs) affect 0.5% of the population, predisposing to serious neurologic sequelae from brain bleeding. A leaky gut epithelium associated with a permissive gut microbiome, was identified in patients who develop CAs, favoring lipid polysaccharide producing bacterial species. Micro-ribonucleic acids along with plasma levels of proteins reflecting angiogenesis and inflammation were also previously correlated with CA and CA with symptomatic hemorrhage.MethodsThe plasma metabolome of CA patients and CA patients with symptomatic hemorrhage was assessed using liquid-chromatography mass spectrometry. Differential metabolites were identified using partial least squares-discriminant analysis (p

RESEARCH OBJECTIVE: The article discusses the interplay between language, cognition and culture from a cognitive diachronic perspective, focusing on the relation between religion and metaphorical thought. It investigates the role of the conceptual metaphor UNDERSTANDING IS LIGHT in religious discourse, using the example of The Revelations of Divine Love, written by Julian of Norwich, a late medieval anchoress. THE RESEARCH PROBLEM AND METODS: The paper draws on the Extended Conceptual Metaphor approach, Zoltán Kövecses’s elaboration of the Conceptual Metaphor Theory (CMT). The universalist bias of CMT means that the theory tends to ignore the sociocultural context of historical data, prioritising the influence of universal human embodiment on metaphorical thought. Using Kövecses’s approach, the paper shows how the gap in CMT methodology may be bridged to yield more reliable results. THE PROCESS OF ARGUMENTATION: The present study connects Kövecses’s approach to Cognitive Linguistic research into sociocultural situatedness. To exemplify the problem, the analysis examines the cognitive‑cultural underpinnings of Julian’s use of the metaphor UNDERSTAND‑ ING IS LIGHT. RESEARCH RESULTS: The analysis shows that the metaphorical conceptualisation pattern may well derive from Julian’s sociocultural situatedness. The paper indicates that the anchoress’s metaphorical thought should be seen as embedded in the late medieval sociocultural context, rather than being considered solely in terms of universal aspects of embodiment. CONCLUSIONS, RECOMMENDATIONS AND THE APPLICATIVE VALUE OF RESEARCH: The study concludes that the idea of sociocultural situatedness may be pivotal in the analyses of historical texts. It seems important to incorporate this idea into Kövecses’s approach, which may inform the methodology of cognitive diachronic research into metaphorical conceptualisations. Furthermore, the results may be applied to teaching students how to approach historical texts, helping them gain a better understanding of the relation between metaphorical thought and culture.

Abstract Background We conducted an analysis of the vascular surgery regional center reorganization in response to the first and the second wave of the coronavirus disease-2019 (COVID-19) pandemic to see what lessons we learned from the first wave. Methods The study included a total of 632 patients admitted to the vascular surgery department in three periods: March–May 2020, October–December 2020, and October–December 2019 as a control period. Results In the pandemic periods the number of admitted patients decreased in relation to the control period. There was a reduction in performed procedures. We observed an increase in the ratio of less invasive procedures. There was a significant decline in hospitalization time in comparison to the control period. Conclusions The reduction of scheduled admissions and procedures affected vascular centers all over the world. Minimally invasive procedures were more willingly performed to shorten the hospitalization time and reduce the patient's exposure to hospital infection. It allowed us to treat more patients during the second wave. Nevertheless, an increased number of vascular patients should be expected in the future, which will result from the failure to perform elective procedures during the pandemic.

Abstract Cerebral cavernous malformation (CCM) is a hemorrhagic neurovascular disease with no currently available therapeutics. Prior evidence suggests that different cell types may play a role in CCM pathogenesis. The contribution of each cell type to the dysfunctional cellular crosstalk remains unclear. Herein, RNA-seq was performed on fluorescence-activated cell sorted endothelial cells (ECs), pericytes, and neuroglia from CCM lesions and non-lesional brain tissue controls. Differentially Expressed Gene (DEG), pathway and Ligand-Receptor (LR) analyses were performed to characterize the dysfunctional genes of respective cell types within CCMs. Common DEGs among all three cell types were related to inflammation and endothelial-to-mesenchymal transition (EndMT). DEG and pathway analyses supported a role of lesional ECs in dysregulated angiogenesis and increased permeability. VEGFA was particularly upregulated in pericytes. Further pathway and LR analyses identified vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 signaling in lesional ECs and pericytes that would result in increased angiogenesis. Moreover, lesional pericytes and neuroglia predominantly showed DEGs and pathways mediating the immune response. Further analyses of cell specific gene alterations in CCM endorsed potential contribution to EndMT, coagulation, and a hypoxic microenvironment. Taken together, these findings motivate mechanistic hypotheses regarding non-endothelial contributions to lesion pathobiology and may lead to novel therapeutic targets. Video Abstract

Background and Aim of Study: The war in Ukraine affects the psychological state and life activities of university students. Aim of the study: to identify the state of psychological well-being of students and the peculiarities of students’ use of coping strategies in overcoming life crises on their own. Material and Methods: The study was conducted among 323 Ukrainian university students aged 20-35 in October 2023. According to the impact of the hostilities on them, the respondents were divided into 3 groups: Group 1 – 111 persons living in the area of active hostilities; Group 2 – 104 persons living in the areas where missiles and drones were fired; Group 3 – 108 persons living on the territory of Ukraine, where there were no hostilities and shelling, and in the EU countries. The Psychological General Well-Being Index, PGWBI, and the Coping Strategies Inventory, CSI, were included in an online survey. Both techniques were found to have adequate internal consistency (Cronbach’s alpha was 0.928 and 0.759, respectively). Results: Respondents in all groups are moderately distressed. The highest level of distress (the lowest level of PGWBI) was found among students in Group 1 (55.1 points). Students in Groups 2 and 3 had lower scores (60.1 and 63.5 points, respectively), which corresponds to moderate distress. Students use a variety of coping strategies in stressful situations. However, the coping strategy of cognitive restructuring was used more often (9.8 points in Group 3, 9.5 points in Group 1). This was due to a general rethinking of the meaning of life, of attitudes toward oneself and others because of the war. Coping strategies of social support (8.9 points) and self-criticism (8.7 points) were also important for Group 1. This was due to the importance of social support, reassessment of one’s own behavior and thinking in the war. Conclusions: The obtained data indicate that the war in Ukraine has a negative impact on the psychological state of students. The level of impact was higher the closer the students were to the active combat zone. This influence determined the students' choice of coping strategies in dealing with life crises on their own.

Abstract Particle physics today faces the challenge of explaining the mystery of dark matter, the origin of matter over anti-matter in the Universe, the origin of the neutrino masses, the apparent fine-tuning of the electro-weak scale, and many other aspects of fundamental physics. Perhaps the most striking frontier to emerge in the search for answers involves new physics at mass scales comparable to familiar matter, below the GeV-scale, or even radically below, down to sub-eV scales, and with very feeble interaction strength. New theoretical ideas to address dark matter and other fundamental questions predict such feebly interacting particles (FIPs) at these scales, and indeed, existing data provide numerous hints for such possibility. A vibrant experimental program to discover such physics is under way, guided by a systematic theoretical approach firmly grounded on the underlying principles of the Standard Model. This document represents the report of the FIPs 2022 workshop, held at CERN between the 17 and 21 October 2022 and aims to give an overview of these efforts, their motivations, and the decadal goals that animate the community involved in the search for FIPs.

We aimed to test the common belief, that as the sperm cell is the smallest cell in an organism and, therefore, it contains a small amount of intracellular water, the intracellular ice should not strongly affect the sperm cell during the cryopreservation. To investigate the effect of intracellular ice, we developed a novel approach of ram spermatozoa ultra-rapid freezing with the inhibition of the growth of extracellular ice crystals during freezing. In our approach, ram sperm was supplemented with cell-impermeable synthetic ice blocker 1,4-Cyclohexanediol, leaving a sample unsupplemented as a control. Sperm in cryostraws were ultra-rapidly frozen, and then thawed. We hypothesized, that only in the case when the intracellular ice plays the role in the cryodamage, the post-freezing intactness of spermatozoa frozen in the presence of extracellular ice inhibitors should be equal (or even less) to the intactness of spermatozoa frozen without extracellular inhibitors. No statistically significant difference (p = 0.98) was observed between the post-freezing intactness of sperm ultra-rapidly frozen in the presence of 1,4-Cyclohexanediol and the intactness of sperm frozen without 1,4-Cyclohexanediol. We concluded that the intracellular ice plays the role in sperm cryodamage, at least in the model of ram sperm ultra-rapid freezing.HighlightsHere, we investigated the cryodamaging factors during ram sperm ultra-rapid freezing;Optimized ultra-rapid freezing will provide positive economic implications for the sheep industry worldwide.