C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.

The Novel Coronavirus Disease (nCOVID) has grabed the whole world recently since its origin in Wuhan city of China. There is very dire consequences the whole world is going through because of nCOVID. The unprecedented nCOVID and associated consequences pushed the public health system in the crisis. Undoubtedly, it has affected almost all countries of the world. Nevertheless, hardly a few country it has spared from its dire consequences in terms social and economical losses. However, it is worth of observing that some of the positive consequences are also results of this pandemic. Consequently, this paper discusses the pros and cons of the pandemic from various perspective such as social and economical impacts on human lives and livelihoods.

Background: Cigarette smoking (CS) is a global public health problem and a high-risk factor for various diseases. In December 2019, a novel coronavirus (HCoV-19) was identified in Wuhan, China. Because ACE2 has been identified as a receptor for HCoV-19, we hypothesize that CS affects the expression pattern of ACE2 in respiratory tract, causing differences in susceptibility to the virus. Methods: Three datasets (GSE994, GSE17913, and GSE18344), were downloaded from the Gene Expression Omnibus (GEO) database. Correlation and enrichment analysis were used to evaluate the function of ACE2. Also, the different expression of ACE2 in different groups of three datasets were analyzed. Results: Genes associated with ACE2 were enriched in important biological processes such as viral processes and immune response. Elevated ACE2 were found in intrapulmonary airways (GSE994) and oral epithelial cells (GSE17913) of smokers but not those of non-smokers or former smokers. Significant dose- and time-dependent relationships between CS and ACE2 expression were observed in mouse lung tissues, and long periods without smoking were found to significantly reduce ACE2 expression. Conclusions: Both human and rat data confirmed that CS could induce increased ACE2 in the respiratory tract, indicating that smokers have a higher susceptibility to HCoV-19.

Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn injury-induced pain remain insufficiently explored. Spinal dynorphinergic (Pdyn) neurons contribute to heat hyperalgesia induced by severe scalding-type burn injury through p-S10H3-dependent signaling. Beyond p-S10H3, burn injury may impact various other histone H3 PTMs. Double immunofluorescent staining and histone H3 protein analyses demonstrated significant hypermethylation at H3K4me1 and H3K4me3 sites and hyperphosphorylation at S10H3 within the spinal cord. By analyzing Pdyn neurons in the spinal dorsal horn, we found evidence of chromatin activation with a significant elevation in p-S10H3 immunoreactivity. We used RNA-seq analysis to compare the effects of burn injury and forma-lin-induced inflammatory pain on spinal cord transcriptomic profiles. We identified 98 DEGs for burn injury and 86 DEGs for formalin-induced inflammatory pain. A limited number of shared differentially expressed genes (DEGs) suggest distinct central pain processing mechanisms between burn injury and formalin models. KEGG pathway analysis supported this divergence, with burn injury activating Wnt signaling. This study enhances our understanding of burn injury mechanisms and uncovers converging and diverging pathways in pain models with different origins.

Alpha-methyl-p-tyrosine (AMPT; also referred as metyrosine) is an approved medication for the treatment of pheochromocytoma. As a tyrosine hydroxylase inhibitor AMPT may be a potential candidate for the treatment of diseases involving catecholamine alterations. However, only small-scale clinical trials have tested AMPT repurposing in few other illnesses. Chronic fatigue syndrome (CFS) is an heterogenous disorder with genetically associated vulnerability of catecholamine metabolism (e.g. catechol O-methyltransferase polymorphisms) holding an important impact of environmental factors. The current case report compiles genetic and longitudinal biochemical data for over a year follow-up of one patient sequentially diagnosed with sustained overstress, neurasthenia, CFS, and POTS (postural orthostatic tachycardia syndrome) over a 10-year period, and reports patient’s symptom improvement in response to low-medium doses of AMPT.

Motivated by Kurt's work [Filomat 30 (4) 921-927, 2016], we first consider a class of a new generating function for (p, q)-analog of Apostol type polynomials of order a including Apostol-Bernoulli, Apostol-Euler and Apostol-Genocchi polynomials of order a. By making use of their generating function, we derive some useful identities. We also introduce (p, q)-analog of Stirling numbers of second kind of order v by which we construct a relation including aforementioned polynomials.

The COVID-19 pandemic struck unexpectedly, emergency services and chronic care institutions, including dialysis centers, were overloaded. An important problem was the care of positive COVID patients, but also the care of chronically dialyzed patients who presented emergencies. In our Hospital, which has become a COVID support for dialysis patients with severe forms of the disease, we had to care for PD patients with dialysis-related emergencies. We presented 2 cases of patients managed on an outpatient basis or 1 day hospitalization, treated successfully and without compromising the quality of the care provided. We used remote monitoring, we worked in a multidiscipli-nary team, we shortened the hospitalization of patients (and implicitly the risk of contact). In pandemic conditions, the advantage of PD was represented by the possibility of patient isolation, so that in the first 6 months of the pandemic, we recorded no deaths in this category of patients. In case of hemodialysis patients, in-fection and mortality rates were high. Although we expected an increase in the number of peritoneal dialysis patients in the post-pandemic period, this did not happen. We continue to plead for the popularization of the PD method among patients and doctors, which has proven its advantages under the conditions of the pandemic.

Long Covid is a debilitating condition that has been well-documented over the past 4 years and shares many similarities with other post-viral chronic illnesses. Despite this, clinicians are not confident in recognising the signs of Long Covid, or effectively managing the symptoms of their patients. This paper presents a single patient case report from a biomedical researcher who has had Long Covid for 2 years; it is written in relatively plain language to be accessible to both patients and clinicians across multiple specialities. The author has had the ability and expertise to keep up with the Long Covid research literature, and from that has cobbled together a management strategy that has alleviated her own symptoms, and those of other people with whom she has shared her protocol. The author’s experience of developing and managing her Long Covid is presented here, in the hopes that it may be of assistance to clinicians in identifying and managing Long Covid in their own patients.

Researchers and organizations are pursing 100 Day Vaccine Development to reduce the impact of any new pandemic-causing virus. They propose monitoring viral emergence and developing vaccines for discovered viruses which would undergo safety testing in humans. If one of these viruses emerges, phase III trials would then take place. There are two problems with this approach - first, phase III trials are too long for the 100-day goal and second, the virus that emerged might not have been discovered in their surveillance. An alternative approach would be to first develop vaccines for viral families similar to the pan coronavirus vaccines being proposed for next generation COVID vaccines. Phase III trials for them would be run even if a virus in the family wasn’t having an outbreak. If a virus in a family for which a vaccine has been developed has an outbreak and the phase III trialed vaccine is not effective against it, develop a booster based on the phase III trialed vaccine. Since booster development and approval takes less than 100 days, the 100 Day Vaccine Development goal would be met.

The last decade was characterized by the reduction of hospital beds throughout Europe. When facing Covid pandemic, this has been an issue of major importance as hospitals were seriously overloaded with an unexpected growth in demand. The dichotomy formed by the scarcity of beds and the need for acute care was handled by the Bed Management (BM) function. This study explores how BM was able to help the solidness of the healthcare system, managing hospital beds at best and recruiting others in different set-tings as intermediate care, in a large Local Health Authority (LHA) in central Italy. Ad-ministrative data show how the provision of appropriate care was achieved recruiting approximately 500 beds belonging to private healthcare facilities affiliated with the re-gional healthcare system and exercising at best the BM function. The ability of the system to absorb the extra demand caused by Covid was made possible using intermediate care beds, which allowed to stretch the logistic boundaries of the hospitals, and by the promptness of Bed Management in converting beds in Covid beds and reconverting them and timely managing internal patient logistic, thus creating space according to the healthcare demand.

Long COVID affects a significant number of people after acute coronavirus disease 2019 (COVID-19), and haematological changes can persist in the COVID-19 phase. This study aimed to evaluate these haematological laboratory markers, linking them to clinical findings and long-term outcomes in patients with long COVID. This cross-sectional study selected participants from a ‘long COVID’ clinical care programme in the Amazon region. Clinical data and baseline demographics were obtained, and blood samples were collected for quantification of erythrogram-, leukogram-, and plateletgram-related markers. Long COVID was reported for up to 985 days. Patients hospitalised in the acute phase had higher mean red/white cell, platelet, and plateletcrit levels and red cell distribution width. In addition, haematimetric parameters were higher in shorter periods of long COVID. Patients presenting with more than six concomitant long COVID symptoms had a higher white blood cell count, shorter prothrombin time (PT), and increased PT activity. Within up to 985 days of long COVID, our results suggest a probable benign compensation for erythrogram-related markers. Increased levels of leukogram-related markers and increased coagulation activity were observed in the worse long COVID groups, also indicating an exacerbated response after the acute disturbance, which is uncertain and requires further investigation.

In this paper, bikeshare data in Chicago on weather-friendly days in 2019 and 2020 were analyzed to investigate the variation in bikeshare travel before and during the pandemic. Our results show that bikeshare trips during the pandemic were much longer than prior to the pandemic. The increased rate of bikeshare usage was unbalanced spatially and varied significantly for different user types. Specifically, bikeshare was used significantly more by casual users than by subscribers, and the increase occurred much more in the outskirts of the city. The increase in bikeshare travel was associated with a reduction in travel by ride-hailing and public transit, especially in the urban periphery. The correlation of bikeshare use with the bus system was much less significant than with the rail system. Bike lanes/facilities had a mixed effect on bikeshare travel. Weekend bike trips increased in areas where there was no bike lane. Weekday trips, on the contrary, increased in the vicinity of bike greenways.

The interleukin 6 (IL-6) receptor blocking antibody tocilizumab was repurposed in the coronavirus pandemic with the intention of blocking the excess inflammatory activation associated with severe disease. We retrospectively evaluated the response to tocilizumab based on measured levels of IL-6 as well as other inflammatory markers. In the sample of 41 patients with measured levels, 16 received tocilizumab. In patients who received tocilizumab, there was a statistically significant relationship between both higher IL-6 levels and measured acute phase reactants with mortality, but not in those who did not. Additionally, an improved mortality after tocilizumab was suggested with those with higher IL-6 measurements, but not in those with lower levels, but this finding failed to achieve statistical significance (p=0.14). Though this study is limited by a small sample size and retrospective design, an association is suggested between higher IL-6 levels and improved mortality after tocilizumab.

OBJETIVES: During the COVID-19 pandemic, the risk of collapse of the health system created great difficulties. We will demonstrate that Intermediate Respiratory Care Units (IRCU) provide adequate management of patients with non-invasive respiratory support, which is particularly important in patients with SARS-CoV-2 pneumonia. METHODS: A prospective observational study of patients with COVID-19 admitted to the ICU of a tertiary hospital. Sociodemographic data, comorbidities, pharmacological, respiratory support, laboratory and blood gas variables were collected. The overall cost of the unit was subsequently analyzed. RESULTS: 991 patients were admitted, 56 to the IRCU (of the 81 a critical care unit). Mean age was 65 years (SD 12.8), Barthel Index 75 (SD 8.3), Charlson 3.1 (SD 2.2), HTN 27%, COPD 89% and obesity 24%. Significant relationship (p <0.05) with higher mortality of the following: fever greater than or equal to 39oC [OR 5.6; 95% CI (1.2-2.7); p = 0.020], protocolized pharmacological treatment [OR 0.3; 95% CI (0.1-0.9); p = 0.023] and IOI [OR 3.7; 95% CI (1.1-12.3); p = 0.025]. NIMV showed less of a negative impact [OR 1.8; 95% CI (0.4-8.4); p = 0.423] than IOI. The total cost of the IRCUs amounted to €66,233. The cost per day of stay in the IRCU was €164 per patient. The total cost avoided was €214,865. CONCLUSION: The pandemic has highlighted the importance of IRCUs in facilitating the management of a high patient volume. The treatment carried out in IRCUs is effective and efficient, reducing both admissions to and stays in the ICU.

Background The World Health Organization has recently recognized Long COVID, calling the international medical community to strengthen research and comprehensive care of patients with this condition. However, if Long COVID pertains to children as well is not yet clear. Methods An anonymous, online survey was developed by an organization of parents of children suffering from persisting symptoms since initial infection. Parents were asked to report signs and symptoms, physical activity and mental health issues. Only children with symptoms persisting for more than four weeks were included. Results 510 children were included (56.3% females) infected between January 2020 and January 2021. At their initial COVID-19 infection, 22 (4.3%) children were hospitalized. Overall, children had persisting COVID-19 for a mean of 8.2 months (SD 3.9). Most frequent symptoms were: Tiredness and weakness (444 patients, 87.1% of sample), Fatigue (410, 80.4%), Headache (401, 78.6%), Abdominal pain (387, 75.9%), Muscle and joint pain (309, 60.6%), Post-exertional malaise (274, 53.7%), rash (267, 52.4%). 484 (94.9%) children had had at least four symptoms. 129 (25.3%) children have suffered constant COVID-19 infection symptoms, 252 (49.4%) have had periods of apparent recovery and then symptoms returning, and 97 (19.0%) had a prolonged period of wellness followed by symptoms. Only 51 (10.0%) children have returned to previous levels of physical activity. Parents reported a significant prevalence of Neuropsychiatric symptoms. Conclusions Our study provides further evidence on Long COVID in children. Symptoms like fatigue, headache, muscle and joint pain, rashes and heart palpitations, and mental health issues like lack of concentration and short memory problems, were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. A better comprehension of Long COVID is urgently needed..

Historically, macrophages have been long implicated in the control of the severity of infectious diseases. This has been based on the observations of a higher risk of severe disease and death upon rechallenge with viral variants due to antibody dependent enhance-ment (ADE) of infection into macrophages. The question remains as to what can account for this potent heterologous protection in macrophages? Here it is argued that the elusive defense mechanism of M1-like pro-inflammatory macrophages may pertain to a novel virus anti-virus response. This system initiates with high replication of human endogenous retrovirus K102 (HERV-K102), a non-pathogenic, protector foamy retrovirus of humans which generates M1-like pro-inflammatory foamy macrophages, glycolysis, and epigenetic changes, all characteristic of trained immunity. This virus-anti-virus system kills virally infected cells by several mechanisms, amplifies the innate interferon response via ‘viral mimicry’, has many unique components that interfere with exoge-nous virus replication, and may be especially adept at neutralizing enveloped exogenous pandemic viruses, such as SARS-CoV-2 and HIV-1. The goal of this treatise is to introduce the multifaceted HERV-K102 protector system, to illustrate how SARS-CoV-2 may target the HERV-K102 protector system by ADE, and to explore how this innate defense system may be exploited for pandemic preparedness.

One of the main problems for managing global crises is to clarify and reduces drivers of systemic weaknesses to face complex emergencies. This study here analyzes the relation between public debt, healthcare expenditures and fatality rates in the presence of pandemic crises, such as COVID-19. Statistical evidence, based on a sample of European countries, here shows that high public debt over time reduces health expenditures and increases the vulnerability of countries to face emergencies, such as COVID-19 pandemic crisis. Regression analysis with a log-log model suggests that when European countries experience a 1% increase in healthcare expenditure per capita, in general they have a 1.2% reduction in the COVID-19 fatality rate. Main implications of this study to reduce the systemic risk and vulnerability to environmental threats are that countries must reduce public debt with good governance and institutions without reducing the allocation of economic resources to the healthcare sector in order to improve the preparedness to unforeseen emergencies and crises, such as pandemics, natural disasters, conflicts, and other environmental threats.

The prevalence of internet gaming disorders (IGD) is considerably high among youth, especially with social isolation imposed by the ongoing COVID-19 pandemic. IGD adversely affects mental health, quality of life, and academic performance. The Internet Gaming Disorder Scale (IGDS9-SF) is designed to detect IGD according to DSM-IV diagnostic criteria. However, inconsistent results are reported on its capacity to diagnose IGD evenly across different cultures. To ensure the suitability of the IGDS9-SF as a global measure of IGD, this study examined the psychometric properties of the IGDS9-SF in a sample of Sri Lankan university students (N = 322, mean age =17.2 ± 0.6, range = 16-18 years, 56.5% males) and evaluated its measurement invariance across samples from Sri Lanka, Turkey, Australia, and the USA. Among Sri Lankan students, a unidimensional structure expressed good fit, invariance across different groups (e.g., gender, ethnicity, and income), adequate criterion validity (strong correlation with motives of internet gaming, daily gaming duration, and sleep quality), and good reliability (alpha = 0.81). Males and online multiplayers expressed higher IGD levels, greater time spent gaming, and more endorsement of gaming motives (e.g., Social and Coping) than females and offline players. Across countries, the IGDS9-SF was invariant at the configural, metric, and scalar levels, albeit strict invariance was not maintained. The lowest and highest IGD levels were reported among Turkish and American respondents, respectively. In conclusion, the IGDS9-SF can be reliably used to measure IGD among Sri Lankan youth. Because the scale holds scalar invariance across countries, its scores can be used to compare IGD levels in the studied countries.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance - capillary ischemia-reperfusion - which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.

The goal of the manuscript is to design a relatively best control structure for the noise suppression of a drone’s camera gimbal action. The gimbal’s movement can be simplified as a rest-to-rest reorientation system that can achieve the boundary result of a dynamic system. Six different control architectures are proposed and evaluated based on their ability to control the trajectory of the dynamic-system position and speed, their running time, and quadratic cost. The robustness of the control architecture to uncertainties in inertia and sensor noise is also analyzed. Monte Carlo figures are used to assess the performance of the six control systems. The conditions for applying different architectures are identified through this analysis. The analysis and experimental tests reveal the most suitable control of the drone’s camera gimbal rotation.

This article analyzes and compares the integration of two different maximum power point tracking (MPPT) control methods, which are tested under partial shading and fast ramp conditions. These MPPT methods are designed by Improved Particle Swarm Optimization (IPSO) and a combination technique between Neural Network and Perturb & Observe method (NN_P&O). These two methods are implemented and simulated for photovoltaic systems (PV), where various system responses, such as: voltage and power are obtained. The MPPT techniques were simulated using Matlab/Simulink environment. A comparison of the performance of IPSO and NN_P&O algorithms is carried out to confirm the best accomplishment of the two methods in terms of speed, accuracy and simplicity.

The integration of Artificial Intelligence (AI) and the Internet of Things (IoT) in healthcare is transforming chronic disease management and pandemic response, particularly for vulnerable populations such as the elderly and those with multiple chronic conditions. This review systematically examines the current applications of AI and IoT technologies in managing chronic diseases like diabetes, cardiovascular disease, and chronic obstructive pulmonary disease (COPD), alongside their role in enhancing healthcare response during the COVID-19 pandemic. Key findings demonstrate significant improvements in patient outcomes, including enhanced glycemic control in diabetes management, early detection of cardiovascular anomalies, and a reduction in hospital admissions for chronic disease patients through AI-enabled remote monitoring. Despite these advancements, challenges remain, including data security, algorithmic bias, and the high cost of implementing AI and IoT systems. This review explores future directions for overcoming these obstacles, emphasizing the potential of multi-dimensional data integration, real-time predictive analytics, and personalized AI models to further revolutionize healthcare. Additionally, the accompanying Graphic Abstract visually illustrates how AI-driven insights, generated from IoT-enabled devices, are transforming healthcare delivery by facilitating real-time monitoring, personalized interventions, and proactive patient care. The article concludes with recommendations for addressing the technological, ethical, and regulatory challenges that must be overcome to fully realize the potential of AI and IoT in healthcare.

On February 24, 2022 Russia started the full-scale invasion of Ukraine, which created an unprecedented number of refugees. To estimate the influence of this humanitarian disaster on the COVID-19 pandemic dynamics, the averaged daily numbers of cases and reproduction numbers in Ukraine, the UK, Poland, Germany, the Republic of Moldova, and in the whole world were calculated for the period February-April 2022. The registered numbers of cases were compared with ones calculated with the use of the generalized SIR-model and corresponding parameter identification procedure for the previous epidemic waves in Ukraine, Poland, Germany, and the world. Since before February 24, 2022 the estimation of the number of infectious persons per capita in Ukraine 3.6 times exceeded the global figure, the increase of the number the new cases and the pandemic duration was expected. In March 2022 the increase of the averaged number of new cases in the UK, Germany, and worldwide was visible. A simple formula to estimate the effective reproduction number based on the smoothed accumulated numbers of cases is proposed. The results of calculations agree with the figures presented by John Hopkins University and demonstrate a short-term growth of the reproduction number in the UK, Poland, Germany, Moldova, and worldwide in March 2022.

Telehealth has been playing a progressively major role in the management of the NCOVID-19 crisis. The enforcement of social distancing measures has had the consequence of reduced technology distance in almost every walk of life. In this paper, based primarily on the still unfolding experiences of deploying it during the current situation, we argue that telehealth has finally come of age and that it is time to move it from the peripheries to the center of the 21st century healthcare. To provide a live context to the discussion, several instances of how telehealth strengthened our healthcare systems during the NCOVID-19 crisis are presented.

Background/Objectives: Survival prospects following SARS-CoV-2 infection may extend beyond the acute phase, influenced by various factors including age, health conditions, and infection se-verity. However, this topic has not been studied in detail. We therefore investigated mortality risk post-acute COVID-19 in the CRIT-COV-U cohort. Methods: We could retrieve survival data from 651 patients and also assess the association between urinary peptides and future death. Data spanning until December 2023 were collected from six countries, comparing mortality trends with age- and sex-matched non-infected controls. A death prediction classifier was developed and validated using pre-existing urinary peptidomics datasets. Results: Notably, 13.98% of post-COVID-19 patients succumbed during the follow-up, with mortality rates significantly higher than non-infected controls, particularly evident in younger individuals (&lt;65 years). These data for the first time demonstrate that SARS-CoV-2 infection highly significantly increases the risk of mortality not only during the acute phase of the disease, but also beyond, for a period of about one year. In our study we were further able to identify 201 Urinary peptides linked to mortality, and integrated these into a predictive classifier (DP201). Higher DP201 scores, alongside age and BMI, significantly predicted death. Conclusions: Our findings underscore the utility of urinary peptides in prognosticating post-acute COVID-19 mortality, offering insights for targeted interventions. Our data also suggest that mortality should be considered as one possible symptom or conse-quence of post-acute sequelae of SARS-CoV-2 infection, a fact that is currently overlooked.

BACKGROUND Studies concerning multisystem inflammatory syndrome in children (MIS-C) and how those patients present to the Emergency Department (ED) are scarce. Our study sought to investigate whether abnormal laboratory values were associated with worse outcomes. METHODSThis was a retrospective case-control study from March 2020 to June 2020. Patients with MIS-C were compared to a control group. Laboratory values were compared whether admitted to PICU or not. The Pearson’s Chi-square test and Fisher’s exact test were conducted for associations. RESULTSA total of 80 patients were included in the study (41MISC, 39 control). There were significant associations between patients admitted to the PICU and neutrophilia (p = 0.03) and elevated troponin (p = 0.01). There were no significant associations between having a non-good outcome and obesity, neutrophilia, lymphopenia, or elevated troponin. When MIS-C patients were compared to the control group MISC-C patients had more obesity and elevated troponin. CONCLUSIONSPatients admitted to the PICU had more neutrophilia and elevated troponin yet had a fairly good outcome. When compared to control patients, there was a significant association with obesity and elevated troponin in the MIS-C group.

Internships can foster educational alliances between industry (business environment) and academic institutions, which can facilitate both flexibility and accelerated innovation. The purpose of this research is to search for the factors that determine HRD through the implementation of the Internship program among the students of Democritus University of Thrace and reveal the correlation between the factors. Also, this paper investigated the impact of the COVID-19 Eras on Human Resource Development (HRD) Factors and finally, investigated the correlation between the two variables "Recruitment in the specialization" and "Covid Eras". The sample of the research consisted of 1398 students of DUTh who implemented Internships during the academic years 2015-2016 to 2021-2022. A questionnaire with 60 variables was created for data collection. A random sampling method was applied to collect the sample. From the results of the survey, ten factors were extracted for human resource training that explained 75.512% of the total variance and for each one, Cronbach's Alpha reliability was tested, which was high. In detail, the factors revealed were Learning Outcomes, Efficacy, Emotional Commitment, Satisfaction, Participation, Empowerment, Role Ambiguity, Role Conflict, Supervisor and Collaboration. From the results of the study, it was evident that HR development - training is a multi-dimensional concept and is a necessary condition for the competitiveness of the firms. Training can help to improve the flexibility of the firm, but also to motivate the staff by implementing multidisciplinary training programs. In general, internship programs are valuable ways for students to acquire broad competences, where the practical knowledge gained supports and complements the theoretical studies acquired in educational institutions.

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Background: There have been few reports of cutaneous skin lesions in severe COVID-19 hospitalized patients which exhibit different behavior compared to outpatients. Furthermore, a notable lack of rigorous studies exits. In this study we included patients with generalized rash during the first wave of the pandemic for characterization.Methods: Hospitalized patients with severe confirmed pulmonary COVID-19 infection and a generalized cutaneous rash during the first wave in March-May 2020 were included. The study received approval from the ethics committee. Clinical presentation, histo-logical examination, blood test, and complete blood interleukin profile were assessed. Special immunohistochemical investigations were conducted. Long term follow-up of the patient was performed throuhg a phone call 24 months later. Results: A total 28 patients were studied and classified by histological examination into three groups: G1: perivascular dermatitis (18/28, 64%); G2: Drug reaction (7/28, 25%); and G3: Generalized exanthema and chilblain (3/28, 11%). The virus was not detected in the skin, by PCR and by immunohistochemical analysis, and the interleukin expression in the skin were undetectable results. Vascular cell adhesion molecule 1 (VCAM1), E-selectine, and IT Galpha 5 were unspecific. G1 exhibited the least inflammation, G2 the most in-flammatory, and G3 had previous inflammation. Discussion: Our data suggest that generalized exanthemas during severe SARS-Cov-2 infection exhibit unspecific finding and are similar to other rashes caused by inflammation. Drug reaction should be considered, as they accounted for 25% of the rashes. Further studies including higher number of patients are necessary.

The collective considerations presented here lead to a crucial question: What truly constitutes the primary public health challenge posed by SARSCoV-2 infection and its variants?The findings of Bowen et al.(1) and Noé et al.(4) have offered us new insights into the actual repercussions of SARSCoV-2 virus infections on public health. They unmistakably point to the late sequelae and complications arising as secondary effects of the viral infection, causing severe and long-term damage to global public health. Rather than the acute infection which has a very low mortality rate in the general population, as initially and commonly believed.

Global research on the Covid-19 vaccine’s effectiveness is using methods that are misleading the scientific community and public opinion. There is a golden rule in medicine: to measure the effectiveness of an experimental medicine you need to have two groups. The group that will take medicine and the group that will not take medicine. You follow the health status of both groups for a few months and you will get objective results. This is the only proper methodology to verify the effectiveness of a new medicine. Articles cited from 1-5 did not use the gold rule. They develop different kinds of methodologies that all have no statistical significance. On the basis of their methodologies, they conclude that Covid-19 vaccines have a positive effect on public health. By comparing graphs of the intensity of vaccination and the rate of mortality we see that after the period of intense vaccination follows the period of higher excess mortality. Basic statistical data are confirming that Covid-19 vaccines increased the mortality rate.

Medical surveillance and risk mitigation protocols to reduce viral transmission have underpinned the return of elite football during the COVID-19 pandemic. This article describes the evidence-informed approach and surveillance findings from the English Football League across a 9-week period at the end of the 2019-20 season. Protocols were devised by the lead EFL Medical Advisor with specialist occupational medicine input. Isolation requirements for cases and contacts were in-line with UK Government regulations, with external contact tracing conducted by local public health authorities. Quantitative PCR testing was conducted twice weekly and within 72 hours of fixtures. 43 individuals, including 18 players returned positive tests. No positive results were returned after week 5 (round 10). Our findings support those from other leagues that with appropriate compliance, elite football can continue safely during this pandemic. We recommend that protocols and compliance should be revised as necessary according to community prevalence and changes in viral transmission dynamics.

Like all RNA viruses, SARS-CoV-2 shows high mutation rate, which has led to the emergence of new variants. Among them, Gamma and Delta developed at the turn of 2020-2021 in Amazonas and India, two ecoregions characterized by hot-humid weather, very similar to that of the summer season due to climate change in Italy, the first Western country to have been hit hard by COVID-19 and to experience lockdown restrictions in a democratic framework of 58,85 million people. Methods: during the state of national health emergency and the Draghi government, the Civil Defense Department daily released the aggregate data coming from the Ministry of Health, the Higher Institute of Health, the Independent Provinces and the Italian Regions, in order to inform about the pandemic situation in Italy. Among these data there were the number of deaths, hospitalizations in intensive care units (ICU), non-ICU patients, contagions, and performed swabs. By means of a team effort, we have collected and elaborated all these data, comparing COVID-19 pandemic in Italy during the summers 2020 (following the nationwide lockdown), 2021 and 2022. Results: from summer 2020 (before mass vaccination) to summers 2021 (after primary mass vaccination) and 2022 (after booster mass vaccination) all pandemic trend indicators have showed a sharp worsening in Italy. COVID-19 deaths increased by ≈298% and ≈834%, ICU hospitalizations by ≈386% and ≈310%, non-ICU hospitalizations by ≈224% and ≈600%, contagions by ≈627% and ≈6.850% (i.e. ≈68,50 times), swabs by ≈354% and ≈370%, and the mean positivity rate passed from ≈1% to ≈2% and ≈20%, respectively. Conclusions: SARS-CoV-2 can be transmitted in any climate, including areas with hot and humid weather, and the emergence of variants adapted to hot-humid climate may result in summer COVID-19 outbreaks, even in neither tropical nor subtropical countries. Although COVID-19 vaccines can confer cross-protection against newly emerging variants, this cross-immunity is obviously not absolute but limited, also taking into account that vaccine protection wanes considerably after 6 months. It follows that a subject vaccinated at the beginning of winter will not be completely covered in the height of summer, without forgetting the unvaccinated. As a final remark, the long nationwide lockdown made it possible to flatten SARS-CoV-2 circulation and, therefore, its negative impact on Italy during summer 2020.

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.

The COVID-19 pandemic drew public attention back to the living conditions related to housing, access to green areas in close neighbourhood and nearby recreation. Several studies confirm that visiting green spaces improved the health and wellbeing in times of crisis. This representative study for the metropolitan area of Vienna, Austria’s capital, confirms the high relevance of contact with nature, particularly for citizens to cope with the negative consequences and perceived stress, anxiety, nervousness and many other negative symptoms experienced during the health crisis. It highlights the importance of nearby smaller but also medium to large scale green areas in cities for health and wellbeing of the population. Moreover, it specifically adds novel insights on age effects in use and perception of urban green spaces during COVID-19 pandemic. The online panel survey (n=1012) was conducted in summer 2021. In order to obtain a representative sample reflective of the population’s characteristics, a (stratified) random sample was selected by applying the quota method. The objective was to obtain a sample which represented gender, age and regional distribution of the population of the City of Vienna as well as the immediately surrounding local communities. Interestingly, particularly young people spent more time outside in green areas during the pandemic, discovered novel spaces for the first time and stated a high relevance of contact with nature for their wellbeing. Elderly people above sixty five, on the contrary, stayed more frequently at home. Significant differences are visible between the age groups also with regard to negative symptoms experienced in case of restricted access to green areas due to strict pandemic measures such as lockdowns and quarantine. All age groups, however, similarly acknowledged the importance of green areas for their physical, mental and emotional health in general during the pandemic.

Materials based on platinum metals with very good catalytic activity were tested in the reduction of p–nitrophenol (pNP) to p–aminophenol (pAP). The majority of presented catalytic materials are based on the adsorption of p–nitrophenol on the surface of the catalyst simultaneously with molecular hydrogen, coming from sodium borohydride in an aqueous medium, which reduces it. In the present paper, a catalytic material based on osmium dispersed in n–decanol or n–dodecanol is presented, which also works as an emulsion membrane, for the absorption of p–nitrophenol and molecular hydrogen at the n–alcohol aqueous solution interface. The hydrogenation of p–nitrophenol is carried out in a reaction and separation column in which the acid receiving phase emulsion is dispersed in the osmium nanodispersion, in n–alcohols. This emulsion circulates from the base of the column to its upper part in co-current or counter-current with the source phase consisting of p–nitrophenol and sodium borohydride. Experiments show that the circulation of counter-current phases is superior to that in co-current, and the emulsion based on n–decanol is more efficient than the one based on n–dodecanol. The increase in the pH difference between the source and receiving phases leads to the increase in the conversion of p–nitrophenol to p–aminophenol. The efficiency of separation of the reaction product in the receiving phase is lower than the conversion at the same operating time. The apparent catalytic rate constant (kapp) of the new catalytic material based on the emulsion membrane with nanodispersion of osmium nanoparticles (0.1×10−3 for n–dodecanol and 0.9×10−3 for n-decanol) is lower by an order of magnitude compared to those based on adsorption on catalysts from platinum metal group. The advantage of the tested membrane catalytic material is that it extracts p–aminophenol in the acid receiving phase. The paper proposes a mechanism of the studied reduction system.

The development of mineral resources in China has gradually entered the stage of deep mining. Rock burst, collapse and other ground pressure disasters caused by deep high stress have become major hidden dangers restricting mine safety production. Microseismic monitoring technology is an important means of ground pressure risk prediction. In this paper, the wavelet coefficient threshold denoising method in time-frequency domain, STA/LTA method, AIC method, Skew and Kurtosis method are studied, and the automatic P-phase onset time picking model based on noise reduction and multiple detection indexes is established. Through the effect analysis of microseismic signals collected by microseismic monitoring system of coral Tungsten Mine in Guangxi, automatic P-phase onset time picking is realized. the reliability of the P-phase onset time picking method proposed in this paper based on noise reduction and multiple detection indexes is verified. The picking accuracy can still be guaranteed under the severe signal interference of background noise, power frequency interference and manual activity underground mine, Which is of great significance to the data processing and analysis of microseismic monitoring.

proposal for a fundamental theory is described in which classical and quantum physics as a representation of the universe as a gigantic dendrogram are unified. The latter is the explicate order structure corresponding to the purely number-theoretical implicate order structure given by p-adic numbers. This number field was zero-dimensional, totally disconnected, and disordered. Physical systems (such as electrons, photons) are sub-dendrograms of the universal dendrogram. Measurement process is described as interactions among dendrograms; in particular, quantum measurement problems can be resolved using this process. The theory is realistic, but realism is expressed via the the Leibnitz principle of the Identity of Indiscernible. The classical-quantum interplay is based on the degree of indistinguishability between dendrograms (in which the ergodicity assumption is removed). Depending on this degree, some physical quantities behave more or less in a quantum manner (versus classic manner). Ideologically, our theory is very close to Smolin’s dynamics of difference and Rovelli’s relational quantum mechanics. The presence of classical behavior in nature implies a finiteness of the Universe-dendrogram. (Infinite Universe is considered to be purely quantum.) Reconstruction of events in a four-dimensional space type is based on the holographic principle. Our model reproduces Bell-type correlations in the dendrogramic framework. By adjusting dendrogram complexity, violation of the Bell inequality can be made larger or smaller.

The toxin-antitoxin (TA) systems have been attracting attention due to their role in regulating prokaryotic cell responses to stress and their biotechnological potential. Much recognition has been given to type II TA system of mesophiles, but so far, limited attention has been given to thermophiles. Here, we are presenting the putative type II TA families encoded on the genomes of four Geobacillus strains. We employed the TA finder tool to mine for TA-coding genes and manually curated the results using various tools. We identified 28 putative TA pairs, distributed over 8 TA families. Among the identified TAs, 15 represent putative novel toxins and antitoxins that have been overlooked or annotated as hypothetical proteins in their genome records. We also identified a potentially new TA composite, AbrB-ParE. Furthermore, we are suggesting the Geobacillus acetyltransferase toxin-antitoxin (GacTA) family which potentially represents one of the unique TA families that has a reverse gene order. Moreover, we are proposing a hypothesis on the regulation of the xre-cog2856 gene expression, which seems to involve c-di-AMP. This study aims for highlighting the significance of studying TAs in Geobacillus, since they have special features. It also aims for facilitating future experimental research.

In the present paper, the (p,q)-Hermite based Apostol type Frobenius-Euler polynomials and numbers are firstly considered and then diverse basic identities and properties for the mentioned polynomials and numbers, including addition theorems, difference equations, integral representations, derivative properties, recurrence relations. Moreover, we provide summation formulas and relations associated with the Stirling numbers of the second kind.

Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We here ask the question as to whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known ‘risk factors’ for AF, and in particular exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots are cytotoxic by inducing hypoxia/reperfusion and other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.

HIV/AIDS and COVID-19 discourses are often compared; however, theorizing them together in terms of political efficacy and possibility is more novel. The collective of academics, activists, artists, and others–What Would an HIV Doula Do? (WWHIVDD) which for years has responded to the HIV/AIDS pandemic, has turned their attention to experiences of living with COVID-19. Through a qualitative analysis of two texts–a zine and a guide for authors writing about these pandemics–that specifically address experiences of/with COVID-19 by WWHIVDD, we examine how HIV/AIDS and COVID-19 discourses can productively be considered as chronic illness/COVID discourses that have the potential for more fruitful collective/political action and scholarly theorization of people living with pandemics.

COVID-19 affected health and wellbeing globally. Graduating nursing students face a variety of stressors and entering the nursing profession during the pandemic added additional stress. Mood, perceived stress, resilience, and coping were assessed in an Australian sample of 112 graduating nursing students, who completed the Brunel Mood Scale (BRUMS), Perceived Stress Scale (PSS-4), and Brief Resilient Coping Scale (BRCS). Mean BRUMS scores for tension, fatigue, and confusion were significantly above population norms, and vigour scores significantly below. Mean PSS-4 scores were reflective of population norms, but showed higher levels of stress for younger and on-campus students compared to those who were older or who studied externally. BRCS data showed that 82.1% of the graduating nursing students were medium or high resilient copers. Mood profiles suggested that 19.6% of participants had elevated mental health risk, 23.2% showed potential risk of burnout, and only 17.9% reported mood profiles associated with positive mental health. High mean tension scores reported by the graduating nursing students indicated apprehension about joining the profession, although stress, resilience and coping scores suggested they were adequately managing the additional stressors generated by a global pandemic.

The pandemic was an enormous experience all over the world. The type of living, working and study were changed irreversibly. Facing the opportunity to establish old frames of education in universities is impossible. The adoption of new ways of teaching and assessments reveal their convenience and in the same way their weak points. In response to that stage, on 14 December 2022, the EU parliament accepted the "Digital Decade Policy Programme 2030", for the establishment of a digital transformation community (EU 2022). Trakia University had an online assessment system, quizzes for self-training, and final exams, developed in 2008 on Moodle virtual learning environment. During the pandemic, online exams and lectures were conducted using platforms like BigBlueButton in Moodle or Google Meets. The article gives the results of online exams before, during, and after the pandemic. The outcome, without doubt, displays the lowering knowledge level or performance during the social isolation due to COVID-19, and after, and the reasons are discussed. During the second year of the pandemic was mentioned also a high dropout of students. Now the situation is returning to the previous levels, before the pandemic, but the quality of education is not yet reached. The article values the grades results of session exams and has the intention to clarify the influence of the pandemic period on the excellence of high institution education.

Background. The SARS-CoV-2pandemic has become the greatest public health challenge worldwide. Intensive research started to develop vaccines and by the late 2020 vaccination campaign started. Objective. Collecting information from European countries, how and in what extent were family physicians/general practitioners/FPs/GPs involved in the vaccinations-campaign in 2021 and how was it organized at national level. Method. A short questionnaire was distributed through the secretariats of WONCA-Europe and the European Forum for Primary Care. Results. In most of the countries participation of FPs/GPs was compulsory. The vaccination was usually centrally organized by governmental authorities. At the beginning (web-based) registration of patients was required, mainly at national level. By the mid of 2021, vaccination on walk in basis became available in almost every country for the first and for the booster injections. The remunerations of GPs/FPs were differed, in some countries without extra payment. The Pfizer’s vaccine was used in all countries; while in 9 countries not EMA approved vaccines were also used in primary care settings and at vaccination centres. In some countries, professional homepages helped the GPs. The involvement of PHC providers did not correlate to the vaccination coverage of the entire population of the respective countries. It was the highest in the more developed countries with higher living standard, where participation of GPs was voluntary and appropriate financial incentives were offered for them. Conclusion. The vaccination campaign was a professional and logistic challenge and an excellent performance of PC providers. Experiences gained could be used in the future to manage similar pandemic challenges.

The Covid 19 pandemic threaten the life of individuals and there was a lack of information in treatment, handling of patients and disposal of waste. The psychological and behavioral impact on Humans due to outbreak of Covid is studied and based on that a person-centered care center is suggested. The research methodology used are surveys, interviews among stake holders and design details of person-centered care center. Based on the surveys and interviews conducted during pandemic, it is found that 94% of the respondents prefer to use private vehicles with at least one member to ac-company them. People prefer to use 3 ply facemasks, followed by cotton masks and N95. Existing literature discusses the physical effects on the individual, but this paper focuses more on pros and cons on human life during the pandemic and lock down period. Based on the study, care center with facilities to treat patients with different levels of infections and counselling center for the persons suffered from Covid and other infectious diseases to overcome their psycho-logical and behavior changes are recommended.

Background: The COVID-19 pandemic has disproportionately affected people from more deprived communities. The experience of Long Covid is similarly distributed but very few investigations have concentrated on the needs of this population. The aim of this project was to co-produce an acceptable intervention for people with Long Covid, living in communities recognised as more deprived. Methods: The intervention was based on a multi-disciplinary team using approaches from sport and exercise medicine and functional rehabilitation. The co-production process was undertaken with a stakeholder advisory group and patient public involvement representation. This study identified participants by postcode and the indices of multiple deprivation (IMD); recruitment and engagement were supported by an existing health and wellbeing service. A virtual ‘clinic’ was offered with a team of professional practitioners who met participants three times each; to directly consider their needs and offer structured advice. The acceptability of the intervention was based on the individual’s participation and their completion of the intervention. Results: Ten participants were recruited with eight completing the intervention. The partnership with an existing community health and wellbeing service was deemed to be an important way of reaching participants. Two men and six women ages ranging from 38 to 73 were involved and their needs were commonly associated with fatigue, anxiety and depression with overall de-conditioning. None reported serious hardship associated with the pandemic although most were in self-employment/part-time employment or were not working due to retirement or ill-health. Two older participants lived alone, and others were single parents and had considerable challenges associated with managing a household alongside their Long Covid difficulties. Conclusions: This paper presents the needs and perspectives of eight individuals involved in the process and discusses the needs and preferences of the group in relation to their support for self- managed recovery from Long Covid.

Abstract: Service polycentricism, in the face of the pandemic, took on a new significance because of sanitary requirements. Population concentrations in large service centres face a high risk of infection both at their destination and during the trip. Higher-tier services were largely closed during the threat’s peak. In this paper, the focus of the study has been placed on the urban scale of a large city’s polycentricism as seen through the prism of service concentrations, which, to a degree, are commuter destinations, but primarily act as attractors that are not associated with work—they satisfy higher-tier service needs. To formulate the investigative apparatus used to study the functio-spatial structure of Cracow. The current threat, as well as the high probability of similar situations happening in the future, will probably lead to changes in behaviour patterns of consumers and service providers in reference to siting. Local service centres that are accessible to pedestrians, due to safety-related considerations, can gain significant popularity.

The purpose of this research article is to provide a comprehensive method that allows the evaluation of the public transportation in their different transport lines that offer in Ciudad Juárez, Chihuahua. This study presents a description of the public transport system as part of the literature review that describes an appropriate model based on the more outstanding publications about urban mobility and public transportation for passengers’ as well as success cases published which serves as a starting point to check the actual state of the public transportation system based on the Pythagorean Fuzzy CODAS to analyze and evaluate the alternatives through criteria that defines the general performance. The integration of these methods provides an adequate methodology for decision-making concerning urban planning and mobility to detect and improve the performance of criteria not considered within sustainable urban mobility plans.

COVID-19 induces coagulopathy at the base of SIC (sepsis-induced coagulopathy) and it is an important cause of death in the patients. Cytokine storm causes imbalance in coagulation and fibrinolytic system. A combination of hypercoagulability state, decrease or inhibition of fibrinolytic and endothelialopathy causes thromboembolic events. Underlined disease with a high rate of mortality in COVID-19 like diabetes, hypertension and some conditions like aging and obesity are the main disorders with hemostatic disturbance and increase of coagulopathy. Therefore, it seems that the combination of COVID-19 infection and these risk factors increase the risk of thromboembolic all together.

The COVID-2019 disease caused by the SARS-CoV-2 virus (aka 2019-nCoV) has raised significant health concerns in China and worldwide. While novel drug discovery and vaccine studies are long, repurposing old drugs against the COVID-2019 epidemic can help identify treatments, with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4 or can be used directly in clinical settings. In this study, we presented a novel network based drug repurposing platform to identify potential drugs for the treatment of COVID-2019. We first analysed the genome sequence of SARS-CoV-2 and identified SARS as the closest disease, based on genome similarity between both causal viruses, followed by MERS and other human coronavirus diseases. Using our AutoSeed pipeline (text mining and database searches), we obtained 34 COVID-2019-related genes. Taking those genes as seeds, we automatically built a molecular network for which our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules and finally suggested 78 drugs to repurpose. Following manual filtering based on clinical knowledge, we re-prioritized 30 potential repurposable drugs against COVID-2019 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide) . We hope that this data can provide critical insights into SARS-CoV-2 biology and help design rapid clinical trials of treatments against COVID-2019.

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available and investigations regarding COVID-19 treatment are lacking. Liu et al. (2020) successfully crystallised the COVID-19 main protease (M^pro), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 M^pro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. COVID-19 M^pro was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 M^pro inhibitors. However, further research is necessary to investigate their potential medicinal use.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

INTRODUCTION: The purpose of the study was to determine (a) the overall preclinical character; (b) the cumulative cutoff values and the risk ratio, and (c) the factors associated with severity by a unidimensional and multidimensional analysis on 2173 Sars-Cov2 patients. METHODS: The machine learning study population consisted of 2173 patients (1587 mild and non symptoms patients, 377 moderate patients, 209 severe patients). The status of the patients was recorded from September 2021 to March 2022. RESULTS: The Covid19 Severity directly links with a significant correlation to Age, Score index of the chest X-ray, percentage and quantity of neutrophils, Albumin, C reactive protein, and ratio of Lymphocytes. Their important cut off values (from regression analysis) respectively are: 77.56 years old (the mild-moderate group), 5.53 (the mild-moderate group) and 10.51 (the moderate-severe group), 84.80% (the mild-moderate group) and 87.74%(the moderate-severe group), 11.77G/L (the moderate-severe group), 29.73g/L (the moderate-severe group), 7.46mg/dL (the mild-moderate group), 6.32% (the moderate-severe group). Their significant (p<0.0001) R score correlation with the severity of Covid19, are: 0.44, 0.52 and 0.52, 0.33 and 0.44, 0.42, -0.43, 0.40, -0.41. Their significant risk ratio (p<0.00001) from the meta-analysis, respectively are: 4.19 [3.58-4.95], 3.29 [2.76-3.92] and 3.03 [2.4023;3.8314], 3.18 [2.73-3.70] and 3.32 [2.6480;4.1529], 3.15 [2.6153;3.8025], 3.4[2.91-3.97], 0.46 [0.3650;0.5752] (p<0.00001), 0.34 [0.2743;0.4210]. The pair ALT – Leucocytes and Transferrin – Anion Chloride get the most important correlation shift. ALT – Leucocytes show the important negative link (R=-1, p<0.00001) in the mild group to the significant positive correlation in the moderate group (R=1, p<0.00001). Transferrin–anion Chloride has an important positive association (R=1, p<0.00001) in the mild group with a significant negative correlation in the moderate group (R=-0.59, p<0.00001). The network map and HCA show that in the mild-moderate group, the closest neighbors with the Covid19 severity are ferritins, Age. Then there is C-reactive protein, SI of X-ray, Albumin, and Lactate dehydrogenase, which are the next close neighbors of these three factors. In the moderate-severe group, the closest neighbors with the Covid19 severity are Ferritin, Fibrinogen, Albumin, the quantity of Lymphocytes, SI of X-ray, white blood cells count, Lactate dehydrogenase, and quantity of neutrophils. CONCLUSIONS: Complete multidimensional study in 2173 Covid19 patients in Vietnam shows the whole picture of all the preclinical factors, which may become the clinical reference marker for surveillance and diagnostic management

Measures in the SARS-CoV-2 pandemic were based on rough ideas regarding transmission routes of pathogens. Quantified models of physical transmission routes are mostly lacking, a gap to be filled. Vaccines and medicines, important, are not studied here. We first survey main routes, from primary production in the alveoli and intestines to emissions, environmental routes, to exposure and alveolar infection. Next, specific routes are modelled, mostly at a preliminary state, open to systematic improvement. Starting from a standardized emitter, modelling results show extreme differences in potential exposure, in a range covering up to 4 orders of magnitude. The outcomes are pathogen-specific, already different between SARS-CoV-2 and influenza. Extreme exposures may result in smaller spaces; with lower ventilation rates; with a high density of emitting persons per m3; who stay there for several hours; and visitors staying more than a few minutes. In spaces where a build-up of concentrations is low, exposures are low, lowest in open air situations. A main conclusion for the next pandemic is that a quantified model can give strong guidance on where measures are primarily due. For SARS-CoV-2, ventilation can be improved short-term. Longer-term, effective ventilation rules and adaptation of buildings may reduce high exposures substantially.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

Polyhydroxyalcanoates (PHAs) are biodegradable polymers synthesized in cytoplasmic granules in bacteria, such as Cupriavidus necator (Ralstonia eutropha), Alcaligenes latus, Pseudomonas spp., Comamonas spp. and other species. PHAs accumulation occurs in response to stress conditions, i.e. under high carbon and low nitrogen (24:1 ratio). PHA can be synthesized using recombinant microorganisms (provided with the operon phbA/phbB/phbC), escaping the constrains of nutrient request, except addition of high amount of sugar (glucose, lactose, fructose). In this study; E. coli was genetically modified for PHB production in biofermentors. The production of PHA at industrial scale requires a continuous supplementation of fermentable sugars to support the availability of nutrients and to assess the level of the exponential growth phase; since sugars are required either for bacterial growth either for PHA synthesis and energy storage. The biofermentors need to be run in automated system. Sensors are used at many points in fermentators; in the evaluation of parameters: consumption of sugars; cell density; quantification of PHB synthesis. The need of operational control during the fermentation has prompted us to application of three measurements; one unit linked to a Nanodrop to evaluate OD; one linked to a reaction chamber to measure sugars consumed by enzyme based fluorescence detection; and one for bacteria Nile Blue staining and fluorescence intensity reads. The growth of bacteria on three different plant by-products was monitored and PHB production in four days using a banana by-product feed was optimised. These detectors will make possible to exploit the full potential of bioreactors optimizing the time of use and maximizing the number of bacteria synthesizing PHA.

Abstract: The S1 subunit of SARS-CoV-2 Spike has been found in the blood of covid patients and vaccinated individuals. From BioGRID, we selected 146 significant human proteins experimentally interacting with S1. Then, we derived an interactome model that facilitated the study of functional activities. Through a reverse engineering approach, we identified 27 specific one-to-one interac-tions of S1 with the human proteome. S1 interacts in this manner independently from the biological context in which it operates, be it infection or vaccination. Instead, when it works together with viral proteins, carry multiple attacks on single human proteins out, showing a different functional engagement. Through Cytoscape we showed functional implications and its tropism to human organs/tissues, such as nervous system, liver, blood, and lungs. As a single protein, S1 operates in a complex metabolic landscape which includes 2557 GO biological processes, much more than the 1430 terms controlled when operating in a group. A Data-Merging approach shows that the total proteins involved by S1 in the cell are over 60,000 with an average involvement per single bio-logical process of 26.19. However, many human proteins get entangled in over 100 biological different activities each. Clustering analysis showed statistically significant activations of many molecular mechanisms, like those related to hepatitis-B infections. This suggests potential in-volvement in carcinogenesis, based on a viral strategy that uses the ubiquitin system to impair the tumor suppressor and antiviral functions of TP53, as well as the role of RPS27A in protein turnover and cellular stress responses.

Abstract: A prevalence boundary (PB) marks the point in prevalence where the false omission rate, RFO=FN/(TN+FN), exceeds the tolerance limit for missed diagnoses. Objectives were to mathematically analyze rapid antigen test (RAgT) performance, determine why PBs are breeched, and evaluate the merits of testing three times over five days, now required by the US Food and Drug Administration for asymptomatic persons. Equations were derived to compare test performance patterns, calculate PBs, and perform recursive computations. An independent July 2023 FDA-university-commercial evaluation of RAgTs provided performance data used in theoretical calculations. Tiered sensitivity/specificity comprise: Tier-1) 90%, 95%; Tier-2) 95%, 97.5%; and Tier-3) 100%, ≥99%, respectively. Repeating a T2 test improves the PB from 44.6% to 95.2% (RFO 5%). In the FDA-university-commercial evaluation, RAgTs generated sensitivity of 34.4%, which improved to 55.3% when repeated, then 68.5% with the third test. With RFO=5%, PBs were 7.37/10.46/14.22%, respectively. PB analysis suggests RAgTs should achieve clinically proven sensitivity of 91.0-91.4%. When prevalence exceeds PBs, missed diagnoses can perpetuate virus transmission. Repeating low-sensitivity RAgTs delays diagnosis. In homes, high-risk settings, and hotspots, PB breaches may prolong contagion, defeat mitigation, facilitate new variants, and transform outbreaks into endemic disease. Molecular diagnostics can help avoid these potential vicious cycles

This study describes the development of an automated bag valve mask (BVM) compression system, which, during acute shortages and supply chain disruptions can serve as a temporary emergency ventilator. The resuscitation system is based on the Arduino controller with a real-time operating system installed on a largely RepRap 3-D printable parametric component-based structure. The cost of the system is under $170, which makes it affordable for replication by makers around the world. The device provides a controlled breathing mode with tidal volumes from 100 to 800 milliliters, breathing rates from 5 to 40 breaths/minute, and inspiratory-to-expiratory ratio from 1:1 to 1:4. The system is designed for reliability and scalability of measurement circuits through the use of the serial peripheral interface and has the ability to connect additional hardware due to the object-oriented algorithmic approach. Experimental results demonstrate repeatability and accuracy exceeding human capabilities in BVM-based manual ventilation. Future work is necessary to further develop and test the system to make it acceptable for deployment outside of emergencies in clinical environments, however, the nature of the design is such that desired features are relatively easy to add with the test using protocols and parametric design files provided.

The relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have abnormally hard outer shell (low M disorder; i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far was found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2 especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 amd later in Omicron, is associated with attenuation according to the Shell-Disorder-Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists throughout the world with over 65 million registered cases of survivors with post-COVID-19 sequelae, also known as LongCOVID-19 (LongC). LongC survivors exhibit various symptoms that span multiple organ systems, including the nervous system. To search for neurological biomarkers of LongC, we investigated the soluble proteins present in the plasma and the proteins associated with plasma neuronal-enriched extracellular vesicles (nEVs) in 33 LongC patients with neurological impairment (nLongC), 12 COVID-19 survivors without any LongC symptoms (Cov), and 28 pre-COVID-19 healthy controls (HC). COVID-19 positive participants were infected from 2020-2022, not hospitalized, and were vaccinated or unvaccinated before infection. IL-1b was significantly increased in both nLongC and Cov and IL-8 elevated in only nLongC. Both brain-derived neurotropic factor and cortisol were significantly elevated in nLongC and Cov compared to HC. nEVs from people with nLongC had significantly elevated protein markers of neuronal dysfunction, including amyloid beta 42, pTau181 and TDP-43. This study shows chronic peripheral inflammation with increased stress after COVID-19 infection. Additionally, differentially expressed nEV neurodegenerative proteins were identified in people recovering from COVID-19 regardless of persistent symptoms.

Long COVID is a phenomenon in which individuals experience persistent symptoms after recovering from COVID-19. The symptoms are discovered to be unique for every individual and can affect multiple organs systems in the body. This study aims to identify effective natural remedies for long COVID by analyzing hub genes associated with the symptoms of the condition and evaluating the repurposed drugs catered and used for treating the symptoms of long COVID. The most common and prevalent symptoms of long COVID were identified; Fatigue, Shortness of Breath, Loss of Smell, Headache, Brain Fog, Chest Pain, Insomnia, Heart Palpitations, Dizziness, Joint Pain, Depression, Anxiety, Tinnitus, Loss of Appetite. Hub genes for each of the symptoms provided an insight on the key biological pathways of the symptom. Repurposed drugs identified, provided the template to identify the natural compounds with similar structure as a potential therapeutic drug. The natural compounds were retrieved using fingerprint search of the repurposed drugs from the NPASS Database. The findings of this study suggest several natural remedies for each symptom based on the molecular docking of the hub gene and natural compound using iGEMDOCK. The identified natural remedies may hold promise in treating long COVID, but further research is required to explore the efficacy and effectiveness of the proposed natural compounds. The results of the study pose important implications for the development of effective treatments for long COVID.

Objectives This study aimed to evaluate the eicosanoid and pro-resolutive parameters in Post Covid Syndrome (PCS) patients during 12 weeks of a supplementation with a marine oil enriched in SPMs. Patient and methods The study was conducted in 53 adult patients with a PCS. The subjects included must have had a positive COVID-19 test (PCR, fast antigen test, or serologic test) and persistent symptoms related to COVID-19 at least 12 weeks before their enrolment in the study. The following parameters were evaluated: Polyunsaturated fatty acids: EPA, DHA, ARA, DPA, Specialized Pro-resolving mediators (SPMs) 17-HDHA, 18-HEPE, 14-HDHA, resolvins, maresins, protectins, and lipoxins. The eicosanoids group included prostaglandins, thromboxanes, and leukotrienes. The development of the clinical symptoms of fatigue and dyspnea were evaluated using the Fatigue Severity Scale (FSS) and the Modified Medical Research Council (mMRC) Dyspnea Scale. Three groups with different amounts of intake were evaluated: daily use of 500mg, 1500mg, and 3000mg were compared to a control group without use of the product. Results In the serum from PCS patients, an increase of 17-HDHA, 18-HEPE, 14-HDHA could be observed. Also, a decrease in the ratio between the pro-inflammatory and pro-resolutive lipid mediators was detected. Both differences were significant (p < 0.05). There were no differences between the three treatment groups. Fatigue and dyspnoea showed a trend to improve after supplementation in all groups. Conclusions A clear enrichment in serum of the three monohydroxylated SPMs could be observed also at a dosage of 500 mg per day. In the same way, a clear improvement in fatigue and dyspnoea was observed with this dosage. Clinical Trial Registry: ISRCTN13270662.

Long COVID (Post-Acute Sequelae of COVID-19, PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of Long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that longterm dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.

Neurologic symptoms associated with Long COVID result from the persistent infection of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous sys-tem (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in the olfactory mucosa. Recently published clinical data demonstrate that only 5% of Long COVID anosmia patients have fully recovered during the past 2 years and 10.4% of COVID patients are still symptomatic 18 months post infection. Our group demonstrated that ep-igallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activ-ity against human coronavirus, suggesting this green tea-derived compound in nanoparticle for-mulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to resto-ration of neurologic functions. The objective of the current study is to evaluate the mucociliary safety of the EC16m nasal nanoformulations and the efficacy against human coronavirus. Meth-ods: nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using MucilAir Human Nasal Epi-thelium Model; contact antiviral activity and post-infection inhibition against OC43 viral strain were assessed by TCID50 assay for cytopathic effect on MRC-5 cells. Results: the saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference in comparison to saline (0.9% NaCl) on tissue integrity, cytotoxicity, and cilia beat fre-quency. A 5-minute contact inactivated 99.9% of the β-coronavirus OC43. OC43 viral replication was inhibited by >99% after infected MAR-5 cells were treated with one of the formulations. Con-clusion: the saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety measurements comparable to saline, a solution widely used for nasal applications.

SARS-CoV-2, the virus that causes theCOVID-19 disease, has been demonstrated to cause immune suppression in certain individuals. This can manifest as a reduced ability for the host's immune system to effectively control the infection. Studies have reported that patients with COVID-19 can exhibit a decline in white blood cell counts, including natural killer cells and T cells, which are integral components of the immune system's response to viral pathogens. These cells play critical roles in the immune response to viral infections, and their depletion can make it harder for the body to mount an effective defense against the virus. Additionally, the virus can also directly infect immune cells, further compromising their ability to function. Some individuals with severe COVID-19 pneumonia may develop a "cytokine storm," an overactive immune response that may result in tissue damage and organ malfunction. The underlying mechanisms of immune suppression in SARS-CoV-2 are not entirely comprehended at this time, and ongoing research is being conducted to gain a more comprehensive understanding. Research has shown that severe SARS-CoV-2 infection promotes the synthesis of IgG4 antibodies. In this work, we propose the hypothesis that the IgG4 antibody produced by B cells in response to infection by SARS-CoV2 generates immunological tolerance that prevents its elimination, and leads to persistence and chronic infection. In sum, we believe that this constitutes another immune evasion mechanism that bears striking similarities to that developed by cancer cells to evade immune surveillance.

Chronic diseases affect a disproportionate number of United States (U.S.) Veterans, causing significant long-term health issues and affecting entitlement spending. This longitudinal study examined the health status of U.S. Veterans as compared to non-Veterans pre- and post-COVID utilizing the annual Center for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System (BRFSS) survey data. Age-adjusted descriptive point estimates were generated independently for 2003 through 2021, while complex weighted panel data were generated from 2011 and onward. General linear modeling revealed that the average U.S. Veteran reports a higher prevalence of disease conditions except for mental health disorders when compared to the non-Veteran. These findings were consistent with both pre- and post-COVID, however, both groups reported a higher prevalence of mental health issues during the pandemic years. The findings suggest that there have been no improvements in reducing Veteran comorbidities to non-Veteran levels and that COVID adversely affected the mental health of both populations.

The Coronavirus disease-19 (COVID-19) pandemic dramatically impacted on oncologic patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated also for oncologic population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy de-livery were not available. We aimed to evaluate potential factors influencing the outcome of COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing COVID-19 vaccination with gas-tro-entero-pancreatic and neuroendocrine neoplasms, treated at our Institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection 86.9% received two-doses of Pfizer-BioNTech and the remains Moderna vaccine. All patients obtained a subsequent im-mune-response. A significantly lower values of IgG for patients treated with chemotherapy versus other anti-cancer agents (p=0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs >7 days from the last systemic treatment (p=0.77) and lymphocytes count (p=0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue but rather the quality of the subset of lymphocytes before the vaccination to deter-mine the efficacy level of immune-response in this population.

Neutrophils play an important role as the first line of innate immune defense. One function of neutrophils, called neutrophil extracellular traps (NETs), has been discovered recently. NETs are extensive fibrous structures released extracellularly from activated neutrophils in response to infection. They are composed of cytosolic protein assembled on a scaffold of released chromatin. These structures suppress the dissemination of micro-organisms in blood by trapping them mechanically, and by exploiting coagulant function to segregate them within the circulation. In addition, NET components (DNA, histone, and granule proteins) also contribute to the triggering of an inflammatory process. NET function, however, can be regarded as a double-edged sword. On one hand, NET formation is an efficient strategy for neutralizing invading micro-organisms. On the other hand, NET can be harmful to the host, as its exposed by-products that are toxic to endothelial cells and parenchymal tissue. We present here the analogous biological and physiological features of the harmful positive amplification loop between inflammation and tissue damage induced by NETosis dysregulation and Coronavirus Disease-2019 (COVID-19) pathogenesis. Considering the rapid evolution of this disease symptoms and its lethality, we hypothesize that COVID-19 progresses under an amplifier loop, leading to an massive, uncontrolled inflammation process. We also describe the correlations of COVID-19 symptoms and biological features with those consecutive to uncontrolled NET formation causing various sterile or infectious diseases. General clinical conditions, and numerous pathological and biological features, are analogous with NETs deleterious effects. We postulate that Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) induces a disproportionate virus-induced NET release, and that this plays a key role in COVID-19 pathogenesis. While neutrophils are the principal starting point for extracellular and circulating DNA release, targeting NETs rather than neutrophils themselves may stand for an effective strategy. This paper offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and future therapies to control NET unbalance. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose that, in the short term, deoxyribonuclease I (DNase-1) treatment should be evaluated; we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type Lectin like receptors (CLEC) inhibitors, and on anti-IL26 therapies.

Health services research is a multidisciplinary discipline that aims to improve population health by studying healthcare services' organization, delivery, and financing. Over time, the field has worked to define its boundaries and establish a set of core research topics and methods addressing population wellbeing, access, quality, and cost. Although the influence of health technology is significant, our literature survey on health services research showed that SCs in general—containing their management, cost, and policy—had received little attention. Importantly, our assessment also showed that the system’s readiness to handle supply policy and supply device deficiencies like those encountered during pandemic was hardly ever mentioned. Reduced open areas and water bodies, deteriorating infrastructure, and changes in the biological morphology all affect cities’ uncontrollable and unplanned growth. Urban amenities, facilities, and healthcare services were unevenly distributed due to this unchecked urban population development. In light of this, this research suggests two reliable models for site selection issues for one of Hong Kong’s main hospitals. Levels of uncertainty, infeasibility tolerance, and reliability are taken into consideration. Then, two categories of uncertainty—symmetric and bound-ed—were examined. As a result, the challenge of scheduling in uncertainty has been considered, and potential solutions have been presented using a specified probability distribution function. The paper concludes by introducing the specific justice and health problems and outlining four typical strategies. In order to ensure that medications and other healthcare supplies are produced, distributed, and given to patients, a vast network of systems, components, and procedures must be effectively managed. This research contributes in this regard. Also, its grantee fairness in health systems and the populations health locally, nationally, and globally. It highlights health inequity, advances the measurement of health inequity, and promotes public dialogues on health inequity.

Since the spread of the deadly virus SARS-CoV2 in late 2019, researchers have restlessly been seeking for unraveling how the virus factually enters the host cells. Some proteins on each side of the interaction between the virus and the host cells are involved as the major contributors to this process: 1- the nano-machine Spike protein on behalf of the virus, 2- angiotensin converting enzyme II, the mono-carboxypeptidase and the key component of renin angiotensin system on behalf of the host cell, 3- some host proteases and proteins exploited by SARS-CoV2, In this review, the complex process of SARS-CoV2 entrance into the host cells with the contribution of the involved host proteins as well as the sequential conformational changes in the Spike protein tending to increase the probability of complexification of the latter with angiotensin converting enzyme II, the receptor of the virus on the host cells, are discussed. Besides, the release of the catalytic ectodomain of angiotensin converting enzyme II as its soluble form in the extracellular space and its positive or negative impact on the infectivity of the virus are considered.

Neuromuscular symptoms in long COVID patients are common. Since adequate diagnostics are still missing, investigating muscle function might be beneficial. The holding capacity (maximal isometric Adaptive Force; AFisomax) was previously suggested to be especially vulnerable for impairments. This longitudinal, non-clinical study aimed to investigate the AF in long COVID patients in recovery process. AF parameters of elbow/hip flexors were assessed in 17 patients at three timepoints (pre: long COVID state, post: immediately after first treatment, end: recovery) by an objectified manual muscle test. The tester applied an increasing force on the limb of the patient, who had to resist isometrically for as long as possible. The intensity of 13 common symptoms were queried. At pre, patients started to lengthen their muscles at ~50% of the maximal AF (AFmax), which was then reached during eccentric motion, indicating unstable adaptation. At post and end, AFisomax increased significantly to ~99% and 100% of AFmax, respectively, reflecting stable adaptation. AFmax was statistically similar for all three timepoints. Symptoms intensity decreased significantly from pre to end. In conclusion, maximal holding capacity seems to be impaired in long COVID patients and increases with substantial health improvement. AFisomax might be a suitable sensitive functional parameter to assess long COVID patients and to support therapy process.

Diffuse type of gastric cancer (GC) has an increasing prevalence worldwide, especially in Western countries, is usually diagnosed at advanced stages, and has no efficacious treatment options. Epidemiological studies have reported an increased mortality from GC after occupational exposure to well-studied pro-carcinogen that are metabolically activated by Cyp P450 enzymes through aryl hydrocarbon receptor (AhR). Substantial studies support the involvement of AhR in gastric carcinogenesis. However, little is known about the role of AhR in diffuse GC, as compared to intestinal GC. In a cohort of 29 gastric tumors, we described a significantly increased AhR protein and mRNA expression levels in GCs, independently of subtypes and clinical parameters. AhR and RhoA mRNA expression were correlated in diffuse GC. Further, our study characterized how AhR affects gene expression in diffuse GC. Using qRT-PCR, we compared the expression levels of AhR, Cyp1A1 and Cyp1B1 to the expression of genes in a panel previously described. In diffuse GC, Cyp1A1 expression correlated with genes involved in IGF signalling, EMT (VIM), migration (MMP2). In an in vitro assay using the poorly differentiated KATOIII epithelial cell line, two well-known ligands for AhR (TCDD and BaP) induced mRNA expression of CYP1A1, IL1b, as well as UGT1, NQO1 and AhRR to a lower extent. We also observed a strong increase in Cyp1B1 expression in diffuse GC, along with a lower TCDD-increased Cyp1B1 expression as compared to Cyp1A1 in KATOIII cells, and immunostaining in stromal cells. In intestinal GC, Cyp1B1 inversely correlated with several genes including IDO1 (generating endogenous kynurenin-e AhR ligand). Our data provide evidence for a major role of AhR in GC, as an environmental xenobiotics receptor, through different mechanisms and pathways in diffuse and intestinal GC. Our results support continued efforts to clarify the identities of exogenous AhR ligands in diffuse GC in order to define new therapeutic strategies.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results &amp; conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

Advances in biological sciences have been applied in medicine, agriculture and industry with great benefit. Some recent trends in society, governance structures and communications, however, appear to be hampering the use of new scientific findings for controlling infectious diseases. These limitations are illustrated with examples related to (i) the adaptation of fresh water mosquito vectors of major arboviral diseases to salinity in coastal areas with consequences for disease transmission, (ii) understanding the implications of reduced dengue transmission during the COVID-19 lockdown for dengue control, (iii) causes underlying the rapid spread of the malaria vector Anopheles stephensi in South Asia and Africa, (iv) the application of serodiagnostic techniques for Lyme disease and tick-borne relapsing fever caused by tick-borne bacteria of the genus Borrelia, and (v) COVID-19 prevention.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

Abstract Background COVID-19 vaccination program among Adults in India is one of the highly successful vaccination drives globally. Indian children aged 15–18 years old became eligible for COVID-19 vaccination on 3rd January, 2022 followed by 12-14 years old children on 16th March, 2022. As parents are primary decision-makers for their children, we aimed to assess parents' perceptions and intentions regarding COVID-19 vaccination for children in India. Aim To assess parental perceptions and intention to get COVID-19 vaccination for their children (aged<18 years), Materials and Methods A cross-sectional anonymous web-based survey was designed. Healthcare workers of a tertiary care institute in Eastern U.P. having any children aged <18 years were the study population. They were recruited through snowball sampling and were sent the study questionnaire in Google form through email and WhatsApp. Cross-tabulation was performed by parents' intention to vaccinate their children against COVID-19 virus with socio-demographic characteristics and their risk perception toward COVID-19, trust in the healthcare system, and their history of vaccine hesitancy behavior routine childhood immunization. Bi-variate analysis was performed to find out the predictors of child vaccination intention among the parents. Results A total of 388 healthcare workers parents (HCWPs) having A child < 18 years of age completed the survey. Mean age of the parents were 40.28 ±11.34 years with majority(97.0%) completing recommended 2 doses of COVIID-19 vaccine. Around 91% of the parents agreed that COVID-19 vaccines are important for child’s health whereas about 89% agreed to the statement that COVID-19 vaccines are effective. A total 356 (91.7%) participants were willing to vaccinate their child against COVID-19, 91.3% of them liked to do so as soon as possible. The factors significantly associated with the stated likelihood of child vaccination among the participants were younger age, female gender, urban residence, absence of any chronic illness, lower monthly income, history of COVID-19 in child and the child/children completed with routine childhood vaccines. Parental concerns mainly centered around vaccine need, safety and side effects. Conclusion The healthcare worker parents(HCWPs) have good knowledge and positive attitude towards COVID-19 vaccination for children. Around 92% of them were willing to vaccinate their children with COVID vaccine currently, which implies very low vaccine hesitancy among the HCWPs . Further longitudinal studies are required to be conducted to assess the trend of parental acceptance of COVID vaccine.

Background: Sudden changes in clinical practice and the altered ability to care for patients due to the COVID-19 pandemic have been associated with moral distress and mental health concerns in healthcare workers internationally. This study aimed to investigate the severity, prevalence, and predictors of moral distress experienced by Australian healthcare workers during the COVID-19 pandemic. Methods: A nationwide, voluntary, anonymous, single time-point, online survey of self-identified frontline healthcare workers was conducted between 27th August and 23rd October 2020. Participants were recruited through health organisations, professional associations or colleges, universities, government contacts, and national media. Results: 7846 complete responses were received from nurses (39.4%), doctors (31.1%), allied health staff (16.7%) or other roles (6.7%). Many participants reported moral distress related to resource scarcity (58.3%), wearing PPE (31.7%) limiting their ability to care for patients, exclusion of family going against their values (60.2%), and fear of letting co-workers down if they were infected (55.0%). Many personal and workplace predictors of moral distress were identified, with those working in certain frontline areas, metropolitan locations, and with prior mental health diagnoses at particular risk of distress. Moral distress was associated with an increased risk of adverse mental health outcomes. Feeling appreciated by the community mitigated this risk in healthcare workers. Conclusions: Safeguarding healthcare workforces during crises is important for both patient safety and workforce longevity. Targeted interventions are required to prevent or minimise moral distress and associated mental health concerns in healthcare workers during COVID-19 and other crises.

EGFR mutations are heterogenous but all carry the same weighting in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 256 patients were included with a median overall survival (OS) of 17.2 months. In multivariate analysis of OS, only age (70 versus &lt;70 years, HR:1.71, 95% CI:1.25-2.35, p&lt;0.001), KPS (&lt;70 versus 70, HR:1.71, 95% CI:1.26-2.31, p&lt;0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p=0.037) remained statistically significant. In patients with a Lung-molGPA score 2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.8 vs 12.4 vs 12.1 months, p=0.021). In conclusion, different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.

Background: SARS-CoV-2 infection has spread to over 200 countries since it was first reported in December of 2019. Significant country-specific variations in infection and mortality rate have been noted. Although country-specific differences in public health response have had a large impact on infection rate control, it is currently unclear as to whether evolution of the virus itself has also contributed to variations in infection and mortality rate. Previous studies on SARS-CoV-2 mutations were based on the analysis of ~ 160 SARS-CoV-2 sequences available until mid-February 2020.^{2, 3, 4, 5} By mid-April, > 550 SARS-CoV-2 sequences had been deposited in GenBank, and over 8,200 in the GISAID database. Methods: We performed a sequence analysis on 474 SARS-CoV-2 genomes submitted to GenBank up to April 11, 2020 by multiple alignment using Map to a Reference Assembly and Variants/SNP identification. The results were verified on a larger scale, 8,126 hCoV-19 (SARS-CoV-2) sequences from GISAID database. Results: We identified 5 recently emerged mutations in many isolates (up to 40%). Our analysis highlights 5 frequent new mutations that have emerged since late February 2020. These mutations are: one each missense (non-synonymous) mutation in orf1ab (C1059T), orf3 (G25563T) and orf8 (C27964T), one in 5’UTR (C241T), one in a non-coding region (G29553A). The final mutation (G29553A) was found to be almost exclusive to the US isolates. The first 3 mutations are non-synonymous, leading to amino acid substitutions in the viral protein sequence. Except for C241T, all the novel mutations identified are absent in the isolates from Italy and Spain in the SARS-CoV-2 genomes deposited in GenBank and GISAID by April 13, 2020. Conclusion: The results of current study indicate that new mutations are emerging as COVID-19 pandemic are spreading to different countries and that geography specific mutants may exist. The findings of current study lay the foundation for further investigation into the impact of SARS-CoV-2 mutations on disease incidence, severity, and host immune response. In addition, it may also provide insights into vaccine development and serological response detection for the virus.

In the wake of the novel coronavirus, SARS-CoV-19, the world has undergone a critical situation in which grave threats to global public health emerged. Among human populations across the planet, travel restraints, border enforcement measures, quarantine, and isolation provisions were implemented in an attempt to control and limit the spread of the contagion. Decisions on how to implement and enforce various control policies should be determined based on available real-world evidence and theoretical prediction. In this study, we propose a novel exportation- importation epidemic model associated with the quarantine and hospitalized-isolation policies by considering the two-body system: a source country of a contagious disease and a neighboring country that is initially disease-free. The model is first applied to the original COVID-19 data in China, Italy, and the Republic of Korea (ROK) and observed through consistent fitting results with equivalent goodness-of-fit. Then, the data are estimated per the fitting parameters. Driven by these parametric settings and considering the normalized population, the numerical analysis, and epidemiological exploration, this work further elucidates the substantial impact of quarantine policies, healthcare facilities, and the public counter-compliance effect.

We describe the genomes of two Echovirus isolates from Nigeria as reference enterovirus species B genomes for the region. These Echovirus 7 and 19 genomes have 7,411nt and 7,426nt, and were recovered from sewage contaminated water (in 2010) and an acute flaccid paralysis case (in 2014), respectively.

The SARS-CoV-2 virus (COVID-19) has led to an initiative to develop safe and effective vaccines for public health safety. In December 2020, the United States Food and Drug Administration (FDA) administered an Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine. Other vaccines from Johnson & Johnson, Moderna, and AstraZeneca shortly followed. This paper aims to examine the EUA process for COVID-19 vaccine approvals, including the requirements for the safety and efficacy of data, along with the role of the FDA and EMA in the approval process. Further, public concerns about vaccine approvals, including issues on the approval process's safety, efficacy, and speed, were also discussed. Using qualitative analysis of the extracted studies, trends and insights into the factors influencing public acceptance of COVID-19 vaccines, such as vaccine hesitancy and misinformation, were discussed. Overall, a transparent and rigorous regulatory process for vaccine approval is critical for education efforts between policymakers, vaccine developers, and the public to address concerns for increased population vaccine uptake.

Long COVID, also referred to as post-COVID-19 condition, describes the lingering after-effects of COVID-19 infection. This complex syndrome encompasses a range of symptoms affecting physical well-being, cognitive function, and mental health. The widespread impact of long COVID extends beyond individual sufferers, placing significant strain on healthcare systems and causing far-reaching socioeconomic consequences. The scale of this multifaceted health crisis is unparalleled in recent history, affecting millions globally and challenging our understanding of post-viral conditions. This study aimed to explore the possibility of targeting G protein-coupled receptors (GPCRs) signaling pathway-related genes as therapeutics for long COVID using computational analysis. Targeting GPCRs and their signaling pathways holds significant promise for long COVID therapeutics, as these receptors are involved in crucial physiological processes including immune regulation, inflammation control, and neurotransmission. All of these are implicated in the diverse and persistent symptoms of long COVID, potentially offering a versatile approach to addressing multiple aspects of the condition simultaneously. This study identified 21 genes associated with GPCRs for further exploration as potential targets. Notably, GPCR genes such as HRAS, KRAS, GNAQ, and GNA11 were determined to be possible therapeutic targets for the pathophysiological mechanisms of long COVID. FDA-approved drugs targeting these genes were identified, including Binimetinib, Cabozantinib, Selumetinib, Panitumumab, Cetuximab, Adagrasib, Tipifarnib, and Sotorasib. Additionally, Naltrexone and Tipifarnib have emerged as potential new treatment options for long COVID. SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport, contributing to the pathophysiology of pulmonary edema in patients with COVID-19. Further research is required to translate the findings into the development of therapeutics and to investigate the relationship between viral infection and GPCR signalling.

The COVID-19 pandemic, declared in early 2020, is an unprecedented global health crisis, causing over 7.0 million deaths and ongoing challenges. While the pharmaceutical industry expedited vaccine development, mutant SARS-CoV-2 strains remain a major fear. Moreover, concerns regarding the long-term health repercussions of COVID-19-affected individuals persist since individuals affected by mild and moderate to severe SARS-CoV-2 infection experience long-term cardiovascular complications, liver dysfunction, pulmonary afflictions, kidney impairments, and most importantly neurocognitive deficits. In recent studies, we documented pathophysiological changes in various organs following the post-acute infection of mice with murine hepatitis virus-1 (MHV-1), a coronavirus, at both 7 days and 12 months after infection. One part of the body that can be drastically affected by SARS-CoV-2 is the skin. Studies have shown major changes in the skin post-acute SARS CoV-2 infection in humans. However, long-term dermatologic changes post-COVID have never been explored. For the first time, we show several cutaneous findings both at the acute stages and long-term post-infection of mice with MHV-1 coronavirus (a promising experimental model to study acute and long-COVID). Precisely, we found destruction of the epidermal layer, an increase in the number of hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of the sebaceous glands at the acute stages, along with thinning of the panniculus carnosus, as well as the adventitial layer, which corresponds well with studies in humans. In contrast, the cutaneous investigation in the long-COVID phase shows the absence of hair follicles from both the epidermal and dermal layers, the destruction of adipose tissues, and the devastation of the epidermal layer. Further, treatment of these mice with a 15 amino acid synthetic peptide, SPIKENET (SPK), which was effective in preventing Spike glycoprotein-1 binding with host receptors, as well as has a potent anti-inflammatory response to severe inflammatory stimulus) restored the loss of hair follicles and re-architected the epidermal and dermal layers. Additionally, destruction in fatty tissue in the infected mice was successfully restored post-treatment with SPK. These findings suggest that SARS-CoV-2 initiates the changes early post-infection, leading to devastating skin alterations in the long term which can be prevented by our newly identified peptide drug SPK.

Long COVID-19 syndrom appears after Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection with acute damages to microcapillaries, microthombi and endotheliitis. However, the mech-anisms involved in these processes remain to be identified. All blood vessels are lined with a monolayer of endothelial cells called vascular endothelium of which one of the major properties is to prevent coagulation. VE cadherin is a component of endothelial cell junctions responsible for maintenance of the integrity of the vessels through homophilic interaction of its Ca++- dependent adhesive extracellular domain. We first provide evidence that VE-cadherin is a target in vitro for ACE2 cleavage because its extracellular domain (hrVE-ED) contains two amino acid sequences for ACE2 substrate recognition at the po-sitions 256P-F257 and 321PMKP-325L. Indeed, incubation of hrVE-ED with the active ecto-peptidase hrACE2 for 16 hrs in the presence of 10M ZnCl2 showed a dose-dependent (from 0.2 ng/ul to 2 ng/ul) decrease of the VE-cadherin immunoreactive band. In vivo, in the blood from patients having severe COVID-19, a circulating form of ACE2 was detected with an apparent molecular mass of 70 kDa while it was barely detectable in patients with mild infection. Of importance, in the patients with severe COVID-19 disease, the presence of three soluble fragments of VE-cadherin (70, 62, 54 kDa) were detected using the antiEC1 antibody while only the 54 kDa fragment was present in patients with mild disease. Altogether, these data clearly support a role for ACE2 on VE-cadherin cleavage leading to potential biomarkers in SARS-CoV2 infection related with the vascular disease in “Long COVID-19”.

Despite offering free-of-charge COVID-19 vaccines starting July 2021, Guatemala has one of the lowest vaccination rates in Latin America. During September 28, 2021 to April 11, 2022, we conducted a cross-sectional survey of community members adapting a CDC questionnaire to evaluate COVID-19 vaccine access and hesitancy. Of 233 participants ≥12 years, 127 (55%) received >1 dose of COVID-19 and 4 (2%) reported prior COVID-19 illness. Persons ≥12 years old unvaccinated (n=106) were more likely to be female (73% vs 41%, p<0.001) and homemakers (69% vs 24%, p<0.01) compared with vaccinated participants (n=127). Among those ≥18 years, the main reported motivation for vaccination among vaccinated participants was to protect the health of family/friends (101/117, 86%); 40 (55%) unvaccinated persons reported little/no confidence in public health institutions recommending COVID-19 vaccination. Community- and/or home-based vaccination programs, including vaccination of families through the workplace, may better reach female homemakers and reduce inequities and hesitancy.

Current generation witnesses a huge interest in optical waveguide due to their salient feature such as low cost, immune to electromagnetic interference, easy to multiplex, compact size, etc. These features of the optical fibers makes it an useful tool for various sensing applications including medicine, automotive, biotechnology, food quality control, aerospace, physical and chemical monitoring etc. Among all the reported application, the device has been widely exploited to measure the physical and chemical variation in surrounding environment. Optical fiber based temperature sensor plays a crucial role in this decade to detect high fever and tackle COVID like pandemic. Recognizing the major developments in the field of the optical fibers, this article aims to provide recent progress in temperature sensor utilizing several sensing configuration including standard fiber, photonic crystal fiber, and Bragg grating fibers. Additionally, the article also highlights the advantages, limitations, and future possibilities in this area.

The growth of the fаshion industry in Bаndung, which is increаsing every yeаr, if it is not bаlаnced with the аpplicаtion of digitаlizаtion аnd the use of the lаtest technology, it would be very unfortunаte. Аpаrt from the increаse in the number of internet users, the online shopping style by the community is аlso one of the driving forces for the growth of e-commerce, especiаlly in the midst of the current Covid pаndemic situаtion. This study will exаmine the аdoption of e-commerce technology to sell online in the midst of the Covid pаndemic to fаshion industry plаyers in Bаndung using these vаriаbles: effort expectаncy, performаnce expectаncy, fаcilitаting conditions, sociаl influence, existing hаbits, hedonic motivаtion, and also the price vаlue in the UTАUT2 model. So thаt it cаn show how the contribution of the аdoption of e-commerce technology to the behаviourаl intention аnd use behaviour of the fаshion industry consumers in Bаndung. Our research use quаntitаtive approach, cаusаl research/study with Structurаl Equаtion Modeling (SEM) аnаlysis technique using the SMАRTPLS 3.2.9 softwаre. Reseаrchers chose the аccidentаl sаmpling with а totаl of 400 respondents. Аll exogenous vаriаbles аffect behаviourаl intention by 80.9% аnd 54.9% on use behаviour.

The propagation of the coronavirus disease 2019 (COVID-19) reshaped the relationship between income and food-away-from-home (FAFH) expenditure in Mexico during 2020. Although the number of households participating in this market fell across income deciles and regions due to the pandemic, the impact on their budget shares is not uniform. Using data from the Encuesta Nacional de Ingresos y Gastos de los Hogares (ENIGH) 2020, we estimated an Engel curve of the Working-Lesser functional form for FAFH. Among the independent variables are the number of family members 65 years of age and older, and dummies to indicate whether the household experienced food insecurity or received remittances. The estimation was carried out following the Heckman two-step method, suitable for censored-response data. The results suggest that the budget share for FAFH drops as income increases. The number of older adults and food insecurity discourage the decision to participate in FAFH expenditure and increase its budget share, whereas remittances encourage participation and reduce its budget share. The corrected conditional elasticity is 0.4609; the sign and the magnitude indicate that FAFH is a necessity good.

Recently, several reports have emerged describing the long-term consequences of COVID-19 that may affect multiple systems, suggesting its chronicity. As further research is needed, we conducted a longitudinal observational study to report the prevalence and associated risk factors of long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients discharged from the TCH, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal). We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p<0·00001). Women were more prone than men to develop long-term symptoms and invasive mechanical ventilation also increased the frequency of symptoms at 30-days post-discharge. Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19.

Background: To investigate any associations between new clinical policies implemented because of the COVID-19 pandemic and harm to patients. Methods: Retrospective data collection of incidents and complaints reported through Datix®, and the Patient Liaison Service respectively. The setting was the Family Health division in a University teaching hospital in the UK. Primary and secondary outcome measures included; Proportion of incidents reported on Datix from 23/3/20 to 25/5/20, compared to the period from 23/3/19 to 29/5/19. COVID-19 related incidents and complaints and association with newly published guidelines or pathways from 23/3/20 to 29/5/20. Results: There was no significant difference in the proportion of overall patient activity resulting in incidents reported on Datix in 2020 (2.08%) compared to 2019 (2.09%), with 98% resulting in no/low harm in 2020. Three incident categories had increases in relative proportions of incidents including terms “COVID” or “Corona” compared to incidents that did not; “Child death”, “delay/failure to treatment and procedure” and “information governance”. One of the child deaths was a miscarriage and we were unable to link the second child death to a change in clinical policy at this stage. We were only able to link 2 COVID-19 associated incidents with a pathway or procedural change (one to the Children's Emergency Department admission pathway and the second to the introduction of virtual antenatal clinics). Eighteen complaints related to COVID-19 were logged. However, at this stage, we are unable to link any of these to a published change in clinical policy. Conclusions: Practice in the division was overall deemed to be safe in the designated period, with only 2 COVID-19 related incidents clearly related to a change in pathways and procedures. Continued surveillance and improved metrics for monitoring the impact of changes to pathways and procedures should be sought with the sustained presence of COVID-19 in clinical areas.

Following Smolin, we proceed to unification of general relativity and quantum theory by operating solely with events, i.e., without appealing to physical systems and space-time. The universe is modelled as a dendrogram (finite tree) expressing the hierarchic relations between events. This is the observational (epistemic) model; the ontic model is based on p-adic numbers (infinite trees). Hence, we use novel mathematics—not only space-time but even real numbers are not in use. Here, the p-adic space (which is zero dimensional) serves as the base for the holographic image of the universe. In this way our theory relates to p-adic physics; in particular, p-adic string theory and complex disordered systems (p-adic representation of Parisi matrix for spin glasses). Our Dendrogramic-Holographic (DH) theory matches perfectly with the Mach’s principle and Brans-Dicke theory. We found surprising informational interrelation between the fundamental constants, h, c, G, and their DH-analogues, h(D), c(D), G(D). DH-theory is part of Wheeler’s project on the information restructuring of physics. It is also a step towards the Unified Field theory. The universal potential V is nonlocal, but this is relational DH-nonlocality. V can be coupled to the Bohm quantum potential by moving to the real representation. This coupling enhanced the role of the Bohm potential.

Coronavirus Disease-19 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The virus enters host cells through receptor-mediated endocytosis of angiotensin-converting enzyme-2 (ACE2), leading to systemic inflammation, also known as a “cytokine storm,” and neuroinflammation. COVID-19’s upstream regulator, interferon-gamma (IFNG), is downregulated upon the infection of SARS-CoV-2, which leads to the downregulation of ACE2. The neuroinflammation signaling pathway (NISP) can lead to neurodegenerative diseases, such as Parkinson's disease (PD), which is characterized by the formation of Lewy Bodies made of α-Synuclein protein encoded by synuclein alpha (SNCA). This study presents the pathways involved in the downregulation of ACE2 following SARS-CoV-2 infection and its effect on PD progression. Through QIAGEN’s Ingenuity Pathway Analysis, the study identifies the NISP as a top-five canonical pathway/signaling pathway and SNCA as a top-five upstream regulator. Core Analysis was also conducted on the associated molecules between COVID-19 and SNCA to construct a network connectivity map. The Molecule Activity Predictor tool was used to simulate the infection of SARS-CoV-2 by downregulating IFNG, which leads to the predicted activation of SNCA, and subsequently PD, through a dataset of intermediary molecules. Downstream Effect analysis was further used to quantify the downregulation of ACE2 on SNCA activation.

Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.

Background and objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS is a common complex multi-system disease with a significant impact on the quality of life of patients and their families, yet the majority of ME/CFS patients go unrecognised or undiagnosed. For two decades the medical education establishment in the UK has been challenged to remedy these failings, but little has changed. This study was designed to ascertain the current UK medical school education on ME/CFS and to identify challenges and opportunities to inform the future of medical education. Materials and methods: A questionnaire, developed under the guidance of the Medical Schools Council, was sent to all 34 UK Medical Schools to collect data for the academic year 2018-2019. Results: Responses were provided by 22 out of a total of 34 medical schools (65%). 59% of respondents taught ME/CFS, led by specialists drawn from 6 medical disciplines. Teaching delivery was usually by lecture; however, discussion case studies and e-learning were used. 7 schools included questions on ME/CFS in their examinations and 3 schools reported likely clinical exposure to ME/CFS patients. 64% of respondents were interested in receiving further teaching aids in ME/CFS. None of the schools shared details of their teaching syllabus so it was not possible to ascertain what students were being taught. Conclusions: UK medical school teaching in ME/CFS is shown to be inadequate. Several medical disciplines, with known differences about the disease, need to set these aside to give greater clarity in teaching undergraduates so they can more easily recognise and diagnose ME/CFS. Improvements are proposed in ME/CFS medical education consistent with the international paradigm shift in biomedical understanding of this disease. Many medical schools (64% of respondents) acknowledge this need by expressing a strong appetite for the development of further teaching aids and materials. The GMC and MSC are called upon to use their considerable influence to bring about the appropriate changes to medical school curricula so future doctors can recognise, diagnose and treat ME/CFS. The GMC should also consider creating a registered speciality encompassing ME/CFS, post viral fatigue and Long Covid.

At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the material state of these MLOs. Particular attention was paid to proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consists of completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquid-liquid phase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS is relatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-less organelles. Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the stress-granules dataset with senescence-related processes. Among SG proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS among such proteins, which allows us to consider it as “potentially dangerous.” Proteins common to SGs and P bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

Multi-level shaking table tests were performed on 1:3 reduced scale two-story RC IMRF frames conforming to ACI-318-19. The exterior joints lacked shear reinforcement to assess the viability of the ACI model recommended for determining the design shear strength of the beam-column joint panel. The Northridge-1994 earthquake accelerogram was input to the frame for multi-level shaking table testing. Plastic hinges developed in beams under base input motion with a maximum acceleration equal to 0.40g. The exterior joints incurred extensive damage under base input motion with a maximum acceleration equal to 0.70g. The frame achieved displacement ductility and overstrength factors equal to 2.40 and 2.50 respectively. This gives a response modification factor equal to 6. The satisfactory performance of the frame is attributed to the high efficiency of the beam-column joint, which was confined by spandrel beams on two faces, and the high strength of the concrete. The inherent minimal confinement is sufficient to ensure good seismic behavior. The analysis confirmed overstrength equal to 1.58 for joint shear strength in comparison to the design strength determined using the ACI model. The data might serve as a reference for calibrating and validating numerical modeling techniques for performance evaluation, which are crucial in the context of performance-based engineering.

Long COVID, characterized by persistent symptoms lasting from weeks to several months following initial infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), significantly impacts individuals' quality of life and poses a potential long-term burden on global healthcare systems. Clinical manifestations of Long COVID are diverse, affecting multiple systems including respiratory, cardiovascular, neurological, and gastrointestinal. While the precise mechanisms underlying Long COVID remain unclear, emerging evidence suggests involvement of various bodily pathways. This study employs bioinformatics tools to investigate the mechanisms of Long COVID and identify potential drug targets associated with key pathways, including inflammation, cytokines, immune response, coagulation, mitochondrial function, oxidative stress, and autonomic dysfunction. Tools such as the National Center for Biotechnology Information (NCBI) database, PubChem, UniProt, and iGEMDOCK were utilized for pathway analysis and molecular docking. The analysis aimed to identify drug molecules that may interact with target proteins to regulate or inhibit pathway activity, yielding several potential drug candidates for further investigation.