SARS-CoV-2 virulence is known to increase with lowering of environmental temperature and solar ultraviolet radiation; therefore, we have focused our real-world nationwide study concerning with COVID-19 trends and dynamics on the coldest seasons of the year in Italy, the Western country hardest hit at the onset of the pandemic, comparing the autumn-winter of 2020 (before mass vaccination but when the emergency machinery was fully operative in terms of tracing and swabs) with the autumn-winter of 2021 (after mass vaccination), and analyzing the mortality burden by age groups and life stages in the years 2019 (pre-COVID-19), 2020 (before mass vaccination) and 2021 (after mass vaccination). Methods: During the state of national health emergency, the Civil Defense Department released the aggregate data coming from the Higher Institute of Health, the Ministry of Health, the Italian Regions, and the Independent Provinces, to inform the population (58.85 million people) about the pandemic situation, daily. Among these data there were the number of contagions, performed swabs, hospitalizations in Intensive Care Units (ICU), non-ICU patients, and deaths. By means of a team effort, we have collected and elaborated all these data, comparing the COVID-19 pandemic in Italy during the autumn-winter of 2020 with the autumn-winter of 2021. Moreover, we have extracted from the database of the National Institute of Statistics the total number of annual deaths in Italy during the years 2019, 2020 and 2021, comparing them to each other in order to evaluate the mortality burden attributable to COVID-19. Results: From the autumn-winter of 2020 to the autumn-winter of 2021, the contagions increased by ≈285%, however against a ≈290% increase in the performed swabs; therefore, the mean positivity rate passed from 8.74% before mass vaccination to 8.59% after mass vaccination. The unprecedent vaccination campaign allowed a ≈251% abatement in COVID-19 deaths, and a reduction of ≈224% and ≈228% in daily ICU and non-ICU hospitalizations due to COVID-19, respectively. Regarding COVID-19 deaths, in 2020 there was a mortality excess of ≈14.3% quantifiable in 105,900 more deaths compared to 2019, the pre-COVID-19 year; 103,183 out of 105,900 deaths occurred in older adults (≥60 years), which is equivalent to ≈97.4%, while in adults over 50, the segment of population just below older adults, in 2020 there were 2807 more deaths than in 2019. Surprisingly, from the analysis of our data, it is emerged that under the age of 40 in the years 2019, 2020 and 2021 there were 7103, 6808 and 7165 deaths, respectively. This means that in subjects under 40 during 2020 there were 295 fewer deaths than in 2019, while during 2021 there were 357 more deaths than in 2020, equivalent to ≈5.2% more. Conclusions: COVID-19 is a potential life-threatening disease mainly in older adults, as they are the most vulnerable due to inherent immunosenescence and inflammaging. Extensive vaccination in this segment of population with up-to-date vaccines is the means to reduce deaths, hospitalizations, and ICU pressure in the public interest. In the event of future threats, a new mass vaccination campaign must not be implemented without taking into account the individual age; it should primarily be aimed at people over 60 and at patients of any age with immune deficits, and secondly at people over 50. COVID-19 vaccination shows a favorable benefit-risk balance in older adults, while this balance falls under the age of 40; this younger segment of population should be therefore exempt from any mandatory vaccination.

The Single Site Order – a policy restricting staff from working at multiple long-term care homes – was mandated by the Public Health Agency of Canada to control the spread of COVID-19 in long-term care homes, where nearly 70% of COVID-19-related deaths in Canada occurred. This mixed methods study assesses the impact of Single Site Order on long-term care residents in British Columbia. Interviews were conducted (residents (n=6), family members (n=9), staff (n=18), and leadership (n=10) from long-term care homes (n=4)) and analyzed using thematic analysis. Administrative data was collected between April 2019 – March 2020 and April 2020 – March 2021 and analyzed using descriptive statistics and data visualization. Qualitative and quantitative data were triangulated and demonstrate staffing challenges became worse during implementation of the SSO resulting in the mental and physical health deterioration of LTC residents. Qualitative data demonstrated decreased time for personalized and proactive care, increased communication challenges, and increased loneliness and isolation. Quantitative data showed a decline in activities of daily living, increased antipsychotic medication use, pressure ulcers, behavioural symptoms, and an increase in falls. Addressing staff workload and staffing shortages during SSO-related policy implementation is essential to avoid resident health deterioration.

Background: The manifestations, severity, and mortality of COVID-19 are considered to be associated with the changes in various hematological parameters and in immunity. Associations of immunoglobulin G antibodies against severe acute respiratory syndrome-linked coronavirus (IgG-SARS)-positive status with cardiac function and hematological and biochemical parameters in apparently health subjects are poorly understood. Methods: The present cross-sectional study included 307 healthy volunteers (24-69 years of age; 44.8±8.6 years; 80.4% men) and was initiated in 2019 before the COVID-19 pandemic. COVID-19 episodes were confirmed by detection of IgG-SARS against SARS-CoV-2 S1 RBD to reveal 70 IgG-SARS-positive and 237 negative participants. Numerous ultrasound characteristics were assessed by echocardiography, and 15 hematological and biochemical parameters were assayed in the blood. Descriptive and comparative analysis was based on the IgG-SARS status of the participants. Results: The left ventricular mass index, mitral ratio of peak early to late diastolic filling velocity or flow velocity across the mitral valve, and deceleration time of early mitral inflow were decreased (P<0.05) in IgG-SARS-positive participants versus those in IgG-SARS-negative participants according to multivariate logistic regression analysis. Erythrocyte sedimentation rate and platelet count were slightly increased, and blood hemoglobin was decreased in IgG-SARS-positive participants compared with those in IgG-SARS-negative participants. Conclusions: LV filling, inflammation, blood coagulation, and hemoglobin appear to be influenced by COVID-19 infection in healthy participants. These observations contribute to the development of a population recovery strategy after the episodes of COVID-19.

After three years of the onset of the pandemic, there is scarce evidence about how COVID-19 disease affect the female reproductive system, and consequently, the menstrual cycle. Since the common causes of secondary amenorrhea are considered as exclusion criteria in the studies about menstrual changes following SARS-CoV-2 infection, the prevalence of this event and the influencing factors in formerly menstruating women remains unknown. A retrospective observational cross-sectional study was conducted on Spanish adult women (N= 17,512), using an online survey; a subpopulation of SARS-CoV-2-infected-formerly menstruating women was included in the present analysis (n= 72). Collected data included general characteristics, medical history, and specific information about COVID-19 disease. 38.9% of the respondents experienced menstrual-related disturbances after suffering from the COVID-19 disease, unexpected vaginal bleeding being the most common (20.8%). Other alterations related with the length – “shorter” by 12.5% − and the flow − “heavier than usual” 30.3% − of the menstrual bleeding were reported. The binary logistic regression showed that being a perimenopausal woman (AOR 4.608, CI 95%, 1.018 – 20.856, p = 0.047) and having heavy menstrual bleeding (AOR 4.857, CI 95%, 1.239 – 19.031, p=0.023) are influential factors. This evidence could help health professionals to provide scientifically up-to-date information to their patients, empowering them to actively manage their reproductive health, especially in those societies where menstrual health is still a taboo.

All severe cases of SARS-CoV-2 infections are characterized by a high risk of disease progression towards ARDS, leading to bad outcome. Respiratory symptoms in COVID-19 patients often do not correspond to disease’s worsening. A dysregulated host response to the large viral load could play a key role in the disease progression. In our sample median age was 74 years (72-75) and 54% were men. Median period of hospitalization was 9 days. Firstly, we observed an asynchronous trend of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in 764 selected among 963 patients who were consecutively recruited in two hospitals (Cannizzaro, S. Marco) in Catania, Italy. NLR values in deceased patients showed an increase from baseline over time. By contrast, CRP tended to fall from baseline to median day of hospitalization in all four subgroups, but steeply increased at the end of hospitalization only in ICU-admitted patients. Then we evaluated the relationships between NLR and CRP as continuous variables with PaO2/FiO2 ratio (P/F). Finally, we made mediation and moderation analyses to determine the link between inflammation (CRP), immune system (neutrophils and lymphocytes) and respiratory failure (P/F). CRP, neutrophils and P/F are linked in the same pathogenetic chain leading to respiratory failure.

One of the most important problems in the presence of epidemics and pandemics is an accurate prediction and preparedness. Scholars and experts argue that future pandemics and/or epidemics are almost inevitable events and is not whether next pandemics will happen, but when a new heath emergency will emerge. Epidemiologic models for prediction of Coronavirus Disease 2019 (COVID-19) have shown many limitations because of unpredictable dynamics of the new viral agent SARS-CoV-2 in environment and society. The main goals of this study are twofold: first, the analysis of anthropogenic activities and factors that may trigger pandemic threats; second, the planning of new directions for strategies to reduce risks that a pandemic threat emerges and/or in the initial phase to reduce vast diffusion and negative impact of new viral agents that can generate hazards and problems in public health, environment and socioeconomic systems. In particular, the investigation and understanding of sources and driving factors concerning the emergence and diffusion of new pandemics have critical aspects for strategic actions of forecast, prevention and preparation of effective policy responses to cope with next pandemic crises and health emergencies. Insights here endeavor, whenever possible, to clarify these problems to increase the knowledge of the sources and factor determining the emergence of new viral agents in order to design optimal response policies to face next pandemic diseases similar to COVID-19. .

Objectives To develop and validate a prediction model for 28-day in-hospital mortality among adult patients critically ill with COVID-19 in the UK. Design Observational cohort study. Setting 287 adult critical care units in England, Wales and Northern Ireland, of which 260 admitted at least one eligible patient. Participants 10,933 patients with confirmed COVID-19 of whom 10,401 were eligible (excluding 532 patients with a duration of critical care less than 24 hours and 1 patient with unknown 28-day outcome): 8,666 development (March-April 2020) and 1,735 temporal validation (May-August 2020). Main outcome measures 28-day in-hospital mortality from start of critical care. Results Two models were developed using 14 patient level predictors selected from 30 candidate predictors, with and without adjustment for calendar time. In the temporal validation data, the model discrimination was maintained (c index 0.78) but calibration was poor, particularly for the model not adjusted for calendar time (ratio of observed to predicted mortality 0.74 versus 0.88 for the model adjusted for calendar time). Conclusions We developed and validated a prediction model for 28-day in-hospital mortality for patients critically ill with COVID-19. Although absolute predictions were inaccurate due to changing outcomes, the models will support risk-adjustment in analyses and monitoring changes in risk-adjusted outcome over time.

To assist firefighters and other first responders to use their existing equipment for respiration during the COVID-19 pandemic without using single-use, low-supply, masks, this study outlines an open source kit to convert a 3M-manufactured Scott Safety self-contained breathing apparatus (SCBA) into a powered air-purifying particulate respirator (PAPR). The open source PAPR can be fabricated with a low-cost 3-D printer and widely available components for less than $150, replacing commercial conversion kits saving 85% or full-fledged proprietary PAPRs saving over 90%. The parametric designs allow for adaptation to other core components and can be custom fit specifically to fire-fighter equipment, including their suspenders. The open source PAPR has controllable air flow and its design enables breathing even if the fan is disconnected or if the battery dies. The open source PAPR was tested for air flow as a function of battery life and was found to meet NIOSH air flow requirements for 4 hours, which is 300% over expected regular use.

The goal of this paper is to contribute the perspective of a systems engineer to the effort to fight pandemics. The availability of low latency case data and effectiveness of social distancing suggest there is sufficient control for successful smoothing and targeting almost any desired level of low or high cases and immunity. This control proceeds from spontaneous public reaction to caseloads and news as well as government mediated recommendations and orders. We simulate multi-step and intermittent-with-feedback partial unlock of social distancing for rapidly-spreading moderate-mortality epidemics and pandemics similar to COVID-19. Optimized scenarios reduce total cases and therefore deaths typically 8% and up to 30% by controlling overshoot as groups cross the herd immunity threshold, or lower thresholds to manage medical resources and provide economic relief. We analyze overshoot and provide guidance on how to damp it. However, we find overshoot damping, whether from expert planning or natural public self-isolation, increases the likelihood of transition to an endemic disease. An SIR model is used to evaluate scenarios that are intended to function over a wide variety of parameters. The end result is not a case trajectory prediction, but a prediction of which strategies produce near-optimal results over a wide range of epidemiological and social parameters. Overshoot damping perversely increases the chance a pathogen will transition to an endemic disease, so we briefly describe the undershoot conditions that promote transition to endemic status.

In this paper we provide an ``expository overview" of classic epidemic projection models. Starting with the simple case of an epidemic that grows exponentially we then investigate ``compartmental" models. These assume that the growth of an infected population is limited endogenously by the size of the underlying pool of susceptibles. We then describe a new family of so-called "Exo-r" statistical models, which hinge on an exogenously driven growth rate of the infected population. This family, which can be used to model both infections and deaths, captures parsimoniously both the depletion of susceptibles and the effect of interventions such as lockdowns and ``social distancing". The model is used to fit numbers of Covid-19 infections in China. It is also used to model and project deaths in the United States. Results are used to inform a discussion on i) the challenges at hand and ii) the extent to which epidemic projection models may be useful despite being wrong.

COVID-19 represents an unprecedented threat to global public health and economies. Assays are urgently needed for rapid detection and diagnosis of SARS-CoV-2-infected patients in order to inform treatment and quarantine strategies. Establishing globally accepted easy-to-access diagnostic tests is extremely important to understanding the epidemiology of the present pandemic. While nucleic acid-based tests are considered to be more sensitive with respect to serological tests, but the present gold standard RT-PCR-based assays possess limitations such as low sample throughput, requirement for sophisticated reagents and instrumentation. To overcome these shortcomings, recent efforts of incorporating LAMP-based isothermal detection, and minimizing the number of reagents required are on rise. Novel CRISPR- and other nuclease-based techniques, when merge with isothermal and allied technologies, promises to provide sensitive and rapid detection of SARS-CoV-2 nucleic acids. Here we discuss and present compilation of state-of-the-art CRISPR based detection techniques for use in COVID diagnosis and epidemiology.

In the era of the post-quantum Internet of Things (IoT), the implementation of anti-quantum cryptographic algorithms in numerous terminals can successfully defend against prospective quantum computing assaults. Lattice-based cryptography can withstand quantum computing attacks, making it a viable substitute for the currently prevalent classical public-key cryptographic technique. Nevertheless, the algorithm’s significant time complexity will result in a substantial computational burden on the edge computing chip in the IoT terminal. The computation of polynomial multiplication is the most demanding task in lattice-based cryptographic algorithms. Therefore, the investigation into efficient methods for calculating polynomial multiplication is highly important. Quick number theory transformations (NTT) are a widely employed technique to accelerate polynomial multiplication. This study presents a hardware implementation of an efficient number theory transformation. We utilize a multi-level pipeline architecture in the design to accomplish parallel calculations and execute it on a low-profile Artix7-XC7A100T FPGA device. The performance evaluation results demonstrate that our implementation significantly enhances performance and reduces resource usage compared to other existing proposals on the same platform. We suggested NTT core can be implemented in edge computing chips to enhance computational speed due to its small and low-latency design. The experimental results show that the proposed design, which supports both NTT and inverse NTT, achieves 417-Megahertz and consumes only 541-LUTs on Artix-7 XC7A100T.

The assessment of existing bridges constitutes a serious challenge for the researchers since their safety evaluation is a complex task due to several sources of uncertainty affecting the parameters identified in the knowledge process. In particular, a high level of uncertainties may arise in the case of prestressing systems requiring special investigation strategies and experimental technologies. The paper aims to investigate how the knowledge uncertainties influence the safety assessment of existing post-tensioned bridges. The semi-probabilistic approach is used, and uncertainties related to the knowledge process are described considering the number of tests, the confidence level assumed for the estimation of the problem parameters, and the measurement errors of in-situ tests. Results concerning a typical post-tensioned bridge are reported and the variability of the outcomes is discussed and compared with a reference case of “perfect knowledge”. The main results of the study confirm the general robustness of the semi-probabilistic Eurocodes safety format and provide an overview of dispersion due to different choices about the number of tests and confidence level. The measurement errors may lead to significant under-estimation of the computed structural capacity with respect to the reference one.

A The aim of this study is to analyze the effect of different endodontic irrigants and adhesive systems on resin bond strength of fiber post cementation. 144 single-rooted, unrestored human teeth were endodontically treated and randomly divided into 12 groups according to 4 endodontic irrigants (distilled water as control; EDTA 17%; NaOCl 5%; clorhexidine 2%) and 3 different adhesive/resin cement systems (etch-and-rinse: ortofosforic acid, Parabond® A+B/Paracore®; self-etch: ParaBond® Non-Rinse Conditioner, Parabond® A+B /Paracore®; Universal: ClearfilTM Universal Bond/ ClearfilTM DC Core Plus). 48 h after post cementation ten teeth from each group were cross sectioned into 3 discs (cervical, middle and apical regions). 30 specimens of each group (n=30) were submitted to push-out test at a crosshead speed of 1 mm/min. The remaining 2 teeth of each group were sectioned in the same manner and the resin-dentin interface was evaluated using scanning electron microscopy (SEM). The results were statistically analyzed with the ANOVA and Tukey’s test (< 0,01). The adhesive protocols and post space region showed no significant effect on bond strength (> 0.01). The combination of NaOCl 5% and ClearfilTM Universal Bond reduced the adhesive strength (< 0.01). The NaOCl 5%, in relation with other irrigants, significantly decreased the push-out bond strength.

Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD, due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive cure available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cells-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to higher-risk subpopulations of premature infants. Hence the need for easy-to-use noninvasive tools for a standardized, precise and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).

BACKGROUNDː The so-called Low Cardiac Output Syndrome (LCOS) is one of the most common complications in pediatric patients with congenital heart disease undergoing corrective surgery. LCOS requires high concentrations of inotropes to support cardiac contractility and improve cardiac output, allowing for a better systemic perfusion. To date, serum lactate concentrations and central venous oxygen saturation (ScVO2) are the most commonly used perfusion markers, but they are not completely reliable to identify a state of global tissue hypoxia. The study aims to evaluate whether the venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio [P(v-a)CO2/C(a-v)O2] can be a good index to predict the development of LCOS in the aforemen-tioned patients, so as to treat it promptly. METHODSː This study followed a population of 98 children undergoing corrective cardiac surgery from June 2018 to October 2020 at the Department of Cardiac Surgery of University Hospital Inte-grated Trust and their subsequent admission at the Postoperative Cardiothoracic Surgery Intensive Care Unit. During the study, central arterial and venous blood gas analysis were carried out before and after cardiopulmonary bypass (CPB) (pre-CPB and post-CPB), at admission to intensive care unit, before and after extubation and at any time of instability or modification of the patient’s clinical and therapeutic conditions. RESULTSː The data analysis shows that 46.9% of the children developed a LCOS (in line with the current literature) but that there is no statistically significant association between the P(v-a)CO2/C(a-v)O2 ratio and LCOS onset. Despite the limits of statistical significance, however, a 31% increase in the ratio emerged from the pre-CPB phase to the post-CPB phase when LCOS is present. CONCLUSIONSː This study confirms a statistically significant association between the most used markers in adult patients (serum lactate concentration, ScVO2 and oxygen extraction ratio-ERO2) measured in the pre-CPB phase and the incidence of LCOS onset, especially in patients with he-modynamic instability before surgery.

Background: Post-delivery period could be characterized by psychological distress (e.g., anxiety, sadness, and irritability), leading to post-partum depression (PPD). Objective: The present clinical study assess the effect of probiotic supplementation containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) on mother’s mood and breastfeeding quality during the first trimester after delivery. Methods: A Randomized Double Blind Controlled (RDBPC) trial has been carried out in 200 healthy new mothers divided into an active group taking a supplement containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) plus multivitamins, and a control group (multivitamin complex only) for 90 days. Symptoms related to maternal depression and breastfeeding quality were evaluated at days 45 and 90 by Edinburgh Postnatal Depression Scale (EPDS) and Breastfeeding Self-Efficacy Scale Short-Form (BSES-SF). Results: At days 45 and 90, probiotic treatment significantly ameliorated the mothers’ mood compared to the control treatment (p<0.001). Likewise, breastfeeding quality and baby’s cries significantly improved in the probiotic group (p<0.001). Conclusions: Microbiota alterations could influence post-delivery woman’s mental state. According to our results, L. reuteri PBS072 and B. breve BB077 are potential candidates able to improve stress resilience in the post-partum period.

BackgroundIndex level disc herniation following lumbar spinal decompression is somewhat overlooked as postoperative complication, resulting in return of symptoms. It is proposed that the combination of local instability and degenerated disc is more likely to result in disc herniation. There is no literature comparing post-decompression disc herniation rates between different techniques. This study compares the postoperative disc herniation rates of the "mini-open" laminectomy versus the tubular system decompression.MethodsIn a retrospective comparative study, 563 patient files who underwent primary lumbar spinal decompression, were reviewed and divided into two groups, distinguished by surgical technique. Demographic, clinical, and postoperative data were collected and compared using independent two-tailed t-test and Fisher's exact test with significance set at p<0.05. Primary outcome: comparison of post-decompression surgery, index level, disc herniation occurrence between two surgical techniques.ResultsPostoperative index level disc herniation was significantly lower in the minimally invasive surgery group with 2 cases (0.8%) versus 19 cases (5.8%) in the "mini-open" group [p=0.002]. Disc herniation following single level and multi-level operations were also significantly lower in the minimally invasive group compared with the "mini-open" group (2 versus 11 and 0 versus 8 respectively; p<0.05).ConclusionPostoperative index level disc herniation following lumbar spinal decompression occurs in 3.7% of surgeries. Minimally invasive surgery is found to result in less herniations then "mini-open".

Plants attained cellular homeostasis of phosphate (Pi) through an integrated response pathway regulated by different families of transcription factors including MYB, WRKY, bHLH and ZFP. The systemic response to Pi limitation showed the critical role played by inositol pyrophosphate (PP-InsPs) as signaling molecule and SPX (SYG1/PHO81/XPR1) domain proteins as sensor of cellular Pi status. Binding of SPX to PP-InsPs regulates the transcriptional activity of the MYB-CC proteins, phosphate starvation response factors (PHR/PHL) as the central regulator of Pi-deficiency response in plants. Vacuolar phosphate transporter, VPT may sense the cellular Pi status by its SPX domain, and vacuolar sequestration is activated under Pi replete condition and the stored Pi is an important resource to be mobilized under Pi deficiency. Proteomic approaches led to new discoveries of proteins associated with Pi-deficient response pathways and post-translational events that may influence plants in achieving Pi homeostasis. This review provides current understanding on the molecular mechanisms at the transcriptional and translational levels for achieving Pi homeostasis in plants highlighting the importance of DNA-protein and protein-protein interactions. The potential strategies for employing the CRISPR technology to modify the gene sequences of key regulatory and response proteins for attaining plant Pi homeostasis are discussed.

The COVID-19 pandemic has invited us to envision education anew, embracing a new era of instructional practices and learning environments. This study explores language teachers' and students' experiences in the post-pandemic landscape, providing valuable insights into the challenges, adaptations, and opportunities. Grounded in socio-cultural perspectives and educational theories, such as Vygotsky's socio-cultural theory and Deci and Ryan's self-determination theory, the study employs Interpretative Phenomenological Analysis (IPA) to comprehensively analyze secondary data sources. Findings reveal the significant role of social interaction and cultural context in language learning, amid reduced face-to-face contact and increased reliance on technology. The study uncovers the intricate interplay between individual, interpersonal, and environmental factors, shedding light on educators' and learners' challenges. Autonomy, competence, and relatedness emerge as crucial for intrinsic motivation and optimal learning outcomes. While acknowledging limitations related to secondary data sources, the study offers a comprehensive overview of the literature, informing language education practices in the post-pandemic era. It contributes to understanding the complex dynamics and interactions within language education and calls for future research using primary data collection methods to explore experiences and perspectives further. By understanding post-pandemic experiences, this study aims to shape education policies, practices, and pedagogical approaches, supporting effective language learning and the well-being of educators and learners in this transformed educational context.

Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that occurs following exposure to traumatic events. The prevalence of PTSD is estimated to be 5-10% worldwide, and it is associated with significant distress and disability. Recent evidence suggests that PTSD may be a risk factor for the development of subsequent neurodegenerative disorders, including Alzheimer’s dementia and Parkinson’s disease. Identification of biomarkers known to be associated with neurodegeneration in patients with PTSD would shed light on the pathophysiological mechanisms linking these disorders, and would also help in the development of preventive approaches aimed at reducing the risk of neurodegenerative disorders in PTSD. In the current review, the PubMed and Scopus databases were searched for studies aimed at identifying genetic, biochemical, neuroimaging or behavioral markers associated with neurodegeneration in patients with PTSD. Out of a total of 342 citations retrieved, 29 relevant studies were identified for inclusion in the review. The results of these studies suggest that several potentially relevant biological markers, including cerebral cortical thinning, disrupted white matter integrity, specific genetic polymorphisms, immune-inflammatory alterations, vitamin D deficiency, metabolic syndrome and parasomnias, may be associated with an increased risk of neurodegeneration in patients with PTSD. Though many of these results need replication, they highlight a number of biological pathways that plausibly link PTSD with neurodegenerative disorders, and suggest potentially valuable avenues for prevention and early intervention in this patient population.

This study aimed to investigate the prevalence, location, and characteristics of new-onset chronic pain by using a new definition in long-term survivors after discharge from a tertiary emergency center. We conducted a single-center ambidirectional cohort study from January to May 2022. A survey of patients was conducted by postal mail 2-2.5 years since their discharge from a tertiary emergency center. We used the Brief Pain Inventory to investigate chronic pain parameters, and the painDETECT questionnaire to investigate neuropathic pain. Patient information during hospitalization was collected retrospectively from medical records. The survey was sent to 78 patients, 63 (81%) of whom responded and were included in the analysis. Nine of the 63 patients (14%) had new-onset chronic pain. Of these, six (67%) had chronic pain of moderate or severe intensity which interfered with daily life. The most frequent location of chronic pain was the ankle/foot (n=4, 44%). Neuropathic pain was present in four (44%) patients with new-onset chronic pain. New-onset chronic pain may occur for up to 2-2.5 years after discharge from a tertiary emergency center, and this may interfere with daily life. Therefore, a follow-up system for chronic pain is warranted.

Passive and forced drinking harm was prevalent but less recognized in Chinese adolescents. We educated adolescents on such harm to reduce their intention to drink. Students (n=1244) from 7 secondary schools in Hong Kong participated in a video-based health talk on passive and forced drinking harm. Paired t-test was used to assess their change in knowledge of passive and forced drinking, health and social harm of drinking after the health talk. McNemar's chi-squared test and adjusted multivariable logistic regression (AOR) were used to assess their change in intention to drink and intention to quit. Students were less likely to drink (OR 0.29, 95% CI 0.19-0.42) and more likely to quit drinking (OR 3.50, 1.10-14.6) after the health talk. Increased knowledge of passive drinking was associated with less intention to drink (AOR 0.93, 0.90-0.97), increased knowledge of health harm (adjusted b 0.06, 0.05-0.08), and social harm of drinking (adjusted b 0.12, 0.10-0.16). Similar associations were observed in forced drinking (intention to drink: AOR 0.87, 0.79-0.96; health harm: adjusted b 0.16, 0.12-0.19; social harm: adjusted b 0.36, 0.28-0.43). We showed preliminary evidence that the health talk on passive and forced drinking reduced the intention to drink in adolescents.

The traditional bored pile technology has some arduous problems, such as the sediment at the pile tip, the mud skin along the pile shaft, and the stress release due to borehole construction. The post-grouted technology at the pile tip of bored pile has emerged because of demand. The grouting migration height (GMH) is of great significance to the strengthen and reinforcement of the pile foundation. This paper derives the calculation formula of the GMH based on the theory of the column hole expansion and Herschel-Bulkley model. The influence of relevant parameters on the GMH is discussed. Aiming at the problem of the grouting migration along the pile shaft in layered soils, the iterative calculation method of the GMH is proposed. The correctness of the GMH is verified by an engineering case, which can guide the engineering practice. The result shows that the GMH increases with the increase of the grouting pressure, the pile diameter and the thickness of the mud skin, and the grouting pressure is positively correlated with the GMH. The GMH decreases with the increase of the buried depth, the consistency coefficient and the rheological index. On this basis, the correctness of the GMH is verified by an engineering case.

A critical challenge underpinning the adoption of Additive Manufacture (AM) as a technology is the postprocessing of manufactured components. For Selective Laser Sintering (SLS) this can involve the removal of powder from the interior of the component, often by vibrating the component to fluidise the powder to encourage drainage. In this paper we develop and validate a computational model of the flow of metal powder suitable for predicting powder removal from such AM components. The model is a continuum Eulerian multiphase model of the powder including models for the granular temperature; the effect of vibration can be included through appropriate wall boundaries for this granular temperature. We validate the individual sub-models appropriate for AM metal powders by comparison with in-house and literature experimental results, and then apply the full model to a more complex geometry typical of an AM Heat Exchanger. The model is shown to provide valuable and accurate results at a fraction of the computational cost of a particle-based model.

Prestress loss evaluation in prestressed strand is essential for prestressed structures. However, the sensors installed outside the duct can only measure the total prestress loss. The sensors attached on strand inside the duct also have several problems, such as inadequate durability in an aggressive environment, vulnerable damage at tensioning and so on. This paper proposes a new installation method for long-gauge fiber Bragg grating (LFBG) sensor to prevent accidental damage. Then the itemized prestress losses were determined in each stage of the pre-tensioning and post-tensioning according to the LFBG measurements. We verified the applicability of the LFBG sensors for prestress monitoring and the accuracy of the proposed prestress loss calculation method during pre-tensioning and post-tensioning. In the pre-tensioning case, the calculated prestress losses had less deviation from the true losses than those obtained from foil-strain gauges, and the durability of the LFBG sensors was better than foil-strain gauges, whereas in post-tensioning case, the calculated prestress losses were close to those derived from theoretical predictions. Finally, we monitored prestress variation in the strand for 90 days. The itemized prestress losses at each stages of post-tensioning were obtained by the proposed calculation method to show the prospect of the LFBG sensors in practical evaluation.

Land-cover classification that uses very-high-resolution (VHR) remote sensing images is a topic of considerable interest. Although many classification methods have been developed, there is still room for improvements in the accuracy and usability of classification systems. In this paper, a novel post-processing approach based on a dual-adaptive majority voting strategy (D-AMVS) is proposed for improving the performance of initial classification maps. D-AMVS defines a strategy for refining each label of a classified map that is obtained by different classification methods from the same original image and fusing the different refined classification maps to generate a final classification result. The proposed D-AMVS contains three main blocks. 1) An adaptive region is generated by extending gradually the region around a central pixel based on two predefined parameters (T1 and T2) in order to utilize the spatial feature of ground targets in a VHR image. 2) For each classified map, the label of the central pixel is refined according to the majority voting rule within the adaptive region. This is defined as adaptive majority voting (AMV). Each initial classified map is refined in this manner pixel by pixel. 3) Finally, the refined classified maps are used to generate a final classification map, and the label of the central pixel in the final classification map is determined by applying AMV again. Each entire classified map is scanned and refined pixel by pixel based on the proposed D-AMVS. The accuracies of the proposed D-AMVS approach are investigated through two remote sensing images with high spatial resolutions of 1.0 and 1.3 m, respectively. Compared with the classical majority voting method and a relatively new post-processing method called general post-classification framework, the proposed D-AMVS can achieve a land-cover classification map with less noise and higher classification accuracies.

Background: The COVID-19 pandemic has exacerbated existing healthcare disparities among American Indian/Alaska Native (AI/AN) populations, rooted in historical traumas and systemic marginalization. Methods: This study conducted at a single Indian Health Service (IHS) clinic in central Michigan examines the effectiveness of educational interventions in enhancing COVID-19 knowledge and attitudes among AI/AN populations. Utilizing a pre/post prospective study design, participants received either a video or infographic educational intervention, followed by a survey assessing COVID-19 knowledge and attitudes. Results: The results indicate significant improvements in knowledge and attitudes post-intervention, with both modalities proving effective. However, specific factors such as gender, political affiliation, and place of residence influenced COVID-19 attitudes and knowledge, emphasizing the importance of tailored interventions. Conclusions: Despite limitations, this study highlights the critical role of educational interventions in addressing vaccine hesitancy and promoting health equity within AI/AN communities. Moving forward, comprehensive strategies involving increased Indian Health Service funding, culturally relevant interventions, and policy advocacy are crucial in mitigating healthcare disparities and promoting health equity within AI/AN communities.

Background: The exacerbation of psychosocial problems among children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic necessitates an assessment of the long-term mental health impact of pandemic interventions. Focusing on both pandemic-related factors and demographic variables, such as gender and daily habits, an analysis was conducted to under-stand how these elements continue to affect young populations in the post-pandemic era. Methods: In April 2023, a comprehensive online survey was administered to families in South Tyrol, Italy, with children aged 7–19 years, to ensure age and gender representation. The survey included par-ent ratings and adolescent (11–19 years) self-reports using standardized instruments to measure the symptoms of mental health problems (Strengths and Difficulties Questionnaire, SDQ), anxiety (Screen for Child Anxiety Related Emotional Disorders, SCARED), and depression (Patient Health Questionnaire-2, PHQ-2). Statistical analyses included descriptive statistics, chi-square tests, and unadjusted odds ratios (ORs). Results: Of the 4,525 valid responses, 1,831 were self-reported by adolescents. Notable gender differences in mental health outcomes were identified, along with significant demographic predictors, such as age, single parenthood, parental mental health problems, and immigrant background. Negative effects were associated with reduced family climate and increased screen time, whereas physical activity showed beneficial effects. Proxy reports overestimated adolescents' mental health problems, whereas self-report tended to underestimate them. Conclusions: Persistent mental health problems and gender disparities high-light the need for a public health approach. This should include accessible support services, resili-ence building, targeted support for vulnerable families and gender-specific interventions.

Irrational belief is a product of complex personality traits and Machiavellianism Intelligence. The present study is conducted to trace the significance of predictive nature of personality characteristics and Machiavellianism Intelligence (Mach Intelligence) on irrational beliefs among chronically ill older people. The research method is cross-sectional with correlational design, purposive sampling with a total of 200 chronically ill older people aged between 40–60 years with disease type such as Systemic lupus erythematosus, Complicated Diabetes, Glomerulonephritis and Chronic Heart Failure. The analysis revealed that personality characteristics and irrational belief subscales such as worrying, rigidity, problem avoidance and Mach Intelligence are significantly positively correlated; however, Emotional irresponsibility has significant negative correlation with personality characteristics and Mach Intelligence. Gender differences revealed that males are high on all the subscales of personality characteristics, irrational beliefs (except emotional irresponsibility) and Mach Intelligence as com-pared to female chronically ill older people. Predictive analysis also revealed that overall personality characteristics explained a total of 67% variance in irrational beliefs. Moreover, Mach Intelligence predicts irrational beliefs. Future health related recommendations should be planned accordingly.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe adverse event that was first observed during the global vaccination campaign against SARS-CoV-2 infection, specifically in those receiving adenoviral vector-based vaccines for Coronavirus disease 2019 (COVID-19). VITT develops 4 to 42 days post-vaccination and is characterized by the development of platelet-activating anti-platelet factor 4 (PF4) antibodies, leading to thrombocytopenia and thrombosis at unusual sites. The rise in awareness and subsequent prompt recognition of VITT was paramount in reducing mortality. Moreover, as vaccination campaigns around the world continue, a better understanding of VITT not only has important clinical implications but is also crucial for future vaccine development. In this review, we summarize the clinical features, pathophysiology, and incidence rates of VITT as well as highlight other anti-PF4 antibody-mediated disorders of growing clinical significance.

We study here what can be learned from our experience with COVID-19 vaccination for an initially naïve population, that can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in early 2022, few people were still SARS-CoV-2-naïve. Almost all were vaccinated, infected, or often both. We review the evidence on COVID-19 vaccine effectiveness (VE), waning effectiveness over time, and what we should expect about VE and waning from a future pathogen. As a basis for our analysis, we conducted a PRISMA-compliant review of all studies on PubMed through August 15, 2022 reporting VE against four endpoints: any infection, symptomatic infection, hospitalization, and death, for the four principal vaccines used in developed Western countries (BNT162b2, mRNA1273, Ad26.CoV2.S, and ChAdOx1-S). The mRNA vaccines (BNT162b2, mRNA1273) had high initial VE against all endpoints but protection waned after approximately six months, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines initially outperformed the viral vector vaccines. A third “booster” dose, roughly six months after the primary doses, substantially reduced symptomatic infection, severe disease, and mortality, and in hindsight should be seen as part of the normal vaccination schedule.

Healthcare workers' stress, burnout, and job dissatisfaction were exacerbated by the Covid-19 pandemic, whose mid-term negative effects are still present. The aim of this study was to investigate in healthcare workers the effect of the dimensions of burnout (Psychophysical exhaustion, Relational deterioration, and Professional inefficacy) on Career satisfaction. These relationships were evaluated by considering the direct and mediated effects of Disillusion. For these purposes, the Link Burnout Questionnaire (LBQ) and the Career Satisfaction Scale (Occupational Stress Indicator - OSI) were administered to 295 healthcare professionals working at three Italian public hospitals in Cagliari, Italy. The analyses were conducted using the Partial Least Square Structural Equation Model (PLS-SEM) method. Findings highlight that healthcare workers were in a condition of work distress, high risk of burnout, and career dissatisfaction. Also recognized was the direct negative effect of burnout dimensions on career satisfaction. Finally, the mediated negative effect of Disillusion in the relationship between burnout and career satisfaction was identified. This study emphasizes the relevance of the dimension of Disillusion, and its “bright side” Fulfilment, in healthcare workers, specifically referring to the disregarded relationship between burnout and career satisfaction.

The main objective of this article was to evaluate the repercussions of the crises resulting from the COVID-19 pandemic and the war in Ukraine on changes in the European Union's reliance on energy raw material imports, particularly from Russia. Furthermore, several specific objectives were outlined: to ascertain the EU's energy balance and any alterations therein, to identify changes in the concentration of energy raw material imports among EU countries during the crises, to determine the level and fluctuations in energy raw material import dependence within the EU and individual member states throughout the crises, and lastly, to assess changes in the concentration of energy raw material imports from Russia in EU countries during the crises. The research encompassed all 27 EU Member States as of 31st December 2022, and the examination period spanned from 2010 to 2022. The information sources included relevant literature on the subject and data sourced from Eurostat. In conducting the analysis and presenting the data, several methodologies were employed, including descriptive, tabular, and graphical techniques. Additionally, quantitative measures such as the Gini structure concentration coefficient and concentration analysis through the Lorenz curve were utilized. During the COVID-19 pandemic, the EU experienced a slight reduction in dependence on energy raw material imports. However, this reduction was short-lived and mainly attributed to the decrease in energy demand caused by the pandemic. Conversely, the war in Ukraine had a substantial impact, leading to a notable surge in energy raw material imports as a result of stockpiling efforts and the need to safeguard against further disruptions in the energy market. Notably, the EU's reliance on energy imports from Russia was already considerable. Following the outbreak of the conflict in Ukraine, imports of oil, petroleum products, and solid fossil fuels experienced significant decline due to imposed sanctions. Nonetheless, restrictions on natural gas imports were comparatively less severe.

People must have particular personality traits and social resources, also known as health literacy, in order to access, comprehend, and use information to make decisions about their health. Patients' ability to engage in complex disease management and self-care is strongly related to their level of health literacy. It can help us stay healthy by preventing illness and effectively managing existing illnesses. People with low health literacy (LHL) may find it difficult to manage their condition and prevent illness, which may lead to increased use of healthcare services. Furthermore, LHL is associated with increased hospitalizations, increased use of emergency care, decreased use of preventative services, and a worsened ability to understand labels and health messages, a worsened state of health, higher mortality, and more expensive medical care.

COVID-19 and long COVID-19 vulnerabilities may be caused indirectly by albumin binding deficiency (ABD) which can be corrected by the correct administration of human serum albumin (HSA). The liver is the primary site of nutrient regulation and fluid volume maintenance, control of both is by changes to albumin concentration. In healthy subjects the HSA lymphatic nutrient pump (HSALNP) ensures continual pumping of nutrients from the liver are appropriately distributed to organs. Nutrients are delivered to cells according to the availability of binding to HSA. The HSALNP therefore maintains the correct nutrients and colloidal pressure balance in all tissues independently. In unhealthy tissues, following COVID-19 infection, the passage of HSA/nutrients through the interstitial spaces and lymph will be impeded. Fluid therapy into the periphery leads to dilution of essential nutrients attached to the protein-carriers such as albumin. The levels of albumin being charged by the liver with nutrients is critical in maintaining immune stability by maintaining nutrient support and colloidal pressure of cellular structures. The site of HSA binding by the liver is of great importance and direct infusion of albumin into the Hepatic Portal Vein is the most appropriate method of maintaining colloid pressure and cellular nutrient levels.

The review of previous works shows this study is the first attempt to analyse the lockdown effect using Natural Language Processing Techniques, particularly sentiment analysis methods applied at large scale. On the other hand, it is also the first of its kind to analyse the impact of COVID 19 on the university community jointly on staff and students and with a multi-country perspective. The main overall findings of this work show that the most often related words were family, anxiety, house and life. On another front, it has also been shown that staff have a slightly less negative perception of the consequences of COVID in their daily life. We have used artificial intelligence models like swivel embedding and the Multilayer Perceptron, as classification algorithms. The performance reached in terms of accuracy metric are 88.8% and 88.5%, for student and staff respectively. The main conclusion of our study is that higher education institutions and policymakers around the world may benefit from these findings while formulating policy recommendations and strategies to support students during this and any future pandemics.

G-protein-coupled receptors (GPCR) belong to a large family of molecules eliciting different responses to a variety of signaling molecules. These receptors participate in various physiologic pathways such as metabolism, growth, immune responses, inflammation, vision, taste, olfaction, neurotransmission and even and pathologic responses including chronic inflammatory and vascular diseases. Receptors contributing to the biological responses of renin-angiotensin system (RAS) are members of GPCR family. COVID-19-induced inflammatory cascade has been attributed to acute ACE2 downregulation and imbalance of proinflammatory ACE/AngII/AT1R and anti-inflammatory ACE2/angiotensin (1-7)/Mas axes in favor of the former. Some of the receptors contributing to activities of proteins in RAS including AT1R, AT2R and Mas receptors are members of GPCR family. It is notable that these receptors induce their effects both through G protein and β-arrestin pathway; the former exerts temporary and the latter more sustained effects. In addition to the imbalance of GPCR responses contributing to RAS activities, it has been suggested that SARS-CoV2 pathogenesis might be attributed to the activation of GPCRs or modulating G-proteins involved in adenosine-CFTR regulation system and epithelial Na channel function.This article includes a minireview about the physiological functions of GPCRs and their contribution to COVID-19.

Background: The epidemiological situation generated by COVID-19 has cast into sharp relief the delicate balance between public health priorities and the economy, with businesses obliged to toe a line between employee health and continued production. In an effort to detect as many cases as possible, isolate contacts, cut transmission chains and limit the spread of the virus in the workplace, mass testing strategies have been implemented in both public health and industrial contexts to minimize the risk of disruption in activity. Objective: To evaluate the economic impact of mass workplace testing strategy as carried out by a large automotive company in Catalonia in terms of health and healthcare resource savings. Methodology: Analysis of health costs and impacts based on the estimation of mortality and morbidity avoided because of screening and the resulting savings in healthcare costs. Results: The economic impact of the mass workplace testing strategies (using both PCR and RAT tests) was approximately €10.44 per test performed or €5,575.49 per positive detected. 38% of this figure corresponds to savings derived from better use of health resources (hospital beds, ICU beds and follow-up of infected cases), while the remaining 62% corresponds to improved health rates due to avoided morbidity and mortality. In scenarios with higher positivity rates and a greater impact of the infection on health and the use of health resources, these results could be up to ten times higher (€130.24 per test performed or €69,565.59 per positive detected). Conclusion: In the context of COVID-19, preventive actions carried out by the private sector to safeguard industrial production also have concomitant public benefits in the form of savings in healthcare costs. Thus, governmental bodies need to recognize the value of implementing such strategies in private settings and facilitate them through, for example, subsidies.

Research on the chemical mechanism and reciprocal behavior of the coronavirus relate to living organisms, engaging in the give and take of electrochemical mediators, is a very important, controversial and vital issue. What we should accept is the chemical identity of this scenario, and not preferably a characteristic of a biological system. This chemical reaction should be familiar, referring to the theory of chemical pathways involved in DNA/proteins in the body against aggressive guests (such as viruses). From the point of view of a chemist, this simple reaction is nothing more than an oxidation-reduction reaction (redox-stress signaling) which conducted and carried out by coronavirus in a biointerface medium. Thereby, oxidizing as well as reducing reagents should be very constructive, promoting development in such chemical process. We understand redox reactions as switchable thiol/disulfide exchanges (formation and cleavage of inherent disulfide bonds), then, we can hugely profit from redox-responsive nano-surfaces equipped with multiple new ionic and covalent interactions. This game-changing idea can substantiate by surface modified-nanoparticles to play powerful roles in synthesis of nano oxidizers as well as reducing agents in nanomedicine. Chemists and pharmacists must then explore new thoughts and present modern experiences/approaches of preparation nanoparticles and nanocomposites to create novel vaccines as well as coronavirus drugs. In this regard, this experience can also be so helpful for HIV/AIDS, which is caused by viruses.

We present a model of infection dynamics that might explain slower approaching the herd immunity during the covid-19 epidemy in Sweden than it was predicted by a variety of other models; see graphs Fig. \ref{GROWTH2}. The new model takes into account the hierarchic structure of social clusters in the human society. We apply the well developed theory of random walk on the energy landscapes represented mathematically with ultrametric spaces. This theory was created for applications to spin glasses and protein dynamics. To move from one social cluster (valley) to another, the virus should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider linearly increasing (with respect to hierarchy's levels) barriers. This structure of barriers matches with a rather soft regulations imposed in Sweden in March 2020. In this model, the infection spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This model's feature matches with the real situation during the covid-19 epidemy, with its cluster spreading structure. Clusters need not be determined solely geographically, they are based on a number of hierarchically ordered social coordinates. The model differs crucially from the standard models of spread of disease, such as the SIR-model. Our model describes such a specialty of spread of covid-19 virus as the presence of ``super-infectors'' who by performing a kind of random walk on a hierarchic landscape of social clusters spreads infection. In future, this model will be completed by adding the SIR-type counterpart. But, the latter is not a specialty of covid-19 spreading.

COVID-19 has affected 212 countries around the world, killing nearly 300,000 and infecting more than 4.4 million by May 14, 2020. Bangladesh, a South Asian low-middle-income economy, has experienced a demographic and epidemiological transition with rapid urbanization and a gradual increase in life expectancy. It is the seventh most populous country in the world and population of the country is expected to be nearly double by 2050. The increasing burden of communicable diseases in Bangladesh can be attributable to rapid urbanization and nearly 50% of all slum dwellers of the country live in Dhaka division. In 2017, National Rapid Response Team of IEDCR investigated 26 incidents of disease outbreak. The joint survey of the Power and Participation Research Centre and BRAC Institute of Governance and Development reveals that per capita daily income of urban slum and rural poor drops by 80% due to present countrywide shutdown enforced by the government to halt the spread of Covid-19. 40%-50% of these population took loans to meet the daily expenses. However, the country has just 127,000 hospital beds, 91,000 of them in government-run hospitals. Researchers say, the country’s economy is economy is losing BDT 33 billion every day from its service and agriculture sectors during the nationwide shutdown.

Since severe acute respiratory syndrome coronavirus (SARS-CoV)-2 emerged in December 2019, significant research has been conducted around the world to understand the virus- and vaccine-generated immune response, and to identify the drivers of severe coronavirus disease 19 (COVID-19). Although viral tropism is largely limited to the respiratory tract, SARS-CoV-2 infection can lead to severe COVID-19 disease, which is characterized by multiorgan failure and permanent cognitive disorders. The combined effects of virus-mediated inhibition of host antiviral mechanisms and the recognition of pathogen-associated molecules by pattern recognition receptors (PRRs) are the main drivers in the pathogenesis of severe disease. The innate immune system constitutes the first line of defense against SARS-CoV-2 by limiting the entry of the virus into the host cell, suppressing viral replication, detecting virus-infected cells, and accelerating the formation of the adaptive immune response. The adaptive immune system is composed of two basic cells, B and T cells, which serve different but complementary functions in viral infections. Although the critical role of adaptive immunity in clearing SARS-CoV-2 infection is well known, its function in the development of virus-induced immunopathogenesis remains poorly understood. The basic characteristic of the humoral immune response is the creation of specific antibodies to each foreign antigen encountered. Antibodies that sense pathogens are classified as neutralizing antibodies (nAbs) and non-neutralizing antibodies (non-nAbs) based on their capacity to neutralize pathogens and inhibit membrane fusion. While nAbs exert their activities by blocking ACE2-dependent viral entry into host cells and neutralizing pathogens, the functions of non-nAbs are often undetectable. The level of anti-SARS-CoV-2 antibodies in serum and mucosal tissues varies with the stage and severity of the COVID-19 infection. Although current COVID-19 vaccines elicit robust antibody responses, this effect decreases over time, due to the weakening of immunity and the emergence of novel variants that evade the antibody response, such as Delta and Omicron. SARS-CoV-2 may evade host innate immune surveillance by minimizing host recognition and interfering with cellular immune signaling. In this review article, the central role of host immune responses in the pathogenesis of COVID-19 and the effectiveness of COVID-19 vaccines, as well as the immune evasion strategies of SARS-CoV-2 are discussed in detail in the light of novel knowledge.

Abstract: Thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge for their delivery wherever needed. Freeze-drying of viral vectored vaccines is a prom-ising approach but remains challenging due to the water removal process from the outer and in-ner parts of the virus. In the case of enveloped viruses, freeze-drying induces increased stresses on the envelope, which often leads to inactivation of the virus. In this study, we design a method to freeze-dry a recombinant Vesicular Stomatitis Virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. Since the envelope of VSV is composed of 50% lipid and 50% protein, the formula-tion study focused on both the protein and lipid portions of the vector. Formulations were pre-pared primarily using sucrose, trehalose, and sorbitol as cryoprotectants; mannitol as a lyopro-tectant; and histidine as a buffer. Initially, the infectivity of rVSV-SARS-CoV-2 and cake stability were investigated at different final moisture contents. High recovery of the infectious viral titer ( 0.5 to 1 log loss) was found at 3-6% moisture content with no deterioration of the freeze-dried cakes. To further minimize infectious viral titer loss, the composition and concentration of the ex-cipients were studied. An increase from 5 to 10% of both cryoprotectants and lyoprotectant, to-gether with the addition of 0.5% gelatin, resulted in the improved recovery of infectious virus titer and stable cake formation. Moreover, the secondary drying temperature of the freeze-drying pro-cess showed a significant impact on the infectivity of rVSV-SARS-CoV-2. The infectivity of the vector declined drastically when the temperature was raised above 20°C. Throughout a long-term stability study, formulations containing 10% sugar (sucrose/trehalose), 10% mannitol, 0.5% gelatin, and 10 mM of histidine showed satisfactory stability for six months at 2-8°C. The development of this freeze-drying process and the optimized formulation minimizes the need for a costly cold chain distribution system.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

Background: Antiphospholipid antibodies (aPL) are a laboratory criterion for the classification of antiphospholipid syndrome (APS), and are known to cause clinical symptoms: vascular thrombosis or obstetric complications. It is suggested that aPL may be associated with thromboembolism in severe COVID-19 cases. Aim: to combine clinical data with aPL findings at 4 time points (admission, worsening, discharge, 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. Methods: current and past history of thrombosis and obstetric complications; aPL determined at 4 time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG or IgA isotypes. Results: 111 patients with COVID-19 pneumonia were enrolled. During hospitalization, 7 patients died, 3 of them due to pulmonary artery thromboembolism (none was aPL positive). Only one of the five who developed pulmonary artery thrombosis was aPL positive. Of 9/101 patients with a history of thrombosis, 5 had arterial thrombosis and none was aPL positive at admission and follow-up; 4 had venous thrombosis and one was aPL positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPL positive at discharge only, compared to 26.1% without history of thrombosis (p=0.05). Conclusions: aPL were not associated with fatal outcomes and vascular thrombosis; aPL were transiently positive in more than half of patients with a history of thrombosis.

Several vaccines against COVID -19 have been developed and licenced to enhance the immune response against SARS-CoV-2. Similarly, infection with SARS-CoV-2 before vaccination has been shown to provide significant protection against severe infection and hospitalisation. The aim of this study was to investigate the effect of three doses of Sinopharm vaccine and SARS-CoV-2 infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies and interferon γ. Our results showed that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while endocrinological diseases decreased the level of neutralizing antibodies and anti-N-IgG antibodies, suggesting that these diseases alter the effect of vaccine immunity. In addition, there was a significant decrease in anti-S1 IgG levels 6 months and in anti-N IgG levels 18 months post-infection, while neutralizing antibody and interferon γ levels were constant at 3, 6 and 18 months post-infection. Therefore, our results confirm the importance of hybrid immunity as the strongest and most durable compared to exclusively natural or vaccine-induced immunity. Significant positive correlations were found between humoral and cellular immunity markers: neutralizing antibodies, anti-S1 IgG, anti-N IgG and interferon γ, indicating a unique coordinated response specific to COVID-19.

Background:Although highly strict social distancing and viral spread protection guidelines are in force, the reported numbers of COVID-19 cases across the world are still increasing. This indicates that we are still unable to completely understand the transmission routes of SARS-CoV-2. One of the possible routes that can play a significant role is the fecal-oral transmission since SARS-CoV-2 can replicate in the intestines as demonstrated by isolation of infectious virus from fecal samples of COVID-19 cases. Scope and approach:In this review, we compare the characteristics of SARS-CoV-2 with the distinctive characteristics of enteric foodborne viruses. We also discuss and respond to the arguments given in some reports that downplay the importance of foodborne transmission route of SARS-CoV-2. Key findings and conclusions:Enteric viruses such as human noroviruses (HuNoVs) and hepatitis A virus (HAV) are known to transmit through foods such as fresh produce and berries, leading to frequent multistate foodborne disease outbreaks all over the world. SARS-CoV-2 was found to share four distinctive characteristics of foodborne viruses that allow them to transmit through foods. This similarity in characteristics, recent report of detecting SARS-CoV-2 particles from frozen food packages in China, and recent suspected foodborne COVID-19 case in New Zealand, indicate that foodborne transmission of SARS-CoV-2 is more evident than previously thought possible. To support or deny this route of transmission, urgent research needs to be undertaken to answer two primary questions and many secondary ones as described in this review.

Reciprocal Personal/Public Protection (RPPP) featured with source control is introduced, Mask Discriminating Mouth and Nose (MDMN) is employed to serve the purpose, which includes polymer based mouth cover with optional nose cover. The new knowledge that mouth is a primary, active and dominant source of the virus has been well established, which is the base of MDMN. Source classification and related source control tools are discussed, mouth cover is recommended as the tool prioritized to use. Liquid droplets is identified as a hard issue related to mask, liquid droplets, mask fitting, comfort and facial recognition constitute real challenges of mask in addition to efficiency, All of these have been addressed with MDMN. Comparisons between MDMN and masks/face covering are taken on four aspects: efficiency and efficacy, tolerance and comfort, cost and waste, and civil rights and public interest. Mouth cover is recommended to replace the face covering and act as both a personal tool and a public utensil, mouth cover with nose cover can provide better protection than N95 etc. RPPP with MDMN, could be an alternative for lockdown, a parallel strategy to vaccine, and a collectively living way during the pandemic era. MDMN, featured with high efficiency protection, high degree comfort, easy wearing, tight-fitting, easy facial recognition & communication, reusability, cost-effective, environment friendly and scale manufacturing more readily and widely etc., is a simple and sustainable solution, which is essential for ordinary people to keep wearing it properly for protection.

In Kenya, millions of children have limited access to nurturing care. With the COVID-19 pandemic, it is anticipated that vulnerable children will bear the biggest brunt of the direct and indirect impacts of the pandemic. This review aimed to deepen understanding of the effects of COVID-19 on nurturing care from conception to four years of age, a period where the care of children is often delivered through caregivers or other informal platforms. The review has drawn upon the empirical evidence from previous pandemics and epidemics, and anecdotal and emerging evidence from the ongoing COVID-19 crisis. Multifactorial impacts fall into five key domains: direct health; health and nutrition systems, economic, social and child protection, and child development and early learning. The review proposes program and policy strategies to guide the re-orientation of nurturing care, prevent the detrimental effects associated with deteriorating nurturing care environments, and support the optimal development of the youngest and most vulnerable children. These include the provision of cash transfers and essential supplies for vulnerable households, and strengthening of community-based platforms for nurturing care. Further research on COVID-19 and the ability of children’s ecology to provide nurturing care is needed, as is further testing of new ideas.

To predict how the COVID-19 pandemic progresses, we developed a systematic method for predicting disease outcomes. In the method, we evaluate how personal disease outcomes are mainly affected by viral concentration and exposure time and four defense mechanisms: human innate immunity/host response, acquired immune response, inflammation resolution and micro circulation, and the available space in the thorax cage. By considering how pandemic measures affect viral exposure and those mechanisms, we found many pandemic measures are misused or abused to deliver long-term adverse impacts. We noted that lifestyles have been changed as a result of movement restriction measures. By using the method, we found that altered lifestyles are predicted to raise infection rate, disability and death risks in the future. We show that a person can use personal, environmental, emotional factors to reduce infection rate and death risk. To prove the validity of this finding, we extensively examined medical research models, holistic and reductionist models, epidemiological models, disease risk factors, etc, and found that population methods are unfit for studying holistic health, statistical population does not exist in most clinical trials, mathematical models were misused for studying disease properties for a population, mathematical equations for modeling personal diseases are beyond human ability to solve, statistical models are misused, population-derived treatments are inherently dangerous to patients, vaccines have limited benefits due to unique lung structure and rapid RNA mutation, and immune system damage is caused by fast viral replication rate. We found that altering biological properties to improve the defense mechanisms could prevent a super majority of deaths and prevent the virus from reaching a point to damage the immune system. For vulnerable persons, such measure is a viable strategy for surviving from the pandemic. As a whole, holistic personalized medicine is more powerful than population-based reductionist treatment by one to several orders of magnitudes. We urge people do their parts to force the medical establishment to abandon population treatment models that are responsible for failure of medicine and dissemination of misleading and factually wrong information on the effectiveness of medical treatments.

The spread of the infection caused by the new coronavirus SARS-CoV-2 (COVID-19) became pandemic on March 11, 2020. From the time of the first cases (in November 2019, Wuhan, China), to date, a large number of COVID-19 observations have been accumulated in different age groups of patients both in China and abroad. Published scientific data allows us to conclude that children suffer from COVID-19 much less often than adults and tolerate the disease in a milder form, often appear to be asymptomatic. There is currently no final answer why children are less susceptible to this virus; however, scientists are increasingly inclined to consider a complex effect of the immune response and components of the renin-angiotensin system (RAS), which according to recent studies affects not only the cardiovascular system, but is also responsible for the activation of inflammatory reactions. A hypothesis of genetic predisposition to the development of severe forms of COVID-19 has recently been made. We conducted a search for publications in the databases and showed current scientific ideas about COVID-19 pathogenesis and factors influencing the disease development in childhood. Childhood immunity may have several protective features against SARS-CoV-2: immaturity of particular elements of the innate immune response, constitutional lymphocytosis with a shift towards anti-inflammatory Th2-response, as well as "trained" immunity. The influence of renin-angiotensin system reactions in this review is shown from two perspectives: expression of ACE2 receptors and polymorphisms of certain genes of this system. It was established that ACE2 transmembrane protein is not only the entry point for the virus but also plays a regulatory role, turning the pro-inflammatory vasoconstrictor angiotensin II into anti-inflammatory angiotensin (1-7), which has vasodilating properties. Higher ACE2 content in children compared with adults helps maintain balance in the renin-angiotensin system and prevents the development of complications. It was also shown that the presence of certain genetic polymorphisms (AGTR1, AGTR2, ACE2, ACE) could determine the imbalance inside the RAS, leading to more pronounced reactions of alveolocytes, vascular endothelium and smooth muscle fibers in response to SARS-CoV-2 infection due to a shift towards vasoconstrictor, proliferative and profibrotic mechanisms.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

The nonlinear dynamics exhibited by aircraft flying at high angle of attack (AOA) pose great challenges to the design of flight control. The control design based on nonlinear dynamic inversion (NDI) is to reversely find the required control input based on the current nonlinear dynamics of the aircraft and the control objectives to be achieved. Since it is derived from the nonlinear dynamics of the aircraft, a single NDI controller can cover the entire flight envelope without the need for controller switching or gain scheduling. This paper employs the layered structure of the flight control loop to implement the NDI controller through the combination of aerodynamic control and thrust vectoring control (TVC). The resulting NDI controller is applied to an experimental F-16 installed with TVC to verify its high AOA maneuverability in the post-stall region. The verification simulation shows that the experimental F-16 under the NDI control can effectively track the high AOA command and successfully demonstrate the Herbst maneuver by performing the heading reversal with 70° AOA.

The seismic events of 2015 in Nepal exposed the challenges associated with constructing earthquake-resistant 2-story self-built stone masonry structures in high-elevation rural regions, especially post-disaster. The Department of Urban Development and Building Construction (DUDBC) provided designs that failed to preserve the local architectural landscape and craftsmanship while adding unfamiliar knowledge and technology. To address the challenges related to architecture, structure, and socio-economic concerns in designing and implementing post-earthquake houses, a need-based building development framework is required for standardized practice. This study presents a novel framework to assess, design, and implement a self-built house after a disaster, consisting of five stages: 1) post-disaster problem assessment, 2) need identification, 3) material selection, 4) design development, and 5) validation and implementation. Based on this framework, we proposed a novel gabions building construction technology for two-story stone masonry structures that effectively mitigate post-disaster challenges such as logistic, resilience, and socioeconomic aspects while improving disaster resiliency specifically in the high-elevation rural areas of Nepal. The proposed two-story gabion building preserves architectural values, enhances structural integrity, and provides cost-effectiveness when compared with its DUDBC peer models while providing much-needed relief to the vulnerable community. The proposed resilient house, G- 2.1, utilizes locally sourced materials and craftsmanship, and innovative gabion technology that ensures affordability and facilitates knowledge transfer. The contribution of this study includes a development framework and a two-story gabions house that is most suitable for self-built post-disaster reconstruction and resilient to local architecture and socio-economic conditions while providing structural integrity and safety.

This perspective discusses the ongoing real-world practice using nitazxoanide, NSAIDs and/or azithromycin (Kelleni’s protocol) to manage the evolving manifestations of SARS CoV-2 Omicron EG.5.1, its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt. These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever, persistent severe cough, change of voice, loss of taste and smell, epigastric pain, nausea, vomiting, diarrhea, generalized malaise and marked bone aches in adults including the high risk groups. It’s suggested that the ongoing SARS CoV-2 evolution is continuing to mostly affect the high risk groups of patients, to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts. We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients, at least until the currently encountered surge of infections subsides.

Analysis of liquid biopsy samples can reveal a wealth of molecular as well as cellular entities circulating in various body fluids. These entities include circulating tumor cells, circulating cell-free and tumor DNA, RNA, and proteins. Detection and characterization of this genetic and proteomic material can provide crucial information on tumor characteristics, including its heterogeneity, biology, tumor progression, staging, associated gene mutations and the course of therapy. The increased use of liquid biopsy in clinical oncology offers in non-invasive manner easier tumor sampling and continuous monitoring of the disease evolution through repetitive sampling from cancer patients. The continuous monitoring offered by this method is highly relevant to the assessment of a given therapeutic regime and early detection of markers associated with possible drug resistance, which may develop in the course of the therapy. The use of proteomic approaches, including mass spectrometry-based proteomics for the analysis of biofluids extends for over three decades, yet only in the last few years such methods have found their way to clinical oncology. The non-invasive nature of liquid biopsy and the simple procedures for sample collection made this approach far more attractive than the traditional and well-established tissue biopsy. Such preference becomes more practical in the analysis of solid tumors, particularly in pediatric population. In this review we discuss some works on the emerging role of liquid biopsy analyses in clinical oncology, and how such use allows a better understanding of diagnosis, prognosis, disease evolution and response to therapy of various forms of cancer. We also discuss the role of MS-based methods in the characterization of post-translational modifications of proteins circulating in liquid biopsies.

This article describes the POTENTIALS project, which aimed to develop business models for the reuse of former industrial and mining sites in different regions. The project focused on the creation of eco-industrial parks as a result to enable sustainable energy production and reduce waste and pollution. A key aspect was the Territorial Impact Assessment (TIA), a new and complex policy assessment tool. Therefore, the TEQUILA (Territorial Efficiency Quality and Identity Layer Assessment) approach is used to describe the TIA and emphasizes its application in assessing the impact of EU policies and projects on territorial cohesion. It underlines the need for a differentiated understanding of the regional characteristics and potential impacts of policies; and stresses the importance of regionalized impact models for the assessment. Furthermore, the process and results of applying the TEQUILA methodology to assess the territorial impact of different scenarios of business models within the POTENTIALS project is given.

Numerous genes expression lead to inflammation in the individuals’ lungs that have chronic obstructive pulmonary disease (COPD) may be affected by epigenetic alteration. Important epigenetic processes include methylation of DNA and different histones post-translational changes, including ubiquitination, phosphorylation, methylation, SUMOylation and acetylation. Smoking can trigger the enzymes that control these epigenetic changes. According to the majority of publications, both environmental and genetic variables have a substantial role in the development of COPD. Although, the information about COPD epigenetic is not much but, a better perception of the disease pathophysiology and identifying new markers to create novel therapeutics for patients can be achieved via a better understanding of the epigenetic processes involved.

Lattice and code cryptography can replace existing schemes such as Elliptic Curve Cryptography because of their resistance to quantum computers. In support of public key infrastructures, the distribution, validation and storage of the cryptographic keys is then more complex to handle longer keys. This paper describes practical ways to generate keys from physical unclonable functions, for both lattice and code based cryptography. Handshakes between client devices containing the PUFs and a server are used to select sets of addressable positions in the PUFs, from which streams of bits called seeds are generated on demand. The public and private cryptographic key pairs are computed from these seeds together with additional streams of random numbers. The method allows the server to independently validate the public key generated by the PUF, and act as a certificate authority in the network. Technologies such as High performance computing, and graphic processing units can further enhance security by preventing attackers to make this independent validation when only equipped with less powerful computers.

The livelihood of most of the fishers in Indian Sundarbans is dependent on Penaeus monodon post larvae fishing. These post larvae collectors are socially backward lacking economic security. The activity of collecting Penaeus monodon post larvae for rearing in aquaculture, destroy other aquatic species. Many other juveniles of shellfish and fin fish were destroyed in the process of collection of Penaeus monodon post larvae. The removal of juveniles before they reach maturity disturbs the ecological chain by hampering breeding processes and may cause extinction of some fish species in the long run. The present study is an attempt to estimate the economic value of juveniles destroyed in the collection of (Penaeus monodon) post larvae. In total 32 species were identified in P.monodon the post larval by-catch. The economic loss is assessed based on estimating biomass by taking a length-weight relationship from published literature. Further, the paper illustrates how does a profit enterprise is linked with natural resource exploitation. The paper explores government policy and nature conservation issues for social justice and effective conservation.In conclusion, suggestions are given to reduce the burden of livelihood on natural resources to the extent of exploitation and to strengthen institution and policy-making considering socio-ecological vulnerabilities of the area.

The objective of the study was to report the health-related quality of life (HRQOL) following road traffic accidents (RTAs) among children. A community-based survey using EuroQol five-dimension questionnaire (EQ-5D-5L) in Hindi was used to collected data from community. The survey included 2620 households from urban and rural areas of Ujjain, India. From these households 229 children aged 5–18 years with a history of RTA in the last 1 year were identified, with 27%, 63%, and 10% children reporting mild, moderate, and severe injury based on length of hospitalization. Motorcycles, bicycles, and pedestrians constituted most RTAs. Helmet use was low (12%). EQ-5D-5L revealed that the most severe and extreme problem was pain and discomfort, whereas the least severe problem was usual activity and self-care. The most common (65%) injuries were either abrasion or fracture and dislocation. EQ-5D-5L severity index was maximum (mean 72) for lower extremity injuries. The results of the present study highlight the ability and requirement for quality of life measurement using EQ-5D-5L among children post-RTA.

For centuries, crop plants have represented the basis of the daily human diet. Among them, cereals and legumes, accumulating oils, proteins and carbohydrates in their seeds, distinctly dominate modern agronomic practice. Indeed, these plants play an essential role in the food industry and fuel production. Therefore, the seeds of crop plants are intensively studied by food chemists, biologists, biochemists, and nutritional physiologists. Accordingly, not only seed development and germination, but also age- and stress-related alterations in seed vigor, longevity, nutritional value and safety can be addressed by a broad panel of analytical, biochemical and physiological methods. Currently, functional genomics is one of the most powerful tools, giving direct access to characteristic metabolic changes, accompanying plant development, senescence and response to biotic or environmental stress. Among individual methodological platforms, proteomics represents one of the most effective ones, giving access to cellular metabolism at the level of proteins. Here we discuss the main methodological approaches employed by seed proteomics in the context of physiological changes related to seed development, ageing and response to environmental stress.

Objective: To analyze prevalence of tuberculosis among the people who presented PIMS with complaints of fever, cough, difficulty in breathing during COVID pandemic.Study Design: Retrospective/ Cross-sectional study.Place and Duration: Department of Radiology, Pakistan Institute of Medical Sciences, Islamabad. 2020-2023. Methods: Total 17121 patients who presented PIMS during COVID pandemic with complaints of high grade fever, cough, difficulty in breathing ,were included in this study. Following the acquisition, the HRCT scans were conducted by a skilled and experienced technician and researcher, utilizing GE Healthcare equipment for HRCT Chest procedures. The scans covered the lung apices to the bases and were executed with maximal inspiration, employing a CT scanner from Toshiba Aquilion. Frequency of TB among all cases was recorded. SPSS 21.0 was used to analyze all data.Results: This study incorporated a total of 17,121 patients, comprising 9,961 (58.1%) males and 7,160 (41.8%) females. The mean age of the enrolled cases was 49.11±7.67 years, demonstrating consistency with the findings of a prior study [33]. This study also examined the prevalence of Tuberculosis in different years based on imaging findings of HRCT chest as follows: in 2020, 582 cases out of 2,450, equivalent to 23.7%; in 2021, 2,377 cases out of 9,584, equivalent to 24.8%; in 2022, 1,099 cases out of 3,913, equivalent to 28.1% and in 2023, 295 cases out of 1,174, equivalent to 25.1%. The average prevalence of TB cases from 2020 to 2023 was determined to be 4,353 cases out of 17,121, which is equal to 25.42%.Conclusion: As per the National Tuberculosis Program (NTP) in Pakistan, the prevalence rate of tuberculosis stands at 340 cases per 100,000 population, equivalent to 0.34%. However, our study reveals an exceptionally high frequency of TB cases. Specifically, the prevalence of Tuberculosis in 2020 was 23.7% (582 out of 2,450), in 2021 it was 24.8% (2,377 out of 9,584), in 2022 it surged to 28.1% (1,099 out of 3,913), and in 2023 it was 25.1% (295 out of 1,174). The average prevalence of TB cases over the period from 2020 to 2023 was calculated at 25.4% (4,353 out of 17,121). Consequently, our findings suggest the presence of a substantial tuberculosis burden in Pakistan, equating to a TB Tsunami in Pakistan.

Background: The interruption of the activity of the population-based organized colorectal cancer (CRC) screening programs due to the COVID pandemic may have affected their results in terms of detection of preneoplastic lesions and CRC. We evaluated the impact of the COVID pandemic on the delays, participation, adherence to colonoscopies, lesions detected, and CRC stage at di-agnosis in a CRC screening program. Methods: We analyzed all the invitations between January 1, 2019, and December 31, 2021. We defined the pandemic period as the period after March 12, 2020. We calculated the delay intervals (successive and all rounds), the rates of participation, adherence to colonoscopy after a positive fecal immunochemical test (FIT), and the diagnostic yield of colonoscopy, specifically CRC and colorectal neoplasia (CRC and/or adenoma), as well as CRC stage at diagnosis. Results: In the period analyzed, 976,187 invitations were sent (61.0% pandemic), 439,687 FIT were returned (62.4% pandemic) and 23,092 colonoscopies were performed (59.1% pandemic). Colon-oscopies were normal in 7,378 subjects (32.4%) and a CRC was detected in 916 subjects (4.0%). In successive rounds, the delay increased significantly seven months during the pandemic period (p<0.001). In all the invitations, the delay from the invitation to the colonoscopy increased sig-nificantly by 8 days (p<0.001). Once adjusted for the confounding variables, participation in the screening program increased significantly (OR=1.1; 95% CI=1.09-1.11), with no changes in the adherence to colonoscopy (OR=0.9; 95% CI=0.8-1.0). We found no differences in the diagnostic yield of colonoscopy in terms of CRC (OR=0.90; 95% CI=0.78-1.02) or colorectal neoplasia (OR=0.98; 95% CI=0.92-1.03) detection. Finally, we found no differences in CRC stage at diagnosis (p=0.2). Conclusions: Although the interruption of the CRC screening program due to the COVID pan-demic increased the delays, it did not reduce participation, adherence to colonoscopy, or the di-agnostic yield of colonoscopy.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

In Los Angeles, at one point, the Covid-19 testing positivity rate was 6.25%, or one in sixteen. This translates to, on average, one in sixteen specimens testing positive and the vast majority testing negative. Usually, we run sixteen tests on sixteen specimens to identify the positive one(s). This process can be time consuming and expensive. Since a group of negative specimens pooled together for testing will produce a negative result, one single test could potentially eliminate many specimens. Only when the pooled specimen tests positive do we need further testing to identify the positive one(s). Based on this concept, we designed a strategy that will identify the positive specimen(s) efficiently. Assuming one in sixteen specimens is positive, we find that only four tests are needed. Furthermore, we can run them simultaneously, saving both resources and time. Although, in the real world, we cannot make the assumption of only one positive specimen, the same strategy works with slight modification and proves to be much more efficient than the conventional testing. Our strategy returns an answer 48% of the time in four tests and one time cycle. Overall, the average number of tests is seven or eight depending on the follow-up testing, and the average time cycle is about one and a half.

Introduction: The COVID-19 pandemic highlighted the necessity for rapid, efficient testing at large-scale events. Developing rapid and efficient testing methods was critical, especially for events with a high risk of virus spread. The queueing theory offers a powerful tool to manage the flow of people through testing centers. This study uses the M/M/c model to examine how different floor plan configurations impact the efficiency of RADT testing centers. Aim of the study: This research applies queueing theory to optimize the Rapid Antigen Diagnostic Test (RADT) processes at mass gatherings. The study uses the M/M/c queueing model to evaluate the dynamics of RADT centers configured in U-shaped and straight-line layouts. The primary goal is to assess the feasibility of using RADTs efficiently at events and mass gathering entrances, aiming to enhance throughput and minimize wait times. Methodology: The study involved 500 healthy participants, managed by medical staff across a U-shaped and a straight floor plans. Agile management techniques were employed to enhance operational efficiency. The process stages included queue number issuance, registration, sample collection, sample mixing, and results dissemination. Results: Both floor plans enabled the completion of RADT screening in approximately 2 minutes per participant. The U-shaped layout slightly outperformed the straight-line setup in efficiency, demonstrating its effectiveness in optimizing the testing process. Conclusion: This study confirms the feasibility of implementing Rapid Antigen Diagnostic Test (RADT) processes at mass gatherings. It was found that the U-shaped floor plan configuration is particularly effective, indicating its potential suitability for future mass testing scenarios.

Introduction: In Part II of this three-part series, we expose techniques that can be used by the U.S. Centers for Disease Control and prevention (CDC) and Food and Drug Administration (FDA) to manipulate and throttle the Vaccine Adverse Event Reporting System (VAERS), a vaccine safety monitoring system open to the public. The U.S. government’s recommendation of COVID-19 vaccines during pregnancy was more a product of propaganda than of science and plagued with conflicts of interest. The extreme breach of COVID-19 vaccine pregnancy complication safety signals documented in VAERS cannot be disregarded or concealed. As a result, CDC/FDA are moving to closed, government captured platforms, including V-safe, Vaccine Safety Datalink (VSD) system, and the Biologics Effectiveness and Safety (BEST) system. Public transparency of adverse events following COVID-19 vaccination in pregnancy should be increased, not thwarted. Methods: In Part I the CDC/FDA Vaccine Adverse Event Reporting System (VAERS) database was queried from January 1, 1990, to April 26, 2024 for adverse events (AEs) involving pregnancy complications following vaccination. In Part II we investigate tactics discovered in VAERS that concealed vaccine injuries and deaths. Conflicts of interest, as well as specific communications and publications from the CDC/FDA and the New England Journal of Medicine (NEJM) are analyzed. Results: Of all VAERS AE reports, 8.47% (138,983) of COVID-19 reports had no vaccination date and thus were missing from the data presented in Part I of this series. We unconcealed data presented in Part I of this series to include VAERS case reports that were excluded when using standard queries because of an “unknown vaccination date”. The unconcealed data in the 37 AE cases reported in this study (Part II) ranged from 0 - 38% with a mean of 8.2% (standard deviation 9.7%) and the significant breaches of VAERS safety signals in Part I of this series were largely underestimated. Another method of concealing vaccine associated AEs is to exclude the specific vaccine type rendering it as an “unknown vaccine type”. “Unknown vaccine type” has logarithmically increased since the rollout of the COVID-19 vaccines in 2021, ranging from 1 to 400 cases between 1990 to 2018 to 11,461 cases in 2021. CDC/FDA granted $67 million via a Cooperative Agreement grant to Massachusetts Department of Public Health (MDPH) between July 1, 2019, to June 30, 2025. MDPH then made subawards under this grant to 21 influential public and private health and civic organizations, including NEJM’s owner, Massachusetts Medical Society (MMS). As one of the subawardees under the grant, MMS as owner of NEJM received over $426,000 in federal HHS/CDC grant money from 2019 to 2020 for “public health and medical emergency preparedness projects”. Conclusions: CDC/FDA has failed to capture and account for a significant number of AE case reports following COVID-19 in VAERS by a variety of techniques in an apparent attempt to sanitize the data. CDC’s Rochelle Walensky and NEJM’s Editor-in-Chief Eric Rubin pushed novel untested COVID-19 vaccines in pregnant women despite clear evidence from multiple sources that safety signals had been breached.

This study presents the interaction with human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a Protein-Protein-Interaction Networks analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2,753 proven interactions and 1,708 interactors, specific to ORF7b. We used these proteins as functional seeds and we got a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. Seven high ranked proteins as hub and seven as bottleneck following a hub-and-spoke network-architectural-model were found. Through this interaction model, we identified significant GO-processes (5,057 terms in 15 categories) induced in human metabolism by ORF7b. High statistical significance processes of dysregulated molecular cell mechanisms by the action of ORF7b were discovered. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems and the molecular mechanisms that supervise to programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant-Connected-Components core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b mainly acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation, transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes, within the limits of the poor knowledge that these sectors still impose.

Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

We tested the possibility of using “adverse events count” (AEC) as a drug-risk indicator and side-effect severity indicator. Data from 3938 adverse event (AE) reports for COVID-19 vaccines (Comirnaty, Moderna, Vaxzevria, and Janssen) and 6869 AE reports for other medicines were collected from the Bulgarian Drug Agency database (01.01.2018–31.03.2022). AEC was modeled with zero-adjusted negative binomial (ZANBI) and zero-adjusted Poisson inverse Gaussian (ZAPIG) regression models, which account for zero absence and overdispersion. The models’ fit was checked with residual diagnostic plots and parametric correspondence to normality. Explanatory variables were: age, sex, sequence number (order of submission), severity of AE, and vaccine type. Average AEC was higher in severe vs. non-severe AE, and in females vs. males; it decreased with age and was lower in Comirnaty than other vaccines. Variability of AEC for COVID-19 data decreased with sequence number in severe AE and increased in non-severe AE. Full ZANBI models had greater sensitivity than parametric ZANBI or ZAPIG models. Results showed correlation between AEC and AE severity, suggesting AEC as a simple and reliable measure of drug-risk and side-effect severity for clinicians and regulators, especially for COVID-19 vaccines.

Global rapidly evolving events, e.g., COVID-19, are usually followed by countermeasures and policies. As a reaction, the public tends to express their emotions on social media platforms. Therefore, predicting emotional responses to events is critical to put a plan to avoid risky behaviors. This paper proposes a machine learning-based framework to detect public emotions based on social media posts in response to specific events. It presents a precise measurement of population-level emotions which can aid governance in monitoring public response and guide it to put in place strategies such as targeted monitoring of mental health, to react to a rise in negative emotions in response to lockdowns, or information campaigns, for instance in response to elevated rates of fear in response to vaccination programs. We evaluate our framework by extracting 15,455 tweets. We annotate and categorize the emotions into 11 categories based on Plutchik’s study of emotion and extract the features using a combination of Bag of Words and Term Frequency-Inverse Document Frequency. We filter 813 COVID-19 vaccine-related tweets and use them to demonstrate our framework’s effectiveness. Numerical evaluation of emotions prediction using Random Forest and Logistic Regression shows that our framework predicts emotions with an accuracy up to 95%.

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declined within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster shots of BNT162b2 or ChAdOx1 among health care workers who previously received CoronaVac as their primary immunization. Fifty-six participants received ChAdOx1 and forty-two participants received BNT162b2 were enrolled into this study which evaluated the immune responses including anti-SARS-CoV-2 spike total antibodies (Elecsys®), surrogated viral neutralization test (sVNT) to ancestral strain (cPass™; GenScript) and five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) (Luminex; multiplex sVNT) and the ELISpot with spike (S1 and S2) peptide pool against the ancestral SARS-CoV-2 strain. The samples were analyzed at baseline, 4, and 12 weeks after primary immunization as well as 4 and 12 weeks after receiving the booster. This study showed a significantly higher B-cell response among the BNT162b2 than the ChAdOx1 booster group, particularly against the Omicron variant, as well as a trend of good T-cell immune response in the BNT162b2 group. Moreover, the immune response rapidly declined at 12 weeks after the booster. A fourth dose or a second booster should be recommended, especially for reducing Omicron severity.

Background: Acceleration of mass vaccination strategies is the only pathway to overcome the COVID-19 pandemic. Healthcare professionals and students have a key role in shaping public opinion about vaccines. This study aimed to evaluate the attitudes of dental students globally towards COVID-19 vaccines and explore the potential drivers for students' acceptance levels; Methods: A global cross-sectional study was carried out in February 2021 using an online ques-tionnaire. The study was liaised by the scientific committee of the International Association of Dental Students (IADS), and data was collected through the national and local coordinators of IADS member organizations. The dependent variable was the willingness to take the COVID-19 vaccine, and the independent variables included demographic characteristics, COVID-19-related experi-ence, and the drivers of COVID-19 vaccine-related attitude suggested by the WHO-SAGE; Results: A total of 6639 students from 22 countries representing all world regions responded to the ques-tionnaire properly. Their mean age was 22.06 ± 2.79 (17-40) years, and the majority were females (70.5%), in clinical years (66.8%), and from upper-middle-income economies (45.7%). In general, 22.5% of dental students worldwide were hesitant, and 13.9% rejected COVID-19 vaccines. The students in low- and lower-middle-income (LLMI) economies had significantly higher levels of vaccine hesitancy compared to their peers in upper-middle- and high-income (UMHI) economies (30.4% vs 19.8%; p < 0.001); Conclusions: The global acceptance level of dental students for COVID-19 vaccines was suboptimal, and their worrisome level of vaccine hesitancy was influenced by the socioeconomic context where the dental students live and study. The media and social media, public figures, insufficient knowledge about vaccines, and mistrust of governments and the pharmaceutical industry were barriers to vaccination. The findings of this study call for further implementation of epidemiology (infectious diseases) education within undergraduate dental curricula.

Background Hokkaido is the northernmost, least populous, and coldest of the Japanese islands. It was the first prefecture to be affected by COVID-19, while Kanagawa is home to one of the most populous areas of Japan, namely the Tokyo metro area. The Japanese government responded early during the pandemic by identifying infected patients, contact tracing, and performing PCR analysis on anyone who was suspected of having been exposed to SARS-CoV-2. The government has also been publishing information about each individual who tested positive for the virus. Both Hokkaido and Kanagawa started recording COVID-19 cases in the winter of 2020 and have detailed records of thousands of patients, thus providing an invaluable resource for the transmission and behavior of the virus. Methods The current study analyzed the COVID-19 registry data from the Hokkaido and Kanagawa prefectures. The Hokkaido registry contained 1,269 cases (674 (53%) females and 595 (47%) males) recorded between February 14 and July 22, 2020. The Kanagawa registry had 3,123 cases (1,346 (43%) females and 1,777 (57%) males. The final data contained a total of 4,392 cases (2,020 (46%) females and 2,372 (54%) males). By leveraging the information on viral transmission paths available in the registry data, we performed exponential random graph model (ERGM) network analysis to examine demographic and symptomological homophilies of the SARS-CoV-2 viral transmission networks. Results We observed age, symptomatic, and asymptomatic homophilies in both prefectures. Furthermore, those patients who contracted the virus through secondary or tertiary contacts were more likely to be asymptomatic than those who contracted it from primary infection cases. The transmission networks showed that transmission occurred significantly in healthcare settings, as well as in families, although the size of the networks was small in the latter. Most of the transmissions stopped at the primary and secondary levels and no transmission beyond quaternary was observed. We also observed a higher level of asymptomatic transmission in Kanagawa than in Hokkaido. Conclusions Symptom homophilies are an important component of COVID-19 and suggest that nuanced genetic differences in the virus may affect its epithelial cell type range and can thus result in the diversity of symptoms seen in individuals infected by SARS-CoV-2. Moreover, environmental variables such as temperature and humidity may also be playing an important role in the overall pathogenesis of the virus.

The COVID-19 pandemic has resulted in a wide range of spatial interventions to slow down the spread of the virus. The spatial limitations of narrow public circulation spaces within informal settlements, which house over one billion people around the world, make it impossible for pedestrians to practice physical distancing (or social distancing). In this paper, we propose a flexible mathematical method, named the Cluster Lane Method, for turning a planar circulation network of any size or complexity into a network of unidirectional lanes, making physical distancing possible in narrow circulation spaces by limiting face-to-face interactions. New notions and theorems about oriented graphs in graph theory are introduced. The paper ends with a discussion of the potential implementation of this cost-efficient, low-tech, sustainable solution, and with the introduction of a novel unidirectional tactile paving for the visually impaired.

Thermal sterilization is generally avoided for 3-D printed components because of the relatively low deformation temperatures for common thermoplastics used for material extrusion-based additive manufacturing. 3-D printing materials required for high-temperature heat sterilizable components for COVID-19 and other applications demands 3-D printers with heated beds, hot ends that can reach higher temperatures than polytetrafluoroethylene (PTFE) hot ends and heated chambers to avoid part warping and delamination. There are several high temperature printers on the market, but their high costs make them inaccessible for full home-based distributed manufacturing required during pandemic lockdowns. To allow for all these requirements to be met for under $1,000, the Cerberus – an open source three-headed self-replicating rapid prototyper (RepRap) was designed and tested with the following capabilities: i) 200^oC-capable heated bed, ii) 500^oC-capabel hot end, iii) isolated heated chamber with 1kW space heater core and iv) mains voltage chamber and bed heating for rapid start. The Cereberus successfully prints polyetherketoneketone (PEKK) and polyetherimide (PEI, ULTEM) with tensile strengths of 77.5 and 80.5 MPa, respectively. As a case study, open source face masks were 3-D printed in PEKK and shown not to warp upon widely home-accessible oven-based sterilization.

Introduction: Due to COVID-19 pandemic, performance of many program has been declined and Tuberculosis (TB) program is not an exception. TB case detection and notification has been recognized as one of worst hit area. The objective of this study was to explore the TB notification status of India during this pandemic and explore options to mitigate the issue. Methods: A secondary data analysis was performed on open source TB notification database of India. Relevant literature review was done to find out remedies based on the different initiative taken by different states of India. Results: In 2020, total TB notification decreased in all the states in comparison to 2019. The percentage of loss in the country was 34%. Private TB notification also decreased in 2020 in all the states except in Jharkhand. The percentage of loss in private TB notification in the country was 35%. Notification started declining in the month of February 2020 and it was lowest in the month of April-2020. The trend of notification began to improve since May 2020 when the States started taking innovative initiatives like Integrated TB Covid Case Search. Conclusion: Due to the ongoing COVID-19 pandemic the notifications of TB cases declined noticeably which has a serious implication in terms of silent spread within household and community. But the picture can be improved with integrated approach for TB-COVID case finding and management.

This narrative review examines the crucial role of physical activity in managing long COVID, characterized by persistent symptoms such as fatigue, breathlessness, and cognitive impairments following SARS-CoV-2 infection. The methodology involved a comprehensive literature search across PubMed, EBSCO (EDS), and Google Scholar, selecting peer-reviewed articles from December 2019 focusing on long-term COVID physical activity interventions. The review highlights that tailored exercise programs, adjusted to individual health status and abilities, significantly alleviate symptoms and enhance psychological well-being. Key findings emphasize the importance of personalized exercise prescriptions due to the variability in patient responses and the need for a multidisciplinary approach in developing and monitoring interventions. Despite promising outcomes, the review identifies research gaps, including the need for long-term studies, randomized controlled trials, and deeper mechanistic insights. It suggests that standardized reporting, templates like CERT, and integrating digital health tools are essential for optimizing interventions. Overall, the review advocates including personalized physical activity programs in standard care for long COVID to improve patient outcomes and quality of life.

It is axiomatic to underscore that a well-managed education system is deemed globally as one of the crucial prerequisites for not only the growth and development of every society or geopolitical space but also one of the veritable hallmarks of a diversified and functional economy that will, in the long run, culminate in economic emancipation of the people. The education industry faces enormous challenges in several countries in Africa, and Nigeria is not an exception. Even though education remains the bedrock or superstructure on which other societal structures such as politics, culture, religion, economics, etc. are laid; it is quite disheartening that education in Nigeria is not effectively and efficiently managed for economic diversification and emancipation of the recipients of such education. Indeed, the industry faces innumerable challenges, especially in contemporary times than in the pre-colonial era when the education system was essentially functional. The hydra-headed nature of the challenges with Nigeria’s educational system has inevitably resulted in different dimensions of economic quagmires entangling the country and making most of its citizens find it extremely difficult to eke out and or survive. The level of dysfunctionalities in various sections of the education system has made it seemingly intractable to palliate the economic predicaments that have been confronting the country let alone emancipate it from the monoculture of its overdependence on oil. The author of this treatise is diagnostic in his approach to understanding the intricacies of the challenges that frontally battle the Nigerian education system and deprive it of being a veritable tool for a functional economy as well catalyst for the economic emancipation of its people. The paper, through the analyses of relevant literature, amplifies the conceptual and operational dimensions of the identified challenges, offers probable suggestions on the ways by which the challenges can be tackled and finally draws a conclusion.

Acoustic emission monitoring (AEM) has emerged as an effective technique for detecting wire-breaks resulting from, e.g., stress corrosion cracking, and its application on prestressed concrete bridges is increasing. The success of this monitoring measure depends crucially on a carefully designed sensor layout. For this the attenuation of elastic waves within the structure’s material is determined ideally in-situ through object-related measurements with a reproducible signal source, typically a rebound-hammer. This assumes that the attenuation coefficients derived from rebound-hammer tests are comparable to those from wire-breaks, thus allowing their results to be directly applied to wire-break detection without further adjustments. This study challenges this assumption by analysing attenuation behaviour through an extensive dataset. Employing time-domain and frequency analysis, the research generates attenuation profiles from laboratory experiments and in-situ measurements across various girders and bridge structures, extracting the slope and standard deviation of the residuals. While generally validating this approach, the findings highlight differences in attenuation behaviour from among wire-break signals and rebound-hammer impulses, whereby the latter potentially underestimates the relevant attenuation of wire-breaks by approximately 20 %. Consequently, a transfer factor is proposed to adjust object-related measurement results for wire-break scenarios, including a variance of 1.0 dB/m to cover a 95 % confidence interval for sample scattering. Moreover, the anisotropic attenuation behaviour across different structures was studied, showing that transverse attenuation consistently exceeds the longitudinal, significantly influenced by structural features such as voids. In prefabricated concrete bridges with in-situ-cast concrete slabs, transverse signal transmission remains unhindered across multiple elements. Finally, the results provide a valuable reference for the design of sensor layouts in bridge monitoring, particularly benefiting scenarios where direct in-situ experiences are lacking.

Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adenoassociated virus (AAV-HDV) as gene delivery vehicles offers a unique platform to investi-gate the molecular aspects of HDV and associated liver damage. Here, we generated HDV ge-nomes modified by site directed mutagenesis aimed to: i) prevent some post-translational modi-fications of HDV antigens (HDAgs) such as Large-HDAg (L-HDAg) isoprenylation or Short-HDAg (S-HDAg) phosphorylation ii) alter the localization of HDAgs within the subcellular compartments and iii) inhibit the right conformation of the delta ribozyme. First, the different HDV mutants were tested in vitro using plasmid-transfected Huh-7 cells and then in vivo in C57BL/6 mice using AAV vectors. We found that Ser 177 phosphorylation and the ribozymal ac-tivity are essential for HDV replication and HDAg expression. Mutation of the isoprenylation domain prevent the formation of infectious particles and increase cellular toxicity and liver dam-age. Finally, altering the intracellular localization od HDAg have a profound on viral replication in vivo but liver toxicity is maintained. Mutation in the nuclear export signal impair the for-mation of infectious viral particles. These findings contribute valuable insights into the intricate mechanisms of HDV biology and have implications for therapeutic considerations

background: The Islamic Republic of Iran has been under sanctions since 1979. These sanctions were further reinforced between the years 2005 and 2012. This study utilizes available data from Iran post-sanctions to review the impact of economic sanctions on both the mental health and the quality of life of Iranian citizens.Methods: A comprehensive scoping review was conducted to identify studies examining the impact of sanctions on health in Iran. Searches were initiated in 2012 using PubMed/Medline, Embase, Web of Science, Scopus, and the Scientific Information Database (Iranian Database) with keywords such as sanctions, implications, mental health, quality of life, civilian mental health, and Iran. Subsequent to the screening process, secondary reports and letters to the editor were excluded. Only original studies—those collecting data via observation, interviews, surveys, experiments, or literature reviews—were retained for analysis. In addition to these search strategies, reference scanning was undertaken to identify additional articles pertinent to the scope of the current study. This thorough approach facilitated the discovery of relevant and significant articles exploring the effects of sanctions against Iran on the mental health and overall well-being of its civilian population. Following the search, duplicate articles were meticulously identified and removed by the authors. Data were subsequently extracted and summarized, focusing on study characteristics and the observed effects of sanctions on civilian mental health and quality of life in Iran.Result: Out of 165 items identified in the preliminary search, ten articles met the inclusion criteria. These selected articles highlighted the pronounced effects of sanctions on various health-related domains.Conclusion: Since 2012, Iran has been subject to intensified sanctions. There is evidence to suggest that the economic sanctions, imposed by Western nations, and have exerted a negative and detrimental impact on the health of individual Iranians.

One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.

This study assessed health inequality trends and the degree of maternal healthcare services utilization in the DRC, using two consecutive Demographic and Health Surveys, 2007 and 2013-2014. First, we assessed the changes in the magnitude of inequality in the utilization of MHCS using logistics and regressions. Second, we analyzed the distribution of inequality in each MHCS utilization variable using the Gini coefficient and the Lorenz curve. Third, we used the Wagstaff two groups concentration indices comparison method to assess health inequality trends. Finally, we fitted the concentration curves to estimate the inequality in the utilization of MHCS to the economic condition of women. Women were less likely to have their first ANC visit within the first trimester, less likely to receive checkups during ANC visits, and less likely to attend more ANC visits when living in eastern DRC compared to western DRC. Women in rural areas were less likely to have their last birth by C-section, and less likely to receive PNC than women in urban areas. Women with middle, richer, and richest wealth indexes were more likely to complete more ANC visits, more likely to deliver by C-section, most likely to receive PNC, and more likely to receive ANC than those with lower wealth indexes. Over time, inequality in the utilization of MHCS decreased for ANC and PNC but increased for the delivery by C-sections. These findings suggest that innovative strategies are still needed to improve the utilization of MHC services among poorer, rural, and underserved women in post-conflict DRC.

The Mine Internet of Things (MIoT), as a key technology for reconstructing post-disaster communication networks, enables to realize the safety monitoring and controlling of the affected roadway. However, due to the challenging underground mine environment, the MIoT suffers from severe signal attenuation, vulnerable nodes, and limited energy, which result in low network reliability of the post-disaster MIoT. To improve the transmission reliability as well as to reduce energy consumption, a directional-area-forwarding-based energy-efficient opportunistic routing (DEOR) for the post-disaster MIoT is proposed. DEOR defines a forwarding zone (FZ) for each node to route packets toward the sink. The candidate forwarding set (CFS) is constructed by the nodes within the FZ that satisfy the energy constraint and the neighboring node degree constraint. The nodes in CFS are prioritized based on the routing quality evaluation by taking the local attributes of nodes into consideration, such as the directional angle, transmission distance, and residual energy. DEOR adopts a recovery mechanism to address the issue of void nodes. The simulation results validate that the proposed DEOR outperforms ORR, OBRN and ECSOR in terms of energy consumption, average hop count, packet delivery rate, and network lifetime.

Applications in security and electronic surveillance require combination of excellent magnetic softness with good mechanical and anti-corrosive properties and low dimensionality. We overviewed the properties of soft magnetic glass-coated microwires and different post-processing making them quite attractive for electronic article surveillance and security applications. We studied the magnetostatic interaction between the microwires and routes to tune the non-linear hysteresis loops by using the arrays of different types of amorphous microwires. The presence of neighbouring microwire (either Fe or Co-based) significantly affects the hysteresis loop of the whole microwires array. In a microwires array containing magnetically bistable microwires we observed splitting of the initially rectangular hysteresis loop with a number of Barkhausen jumps correlated with the number of magnetically bistable microwires. Essentially, non-linear and irregular hysteresis loops have been observed in mixed arrays containing Fe and Co-rich microwires. The observed non-linearity in hysteresis loops allowed to increase the harmonics and tune their magnetic field dependencies. Non-linear hysteresis loops have been also observed upon devitrification of amorphous microwires. On the other hand, several routes allowing to tune the switching field by either post-processing or modifying the magnetoelastic anisotropy have been reviewed. Observed unique combination of magnetic properties together with thin dimensions and excellent mechanical and anti-corrosive properties provide excellent perspectives for the use of glass-coated microwires for security and electronic surveillance applications.

Post-concussion syndrome, recently recognized as a complication of mild traumatic brain injury, is considered a consequence of the summative effect of multiple concussions received over lifetime. In elderlies, the main mild brain trauma mechanism is fall (low impact force). Many falls are often not reported or noticed but may generate serious medical and medico-legal consequences. Our research question was to find if a single, very mild brain trauma can induce neuro-behavioral consequences in elderlies. One database was queried (PubMed – MeSH terminology) looking for histopathological, neuro-cognitive and behavioral changes that can be generated by sub-concussional trauma in senescent rodents, in comparison with young animals. 41 published research articles were selected. 17 of them used very mild brain trauma in young and senescent animals, in the same experiment (6 rats and 11 mice). 24 articles evaluated the effect of sub-threshold brain trauma in adult animals (no control group). Five trauma models were used (blast models were excluded). Neuro-inflammatory changes were detected immediate after very mild primary impact. In young animals, observed pathology disappeared fast (after 3 to 7 days). Increased apoptosis, mild axonal injury in white matter tracts plus maladaptive astrogliosis and microglial activation was stronger in aged animals, persisted over time (8 months) and significantly altered animals’ cognition and behavior. Associated preexisting pathology (hypertension, tau protein deposits, microbleeds, reactive inflammation) was often responsible for amplification of the primary impact results. As translation of observation is the weak spot of pathology and behavior animal research, further investigation is needed before to conclude that even a single, very mild brain trauma may have medical consequences on human senescent brain.

Surfactants based on polyfluoroalky ethers are commonly used in fire-fighting foams on airport platforms, including for training sessions. Because of their persistence into the environment, their toxicity and their bioaccumulation, abnormal amounts can be found in ground and surface water following operations of airport platforms. As many other anthropogenic organic compounds, some concerns raised about their biodegradation. That is why the OECD 301 F protocol was implemented to appreciate the oxygen consumption during the biodegradation of a commercial fire-fighting foam. However, a Raman spectroscopic monitoring of the process was also attached to this experimental procedure to evaluate to what extent a polyfluoroalkyl ether disappeared from the environmental matrix. The relevance of our approach is to use chemometrics, including the Principal Component Analysis (PCA) and the Partial Least Square (PLS), in order to monitor the kinetics of the biodegradation reaction of one fire-fighting foam, Tridol S3B, containing a polyfluoroalkyl ether. This study provided a better appreciation of the partial biodegradation of some polyfluoroalkyl ethers by coupling Raman spectroscopy and chemometrics. This will ultimately facilitates the design of a future purification and remediation devices for the airport platforms.

Impervious surface mapping with high-resolution remote sensing imagery has attracted increasing interest as it can provide detailed information for urban structure and distribution. Previous studies have suggested that the combination of LiDAR data and high-resolution imagery for impervious surface mapping performs better than using only high-resolution imagery. However, due to the high cost of the acquisition of LiDAR data, it is difficult to obtain the multi-sensor remote sensing data acquired at the same acquisition time for impervious surface mapping. Consequently, real landscape changes between multi-sensor remote sensing data at different acquisition times would lead to the error of misclassification in impervious surface mapping. This issue has mostly been neglected in previous works. Furthermore, the observation differences generated from multi-sensor data, including the problems of misregistration, missing data in LiDAR data, and shadow in high-resolution images would also challenge the final mapping result in the fusion of LiDAR data and high-resolution images. In order to conquer these problems, we propose an improved impervious surface mapping method incorporating both LiDAR data and high-resolution imagery at different acquisition times in consideration of real landscape changes and observation differences. In the proposed method, a multi-sensor change detection by supervised multivariate alteration detection is employed to obtain changed areas and misregistration areas. The no-data areas in the LiDAR data and the shadow areas in the high-resolution imagery are extracted by independent classification yielded by its corresponding single sensor data. Finally, an object-based post-classification fusion is proposed to take advantage of independent classification results with single-sensor data and the joint classification result with stacked multi-sensor data. Experiments covering the study site in Buffalo, NY, USA demonstrate that our method can accurately detect landscape changes and obviously improve the performance of impervious surface mapping.

Mining for resources extraction may lead to several geological and associated environmental changes due to ground movements, collision with mining cavities and deformation of aquifers. Geological changes may continue in a reclaimed mine area, and the deformed aquifers may entail a breakdown of substrates and an increase in ground water tables, which may cause surface area inundation. Consequently, a reclaimed mine area may experience surface area collapse, i.e. subsidence, and degradation of vegetation health. Thus, monitoring short-term landscape dynamics in a reclaimed mine area may provide important information on the long-term geological and environmental impacts of mining activities. We studied landscape dynamics in Kirchheller Heide, Germany, which experienced extensive soil movement due to longwall mining without stowing, using Landsat imageries between 2013 and 2016. A Random Forest image classification technique was applied to analyse land-use and land-cover dynamics and the growth of wetland areas was assessed using a Spectral Mixture Analysis (SMA). We also analyzed the changes in vegetation health using a Normalized Difference Vegetation Index (NDVI). We observed a 19.9% growth of wetland area within the four years with 87.2% of growth in the coverage of two major waterbodies in the reclaimed mine area. NDVI values indicate that 66.5% of the vegetation of the study area was degraded due to changes in ground water tables and surface flooding. Our results inform environmental management and mining reclamation authorities about the subsidence spots and priority mitigation areas from land surface and vegetation degradation in Kirchheller Heide.

During the last few years, the world witnessed one of the worst calamities to humankind- the COVID-19 pandemic. We also witnessed the development of vaccines at an unprecedented pace against the SARS-CoV-2- the causative agent. India was among the hard-hit countries by COVID-19, developed its indigenous vaccine and implemented vaccines developed in other countries as well. Initially, the antibody level and the neutralizing antibody titer against the pathogen were considered as the correlates of immune protection from the disease. However, the long-term protection from the pathogen was provided by the immune memory cells viz. T and B memory cells and their ability to efficiently make recall responses. In this regard, globally the research studies focused mainly on the mRNA-based vaccines. The studies on immune memory response, particularly- the B cell memory response bestowed by the vaccines given to Indians is relatively obscure. We studied the level of RBD specific memory B cells in the peripheral circulation of the study participants and the ability of B cells to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D) and Sputnik Light (Gam-COVID-Vac) as well as unvaccinated individuals. Our study revealed that Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses.

The relentless challenges posed by the COVID-19 pandemic have placed immense pressure on densely populated regions, such as Hong Kong, particularly in the context of an aging population. The burgeoning demand for healthcare services has necessitated the optimization of resource al-location within healthcare systems. This research presents an innovative analytical queueing model specifically tailored to address the intricate gridlock dynamics prevalent in healthcare systems, with a focused application in the challenging landscape of COVID-19 management. Hong Kong, like numerous other regions, has experienced a demo-graphic transition leading to heightened healthcare demands. Traditional methodologies for scrutinizing gridlock issues in healthcare settings, including simulation models, often prove suboptimal within the context of sophisticated optimization frameworks. This study, however, delves into analytical queueing models, offering a more efficient and effective approach. These models have been underexplored, primarily due to the intricacies involved in modeling gridlock propagation within restricted capacity, a critical concern magnified by the COVID-19 pandemic. The novel Queueing Model introduced in this research incorporates the maintenance of queue capacities and topological aspects as exogenous parameters, rendering it exceptionally adaptable for diverse gridlock-related applications. This adaptability is especially pertinent to healthcare management during the COVID-19 crisis. The model meticulously integrates the concept of gridlock, furnishing a comprehensive comprehension of its origins and repercussions. Validation of this model involves rigorous comparison with established methodologies, exact results, and simulation data, consistently high-lighting its versatility and precision. By applying the model to healthcare management, we scrutinize the dynamics of patient flow within a Hong Kong hospital, placing specific emphasis on the critical issue of bed blockage, further exacerbated by the COVID-19 pandemic. The model's gridlock decomposition unearths the nuanced impact of bed blockage on distinct hospital units, addressing the imperative requirement for quantifying in-patient bed blockage within healthcare systems during a pandemic.

The new coronavirus SARS-CoV-2 is the cause of the COVID-19 pandemic, which has created an incomparable global health problem. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. The review begins by elucidating the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Employing homology modeling, a tertiary structure model of PLpro is constructed, laying the groundwork for subsequent investigations. To expedite the search for potential therapeutic candidates, the study harnesses computational methodologies. Molecular docking techniques are employed to explore binding sites for antiviral drugs within the catalytic region of PLpro. This computational approach not only aids in drug development but also provides crucial preliminary data before experimental research commences. The stability of drug-PLpro complexes is assessed through comprehensive all-atom molecular dynamics (MD) simulations, affording dynamic insights into drug-PLpro interactions. By evaluating binding energy estimates from MD simulations, stable drug-PLpro complexes with potential antiviral properties are identified. However, it is emphasized that experimental validation is imperative to confirm these computational findings, necessitating in vitro and in vivo tests to assess safety and efficacy. This pivotal stage bridges the computational realm with real-world clinical applications. The review emphasizes the imperative need for enhancements in the existing PLpro-targeting drugs currently on the market. Their actions are insufficient for clinical use and necessitate thorough characterization and improvement. The Supervised Molecular Dynamics (SuMD) simulation technique reveals critical information about drug unbinding pathways, shedding light on opportunities for refinement. In addition to optimizing existing drugs, the investigation of sub-structurally similar molecules emerges as a promising avenue for drug development. In conclusion, the review underscores the pivotal role of targeting SARS-CoV-2 PLpro in the ongoing battle against COVID-19. By integrating molecular dynamics simulations, structural modeling, and computational insights, a robust foundation is established for identifying promising antiviral drug candidates. The continual need for improvement in existing drugs and the exploration of novel compounds remain paramount in the global effort to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, illustrating the interdisciplinary synergy crucial to this endeavor.

Home confinement during the COVID-19 pandemic has been accompanied by dramatic changes in household food dynamics that can significantly influence health. This systematic literature review presents parental perspectives of the impact of COVID-19 lockdown on food preparation and meal routines, as well as other food-related behaviors, capturing both favorable and unfavorable changes in the family food environment (FFE). Themes and trends are identified and associations with other lifestyle factors are assessed. In overall, families enjoyed more time together around food, including planning meals, cooking, and eating together. Eating more diverse foods and balanced meals was combined with overeating and increased snacking, as parents became more permissive towards food; however, food insecurity increased among families with the lowest income. Adoption of meal planning skills and online shopping behavior emerged alongside behaviors aimed at self-sufficiency, such as bulk purchasing and stockpiling. These results are an important first step in recognizing how this pandemic may be affecting the FFE, including low-income families. Future obesity prevention and treatment initiatives, but also ongoing efforts to address food management, parental feeding practices, and food insecurity, can account for these changes moving forward.

Identifying anti-spike antibodies that exhibit strong neutralizing activity against current dominant circulating variants and antibodies that are escaped by these variants have important implications in the development of therapeutic and diagnostic solutions as well as in improving understanding of the humoral response to SARS-CoV-2 infection. We characterized seven anti-RBD monoclonal antibodies for their binding activity, pairing capability and neutralization activity to SARS-CoV-2 and three variant RBDs (UK, SA and BR P.1) via lateral flow immunoassays. The results allowed us to group these antibodies into three distinct epitope bins. Our studies showed that two antibodies had broadly potent neutralizing activity against SARS-CoV-2 and these variant RBDs and that one antibody did not neutralize the SA and BR P.1 RBDs. The antibody escaped by the SA and BR P.1 RBDs retained binding activity to SA and BR P.1 RBDs but was unable to induce neutralization. Further, we demonstrated that the lateral flow immunoassay can be a rapid and effective tool for antibody characterization, including epitope classification and antibody neutralization kinetics. From these studies, the potential contributions of the mutations (N501Y, E484K and K417N/T) contained in these variants’ RBDs on antibody pairing capability, neutralization activity and therapeutic antibody targeting strategy are discussed.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

We present a new mathematical model of disease spread reflecting specialties of covid-19 epidemic by elevating the role social clustering of population. The model can be used to explain slower approaching herd immunity in Sweden, than it was predicted by a variety of other mathematical models; see graphs Fig. \ref{GROWTH2}. The hierarchic structure of social clusters is mathematically modeled with ultrametric spaces having treelike geometry. To simplify mathematics, we consider homogeneous trees with $p$-branches leaving each vertex. Such trees are endowed with algebraic structure, the $p$-adic number fields. We apply theory of the $p$-adic diffusion equation to describe coronavirus' spread in hierarchically clustered population. This equation has applications to statistical physics and microbiology for modeling {\it dynamics on energy landscapes.} To move from one social cluster (valley) to another, the virus (its carrier) should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider {\it linearly increasing barriers.} This structure matches with mild regulations in Sweden. The virus spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This behavior matches with the covid-19 epidemic, with its cluster spreading structure. Our model differs crucially from the standard mathematical models of spread of disease, such as the SIR-model. We present socio-medical specialties of the covid-19 epidemic supporting our purely diffusional model.