Mathematical models are useful in epidemiology to understand the COVID-19 contagion dynamics. Our aim is to demonstrate the effectiveness of parameter regression methods to calibrate an established epidemiological model describing COVID-19 infection rates subject to active and varying non-pharmaceutical interventions (NPIs). To do this, we assess the potential of some established chemical engineering modelling principles and practice for application to modelling of epidemiological systems. This allows us to exploit the sophisticated functionality of a commercial chemical engineering simulator capable of parameter regression with piecewise continuous integration and event and discontinuity management. Our results provide insights into the outcomes of on-going disease suppression measures, while visualisation of reported data also provides up-to-date condition monitoring of the status of the pandemic. We observe that the effective reproduction number response to NPIs is non-linear with variable response rate, magnitude and direction.

The critical role of IgE in allergic diseases is well-documented and clinically proven. Omalizumab, a humanized anti-IgE antibody, was the first approved antibody for the treatment of allergic diseases. Nevertheless, omalizumab still has some limitations, such as product instability and dosage restriction in clinical application. In this study, we attempted to develop an omalizumab biobetter antibody with the potential to overcome its limitations. We removed two aspartic acid isomerization hotspots in CDRs of omalizumab to improve antibody candidates stability. Meanwhile, several murine amino acids in the framework region of omalizumab were replaced with human source to reduce the potential immunogenicity. Yeast display technology was then applied to screen antibody candidates with high binding affinity to IgE. Moreover, YTE mutation in Fc fragment was introduced into the candidates for extending their serum half-life. A lead candidate, AB1904Am15, was screened out, which showed desired biophysical properties and improved stability, high binding affinity and elevated potency in vitro, prolonged half-life in human FcRn transgenic mouse, and enhanced in vivo efficacy in cynomolgus monkey asthma model. Overall, our study developed a biobetter antibody of omalizumab, AB1904Am15, which has the potential to show improved clinical benefit in the treatment of allergic diseases.

Porcine NK cells are small to medium lymphocytes which are lytic for tumours and virally infected cells when co-cultured for long periods ( approximately 16 h). The frequency and function of NK cells were examined in generation 8 of pigs genetically selected for high (H), low (L), and control (C) antibody (Ab) and cell-mediated immune response (CMIR). The NK phenotype was identified using a pan-species NK-specific murine monoclonal antibody (5C6) and both binding and lysis of the NK target, K562. Vaccination with modified live transmissible gastroenteritis virus (TGEV) had no effect on blood leucocyte NK cell frequency. In interactions with K562 targets, NK cells of H and C pigs responded similarly in frequency of conjugate formation and lytic activity, while L pigs had very little or no response. Therefore, in pigs selected for high Ab and CMIR, there was no correlated enhancement of NK-cell-related traits following vaccination with TGEV, while selection for low immune response was associated with reduced NK response in pigs. This may suggest that low immune response can reflect reduced contribution of NK cells in pigs.

BACKGROUND AND PURPOSE: The outbreak of the COVID-19 pandemic has resulted in an overall decline in fractures. However, the amount of hip fractures has remained relatively stable throughout the period. The objective of this study is to investigate the impact of perioperative COVID-19 infections on mortality among hip fracture patients. METHODS: A meta-analysis was performed by collecting current data available through a systematic literature search in the PubMed database. The search was performed Oct 18 2020. RESULTS: The meta-analysis was conducted on a trial population consisting of 1.272 hip fracture patients with a pooled prevalence of COVID-19 of 18%. Mortality among hip fracture patients without a perioperative COVID-19 infection was 7.49%. Mortality among hip fracture patients infected with COVID-19 perioperatively was associated with an odds ratio of 6.70 [(95% CI 4.64C9.68), p < 0.00001, I(2) = 41%]. A sensitivity analysis showed no major impact of assumptions regarding varying definitions of COVID-19 statuses among the included studies. CONCLUSION: Perioperative infections with COVID-19 in hip fracture patients are correlated with a significantly increased mortality. The meta-analysis showed a pooled odds ratio of 6.70 [(95% CI 4.64C9.68), p < 0.00001, I(2) = 41%].

The clinical characteristics and biological effects on the nervous system of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain poorly understood The aim of this study is to advance epidemiological and mechanistic understanding of the neurological manifestations of coronavirus disease 2019 (COVID-19) using stroke as a case study In this study, we performed a meta-analysis of clinical studies reporting stroke history, intensive inflammatory response and procoagulant state (C-reactive protein (CRP), Procalcitonin (PCT) and coagulation indicator (D-dimer) in patients with COVID-19 Via network-based analysis of SARS-CoV-2 host genes and stroke-associated genes in the human protein-protein interactome, we inspected the underlying inflammatory mechanisms between COVID-19 and stroke Finally, we further verified the network-based findings using three RNA-sequencing datasets generated from SARS-CoV-2 infected populations We found that the overall pooled prevalence of stroke history was 2 98% (95% CI, 1 89 - 4 68;I2=69 2%) in the COVID-19 population Notably, the severe group had a higher prevalence of stroke (6 06%;95% CI 3 80 - 9 52;I2 = 42 6%) compare to the non-severe group (1 1%, 95% CI 0 72 - 1 71;I2 = 0 0%) There were increased CRP, PCT and D-dimer in severe illness, and the pooled mean difference was 40 7mg/L (95% CI, 24 3 - 57 1), 0 07?g/L (95% CI, 0 04 - 0 10) and 0 63mg/L (95% CI, 0 28 - 0 97) respectively Vascular cell adhesion molecule 1 (VCAM-1), one of the leukocyte adhesion molecules, is suspected to play a vital role of SARS-CoV-2 mediated inflammatory responses RNA-sequencing data analyses of the SARS-CoV-2 infected patients further revealed the relative importance of inflammatory responses in COVID-19-associated neurological manifestations In summary, we identified an elevated vulnerability of those with a history of stroke to severe COVID-19 underlying inflammatory responses (i e , VCAM-1) and procoagulant pathways, suggesting monotonic relationships, thus implicating causality

Pathogenesis induced by SARS-CoV-2 is thought to result from both an inflammation-dominated cytokine response and virus-induced cell perturbation causing cell death. Here, we employ an integrative imaging analysis to determine morphological organelle alterations induced in SARS-CoV-2-infected human lung epithelial cells. We report 3D electron microscopy reconstructions of whole cells and subcellular compartments, revealing extensive fragmentation of the Golgi apparatus, alteration of the mitochondrial network and recruitment of peroxisomes to viral replication organelles formed by clusters of double-membrane vesicles (DMVs). These are tethered to the endoplasmic reticulum, providing insights into DMV biogenesis and spatial coordination of SARS-CoV-2 replication. Live cell imaging combined with an infection sensor reveals profound remodeling of cytoskeleton elements. Pharmacological inhibition of their dynamics suppresses SARS-CoV-2 replication. We thus report insights into virus-induced cytopathic effects and provide alongside a comprehensive publicly available repository of 3D datasets of SARS-CoV-2-infected cells for download and smooth online visualization.

The world is now strengthening its Information and Communication Technology (ICT) capabilities to secure economic growth and national competitiveness. The role of ICT is important for problems like COVID-19. ICT based innovation is effective in responding to problems for industry, economy, and society. However, we need to understand, not from the perspective of performance or investment, that the use and performance of ICT technology are promoted when each country's ICT related environment, policies, governance, and regulations are effective. We need to share sustainable ICT experiences, successes, and challenges to solve complex problems and reorganize policies. This study proposes a Text Mining methodology from a future-oriented perspective to extract semantic system patterns from International Telecommunication Union (ITU) professional reports. In the text extracted from the report, we found a new relationship pattern and a potential topic. The research results provide insights into a diverse perspective for policymakers to search for successful ICT strategies.

Background: The Nepal government issued a nationwide lockdown due to COVID-19 from 24 March to 21 July 2020 This halted elective medical services in our hospital A number of modifications in the orthopaedic practices at our department were made

Introduction Health risk factors, including lifestyle risks and health literacy, are known to contribute to the chronic disease epidemic. According to the Centers for Disease Control and Prevention (CDC), chronic diseases account for 90% of healthcare costs, morbidity, and mortality. In the United States, healthcare providers attempt to modulate a limited set of risks. However, chronic diseases continue to proliferate despite expansion of wellness programs and drugs to manage and prevent chronic conditions. Pandemics, exemplified by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), show that people in good health suffer mortality rates at 10% the rate compared to those with pre-existing chronic conditions. Healthcare costs and morbidity rates often parallel mortality rates. New root-cause risk and health tools that accommodate low health literacy and are linked to personalized health improvement care plans are needed to reverse the chronic disease epidemic. Reported here is a study on 70 manufacturing employees in the Midwest US using a personalized and group approach to chronic disease reversal and prevention which may also find utility in pandemic severity and policy decisions. Methods Health, lifestyle, behavior, and motivation data were collected on 70 individuals at the beginning of a nine-month disease reversal and prevention program. The data were updated every two to six months over the period. Inputs included information from a novel health risk assessment, serum biomarkers specific for chronic disease, and traditional medical information. Using all these data we generated robust, personalized, and modifiable care plans that were implemented by the participant and guided by a care team including health coaches and medical providers. Periodic renewal of profile data and biomarkers facilitated adjustment of care plans to optimize the path toward health goals set mutually by the participant and the care team. Results Ninety percent of participants experienced a favorable reduction in chronic disease biomarkers. The reduction in serum biomarkers coincided with a reduction in disease and risk attributes based on medical chart data and before and after interviews. Hemoglobin A1C, for example, lowered in all but one participant concomitant with reported improved energy and reduced need for medications in the majority of participants. Markers of inflammation lowered across the population. Most importantly each individual reported improvement in their overall health. Conclusions This simple, inexpensive, root-cause based risk and health approach generates a do no harm action plan that guides a care team, including the participant, on a path to improved health. The data demonstrate that changes in a novel risk calculator score coincide with changes in sensitive biomarkers for chronic disease. When the risks of an individual are reduced, the biomarkers reflect that change with self-reported wellbeing also improved. This program and process may be of value to society plagued with escalating levels of chronic disease and merits further study and implementation.

Introduction: The current pandemic coronavirus (COVID-19) is a novel disease with no standardized course of treatment and cure. This novelty, origin, and dispersion of COVID-19 have been reported to cause chaos, anxiety, and fear among the general population. Aim: The present study aimed to explore the correlation between different age groups, in relation to their general coping strategies, fear, and anxiety due to COVID-19. Methodology: The research study employed a total sample of 135 participants. The sample was divided into four age groups: 12-18, 19-25, 26-55, and 56-85. Participants were selected through convenience sampling. General coping strategies employed by these participants were assessed using a brief COPE scale, the COVID-19 fear scale was used to assess fear, and coronavirus anxiety scale was used to screen anxiety. Results: Our results indicated that age has a negative correlation with adaptive coping and positive correlation with problem-focused coping, emotion-focused coping, and fear of COVID-19. The most used coping strategy among the age groups 12-18 and 19-25 age group was adaptive coping;for the 26-55 age group, it was problem-focused coping;and for the age group 56-85, emotion-focused coping was used the most. Conclusion: The findings of the current research could help to make the intervention procedure tailor-made for different age groups, thereby ensuring adherence and relatability to the precautionary directions.

Hypertension (HTN) and chronic kidney disease (CKD) are increasingly recognized in pediatric patients and represent risk factors for cardiovascular morbidity and mortality later in life. In CKD, enhanced tubular sodium reabsorption is a leading cause of HTN due to augmented extracellular fluid volume expansion. The renin-angiotensin-aldosterone system (RAAS) upregulates various tubular sodium cotransporters that are also targets of the hormone fibroblast growth factor 23 (FGF23) and its co-receptor Klotho. FGF23 inhibits the activation of 1,25-dihydroxyvitamin D that is a potent suppressor of renin biosynthesis. Here we review the complex interactions and disturbances of the FGF23CKlotho axis, vitamin D, and the RAAS relevant to blood pressure regulation and discuss the therapeutic strategies aimed at mitigating their pathophysiologic contributions to HTN.

Saponins are one of the most numerous and diverse groups of plant natural products. They serve a range of ecological roles including plant defence against disease and herbivores and possibly as allelopathic agents in competitive interactions between plants. Some saponins are also important pharmaceuticals, and the underexplored biodiversity of plant saponins is likely to prove to be a vital resource for future drug discovery. The biological activity of saponins is normally attributed to the amphipathic properties of these molecules, which consist of a hydrophobic triterpene or sterol backbone and a hydrophilic carbohydrate chain, although some saponins are known to have potent biological activities that are dependent on other aspects of their structure. This chapter will focus on the biological activity and the synthesis of some of the best-studied examples of plant saponins and on recent developments in the identification of the genes and enzymes responsible for saponin synthesis.

Adopter le travail a distance, en tout ou en partie, permet aux employeurs d'offrir la flexibilit que de nombreux employs recherchent et de raliser diverses conomies de co?ts. Au moment de s'engager dans cette voie, il est toutefois important que les entreprises examinent des le dpart beaucoup d'aspects touchant la fiscalit et la paie pour attnuer les risques lis a la non-conformit. Quels sont ces aspects lis a l'imp?t sur les socits et a la paie? Une politique officielle peut-elle aider a attnuer les risques de non-conformit? Quels autres aspects faut-il prendre en compte outre l'imp?t et la paie? La politique gouvernementale doit-elle soutenir ce changement? Cet article rsume les divers aspects de l'laboration d'une politique organisationnelle en matiere de travail a distance et conclut que, comme c'est le cas pour toute autre stratgie d'entreprise, le travail a distance comporte des avantages, a condition de grer efficacement la complexit et les co?ts qui y sont associs.Alternate abstract:Embracing remote work, either fully or partially, allows employers to offer the flexibility that many employees are seeking and also to benefit from various cost savings. As organizations embark on this journey, there are many tax and payroll considerations that should be reviewed up front so that risks relating to non-compliance can be mitigated. What are these corporate tax and payroll considerations? Can a formal policy help to mitigate compliance risks? What are other considerations besides tax and payroll? Should government policy support this workforce shift? This article summarizes the various considerations in developing an organizational remote work policy and concludes that, as is the case for any other business strategy, remote work arrangements have their benefits provided that the associated complexity and costs can be effectively managed.

Research Objectives To better understand rehabilitation practitioner experiences with transitioning to telerehabilitation services during COVID-19, specifically around the use of technology and client assessment and treatment. Design This was a qualitative study of cross-sectional design. Rehabilitation practitioners completed semi-structured interviews via Zoom. Transcribed interviews were analyzed for themes. Setting With the onset of COVID-19, rehabilitation practitioners quickly adapted and started offering telerehabilitation services where they interacted directly with the client and evaluate, diagnose, and treat their condition virtually. These services differed from prior methods of telehealth, where healthcare practitioners delivered care from one healthcare facility to another. Practitioners from both public and private clinics shifted their services to virtual platforms quickly to provide continued care to patients needing acute and prolonged rehabilitation care. Participants Twenty-four rehabilitation practitioners were recruited to participate in the study (14 physiotherapists, 4 occupational therapists, 2 speech language pathologists, 1 psychologist, 1 kinesiologist, 1 social worker, 1 orthopedic surgeon) from rural and urban clinics as well as private and publicly funded practices. Inclusion criteria required practitioners to have transitioned to telerehabilitation, either through video conferencing or telephone. Interventions N/A. Main Outcome Measures N/A. Results The overarching theme which emerged from the data was providing continued access to care. Rehabilitation practitioners quickly transitioned to using the telephone or video conferencing platforms such as Zoom to connect with clients. Multiple subthemes emerged allowing for a better understanding of the transition to telerehabilitation during COVID-19. Barriers to offering telerehabilitation services included adequate access to technology (computer, laptop, tablet) and IT support for the client and sufficient internet bandwidth. Limited availability of validated virtual assessments made the transition difficult for practitioners. However, many benefits emerged such as easier scheduling of interdisciplinary meetings, increased client accountability, better access to group programming, and decreased travel times to clinics. Conclusions Although there were challenges, especially surrounding technology, the switch to telerehabilitation had many benefits and could be a viable method of delivering care that goes beyond the COVID-19 pandemic. Author(s) Disclosures Authors have no conflicts of interest to disclose.

The ongoing COVID-19 pandemic brought about several challenges in both learning and instructive styles. Chief among these was engagement in classrooms that were remote, in-person or switched between the two due to quarantine periods. In a content centric biomaterials core course, here we describe an inclusive engagement toolkit that combines peer-supported learning with a structured reflection of learning objectives that allowed learners to be engaged at high levels and take responsibility for their own learning and course progression.

In the last 30 years, the study of virus evolution has undergone a transformation. Originally concerned with disease and its emergence, virus evolution had not been well integrated into the general study of evolution. This chapter reviews the developments that have brought us to this new appreciation for the general significance of virus evolution to all life. We now know that viruses numerically dominate all habitats of life, especially the oceans. Theoretical developments in the 1970s regarding quasispecies, error rates, and error thresholds have yielded many practical insights into virusChost dynamics. The human diseases of HIV-1 and hepatitis C virus cannot be understood without this evolutionary framework. Yet recent developments with poliovirus demonstrate that viral fitness can be the result of a consortia, not one fittest type, a basic Darwinian concept in evolutionary biology. Darwinian principles do apply to viruses, such as with Fisher population genetics, but other features, such as reticulated and quasispecies-based evolution distinguish virus evolution from classical studies. The available phylogenetic tools have greatly aided our analysis of virus evolution, but these methods struggle to characterize the role of virus populations. Missing from many of these considerations has been the major role played by persisting viruses in stable virus evolution and disease emergence. In many cases, extreme stability is seen with persisting RNA viruses. Indeed, examples are known in which it is the persistently infected host that has better survival. We have also recently come to appreciate the vast diversity of phage (DNA viruses) of prokaryotes as a system that evolves by genetic exchanges across vast populations (Chapter 10). This has been proposed to be the big bang of biological evolution. In the large DNA viruses of aquatic microbes we see surprisingly large, complex and diverse viruses. With both prokaryotic and eukaryotic DNA viruses, recombination is the main engine of virus evolution, and virus host co-evolution is common, although not uniform. Viral emergence appears to be an unending phenomenon and we can currently witness a selective sweep by retroviruses that infect and become endogenized in koala bears.

Viruses utilize cellular lipids and manipulate host lipid metabolism to ensure their replication and spread. Therefore, the identification of lipids and metabolic pathways that are suitable targets for antiviral development is crucial. Using a library of compounds targeting host lipid metabolic factors and testing them for their ability to block pseudorabies virus (PRV) and vesicular stomatitis virus (VSV) infection, we found that U18666A, a specific inhibitor of Niemann-Pick C1 (NPC1), is highly potent in suppressing the entry of diverse viruses including pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). NPC1 deficiency markedly attenuates viral growth by decreasing cholesterol abundance in the plasma membrane, thereby inhibiting the dynamics of clathrin-coated pits (CCPs), which are indispensable for clathrin-mediated endocytosis. Significantly, exogenous cholesterol can complement the dynamics of CCPs, leading to efficient viral entry and infectivity. Administration of U18666A improves the survival and pathology of PRV- and influenza A virus-infected mice. Thus, our studies demonstrate a unique mechanism by which NPC1 inhibition achieves broad antiviral activity, indicating a potential new therapeutic strategy against SARS-CoV-2, as well as other emerging viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-021-1929-y and is accessible for authorized users.

In order to solve the problems of the traditional anti-jamming algorithm of broadband wireless communication, such as poor anti-jamming performance and high bit error rate, an anti-jamming algorithm of broadband wireless communication based on Embedded MCU is proposed. In the broadband wireless communication based on embedded single-chip microcomputer, the m-sequence of communication signal data is constructed, encoded and decoded. Finally, CRC redundancy test and error correction are carried out for the decoded communication data, so far the design of broadband wireless communication anti-interference algorithm based on embedded single-chip microcomputer is completed. Through the contrast experiment, compared with the traditional anti-jamming algorithm of broadband wireless communication, the experimental results show that compared with the traditional anti-jamming algorithm of broadband wireless communication, the proposed anti-jamming algorithm of broadband wireless communication based on Embedded MCU has lower bit error rate, which shows that it has better anti-jamming ability.

Individuals with Acquired Brain Injury (ABI) suffer chronic impairment across cognitive, physical and psycho-social domains, and the experience of anxiety, isolation and apathy has been amplified by the COVID-19 pandemic A qualitative evaluation was conducted of 14 individuals with ABI who had participated in series of COVID adapted group-based intervention(s) that had been designed to improve wellbeing Eight themes were identified: Facilitating Safety, Fostering Positive Emotion, Managing and Accepting Difficult Emotions, Promoting Meaning, Finding Purpose and Accomplishment, Facilitating Social Ties, (Re)Connecting to Nature, and Barriers to Efficacy Findings are discussed with respects to recent theoretical developments in positive psychology and wellbeing science and support the use of online and outdoor interventions to enhance wellbeing in individuals living with ABI during the COVID-19 pandemic This paper makes a unique contribution to second wave positive psychology (PP2 0) through the application of recent advances in wellbeing science to an ABI population during the COVID-19 pandemic In doing so, this paper lays the foundation for new interventions that not only reduce impairment and distress, but also create opportunities for meaning and enhanced wellbeing in people living with chronic conditions and those individuals living with ABI in particular

INTRODUCTION: Statins have been commonly used for primary and secondary cardiovascular prevention. We hypothesized that statins may improve in-hospital outcomes for hospitalized patients with COVID-19 due to its known anti-inflammatory effects. METHODS: We conducted a retrospective study at the largest municipal healthcare system in the United States including adult patients who were hospitalized for COVID-19 between 03/01/2020 and 12/01/2020. The primary endpoint was in-hospital death. Propensity score matching was conducted to balance possible confounding variables between patients receiving statins during hospitalization (statin group) and those not receiving statins (non-statin group). Multivariate logistic regression was used to evaluate the association of statin use and other variables with in-hospital outcomes. RESULTS: 8897 patients were eligible for study enrollment with 3359 patients in the statin group and 5538 patients in the non-statin group. After propensity score matching, both the statin and non-statin groups included 2817 patients. Multivariate logistic regression analysis showed that the statin group had a significantly lower risk of in-hospital mortality (OR 0.71; (0.63, 0.80); P<0.001) and mechanical ventilation (OR 0.80; (0.71, 0.90); p<0.001) compared to the non-statin group. CONCLUSION: Statin use was associated with lower likelihood of in-hospital mortality and invasive mechanical ventilation in hospitalized patients with COVID-19.