Isolation, structural elucidation and molecular docking studies against SARS-CoV-2 main protease of new stigmastane-type steroidal glucosides isolated from the whole plants of Vernonia gratiosa.

Phytochemical investigation of the whole plants of Vernonia gratiosa Hance. led in the isolation and identification of two new stigmastane-type steroidal glucosides (1-2), namely vernogratiosides A (1), and B (2). Their chemical structures were fully elucidated based on 1 D/2D NMR spectroscopic, HR-ESI-MS data analyses, and by producing derivatives by chemical reactions. The binding potential of the isolated compounds to replicase protein - main protease of SARS-CoV-2 were examined using the molecular docking simulations. Our results show that the isolated steroidal glucosides (1-2) bind to the substrate-binding site of SARS-CoV-2 main protease with binding affinities of -7.2 and -7.6 kcal/mol, respectively, as well as binding abilities equivalent to N3 inhibitor that has already been reported (-7.5 kcal/mol).

Lessons for Vietnam on the Use of Digital Technologies to Support Patient-Centered Care in Low- and Middle-Income Countries in the Asia-Pacific Region: Scoping Review.

BACKGROUND: A rapidly aging population, a shifting disease burden and the ongoing threat of infectious disease outbreaks pose major concerns for Vietnam's health care system. Health disparities are evident in many parts of the country, especially in rural areas, and the population faces inequitable access to patient-centered health care. Vietnam must therefore explore and implement advanced solutions to the provision of patient-centered care, with a view to reducing pressures on the health care system simultaneously. The use of digital health technologies (DHTs) may be one of these solutions. OBJECTIVE: This study aimed to identify the application of DHTs to support the provision of patient-centered care in low- and middle-income countries in the Asia-Pacific region (APR) and to draw lessons for Vietnam. METHODS: A scoping review was undertaken. Systematic searches of 7 databases were conducted in January 2022 to identify publications on DHTs and patient-centered care in the APR. Thematic analysis was conducted, and DHTs were classified using the National Institute for Health and Care Excellence evidence standards framework for DHTs (tiers A, B, and C). Reporting was in line with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. RESULTS: Of the 264 publications identified, 45 (17%) met the inclusion criteria. The majority of the DHTs were classified as tier C (15/33, 45%), followed by tier B (14/33, 42%) and tier A (4/33, 12%). At an individual level, DHTs increased accessibility of health care and health-related information, supported individuals in self-management, and led to improvements in clinical and quality-of-life outcomes. At a systems level, DHTs supported patient-centered outcomes by increasing efficiency, reducing strain on health care resources, and supporting patient-centered clinical practice. The most frequently reported enablers for the use of DHTs for patient-centered care included alignment of DHTs with users' individual needs, ease of use, availability of direct support from health care professionals, provision of technical support as well as user education and training, appropriate governance of privacy and security, and cross-sectorial collaboration. Common barriers included low user literacy and digital literacy, limited user access to DHT infrastructure, and a lack of policies and protocols to guide the implementation and use of DHTs. CONCLUSIONS: The use of DHTs is a viable option to increase equitable access to quality, patient-centered care across Vietnam and simultaneously reduce pressures on the health care system. Vietnam can take advantage of the lessons learned by other low- and middle-income countries in the APR when developing a national road map to digital health transformation. Recommendations that Vietnamese policy makers may consider include emphasizing stakeholder engagement, strengthening digital literacy, supporting the improvement of DHT infrastructure, increasing cross-sectorial collaboration, strengthening governance of cybersecurity, and leading the way in DHT uptake.

Online knowledge sharing and creativity in the context of working from home during the COVID-19 pandemic: Very Informal Newsletter on Library Automation

PurposeThe COVID-19 lockdown has forced many organizations and employees to work from home. In such uncertain and unprecedented context, it is crucial for organizations to stimulate their employees' creativity to adapt to new working environment and thus to sustain and improve organizational performance. This paper aims to examine how to stimulate employees' creativity by focusing on their online knowledge sharing (OKS) behaviors, their use of online platforms and their organizations' innovation climate in a working from home (WFH) context because of the lockdown. For empirical analysis, this research uses data from Vietnam – a developing country in the Southeast Asia.Design/methodology/approachData are collected from employees working in Ho Chi Minh City but WFH during the COVID-19 lockdown. Structural equation models are used for analyzing the data.FindingsOnline platform use and organizational innovation climate are positively associated with creativity directly and indirectly via the mediating roles of internal and external OKS.Research limitations/implicationsThis research provides policymakers, organizational leaders and managers with an important evidence on how to stimulate creativity by emphasizing the roles of knowledge sharing, online platforms and innovation climate. Accordingly, relevant practical implications are also drawn to sustain or improve organizational performance in the context of WFH context because of COVID-19 lockdown. This research also contributes to knowledge management literature by providing an evidence on the relationships between online platform use, organizational innovation climate, OKS and creativity.Originality/valueThis research is among the early attempts that explore the associations between employees' use of online platforms, their organizations' innovation climate, their internal and external OKS behaviors and their creativity in the context of WFH because of a lockdown.

Medical Waste Treatment Process Based on Blockchain Technology - A Case Study of Covid-19 Waste Handling in Vietnam

Medical waste management is a challenging problem that not only directly affects the environment but also people's health. This urgent issue is getting more and more attention in the context of the Covid-19 pandemic. New infections are increasing exponentially in all countries globally, especially developing countries with large populations (e.g., India, Brazil, Bangladesh). Studies on the spread of the disease have listed one of the causes of this crisis as the Covid-19 waste treatment process not being followed correctly and the difficulty of data retrieval. Vietnam was also severely damaged by the Covid-19 epidemic, although the government initially controlled the disease very well. The Covid-19 waste treatment process in Vietnam is still being processed manually and with a combination of many departments. Data sharing and tracking are also tricky because they are centrally stored in different facilities/departments. In addition, there is a lack of synchronization and transparency of shared data. This paper is one of the first attempts to fill that gaps by applying Blockchain technology and decentralized storage. Relevant parties will retrieve all data, and the source of waste can be easily traced. We also implemented a proof-of-concept based on the Hyperledger Fabric platform to demonstrate the idea's feasibility. In the evaluation, we observe the process of initializing and querying data. These initial efforts will lay the groundwork for more in-depth studies to create an initiative for Vietnam's medical waste treatment process when faced with a new wave of infections or another epidemic. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies Among Vietnamese Healthcare Workers by Dosing Interval for ChAdOx1 nCoV-19 Vaccine.

BACKGROUND: Before the SARS-CoV-2 Delta variant arrived in Vietnam, case rates suggested seroprevalence of SARS-CoV-2 was low. Beginning in March 2021, we assessed different dosing schedules and adverse events following immunization (AEFIs) for ChAdOx1 nCoV-19 vaccine among healthcare workers (HCWs). METHODS: We performed a prospective cohort study to estimate the prevalence of IgG antibodies to SARS-CoV-2 before and after ChAdOx1 nCoV-19 vaccination. We conducted antibody testing among HCWs in February 2021 (baseline), before the second dose (June-July 2021), and 1 and 3 months after the second dose. We detected antibodies to SARS-CoV-2 using Tetracore® FlexImmArray™, and surrogate neutralizing antibodies using GenScript cPass™. Neither assay can distinguish natural from vaccine-induced antibodies. We assessed AEFIs through interview post-dose 1 and 1 month post-dose 2. RESULTS: Before vaccination, 1/617 participants (0.16%) had antibodies to SARS-CoV-2. Of these 617, 405 were vaccinated with ChAdOx1 nCoV-19 with 4-8- (60%), 9-12- (27%), or ≥13-week (13%) intervals between the 2 doses. Three months following series completion, 99% and 97% of vaccinated participants had ≥1 sample with detectable antibodies and surrogate neutralizing antibodies against SARS-CoV-2, respectively. We observed no significant differences among those with different dosing intervals at last follow-up. All participants reported PCR testing for SARS-CoV-2 during the study; 2 (0.5%) were laboratory-confirmed. AEFIs were more frequent post-dose 1 (81%) vs post-dose 2 (21%). CONCLUSIONS: In this population, regardless of dosing interval, ChAdOx1 nCoV-19 induced antibodies within 3 months of the second dose. These findings may offer flexibility to policymakers when balancing programmatic considerations with vaccine effectiveness.

Online knowledge sharing and creativity in the context of working from home during the COVID-19 pandemic

Purpose The COVID-19 lockdown has forced many organizations and employees to work from home. In such uncertain and unprecedented context, it is crucial for organizations to stimulate their employees' creativity to adapt to new working environment and thus to sustain and improve organizational performance. This paper aims to examine how to stimulate employees' creativity by focusing on their online knowledge sharing (OKS) behaviors, their use of online platforms and their organizations' innovation climate in a working from home (WFH) context because of the lockdown. For empirical analysis, this research uses data from Vietnam - a developing country in the Southeast Asia. Design/methodology/approach Data are collected from employees working in Ho Chi Minh City but WFH during the COVID-19 lockdown. Structural equation models are used for analyzing the data. Findings Online platform use and organizational innovation climate are positively associated with creativity directly and indirectly via the mediating roles of internal and external OKS. Research limitations/implications This research provides policymakers, organizational leaders and managers with an important evidence on how to stimulate creativity by emphasizing the roles of knowledge sharing, online platforms and innovation climate. Accordingly, relevant practical implications are also drawn to sustain or improve organizational performance in the context of WFH context because of COVID-19 lockdown. This research also contributes to knowledge management literature by providing an evidence on the relationships between online platform use, organizational innovation climate, OKS and creativity. Originality/value This research is among the early attempts that explore the associations between employees' use of online platforms, their organizations' innovation climate, their internal and external OKS behaviors and their creativity in the context of WFH because of a lockdown.

PHILM2Web: A high-throughput database of macromolecular host-pathogen interactions on the Web.

During infection, the pathogen's entry into the host organism, breaching the host immune defense, spread and multiplication are frequently mediated by multiple interactions between the host and pathogen proteins. Systematic studying of host-pathogen interactions (HPIs) is a challenging task for both experimental and computational approaches and is critically dependent on the previously obtained knowledge about these interactions found in the biomedical literature. While several HPI databases exist that manually filter HPI protein-protein interactions from the generic databases and curated experimental interactomic studies, no comprehensive database on HPIs obtained from the biomedical literature is currently available. Here, we introduce a high-throughput literature-mining platform for extracting HPI data that includes the most comprehensive to date collection of HPIs obtained from the PubMed abstracts. Our HPI data portal, PHILM2Web (Pathogen-Host Interactions by Literature Mining on the Web), integrates an automatically generated database of interactions extracted by PHILM, our high-precision HPI literature-mining algorithm. Currently, the database contains 23 581 generic HPIs between 157 host and 403 pathogen organisms from 11 609 abstracts. The interactions were obtained from processing 608 972 PubMed abstracts, each containing mentions of at least one host and one pathogen organisms. In response to the coronavirus disease 2019 (COVID-19) pandemic, we also utilized PHILM to process 25 796 PubMed abstracts obtained by the same query as the COVID-19 Open Research Dataset. This COVID-19 processing batch resulted in 257 HPIs between 19 host and 31 pathogen organisms from 167 abstracts. The access to the entire HPI dataset is available via a searchable PHILM2Web interface; scientists can also download the entire database in bulk for offline processing. Database URL: http://philm2web.live.

Treatment of COVID-19 Patients with Two Units of Convalescent Plasma in a Resource-Constrained State.

IMPORTANCE: Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. OBJECTIVE: Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. Our study aims to determine the safety and efficacy of treating hospitalized COVID-19 patients with 2 units of COVID-19 convalescent plasma (CCP). METHOD: This was a retrospective study of Arkansas patients treated with CCP using the (US) Food and Drug Administration (FDA) emergency Investigational New Drug (eIND) mechanism from April 9, 2020, through August 9, 2020. It was a multicenter, statewide study in a low-resource setting, which are areas that lack funding for health care cost coverage on various levels including individual, family, or social. Adult patients (n = 165, volunteer sample) in Arkansas who were hospitalized with severe or life-threatening acute COVID-19 disease as defined by the FDA criteria were transfused with 2 units of CCP (250 mL/unit) using the FDA eIND mechanism. The primary outcome was 7- and 30-day mortality after the second unit of CCP. RESULTS: Unadjusted mortality was 12.1% at 7 days and 23.0% at 30 days. The unadjusted mortality was reduced to 7.7% if the first CCP unit was transfused on the date of diagnosis, 8.7% if transfused within 3 days of diagnosis, and 32.0% if transfused at or after 4 or more days of diagnosis. The risk of death was higher in patients that received low, negative, or missing titer CCP units in comparison to those that received higher titer units. CONCLUSION: The provision of 2 units of CCP was associated with a reduction in mortality in patients treated with high titer units within 3 days of COVID-19 diagnosis. Given the results, CCP is a viable, low-cost therapy in resource-constrained states and countries.

SARS-CoV-2 main protease and papain-like protease inhibition by abietane-type diterpenes isolated from the branches of Glyptostrobus pensilis using molecular docking studies.

Using various chromatographic methods, five abietane-type diterpenes were isolated from the branches of Glyptostrobus pensilis for the first time. The chemical structures of the isolates were identified by modern spectroscopic techniques, including 1H and 13C nuclear magnetic resonance spectroscopy and by comparison with the literature. In addition, the binding potential of the isolated compounds to replicase protein, SARS-CoV-2 main protease and papain-like protease, were examined using molecular docking studies. In silico results suggested that G. pensilis as well as abietane-types diterpenes are potential candidates for the prevention and treatment of SARS-CoV-2.

Potent and Selective Knockdown of Tyrosine Kinase 2 by Antisense Oligonucleotides.

Tyrosine kinase 2 (TYK2) is a member of the JAK family of nonreceptor tyrosine kinase, together with JAK1, JAK2, and JAK3. JAKs are important signaling mediators of many proinflammatory cytokines and represent compelling pharmacological targets for autoimmune and inflammatory diseases. Pan-acting small-molecule JAK inhibitors were approved for the treatment of rheumatoid arthritis and ulcerative colitis. However, their limited selectivity among JAK members have led to undesirable side effects, driving a search toward specific JAK inhibitors. Recently, TYK2 has emerged as a target of choice for the treatment of autoimmune diseases and severe COVID-19 with an optimum balance between efficacy and safety, based on observations from human genetics studies and clinical outcomes of several agents targeting cytokine pathways for which TYK2 plays an essential role. In this article, we address selective targeting of TYK2 from the genetic sequence space through development of antisense oligonucleotides (ASOs) against TYK2 mRNA. Potent ASO candidates were identified from the screening of over 200 ASOs using locked nucleic acid gapmer design. The lead ASOs exhibited potent and selective knockdown of TYK2 mRNA and protein across a panel of model human cell lines in a dose-dependent manner, showing no reduction in the mRNA and protein expression levels of other JAK paralogs. In agreement with the depletion of TYK2 proteins, several TYK2-mediated cytokine signaling pathways, including IFN-α and IL-12, were inhibited upon ASO treatment. Our results established the TYK2 ASOs as investigational tool compound and potential therapeutic agent for the treatment of autoimmune diseases and severe COVID-19.

Influences of reopening businesses and social venues: COVID-19 incidence rate in East Texas county.

As the on-going severe acute respiratory syndrome coronavirus 2 pandemic, we aimed to understand whether economic reopening (EROP) significantly influenced coronavirus disease 2019 (COVID-19) incidence. COVID-19 data from Texas Health and Human Services between March and August 2020 were analysed. COVID-19 incidence rate (cases per 100 000 population) was compared to statewide for selected urban and rural counties. We used joinpoint regression analysis to identify changes in trends of COVID-19 incidence and interrupted time-series analyses for potential impact of state EROP orders on COVID-19 incidence. We found that the incidence rate increased to 145.1% (95% CI 8.4-454.5%) through 4th April, decreased by 15.5% (95% CI -24.4 -5.9%) between 5th April and 30th May, increased by 93.1% (95% CI 60.9-131.8%) between 31st May and 11th July and decreased by 13.2% (95% CI -22.2 -3.2%) after 12 July 2020. The study demonstrates the EROP policies significantly impacted trends in COVID-19 incidence rates and accounted for increases of 129.9 and 164.6 cases per 100 000 populations for the 24- or 17-week model, respectively, along with other county and state reopening ordinances. The incidence rate decreased sharply after 12th July considering the emphasis on a facemask or covering requirement in business and social settings.

Ensembl 2021.

The Ensembl project (https://www.ensembl.org) annotates genomes and disseminates genomic data for vertebrate species. We create detailed and comprehensive annotation of gene structures, regulatory elements and variants, and enable comparative genomics by inferring the evolutionary history of genes and genomes. Our integrated genomic data are made available in a variety of ways, including genome browsers, search interfaces, specialist tools such as the Ensembl Variant Effect Predictor, download files and programmatic interfaces. Here, we present recent Ensembl developments including two new website portals. Ensembl Rapid Release (http://rapid.ensembl.org) is designed to provide core tools and services for genomes as soon as possible and has been deployed to support large biodiversity sequencing projects. Our SARS-CoV-2 genome browser (https://covid-19.ensembl.org) integrates our own annotation with publicly available genomic data from numerous sources to facilitate the use of genomics in the international scientific response to the COVID-19 pandemic. We also report on other updates to our annotation resources, tools and services. All Ensembl data and software are freely available without restriction.

Provision of COVID-19 Convalescent Plasma in a Resource-Constrained State.

BACKGROUND: Arkansas is a rural state of 3 million people. It is ranked fifth for poverty nationally. The first case of coronavirus disease 2019 (COVID-19) in Arkansas occurred on 11 March 2020. Since then, approximately 8% of all Arkansans have tested positive. Given the resource limitations of Arkansas, COVID-19 convalescent plasma (CCP) was explored as a potentially lifesaving, therapeutic option. Therefore, the Arkansas Initiative for Convalescent Plasma was developed to ensure that every Arkansan has access to this therapy. STUDY DESIGN AND METHOD: This brief report describes the statewide collaborative response from hospitals, blood collectors, and the Arkansas Department of Health (ADH) to ensure that CCP was available in a resource-limited state. RESULTS: Early contact tracing by ADH identified individuals who had come into contact with "patient zero" in early March. Within the first week, 32 patients tested positive for COVID-19. The first set of CCP collections occurred on 9 April 2020. Donors had to be triaged carefully in the initial period, as many had recently resolved their symptoms. From our first collections, with appropriate resource and inventory management, we collected sufficient CCP to provide the requested number of units for every patient treated with CCP in Arkansas. CONCLUSIONS: The Arkansas Initiative, a statewide effort to ensure CCP for every patient in a resource-limited state, required careful coordination among key players. Collaboration and resource management was crucial to meet the demand of CCP products and potentially save lives.