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164 lines
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<title>04 January, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population.</strong> -
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Background: During the current COVID 19 pandemic, the rate of morbidity and mortality was considerably lower in BCG vaccinated countries like Pakistan. BCG has been shown to provide cross protection to both disseminated TB as well as non related viral infections in BCG vaccinated children which is consistent with COVID 19 morbidity in the younger age group. Recently, this cross protection was attributed to trained immunity (TI) associated with BCG recall responses in the innate arm of the immune system. Little is known about the longevity of BCG Trained Immunity (TI) beyond early childhood. Objective: To assess the BCG induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross protection against COVID 19 and other viral infections. Study Design: In this cross sectional study, healthy young adults and adolescents (n=20) were recruited from 16-40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition. Methods: BCG induced cytokine responses were assessed using prototypic markers for cells of the TI network macrophages [M1 (TNF alpha, IFN gamma), M2 (IL10)], NK (IL2), Gamma delta (gamma delta]) T (IL17, IL4)} and SARS CoV2 IgG antibodies against RBD using short term (12 hours) cultures assay. Results: Significant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNF alpha (9148 pg/ml) followed by IL10 (488 pg/ml) and IFN gamma(355 pg/ml). The ratio of unstimulated vs BCG stimulated cytokines was 132 fold higher for TNF alpha, 40 fold for IL10, and 27 fold for IFN gamma. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG. Conclusion: The presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro and anti inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID 19 pandemic in the younger age groups resulting in lower morbidity and mortality.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.02.573408v1" target="_blank">BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population.</a>
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<li><strong>VLP-Based Model for Study of Airborne Viral Pathogens</strong> -
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The recent COVID-19 pandemic has underscored the danger of airborne viral pathogens. The lack of model systems to study airborne pathogens limits the understanding of airborne pathogen distribution, as well as potential surveillance and mitigation strategies. In this work, we develop a novel model system to study airborne pathogens using virus like particles (VLP). Specifically, we demonstrate the ability to aerosolize VLP and detect and quantify aerosolized VLP RNA by Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) in real-time fluorescent and colorimetric assays. Importantly, the VLP model presents many advantages for the study of airborne viral pathogens: (i) similarity in size and surface components; (ii) ease of generation and noninfectious nature enabling study of BSL3 and BSL4 viruses; (iii) facile characterization of aerosolization parameters; (iv) ability to adapt the system to other viral envelope proteins including those of newly discovered pathogens and mutant variants; (v) the ability to introduce viral sequences to develop nucleic acid amplification assays.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.03.574055v1" target="_blank">VLP-Based Model for Study of Airborne Viral Pathogens</a>
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<li><strong>Antigen non-specific CD8+ T cells accelerate cognitive decline in aged mice following respiratory coronavirus infection</strong> -
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Primarily a respiratory infection, numerous patients infected with SARS-CoV-2 present with neurologic symptoms, some continuing long after viral clearance as a persistent symptomatic phase termed long COVID. Advanced age increases the risk of severe disease, as well as incidence of long COVID. We hypothesized that perturbations in the aged immune response predispose elderly individuals to severe coronavirus infection and post-infectious sequelae. Using a murine model of respiratory coronavirus, mouse hepatitis virus strain A59 (MHV-A59), we found that aging increased clinical illness and lethality to MHV infection, with aged animals harboring increased virus in the brain during acute infection. This was coupled with an unexpected increase in activated CD8+ T cells within the brains of aged animals but reduced antigen specificity of those CD8+ T cells. Aged animals demonstrated spatial learning impairment following MHV infection, which correlated with increased neuronal cell death and reduced neuronal regeneration in aged hippocampus. Using primary cell culture, we demonstrated that activated CD8+ T cells induce neuronal death, independent of antigen-specificity. Specifically, higher levels of CD8+ T cell-derived IFN-{gamma} correlated with neuronal death. These results support the evidence that CD8+ T cells in the brain directly contribute to cognitive dysfunction following coronavirus infection in aged individuals.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.02.573675v1" target="_blank">Antigen non-specific CD8+ T cells accelerate cognitive decline in aged mice following respiratory coronavirus infection</a>
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<li><strong>Four Years of COVID-19: Saudi Arabia, Egypt and Pakistan Have the Highest Research Growth Rates From 2020-2023</strong> -
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We tried to assess the global research scholarly output after COVID-19 (from 2020 to 2023). Based on Scopus record, the world has produced 15, 041, 579 publications with 86, 165, 933 citations. We analyzed those countries, which have published at least 150, 000 research papers. For each country, we retrieved total number of publications, % growth rate, total citations, citations per paper, Field Weighted Citation Impact (FWCI), and % international collaboration. Twenty-seven (n=27) countries were found to be highly productive, with China leading the way in number of publications. Citation metrics are dominated by the USA, China, and European countries. Specifically, Switzerland, Netherlands, and Australia are notable for their high impact and influence. Saudi Arabia achieved the highest growth rate of 53.5%, and highest international collaboration (76.5%). Infact Saudi Arabia also attained high citations per article (8.8), and an FWCI of 1.63. While, Pakistan exhibited an 8.4 citations per article, FWCI of 1.54, growth rate of 34.9%, and collaborative percentage of 64.9%. Egypt also attained the 2nd highest growth rate (n=36.1). Based on four (n=4) distinct performance metrics, Pakistan and Saudi Arabia were in the top ten group.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.31.573759v1" target="_blank">Four Years of COVID-19: Saudi Arabia, Egypt and Pakistan Have the Highest Research Growth Rates From 2020-2023</a>
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<li><strong>Complex changes in serum protein levels in COVID-19 convalescents</strong> -
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The COVID-19 pandemic, triggered by severe acute respiratory syndrome coronavirus 2, has affected millions of people worldwide. Much research has been dedicated to our understanding of COVID-19 disease heterogeneity and severity, but less is known about recovery associated changes. To address this gap in knowledge, we quantified the proteome from serum samples from 29 COVID-19 convalescents and 29 age-, race-, and sex-matched healthy controls. Samples were acquired within the first months of the pandemic. Many proteins from pathways known to change during acute COVID-19 illness, such as from the complement cascade, coagulation system, inflammation and adaptive immune system, had returned to levels seen in healthy controls. In comparison, we identified 22 and 15 proteins with significantly elevated and lowered levels, respectively, amongst COVID-19 convalescents compared to healthy controls. Some of the changes were similar to those observed for the acute phase of the disease, i.e. elevated levels of proteins from hemolysis, the adaptive immune systems, and inflammation. In contrast, some alterations opposed those in the acute phase, e.g. elevated levels of CETP and APOA1 which function in lipid/cholesterol metabolism, and decreased levels of proteins from the complement cascade (e.g. C1R, C1S, and VWF), the coagulation system (e.g. THBS1 and VWF), and the regulation of the actin cytoskeleton (e.g. PFN1 and CFL1) amongst COVID-19 convalescents. We speculate that some of these shifts might originate from a transient decrease in platelet counts upon recovery from the disease. Finally, we observed race-specific changes, e.g. with respect to immunoglobulins and proteins related to cholesterol metabolism.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.26.513886v2" target="_blank">Complex changes in serum protein levels in COVID-19 convalescents</a>
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<li><strong>Rapid and specific detection of single nanoparticles and viruses in microfluidic laminar flow via confocal fluorescence microscopy</strong> -
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Mainstream virus detection relies on the specific amplification of nucleic acids via polymerase chain reaction, a process that is slow and requires extensive laboratory expertise and equipment. Other modalities, such as antigen-based tests, allow much faster virus detection but have reduced sensitivity. In this study, we report the development of a flow virometer for the specific and rapid detection of single nanoparticles based on confocal microscopy. The combination of laminar flow and multiple dyes enable the detection of correlated fluorescence signals, providing information on nanoparticle volumes and specific chemical composition properties, such as viral envelope proteins. We evaluated and validated the assay using fluorescent beads and viruses, including SARS-CoV-2. Additionally, we demonstrate how hydrodynamic focusing enhances the assay sensitivity for detecting clinically-relevant virus loads. Based on our results, we envision the use of this technology for clinically relevant bio-nanoparticles, supported by the implementation of the assay in a portable and user-friendly setup.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.31.573251v1" target="_blank">Rapid and specific detection of single nanoparticles and viruses in microfluidic laminar flow via confocal fluorescence microscopy</a>
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</div></li>
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<li><strong>DNA origami vaccine (DoriVac) nanoparticles improve both humoral and cellular immune responses to infectious diseases</strong> -
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Current SARS-CoV-2 vaccines have demonstrated robust induction of neutralizing antibodies and CD4+ T cell activation, however CD8+ responses are variable, and the duration of immunity and protection against variants are limited. Here we repurposed our DNA origami vaccine platform, DoriVac, for targeting infectious viruses, namely SARS-CoV-2, HIV, and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific HR2 peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induced neutralizing antibodies, Th1 CD4+ T cells, and CD8+ T cells in naive mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validated that DoriVac, when conjugated with antigenic peptides or proteins, induced promising cellular immune responses in human cells. These results suggest that DoriVac holds potential as a versatile, modular vaccine platform, capable of inducing both humoral and cellular immunities. The programmability of this platform underscores its potential utility in addressing future pandemics.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.29.573647v1" target="_blank">DNA origami vaccine (DoriVac) nanoparticles improve both humoral and cellular immune responses to infectious diseases</a>
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<li><strong>Major role of S-glycoprotein in providing immunogenicity and protective immunity in mRNA lipid nanoparticle vaccines based on SARS-CoV-2 structural proteins</strong> -
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Recently we have developed an mRNA lipid nanoparticle (mRNA-LNP) platform providing efficient long-term expression of an encoded gene in vivo after both intramuscular and intravenous application. Based on this platform, we have generated mRNA-LNP coding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combinations in vivo. As a result, all candidate vaccine compositions coding S and N proteins induced excellent anti-RBD and N titers of binding antibodies. T cell responses mainly represented specific CD4+ T cell lymphocyte producing IL-2 and TNF-. mRNA-LNP coding M protein did not show high immunogenicity. High neutralizing activity was detected in sera of mice vaccinated with mRNA-LNP coding S protein (alone or in combinations) against closely related strains but was not detectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to the mRNA-N in the vaccine composition enhanced immunogenicity of mRNA-N inducing more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancement of immune response to the N protein in the mRNA-LNP vaccine.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.30.573713v1" target="_blank">Major role of S-glycoprotein in providing immunogenicity and protective immunity in mRNA lipid nanoparticle vaccines based on SARS-CoV-2 structural proteins</a>
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<li><strong>An ATP-Binding Cassette Transporter Gene Links Innate and Adaptive Immune Responses</strong> -
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Positive-strand RNA viruses and DNA viruses generate double-stranded RNA (dsRNA) during their replication processes and innate immune responses against viral infections are orchestrated by numerous interferon-stimulating genes, yet the detailed coordination of downstream signaling of anti-viral immune responses is not fully understood. Recent studies suggest 2’-5’-Oligoadenylate Synthetase 1 (OAS1) may have a protective role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections; however, the mechanism regulating OAS1 remains uninvestigated. Our aim is to understand the regulation of OAS1 and its modulation of RNaseL activity, as this has significant implications for responses to RNA viruses, including Vesicular stomatitis virus (VSV) and SARS-CoV-2. We explore the hypothesis that ABCF1 an ATP-binding cassette family member protein, a key regulator of innate immune responses and macrophage polarization and cytokine storm, play a role in regulating the antiviral responses and downstream dsRNA signaling revealed by measuring responses to the synthetic dsRNA analog termed poly (I:C). We utilize ABCF1 haplo-insufficient mice to discover that ABCF1 modulates the amplitude and frequency of VSV-specific Cytolytic T lymphocyte in anti-viral immune responses and suggests that innate immune responses underpin this process. To understand this mechanism, we describe that ABCF1 interacts with 2’-5’-oligoadenylate synthetase 1 (OAS1) which in turn modulates essential proteins that leads to the modulation of RNaseL activity via ABCE1. Furthermore, we find that ABCF1, possibly acting through IRF3 phosphorylation and dimerization, also influences the production of interferon-alpha (IFN-a) and interferon-beta (IFN-b) in bone marrow-derived macrophages. Overall, we unexpectedly discovered that ABCF1 acts as a crucial link between innate and adaptive immunity, regulating the development of adaptive Cytolytic T lymphocyte responses and interacting with OAS1, a key regulator of innate immune responses against viral infections. Exploring pharmacological agents that target ABCE1 or ABCF1 may lead to the discovery of novel modalities for countering SARS CoV-2 and other viruses where OAS1 is a crucial innate immune response gene.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.31.573785v1" target="_blank">An ATP-Binding Cassette Transporter Gene Links Innate and Adaptive Immune Responses</a>
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<li><strong>Identifying Best Practices for Future Pandemic Preparedness: A Comparative Policy Analysis</strong> -
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Background: This comparative policy analysis studies government responses to the COVID-19 pandemic, with a focus on countries severely impacted by the virus. The study aims to assess the impact of various confounding variables, including GDP, healthcare spending per capita, poverty rate, and population density, on the effectiveness of pandemic response policies. Methods: The data obtained for the policies employs a multifaceted approach that incorporates both economic and non-economic policies. The analysis includes fiscal policies encompassing healthcare and economic sectors, adaptability in policy adjustments, and non-economic measures. The study also utilizes a principal component analysis (PCA) to identify similarities and differences among countries with varying levels of success. Results: Key findings indicate that successful countries adopted proactive fiscal policies addressing healthcare and economic challenges simultaneously. Flexibility and adaptability in policy adjustments emerged as significant traits among effective responses. Stricter non-economic policies were generally associated with improved pandemic outcomes. Additionally, effective contact tracing played a pivotal role in case identification and isolation. Conclusions: This research underscores the importance of a comprehensive and adaptable approach to pandemic response, considering economic, healthcare, and social factors. The study’s insights offer valuable guidance to governments and policymakers seeking to enhance preparedness plans for future global health crises. As the world continues to grapple with ongoing and evolving pandemic challenges, the lessons drawn from the pandemic can be used as a model of future success.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/7mwbj/" target="_blank">Identifying Best Practices for Future Pandemic Preparedness: A Comparative Policy Analysis</a>
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<li><strong>Assessing the differentiated impacts of COVID-19 on the immigration flows to Europe</strong> -
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The immediate effects of COVID-19 on mortality, fertility, and internal and international migration have been widely studied. Particularly, immigration to high-income countries declined in 2020. However, the persistence of these declines, and the extent to which they have impacted different migration corridors are yet to be established. Drawing on immigration flows from Eurostat and ARIMA time-series models, we assess the impact of COVID-19 on different immigration streams to seven European countries. We forecast counterfactual levels of immigration in 2020 and 2021 assuming no pandemic, and compare these estimates with actual immigration counts. We use regression modelling to explore the role of immigrants´ origin, distance, stringency measures and GDP trends at origins and destinations as potential driving forces of changes in immigration during COVID-19. Our results show that, while there was a general decline in immigration during 2020, inflows returned to expected levels in 2021, except for Spain. However, immigration corridors originating from outside the Schengen Area were still hardly affected in 2021. Immigrant´s origin emerged as the main factor modulating immigration changes during the pandemic, and to a lesser extent stringency measures and GDP trends in destination countries. Contextual factors at origin seem to have been less important.
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🖺 Full Text HTML: <a href="https://osf.io/bsezk/" target="_blank">Assessing the differentiated impacts of COVID-19 on the immigration flows to Europe</a>
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<li><strong>Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Improve Vaccine Immunomodulation</strong> -
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Over the past few decades, the development of potent and safe immune-activating adjuvant technologies has become the heart of intensive research in the constant fight against highly mutative and immune evasive viruses such as influenza, SARS-CoV-2, and HIV. Herein, we developed a highly modular saponin-based nanoparticle platform incorporating toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, TLR7/8a adjuvants and their mixtures. These various TLRa-SNP adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific Th-responses that could be of interest depending on the target disease for prevention. In a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform which could improve the design of vaccines for and dramatically impact modern vaccine development.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.16.549249v2" target="_blank">Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Improve Vaccine Immunomodulation</a>
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<li><strong>The Double-Edged Sword Mediatized Integration Processes during the COVID-19 Pandemic</strong> -
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The issue of media appropriation by refugees experienced a boom in 2015, but since then the topic has received less attention over the years. In addition, refugees have faced significant challenges since the appearance of COVID-19. In this paper, I discuss how Syrian migrants and refugees who have lived in Germany for at least four years used media technologies during COVID-19. I present findings from twelve guided interviews conducted in a northern German city. In summary, media use in general has increased, as has that of the majority society. On the other hand, media use during the pandemic has proven to be a double-edged sword: Some refugees had great(er) problems coping with the situation, while others gained self-empowerment and agency through using media during the pandemic.
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🖺 Full Text HTML: <a href="https://osf.io/yjt23/" target="_blank">The Double-Edged Sword Mediatized Integration Processes during the COVID-19 Pandemic</a>
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<li><strong>Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response</strong> -
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Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. It also imposes a substantial economic burden through increased absenteeism during periods of active pathogen circulation. Vaccination is generally accepted as the most effective strategy for influenza prevention. As both influenza A and B viruses circulate and cause seasonal epidemics, vaccines need to include multiple antigens derived from different viral subtypes. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains. Additionally, the rapid variability of the virus poses challenges in providing extended protection beyond a single season. Therefore, mRNA technology is particularly promising for influenza prevention, as it enables the rapid development of multivalent vaccines and allows for quick updates of their antigenic composition. mRNA vaccines have already proven successful in preventing COVID-19 by eliciting rapid cellular and humoral immune responses. In this study, we present the development of a trivalent mRNA vaccine candidates, evaluate its immunogenicity using the hemagglutination inhibition assay, and assess its efficacy in animals. We demonstrate the higher immunogenicity of the mRNA vaccine candidates compared to the inactivated split influenza vaccine and its enhanced ability to generate a cross-specific humoral immune response. These findings highlight the potential mRNA technology in overcoming current limitations of influenza vaccines and hold promise for ensuring greater efficacy in preventing seasonal influenza outbreaks.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.30.573722v1" target="_blank">Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response</a>
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<li><strong>Tying the Knot: Unraveling the Intricacies of the Coronavirus Frameshift Pseudoknot</strong> -
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Understanding and targeting functional RNA structures towards treatment of coronavirus infection can help us to prepare for novel variants of SARS-CoV-2 (the virus causing COVID-19), and any other coronaviruses that could emerge via human-to-human transmission or potential zoonotic (inter-species) events. Leveraging the fact that all coronaviruses use a mechanism known as -1 programmed ribosomal frameshifting (-1 PRF) to replicate, we apply algorithms to predict the most energetically favourable secondary structures (each nucleotide involved in at most one pairing) that may be involved in regulating the -1 PRF event in coronaviruses, especially SARS-CoV-2. We compute previously unknown most stable structure predictions for the frameshift site of coronaviruses via hierarchical folding, a biologically motivated framework where initial non-crossing structure folds first, followed by subsequent, possibly crossing (pseudoknotted), structures. Using mutual information from 181 coronavirus sequences, in conjunction with the algorithm KnotAli, we compute secondary structure predictions for the frameshift site of different coronaviruses. We then utilize the Shapify algorithm to obtain most stable SARS-CoV-2 secondary structure predictions guided by frameshift sequence-specific and genome-wide experimental data. We build on our previous secondary structure investigation of the singular SARS-CoV-2 68 nt frameshift element sequence, by using Shapify to obtain predictions for 132 extended sequences and including covariation information. Previous investigations have not applied hierarchical folding to extended length SARS-CoV-2 frameshift sequences. By doing so, we simulate the effects of ribosome interaction with the frameshift site, providing insight to biological function. We contribute in-depth discussion to contextualize secondary structure dual-graph motifs for SARS-CoV-2, highlighting the energetic stability of the previously identified 3_8 motif alongside the known dominant 3_3 and 3_6 (native-type) -1 PRF structures. Integrating experimental data within minimum free energy (MFE) hierarchical folding algorithms provides novel structure predictions to distill the relationship between RNA structure and function. In particular, fully categorizing most stable secondary structure predictions via hierarchical folding supports our identification of motif transitions and critical site targets for future therapeutic research.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.28.573501v1" target="_blank">Tying the Knot: Unraveling the Intricacies of the Coronavirus Frameshift Pseudoknot</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID Ultrasound Trial</strong> - <b>Conditions</b>: Long Covid <br/><b>Interventions</b>: Device: Splenic Ultrasound <br/><b>Sponsors</b>: SecondWave Systems Inc.; University of Minnesota; MCDC (United States Department of Defense) <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity After COVID-19 Vaccines in Adapted Schedules</strong> - <b>Conditions</b>: Coronavirus Disease 2019; COVID-19 <br/><b>Interventions</b>: Drug: BNT162b2 30µg; Drug: BNT162b2 20µg; Drug: BNT162b2 6µg; Drug: mRNA-1273 100µg; Drug: mRNA-1273 50µg; Drug: ChAdOx1-S [Recombinant] <br/><b>Sponsors</b>: Universiteit Antwerpen <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Could Wearing Face Mask Have Affected Demodex Parasite</strong> - <b>Conditions</b>: Pandemic, COVID-19; Demodex Infestation <br/><b>Interventions</b>: Diagnostic Test: standard superficial skin biopsy (SSSB) <br/><b>Sponsors</b>: Nurhan Döner Aktaş <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>TDCS Stimulation After Covid-19 Infection</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Procedure: Transcranial Direct Stimulation <br/><b>Sponsors</b>: Istanbul Medipol University Hospital; Alanya Alaaddin Keykubat University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of a Booster Vaccination With an Adapted Vaccine</strong> - <b>Conditions</b>: SARS-CoV2 Infection <br/><b>Interventions</b>: Biological: PHH-1V81; Biological: Comirnaty Omicron XBB1.5 <br/><b>Sponsors</b>: Hipra Scientific, S.L.U <br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Combined Modified RNA Vaccine Candidate Against COVID-19 and Influenza.</strong> - <b>Conditions</b>: Influenza; COVID-19 <br/><b>Interventions</b>: Biological: Influenza and COVID-19 Combination A; Biological: Licensed influenza vaccine; Biological: COVID-19 Vaccine; Biological: Influenza and COVID-19 Combination B; Biological: Placebo <br/><b>Sponsors</b>: BioNTech SE; Pfizer <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Transcranial Pulse Stimulation (TPS) in Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Fatigue <br/><b>Interventions</b>: Device: Transcranial pulse stimulation Verum; Device: Transcranial pulse stimulation Sham <br/><b>Sponsors</b>: Medical University of Vienna; Campus Bio-Medico University <br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plant extracts modulate cellular stress to inhibit replication of mouse Coronavirus MHV-A59</strong> - The Covid-19 infection outbreak led to a global epidemic, and although several vaccines have been developed, the appearance of mutations has allowed the virus to evade the immune response. Added to this is the existing risk of the appearance of new emerging viruses. Therefore, it is necessary to explore novel antiviral therapies. Here, we investigate the potential in vitro of plant extracts to modulate cellular stress and inhibit murine hepatitis virus (MHV)-A59 replication. L929 cells were…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A randomized double-blind placebo-controlled trial of an inhibitor of plasminogen activator inhibitor-1 (TM5614) in mild to moderate COVID-19</strong> - An inhibitor of plasminogen activator inhibitor (PAI)-1, TM5614, inhibited thrombosis, inflammation, and fibrosis in several experimental mouse models. To evaluate the efficacy and safety of TM5614 in human COVID-19 pneumonia, phase IIa and IIb trials were conducted. In an open-label, single-arm trial, 26 Japanese COVID-19 patients with mild to moderate pneumonia were treated with 120-180 mg of TM5614 daily, and all were discharged without any notable side effects. Then, a randomized,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral effect of palmatine against infectious bronchitis virus through regulation of NF-κB/IRF7/JAK-STAT signalling pathway and apoptosis</strong> - 1. Infectious bronchitis virus (IBV), a gamma-coronavirus, can infect chickens of all ages and leads to an acute contact respiratory infection. This study evaluated the anti-viral activity of palmatine, a natural non-flavonoid alkaloid, against IBV in chicken embryo kidney (CEK) cells.2. The half toxic concentration (CC(50)) of palmatine was 672.92 μM, the half inhibitory concentration (IC(50)) of palmatine against IBV was 7.76 μM and the selection index (SI) was 86.74.3. Mode of action assay…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>One-step silver coating of polypropylene surgical mask with antibacterial and antiviral properties</strong> - Face masks can filter droplets containing viruses and bacteria minimizing the transmission and spread of respiratory pathogens but are also an indirect source of microbes transmission. A novel antibacterial and antiviral Ag-coated polypropylene surgical mask obtained through the in situ and one-step deposition of metallic silver nanoparticles, synthesized by silver mirror reaction combined with sonication or agitation methods, is proposed in this study. SEM analysis shows Ag nanoparticles fused…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A novel inhibitor of SARS-CoV infection: Lactulose octasulfate interferes with ACE2-Spike protein binding</strong> - The ongoing challenge of managing coronaviruses, particularly SARS-CoV-2, necessitates the development of effective antiviral agents. This study introduces Lactulose octasulfate (LOS), a sulfated disaccharide, demonstrating significant antiviral activity against key coronaviruses including SARS-CoV-2, SARS-CoV, and MERS-CoV. We hypothesize LOS operates extracellularly, targeting the ACE2-S-protein axis, due to its low cellular permeability. Our investigation combines biolayer interferometry…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IFN-γ-mediated control of SARS-CoV-2 infection through nitric oxide</strong> - INTRODUCTION: The COVID-19 pandemic has highlighted the need to identify mechanisms of antiviral host defense against SARS-CoV-2. One such mediator is interferon-g (IFN-γ), which, when administered to infected patients, is reported to result in viral clearance and resolution of pulmonary symptoms. IFN-γ treatment of a human lung epithelial cell line triggered an antiviral activity against SARS-CoV-2, yet the mechanism for this antiviral response was not identified.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>HDAC1-3 inhibition increases SARS-CoV-2 replication and productive infection in lung mesothelial and epithelial cells</strong> - CONCLUSION: This study highlights a previously unrecognized effect of HDAC1-3 inhibition in increasing SARS-CoV-2 cell entry, replication and productive infection correlating with increased expression of ACE2 and TMPRSS2. These data, while adding basic insight into COVID-19 pathogenesis, warn for the use of HDAC inhibitors in SARS-CoV-2 patients.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Should Virtual Objective Structured Clinical Examination (OSCE) Teaching Replace or Complement Face-to-Face Teaching in the Post-COVID-19 Educational Environment: An Evaluation of an Innovative National COVID-19 Teaching Programme</strong> - Background The COVID-19 pandemic brought about drastic changes to medical education and examinations, with a shift to online lectures and webinars. Additionally, social restrictions in the United Kingdom (UK) inhibited students’ ability to practice for objective structured clinical examination (OSCE) with their peers. Methods The Virtual OSCE buddy scheme (VOBS) provided a means to practice OSCE skills virtually by linking groups of 2-6 final-year medical students with a junior doctor who had…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Valorizing pomegranate wastes by producing functional silver nanoparticles with antioxidant, anticancer, antiviral, and antimicrobial activities and its potential in food preservation</strong> - The food sector generates massive amounts of waste, which are rich in active compounds, especially polyphenols; therefore, valorizing these wastes is a global trend. In this study, we produce silver nanoparticles from pomegranate wastes, characterized by enhanced antioxidant, anticancer, antiviral, and antimicrobial properties and investigated their potential to maintain the fruit quality for sixty days in market. The pomegranate waste-mediated silver nanoparticles (PPAgNPs) were spherical shape…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody-Conjugated Magnetic Nanoparticle Therapy for Inhibiting T-Cell Mediated Inflammation</strong> - Tolerance induction is critical for mitigating T cell-mediated inflammation. Treatments based on anti-CD3 monoclonal antibody (mAb) play a pivotal role in inducing such tolerance. Anti-CD3 mAb conjugated with dextran-coated magnetic nanoparticles (MNPs) may induce inflammatory tolerance is posited. MNPs conjugated with anti-CD3 mAb (Ab-MNPs) are characterized using transmission and scanning electron microscopy, and their distribution is assessed using a nanoparticle tracking analyzer. Compared…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Optimization of the 5-plex digital PCR workflow for simultaneous monitoring of SARS-CoV-2 and other pathogenic viruses in wastewater</strong> - Wastewater-based epidemiology is a valuable tool for monitoring pathogenic viruses in the environment, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). While quantitative polymerase chain reaction (qPCR) is widely used for pathogen surveillance in wastewater, it can be affected by inhibition and is limited to relative quantification. Digital PCR (dPCR) offers potential solutions to these limitations. In this…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Porcine delta coronavirus inhibits NHE3 activity of porcine intestinal epithelial cells through miR-361-3p/NHE3 regulatory axis</strong> - Porcine deltacoronavirus (PDCoV) infection in piglets can cause small intestinal epithelial necrosis and atrophic enteritis, which leads to severe damages to host cells, and result in diarrhea. In this study, we investigated the relationship between miR-361, SLC9A3(Solute carrier family 9, subfamily A, member 3), and NHE3(sodium-hydrogen exchanger member 3) in in porcine intestinal epithelial cells (IPI-2I) cells after PDCoV infection. Our results showed that the ssc-miR-361-3p expression…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In silico</em> study of inhibition activity of boceprevir drug against 2019-nCoV main protease</strong> - Boceprevir drug is a ketoamide serine protease inhibitor with a linear peptidomimetic structure that exhibits inhibition activity against 2019-nCoV main protease. This paper reports electronic properties of boceprevir and its molecular docking as well as molecular dynamics simulation analysis with protein receptor. For this, the equilibrium structure of boceprevir has been obtained by DFT at B3LYP and ωB97XD levels with 6-311+G(d,p) basis set in gas and water mediums. HOMO-LUMO and absorption…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Novel sofosbuvir derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective</strong> - The human coronavirus, SARS-CoV-2, had a negative impact on both the economy and human health, and the emerging resistant variants are an ongoing threat. One essential protein to target to prevent virus replication is the viral RNA-dependent RNA polymerase (RdRp). Sofosbuvir, a uridine nucleotide analog that potently inhibits viral polymerase, has been found to help treat SARS-CoV-2 patients. This work combines molecular docking and dynamics simulation (MDS) to test 14 sofosbuvir-based…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Differential Roles of Interleukin-6 in Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Cardiometabolic Diseases</strong> - Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can lead to a cytokine storm, unleashed in part by pyroptosis of virus-infected macrophages and monocytes. Interleukin-6 (IL-6) has emerged as a key participant in this ominous complication of COVID-19. IL-6 antagonists have improved outcomes in patients with COVID-19 in some, but not all, studies. IL-6 signaling involves at least 3 distinct pathways, including classic-signaling, trans-signaling, and trans-presentation…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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