Beliefs in Conspiracy Theories and Online News Consumption during the onset of the COVID-19 pandemic -
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+Using an original survey covering 17 countries, this paper documents the prevalence of beliefs in theories related to the COVID-19 pandemic and characterizes the informational, demographic, and trust profiles of individuals who believe in conspiracy theories. There is considerable variation across countries in the level of conspiracy beliefs, with people in a set of countries like Romania, Poland, Greece, and Hungary being relatively more susceptible than respondents in northern Europe. We find several factors are correlated with conspiracy beliefs across countries. Relative to respondents who do not read news on social media, social media users tend to endorse more conspiracies, and this is the case for Facebook, Instagram, and YouTube users in particular. We also observe a link between distrust in medical experts or government and endorsement of conspiracy theories in most countries. In a subset of countries, we also find individuals with medium level of education and those who are younger to believe in a higher number of conspiracy theories.
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Global Sensitivity Analysis of the Onset of Nasal Passage Infection by SARS-CoV-2 With Respect to Heterogeneity in Host Physiology and Host Cell-Virus Kinetic Interactions -
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+Throughout the COVID-19 pandemic, positive nasal swab tests have revealed dramatic population heterogeneity in viral titers spanning 6 orders-of-magnitude. Our goal here is to probe potential drivers of infection outcome sensitivity arising from (i) physiological heterogeneity between hosts and (ii) host-variant heterogeneity in the detailed kinetics of cell infection and viral replication. Toward this goal, we apply global sensitivity methods (Partial Rank Correlation Coefficient analysis and Latin Hypercube Sampling) to a physiologically faithful, stochastic, spatial model of inhaled SARS-CoV-2 exposure and infection in the human respiratory tract. We focus on the nasal passage as the primary origin of respiratory infection and site of clinical testing, and we simulate the spatial and dynamic progression of shed viral load and infected cells in the immediate 48 hours post infection. We impose immune evasion, i.e., suppressed immune protection, based on the preponderance of clinical evidence that nasal infections occur rapidly post exposure, largely independent of immune status. Global sensitivity methods provide the de-correlated outcome sensitivities to each source of within-host heterogeneity, including the dynamic progression of sensitivities at 12, 24, 36, and 48 hours post infection. The results reveal a dynamic rank-ordering of the drivers of outcome sensitivity in early infection, providing insights into the dramatic population-scale outcome diversity during the COVID-19 pandemic. While we focus on SARS-CoV-2, the model and methods are applicable to any inhaled virus in the immediate 48 hours post infection.
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Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants -
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+Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes. Increasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, NETosis, and T-cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma immunoglobulins and B cells, as well as dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to the failure of viral clearance in patients with fatal illness. Our longitudinal multi-omics profiling study revealed novel temporal coordination across diverse omics that potentially explain disease progression, providing insights that inform the targeted development of therapies for hospitalized COVID-19 patients, especially those critically ill.
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Dynamic gene expression analysis reveals distinct severity phases of immune and cellular dysregulation in COVID-19 -
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+Background: COVID-19 patients experience dynamic changes in immune and cellular function over time with potential clinical implications. However, there is insufficient research investigating, on a gene expression level, the mechanisms that become activated or suppressed over time as patients deteriorate or recover, which can inform use of repurposed and novel drugs as therapies. Objective: To investigate longitudinal changes in gene expression profiles throughout the COVID-19 disease timeline. Methods: Three-hundred whole blood samples from 128 adult patients were collected during hospitalization from COVID-19, with up to five samples per patient. Transcriptome sequencing (RNA-Seq), differential gene expression analysis and pathway enrichment was performed. Drug-gene set enrichment analysis was used to identify FDA-approved medications that could inhibit critical genes and proteins at each disease phase. Prognostic gene-expression signatures were generated using machine learning to distinguish 3 disease stages. Results: Samples were longitudinally grouped by clinical criteria and gene expression into six disease phases: Mild, Moderate, Severe, Critical, Recovery, and Discharge. Distinct mechanisms with differing trajectories during COVID-19 hospitalization were apparent. Antiviral responses peaked early in COVID-19, while heme metabolism pathways became active much later during disease. Adaptive immune dysfunction, inflammation, and metabolic derangements were most pronounced during phases with higher disease severity, while hemostatic abnormalities were elevated early and persisted throughout the disease course. Drug-gene set enrichment analysis predicted repurposed medications for potential use, including platelet inhibitors in early disease, antidiabetic medications for patients with increased disease severity, and dasatinib throughout the disease course. Disease phases could be categorized using specific gene signatures for prognosis and treatment selection. Disease phases were also highly correlated to previously developed sepsis endotypes, indicating that severity and disease timing were significant contributors to heterogeneity observed in sepsis and COVID-19. Conclusions: Higher temporal resolution of longitudinal mechanisms in COVID-19 revealed multiple immune and cellular changes that were activated at different phases of COVID-19. Understanding how a patient's gene expression profile changes over time can permit more accurate risk stratification of patients and provide time-dependent personalized treatments with repurposed medications. This creates an opportunity for timely intervention before patients transition to a more severe phase, potentially accelerating patients to recovery.
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Supply Chain Resilience and Medicine Availability in Saudi Arabian Pharmacies: A Case Study in Jeddah -
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+This article investigates the critical issue of supply chain resilience and its impact on medicine availability in Saudi Arabian pharmacies, focusing on a case study in Jeddah. During the COVID-19 pandemic, pharmacies in Jeddah experienced significant supply chain disruptions, leading to challenges in maintaining medicine availability. The study explores the resilience measures implemented by these pharmacies during the crisis and offers practical recommendations to enhance supply chain resilience. These recommendations include regulatory adjustments, the adoption of advanced technology, and strategic approaches to ensure uninterrupted access to essential medicines. This research underscores the crucial role of resilient supply chains in the context of public health and emphasizes the need for proactive measures to safeguard medicine availability in Saudi Arabian pharmacies and similar healthcare settings.
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Zheln.com: A protocol for a universal living overview of health-related systematic reviews -
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+BACKGROUND Objectives. 1. Identify and monitor most of published systematic reviews. 2. Tag the identified systematic records with medical specialties. 3. Select or crowdfund reviews for further appraisal. 4. Critically appraise and replicate the selected systematic reviews. 5. Disseminate practice implications of positively appraised reviews to both the public and evidence-based practitioners in health care and other fields associated with intervention into a human life, such as education, business, policy, or ecology. METHODS Eligibility criteria. Record eligibility is assessed by checking the record title and, if the title failed, abstract against the âtrue positive criteriaâ for systematic reviews taken from the publication by Shojania & Bero, 2001 (PMID 11525102). The record/study flow is as follows: All eligible records are amenable for tagging, selection, and crowdfunding process; Only those eligible records that have been selected or crowdfunded are subject to critical appraisal; For all records that have been selected, all relevant reports are collected; Reports are grouped into studies; Only for the studies appraised positively, practical implications are summarized and disseminated. COVID-19 publications are not selected. Crowdfunding an appraisal of any eligible record is possible for any individual or organization. Information sources. MEDLINE via PubMed. Adding other search sources, such as Scopus, OSF, and medRxiv, is planned in the future when more appraisers become available. The Replicated Version of the PubMed Systematic Review Subset Query Zheln Edition (DOI 10.17605/OSF.IO/Z3JU7) will be used. The searches are run daily. Risk of bias. Critical appraisal will feature: Duplication assessment; Replication; Assessment against the MECIR conduct standards; ROB-ME assessment; GRADE assessment. Synthesis of results. No across-studies synthesis is planned. Within-studies, I will formulate explicit practice-relevant statements based on the extracted health outcomes and quality-of-conduct assessment. Also, the process of each critical appraisal is video-recorded and published on YouTube daily. OTHER Funding. The review is crowdfunded; the details are available from the Zheln website (https://zheln.com). Crowd funders had no role in the design of the protocol. They will be able to request critical appraisal and additional critical appraisal (with new data provided) of any eligible record but will not influence the review process otherwise. Registration. The project is hosted on GitHub. Also, there is an umbrella Open Science Framework project that links repositories and preprints (DOI 10.17605/OSF.IO/EJKFC). The protocol for this overview of systematic reviews has been submitted for registration in PROSPERO.
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Not Causal or Descriptive But Some Secret, Other Thing: Entropy as a Criterion for Causal Learning -
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+While many classify studies as either descriptive or causal, I argue that causality is a continuous construct, and different inference modesâexperimental, observational and mechanisticâcan at best provide only partial causal information. To discriminate between the relative value of different inference modes, I employ statistical entropy as a possible yardstick for evaluating research designs as different operations on causal graphs. Rather than dichotomize studies as either causal or descriptive, the concept of entropy instead emphasizes the relative causal knowledge gained from a given research finding. I employ this theory to clarify why and when researchers relied on divergent modes of inference to determine the efficacy of vaccines over the course of the COVID-19 pandemic.
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Exploring the trajectory and correlates of social isolation for veterans across a 6-month period during COVID-19 -
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+Social isolation is a relevant problem for veterans who are at risk for disengaging from others as a function of transition stress from military life to civilian life, and given high rates of exposure to trauma and psychological distress. Few researchers have examined social isolation in veterans over time, particularly during COVID-19 that led to significant barriers and restrictions on social interactions. The purpose of this longitudinal study was to assess veteransâ experience of social isolation and its mental health and social functioning correlates during a 6-month period of the COVID-19 pandemic. Participants were 188 United States veterans of the Iraq and Afghanistan wars, who completed a total of four assessments: one every two months for a total duration of six months. Surveys included measures of global mental health and social functioning as indicated by perceived emotional support, quality of marriage, and couple satisfaction. Multilevel modeling was used to assess 1) growth models to determine whether social isolation changed over time and the trajectory of that change (i.e., linear or quadratic); and 2) whether social isolation was related to both concurrent and prospective indicators of mental health and social functioning. All analyses included person mean centered and grand mean centered isolation to assess for within-and between-person effects. Veterans reported a quadratic trajectory in social isolation that decreased slightly and stabilized over time. Findings indicate that higher social isolation, at both the within- and between-person level, was negatively associated with concurrent emotional support, mental health, quality of marriage, and couple satisfaction. However, all prospective effects were nonsignificant at the within-person level. Results suggest although isolation may decrease over time, veterans report worse mental health and social functioning during times when they report higher levels of social isolation compared to themselves and others. Future work is needed to determine if interventions can be applied during those times to prevent or target those negative associations.
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Associations among anxiety, risk perception, preventive behaviors, and personality in Japanese older adults aged 78 to 99 years during the COVID-19 pandemic -
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+Background and Objectives: To deepen the understanding of processes underlying older adultsâ behavior during the COVID-19 pandemic, we investigated associations among affective (anxiety about the coronavirus), cognitive (perceived risk of infection and fatality), and behavioral (engagement in preventive behaviors) variables. We also examined how these variables were predicted by personality traits measured before the pandemic. Research Design and Methods: Older adults (N = 1,727; 78â99 years old) were recruited from an ongoing longitudinal cohort study started in 2010. They responded to a questionnaire sent in August 2020, which included four items measuring COVID-19 anxiety, infection risk perception, fatality risk perception, and engagement in preventive behaviors. Big Five personality traits were measured years ago when the participants had first participated in the study. Results: Most participants felt anxious, engaged in preventive behaviors, and overestimated infection and fatality risks. Older age was associated with low anxiety, a low perception of infection risk, a high perception of fatality risk, and a little engagement in preventive behaviors. Women were more susceptible to the pandemic than men were, demonstrated by higher scores on all four items. Partial correlation analysis controlling for age and sex demonstrated positive associations among all four items except for infection risk perception and preventive behaviors. Anxiety and perceived infection risk were positively predicted by neuroticism and conscientiousness, respectively. Engagement in preventive behaviors was positively predicted by extraversion, openness to experience, and conscientiousness. Discussion and Implications: We highlighted the critical distinction between infection and fatality risk perceptions and demonstrated the need to consider each individualâs attributes.
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Long-term serial passaging of SARS-CoV-2 reveals signatures of convergent evolution -
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+Measures to control the COVID-19 pandemic such as antiviral therapy and vaccination have been challenged by ongoing virus evolution under antiviral and immune pressures. Understanding viral evolutionary dynamics is crucial for responding to SARS-CoV-2, and preparing for the next pandemic, by informing prediction of virus adaptation, public health strategies, and design of broadly effective therapies. Whole-genome sequencing (WGS) of SARS-CoV-2 during the pandemic enabled fine-grained studies of virus evolution in the human population. Serial passaging in vitro offers a controlled environment to investigate the emergence and persistence of genetic variants that may confer selective advantage. Nine virus lineages, including four "variants of concern" and three former "variants under investigation" as designated by the World Health Organisation, were chosen to investigate intra- and inter-lineage evolution through long-term serial passaging in Vero E6 cells. Viruses were sampled over at least 33 passages (range 33-100) and analysed using WGS to examine evolutionary dynamics and identify key mutations with implications for virus fitness, transmissibility, and immune evasion. All passages continued to replicate in culture, despite regular accumulation of mutations. There was evidence of convergent acquisition of mutations both across passage lines and compared with contemporaneous SARS CoV-2 clinical sequences from population studies. Some of these convergent mutations are hypothesised to be important in proliferation of SARS-CoV-2 lineages, such as by evading host immune responses (e.g. S:A67V, S:H655Y). Given these mutations arose in vitro, in the absence of a multicellular host immune response, this suggests virus genome mutation resulted from stochastic events, rather than immune-driven mutation. There was a regular gain and loss of low-frequency variants during serial passaging, but some became fixed in subsequent multiple passages, suggesting either a benefit of the mutation in vitro, or at least a lack of deleterious effect. Our findings reveal valuable insights into the evolution of SARS-CoV-2 by quantitatively investigating evolutionary dynamics of the virus over the greatest number of serial passages to date. Knowledge of these evolutionary trends will be useful for public health and the development of antiviral and vaccine measures to reduce the effects of SARS CoV-2 infection on the human population.
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Blood transcriptomics analysis offers insights into variant-specific immune response to SARS-CoV-2 -
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+Bulk RNA sequencing (RNA-seq) of blood is typically used for gene expression analysis in biomedical research but is still rarely used in clinical practice. In this study, we argue that RNA-seq should be considered a routine diagnostic tool, as it offers not only insights into aberrant gene expression and splicing but also delivers additional readouts on immune cell type composition as well as B-cell and T-cell receptor (BCR/TCR) repertoires. We demonstrate that RNA-seq offers vital insights into a patient's immune status via integrative analysis of RNA-seq data from patients infected with various SARS-CoV-2 variants (in total 240 samples with up to 200 million reads sequencing depth). We compare the results of computational cell-type deconvolution methods (e.g., MCP-counter, xCell, EPIC, quanTIseq) to complete blood count data, the current gold standard in clinical practice. We observe varying levels of lymphocyte depletion and significant differences in neutrophil levels between SARS-CoV-2 variants. Additionally, we identify B and T cell receptor (BCR/TCR) sequences using the tools MiXCR and TRUST4 to show that - combined with sequence alignments and pBLAST - they could be used to classify a patient's disease. Finally, we investigated the sequencing depth required for such analyses and concluded that 10 million reads per sample is sufficient. In conclusion, our study reveals that computational cell-type deconvolution and BCR/TCR methods using bulk RNA-seq analyses can supplement missing CBC data and offer insights into immune responses, disease severity, and pathogen-specific immunity, all achievable with a sequencing depth of 10 million reads per sample.
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+SARS-CoV-2 typically utilises host angiotensin-converting enzyme 2 (ACE2) as a cellular surface receptor and host serine protease TMPRSS2 for the proteolytic activation of viral spike protein enabling viral entry. Although macrophages express low levels of ACE2, they are often found positive for SARS-CoV-2 in autopsied lungs from COVID-19 patients. As viral-induced macrophage inflammation and overwhelming cytokine release are key immunopathological events that drives exacerbated tissue damage in severe COVID-19 patients, insights into the entry of SARS-CoV-2 into macrophages are therefore critical to understand COVID-19 pathogenesis and devise novel COVID-19 therapies. Mounting evidence suggest that COVID-19 pathogenesis is associated with apoptosis, a type of programmed cell death that often leads to the release of numerous large extracellular vesicles (EVs) called apoptotic bodies (ApoBDs). Here, we showed that ApoBDs derived from SARS-CoV-2-infected cells carry viral antigens and infectious virions. Human monocyte-derived macrophages readily efferocytosed SARS-CoV-2-induced ApoBDs, resulting in SARS-CoV-2 entry and pro-inflammatory responses. To target this novel ApoBD-mediated viral entry process, we screened for ApoBD formation inhibitors and discovered that T-type voltage-gated calcium channel (T-channel) blockers can inhibit SARS-CoV-2-induced ApoBD formation. Mechanistically, T-channel blockers impaired the extracellular calcium influxes required for ApoBD biogenesis. Importantly, blockade of ApoBD formation by T-channel blockers were able to limit viral dissemination and virus-induced macrophage inflammation in vitro and in a pre-clinical mouse model of severe COVID-19. Our discovery of the ApoBD-efferocytosis-mediated viral entry reveals a novel route for SARS-CoV-2 infection and cytokine storm induction, expanding our understanding of COVID-19 pathogenesis and offering new therapeutic avenues for infectious diseases.
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Can a pan-coronavirus vaccine limit the threat of SARS-CoV-2 emerging variants and prevent any future pandemic? -
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+During coronavirus disease 2019 (COVID-19) pandemic, the initial application of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines were deemed to be effective in preventing infection. However, the efficacy of these vaccines was then significantly reduced due to the emergence of SARS-CoV-2 variants that can evade host immune response. Moreover, waning of SARS-CoV-2 neutralizing antibodies (nAbs) level over time represents another challenge to control COVID-19 ongoing waves. The short-term immunity conferred by the currently available vaccines may lead to a never-ending cycle of SARS-CoV-2 variants emergence and ongoing waves of COVID-19. In addition, the presence of animal reservoir for coronaviruses is complicating efforts to eradicate these pathogens. As such, by employing different designs and approaches, broad-spectrum or pan-coronavirus vaccines may represent a potential tool to fight various emergent variants of SARS-CoV-2 through the generation of long-lasting and cross-reactive neutralizing antibodies. The production of these broad-spectrum neutralizing antibodies is currently explored through application of strategies like the use of pathogen conserved (consensus) epitopes, heterologous sequential immunization, and mosaic nanoparticle platform. But the big questions that need answers: Can these proposed broad-spectrum or pan-coronavirus vaccines be effective against the emergent variants for SARS-CoV-2? And can they prevent any future pandemic driven by coronaviruses?
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MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with the COVID-19 Pandemic (MIP-C) -
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+Background: Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5+-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 senses single-stranded RNA and is a key pattern recognition receptor for the SARS-CoV-2 virus. Methods: This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018-December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5+-DM outbreak. Results: Sixty new anti-MDA5+, but not other MSAs surged between 2020-2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. Few (8/60) had a prior history of COVID-19, whereas 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response. Conclusions: A distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms.
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M3NetFlow: a novel multi-scale multi-hop multi-omics graph AI model for omics data integration and interpretation -
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+The integration and interpretation of multi-omics data play a crucial role in systems biology for prioritizing vital molecular targets and deciphering core signaling pathways of complex diseases, such as cancer, COVID-19 and Alzheimerâs disease. However, it remains a challenge that has not been adequately addressed. Graph neural networks (GNN) have emerged as powerful artificial intelligence models for analyzing data with a graphical structure. Nevertheless, GNN models have not been sufficiently designed for integrative and interpretable multi-omics data analysis. In this study, we propose a novel multi-scale multi-hop multi-omics GNN model, M3NetFlow, to integrate and interpret multi-omics data to rank key targets and infer core signaling pathways. Specifically, we applied the M3NetFlow model to infer cell-line-specific core signaling networks explaining drug combination response. The evaluation and comparison results on drug combination prediction showed that the M3NetFlow model achieved significantly higher prediction accuracy than existing GNN models. Furthermore, M3NetFlow can predict key targets and infer essential signaling networks regulating drug combination response. It is critical for guiding the development of personalized precision medicine for patients with drug resistance. This model can be applied to general multi-omics data-driven research. Aside from that, we developed the visualization tool, NetFlowVis, the better analysis of targets and signaling pathways of drugs and drug combinations.
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Pilot Randomized Study of RD-X19 Tx Device in Subjects With PCC (Long Covid) in the Outpatient Setting - Conditions: Post COVID-19 Condition (PCC) Interventions: Device: RDX-19 Sponsors: KNOWBio Inc.; NAMSA Recruiting
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A Phaseâ Ą Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 (COVID-19) Vaccine( ZSVG-02-O) - Conditions: SARS-CoV-2 Infection Interventions: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated Sponsors: CNBG-Virogin Biotech (Shanghai) Ltd. Recruiting
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CPAP Therapy Through a Helmet or a Full Face Mask in Patients With Acute Hypoxemic Respiratory Failure: Cross-over Study - Conditions: Pneumonia, Bacterial; Respiratory Failure; COVID-19 Pneumonia Interventions: Diagnostic Test: Arterial blood gases; Diagnostic Test: Respiratory rate (RR); Diagnostic Test: Pulseoximeter; Diagnostic Test: Assessment of accessory respiratory muscles work; Diagnostic Test: Esophageal pressure measurement; Diagnostic Test: Discomfort Visual Analog Scale (VAS); Diagnostic Test: Noninvasive blood pressure; Diagnostic Test: Heart rate Sponsors: I.M. Sechenov First Moscow State Medical University Recruiting
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Investigation of Efficacy and Safety of Electrical Signal Therapy Provided by Dr BiolyseÂź Device in COVID-19 Disease - Conditions: COVID-19 Pneumonia; Virus Diseases; COVID-19 Interventions: Device: Signal Therapy provided by Dr.Biolyse device; Other: Liquid Support Treatment Sponsors: AVB Biotechnology Recruiting
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A Phaseâ Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 (COVID-19) Vaccine( ZSVG-02-O) - Conditions: SARS-CoV-2 Infection Interventions: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: Placebo; Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated Sponsors: CNBG-Virogin Biotech (Shanghai) Ltd.; Shulan (Hangzhou) Hospital Recruiting
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SAFE Workplace Intervention for People With IDD - Conditions: Developement of Infectious Airborne Disease Prevention Workplace Curriclulm Interventions: Behavioral: SAFE Employment Training Sponsors: Temple University; National Institute on Disability, Independent Living, and Rehabilitation Research Recruiting
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Effects of an EMDR Intervention on Traumatic and Obsessive Symptoms - Conditions: Adult ALL; Post-traumatic Stress Disorder; Obsessive-Compulsive Disorder; Disgust; Guilt; Shame Interventions: Behavioral: EMDR Sponsors: University of Pisa Completed
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Lithium Long COVID Dose-finding Study - Conditions: Long COVID Interventions: Dietary Supplement: Lithium Sponsors: State University of New York at Buffalo Not yet recruiting
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Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Renal Function - Conditions: COVID-19 Pneumonia Interventions: Drug: GST-HG171 Tablets Sponsors: Fujian Akeylink Biotechnology Co., Ltd. Recruiting
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Preoperative Educational Videos on Maternal Stress Whose Children Received Congenital Heart Disease Surgery: During COVID-19 Panic - Conditions: COVID-19; Educational Videos; Maternal; Uncertainty; Anxiety; Depression; Congenital Heart Disease; Children Interventions: Other: Preoperative educational videos plus routine education; Other: Preoperative routine education Sponsors: Chung Shan Medical University Completed
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Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Liver Function - Conditions: COVID-19 Pneumonia Interventions: Drug: GST-HG171 Tablets Sponsors: Fujian Akeylink Biotechnology Co., Ltd. Completed
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Evaluation of Concordance Between Exhaled Air Test (eBAM-CoV) and RT-PCR to Detect SARS-CoV-2 - Conditions: SARS-CoV-2 Infection; COVID-19; Coronavirus Interventions: Device: eBAM Cov Testing Sponsors: Centre Hospitalier Universitaire de NÄ«mes; University of Nimes; brainsâ laboratory sas, FRANCE Not yet recruiting
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Study to Safety, Tolerability and Immunogenicity of EG-COVII in Healthy Adult - Conditions: COVID-19 Interventions: Biological: EG-COVII Sponsors: EyeGene Inc. Recruiting
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Pharmacokinetics and Bioequivalence of Aterixen 100 mg Tablets and Aterixen 100 mg Film-coated Tablets in Healthy Volunteers - Conditions: Viral Infection COVID-19 Interventions: Drug: Aterixen Sponsors: Valenta Pharm JSC Not yet recruiting
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From PubMed
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Inhibition of SARS-CoV-2 infection in human airway epithelium with a xeno-nucleic acid aptamer - CONCLUSIONS: Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa.
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Broad spectrum post-entry inhibitors of coronavirus replication: Cardiotonic steroids and monensin - A small molecule screen identified several cardiotonic steroids (digitoxin and ouabain) and the ionophore monensin as potent inhibitors of HCoV-229E, HCoV-OC43, and SARS-CoV-2 replication with EC(50)s in the low nM range. Subsequent tests confirmed antiviral activity in primary cell models including human nasal epithelial cells and lung organoids. Addition of digitoxin, ouabain, or monensin strongly reduced viral gene expression as measured by both viral protein and RNA accumulationâŠ.
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Lipin-2 regulates the antiviral and anti-inflammatory responses to interferon - Interferons (IFN) are crucial antiviral and immunomodulatory cytokines that exert their function through the regulation of a myriad of genes, many of which are not yet characterized. Here, we reveal that lipin-2, a phosphatidic acid phosphatase whose mutations produce an autoinflammatory syndrome known as Majeed syndrome in humans, is regulated by IFN in a STAT-1-dependent manner. Lipin-2 inhibits viral replication both in vitro and in vivo. Moreover, lipin-2 also acts as a regulator ofâŠ
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Saying no to SARS-CoV-2: the potential of nitric oxide in the treatment of COVID-19 pneumonia - Nitric oxide (NO), a gaseous free radical produced from L-arginine catalyzed by NO synthase, functions as an important signaling molecule in the human body. Its antiviral activity was confirmed in the 1990s, and has been studied more extensively since the outbreak of the SARS pandemic in 2003. In the fight against the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, some recent studies have revealed the potential of NO in the treatment of coronavirus disease 2019âŠ
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Understanding psychology studentsâ perspective on video psychotherapy and their intention to offer it after graduation: a mixed-methods study - INTRODUCTION: Video psychotherapy (VPT) demonstrated strong clinical efficacy in the past, with patients and psychotherapists expressing satisfaction with its outcomes. Despite this, VPT only gained full recognition from the German healthcare system during the COVID-19 pandemic. As society increasingly relies on new media, it seems likely that VPT will become even more relevant. Previous studies surveyed practicing psychotherapists and patients about advantages and disadvantages of VPT. InâŠ
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Oral mucosa immunity: ultimate strategy to stop spreading of pandemic viruses - Global pandemics are most likely initiated via zoonotic transmission to humans in which respiratory viruses infect airways with relevance to mucosal systems. Out of the known pandemics, five were initiated by respiratory viruses including current ongoing coronavirus disease 2019 (COVID-19). Striking progress in vaccine development and therapeutics has helped ameliorate the mortality and morbidity by infectious agents. Yet, organism replication and virus spread through mucosal tissues cannot beâŠ
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Intracellular delivery of nuclear localization sequence peptide mitigates COVID-19 by inhibiting nuclear transport of inflammation associated transcription factors - The novel coronavirus SARS-CoV-2, responsible for COVID-19, can trigger dysregulated immune responses known as cytokine release syndrome (CRS), leading to severe organ dysfunction and respiratory distress. Our study focuses on developing an improved cell-permeable nuclear import inhibitor, iCP-NI, capable of blocking the nuclear transport of inflammation-associated transcription factors (IATFs), specifically nuclear factor kappa B (NF-ÎșB). By fusing advanced macromolecule transduction domainsâŠ
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Hyperbaric Oxygen Treatment for Long COVID: From Molecular Mechanism to Clinical Practice - Long COVID symptoms typically occur within 3 months of an initial COVID-19 infection, last for more than 2 months, and cannot be explained by other diagnoses. The most common symptoms include fatigue, dyspnea, coughing, and cognitive impairment. The mechanisms of long COVID are not fully understood, but several hypotheses have been put forth. These include coagulation and fibrosis pathway activation, inflammatory and autoimmune manifestations, persistent virus presence, and Epstein-Barr virusâŠ
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The extracellular polysaccharide inhibit porcine epidemic diarrhea virus with extract and gene editing Lacticaseibacillus - Lacticaseibacillus is one of the predominant microorganisms in gut from human and animal, and the lacticaseibacillus have effective applications against the viral diarrhea of piglets in the farm. However, the function and the concrete cell single pathways of the active ingredient from lacticaseibacillus was not clear within anti-infection in the postbiotics research. Here, we compared the biological function of extracellular polysaccharides (EPS) purified from lacticaseibacillus casei (L. casei)âŠ
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Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story - Fundamental insight gained over the last decades led to the discovery of cytokines as pivotal drivers of inflammatory diseases such as rheumatoid arthritis, psoriasis/psoriasis arthritis, inflammatory bowel diseases, atopic dermatitis and spondylarthritis. A deeper understanding of the pro-inflammatory and anti-inflammatory effects of various cytokines has prompted new cytokine-targeting therapies, which revolutionised the treatment options in the last years for patients with inflammatoryâŠ
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Veratramine Inhibits Porcine Epidemic Diarrhea Virus Entry through Macropinocytosis by Suppressing PI3K/Akt Pathway - Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by α-coronavirus porcine epidemic diarrhea virus (PEDV). At present, no effective vaccine is available to prevent the disease. Therefore, research for novel antivirals is important. This study aimed to identify the antiviral mechanism of Veratramine (VAM), which actively inhibits PEDV replication with a 50% inhibitory concentration (IC(50)) of ⌠5 ”M. Upon VAM treatment, both PEDV-nucleocapsid (N) protein level and virusâŠ
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Promising role of Vitamin D and plant metabolites against COVID-19: Clinical trials review - Vitamin D possesses immunomodulatory qualities and is protective against respiratory infections. Additionally, it strengthens adaptive and cellular immunity and boosts the expression of genes involved in oxidation. Experts suggested taking vitamin D supplements to avoid and treat viral infection and also COVID-19, on the other hand, since the beginning of time, the use of plants as medicines have been vital to human wellbeing. The WHO estimates that 80 % of people worldwide use plants or herbsâŠ
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Plant-Derived Antioxidants for Management of COVID-19: A Comprehensive Review of Molecular Mechanisms - We aimed to review the literature to introduce some effective plant-derived antioxidants to prevent and treat COVID-19. Natural products from plants are excellent sources to be used for such discoveries. Among different plant-derived bioactive substances, components including luteolin, quercetin, glycyrrhizin, andrographolide, patchouli alcohol, baicalin, and baicalein were investigated for several viral infections as well as SARS-COV-2. The mechanisms of effects detected for these agents wereâŠ
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SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-Îł and NK cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used a model of viral infection in macaques to address whether SARS-CoV-2 persists in the body and which mechanisms regulate its persistence. Replication-competent virus was detected in bronchioalveolar lavage (BAL) macrophages beyond 6 months postinfection. Viral propagation in BAL macrophages occurred from cell to cell and wasâŠ
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A novel cell-permeable peptide prevents protein SUMOylation and supports the mislocalization and aggregation of TDP-43 - SUMOylation is a post-translational modification (PTM) that exerts a regulatory role in different cellular processes, including protein localization, aggregation, and biological activities. It consists of the dynamic formation of covalent isopeptide bonds between a family member of the Small Ubiquitin Like Modifiers (SUMOs) and the target proteins. Interestingly, it is a cellular mechanism implicated in several neurodegenerative pathologies and potentially it could become a new therapeuticâŠ
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From Patent Search
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+ 07 November, 2023
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+Daily-Dose
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The Agony of Waiting for a Ceasefire That Never Comes - When the war in Gaza started, my family fled to the Jabalia refugee camp. Then Israel started bombing the camp. - link
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Can Seawalls Save Us From Rising Seas and Surging Storms? - Huge coastal barriers could protect the worldâs cities. But theyâll have unexpected costs. - link
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What Will It Take to Win Brooklynâs First Majority-Asian District? - In a recently redrawn City Council district, two Chinese American candidates are both trying to claim the mantle of âpublic safety.â - link
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The Line Between Gaza and America - Fragments of life and death from Palestinians inside the Strip and their relatives abroad, four weeks into Israelâs war. - link
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Donald Trumpâs Contentious Day on the Witness Stand - Appearing at his civil fraud trial, the former President made some potentially damaging admissions, even as he dismissed the case against him as a witch hunt. - link
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From Vox
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The dire medical crisis in Gaza, explained -
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+A wounded girl waits for treatment at al-Shifa hospital on November 5, 2023. | Bashar Taleb/AFP/Getty Images
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+Multiple hospitals have closed due to airstrikes and lack of fuel. Others are struggling to stay open.
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+As Israel steps up its air raids and ground assault in its ongoing war against Hamas, the medical situation in Gaza is growing more and more dire, with the northâs major remaining hospitals warning theyâll soon run out of fuel and supplies. Once they do, a humanitarian crisis thatâs already untenable is only expected to get worse.
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+âIf the airstrikes continue, thereâll be these dual forces of bombing, all of the trauma injuries that come from that. And then just as the health system deteriorates ⊠[an] inability to deal with infectious disease, people who need other types of care,â says Yara Asi, a professor of global health management at the University of Central Florida who has studied health care systems in the Occupied Palestinian Territories. âIt is a disaster from the top to the bottom.â
+
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+The need for quality medical care in Gaza has only deepened following weeks of devastating airstrikes by the Israeli government, which have killed more than 10,000 people and injured more than 25,000, according to the Gaza Health Ministry. These airstrikes are in response to a brutal attack by Hamas on Israel on October 7, during which the Palestinian militant group killed 1,400 people and took roughly 240 people hostage.
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+As a result of the Israeli governmentâs airstrikes and full siege on Gaza, hospitals are not just running out of fuel, food, and water, theyâre also suffering damage from ongoing bombardment. Solar panels keeping one of Gazaâs largest hospitals going have reportedly been destroyed in the fighting, while other hospitals have suffered extensive structural damage.
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+That means existing patients, including pregnant people, babies, and people with chronic illnesses, canât get treatment and are more likely to die as a result. As a doctor in southern Gaza told the New York Times, âThe hospital doors are open, but the care we are able to give â it is negligible.â
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+Additionally, hospitals have become refuges for displaced people, making facilities already full of the ill and wounded even more packed. Medical experts worry that infectious diseases â such as cholera â will increase as people in Gaza are exposed to contaminated water and forced to shelter in cramped, crowded spaces.
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+âWeâre running out of words to describe the horrors unfolding in Gaza,â World Health Organization Director-General Tedros Adhanom Ghebreyesus said in a news briefing on Thursday. âHospitals crammed with the injured lying in corridors. Morgues overflowing. Doctors performing surgery without anesthesia. Thousands of people seeking shelter from the bombardment. Families crammed into overcrowded schools desperate for food and water. Toilets overflowing and the risk of disease outbreak spreading. And everywhere, fear, death, destruction, loss.â
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+Hospitals are suffering from supply shortages and airstrikes
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+Of Gazaâs 35 hospitals, 16 have already been shuttered, and a number of those that remain â particularly in the north, which has borne the brunt of Israelâs attacks â say they can last days more at best. Smaller practices are in dire shape as well, with about 70 percent of primary care clinics reportedly forced to shut their doors.
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+Due to both dwindling fuel and damage from airstrikes, Gazaâs only cancer hospital, the Turkish-Palestinian Friendship Hospital, ceased operations last week, according to Palestinian health officials. The Indonesian Hospital, a major provider of medical care in northern Gaza, also saw its main generator go out last week, severely limiting its ability to provide key services, including oxygen and ventilators. And on Friday, al-Shifa hospital, the largest hospital in Gaza, said it was running so short on fuel that it only had enough energy to power the neonatal intensive care unit. The UN has been able to keep some services at hospitals in the south afloat by sharing its fuel reserves, but the organization hasnât been able to get any fuel to the north, where all three of the aforementioned hospitals are.
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+Without fuel, these hospitals arenât able to ensure that they can keep their power or life-saving machines on. Beyond these struggles, Gazaâs hospitals are also short key medical supplies including everything from gauze to IV bags to antiseptic. These shortages have forced physicians to ration their existing supplies, and to perform procedures â including surgeries â with little or no anesthesia.
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+âEven the most basic of supplies weâve run out,â Ghassan Abu-Sittah, a surgeon in Gaza, told Australiaâs SBS News. âWeâve run out of dressings, weâve run out of intravenous fluids, weâve run out of blade sutures. Anything that we require is finished or in the last few boxes left in the department.â
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+MSFâs Dr. Tanya Haj-Hassan, talking about what hospitals in Gaza need:
Fuel for generators. Clean water. Blood.
When fuel runs out, every person on a ventilator, premature baby in an incubator will die.
+As their supplies dwindle, hospitals are also becoming more crowded with an influx of patients as well as other civilians seeking shelter after theyâve been displaced from their homes. âThereâs no space in the hospital,â Abu-Sittah added in his SBS News interview. âWe have over 2,000 wounded patients in a hospital that had a bed capacity of around 600.â
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+âIn terms of the patient load of hospitals, itâs indescribable,â says Tanya Haj-Hassan, a physician with Doctors Without Borders who is based in Jordan, but in regular communication with doctors in Gaza. âTheyâre having to resuscitate patients on the floor, to do surgical procedures on the floor because thereâs no room anywhere else.â
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+Hospitals have been the targets of or near repeated airstrikes and bombings as well. According to the WHO and the Palestinian Health Ministry, there have been 218 attacks on health care-related facilities in the Palestinian territories, and at least 135 health care personnel are among the casualties of the overall Israeli offensive. That includes airstrikes that were near the al-Shifa hospital, the al-Quds hospital, and the Indonesian hospital, as well as a bombing that hit an ambulance convoy. Many hospitals have been told to evacuate due to bombings in the region, but physicians have said this is impossible and an effective death sentence for patients who rely on ventilators and life support.
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+âMoving a baby on life support would be hazardous in a high-income country. Doing so in Gaza would gravely endanger a child whose life has only just begun,â said Ghebreyesus.
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+At least 81 wounded people are expected to be able to evacuate to Egypt for further treatment, and both Turkey and the United Arab Emirates have offered to provide medical care for those in need. But not every evacuation attempt works: Friday, for instance, a convoy attempting to leave al-Shifa was hit by an Israeli bomb, killing at least 13 and injuring many more, including people taking shelter in the facility. Additionally, the number of patients who are evacuated pales in comparison to the degree of need and the scope of people whoâve been injured.
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+The Israeli government claimed it was targeting â and killed â Hamas combatants in the al-Shifa ambulance strike, and has often sought to justify some of its airstrikes on healthcare by claiming that Hamas has a presence. Al-Shifa hospital, for example, has been cited as the location of a Hamas command center by Israeli leaders, an accusation Hamas has denied.
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+The WHO has raised concerns that attacks on health facilities are a violation of international humanitarian law. As experts told Al Jazeera, attacks on hospitals are a breach of the Geneva Conventions, which state, âDirecting an attack against a zone established to shelter the wounded, the sick and civilians from the effects of hostilities is prohibited.â There are exceptions if thereâs evidence that medical facilities are being weaponized to harm an opposing force, however. But Israelâs claims aside, itâs not clear Hamas is weaponizing hospitals. Thursday, WHO officials said they had not independently verified whether the al-Shifa hospital was being used as a base by Hamas.
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+âWe have no information about what may be happening elsewhere underneath these facilities, thatâs not information we would have, thatâs not information we could verify,â Michael Ryan, executive director of the WHOâs Health Emergencies Program, said on Thursday. âThe difficulty here is separating the needs of 50,000 people at al-Shifa hospital, civilians, doctors, patients, and others.â
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+Thereâs immense fallout for patients and providers
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+The fallout for patients from these hospital closures and shortages has been enormous â and is poised to increase.
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+For patients with chronic illnesses, hospitals are increasingly unable to provide the vital medication and care they need to survive. âIf you donât have electricity, you canât give dialysis [to patients with kidney illnesses],â says Haj-Hassan. âIf you cannot do those things, you will ultimately become very unwell and die. [If] you canât get cancer therapy, you will also die.â
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+For people with acute conditions, like a heart attack or stroke, there are limited medical resources â both when it comes to staffing and supplies â to be as responsive to these needs as before. âFor acute problems, thereâs just no capacity to care for anything thatâs not a war injury at this point,â says Haj-Hassan. Care International told CNN roughly 160 people are expected to give birth in Gaza each day over the next month. Those pregnant people â including those who need C-sections â are among those who may be unable to secure the care they need.
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+Data from Al Jazeera and the WHO also notes that there are 130 infants relying on incubators, 1,000 kidney dialysis patients, and 350,000 patients with noncommunicable diseases such as diabetes, cancer, and heart disease who have to bear these effects.
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+And for patients with traumatic injuries â including thousands whoâve been injured during the airstrikes â it has meant incomplete treatments and little pain management. âHow can you care for patients [when a] large part of their body is burned if you donât have pain relief? It is completely inhumane,â says Haj-Hassan.
+
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+On top of the existing patient needs, many experts worry about the spread of infectious disease as clean water supplies continue to run low and people continue to shelter in cramped spaces. Roughly 50,000 people were believed to be taking shelter in al-Shifa as of late October, while the UN said 670,000 people were packed into its shelters. Asi pointed to a cholera outbreak that occurred during the war in Yemen and said a similar scenario could take place in Gaza.
+
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+â[Water-borne illness] is one of the number one killers of children in Gaza even before this, and the potable water situation there has always been poor since the siege started in 2006,â she says.
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+Doctors, too, are completely overwhelmed by the degree of need they are seeing as well as having to make impossible decisions about who is able to receive care and use supplies. âWhat Iâm hearing from speaking with them is just desperation that they canât do anything,â says Asi. âThe hospitals are to the point where theyâre so full that when patients arrive, sometimes doctors have to choose between who we bring into the hospital, who may have a chance of survival, and who we canât.â
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+âDoctors are distressed. They are calling us cryingâŠby the horror they are seeingâŠThis has to stop. Weâre operating on children without anesthetics. We donât have morphine for them.â
+The WHO and Doctors Without Borders are calling for a ceasefire, the ability to provide humanitarian aid to hospitals, and security for health care providers in light of these conditions.
+
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+In her description of doctorsâ experiences in Gaza, Haj-Hassan read a text message she received on Friday from a pediatric intensive care physician based there.
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+âUnfortunately, we are on our way to collapsing from the horror of the scenes we see despite our strength,â it reads. âAnd the world is watching as if we were in a movie theater showing a horror movie and the viewers are silent.â
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A boneheaded state official may have just handed the NRA a big Supreme Court victory -
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+A guest looks at a rifle at the Palmetto State Armory booth during the National Rifle Associationâs Annual Meetings & Exhibits at the Indiana Convention Center in Indianapolis on April 16, 2023. | Jeremy Hogan/SOPA Images/LightRocket via Getty Images
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+Democrats need to be smarter while the GOP controls the Supreme Court.
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+Every now and then, the Supreme Court takes up a case involving a public official who acted so foolishly â without any regard for the ordinary norms governing law enforcement, or without any insight into how their actions could undermine some of the governmentâs most important work â that you wish the justices could each take turns smacking them upside the head.
+
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+National Rifle Association v. Vullo, which the Court announced that it would hear last Friday, is such a case. It involves two unrelated actions which former New York State Department of Financial Services (DFS) Superintendent Maria Vullo took against the NRA, one of which successfully shut down an NRA program that recklessly endangered countless New Yorkersâ lives â and one of which recklessly endangered Vulloâs effort to shut down this potentially deadly program.
+
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+In 2017, DFS opened an investigation into âCarry Guard,â an NRA-endorsed insurance program that, according to the federal appeals court that heard the Vullo case, âprovided liability defense coverage for criminal proceedings resulting from firearm use even where the insured acted with criminal intent.â
+
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+Carry Guard offered to pay both the civil and criminal legal costs (up to $1 million for a civil case, and up to $150,000 for a criminal case) of its customers who shot another person, allegedly in self-defense. The NRA actively promoted this insurance to its members as a product that would give them peace of mind if they shot another human being. One pitch to the NRAâs members told them that âyou should never be forced to choose between defending your life ⊠and putting yourself and your family in financial ruin.â
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+For reasons that should be obvious, New York generally does not permit insurance contracts intended to âinsure a person for that personâs intentional criminal acts,â and it certainly doesnât permit the kind of insurance that may pay out if a beneficiary commits a violent crime with a deadly weapon. And so, not long after DFS opened its investigation into Carry Guard, three insurance companies that underwrote or administered Carry Guard or similar programs entered into a consent decree where they agreed to stop providing this kind of insurance.
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+All of this is well and good. Nothing in the Constitution prohibits New York from targeting insurers who sell a product that will encourage people to shoot other people. And nothing in the First Amendment prohibits New York from targeting illegal insurance that is backed by the NRA, even though the NRA also engages in First Amendment-protected advocacy.
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+But then Vullo did something incomprehensibly stupid.
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+In February 2018, the Parkland, Florida, school shooting happened â killing 17 high school students and school staff. After this shooting, DFS issued a âguidance,â signed by Vullo, which encouraged insurers to âcontinue evaluating and managing their risks, including reputational risks, that may arise from their dealings with the NRA or similar gun promotion organizations.â
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+To be clear, this guidance did not explicitly threaten to take any action against insurers who continued to do lawful business with the NRA. But that does not change the fact that DFS, an agency whose responsibilities include law enforcement, and that had recently brought a $13 million enforcement action against insurance companies that did illegal business with the NRA, was now suggesting that those same companies might face consequences if they did other, legal business with the NRA.
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+This guidance, and similar post-Parkland communications between DFS and the insurance industry, do potentially violate the First Amendment. While the Constitution permits a government official to ask any company to stop doing business with the NRA, it does not typically permit the government to coerce private businesses into halting lawful business with an advocacy group. And DFSâs guidance, which was issued so soon after DFS opened its Carry Guard investigation, looks suspiciously like coercion.
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+The First Amendment places special burdens on law enforcement agencies
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+As a general rule, the government has a virtually unlimited right to express its own viewpoint, as do government officials. They may condemn the NRA. They may call for strict gun laws that the NRA opposes. They may say unkind things about the NRA to business leaders who may wish to do business with the NRA. And, if the NRA does something illegal, they may warn businesses against the legal risks of joining that illegal activity.
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+But, in Bantam Books v. Sullivan (1963), the Supreme Court recognized that âpeople do not lightly disregard public officersâ thinly veiled threats to institute criminal proceedings against them if they do not come around.â While the government may express whatever opinion it wants about any organization its leaders do not like, it may not use law enforcement officials to implicitly threaten someone with criminal charges unless that person abandons activity that is protected by the First Amendment.
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+Bantam Books involved the ominously named âRhode Island Commission to Encourage Morality in Youth,â a government body that identified books and magazines it deemed âobjectionable for sale, distribution or display to youths under 18 years of age.â It then sent notices to booksellers and distributors seeking their âcooperationâ with the commission in removing such books â and reminding those sellers of the commissionâs âduty to recommend to the Attorney General prosecution of purveyors of obscenity.â
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+According to one book distributor, he was often visited by a police officer shortly after receiving such a notice, and the officer asked the distributor what steps he had taken in response to the notice.
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+Bantam Books held that this level of pressure â a letter that explicitly mentioned the possibility of a prosecution, followed by a visit from an inquisitive police officer â crosses the line from permissible persuasion to impermissible coercion.
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+The facts of Vullo arenât quite as egregious as those in Bantam Books. DFSâs guidance does not mention the possibility of any kind of enforcement action against an insurer who continues to work with the NRA. And thereâs no indication that DFS sent an armed police officer to New York insurance companies to check in on whether they had, in fact, dropped their business with the NRA.
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+Even so, the guidance does raise serious First Amendment concerns. Imagine, for example, that a police officer arrested you for shoplifting â or some other crime that you legitimately did commit, and that a police officer legitimately may arrest you for committing. Then imagine that this same police officer shows up at your workplace a few months later and pressures you to end your relationship with another company. Would you feel free to refuse? Or would you think that this officer, who so recently placed you under arrest, was implicitly threatening to do so again?
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+Thatâs basically what happened in Vullo. DFS brought a completely legitimate enforcement action against three insurance companies, arising out of those companiesâ decision to administer or underwrite an insurance product that no sensible government would allow to exist. Then, months later, the same agency sent a guidance to all New York insurers â including these same three companies â informing them that DFS âencourages regulated institutions to review any relationships they have with the NRA or similar gun promotion organizations, and to take prompt actions to managing these risks and promote public health and safety.â
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+Itâs not hard to read that guidance as a coercive attempt to punish the NRA because New Yorkâs government disagrees with the NRAâs political advocacy in favor of looser gun laws.
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+Law enforcement agencies should be exceedingly cautious before they opine on politics
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+The NRA has sought an extraordinary remedy in the Vullo case. According to the complaint it filed in the trial court that heard this case, the NRA wants a court order requiring DFS to âimmediately cease and refrain from engaging in any conduct or activity which has the purpose or effect of interfering with, terminating, or diminishing any of the NRAâs contracts and/or business relationships with any organizations.â
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+Among other things, that could prevent New York from enforcing its law prohibiting insurers from selling products that encourage people to shoot other people.
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+Hopefully, the Supreme Court wonât impose such a catastrophic consequence on the people of New York because of a misstep byone of its former officials. But, by bringing herself and her agency into a political dispute about gun advocacy, Vullo gave this highly partisan Supreme Court an opportunity to insert itself into what should have been a routine insurance enforcement action.
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+
Iran could determine how far the Israel-Hamas war spreads -
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+Supporters of Hezbollah wave flags as they watch a televised speech by its leader, Hassan Nasrallah, in Beirut, Lebanon, on November 3, 2023. | Ahmad Al-Rubaye/AFP via Getty Images
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+Hezbollah and other Iran-backed groups support Hamas but havenât opened new fronts.
+
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+In his first public statement about Israelâs war with Hamas,Lebanese Hezbollah leader Hassan Nasrallah on Friday indicated that the Shia militant group â though supportive of Hamasâs bloody October 7 attack on Israel â wouldnât be opening up another front in the war just yet.
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+Hezbollah, which the US and other countries have designated as a terror group, has engaged in cross-border firefights with Israel since the October 7 attack. Thatâs not particularly new; there is regularly low-level conflict across the so-called Blue Line, the line of demarcation between Lebanon and Israel, which UN peacekeepers have been deployed to monitor since 2006. But given its proximity to the conflict and Hezbollahâs close affiliation with Iran, itâs a possible front to expand the war.
+
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+Lebanon is not the only place at risk of spillover conflict; Iran-backed militias have been attacking US forces in Iraq and Syria, launching 27 attacks at US bases since October 17 after several months without any such attacks. And the Houthis, an Iran-backed Shia group which controls much of western and northwestern Yemen, have lobbed missiles and drones in Israelâs direction, though those have been intercepted by US warships in the eastern Mediterranean, as well as by Israeli missile defense systems. âThe Iranians are happy to activate their proxy groups and let other people do the fighting and dying â and frankly a lot of the proxy groups are happy to do the fighting and dying,â Jon Alterman, director of the Middle East program at the Center for Strategic and International Studies, told Vox.
+
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+Iran, to varying degrees, funds and provides resources to each of these groups, as well as Hamas. âIranâs relationship with other groups really fits onto a spectrum,â Ali Vaez, director of the Iran project at the International Crisis Group, told Vox. âAt one side of the spectrum you have Hezbollah, because Iranâs relationship with Hezbollah is really like two NATO allies.â Hezbollah has only Iran as a state backer, while Hamas and militant groups in Iraq and Syria have relationships with other nations.
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+Though Nasrallah and Iranian leadership have praised Hamasâs attack and threatened retaliation for Israelâs aggressive bombing and ground campaign in Gaza â whether through a proxy group or outright â a âred lineâ for doing so isnât clear nearly a month into the war.
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+All of these groups give Iran options about where and how it wants to send messages to its adversaries â the US and Israel â while ostensibly giving the Islamic Republic a measure of plausible deniability. But this tactic is not without risk, especially without direct diplomatic channels between the adversaries.
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+The US, in addition to providing Israel with weapons and material support, has moved major military assets to the region â two carrier strike groups, and now a guided missile submarine carrying up to 154 Tomahawk cruise missiles. The move is meant as a further deterrent to Iran and its related groups in the region as Secretary of State Antony Blinken makes another trip to the Middle East, in part to try and contain the conflict to Gaza.
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+âTo me, there are two ways this could expand: one is by calculation, and one is by miscalculation,â Alterman said. Iran likely would not want to attack Israel or the US decisively and directly, but an error or a step too far by Iran or any of its proxies could push the conflict outside the bounds of Gaza. âAt a time of heightened alert ⊠somebodyâs missile could go awry, it may kill somebody. You could have commanders who are freelancing,â or working outside the directions of Iran or another proxy group, âanything can happen, and you can get yourself into a pretty rapid escalation pretty quickly.â
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+Hezbollah has fought Israel before â and itâs better equipped now
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+
+Though none of the proxy groups would act without Iranâs go-ahead, Hezbollah is in lock-step with Iran ideologically and tactically; Nasrallah and his group are not acting independently. But Lebanon has its own longstanding conflict with Israel, and Hezbollah plays a big role in that.
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+Israel has occupied the Shebaa Farms area, which was once part of southern Lebanon, since 1967, and invaded southern Lebanon in 1978 and 1982, ultimately occupying part of the country south of the Litani River until 2000. Lebanon was in the midst of a brutal, sectarian civil war, and Hezbollah emerged in the early 1980s in part to serve and represent the Shia population in the south, which wasbeing marginalized by the Lebanese Christian ruling minority as well as an influx of Sunni Muslim Palestinian refugees and resistance groups, upsetting Lebanonâs precarious political balance.
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+Over time, and with significant Iranian support, Hezbollah emerged as a potent political and militant force in southern Lebanon and on the national stage. Militarily, Hezbollah aimed to push the Israel Defense Forces (IDF) out of southern Lebanon. When Hezbollah in July 2006 fired rockets at Israeli positions and crossed the border to kill and kidnap IDF soldiers, Israel attacked Lebanon, setting off just over a month of war until a UN-mediated ceasefire took effect August 14.
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+Since that conflict, Hezbollah has grown its capabilities; Nasrallah claims his group has 100,000 fighters, thousands of whom have been honing their skills by supporting Bashar al-Assadâs forces in Syria over the past 12 years. Iran has also maintained its support, helping the group obtain a vast arsenal of rockets and artillery, including longer-range Iranian models with higher payloads. Hezbollah also now possesses the ability to retrofit older rockets and turn them into precision-guided missiles, according to Reuters. That means Hezbollah could fire deeper into Israel and target critical infrastructure.
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+Hezbollah is also a political actor, holding 62 seats as part of a coalition in Lebanonâs parliament. It lost a number of seats in the last round of elections and a war would be extremely unpopular in Lebanon, which is undergoing both a political and economic crisis; the country has been without a government for a year, and its currency, the lira, is at an all-time low value of 100,000 to the US dollar. US officials have met with the Lebanese caretaker government in an effort to try and prevent the conflict from spreading into Lebanon.
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+Hezbollah maintaining power in Lebanon also means Iran keeping power in the country â power which it aims to deploy when necessary. âOnce Iran needs to use Hezbollah, they will, despite what happens to Lebanon,â Hanin Ghaddar, a senior fellow at the Washington Institute for Near East Policy, told Vox. And though it has a larger ground force than Hamas, âthey would be running up against probably 100,000 fully alert, dug-in Israeli troops â and that is a suicidal mission,â James Jeffrey, former US special envoy to the Coalition to Defeat ISIS, told Vox. For now, Iran has likely calculated the threat of Hezbollahâs increased missile arsenal is enough to keep Israel from taking significant action in Lebanon.
+
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+Hamas officials have met with Hezbollah senior leaders in Lebanon â and likely encouraged them to do more to support Hamas or otherwise challenge Israel, Ghaddar said. But whether they do so will depend entirely on Iran, she added. âHezbollahâs job today is to protect Iranian interests, not to support Hamas or the Palestinians.â
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+Though Hamas and Hezbollah do coordinate regarding attacks on Israel, Ghaddar said, âHamasâs expectation was a lot more [support]â against Israel. âI think what happened is [Hamas] realized they are being thrown into the fire for Iran to establish certain political gains,â such as scuttling normalization processes between Israel and Arab states. âHezbollahâs job is to protect these gains and help Iran use the Hezbollah threat to translate these gains into more political, economic gains. And Hamas really has been duped into this [conflict].â
+
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+More peripheral groups also present a risk
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+The US, meanwhile, has launched multiple airstrikes against proxy groups in Iraq and Syria since attacks on US installations resumed on October 17. But rather than real threats of a new front in the war, these and Houthi missiles launched toward Israel look more like a signal of Iranâs displeasure about Israel and the USâs military actions than they do a real threat of escalation â for now.
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+âThere is a core network of Iranian-controlled groups in Iraq that run these front groupsâ which are carrying out rocket attacks on US bases in Iraq and Syria, according to Phillip Smyth, an independent analyst who focuses on Hezbollah and jihadi groups in the region. Several core jihadi groups affiliated with the Iranian Revolutionary Guard Force, or IRGC, are directing a number of front groups in Iraq and Syria.
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+These groups have been launching rocket attacks since about 2020, after the assassination of Qasem Soleimani, a revered leader in the Iranian military. Some of the groups have been around much longer â since 2005 at least â and are trusted allies of the Iranian regime. Theyâre unlikely to deviate from Iranâs strategy and interests in the region. But other, smaller front groups arenât necessarily quite so closely aligned, Smyth said, and can sometimes mistakenly go off-course or outright flout Iranâs orders.
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+Hamas official Osama Hamdan did meet with the leader of the front group Asaib Ahl al-Haq, according to the UAE outlet the National. Hamdan told Lebanese pro-Iran TV channel Al Mayadeen that Hamas is âlooking forward to an important role to be played by Iraq for the Palestinian cause.â
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+But that meeting doesnât signal that these front groups will do anything more than lob rockets at US military installations â unless Iran decides it serves their interest.
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+As for the Houthis, many factions of the group are intensely loyal to Iran, but they have their own interests, too â namely regaining control in Yemen. For 1,000 years, a Zaydi Shia imamate ruled Yemen, but it was overthrown in 1962 and Yemenâs Zaydi Muslims â including the Houthis â were stripped of their political power. The Houthi movement started in the 1990s, as a protest against increasing Saudi financial and religious power in northern Yemen. Iran and Hezbollah support the Houthis because they see the Houthis as part of a Shia revival and struggle against Sunni Islam.
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+Yemen has been in a brutal civil war between the Houthis and the Saudi-backed central government, creating the worst humanitarian crisis in the world, according to the UN. Though the Houthis have made gestures of solidarity with Hamas by launching rockets, theyâre also unlikely to open up another front in the war simply because they have their own concerns, namely trying to negotiate a political settlement and officially end the conflict. Thereâs also the issue of serious, unrelenting poverty in Yemen and increased terrorist violence by al-Qaeda in the Arabian Peninsula (AQAP).
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+Iran, for its part, also has significant domestic problems that make it difficult to imagine theyâd risk directconflict with the US and Israel; the government and the supreme leader are extremely unpopular, as evidenced by widespread protests over the past year. Surging poverty, unemployment, and inflation are further angering ordinary Iranians; open conflict isnât likely to help the governmentâs problems.
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+Israel has thus far ignored those calls âfrom the US, its neighbors, and from its own citizens. So far in the conflict, IDF strikes have killed more than 10,000 Palestinians, according to the Gaza Health Ministry, and 12 Hamas leaders, according to the IDF.
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+Update, November 6, 10:50 am ET: This story, originally published November 4, has been updated to include the deployment of US military assets to the region.
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From The Hindu: Sports
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Prideâs Angel shines -
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PSG football fan stabbed in overnight clashes in Milan - Two police officers were also hurt after police baton-charged the French fans to try to restore order.
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Sunil Chhetri admits heâs in âbonus periodâ but yet to decide on retirement - One thing is, however, certain that the 39-year-old Chhetri will not be playing in 2026 when the football World Cup happens
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Shakib Al Hasan ruled out of Bangladeshâs last World Cup match due to injury - The star all-rounder sustained the injury on his left index finger while batting during Bangladeshâs 3-wicket win over Sri Lanka.
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AUS vs AFG | Afghanistan win toss, elect to bat against Australia - Steve Smith, who complained of suffering from a bout of vertigo before the match, was ruled out, while Mitch Marsh and Glenn Maxwell are back in the team
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From The Hindu: National News
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Hearing aids to be distributed to children of BPL families on Nov. 9 -
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Experts call for a robust cybersecurity strategy for Vizhinjam seaport -
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Here are the big stories from Karnataka today - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated and written by Nalme Nachiyar.
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ISF leader Nawshad keen to contest from Diamond Harbour Lok Sabha seat - The Diamond Harbour Lok Sabha constituency is presently represented by Trinamool leader Abhishek Banerjee
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India needs to integrate into global value chains and adapt to emerging trading systems: NITI Aayog CEO - While addressing a thematic workshop on âInclusive Trade for Growth & Prosperityâ, NITI Aayog CEO Subrahmanyam highlighted the need for a non-discriminatory and inclusive trading system which facilitates trade as an engine of growth and prosperity
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From BBC: Europe
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Ukraine war: Grenade birthday gift kills army chief Zaluzhnyâs aide - Maj Hennadiy Chastyakov was opening presents at home near Kyiv with his son at the time of the blast.
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Polish president gives Mateusz Morawiecki opportunity to form government - Mateusz Morawieckiâs party came top in recent elections, but will have a hard job finding allies.
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Europe migrant crisis: Italy to build migrant centres in Albania - The centres will be able to process more than 30,000 asylum seekers a year, Italyâs PM has said.
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Letters from Seven Yearsâ War opened 250 years later - The academic who discovered the letters said reading them was âvery emotionalâ.
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Watch divers recover trove of ancient Roman coins - Over 30,000 bronze coins, possibly from a 4th Century shipwreck, have been found off the coast of Italy.
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From Ars Technica
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âI cannot wait to possess youâ: Reading 18th century letters for the first time - Some things are universal: One sailorâs mother chided him for not writing more often. - link
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Critical vulnerability in Atlassian Confluence server is under âmass exploitationâ - Atlassianâs senior management is all but begging customers to take immediate action. - link
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Supermassive black hole found only half a billion years after Big Bang - There just isnât time for something that big to grow from a supernova remnant. - link
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Toxic toddler fruit pouches: âExtremely highâ lead levels sicken 7 in 5 states - Three brands of apple cinnamon fruit pouches have now been recalled. - link
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OpenAI introduces GPT-4 Turbo: Larger memory, lower cost, new knowledge - Novel-sized context window, DALL-E 3 API, more announced on OpenAI DevDay 2023. - link
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From Jokes Subreddit
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A Mormon and the Irishman are on a plane -
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+A Mormon was seated next to an Irishman on a flight from London to the US. After the plane was airborne, drink orders were taken. The Irishman asked for a whiskey, which was promptly brought and placed before him.
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+The flight attendant then asked the Mormon if he would like a drink. He replied in disgust, âIâd rather be savagely raped by a dozen whores than let liquor touch my lips.â
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+The Irishman then handed his drink back to the attendant and said, âMe, too, I didnât know we had a choice.â
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A redhead, a blonde and a brunette escape from jail.. -
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+A redhead, a blonde and a brunette escape from jail and hide in a barn. The police close in, so the three women each hide in a sack. The police search the barn, and to check each sack, a police officer kicks it as he walks past. The officer kicks the redheadâs sack, and the redhead says, âMeow!â The officer kicks the brunetteâs sack, and the brunette says, âWoof, woof.â The officer kicks the blondeâs sack, and the blonde shouts, âPotatoes!â
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