Postnatal depression symptom trajectories across the COVID-19 pandemic: Evidence from the United Kingdom -
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+Purpose: Postnatal maternal mental health suffered early in the COVID-19 pandemic; here we explore the continuing trajectory of postnatal depressive symptoms in the UK. Methods: We report descriptive statistics from a six-wave longitudinal online survey, tracking a cohort of 569 mothers giving birth between November 2019 and December 2020, and a subsequent cohort of 70 mothers giving birth in 2022. Results: The percentage of participants meeting the ≥11 Edinburgh Postnatal Depression Scale cut-off for postnatal depression was high early in the pandemic; while declining as social distancing restrictions eased, rates remained above pre-pandemic levels in April 2022: 47.5% (May-June 2020), 32.8% (July 2020), 51.3% (late 2020), 54.0% (February 2021), 38.2% (September 2021), 35.1% (April 2022). Those with greater symptom severity early in the pandemic showed a tendency to remain in depressive range. Symptoms were higher, and the decline in symptoms overtime attenuated, in those experiencing financial difficulty. Of mothers giving birth in 2022, 44.3% scored ≥11. Conclusions: Health services must be alert to high support needs of this cohort in which postnatal depression appears chronic at high rates, particularly in those of lower socioeconomic position.
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Variant mutation in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation -
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+The evolution of SARS-CoV-2 variants and their respective phenotypes represents an important set of tools to understand basic coronavirus biology as well as the public health implications of individual mutations in variants of concern. While mutations outside of Spike are not well studied, the entire viral genome is undergoing evolutionary selection, particularly the central disordered linker region of the nucleocapsid (N) protein. Here, we identify a mutation (G215C), characteristic of the Delta variant, that introduces a novel cysteine into this linker domain, which results in the formation of a disulfide bond and a stable N-N dimer. Using reverse genetics, we determined that this cysteine residue is necessary and sufficient for stable dimer formation in a WA1 SARS-CoV-2 background, where it results in significantly increased viral growth both in vitro and in vivo. Finally, we demonstrate that the N:G215C virus packages more nucleocapsid per virion and that individual virions are larger, with elongated morphologies.
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SARS-CoV-2 Omicron BA.2.87.1 Exhibits Higher Susceptibility to Serum Neutralization Than EG.5.1 and JN.1 -
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+As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions ({Delta}15-26 and {Delta}136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.
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Community structure and temporal dynamics of SARS-CoV-2 epistatic network allow for early detection of emerging variants with altered phenotypes -
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+The emergence of viral variants with altered phenotypes is a public health challenge underscoring the need for advanced evolutionary forecasting methods. Given extensive epistatic interactions within viral genomes and known viral evolutionary history, efficient genomic surveillance necessitates early detection of emerging viral haplotypes rather than commonly targeted single mutations. Haplotype inference, however, is a significantly more challenging problem precluding the use of traditional approaches. Here, using SARS-CoV-2 evolutionary dynamics as a case study, we show that emerging haplotypes with altered transmissibility can be linked to dense communities in coordinated substitution networks, which become discernible significantly earlier than the haplotypes become prevalent. From these insights, we develop a computational framework for inference of viral variants and validate it by successful early detection of known SARS-CoV-2 strains. Our methodology offers greater scalability than phylogenetic lineage tracing and can be applied to any rapidly evolving pathogen with adequate genomic surveillance data.
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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 ‘true positive criteria’ 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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Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion -
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+The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly. BA.2.87.1 is more resistant to neutralization by XBB.15-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines.
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Exploring the therapeutic potential of defective interfering particles in reducing the replication of SARS-CoV-2 -
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+SARS-CoV-2 still presents a global threat to human health due to the continued emergence of new strains and waning immunity amongst vaccinated populations. Therefore, it is still relevant to investigate potential therapeutics, such as therapeutic interfering particles (TIPs). Mathematical and computational modelling are valuable tools to study viral infection dynamics for predictive analysis. Here, we expand on the previous work by Grebennikov et al. (2021) on SARS-CoV-2 intra-cellular replication dynamics to include defective interfering particles (DIPs) as potential therapeutic agents. We formulate a deterministic model that describes the replication of wild-type (WT) SARS-CoV-2 virus in the presence of DIPs. Sensitivity analysis of parameters to several model outputs is employed to inform us on those parameters to be carefully calibrated from experimental data. We then study the effects of co-infection on WT replication and how DIP dose perturbs the release of WT viral particles. Furthermore, we provide a stochastic formulation of the model that is compared to the deterministic one. These models could be further developed into population-level models or used to guide the development and dose of TIPs.
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Assessment for the seasonality of Covid-19 should focus on ultraviolet radiation and not ‘warmer days’ -
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+More attention should be paid to ultraviolet radiation for the seasonality of Covid-19, based on the previous SARS and MERS epidemics, and not the ‘warmer days’ of summer.
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Protein complex heterogeneity and topology revealed by electron capture charge reduction and surface induced dissociation -
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+Herein, we focus on native mass spectrometry (nMS) combined with a fast, tunable gas-phase charge reduction, electron capture charge reduction (ECCR), and illustrate its utility in the characterization of protein complex topology and glycoprotein heterogeneity. ECCR is illustrated to effectively spread the charge states of tetradecameric GroEL, illustrating Orbitrap m/z measurement out to greater than 100,000 m/z. For both the pentameric C-reactive protein and tetradecameric GroEL, our novel device combining ECCR with surface induced dissociation (SID) lowers the charge states and produces more topologically informative fragmentation. While more native-like fragmentation has previously been illustrated for complexes charge reduced by proton abstraction in solution, this is the first illustration that ECCR can lead to more native-like SID fragmentation of protein complexes. Application to protein glycosylation, one of the most common and diverse protein posttranslational modifications, is also illustrated because glycosylation is important for structural and functional properties and plays essential roles in many key biological processes. The immense heterogeneity resulting from variability in glycosylation sites and glycan composition and structure poses significant analytical challenges that hinder a mechanistic understanding of the biological role of glycosylation. Data for stabilized heavily glycosylated SARS-CoV-2 spike protein trimer and thyroglobulin dimer illustrate that ECCR enables significantly improved resolution of glycan heterogeneity. Without ECCR, the charge states of a glycoprotein complex are not resolved and average mass determination is available only through the use of charge detection mass spectrometry or mass photometry. With ECCR after narrow m/z selection, multiple glycoform m/z values are apparent, providing quick global, glycoform profiling and providing a future path for glycan localization on individual intact glycoforms (e.g., though top-down dissociation).
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In silico genomic surveillance by CoVerage predicts and characterizes SARS-CoV-2 Variants of Interest -
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+Rapidly evolving viral pathogens such as SARS-CoV-2 continuously accumulate amino acid changes, some of which affect transmissibility, virulence or improve the virus' ability to escape host immunity. Since the beginning of the pandemic and establishment of SARS-CoV-2 as a human pathogen, multiple lineages with concerning phenotypic alterations, so called Variants of Concern (VOCs), have emerged and risen to predominance. To optimize public health management and to ensure the continued efficacy of vaccines, the early detection of such variants of interest is essential. Therefore, large-scale viral genomic surveillance programs have been initiated worldwide, with data being deposited in public repositories in a timely manner. However, technologies for their continuous interpretation are currently lacking. Here, we describe the CoVerage system (www.sarscoverage.org) for viral genomic surveillance, which continuously predicts and characterizes novel and emerging potential Variants of Interest (pVOIs) together with their antigenic and evolutionary alterations. Using the establishment of Omicron and its current sublineages as an example, we demonstrate how CoVerage can be used to quickly identify and characterize such variants. CoVerage can facilitate the timely identification and assessment of future SARS-CoV-2 Variants of Concern.
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Rapid Degradation of the Human ACE2 Receptor Upon Binding and Internalization of SARS-Cov-2-Spike-RBD Protein -
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+It is widely accepted that the SARS-CoV-2 betacoronavirus infects humans through binding the human Angiotensin Receptor 2 (ACE2) that lines the nasal cavity and lungs, followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) cofactor. ACE2 binding is mediated by an approximately 200-residue portion of the SARS-CoV-2 extracellular spike protein, the receptor binding domain (RBD). Robust interactions are shown using a novel cell-based assay between an RBD membrane tethered-GFP fusion protein and the membrane bound ACE2-Cherry fusion protein. Several observations were not predicted including, quick and sustained interactions leading to internalization of RBD fusion protein into the ACE2 cells and rapid downregulation of the ACE2-Cherry fluorescence. Targeted mutation in the RBD disulfide Loop 4 led to a loss of internalization for several variants tested. However, a secreted RBD did not cause ACE2 downregulation of ACE2-Cherry fluorescence. Thus, the membrane associated form of RBD found on the viral coat may have long-term system wide consequences on ACE2 expressing cells.
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Coronavirus Spike-RBD Variants Differentially Bind to the Human ACE2 Receptor -
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+The SARS-CoV-2 betacoronavirus infects people through binding the human Angiotensin Receptor 2 (ACE2), followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) and Furin cofactors. Analysis of the SARS-CoV-2 extracellular spike protein has suggested critical amino acids necessary for binding within a 197-residue portion, the receptor binding domain (RBD). A cell-based assay between a membrane tethered RBD-GFP fusion protein and the membrane bound ACE2-Cherry fusion protein allowed for mutational intersection of both RBD and ACE2 proteins. Data shows Omicron BA.1 and BA.2 variants have altered dependency on the amino terminus of ACE2 protein and suggests multiple epitopes on both proteins stabilize their interactions at the Nt and internal region of ACE2. In contrast, the H-CoV-NL63 RBD is only dependent on the ACE2 internal region for binding. A peptide inhibitor approach to this internal region thus far have failed to block binding of RBDs to ACE2, suggesting that several binding regions on ACE2 are sufficient to allow functional interactions. In sum, the RBD binding surface of ACE2 appears relatively fluid and amenable to bind a range of novel variants.
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Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1 -
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+The recent emergence of a SARS-CoV-2 saltation variant, BA.2.87.1, which features 65 spike mutations relative to BA.2, has attracted worldwide attention. In this study, we elucidate the antigenic characteristics and immune evasion capability of BA.2.87.1. Our findings reveal that BA.2.87.1 is more susceptible to XBB-induced humoral immunity compared to JN.1. Notably, BA.2.87.1 lacks critical escaping mutations in the receptor binding domain (RBD) thus allowing various classes of neutralizing antibodies (NAbs) that were escaped by XBB or BA.2.86 subvariants to neutralize BA.2.87.1, although the deletions in the N-terminal domain (NTD), specifically 15-23del and 136-146del, compensate for the resistance to humoral immunity. Interestingly, several neutralizing antibody drugs have been found to restore their efficacy against BA.2.87.1, including SA58, REGN-10933 and COV2-2196. Hence, our results suggest that BA.2.87.1 may not become widespread until it acquires multiple RBD mutations to achieve sufficient immune evasion comparable to that of JN.1.
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Resolution of SARS-CoV-2 infection in human lung tissues is driven by extravascular CD163+ monocytes -
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+The lung-resident immune mechanisms driving resolution of SARS-CoV-2 infection in humans remain elusive. Using mice co-engrafted with a genetically matched human immune system and fetal lung xenograft (fLX), we mapped the immunological events defining resolution of SARS-CoV-2 infection in human lung tissues. Viral infection is rapidly cleared from fLX following a peak of viral replication. Acute replication results in the emergence of cell subsets enriched in viral RNA, including extravascular inflammatory monocytes (iMO) and macrophage-like T-cells, which dissipate upon infection resolution. iMO display robust antiviral responses, are transcriptomically unique among myeloid lineages, and their emergence associates with the recruitment of circulating CD4+ monocytes. Consistently, mice depleted for human CD4+ cells but not CD3+ T-cells failed to robustly clear infectious viruses and displayed signatures of chronic infection. Our findings uncover the transient differentiation of extravascular iMO from CD4+ monocytes as a major hallmark of SARS-CoV-2 infection resolution and open avenues for unravelling viral and host adaptations defining persistently active SARS-CoV-2 infection.
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Human Cytokine and Coronavirus Nucleocapsid Protein Interactivity Using Large-Scale Virtual Screens -
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+Understanding the interactions between SARS-CoV-2 and the human immune system is paramount to the characterization of novel variants as the virus co-evolves with the human host. In this study, we employed state-of-the-art molecular docking tools to conduct large-scale virtual screens, predicting the binding affinities between 64 human cytokines against 17 nucleocapsid proteins from six betacoronaviruses. Our comprehensive in silico analyses reveal specific changes in cytokine-nucleocapsid protein interactions, shedding light on potential modulators of the host immune response during infection. These findings offer valuable insights into the molecular mechanisms underlying viral pathogenesis and may guide the future development of targeted interventions. This manuscript serves as insight into the comparison of deep learning based AlphaFold2-Multimer and the semi-physicochemical based HADDOCK for protein-protein docking. We show the two methods are complementary in their predictive capabilities. We also introduce a novel algorithm for rapidly assessing the binding interface of protein-protein docks using graph edit distance: graph-based interface residue assessment function (GIRAF). The high-performance computational framework presented here will not only aid in accelerating the discovery of effective interventions against emerging viral threats, but extend to other applications of high throughput protein-protein screens.
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RECOVER-AUTONOMIC Platform Protocol - Conditions: Long COVID; Long Covid19; Long Covid-19 Interventions: Drug: IVIG + Coordinated Care; Drug: IVIG Placebo + Coordinated Care; Drug: Ivabradine + Coordinated Care; Drug: Ivabradine Placebo + Coordinated Care; Drug: IVIG + Usual Care; Drug: IVIG Placebo + Usual Care; Drug: Ivabradine + Usual Care; Drug: Ivabradine Placebo + Usual Care Sponsors: Duke University Not yet recruiting
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RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine) - Conditions: Long COVID; Long Covid19; Long Covid-19 Interventions: Drug: Ivabradine; Drug: Ivabradine Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care Sponsors: Duke University Not yet recruiting
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RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG) - Conditions: Long COVID; Long Coronavirus Disease 2019 (Covid19); Long Covid-19 Interventions: Drug: IVIG (intravenous immunoglobulin); Drug: IVIG Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care Sponsors: Duke University Not yet recruiting
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SVF for Treating Pulmonary Fibrosis Post COVID-19 - Conditions: Pulmonary Fibrosis Interventions: Biological: Autologous adipose-derived SVF IV administration Sponsors: Michael H Carstens; Ministerio de Salud de Nicaragua; Wake Forest University; National Autonomous University of Nicaragua Completed
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Understanding Adaptive Immune Response After COVID-19 Vaccination Boosters to Improve Vaccination Strategies in Vulnerable Groups. - Conditions: COVID-19 Interventions: Other: Analisys of cellular response and humoral response to SARS-CoV-2 vaccine booster doses Sponsors: IRCCS Sacro Cuore Don Calabria di Negrar Recruiting
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COVIDVaxStories: Randomized Trial to Reduce COVID-19 Vaccine Hesitancy in Populations of Color - Conditions: Vaccine Hesitancy Interventions: Behavioral: Storytelling; Behavioral: Learn More (Active Comparator) Sponsors: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC Recruiting
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An E-health Psychoeducation for People With Bipolar Disorders - Conditions: Bipolar Disorder; Psychoeducation; COVID-19 Pandemic Interventions: Other: e-health psychoeducation Sponsors: University of Cagliari; Alessandra Perra Completed
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Sulfureous Water Therapy in Viral Respiratory Diseases - Conditions: Long-COVID; Post COVID-19 Condition; Chronic COVID-19 Syndrome; Post Acute Sequelae of COVID-19 Interventions: Other: Inhalation of Sulfurous Thermal Water; Other: Inhalation of Sterile Distilled non-pyrogenic Water Sponsors: University of Roma La Sapienza; Università degli studi di Roma Foro Italico; Queen Mary University of London; Bios Prevention Srl Completed
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Phase 3 Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine and Influenza Combination Vaccine - Conditions: COVID-19 Interventions: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection Sponsors: Novavax Not yet recruiting
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Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection. - Conditions: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection Interventions: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo) Sponsors: Sheng-Teng Huang Completed
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SHEN211 Tablets for the Treatment of Mild and Moderate Novel Corona Virus Infections (COVID-19) - Conditions: COVID-19 Interventions: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets Sponsors: JKT Biopharma Co., Ltd. Not yet recruiting
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INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old - Conditions: COVID-19 Pandemic; COVID-19 Vaccines Interventions: Biological: INAVAC (Vaksin Merah Putih - UA-SARS CoV-2 (Vero Cell Inactivated) 5 µg Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia Recruiting
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Study to Evaluate the Safety & Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2 - Conditions: SARS CoV 2 Infection Interventions: Biological: IMNN-101 Sponsors: Imunon Not yet recruiting
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Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults - Conditions: COVID-19 Interventions: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo Sponsors: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited Not yet recruiting
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From PubMed
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AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor - Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and perform early-stage drug discovery. We have developed a machine learning approach that prioritizes interactions by analyzing quantitative data from binary PPI assays or…
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Impact of mutations on the stability of SARS-CoV-2 nucleocapsid protein structure - The nucleocapsid (N) protein of SARS-CoV-2 is known to participate in various host cellular processes, including interferon inhibition, RNA interference, apoptosis, and regulation of virus life cycles. Additionally, it has potential as a diagnostic antigen and/or immunogen. Our research focuses on examining structural changes caused by mutations in the N protein. We have modeled the complete tertiary structure of native and mutated forms of the N protein using Alphafold2. Notably, the N protein…
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Host-Directed Virus-Mimicking Particles Interacting with the ACE2 Receptor Competitively Block Coronavirus SARS-CoV-2 Entry - Herein, we fabricate host-directed virus-mimicking particles (VMPs) to block the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells through competitive inhibition enabled by their interactions with the angiotensin-converting enzyme 2 (ACE2) receptor. A microfluidic platform is developed to fabricate a lipid core of the VMPs with a narrow size distribution and a low level of batch-to-batch variation. The resultant solid lipid nanoparticles are decorated with an…
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In Silico and In Vitro Screening of Some Pregnane Glycosides Isolated from Certain Caralluma Species as SARS-COV-2 Main Protease Inhibitors - SARS-CoV-2 caused pandemic represented a major risk for the worldwide human health, animal health and economy, forcing extraordinary efforts to discover drugs for its prevention and cure. Considering the extensive interest in the pregnane glycosides because of their diverse structures and excellent biological activities, we investigated them as antiviral agents against SARS-COV-2. We selected 21 pregnane glycosides previously isolated from the genus Caralluma from Asclepiadaceae family to be…
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Angiotensin I and II Stimulate Cell Invasion of SARS-CoV-2: Potential Mechanism via Inhibition of ACE2 Arm of RAS - Angiotensin-converting enzyme 2 (ACE2), one of the key enzymes of the renin-angiotensin system (RAS), plays an important role in SARS-CoV-2 infection by functioning as a virus receptor. Angiotensin peptides Ang I and Ang II, the substrates of ACE2, can modulate the binding of SARS-CoV-2 Spike protein to the ACE2 receptor. In the present work, we found that co incubation of HEK-ACE2 and Vero E6 cells with the SARS-CoV-2 Spike pseudovirus (PVP) resulted in stimulation of the virus entry at low and…
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Ginseng and ginsenosides on cardiovascular and pulmonary diseases; Pharmacological potentials for the coronavirus (COVID-19) - Since its outbreak in late 2019, the Coronavirus disease 2019 (COVID-19) pandemic has profoundly caused global morbidity and deaths. The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has major complications in cardiovascular and pulmonary system. The increased rate of mortality is due to delayed detection of certain biomarkers that are crucial in the development of disease. Furthermore, certain proteins and enzymes in cellular signaling pathways play an…
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Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome - The COVID-19 pandemic persists despite the availability of vaccines, and it is therefore crucial to develop new therapeutic and preventive approaches. In this study, we investigated the potential role of the oral microbiome in SARS-CoV-2 infection. Using an in vitro SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effect exerted by Porphyromonas gingivalis on SARS-CoV-2 infection mediated by known P. gingivalis compounds such as phosphoglycerol dihydroceramide (PGDHC) and…
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An allosteric mechanism for potent inhibition of SARS-CoV-2 main proteinase - The main proteinase (M^(pro)) of SARS-CoV-2 plays a critical role in cleaving viral polyproteins into functional proteins required for viral replication and assembly, making it a prime drug target for COVID-19. It is well known that noncompetitive inhibition offers potential therapeutic options for treating COVID-19, which can effectively reduce the likelihood of cross-reactivity with other proteins and increase the selectivity of the drug. Therefore, the discovery of allosteric sites of M^(pro)…
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NLRC5/MHC class I transactivator: A key target for immune escape by SARS-CoV-2 - Antigen presentation to CD8+ T cells by MHC class I molecules is essential for host defense against viral infections. Various mechanisms have evolved in multiple viruses to escape immune surveillance and defense to support viral proliferation in host cells. Through in vitro SARS-CoV-2 infection studies and analysis of COVID-19 patient samples, we found that SARS-CoV-2 suppresses the induction of the MHC class I pathway by inhibiting the expression and function of NLRC5, a major transcriptional…
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Quantitative Assessment of Energetic Contributions of Residues in a SARS-CoV-2 Viral Enzyme/Nanobody Interface - The highly conserved protease enzyme from SARS-CoV-2 (M^(Pro)) is crucial for viral replication and is an attractive target for the design of novel inhibitory compounds. M^(Pro) is known to be conformationally flexible and has been stabilized in an extended conformation in a complex with a novel nanobody (NB2B4), which inhibits the dimerization of the enzyme via binding to an allosteric site. However, the energetic contributions of the nanobody residues stabilizing the M^(Pro)/nanobody interface…
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Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury - SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others’, has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein-resulted in inflammation in…
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Indole Propionic Acid Disturbs the Normal Function of Tryptophanyl-tRNA Synthetase in Mycobacterium tuberculosis - Tuberculosis (TB) is the leading infectious disease caused by Mycobacterium tuberculosis and the second-most contagious killer after COVID-19. The emergence of drug-resistant TB has caused a great need to identify and develop new anti-TB drugs with novel targets. Indole propionic acid (IPA), a structural analog of tryptophan (Trp), is active against M. tuberculosis in vitro and in vivo. It has been verified that IPA exerts its antimicrobial effect by mimicking Trp as an allosteric inhibitor of…
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Effects of Lamiaceae family plants and their bioactive ingredients on coronavirus-induced lung inflammation - Coronaviruses (CoVs) are a family of viruses that cause infection in respiratory and intestinal systems. Different types of CoVs, those responsible for the SARS-CoV and the new global pandemic of coronavirus disease 2019 in people, have been found. Some plants were used as food additives: spices and dietary and/or medicinal purposes in folk medicine. We aimed to provide evidence about possible effects of two Lamiaceae family plants on control or treatment of CoVs-induced inflammation. The…
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Deregulation of interferon-gamma receptor 1 expression and its implications for lung adenocarcinoma progression - Interferon-gamma (IFN-γ) plays a dual role in cancer; it is both a pro- and an antitumorigenic cytokine, depending on the type of cancer. The deregulation of the IFN-γ canonic pathway is associated with several disorders, including vulnerability to viral infections, inflammation, and cancer progression. In particular, the interplay between lung adenocarcinoma (LUAD) and viral infections appears to exist in association with the deregulation of IFN-γ signaling. In this mini-review, we investigated…
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The role of N-acetylcysteine in decreasing neutrophil-lymphocyte ratio in COVID-19 patients: A double-blind, randomized controlled trial - N-acetylcysteine has antioxidant and anti-inflammatory activities that could potentially improve the clinical outcomes of coronavirus disease 2019 (COVID-19) patients. N-acetylcysteine potentially inhibits NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and results in control oxidative stress and cytokine release in COVID-19 patients. The aim of this study was to assess the effect of N-acetylcysteine in reducing the neutrophil-lymphocyte ratio (NLR) in COVID-19 patients. A…
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From Patent Search
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What a Top U.N. Official Sees on His Weekly Trips to Gaza - James McGoldrick describes the challenges of delivering aid during Israel’s bombardment. - link
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Have the Liberal Arts Gone Conservative? - The classical-education movement seeks to fundamentally reorient schooling in America. Its emphasis on morality and civics has also primed it for partisan takeover. - link
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Percival Everett Can’t Say What His Novels Mean - The author of “Erasure” is renowned for his satires of genre, identity, and America. But his great target may be language itself. - link
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The Open-Air Prison for ISIS Supporters—and Victims - Since the Islamic State fell, tens of thousands of people—many of them children—have been herded into Al-Hol, a giant fenced-in camp in Syria, and effectively given life sentences. - link
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Among the A.I. Doomsayers - Some people think machine intelligence will transform humanity for the better. Others fear it may destroy us. Who will decide our fate? - link
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From Vox
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How to talk to boys so they grow into better men -
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+Westend61 via Getty Images
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+Counteracting the Andrew Tate effect isn’t just the purview of parents and teachers.
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+The problem begins in boyhood — and so should the solution, says award-winning health educator Christopher Pepper, writer of the Teen Health Today newsletter and co-author of the forthcoming book Talk To Your Boys. In his view, a future where men are healthier and happier starts with better conversations with boys.
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+Technology has made those conversations harder to have. Back when family phones were in kitchens or living rooms — and casual communication usually involved talking to each other — more of the conversations kids were having with their friends and peers happened within earshot of parents and teachers. That gave adults more opportunities to coach kids on how to talk to each other, says Pepper. Now, kids learn to communicate on cell phones and social media largely out of view of adults during the key years they’re building social skills.
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+Boys suffer the social consequences of that more because while adults typically emphasize social skills in teaching girls how to interact with each other, there’s less of an imperative to guide boys in that way, Pepper says. That might explain why researchers have found that on average, girls demonstrate better social skills than boys as early as kindergarten — and that advantage widens over the course of elementary school as boys’ social abilities decline.
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+“Boys often don’t really learn the basics of social relationships and responsibility and communication,” says Pepper. Social skills adults may take for granted, like all the steps involved in making plans to meet a friend, are skills that aren’t necessarily taught. The consequences for boys aren’t good: As they grow up, they often lose close friendships with other boys, even though they really want them.
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+The absence of clear guidance for many boys on how to be and act creates massive opportunities for internet misogynists like Andrew Tate, says Pepper. “Tate has figured out that boys are actually really interested in talking about gender, talking about masculinity, and thinking about what it means to be a successful man,” says Pepper. Many boys don’t get much other messaging on these issues from their families or schools, leaving a void easily filled by charismatic jerks.
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+Bad behavior among students is worsenow than it was pre-pandemic, perhaps especially among boys. Although the causes are unclear, adults often blame increased social isolation and screen time, plus the popularity of figures like Tate and the viral spread of various dumb TikToktrends.
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+On a broader scale, though, Tate’s popularity shows what boys are missing, says Pepper: “There’s a real opening for adults to step up to more positive conversations about masculinity and what it means to be a man, and how they would like men to be in the world.”
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+I asked Pepper what those conversations could and should look like. Below is what he told me, in his own words, edited for length and clarity.
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+Make it clear you’re a trustworthy adult before you need to have difficult conversations
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+Depression, suicide, substance abuse — these can be scary things to learn about or to talk about. Sometimes adults have the impulse to rush into a conversation about a difficult topic and be very prescriptive and authoritarian — to say, “These are all the things you should not do.”
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+But shame and judgment tend to really shut off conversation. So instead, I would lean into curiosity in conversations before you get to the difficult stuff. When a boy invites you into his world, even in a little way, take that opening. Like if he’s talking about a song, or a funny meme, or a video game that he’s playing that he loves, be curious about it. And really listen, reflect back what he’s saying. Make sure you’re understanding where he’s coming from, and just do what you can to keep those conversations open so that when more challenging topics come up, you still have those lines of communication open — you’re still interested in hearing from each other.
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+Model, celebrate, and reinforce taking care of other people and experiencing a full range of emotions —especially if you’re a father
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+Another thing you can do — and this is especially for fathers, but really, for any parents — is be reflective on your own life: Are you making time to actually see your friends and be a good support, and to let the boys in your life see you doing that? Do you talk about your friends and the people you care about?
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+One of the things that happens as boys are growing up is they learn about a very restrictive version of masculinity, a list of things that you’re not allowed to do or say. Particularly around emotions: You’re allowed to be angry, and you might be able to cry if something’s really bad — like a sports team you’re on loses a really important game, or someone died. But part of being a full human is being able to access and express a fuller range of emotions. So for adults, it’s important to ensure it’s safe for boys to do that, that you’re not criticizing them or judging them for it. If you hear other kids making fun of them for showing their emotions, stick up for them and say, “Hey, it’s actually good and positive to be connected to your feelings and to be able to show them.”
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+When boys are showing care and concern and support for other people, celebrate it in the same way that you might celebrate more traditional things that are celebrated for boys, like sports victories or catching a big fish. You want to celebrate when they care for friends or family, too — like, “I saw how responsible you were with your little sister today when she was upset and really helped our family get through dinner,” for example. Really recognize and celebrate those things. They might be coded as feminine, but they’re really life skills that will help them grow into men who are good fathers, good partners, and good friends.
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+When conversations get complicated: Notice signals that they don’t understand, know your own mind, and get comfortable with do-overs
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+When boys blame girls or feminism for the problems in the world, that’s a big red flag — it often happens when they learn about issues from social media.
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+If you hear a boy talking along these lines, it’s a good moment to engage him in some critical thinking. But rather than saying, “Oh, you’re totally wrong,” try something like, “I was surprised to hear you say that. Can you tell me more about what you’re thinking?” And if they mention learning something from a video, you can ask them to watch the video together and talk about it.
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+Boys often dismiss especially questionable or offensive statements as jokes — Peggy Orenstein got into this in her recent book, Boys & Sex. For example, they’ll say something about rape or the Holocaust and follow it up with, “Can’t you take a joke?” That’s often a signal that they want to learn more about something, or that they don’t understand it.
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+It can make an impact when an adult takes those jokes seriously — especially when men do. You could say: “Joking about sexual harassment or rape is a red line, is not okay with me, and I want to tell you why.” For some boys, hearing from an adult man that the subject is serious and that they want to be able to talk about it — that will feel different than hearing it from a woman. Saying these things is a skill that gets easier with practice, and I think is an important thing for adults to get better at.
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+When adults are having these conversations, it’s good for them to get clear about their own values. Think through what you believe about gender equality, yourself, and what you understand about racism or sexism or homophobia. Recognize they can be hard but important things to talk about.
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+Being able to talk about these issues will be super useful to boys as they’re going through their lives. When they repeat things they hear online, they’ll be better able to decide if that’s something they actually believe.
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+Remember that as a parent, you have lots of chances — so it’s OK if you get it wrong the first time! If you have a conversation that kind of goes sideways, you can come back to it and say, “Hey, we talked about this yesterday and I thought about it later and realized I kind of misspoke. I wonder if we can talk about that again.” You can apologize to young people for getting angry; you can ask for a do-over of tough conversations, for a do-over of trying to understand them. In fact, asking for a do-over helps model and develop self-reflection and taking responsibility for a mistake in a way that can help boys be successful in their own lives.
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+Create places where boys can grow socially and emotionally
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+More schools should have boys’ groups.
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+It’s pretty easy for a boy to go through a whole school day and not talk to anyone, except maybe about the assignments that are due, or to maybe have some sort of surface-level conversation about a sports game or a video game. The surgeon general has said loneliness is a national crisis — but on the whole, schools haven’t been putting a lot of effort into the social and emotional lives of boys. Schools often don’t have spaces where boys can talk reflectively to other boys and talk to a trusted adult about what’s going on in their lives.
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+When they create these spaces — groups where boys can talk to other boys about what it is like to be a boy today and what’s going on in their lives, and get help with the day-to-day struggles in navigating the social and emotional side of the world — boys love them.
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+There are great models of this all over the place. A Canadian nonprofit called Next Gen Men has a free curriculum — in addition to their in-person groups, they have one online on Discord. In Oakland, where I live, there’s a group called the Ever Forward Club, and in New York, there’s A Call to Men, which has a free curriculum. Other programs engage coaches of boys’ sports teams in teaching healthy masculinity to their players. [See the sidebar for more resources.]
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+I’d like to see these kinds of programs expanded into more schools, just to encourage boys to really think about the world they’re living in, how they treat people, how to make friends, and to get support when they need it.
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+Even if you don’t live or work with boys, treating them like caring humans helps
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+There are still lots of ways you can help boys develop into better men [if you’re not a parent or someone who works closely with them]. There are formal mentoring and tutoring programs, but on a more day-to-day basis, I think trying to recognize the humanity of boys is meaningful. Sometimes, the way adults talk about teenage boys, it’s like they’re really scary, or a different species. There are a lot of jokes about how terrible teenage boys are.
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+It’s helpful if we recognize they’re human beings who will grow up to be men in our world. These are going to be our co-workers and neighbors. It’s often easier to build relationships with teenage boys individually, rather than trying to do so with a whole group of kids you don’t know.
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+So treat them as individual people and be curious about them.
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+That could mean building a mentoring relationship, but it could also mean hiring somebody for a job, like to be the dog walker, or thinking about boys as possibly being babysitters or people who can take care of things. I would encourage people to kind of check their stereotypes about who can do that kind of care work — it’s not only teenage girls who could be good babysitters. Recognize everybody’s different.
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The Supreme Court may let Texas get away with a totally unconstitutional deportation law -
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+Migrants cross the US-Mexico border in Texas. | David Peinado/NurPhoto via Getty Images
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+Texas Republicans are trying to rewrite the Constitution — and this Supreme Court could let them.
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+For well more than a century, the federal government has enjoyed near exclusive authority over immigration policy, while states have largely been restricted to assisting in carrying out federal policies. The Supreme Court has reinforced this rule many times over many decisions, such as Truax v. Raich (1915), which said that“the authority to control immigration — to admit or exclude aliens — is vested solely in the Federal Government.”
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+Texas, however, now wants the Supreme Court to abandon this longstanding constitutional rule, and it thinks that the political tumblers have finally aligned in a way that would lead the Court to do just that.
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+The Texas law will go into effect on Wednesday at 5 pm, unless the Supreme Court acts, so it is likely that the Court will hand down some sort of decision before then (although that decision could just be a brief order extending the deadline to some future date).
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+The Supreme Court is as conservative as it’s been since the 1930s, with Republicans controlling six seats on the nine-justice Court. And Texas’s case attempting to seize control of the Texas/Mexico border arrives at the justices’ feet at the same time that an unusually large wave of migrants are arriving at the border.
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+The reason why the federal government has historically had exclusive authority over nearly all questions of immigration policy is to prevent a single state’s mistreatment of a foreign national from damaging US relations with another nation. Indeed, Hines v. Davidowitz (1941) warned that “international controversies of the gravest moment, sometimes even leading to war, may arise from real or imagined wrongs” committed against foreign nationals.
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+Which isn’t to say that the United States must always treat foreign citizens with caution or deference — just that a decision that could endanger the entire nation’s relationship with a foreign state should be made by a government that represents the entire nation.
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+SB 4 is not allowed under Truax, Hines, and countless other decisions, including an Obama-era case involving a very similar Arizona law, Arizona v. United States (2012).
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+But the current Supreme Court has only a weak attachment to following precedent, especially when a precedent is widely disliked by modern-day Republicans. So there is at least some risk that the Court’s GOP-appointed majority will allow SB 4 to go into effect.
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+How does an unambiguously unconstitutional law wind up before the Supreme Court?
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+To a certain extent, an immigration-related conflict between a red state and the federal government was inevitable the minute a Democrat entered the White House. Under President Obama, Arizona’s Republican government enacted a similarly unconstitutional law, known as SB 1070, which imposed registration requirements on immigrants and which gave state police enhanced authority over suspected undocumented immigrants.
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+The Supreme Court struck down several key provisions of SB 1070 in Arizona, in an opinion which also reaffirmed that the national government, and not the states, must have primacy over immigration. “[I]t is fundamental that foreign countries concerned about the status, safety, and security of their nationals in the United States must be able to confer and communicate on this subject with one national sovereign,” Justice Anthony Kennedy wrote for the Court in Arizona, “not the 50 separate States.”
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+But Kennedy is no longer on the Court, and he was replaced by the more hardline conservative Justice Brett Kavanaugh. Also gone is Justice Ruth Bader Ginsburg, who joined the majority opinion in Arizona, and who died in 2020 and was replaced by Trump appointee Justice Amy Coney Barrett.
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+If Kavanaugh and Barrett unite with the three most conservative justices, that’s five votes to overrule Arizona, and to bless Texas’s SB 4.
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+Yet, while Republican-led lawsuits pushing harsher US immigration policies are now a fixture of Democratic administrations,Texas might have a particularly strong political hand right now because of the unusually large number of migrants arriving at the southern US border. For most of the 2010s, US Customs and Border Protection reported about 400,000 to 500,000 “encounters” with migrants at this border every year. Now, that number stands around 2 million a year.
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+There are several reasons why this uptick in migration is happening now.
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+One of the biggest factors is political instability in many parts of Central America and the Caribbean. For many years, the so-called “Northern Triangle” countries — Guatemala, Honduras, and El Salvador — were a major source of migration, as citizens of those nations fled corruption, gang violence, and high levels of poverty. This migration remains ongoing, and is now augmented by migrants fleeing an economic and political crisis in Venezuela, and violence and political instability in Haiti, among other things.
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+This policy (which was known as “Title 42”) always stood on dubious legal grounds. It certainly wasn’t effective in keeping Covid from entering the United States. And the idea that we could prevent the spread of this “communicable disease” by locking down the border became less and less defensible as Covid both became ubiquitous in the United States, and ceased to be a global crisis.
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+By spring of 2023, even Justice Neil Gorsuch, a Republican appointed by Trump, openly mocked the suggestion that Title 42 could remain in place. “The current border crisis is not a COVID crisis,” wrote Gorsuch.
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+SB 4 is one of several illegal steps Texas has taken with respect to the border
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+Texas has since tried to augment a federal border policy that is widely viewed as inadequate with a series of dubiously legal policies. In addition to enacting SB 4, the state has constructed physical barriers — including razor wire fences and floating obstructions in the Rio Grande — intended to keep migrants out of the country (or, in at least one case, to cause them to drown while trying to enter).
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+In January, the Supreme Court ruled 5-4 that Texas could not use razor wire to prevent US Border Patrol agents from entering an area where migrants are present, with Chief Justice John Roberts and Barrett joining the Court’s three Democratic appointees.
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+President Biden, for what it is worth, agrees with Republicans that legal changes are necessary to limit border crossings. Indeed, he pressed Senate Democrats to negotiate a bipartisan bill that would make it harder for migrants to claim asylum, increase funding for immigration officials and detention facilities, and allow the government to close down border crossings if they exceed a certain level.
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+And so, here we are, with an unpopular spike in southern migration overwhelming the US immigration system, and a Congress that is unable to address the problem because the leader of the GOP prefers chaos to a solution.
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+Texas Republicans, meanwhile, have their own answer. It just requires the Supreme Court to toss out more than a century of established law, and strip away the United States’ ability to speak with one voice on matters of foreign policy.
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+If Texas prevails in this lawsuit, the consequences will be unpredictable, and could be catastrophic. It would mean, as the Supreme Court warned in Hines, that states would gain broad leeway to act against foreign nationals — potentially endangering US relations with our allies, or worse.
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How dangerous is New York City, anyway? -
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+Security forces, including National Guard troops and police, take security measures at a subway station in New York City on March 7, 2024. | Lokman Vural Elibol/Anadolu via Getty Images
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+As the National Guard heads into subways, new research examines how the city is faring with gun violence.
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+Last week, New YorkGov. Kathy Hochul announced a new policy that made headlines across the country: Following a handful of high-profile violent crimes, she’s sending 750 members of the National Guard and hundreds of state troopers into the city’s subway system.
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+“No one heading to their job or to visit family or go to a doctor appointment should worry that the person sitting next to them possesses a deadly weapon,” the governor said.
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+But overall the picture is more positive: Crime fell in New York last year; and according to an analysis bythe New York Times, the rate of violent crime on the city’s subway system was roughly one per 1 million rides — meaning your chances of being a victim of violent crime on the subway are really low.
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+There are other reasons a New York Democrat might take an approach to crime that seems aggressively out of proportion: The idea of the city as a crime-ridden hellhole is a perennial of right-wing politics.
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+Last fall, former President Donald Trump tore into New York’s attorney general for pursuing a tax fraud case against him, claiming falsely that the case was happening “while MURDERS & VIOLENT CRIME HIT UNIMAGINABLE RECORDS!”
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+In a big city, there’s almost always going to be a recent example critics can point to to say violence is out of control.
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+So how shouldwe judge how well a city is doing at fighting violent crime?
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+A novel way to evaluate crime levels
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+To start trying to unpack that question, let’s look at one major element of violent crime: gun violence.
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+One way is to judge overall violent crime and per capita crime rates to see how the city is performing compared to past years; that’s what Hochul and the city’s mayor are pointing to when saying their subway deployments are necessary.
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+But another good way would be to look at how much gun violence there is in a given city compared to how well you’d expect it to do for a city of its size.
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+And on the gun homicide front, a new study shows, New York City is majorly overperforming. In fact, it’s performing better than any other big city in the country.
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+That’s one finding of an innovative new study by Rayan Succar and Maurizio Porfiri, the director of the Center for Urban Science and Progress (CUSP) at New York University’s Tandon School of Engineering.
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+You can read the full study in the journal Nature Cities to learn more about their methodology, but to sum up what makes their research unique: They used urban scaling theory — a form of analysis that has only been around for about 10 years and that has primarily been used to research things like wealth distribution and population growth — and applied it to crime.
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+They looked at nearly 1,000 US cities, studying a number of different relationships between gun access, crime, and population, and aggregated multiple data sets in the six years leading up to the pandemic. Their modeling allowed them to compare the actual prevalence of gun violence in a given city to how the model predicted a city of its size would behave.
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+One of their major findings is that gun homicides scale superlinearly to the population in cities — in other words, the bigger the city, the larger the number of gun crimes per capita.
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+In more rural areas, on the other hand, there are more guns but fewer gun homicides. So while cities have fewer guns per capita, Porfiri says, “they are responsible for more violence than what would happen in a rural area.”
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+There are some theories as to why this is, and most have to do with increases in social interaction. As Succar puts it, “If you interact with 200 people per day, there’s way more possibility you’ll get shot than if you’re interacting with five people per day.”
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+Maybe that’s good news for people who believe that they’re safest in a rural area far from big cities with a large stash of firearms (though the research on the risks posed to people who keep firearms in their homes might want to have a word).
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+But it isn’t the entire story.
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+New York has fewer gun homicides per capita than expected
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+The model also predicted that a city of New York’s population size should have way more gun homicides per capita than it does. In fact, of all the big cities they studied, New York had the largest gap between what the model predicted the gun homicide rate per capita would be and what it was.
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+“New York should be applauded,” Porfiri says. Given how large the city is, it’s outperforming expectations on an important measure of gun violence. (The authors don’t delve into the reasons why, but it’s likely a complex mix of culture, law enforcement, and policy.)
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+Is this (admittedly nuanced) finding going to convince Republicans who are certain the city is uniquely crime-plagued because of its purportedly soft-on-crime leaders? Probably not.
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+Getting a better understanding of how gun crime concentrates in cities — and distinguishing how a city performs given that reality — is an important development.
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Amazing Ruler, True Punch, Crime Of Passion excel -
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Lord Eric and Trigger catch the eye -
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Nishant exits a step away from winning a quota place - Busto Arsizio (Italy)
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All England Championship: Sindhu enters second round after Li retires - Sindhu will next face top seed Korean An Se Young, who has proved her nemesis, having defeated her all six times they have crossed paths in international badminton.
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FIH World rankings | Indian men slip to fourth, women’s team ranked ninth - India had directly qualified for the Paris Olympics through an Asian Games gold last year and didn’t need to play in the recently-concluded Olympic Qualifiers.
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From The Hindu: National News
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Telangana State emblem should reflect the democratic aspirations of the people, says Dy CM - Mr. Bhatti spoke at the first meeting of Cabinet sub-committee to finalise the State emblem, statue and song
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MVA’s seat-sharing formula will be finalised after March 17: Chennithala -
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Opposition spreading lies about CAA, claims Amit Shah -
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Sharing login details for typing help is unfathomable, LS Secretariat tells SC on Mahua Moitra’s defence - Ms. Moitra had argued that the sharing of log-in details did not mean giving control of the portal, and cannot be termed as “hacking”
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Sanskrit University Budget 2024-25: Proposals to start Centre for Secular Studies, inter-university centres - Syndicate meeting of university held on main campus at Kalady approves Budget presented by Professor D. Salimkumar, convener of institution’s finance committee
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From BBC: Europe
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Ukraine-based armed groups claim raids into Russia - Russian rebel forces claim villages in Kursk and Belgorod areas - Moscow says the attacks failed.
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The Ukrainian sea drones hunting Russian warships - The BBC meets the drone operators helping to resist Russia’s attempts to dominate the Black Sea.
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Andrew Tate appears in court over UK arrest warrant - Andrew Tate and his brother “categorically reject” the sexual offence charges they are accused of.
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Russia detains South Korean man on spying charges - Korean media report the man is a religious worker who was detained in January in Russia’s far east.
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First Gaza aid ship sets off from Cyprus - The charity ship Open Arms is to deliver 200 tonnes of food to the Strip as part of a new aid corridor.
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From Ars Technica
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An EV that charges 30% faster? Volvo and Breathe think their tech can do it - Real-time battery-management algorithms on an embedded processor? Yes, please. - link
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Never-before-seen Linux malware gets installed using 1-day exploits - Discovery means that NerbianRAT is cross-platform used by for-profit threat group. - link
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Study: Conflicting values for Hubble constant not due to measurement error - Something else is influencing the expansion rate of the Universe. - link
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NASA grapples with budget cuts as it undertakes ambitious programs - “Naturally, we have to make hard choices.” - link
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50 injured on Boeing 787 as “strong shake” reportedly sent heads into ceiling - LATAM Airlines said “technical event” in mid-flight “caused a strong movement.” - link
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From Jokes Subreddit
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I met a pimp who always worked with exactly 1 brunette for every 2 blondes -
A priest and rabbi are sitting on an airline next to each other -
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+The stewardess brings out their meals, the priest a pork dinner, and the rabbi a salad.
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+The priest turns to the rabbi and says “can I ask you a question?” the rabbi nods. The priest asks “you don’t eat pork correct?” The rabbi says “no it is forbidden in Leviticus. An animal must have split hooves and chew it’s cud to be kosher. A pig doesn’t qualify.” The priest asks “but have you ever tried it?” The rabbi says “yes, I must confess I did. In my younger days, before I was religious, I was somewhat rebellious I did try pork.”
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+The rabbi asks the priest “can I ask you a question?” the priest nods. The rabbi says “you can’t have sex, right?” The priest says “no. We must have undivided attention to God and not let marriage or sex cloud that focus so we agree to celibacy.” The rabbi says “but did you ever?” The priest says “yes, I must confess I did. In my younger days, before I considered being a priest I was a bit wild and did experience the pleasure of a woman’s flesh.” After a brief pause the rabbi says “better than pork, huh?”
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