Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic -
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+Background: Antibodies play a key role in the immune defence against infectious pathogens. Understanding the underlying process of B cell recognition is not only of fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas the nature of conformational B cell epitope recognition is inherently complicated, linear B cell epitopes offer a straightforward approach that potentially can be reduced to one of peptide recognition. Methods: Using an overlapping peptide approach representing the entire proteomes of the seven main coronaviruses known to infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents and eight pre-pandemic controls. Using a high-density peptide microarray platform, 13-mer peptides overlapping by 11 amino acids were in situ synthesised and incubated with the pooled primary serum samples, followed by development with secondary fluorochrome-labelled anti-IgG and -IgA antibodies. Interactions were detected by fluorescence detection. Strong Ig interactions encompassing consecutive peptides were considered to represent "high-fidelity regions" (HFRs). These were mapped to the coronavirus proteomes using a 60% homology threshold for clustering. Results: We identified 333 human coronavirus derived HFRs. Among these, 98 (29%) mapped to SARS-CoV-2, 144 (44%) mapped to one or more of the four circulating common cold coronaviruses (CCC), and 54 (16%) cross-mapped to both SARS-CoV-2 and CCCs. The remaining 37 (11%) mapped to either SARS-CoV or MERS-CoV. Notably, the COVID-19 serum was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas the pre-pandemic was skewed towards recognising CCC-mapped HFRs. In terms of absolute numbers of linear B cell epitopes, the primary targets are the ORF1ab protein (60%), the spike protein (21%), and the nucleoprotein (15%) in that order; however, in terms of epitope density, the order would be reversed. Conclusion: We identified linear B cell epitopes across coronaviruses, highlighting pan-, alpha-, beta-, or SARS-CoV-2-corona-specific B cell recognition patterns. These findings could be pivotal in deciphering past and current exposures to epidemic and endemic coronavirus. Moreover, our results suggest that pre-pandemic anti-CCC antibodies may cross-react against SARS-CoV-2, which could explain the highly variable outcome of COVID-19. Finally, the methodology used here offers a rapid and comprehensive approach to high-resolution linear B-cell epitope mapping, which could be vital for future studies of emerging infectious diseases.
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Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques -
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+Antibodies represent a primary mediator of protection against respiratory viruses such as SARS-CoV-2. Serum neutralizing antibodies (NAbs) are often considered a primary correlate of protection. However, detailed antibody profiles including characterization of antibody functions in different anatomic compartments are not well understood. Here we show that antibody correlates of protection against SARS-CoV-2 challenge are different in systemic versus mucosal compartments in rhesus macaques. In serum, neutralizing antibodies were the strongest correlate of protection and were linked to Spike-specific binding antibodies and other extra-neutralizing antibody functions that create a larger protective network. In contrast, in bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved the strongest correlate of protection rather than NAbs. Within BAL, ADCP was linked to mucosal Spike-specific IgG, IgA/secretory IgA, and Fc{gamma}-receptor binding antibodies. Our results support a model in which antibodies with different functions mediate protection at different anatomic sites. The correlation of ADCP and other Fc functional antibody responses with protection in BAL suggests that these antibody responses may be critical for protection against SARS-CoV-2 Omicron challenge in mucosa.
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+The number of publications in biomedicine and life sciences has rapidly grown over the last decades, with over 1.5 million papers now being published every year. This makes it difficult to keep track of new scientific works and to have an overview of the evolution of the field as a whole. Here we present a 2D map of the entire corpus of biomedical literature, and argue that it provides a unique and useful overview of the life sciences research. We based our atlas on the abstract texts of 21 million English articles from the PubMed database. To embed the abstracts into 2D, we used the large language model PubMedBERT, combined with t-SNE tailored to handle samples of our size. We used our atlas to study the emergence of the Covid-19 literature, the evolution of the neuroscience discipline, the uptake of machine learning, the distribution of gender imbalance in academic authorship, and the distribution of retracted paper mill articles. Furthermore, we present an interactive web version of our atlas that allows easy exploration and will enable further insights and facilitate future research.
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Sibling Relationships and Parental Interventions to Sibling Bullying During Covid-19: A Qualitative Comparison of British and Turkish Families of Autistic Adolescents -
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+Background and aims: Despite its high potential for affecting sibling relationships, few studies have explored the impact of the Covid-19 pandemic on this important family dynamic. Of these, the reported evidence has been inconsistent across cultures and lacks cross-cultural comparability. For the first time, we investigated cross-cultural variability in the impact of Covid-19, and the restrictions associated with it, on sibling relationships of autistic adolescents from a Western (United Kingdom) and non-Western (Turkey) country. We also explored how British and Turkish parents intervene in negative sibling interactions â i.e., sibling bullying âwhen witnessed. Methods: Parents of 164 British and 96 Turkish autistic adolescents, aged 9-20 years, were asked how they perceived the effects of Covid-19 on their childrenâs sibling relationships, and how they were most likely to react to instances of sibling bullying. Free response data from parents were analysed using qualitative content analysis. Results: Our findings indicated more cross-cultural similarities than differences between British and Turkish families. The majority of both British and Turkish parents indicated that Covid-19 worsened sibling relationships between their autistic and non-autistic children. An overwhelming majority of British and Turkish parents also said that they would step in directly when witnessing sibling bullying. Despite the high volume of cross-cultural similarities generally, we also found some cross-cultural differences, for instance in relation to the most common negative impact of Covid-19 on sibling relationships and the most preferred parental responses to sibling bullying. Conclusions and implication: Implications and suggestions are discussed in more detail, drawing on the Etic approach to cross-cultural psychology.
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Sputum production and salivary microbiome in COVID-19 patients reveals oral-lung axis -
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+Objective: SARS-CoV-2 is a severe respiratory disease that primarily targets the lungs and was the leading cause of death worldwide during the pandemic. Investigating the intricate interplay between the oral microbiome and inflammatory cytokines during the acute phase of infection is crucial for understanding host immune responses. This study aimed to explore the relationship between the oral microbiome and cytokines in COVID-19 patients, specifically examining those with and without sputum production. Methods: Saliva and blood samples from 50 COVID-19 patients were subjected to 16S ribosomal RNA gene sequencing to analyze the oral microbiome. Additionally, 65 saliva and serum cytokines were assessed using Luminex multiplex analysis. The Mann-Whitney test compared cytokine levels between individuals with and without sputum production. Results: Our study revealed significant differences in the membership (Jaccard dissimilarity: p=0.016) and abundance (PhILR dissimilarity: p=0.048; metagenomeSeq) of salivary microbial communities between COVID-19 patients with and without sputum production. Seven bacterial genera, including Prevotella, Streptococcus, Actinomyces, Atopobium, Filifactor, Leptotrichia, and Selenomonas, were present in statistically higher proportions of patients with sputum production (p<0.05, Fisher's exact test). Eight bacterial genera, including Prevotella, Megasphaera, Stomatobaculum, Leptotrichia, Veillonella, Actinomyces, Atopobium, and Corynebacteria were significantly more abundant in the sputum-producing group, while Lachnoacaerobaculum was notably more prevalent in the non-sputum-producing group (p<0.05, ANCOM-BC).We observed a significant positive correlation between salivary IFN-gamma (Interferon-gamma) and Eotaxin2/CCL24 (chemokine ligand 24) with sputum production. Conversely, negative correlations were noted in serum MCP3/CCL7 (monocyte-chemotactic protein 3/Chemokine ligand 7), MIG/CXCL9 (Monokine induced by gamma/Chemokine ligand 9), IL1 beta (interleukin 1 beta), and SCF (stem cell factor) with sputum production (p<0.05, Mann-Whitney test). Conclusion: Substantial distinctions in salivary microbial communities were evident between COVID-19 patients with and without sputum production, emphasizing the notable impact of sputum production on the oral microbiome and cytokine levels during the acute phase of infection.
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Discovery of anti-SARS-CoV-2 S2 protein antibody CV804 with broad-spectrum reactivity with various beta coronaviruses and analysis of its pharmacological properties in vitro and in vivo -
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+SARS-CoV-2 pandemic alerts us that spillovers of various animal coronaviruses to human in the future may bring us enormous damages. Thus, there is a significant need of antibody-based drugs to treat patients infected with previously unseen coronaviruses. CV804 against the S2 domain of the spike protein, which is less prone to mutations. CV804 shows not only broad cross-reactivities with representative 20 animal-origin coronaviruses but also with diseases-associated human beta coronaviruses including SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-HKU1 and mutant strains of SARS-CoV-2. Other than that, the main characteristics of CV804 are that it has strong antibody-dependent cellular cytotoxicity (ADCC) activity to SARS-CoV2 spike protein-expressed cells in vitro and completely lacks virus-neutralization activity. Comprehensively in animal models, CV804 suppressed disease progression by SARS-CoV-2 infection. Structural studies using HDX-MS and point mutations of recombinant spike proteins revealed that CV804 binds to a unique epitope within the highly conserved S2 domain of the spike proteins of various coronaviruses. Based on the overall data, we suggest that the non-neutralizing CV804 antibody recognizes the conformational structure of the spike protein expressed on the surface of the infected cells and weakens the viral virulence by supporting host immune cells attack through ADCC activity in vivo. CV804 epitope identified in this study is not only useful for the design of pan-corona antibody therapeutics but also to design next-generation coronavirus vaccines and antiviral drugs.
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Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination -
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+Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection from disease progression. Non-neutralizing antibodies cannot directly protect from infection but may recruit effector cells thus contribute to the clearance of infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs from COVID-19 vaccinated individuals. Most of these antibodies exhibited no neutralizing activity in vitro but several non-neutralizing antibodies protected against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs showed a clear dependence on Fc-mediated effector functions. We determined the structures of three non-neutralizing antibodies with two targeting the RBD, and one that targeting the SD1 region. Our data confirms the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.
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Peptide Mold: A Novel Strategy for Mapping Potential Binding Sites in Protein Targets -
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+A novel concept titled Peptide Mold for mapping potential binding sites in protein targets is presented. A large multiconformer tetrapeptide library comprising of 32 million conformations of all possible combinations of naturally-occurring amino acids was constructed and used for molecular docking analysis in the substrate-binding site of SARS-CoV-2 PLpro enzyme. The top-ranking, structurally-diverse tetrapeptide docked conformations (symbolizing peptide mold, analogous to a clay mold) were used then for elucidating a five-point pharmacophore. Ligand-based virtual screening of a large, multiconformer library of phytoconstituents using the derived five-point pharmacophore led to identification of potential binders for SARS-CoV-2 PLpro at its substrate-binding site. The approach is based on generating the imprint of a macromolecular binding site (cavity) using tetrapeptides (clay), thereby generating a reverse mold (with definitive shape and size), which can further be used for identifying small-molecule ligands matching the captured features of the target binding site. The approach is based on the fact that the individual amino acids in the tetrapeptide represent all possible drug-receptor interaction features (electrostatic, H-bonding, van der Waals, dispersion and hydrophobic among others). The peptide mold approach can be extended to any protein target for mapping the binding site(s), and further use of the generated pharmacophore model for virtual screening of potential binders. The peptide mold approach is a robust, hybrid computational screening strategy, overcoming the present limitations of structure-based methods, e.g., molecular docking and the ligand-based methods such as pharmacophore search. Exploration of the peptide mold strategy is expected to yield high-quality, reliable and interesting virtual hits in the computational screening campaigns during the hit and lead identification stages.
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Influencers in Tourism Digital Marketing: A Comprehensive Literature Review -
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+Almost all business sectors in various developed and developing countries have realized the importance of transforming conventional marketing to digital marketing, the goal is to increase sales. Many marketing strategies can be applied to increase sales, including utilizing influencers in digital marketing. This study aims to identify digital marketing strategies that have been widely used by researchers in various countries and look for new models or new strategies that are relevant to be applied in developing countries after COVID-19 through a systematic literature review. The author searched for scientific articles on the Scopus database that were in English and fully accessible. This research reviewed 19 articles using a systematic literature review. The results showed that the majority of related research was published in 2018-2022, ten related articles were published in 2022 with three articles published in Spain. All authors proposed various variables, but generally conventional in digital marketing, while not many authors concentrated on the utilization of influencers in carrying out digital marketing. Therefore, this research offers a digital marketing strategy combined with the role of influencers in tourist destinations that have a competitive advantage.
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Curcumin and turmeric extract inhibit SARS-CoV-2 pseudovirus cell entry and Spike mediated cell fusion -
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+Turmeric extract (TE) with curcumin as its main active ingredient has been studied as a potential COVID-19 therapeutic. Curcumin has been studied in silico and in vitro against a naive SARS-CoV-2 virus, yet little is known about TEâs impact on SARS-CoV-2 infection. Moreover, no study reveals the potential of both curcumin and TE on the inhibition of SARS-CoV-2 cell-to-cell transmission. Here, we investigated the effects of both curcumin and TE on inhibiting SARS-CoV-2 entry and cell-to-cell transmission using pseudovirus (PSV) and syncytia models. We performed a PSV entry assay in 293T or 293 cells expressing hACE2. The cells were pretreated with curcumin or TE and then treated with PSV with or without the test samples. Next, we carried out syncytia assay by co-transfecting 293T cells with plasmids encoding spike, hACE2, and TMPRSS2 to be treated with the test samples. The results showed that in PSV entry assay on 293T/hACE/TMPRSS2 cells, both curcumin and TE inhibited PSV entry at concentrations of 1 M and 10 M for curcumin and 1 g/ml and 10 g/ml for TE. Moreover, both curcumin and TE reduced syncytia formation compared to control cells. Our study shows that TE and curcumin are potential inhibitors of SARS-CoV-2 infection at entry points, either by direct or indirect infection models.
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The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in infected and immune suppressed mice -
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+Objectives: Immunocompromised individuals are susceptible to severe COVID-19 and potentially contribute to the emergence of variants with altered pathogenicity due to persistent infection. This study investigated the impact of immunosuppression on SARS-CoV-2 infection in k18-hACE2 mice and the effectiveness of antiviral treatments in this context. Methods: Mice were immunosuppressed using cyclophosphamide and infected with a B lineage of SARS-CoV-2. Molnupiravir and nirmatrelvir, alone and in combination, were administered and viral load and viral sequence diversity was assessed. Results: Treatment of infected but immune compromised mice with both compounds either singly or in combination resulted in decreased viral loads and pathological changes compared to untreated animals. Treatment also abrogated infection of neuronal tissue. However, no consistent changes in the viral consensus sequence were observed, except for the emergence of the S:H655Y mutation. Molnupiravir, but not nirmatrelvir or immunosuppression alone, increased the transition/transversion (Ts/Tv) ratio, indicative of A>G and C>U mutations. Notably, immunosuppression itself did not appear to promote the emergence of mutations characteristic of variants of concern (VOCs). Conclusions: Further investigations are warranted to fully understand the role of immunocompromised individuals in VOC development and to inform optimised public health strategies. It is more likely that immunodeficiency promotes viral persistence but does not necessarily lead to substantial consensus-level changes in the absence of antiviral selection pressure. Molnupiravir, compared to nirmatrelvir, shows a stronger mutagenic effect in this model.
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Virological traits of the SARS-CoV-2 BA.2.87.1 lineage -
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+The highly mutated SARS-CoV-2 BA.2.87.1 lineage was recently detected in South Africa, but its transmissibility is unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for high transmissibility.
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Attenuated replication and damaging effects of SARS-CoV-2 Omicron in an intestinal epithelial barrier model -
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+Many COVID-19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function may play a key role in Long COVID. Despite its importance, the impact of SARS-CoV-2 on intestinal epithelia is poorly understood. To address this, we established an intestinal barrier model integrating epithelial Caco-2 cells, mucus-secreting HT29 cells and human Raji cells. This gut epithelial model allows efficient differentiation of Caco-2 cells into microfold-like cells, faithfully mimics intestinal barrier function, and is highly permissive to SARS-CoV-2 infection. Early strains of SARS-CoV-2 and the Delta variant replicated with high efficiency, severely disrupted barrier function, and depleted tight junction proteins, such as claudin-1, occludin and ZO-1. In comparison, Omicron subvariants also depleted ZO-1 from tight junctions but had fewer damaging effects on mucosal integrity and barrier function. Remdesivir and the TMPRSS2 inhibitor Camostat prevented SARS-CoV-2 replication and thus epithelial barrier damage, while the Cathepsin inhibitor E64d was ineffective. Our results support that SARS-CoV-2 disrupts intestinal barrier function but further suggest that circulating Omicron variants are less damaging than earlier viral strains.
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Designed mosaic nanoparticles enhance cross-reactive immune responses in mice -
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+Using computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by (i) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 RBD that were predicted to retain proper folding and abrogate antibody responses to variable epitopes (mosaic-2COMs; mosaic-5COM), and (ii) selecting 7 natural sarbecovirus RBDs (mosaic-7COM). These antigens were compared with mosaic-8b, which elicits cross-reactive antibodies and protects from sarbecovirus challenges in animals. Immunizations in naive and COVID-19 pre-vaccinated mice revealed that mosaic-7COM elicited higher binding and neutralization titers than mosaic-8b and related antigens. Deep mutational scanning showed that mosaic-7COM targeted conserved RBD epitopes. Mosaic-2COMs and mosaic-5COM elicited higher titers than homotypic SARS-CoV-2 Beta RBD-nanoparticles and increased potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COM elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons. These results support using mosaic-7COM to protect against highly mutated SARS-CoV-2 variants and zoonotic sarbecoviruses with spillover potential.
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The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2 -
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+The SARS-CoV-2 virus responsible for the COVID-19 global pandemic has exhibited a striking capacity for viral evolution that drives continued evasion from vaccine and infection-induced immune responses. Mutations in the receptor binding domain of the S1 subunit of the spike glycoprotein have led to considerable escape from antibody responses, reducing the efficacy of vaccines and monoclonal antibody (mAb) therapies. Therefore, there is a need to interrogate more constrained regions of Spike, such as the S2 subdomain. Here, we describe a collection of S2 mAbs from two SARS-CoV-2 convalescent individuals that target multiple regions in the S2 subdomain and can be grouped into at least five epitope classes. Most did not neutralize SARS-CoV-2 with the exception of C20.119, which bound to a highly conserved epitope in the fusion peptide and showed broad binding and neutralization activity across SARS-CoV-2, SARS-CoV-1, and closely related zoonotic sarbecoviruses. Several of the S2 mAbs tested mediated antibody-dependent cellular cytotoxicity (ADCC) at levels similar to the S1 mAb S309 that was previously authorized for treatment of SARS-CoV-2 infections. Three of the mAbs with ADCC function also bound to spike trimers from HCoVs, such as MERS-CoV and HCoV-HKU1. Our findings suggest there are diverse epitopes in S2, including functional S2 mAbs with HCoV and sarbecovirus breadth that likely target functionally constrained regions of spike. These mAbs could be developed for potential future pandemics, while also providing insight into ideal epitopes for eliciting a broad HCoV response.
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Phase II Clinical Study of SHEN211 Tablets in the Treatment of Mild and Moderate Novel Corona Virus Infection (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 ”g Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia 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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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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Effectiveness of a Nasal Spray on Viral Respiratory Infections - Conditions: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold Interventions: Device: Nasal Spray HSV Treatment Sponsors: CEN Biotech; Urgo Research, Innovation & Development Recruiting
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GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects - Conditions: COVID-19 Interventions: Drug: GS-441524; Drug: Placebo Sponsors: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc Not yet recruiting
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The Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19 - Conditions: COVID-19 Pneumonia; COVID-19 Interventions: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) Sponsors: Selda Sarıkaya; Zonguldak Bulent Ecevit University Completed
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UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects - Conditions: COVID-19 Pandemic; COVID-19 Vaccines Interventions: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 Όg Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia Active, not recruiting
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Mindfulness-based Mobile Applications Program - Conditions: COVID-19; Cell Phone Use; Nurse; Mental Health Interventions: Device: mindfulness-based mobile applications program Sponsors: Yu-Chien Huang Completed
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World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt - Conditions: Mucormycosis; Rhinocerebral (Etiology); COVID-19 Interventions: Procedure: debridment Sponsors: Nasser Institute For Research and Treatment Completed
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Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial - Conditions: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 Interventions: Drug: Hyperbaric oxygen Sponsors: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk Not yet recruiting
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Attention Training for COVID-19 Related Distress - Conditions: Anxiety Interventions: Behavioral: Attention Bias Modification; Behavioral: Attention Control Training; Behavioral: Neutral training Sponsors: Palo Alto University Not yet recruiting
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From PubMed
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Priming congruence and COVID-19 vaccination intention: a mediation analysis - CONCLUSIONS: Implications of these results are discussed in light of the socially situated cognition perspective and the congruence of (a) a societal context of communication toward the vaccine and the unvaccinated, (b) the participantâs degree of adherence to that communication, (c) the theme of priming, whether or not related to feeling connected to others. Implications of materialism priming are discussed, and the effect of commitment on intention to get vaccinated.
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A subunit-based influenza/SARS-CoV-2 Omicron combined vaccine induced potent protective immunity in BALB/c mice - Infection with influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant risk to human life, health, and the global economy. Vaccination is one of the most effective strategies in the fight against infectious viruses. In this study, we, for the first time, have evaluated the immunogenicity and protective effect of an influenza/SARS-CoV-2 Omicron subunit combined vaccine adjuvanted with MF59 and administered to BALB/c mice. Results showed thatâŠ
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Nudging Public Health Behaviors to Prevent COVID-19: A Systematic Review - Many countries have implemented strict preventive measures and mandatory policies to curb virus transmission during the COVID-19 pandemic. Some have adopted softer approaches, such as nudge-based intervention, to influence public health behavior. This systematic review, conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines, aims to determine if the nudge-based intervention can effectively influence peopleâs preventive behavior during theâŠ
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IFN-gamma decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3beta signaling pathway - Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8^(+) T cells from recovered COVID-19 patients was significantly lower. IFN-Îł in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8^(+) T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3ÎČ may regulate the INF-Îł/PD-1 axis in CD8^(+) T cells from COVID-19âŠ
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Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters - CONCLUSION: Altogether, we show that HSP90 inhibition could serve as a potential treatment option for moderate and severe cases of COVID-19.
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Synthesis, SARS-CoV-2 main protease inhibition, molecular docking and in silico ADME studies of furanochromene-quinoline hydrazone derivatives - Seven furanochromene-quinoline derivatives containing a hydrazone linker were synthesized by condensing a furanochromene hydrazide with 2-, 3-, 4-, 5-, 6-, and 8-quinoline carbaldehydes, including 8-hydroxyquinoline-2-carbaldehye. Structure-activity correlations were investigated to determine the influence of the location of the hydrazone linker on the quinoline unit on SARS-CoV-2 M^(pro) enzyme inhibition. The 3-, 5-, 6- and 8-substituted derivatives showed moderate inhibition of SARS-CoV-2âŠ
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Oligoadenylate synthetase 1 displays dual antiviral mechanisms in driving translational shutdown and protecting interferon production - In response to viral infection, how cells balance translational shutdown to limit viral replication and the induction of antiviral components like interferons (IFNs) is not well understood. Moreover, how distinct isoforms of IFN-induced oligoadenylate synthetase 1 (OAS1) contribute to this antiviral response also requires further elucidation. Here, we show that human, but not mouse, OAS1 inhibits SARS-CoV-2 replication through its canonical enzyme activity via RNase L. In contrast, both mouseâŠ
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SARS-CoV-2 mechanisms of cell tropism in various organs considering host factors - A critical step in the drug design for SARS-CoV-2 is to discover its molecular targets. This study comprehensively reviewed the molecular mechanisms of SARS-CoV-2, exploring host cell tropism and interaction targets crucial for cell entry. The findings revealed that beyond ACE2 as the primary entry receptor, alternative receptors, co-receptors, and several proteases such as TMPRSS2, Furin, Cathepsin L, and ADAM play critical roles in virus entry and subsequent pathogenesis. Additionally,âŠ
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Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies - Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here, we uncover the role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses viaâŠ
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Microfluidics produced ATRA-loaded PLGA NPs reduced tuberculosis burden in alveolar epithelial cells and enabled high delivered dose under simulated human breathing pattern in 3D printed head models - Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is second only to COVID-19 as the top infectious disease killer worldwide. Multi-drug resistant TB (MDR-TB) may arise because of poor patient adherence to medications due to lengthy treatment duration and side effects. Delivering novel host directed therapies (HDT), like all trans retinoic acid (ATRA) may help to improve drug regimens and reduce the incidence of MDR-TB. Local delivery of ATRA to the site of infection leads to higherâŠ
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Miquelianin: primary antioxidant power and Mpro SARS-CoV-2 non-covalent inhibition capabilities from computational investigations - The antioxidant power of quercetin-3-O-glucuronide (miquelianin) has been studied, at the density functional level of theory, in both lipid-like and aqueous environments. In the aqueous phase, the computed pKa equilibria allows the identification of the neutral and charged species present in solution that can react with the âąOOH radical. The Hydrogen Atom Transfer (HAT), Single Electron Transfer (SET) and Radical Adduct Formation (RAF) mechanisms were considered and the individual, total andâŠ
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Exploring Retrograde Trafficking: Mechanisms and Consequences in Cancer and Disease - Retrograde trafficking (RT) orchestrates the intracellular movement of cargo from the plasma membrane, endosomes, Golgi or endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) in an inward/ER-directed manner. RT works as the opposing movement to anterograde trafficking (outward secretion), and the two work together to maintain cellular homeostasis. This is achieved through maintaining cell polarity, retrieving proteins responsible for anterograde trafficking and redirecting proteinsâŠ
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Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study - One of the major pathomechanisms of COVID-19 is the interplay of hyperinflammation and disruptions in coagulation processes, involving thrombocytes. Antiplatelet therapy (AP) by anti-inflammatory effect and inhibition of platelet aggregation may affect these pathways. The aim of this study was to investigate if AP has an impact on the in-hospital course and medium-term outcomes in hospitalized COVID-19 patients. The study population (2170 COVID-19 patients: mean ± SD age 60 ± 19 years old, 50%âŠ
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Pan-viral propagation blockade by inhibiting host cell PNPT1 - Successful viral propagation within infected cells necessitates the virusesâ ability to overcome the cellular integrated stress response (ISR), triggered during viral infection, which in turn inhibits general protein translation. In our study, we unveil a shared tactic employed by viruses to suppress ISR by upregulating host cell polyribonucleotide nucleotidyltransferase 1 (PNPT1). The propagation of adenovirus, murine cytomegalovirus, and hepatovirus within their respective host cells inducesâŠ
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Synergistic Binding of SARS-CoV-2 to ACE2 and Gangliosides in Native Lipid Membranes - Viruses utilize cell surface glycans and plasma membrane receptors to attain an adequate attachment strength for initiating cellular entry. We show that SARS-CoV-2 particles bind to endogenous ACE2 receptors and added sialylated gangliosides in near-native membranes. This was explored using supported membrane bilayers (SMBs) that were formed using plasma membrane vesicles having endogenous ACE2 and GD1a gangliosides reconstituted in lipid vesicles. The virus binding rate to the SMBs isâŠ
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From Patent Search
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+ 02 March, 2024
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+Daily-Dose
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The Legacy of RuPaulâs âDrag Raceâ - The drag star brought the form mainstream, and made an empire out of queer expression. Now he fears âthe absolute worst.â - link
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The Israeli Settlers Attacking Their Palestinian Neighbors - With the worldâs focus on Gaza, settlers have used wartime chaos as cover for violence and dispossession. - link
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What a Major Solar Storm Could Do to Our Planet - Disturbances on the sun may have the potential to devastate our power grid and communication systems. When the next big storm arrives, will we be prepared for it? - link
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A Professor Claimed to Be Native American. Did She Know She Wasnât? - Elizabeth Hoover, who has taught at Brown and Berkeley, insists that she made an honest mistake. Her critics say she has been lying for more than a decade. - link
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Inside North Koreaâs Forced-Labor Program in China - Workers sent from the country to Chinese factories describe enduring beatings and sexual abuse, having their wages taken by the state, and being told that if they try to escape they will be âkilled without a trace.â - link
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From Vox
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How to master the art of small talk -
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+A guide to having actually interesting conversations with strangers.
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+Andy Lowe was not naturally blessed with the gift of gab. But even he, a self-described shy, introverted person, understands its functions. Lowe works at a technology public relations firm where chitchat with clients and journalists is just another part of the job. As a previous user of dating apps (Lowe is happily partnered now), he realized banter reigned supreme. He also plays bass in bands in Seattle; meeting other collaborators involves some amount of introductory small talk.
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+So he decided to get better. To improve his small talk, Lowe says he paid closer attention to his conversation partners to discover âwhat makes them tick, what drives them,â he explains. Heâll ask what books people are reading or movies or television they enjoy. âThen just making sure that when you go into those situations,â Lowe says, âyou are more interested in the person that youâre talking to than talking about yourself.â
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+Small talk gets a bad rap for being too surface-level, too rote, a throwaway filler conversation. But casual chat can be the on-ramp to deeper connection. After all, most of us wouldnât introduce ourselves to a stranger with a question about their biggest fears. Small talk is an opportunity to build trust and to learn about others, and to become a more curious person, says Georgie Nightingall, a conversation specialist and human connectivity researcher. âBeing genuinely curious, that always helps,â she says. âYou can actually realize that you do want to know more rather than having that sense of like, Iâm just asking for the sake of asking.â
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+Even if you find your small talk game lacking, with some practice you can improve. To ensure youâre leading with curiosity, experts and small talk enthusiasts offer their best advice to strike up a conversation with strangers and familiar faces alike, without relying on stereotypical openers.
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+View small talk as an opportunity, not an annoyance
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+Many people bemoan small talk because they âget stuckâ in it, Nightingall says, without moving on to deeper conversation. âOne of the key elements of small talk,â she says, âis having the mindset that actually this is not where weâre going to end up.â Consider all the relationships that began as banter or the job opportunities that came from acquaintances. There is potential for small talk to bloom into something bigger.
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+However, you should avoid viewing chitchat as solely transactional. Research shows people enjoy and appreciate talking with strangers or acquaintances, and these brief interactions contribute to well-being. While these conversations have the potential to be awkward, Gillian Sandstrom, a senior lecturer in the psychology of kindness at the University of Sussex, has found in research that most introductory small talk with strangers does in fact go well. As people engage in these chats with greater frequency, the more confident they are in their abilities to talk to strangers, according to the study. âThatâs enough to allow you to be in the moment more instead of in panic mode,â Sandstrom says.
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+What to talk about instead of your job
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+Popular scripts dominate small talk: comments about traffic and the weather, the questions âSo, what do you do?â and âHow are you?â Often, people give unengaging or throwaway answers that donât give the other person much to respond to. Instead, lead with inquiries related to your interests, says Adam Smiley Poswolsky, a workplace belonging expert and author of Friendship in the Age of Loneliness: An Optimistâs Guide to Connection. Consider asking a barista at your neighborhood cafe about their favorite beverage or if a friend of a friend at a party has also watched the newest season of Love Is Blind. If you want to feel a little more prepared, Poswolsky suggests having a list of five or so questions at the ready that are topical and feel authentic to you â just be sure to refresh your list every few weeks. Maybe your talking points include asking if someone has an upcoming vacation or if they tried any new restaurants recently.
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+However, donât feel like you must write off meteorological small talk. Discussing the weather is ample conversation fodder for my colleague Miles Bryan, a senior producer and reporter (and the self-appointed Philly Bureau Chief) for Today, Explained. âItâs such a shared experience between everybody Iâm talking to,â he says. âItâs a way to connect with somebody else without a lot of pressure on the conversation.â Luxuriating in small talk is thoughtful, Bryan says: âSmall talk is empathetic.â
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+To be better at small talk, actually listen
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+Making the most of small talk â and elevating the conversation to large talk â involves active listening. If someone mentions the city they grew up in, you can use that detail for follow-up questions. What did they like the most about that city? What did they dislike? Why did they move? You can even offer a personal anecdote, Nightingall says, maybe mentioning a trip you may have taken there. âWhenever someone shares anything with you, theyâre sharing a tiny dot in a web of hugeness,â Nightingall says. âOur job is to find out what makes this person different, interesting. What makes their life unique?â
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+The more curious you are about another personâs experiences or perspectives, the more likely the other party will be interested in continuing the conversation, Poswolsky says. The other person, in turn, will readily offer more information, furthering the discussion.
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+Just donât make it weird
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+With any interaction, there is a risk of coming on too strong or rubbing your conversation partner the wrong way. For small talk with strangers, especially, a well-meaning question may not be taken as intended or they may suspect you of trying to flirt with them. Small talk is warm and introductory, with no ulterior motives. It can surely blossom into a more flirtatious exchange but you should lead with curiosity and friendliness. âYou canât realistically be sitting next to someone on the plane and say, âHi, whatâs your favorite superpower,ââ Wiener says. âThat doesnât work on a human interaction level.â Starting with an observation about how packed the flight is or asking whether the person is traveling for work might be more of a context-appropriate introduction.
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+Wiener also suggests avoiding making small talk about someoneâs physical appearance or religious wear. Never make assumptions about or comment on someoneâs background, income level, sexuality, political stance, or other personal identifier.
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+Try not to sound accusatory either, Sandstrom says. One of her go-to opening lines is âWhat are you doing?â âI saw someone who was leaning over a bush and lifting up a leaf,â she says âand Iâm like, âWhatâs going on here?â They taught me some stuff about bugs.â But do your best to keep the mood playful â youâre asking out of curiosity, not suspicion.
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+Every once in a while, someone might bristle at your attempts at small talk or appear confused as to why youâre talking to them, and thatâs okay. Sandstrom finds explicitly stating âIâm just being friendlyâ helps ease some of the awkwardness.
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+What to do if you get stuck
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+Every conversation, including small talk, inevitably encounters roadblocks. Whether you find yourself giving one-word answers or the discussion veers toward potentially contentious territory, there are ways of deftly navigating. For chats that are veering on boring, feel free to direct the conversation to another topic or ask a random question. (Conversations arenât linear anyway, Nightingall notes.)
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+If you find the discussion isnât going anywhere after a few exchanges, donât force it, Poswolsky says. Either politely excuse yourself (âIâve got to run to the bathroomâ is a great exit) if youâre at a social gathering or simply drop the chitchat if youâre mingling with a stranger on public transit. For talks that become prejudiced or offensive, Sandstrom suggests saying âThis conversation is making me uncomfortable.â Just remember, both people need buy-in for small talk to be productive.
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+âIf zero people are excited, itâs over,â Poswolsky says. âIf one person is excited, you can see where youâre heading. What youâre looking for, and this is rare, is when two people are [having] a back-and-forth. Thereâs active listening happening on both parties. There are decent questions happening.â
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+Small talk is what you make it. It can be a delightful way to spend a few minutes with a stranger while in line at the grocery store, it can be your superpower at a party, or it can lead to your next career move. Or, if youâre like Bryan, it can simply be uplifting banter about precipitation.
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+âIf it looks like rain, and youâve got more to say about it, and youâre interested in what your partner has to say, just stay with it,â he says. âThe big stuff will come. But you donât need to rush it. Itâs okay to stay small.â
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The CDC has finally loosened Covid isolation guidelines. Hereâs why thatâs a good thing. -
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+Maria Stavreva/Getty Images
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+Today, the Centers for Disease Control and Prevention (CDC) changed its Covid-19 guidance in a big way: People infected with the virus, or with other respiratory viruses, no longer need to isolate for five days before going back to work or school, the agency said.
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+Instead, the agency advises thatpeople can leave home if theyâve been fever-free for at least 24 hours (without fever-reducing medicine like ibuprofen or acetaminophen) and have improving symptoms.
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+âItâs a reasonable move,â said Aaron Glatt, an infectious disease doctor and hospital epidemiologist at Mount Sinai South Nassau Hospital on Long Island. âWhen youâre doing public health, you have to look at what is going to be listened to, and what is doable.â
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+Guidelines that adhere to the highest standards of infection control might please purists in public health who donât have to make policies for the real world. However, guidelines that seem to acknowledge that workers often donât have paid sick leave and emergency child care, and that social interactions are important to folks, are more likely not only to be followed but to engender trust in public health authorities.
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+This change likely wonât increase exposure risk for the people most vulnerable to severe Covid-19
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+Itâs important to note that the new recommendations are aimed toward the broader community and the people who live, work, and go to school in it â not toward hospitals, nursing homes, and other facilities whose residents are both less socially mobile and more vulnerable to the virusâs worst effects.
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+That means the people who are at higher risk of getting severely ill or dying if they get infected â people who are older and sicker at baseline â are subject to different, more conservative guidelines. Which makes sense, said Glatt: âItâs not the same approach in a 4-year-old kid as it is in a nursing home. It shouldnât be.â
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+Covid-19 hospitalization rates among adults 65 and over are at least four times what they are in other age groups, and rates are particularly high among adults 75 and over, according to the CDC. In a study published in October, the agency reported that those 65 and older constituted nearly 90 percent of Covid-19 deaths in hospitals.
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+The older adults getting hospitalized and dying with Covid-19 now are not the otherwise well people with active work and social lives who were getting severely ill earlier in the pandemic, said Shira Doron, an infectious disease doctor and hospital epidemiologist at Tufts Medicine in Boston. Theyâre people with severe underlying illness and compromised immune systems â and for many, itâs not even clear Covid-19 is whatâs causing their decline. âIâm really struck by how totally different the Covid inpatient population â even the Covid death population that Iâm seeing â is from 2020, or even 2021,â she said.
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+Itâs hard to tell exactly how many of the worst-affected adults are infected in facilities like hospitals and nursing homes â in other words, how many of them would be relatively unaffected by a revised set of guidelines. Itâs also hard to tell how many older adults, aware of their higher risk, take more measures to protect themselves in public, like wearing masks and gathering outdoors.
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+However, itâs worth noting the experiences of states that have already loosened recommendations. Since Oregon loosened its guidelines in May 2023, the state has not seen unusual increases in transmission or severity; California made similar changes in January 2024. In revising their recommendations, state officials hoped to reduce the burdens on workers without sick leave and reduce disruptions on schools and workplaces, according to reporting in the Washington Post.
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+Doron said the reason loosened isolation guidelines havenât led to mayhem in Oregon â nor in Europe, where the recommendations began to loosen two years ago â is because isolation never did much to reduce transmission to begin with. âThis has nothing to do with the science of contagiousness and the duration of contagiousness. It has to do with [the fact that] it wasnât working anyway,â she said.
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+Leaning away from what doesnât work to reduce the virusâs impact â and toward what does work â is a smarter way forward, she said.
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+Revising testing guidelines would free up resources for interventions that actually work
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+Isolation guidelines havenât been effective in mitigating Covid-19 harms because so many people simply do what they want, regardless of whether theyâre sick â and they may avoid reporting symptoms to avoid being forced to comply with an isolation policy.
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+Imagine a workplace or school policy adheres to the current CDC guidelines, which recommend that people who test positive for Covid-19 infection stay home for at least five days. That policy creates a âperverse incentiveâ for some people who have symptoms to avoid getting tested, Doron said, because they donât want to miss school, work, or a social event. Because so many people donât have paid sick time, acknowledging even mild symptoms can lead to real financial losses when it means missing a week of work.
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+At the same time, because these guidelines build testing into their protocols, they lead lots of other people â and the federal government â to spend money on at-home tests, which are often inaccurate early in infection. Thatâs a waste of resources that could save more lives if they were instead spent on providing tests to people likeliest to benefit from Paxlovid and getting them treated, said Doron.
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+âYou should only be testing when it will change something, and that should be because you need Paxlovid or an antiviral,â Doron said. (Clarity and greater focus on who qualifies for Paxlovid would also be helpful, she said â current CDC recommendations are too broad.)
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+The updated guidelines clarify that testing is most useful for making choices about prevention or treatment â âeven better than what I was expecting,â said Doron.
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+In the long term, CDC guidelines should normalize being considerate
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+While the CDCâs guidelines arerecommendations, not requirements, employers and state and local health departments often use them to guide their own policies.
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+In February, before the guidelines had been published,Jay Varma, an epidemiologist and biotechnology executive with extensive experience in state and federal public health practice, said one area where a new set of guidelines could make a big difference is in elevating and normalizing masking. He hoped the new recommendations wouldlean heavily into putting forth masking in public as a matter of routine for people who leave home as soon as they feel well.
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+âCDC should be thinking of this as a decades-long effort to promote cultural acceptance that being in public with a mask is similar to washing your hands, wearing a condom, or smoking outdoors: Itâs a form of politeness and consideration for others,â Varma wrote in an email to Vox.
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+After all, in the long term, itâs a lot easier to change social norms around masking than it is to get people used to giving up their social lives for days or weeks at a time.
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+After the guidelines were released on Friday, Varma wrote on Threads that public health officials shouldâve advised individuals âthat you donât only use ventilation, hygiene, masks âwhen youâre home sickâ but when also you in public for at least 5 days after symptoms resolving.â He also wrote that organizations should improve ventilation and make N95 masks and antigen tests more broadly available to staff and visitors.
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+It would also be helpful for public health officials to encourage people to factor in who gets exposed if they leave isolation soon after a Covid diagnosis, said Glatt. The revised guidelines do note that itâs especially important to use prevention strategies when youâll be around people who have risk factors for severe illness â for example, if they take high-dose immunosuppressive medications, are either older adults or young children, or are pregnant.
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+Update, March 1, 5:40 pm ET: This story, originally published on February 14, has been updated to note the CDCâs revised guidelines on respiratory virus prevention.
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Take a mental break with the newest Vox crossword -
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+New Vox Crossword puzzles come out Monday through Saturday | Amanda Northrop
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+For the curious in all of us. Can you solve it?
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+And if you solve our crosswords often, consider chipping in to help keep them free for everybody.
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+Looking for even more crosswords? Our first-ever crosswords books are now available for purchase wherever you buy books. The first,theVox Mega Book of Mini Crosswords, features 150 of our bite-sized weekday puzzles. The second, theVox Pop Culture Crosswords book, highlights pop culture references in our big Saturday puzzles ranging from Mario Kart to iCarly.
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Ranji Trophy semifinal | Avesh Khanâs four-wicket haul help Madhya Pradesh bowls out Vidarbha - Madhya Pradesh reached 47 for one in their first innings at close, and trail by 123 runs.
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Ranji Trophy semifinal | Deshpande, Thakur shine as Mumbai takes opening day honours - Tamil Nadu struck twice with the ball but Mumbai shaved off a significant chunk of first-innings deficit, reaching 45/2 at stumps
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Eric Dier makes loan move to Bayern Munich permanent - The 30-year-old England midfielder joined Bayern on loan in January in a deal to the end of the season after spending a decade with Tottenham Hotspur
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Saudi Arabia launches bid to host the 2034 FIFA World Cup - The Middle East nation is almost certain to win hosting rights due to lack of bidding competitors
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Gautam Gambhir asks BJP to relieve him of political duties - The cricketer-turned-MP has said that he wants to focus on âupcoming cricket commitmentsâ
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From The Hindu: National News
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Annual synchronised terrestrial bird census begins in Nagapattinam Forest Division - A group of schoolchildren, Forest Department staff, and members of the Bombay Natural History Society begin the two-day exercise at Point Calimere Wildlife Sanctuary
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Kerala govt working towards increasing farmersâ income by 50%, says Pinarayi Vijayan - Production and productivity in Keralaâs agriculture sector will be increased as part of govt efforts to bring State to level of developed middle-income countries in next 25 years, says CM
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âNow double engine government in Bihar,â asserts PM Modi - CM Nitish Kumar assured that the JD(U) would continue its alliance with the BJP
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Corruption noose tightens on former CM KCR over Kaleshwaram project, says TPCC leader -
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Writing âBharatmataâ with saplings: Guinness world record set in Chandrapur - Certificate handed over to state Forest Minister Sudhir Mungantiwar during a ceremony held near the Tadoba Andhari Tiger Reserve.
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From BBC: Europe
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Top Ukrainian general eyes leadership shake-up - Gen Oleksandr Syrskyi insisted the situation on Ukraineâs eastern front âremains difficult, but controlledâ.
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Crowds chant anti-Putin slogans at Navalny funeral - âRussia without Putinâ mourners chanted, as they defied fear of arrest to bid farewell to Alexei Navalny.
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How we tracked down the Ukrainian poison seller - Leonid Zakutenko sold poison to vulnerable people who wanted to die - we confronted him at a post office in Kyiv.
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Suicide poison seller tracked down by BBC - Ukrainian Leonid Zakutenko sells a type of chemical online thought to be linked to at least 130 UK deaths.
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Pogba: The backstory, the wasted talent & why it could be the end - Paul Pogbaâs career could be over after his four-year ban for doping with the feeling the 30-year-old Juventus player never fulfilled his potential.
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From Ars Technica
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2024 Porsche 911 S/T review: Threading the needle - The S/T celebrates the 60th anniversary of the 911 and is limited to just 1963 examples. - link
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Researchers create AI worms that can spread from one system to another - Worms could potentially steal data and deploy malware. - link
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CDC ditches 5-day COVID isolation, argues COVID is becoming flu-like - The agency released a unified âpracticalâ guidance for respiratory viruses. - link
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Report: Boeing may reacquire Spirit at higher price despite hating optics - Spirit was initially spun out from Boeing Commercial Airplanes in 2005. - link
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US prescription market hamstrung for 9 days (so far) by ransomware attack - Patients having trouble getting lifesaving meds have the AlphV crime group to thank. - link
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From Jokes Subreddit
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A man goes to the doctor: âDoctor, Iâm embarrassed, but I have a bright red penis and it itches . . .â -
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+âYes, then get yourself free!â The patient drops his trousers, the doctor takes a look at the magnificent piece and says: âYes, really, itâs really inflamed. That looks very nasty. Are you married?â -
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+âYes!â How often do you have sex?"
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+âYes, if I think about it - Monday, Tuesday, Wednesday, Thursday, Friday - Saturday and Sunday!â Thatâs commendable! Do you have a girlfriend?" -
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+âSure!â âAnd how often do you have sexual intercourse?â
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+âAlso - Monday, Tuesday, Wednesday, Thursday, Friday, Saturday and Sunday!â âHard to believe - and do you have sex any other time?â
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+âYes, I go to the brothel!â âAnd how often?â
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+âMonday, Tuesday, Wednesday, Thursday, Friday, Saturday and Sunday!â âNo wonder, your penis must be inflamed!â
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+âThank God, doctor, and I thought it was from masturbating all the timeâŠâ
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Dave was getting a haircut prior to a trip to Rome. -
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+He mentioned the trip to the barber, who responded,
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+âWhy would anyone want to go there? Itâs crowded and dirty and full of Italians. Youâre crazy to go to Rome. So, how are you getting there?â
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+âWeâre taking United,â was the reply. âWe got a great rate!â
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+âUnited!â exclaimed the barber. âThatâs a terrible airline. Their planes are old, their flight attendants are ugly and theyâre always late. So, where are you staying in Rome?â
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+âWeâll be at the downtown International Marriott.â
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+âThat dump! Thatâs the worst hotel in Rome. The rooms are small, the service is surly and theyâre overpriced. So, whatcha doing when you get there?â
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+âWeâre going to go to see the Vatican and we hope to see the Pope.â
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+âThatâs rich,â laughed the barber. âYou and a million other people trying to see him. Heâll look the size of an ant. Boy, good luck on this lousy trip of yours. Youâre going to need it!â
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+A month later, Dave again came in for his regular haircut. The barber asked him about his trip to Rome.
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+âIt was wonderful,â explained Dave. âNot only were we on time in one of Unitedâs brand new planes, but it was overbooked and they bumped us up to first class. The food and wine were wonderful, and I had a beautiful young stewardess who waited on me hand and foot. And the hotel! Well, it was great! Theyâd just finished a $25 million remodeling job and now itâs the finest hotel in the city. They were overbooked too, so they apologized and gave us the presidential suite at no extra charge!â
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+âWell,â muttered the barber. âI know you didnât get to see the Pope.â
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+âActually, we were quite lucky, for as we toured the Vatican, a Swiss Guard tapped me on the shoulder and explained that the Pope likes to meet some of the visitors, and if Iâd be so kind as to step into his private room and wait, the Pope would personally greet me. Sure enough, five minutes later, the Pope walked in. As I knelt down he spoke to me.â
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+âWhat did he say?â
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+âHe said, âWhereâd you get this shitty haircut?â
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