+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 – i.e., sibling bullying –when 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 children’s 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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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 TE’s 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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Secondary structure of the SARS-CoV-2 genome is predictive of nucleotide substitution frequency -
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+Accurate estimation of the effects of mutations on SARS-CoV-2 viral fitness can inform public-health responses such as vaccine development and predicting the impact of a new variant; it can also illuminate biological mechanisms including those underlying the emergence of variants of concern. Recently, Lan et al reported a high-quality model of SARS-CoV-2 secondary structure and its underlying dimethyl sulfate (DMS) reactivity data. I investigated whether secondary structure can explain some variability in the frequency of observing different nucleotide substitutions across millions of patient sequences in the SARS-CoV-2 phylogenetic tree. Nucleotide basepairing was compared to the estimated mutational fitness of substitutions, a measurement of the difference between observed and expected substitution frequency that is correlated with other estimates of viral fitness. This comparison revealed that secondary structure is often predictive of substitution frequency, with significant decreases in substitution frequencies at basepaired positions. Focusing on the mutational fitness of C[->]T, the most common type of substitution, I describe C[->]T substitutions at basepaired positions that characterize major SARS-CoV-2 variants; such mutations may have a greater impact on fitness than appreciated when considering substitution frequency alone.
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Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome -
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+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 gingipains as well as by unknown bacterial factors. We found that the gingipain-mediated inhibition of infection is likely due to cytotoxicity, while PGDHC inhibited virus infection by an unknown mechanism. Unidentified factors present in P. gingivalis supernatant inhibited SARS-CoV-2 likely via the fusion step of the virus life cycle. We addressed the role of other oral bacteria and found certain periodontal pathogens capable of inhibiting SARS-CoV-2 pseudovirus infection by inducing cytotoxicity on target cells. In the human oral cavity, we observed the modulatory activity of oral microbial communities varied among individuals in that some saliva-based cultures were capable of inhibiting while others were enhancing infection. These findings contribute to our understanding of the complex relationship between the oral microbiome and viral infections, offering potential avenues for innovative therapeutic strategies in combating COVID-19.
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Carboxylated graphene: A novel approach for enhanced IgA-SARS-CoV-2 electrochemical biosensing -
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+Biosensors comprise devices that use a material of biological nature as receptors connected to transducers, these devices are capable of capturing biorecognition signals, called a primary signal, and converting it to a measurable signal. In this study, we report the synthesis of carboxylated graphene (CG) through a carboxylation method in acid medium and further characterization of the materials by different techniques such as scanning electron microscopy, energy-dispersive X-ray spectroscopy, Raman spectroscopy, thermal gravimetric analysis, and X-ray diffraction. Also, the surface of the screen-printed carbon electrodes (SPCEs) was modified with CG for subsequent immobilization of N-protein of SARS-CoV-2, which allowed the detection of antibodies (IgA-SARS-CoV-2). The electrical properties and response of the biosensor were investigated using electrochemical techniques (cyclic voltammetry and electrochemical impedance spectroscopy). Through the chemical characterization techniques, it was possible to confirm the success of the CG synthesis process. The biosensor fabricated shown to be able to detect IgA-SARS-CoV-2 in the range of 1:1000 to1:200 v/v in phosphate buffer solution (PBS) and the limit of detection calculated was 1:1601 v/v. this perspective they comprise a wide range of applications due to its advantages, such as the possibility of a shorter response time, reproducibility, the miniaturization of detection devices such as the use of screen-printed electrodes, the use of small amounts of sample, the high sensitivity and specificity, low limits of detection and the integration of nano materials that make it possible to improve the detected signal.
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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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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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Dose-Escalation 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 μg 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 participant’s 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 that…
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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 people’s preventive behavior during the…
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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-γ 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/GSK3β may regulate the INF-γ/PD-1 axis in CD8^(+) T cells from COVID-19…
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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-2…
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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 mouse…
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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,…
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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 via…
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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 higher…
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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 •OOH radical. The Hydrogen Atom Transfer (HAT), Single Electron Transfer (SET) and Radical Adduct Formation (RAF) mechanisms were considered and the individual, total and…
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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 proteins…
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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%…
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Pan-viral propagation blockade by inhibiting host cell PNPT1 - Successful viral propagation within infected cells necessitates the viruses’ 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 induces…
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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 is…
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From Patent Search
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The Legacy of RuPaul’s “Drag Race” - The drag star brought the form mainstream, and made an empire out of queer expression. Now he fears “the absolute worst.” - link
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The Israeli Settlers Attacking Their Palestinian Neighbors - With the world’s 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 Wasn’t? - 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 Korea’s 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 “killed without a trace.” - link
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From Vox
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Giant worms, dour nuns, and Timothée Chalamet as a super-being: The complicated world of Dune, explained -
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+Warner Bros. Pictures
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+A superfan explains Dune: Part 2 for newbies.
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+The biggest movie released so far this year is admittedly a little confusing. Or maybe not confusing, but it sure has a lot of lore.
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+I’m talking, of course, about Dune: Part Two.
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+Denis Villeneuve’s second installment adapting Frank Herbert’s 1960s sci-fi series of books enters theaters this week. Given it’s been over two years since the first film, and given the complexity of what’s happening in the Dune universe, I figured some of you might have a few questions.
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+Like, what’s up with Timothée Chalamet’s psychic boy king? Who are those dour-looking nuns? And what the hell is going on with the giant worms everywhere?
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+I love sci-fi — catch me any day with a copy of Gideon the Ninth or The Dispossessed — but I’ve never read Dune, so I can’t help you.
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+Patrick Reis, Vox’s senior politics editor and longtime Dune fan, can. I asked him a few questions for us all.
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+Light spoilers ahead about the series’ overall narrative arc.
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+So who’s this Paul Atreides guy that Timothée Chalamet is playing? I’m supposed to like him, right?
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+At the start of Villeneuve’s previous movie, Paul is the only child of House Atreides, son of Duke Leto Atreides (Oscar Isaac) and Lady Jessica (Rebecca Ferguson), a Bene Gesseritt (more on them soon).
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+Paul’s family has been coerced into leaving their home planet to move to Arrakis (also known as Dune), where they’re charged with overseeing the production of spice, the universe’s most precious resource.
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+At the end of the first film, Paul has hidden away with the Arrakis-native Fremen and allied with them against House Harkonnen — the despots who once again rule Arrakis after murdering Paul’s father and almost everyone he loved. (He also meets Chani (Zendaya), a Fremen who becomes his lover.) Over the course of Dune: Part Two, he makes his way up the Fremen ranks to become a messianic figure.
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+This leads to a fairly complicated moral arc over the rest of the series.
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+Right, see, here’s my question: Is he a good a messianic figure … or actually evil? I’m suspicious of this hero worship. And there’s also some weird white savior vibes here, right?
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+Is he “evil”? No in the short term; sort of yes in the medium term; and then mostly no in the extremely, extremely long term — events occurring decades, centuries, and even millennia later with the help of Paul’s descendants.
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+Dune Two is set in that short-term “no” part of the saga, where he’s helping the Fremen free themselves from the cruelty of House Harkonnen.
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+But to the other part of your question — yeah. Dune is fundamentally a white savior story in which the bulk of the agency is exercised by outsiders coming to a nomadic culture.
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+It’s also a pretty clear allegory to the Middle East: Spice is a rare substance that sustains modern life and facilitates empire-wide commerce and travel, so that’s pretty clearly oil. And so much about the Fremen seems to be designed to evoke desert nomads — and some of the most simplistic stereotypes about Arabs. At its worst, it’s Dances With Worms. All of this should, and in many cases does, make fans uncomfortable.
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+I think the movie makes some steps in the right direction. Zendaya’s Chani has much more agency in the movie than the book’s Chani does, which puts some of the power back in the hands of the Fremen.
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+But without basically setting aside a huge chunk of the book’s plot, I’m not sure there’s a way around the white savior trope. Someone tried making a Dune movie without sticking closely to the book, and it’s a hilarious mess.
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+Who are the Bene Gesserit, and more importantly, why aren’t they in charge?
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+To the naked eye, the Bene Gesserit look like a bunch of superpowered nuns — although they’re not exactly nuns — as Paul’s mother Lady Jessica is part of the sisterhood.
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+But let’s back up a bit to understand why they’re so important and what exactly they’re trying to do.
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+Long before the events of the films, humanity had a purge of all “thinking machines.” And so for centuries (and maybe longer), the main advances in technology have not been better machines, but re-engineering humans themselves.
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+That’s the big project the Bene Gesserit are working on: breeding the superbeing.
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+Paul was supposed to be the second-to-last step before that superbeing. Lady Jessica was to have a female — Bene Gesserit can determine their offspring’s gender because of course they can — to mate with the heir to House Harkonnen. But out of love for Oscar Isaac’s Duke Leto (RIP), she granted his wish for a male heir. That brought the superbeing into the universe a generation early, upending the Bene Gesserit plan.
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+So to get back to your question: The Bene Gesserit seem content to let the men fight the relatively small-stakes conflicts over the imperial throne and control of the spice. But behind the scenes, they are fighting a bigger fight: to produce a superbeing whom they can control.
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+Unfortunately for them, they only get halfway there — as Paul is certainly not interested in being under anyone’s control.
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+Okay, but most importantly, talk to me about these giant worms. They’re pretty important to the plot — and super cool to look at — but they don’t seem to make sense.
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+We learned in the first film that the Fremen and desert dwellers seem to know how to avoid getting eaten by the worms, so … just what are the worms feeding on to get so big? And, more importantly, what do they have to do with this all-powerful and precious spice?
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+Reading between the lines, I think they actually feed on something in the desert sand, rather than on the creatures of it. Rather than the apex predator of the ecosystem, they’re better likened to, you know, our regular old earthworms here on Earth. They tunnel through the desert and enrich it — possibly even by aiding in the production of spice.
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+So I think they’re being territorial, rather than predatory, when they swallow spice harvesting machines or Harkonnen corpses or anything else that doesn’t adequately disguise its movements when walking across the sands. I would be happy to discuss sandworm ecology with you for approximately 10 more hours, but I’ve probably said enough here. Enjoy the film!
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Driving at ridiculous speeds should be physically impossible -
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+Kevin Burbach/Associated Press
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+Reckless speeding is epidemic in the US. This simple technology could save tens of thousands of lives.
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+Speeding plays a role in over 12,000 US car fatalities per year, around a third of the national total. But an emergent technology could dramatically reduce that death toll, if not eliminate it entirely.
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+The auto industry has done little to address speeding, and it may be worsening the problem. Although the highest speed limit anywhere in the US is 85 mph (on Texas State Highway 130), most new cars can easily reach triple digits. Speedometers often rise all the way to 155 mph, and even safety-conscious Volvo lets drivers reach 112 mph (those behind the wheel of a Tesla Model S Plaid can top 200 mph).
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+Sure, a driver passing a semitruck on an interstate might need to briefly break the posted limit. But it’s hard to imagine a scenario where hitting 100 mph on a public road is anything short of reckless. Pedestrians are in particular danger; according to a 2011 study by the American Automobile Association, their average risk of death is 10 percent if struck by a car going 23 mph, but 50 percent at 42 mph and 75 percent at 50 mph.
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+Being surrounded by multiple tons of metal affords car occupants some protection, but they are hardly invulnerable. Many of the most catastrophic car crashes involve extreme acceleration, such as one in January in which a driver reached 124 mph on a 45 mph North Carolina highway before flipping the car and killing a University of North Carolina undergraduate.
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+In 2022, a woman flew through a Los Angeles intersection at 130 mph, more than triple the 35-mph speed limit, before striking multiple vehicles and killing five people, including a pregnant woman and her 11-month-old son.
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+At a national level, Americans are far more likely to die in crashes than those living in other rich countries; even comparably spacious and car-clogged Canada has a per capita crash death rate that is 60 percent lower than its southern neighbor.
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+ Steve Story/Getty Images
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+Happily, a common-sense solution is available. A technology known as Intelligent Speed Assistance (ISA) can make it difficult or impossible for drivers to drastically exceed the posted limit. Over the last few months, a bevy of federal, state, and local officials have called for ISA adoption on all new cars, or at least on those driven by public employees or those with a history of reckless driving.
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+From New York City to California, speed-limiting technology is having a moment.
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+The European Union will require speed limiters in new cars. Could the US do the same?
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+It’s been a long time coming. Rudimentary speed limiters have been available for over a century; in 1923, Cincinnati residents voted on a road safety proposal that would have mechanically restricted any car within city limits to 25 mph. That referendum was defeated, and the idea of constraining car speed subsequently faded from popular view.
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+But the recent emergence of ISA has thrust it back into policy conversations. Initially conceived of in France 40 years ago, modern ISA systems can be divided into two categories, both of which use GPS and digital maps to ascertain the speed limit on the roadway where a car is traveling.
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+“Active” ISA systems completely prevent further acceleration after the vehicle hits a given speed ceiling, such as five miles over the posted limit. “Passive” ISA is more permissive, relying on sounds, vibrations, or accelerator resistance to compel the driver to slow down (a determined driver can ignore those warnings and keep speeding up).
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+Both versions of ISA offer something rare and enticing: a straightforward technological fix for a major source of roadway carnage.
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+In 2022, the European Union adopted a rule requiring all new cars to be outfitted with passive ISA, starting this July. That was a watershed moment for ISA adoption — and it raised eyebrows across the Atlantic.
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+Later that year, New York City Mayor Eric Adams announced a groundbreaking pilot program in which ISA would be retrofitted into several dozen city-owned vehicles. The preliminary results are encouraging, showing a 36 percent reduction in hard braking (often used as a proxy for unsafe driving). Adams has spoken about potentially expanding the pilot across tens of thousands of vehicles within the city’s fleet, a move that could amplify safety benefits because cars with ISA also compel drivers behind them to obey the speed limit.
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+The next big move came last October, when the National Transportation Safety Board released its investigation into a particularly gruesome 2022 crash in North Las Vegas, in which the driver of a Dodge Challenger blasted through a red light at 103 mph (speed limit: 35 mph), striking a minivan and killing himself and eight other people. For the first time, NTSB officially recommended that the National Highway Traffic Safety Administration (NHTSA), the vehicle safety division of the federal Department of Transportation, require all new cars sold in the US to contain ISA.
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+Although the NTSB lacks the power to enforce its recommendation, it left an impression on California State Senator Scott Wiener, a San Francisco Democrat. In January, Wiener unveiled a bill that would set a deadline of 2027 for all new cars sold in the Golden State to contain an active version of ISA, set to 10 mph over the speed limit (a to-be-defined override would be available in emergencies). Wiener told me that even if his bill doesn’t pass, he hopes that it inspires elected leaders elsewhere to pick up the ISA baton and run with it.
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+A few weeks later, the District of Columbia City Council unanimously passed a street safety bill that included a new pilot program to install ISA in the vehicles of drivers who “commit serious speeding crimes,” according to Council member Charles Allen. That approach could prevent habitually reckless drivers from further endangering everyone else on the street. (For example, the man who caused the 2022 crash in North Las Vegas already had three prior speeding convictions.)
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+Momentum behind ISA is clearly growing.
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+Speed limiting is commonsense policy — but it’ll be an uphill climb
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+NHTSA has shown no signs of requiring ISA at the federal level but provided a statement that it was “initiating new research this year” into the technology, without offering further detail.
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+Why the lack of urgency, despite US crash deaths being up 27 percent from a decade ago? ISA elicits fierce resistance from carmakers (whose marketing ads often feature their vehicles zooming through streets with a tiny disclaimer that they were filmed with stunt drivers on a closed course). The Alliance for Automotive Innovation, an auto industry lobbying association, responded to the California ISA bill by questioning the technology’s reliability.
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+Some car owners, too, may be wary, imagining scenarios where ISA prevents them from rushing to the hospital. Such occurrences are rare, and when they do happen, an untrained driver blasting past speed limits puts everyone in a dangerous situation. Every ISA proposal I have seen exempts emergency vehicles while permitting regular drivers to go a few mph over the posted limit.
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+Inevitably, there will be visceral opposition from those who view speed-limiting technology as an attack on “freedom,” even though breaking the posted limit is, by definition, already illegal. “Forget your constitutional rights, those can be damned, even your movement controlled,” fulminated Fox News host Laura Ingraham last November, after the NTSB endorsed ISA. (Several decades ago, the introduction of seat belt laws sparked a similar response.)
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+But ISA supporters have logic on their side. It is nonsensical that shared e-scooters weighing a few dozen pounds are widely throttled at 15 mph or less, while cars that are 100 times heavier and able to travel 10 times faster have no such mechanical restrictions. The status quo is even more outrageous at a time when the US is mired in an ongoing road safety crisis, including a 40-year high in pedestrian deaths.
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+With each new ISA bill and pilot program, the Overton window widens, and a federal requirement becomes a little more conceivable. For the sake of everyone on the road — including those who walk, bike, or ride transit as well as those inside a car — let’s hope that day arrives soon.
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More than 100 Palestinians were killed trying to get aid -
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+A Palestinian girl carries a pot of warm meal while others wait to receive food distributed by charity as Gaza’s hunger crisis worsens, on February 29, 2024, in Deir al Balah, central Gaza. | Ali Jadallah/Anadolu via Getty Images
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+The competing narratives about a deadly aid distribution in Gaza, explained.
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+Food, clean water, and other basic goods are nearly impossible to come by throughout Gaza due to ongoing Israeli military operations and the extreme destruction the past four months of war have wrought. Overall, humanitarian aid to Gaza has been extremely limited not only because of the difficult on-the-ground logistics and danger in delivering assistance, but also because Israel has heavily restricted aid from entering the enclave.
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+This is just the latest high-profile incident in which civilians and civilian institutions in Gaza have been killed in large numbers during the war in Gaza; ambulances, hospitals, schools, and other facilities run by the United Nations Relief and Works Agency (UNRWA) have all been attacked in Gaza over the four months of the war, further endangering Palestinian lives already at risk not just due to bombardment, but now also starvation and disease.
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+In the span of five months, this conflict has killed 30,000 Palestinians and injured tens of thousands more; as already-scarce resources dwindle, those numbers are likely to increase exponentially unless there is a sustained ceasefire.
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+How were so many people killed and wounded?
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+Hundreds of people in Gaza City awaited the arrival of the aid convoy — some lining up Wednesday to get the canned goods and flour from aid trucks in the besieged city. People throughout Gaza are in extreme need, but the north, where Gaza City sits, faces particularly serious and pressing shortages of the most basic goods; an aid convoy that arrived earlier this week was reportedly the first in a month.
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+What happened to the people waiting for aid is a matter of debate. In an emailed statement, the Israel Defense Forces acknowledged an incident in Gaza City, saying only that ”Gazan residents surrounded the trucks, and looted the supplies being delivered. During the incident, dozens of Gazans were injured as a result of pushing and trampling. The incident is under review.”
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+However, the IDF’s on-the-record statement contained no acknowledgment of the claim that Israeli forces openedfire on the crowd, nor of casualty reports. That contrasts with accounts from Gaza health authority officials and multiple eyewitnesses of Israeli troops firing into the crowd as people tried to get to the food on the trucks.
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+Around 100 people with gunshot wounds were treated at Kamal Adwan Hospital in Gaza City, the New York Times reported. The hospital also received the bodies of 12 people who had been shot and killed. More than 150 patients, many with shooting injuries, were being treated at al-Awda Hospital in northern Gaza, as Dr. Mohammed Salha, the hospital’s acting director, told the Associated Press.
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+A later press conference by Rear Adm. Daniel Hagari, an IDF spokesperson, mentioned that the IDF fired warning shots but blamed casualties on people trampling each other as they tried to get access to food and supplies. He denied that there was an Israeli strike on the convoy of 38 trucks.
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+One Palestinian eyewitness, Kamel Abu Nahel, told the Associated Press that Israeli troops fired initial shots which scattered the crowd. After the shooting stopped and people returned, Abu Nahel said, troops opened fire again. He was shot in the leg and is being treated at Shifa hospital.
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+The information landscape in Gaza is extremely challenging. Foreign reporters have not been able to enter the area during the ongoing operations since October 7, and details of exactly what happened are still coming to light.
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+But what we do know is that Israel has repeatedly attacked, blocked, and destroyed humanitarian infrastructure and access throughout the war.
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+How desperate is the situation in northern Gaza?
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+Northern Gaza is where the IDF began its initial ground invasion in October; Israel targeted Gaza City as a Hamas stronghold. Though much of the population has been displaced to southern Gaza, there are still thousands of civilians in the area, and they have not had adequate aid distribution in around two months, Jeremy Konyndyk, the president of Refugees International, told Vox.
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+“The biggest obstacle has simply been that the Israeli government has, for the most part, denied aid groups access to that part of the territory,” he told Vox.
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+The UN organization that is usually in charge of distributing aid to Palestine, UNRWA, cannot operate in the area for safety reasons. And aid workers have said they’ve found trying to work with Israel to get aid into Gaza all but impossible.
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+After a UNRWA and World Food Program aid convoy “coordinated with the Israelis,” according to Konyndyk, it was fired upon by Israeli troops. “There’s no confidence amongst professional humanitarians that they can actually have safe access into the north and that they won’t be targeted.”
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+Israel has also accused UNRWA of being in league with Hamas, and that accusation led many countries, including the US, to pause financial contributions to the organization. Aid distribution is challenging and requires significant coordination; without that, it’s easy for a situation in which people are starving and under significant duress to spiral out of control and turn violent.
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+Such infrastructure once existed in Gaza — via UNRWA and with the cooperation of Hamas civilian police — but that has been devastated by Israeli assaults and, in the case of UNRWA, an effort to undermine the organization.
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+“The best way to get humanitarian aid into Gaza is to stop the fighting,” Brian Finucane, senior adviser in the US policy program at the International Crisis Group, told Vox in an interview. “Based on reports today, in recent weeks, the breakdown of any sort of order in Gaza is even complicating that further and that Israel itself is contributing [to] that in no small part, including by targeting the police inside Gaza.”
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+Hagari said during the press conference that a private contractor was coordinating the aid distribution, although he did not name the contractor. Vox reached out to the IDF and to Israel’s Coordinator of Government Activities in the Territories (COGAT) for more information but did not receive a response by press time.
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+As part of potential ceasefire negotiations, the US is pushing for increased humanitarian access in Gaza, but so far has not backed up that rhetoric with meaningful action like pausing the flow of weapons to Israel or proposing a ceasefire resolution in the UN Security Council. So despite the concerted efforts of diplomats and humanitarian workers, Finucane said, “They don’t have much to work with if the US bottom line is unconditional support for this catastrophic conflict.”
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From The Hindu: Sports
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West Brook, Indian Blues, Sekhmet, Armory and The Grey Geranium shine -
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Praggnanandhaa blunders again, goes down to Rapport - The all-Indian duel between Vidit Gujrathi and D. Gukesh ended in a stalemate.
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Ranji Trophy semifinal | Gritty Madhya Pradesh looks to outwit formidable Vidarbha - Two-time champions Vidarbha have played four matches at the VCA Stadium this season, and they have won three of them with the solitary defeat coming against Saurashtra.
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Ranji Trophy semifinal | Shreyas Iyer in spotlight as Mumbai takes on Tamil Nadu - Both Mumbai and Tamil Nadu are coming off impressive wins at the quarterfinal stage.
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BCCI to conduct women’s domestic red-ball tournament in Pune from March 28 - The move comes after the Indian women’s team’s return to Test cricket
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From The Hindu: National News
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‘Operation Valentine’ movie review: Shallow and suffers from a sense of deja vu - ‘Operation Valentine’, directed by Shakti Pratap Singh and starring Varun Tej, has neither depth in writing nor the wow moments for a visual spectacle
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IAF plane lands safely at Begumpet airport after technical snag -
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Some degrees are not enough to land government jobs - State recruitment rules do not recognise some degrees, making candidates ineligible
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India to set up International Big Cat Alliance - The Alliance, to be headquartered in India, will create a corpus fund and disseminate good practices in the conservation of ‘big cats’ across their range; 16 of 96 ‘big cat’ countries have signed on so far
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‘Chaari 111’ movie review: A few humorous lines and nothing more - ‘Chaari 111’, director Keerthi Kumar’s Telugu espionage comedy drama headlined by Vennela Kishore, never rises beyond some silly fun
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From BBC: Europe
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‘We won’t forget you’ - crowds chant as Navalny’s body taken for burial - Crowds of Russians risk arrest by going to the church near Moscow for the opposition leaders’ funeral.
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Crowds shout in defiance at Navalny funeral - “We’re not afraid” mourners chant as the body of the Russian opposition leader arrives for the funeral.
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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 Pogba’s 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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Irish President Higgins in hospital following tests - Michael D Higgins is in “excellent spirits” but will remain in hospital after feeling unwell on Thursday evening.
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From Ars Technica
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For Virgin Galactic, becoming profitable means a pause in flying to space - Virgin Galactic has just one more flight planned for its only operational spaceship. - link
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Gastrointestinal disease explodes in Ala. elementary school; 773 kids out - Highly contagious norovirus is the leading suspect; four other area schools affected. - link
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Emulation community expresses defiance in wake of Nintendo’s Yuzu lawsuit - “EmuDev” coders cite precautions, legal differences they say will offer protection. - link
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Study finds link between marijuana use and cardiovascular disease - Researchers call for more studies to understand why they’re linked. - link
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HP wants you to pay up to $36/month to rent a printer that it monitors - “Never own a printer again.” - link
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From Jokes Subreddit
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A young blonde girl from California in her late teens, who moved to Texas, wanting to earn some extra money for the summer, decided to hire herself out as a “handy woman” and started canvassing a nearby up scale neighborhood. -
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+She went to the front door of the first house and asked the owner if he had any odd jobs for her to do. “Well, I guess I could use somebody to paint the porch” he said. “How much will you charge me?” Delighted, the girl quickly responded, “How about $50?” The man agreed and told her that the paint and brushes and everything she would need were in the garage.
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+The man’s wife, hearing the conversation, said to her husband, “Does she realize that our porch goes ALL the way around the house?”
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+“That’s a bit cynical, isn’t it?” he responded.
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+The wife replied, “You’re right. I guess I’m starting to believe all those blonde jokes.”
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+A few hours later the blonde came to the door to collect her money. “You’re finished already??” the startled husband asked. “Yes,” the blonde replied, “and I even had paint left over so I gave it two coats.”
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+Impressed, the man reached into his pocket for the $50 and handed it to her along with a $20 tip.
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+“Thank you,” the gal said, “And, by the way, it’s not a Porch, it’s a Lexus…”
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Steve Story/Getty Images
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