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+ + + ++ABSTRACT Background The COVID-19 pandemic is likely to represent an ongoing global health issue given the potential for vaccine escape and the low likelihood of eliminating all reservoirs of the disease. Whilst diagnostic testing has progressed at pace, there is an unmet clinical need to develop tests that are prognostic, to triage the high volumes of patients arriving in hospital settings. Recent research has shown that serum metabolomics has potential for prognosis of disease progression. 1 In a hospital setting, collection of saliva samples is more convenient for both staff and patients, and therefore offers an alternative sampling matrix to serum. We demonstrate here for the first time that saliva metabolomics can reveal COVID-19 severity. Methods 88 saliva samples were collected from hospitalised patients with clinical suspicion of COVID-19, alongside clinical metadata. COVID-19 diagnosis was confirmed using RT-PCR testing. COVID severity was classified using clinical descriptors first proposed by SR Knight et al. Metabolites were extracted from saliva samples and analysed using liquid chromatography mass spectrometry. Results In this work, positive percent agreement of 1.00 between a PLS-DA metabolomics model and the clinical diagnosis of COVID severity was achieved. The negative percent agreement with the clinical severity diagnosis was also 1.00, for overall percent agreement of 1.00. Conclusions This research demonstrates that liquid chromatography-mass spectrometry can identify salivary biomarkers capable of separating high severity COVID-19 patients from low severity COVID-19 patients in a small cohort study. +
++In tropical Africa, SARS-CoV-2 epidemiology is poorly described because of lack of access to testing and weak surveillance systems. Since April 2020, we followed SARS-CoV-2 seroprevalence in plasma samples across the Kenya National Blood Transfusion Service. We developed an IgG ELISA against full length spike protein. Validated in locally-observed, PCR-positive COVID-19 cases and in pre-pandemic sera, sensitivity was 92.7% and sensitivity was 99.0%. Using sera from 9,922 donors, we estimated national seroprevalence of SARS-CoV-2 antibodies at 4.3% in April-June 2020 and 9.1% in August-September 2020. The second COVID-19 wave peaked in November 2020. Here we estimate national seroprevalence in early 2021. Between January 3 and March 15, 2021, we collected 3,062 samples from donors aged 16-64 years. Among 3,018 samples that met our study criteria 1,333 were seropositive (crude seroprevalence 44.2%, 95% CI 42.4-46.0%). After Bayesian test-performance adjustment and population weighting to represent the national population distribution, the national estimate of seroprevalence was 48.5% (95% CI 45.2-52.1%). Seroprevalence varied little by age or sex but was higher in Nairobi, the capital city, and lower in two rural regions. Almost half of Kenyan adult donors had evidence of past SARS-CoV-2 infection by March 2021. Although high, the estimate is corroborated by other population-specific estimates in country. Between March and June, 2% of the population were vaccinated against COVID-19 and the country experienced a third epidemic wave. Natural infection is outpacing vaccine delivery substantially in Africa, and this reality needs to be considered as objectives of the vaccine programme are set. +
++Objectives: Although high altitude training has been increasingly popular in endurance athletes, the molecular and cellular bases of this adaptation remain poorly understood. We aimed to define the underlying physiological changes and screen for potential biomarkers of adaptation using transcriptional profiling of whole blood. More generally, we aimed to evaluate the utility of blood RNA sequencing as a modern and sensitive method of athlete9s health monitoring. Methods: Seven elite female speed skaters were profiled before and after 1h intense exercise, on the 18th day of Live High, Train High (LHTH) training programme. Whole blood RNA sequencing (RNA-seq) with globin depletion was used to measure gene expression changes associated with high intensity exercise at high altitude. Eight public microarray datasets were used to identify genes uniquely regulated at high altitude. Gene markers derived from single cell RNA-seq data were used to evaluate the changes of individual cell types in the whole blood. Results: Using individual cell type signatures, we were able to deconvolute the changes of finely defined cell populations from the whole blood RNA-seq. We have detected the increase in neutrophils, platelets, erythrocytes, and CD14 monocytes, and the decrease in natural killers, CD8 T cells, memory CD4 T cells, B cells, and plasmacytoid dendritic cells. The levels of naive CD4 T cells, CD16 monocytes, and myeloid dendritic cells were unchanged. Leveraging the previously published transcriptomic data allowed us to define the expression signature unique to high-altitude adaptation. Among the identified genes we highlight PHOSPHO1, which has a known role in erythropoiesis, and MARC1 with a proposed role in endogenic NO metabolism. Finally, we find that platelets and, to a lesser extent, erythrocytes are the two major cell types that uniquely respond to altitude exercise, while neutrophils represent a more generic marker of intense exercise. Conclusions: Using publicly available data from both single-cell RNA-seq atlases and exercise-related blood profiling dramatically increases the value of whole blood RNA-seq for dynamic evaluation of physiological changes in an athlete9s body. In addition to the measurement of individual gene expression changes, our approach allowed us to estimate changes of blood cell type counts from a small peripheral blood sample, without sorting or other expensive and unfeasible equipment. We also discuss a surprising parallel of hypoxia and increased thrombosis, and hypothesize about the role exercise can play in COVID-19 outcomes. +
++To prevent the catastrophic health and economic consequences from COVID-19 epidemics, some nations have aimed for no community transmission outside of quarantine. To achieve this, governments have had to respond rapidly to outbreaks with public health interventions. But the exact characteristics of an outbreak that trigger these measures differ and are poorly defined. We used existing data from epidemics in Australia to establish a practical model to assist stakeholders in making decisions about the optimal timing and extent of interventions. We found that the number of reported cases on the day that interventions commenced strongly predicted the size of the outbreaks. We quantified how effective interventions were at containing outbreaks in relation to the number of cases at the time the interventions commenced. We also found that containing epidemics from novel variants that had higher transmissibility would require more stringent interventions that commenced earlier. In contrast, increasing vaccination coverage would enable more relaxed interventions. Our model highlights the importance of early and decisive action in the early phase of an outbreak if governments aimed for zero community transmission, although new variants and vaccination coverage may change this. +
++The period from February to June 2021 was one during which initial wild-type SARS-CoV-2 strains were supplanted in Ontario, Canada, first by variants of concern (VOC) with the N501Y mutation (principally alpha, beta and gamma variants), and then by the delta variant. We demonstrate that these emerging VOCs were associated with an increase in virulence, as measured by risk of hospitalization, intensive care unit admission, and death. Compared to non-VOC SARS-CoV-2 strains, and adjusting for comorbidity, age and sex of cases, and temporal trends, the elevation in risk associated with N501Y-positive variants was 74% (62-86%) for hospitalization; 138% (105-176%) for ICU admission; and 83% (57-114%) for death. Increases with delta variant were even larger: 105% (80-133%) for hospitalization; 241% (163-344%) for ICU admission; and 121% (57-211%) for death. The progressive increase in transmissibility and virulence of SARS-CoV-2 variants will result in a significantly larger, and more deadly, pandemic. +
++Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multi-parametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We apply Ig-MS to plasma from subjects with severe & mild COVID-19, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, with compatibility to any recombinant antigen to gauge our immune responses to vaccination, pathogens, or autoimmune disorders. +
++While many transmission models have been developed for community spread of respiratory pathogens, less attention has been given to modeling the interdependence of disease introduction and spread seen in congregate settings, such as prisons or nursing homes. As demonstrated by the explosive outbreaks of COVID-19 seen in congregate settings, the need for effective outbreak prevention and mitigation strategies for these settings is critical. Here we consider how interventions that decrease the size of the susceptible populations, such as vaccination or depopulation, impact the expected number of infections due to outbreaks. Introduction of disease into the resident population from the community is modeled as a branching process, while spread between residents is modeled via a compartmental model. Control is modeled as a proportional decrease in both the number of susceptible residents and the reproduction number. We find that vaccination or depopulation can have a greater than linear effect on anticipated infections. For example, assuming a reproduction number of 3.0 for density-dependent COVID-19 transmission, we find that reducing the size of the susceptible population by 20% reduced overall disease burden by 47%. We highlight the California state prison system as an example for how these findings provide a quantitative framework for implementing infection control in congregate settings. Additional applications of our modeling framework include optimizing the distribution of residents into independent residential units, and comparison of preemptive versus reactive vaccination strategies. +
++To control future epidemics, discovery platforms are urgently needed, for the rapid development of diagnostic assays. Molecular diagnostic tests for COVID-19 emerged shortly after the isolation of SARS-CoV-2, however, serological tests based on antiviral antibody detection, revealing previous exposure to the virus, required longer developmental phases, due to the need for correctly folded and glycosylated antigens. The delay between the identification of a new virus and the development of reliable serodiagnostic tools limits our readiness for the control of a future epidemic. In this context, we propose the protozoan Leishmania tarentolae as an easy-to-handle micro-factory for the rapid production of viral antigens, to be used at the forefront of emerging epidemics. As a study model, we engineered L. tarentolae to express the SARS-CoV-2 Receptor Binding Domain (RBD) and report the ability of the purified RBD antigen to detect SARS-CoV-2 infection, with a sensitivity and reproducibility comparable to that of a reference antigen produced in human cells. This is the first application of an antigen produced in L. tarentolae for the serodiagnosis of a Coronaviridae infection. Based on our results, we propose L. tarentolae as an effective system for viral antigen production, even in countries that lack high-tech cell factories. +
++Abstract Introduction COVID-19 large scale immunization in the US has been associated with infrequent breakthrough positive molecular testing. Whether a positive test is associated with a high viral RNA load, specific viral variant, recovery of infectious virus, or symptomatic infection is largely not known. Methods In this study, we identified 133 SARS-CoV-2 positive patients who had received two doses of either Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) vaccines, the 2nd of which was received between January and April of 2021. The positive samples were collected between January and May of 2021 with a time that extended from 2 to 100 days after the second dose. Samples were sequenced to characterize the whole genome and Spike protein changes and cycle thresholds that reflect viral loads were determined using a single molecular assay. Local SARS-CoV-2 IgG antibodies were examined using ELISA and specimens were grown on cell culture to assess the recovery of infectious virus as compared to a control unvaccinated cohort from a matched time frame. Results Of 133 specimens, 24 failed sequencing and yielded a negative or very low viral load on the repeat PCR. Of 109 specimens that were used for further genome analysis, 68 (62.4%) were from symptomatic infections, 11 (10.1%) were admitted for COVID-19, and 2 (1.8%) required ICU admission with no associated mortality. The predominant virus variant was the alpha (B.1.1.7), however a significant association between lineage B.1.526 and amino acid change S: E484K with positives after vaccination was noted when genomes were compared to a large control cohort from a matched time frame. A significant reduction of the recovery of infectious virus on cell culture as well as delayed time to the first appearance of cytopathic effect was accompanied by an increase in local IgG levels in respiratory samples of vaccinated individuals but upper respiratory tract IgG levels were not different between symptomatic or asymptomatic infections. Conclusions Vaccination reduces the recovery of infectious virus in breakthrough infections accompanied by an increase in upper respiratory tract local immune responses. +
++Abstract Importance: Maintenance hemodialysis (MHD) patients have a high mortality risk after COVID-19 and an altered humoral response to vaccines, but vaccine clinical efficacy remains unknown in this population. Objective: To estimate the association between vaccination and COVID-19 hospitalization rate in MHD patients Design: Using Bayesian multivariable spatiotemporal models, we estimated the expected number of SARS-CoV-2 severe infections (infections with hospital admission) in MHD patients from simultaneous cases in the general population. Setting: French population-based retrospective analysis in MHD and non-dialysis patients. Participants: Models were fitted from 3620 hospitalizations of MHD patients and 457,160 hospitalizations in the general population. Exposure: Severe SARS-CoV-2 infections in the general population and vaccine exposure. Main Outcome and Measure: Weekly incidence of severe infections in MHD patients. Results: During the first epidemic wave, incidence of severe infections in MHD patients was approximately proportional to incidence in the general population. However, our model overestimated incidence during the second wave, suggesting an effect of prevention measures during the 2nd wave. A second model (based on data up to the end of the 2nd wave) estimated that the risk in MHD patients decreased between waves 1 and 2, with incidence rate ratio (IRR) = 0.70 (95% CI: 0.64, 0.76). Moreover, while this model correctly estimated the reported MHD cases up to the end of the 2nd wave, predictions overestimated the expected number of cases from the beginning of the vaccination campaign. Using vaccination coverages as additional predictors permitted to correctly fit the weekly reported number of cases, with IRR in MHD patients of 0.41 (95% CI: 0.28, 0.58) for vaccine exposure in MHD patients and 0.50 (95% CI: 0.40, 0.61) per 10% increase in vaccination coverage in the same-age general population. Conclusions and Relevance: Our findings suggest that both individual and herd immunity due to vaccination may yield a protective effect against severe forms of COVID-19 in MHD patients. +
++Simultaneously tracking the global COVID-19 impact across multiple populations is challenging due to regional variation in resources and reporting. Leveraging self-reported survey outcomes via an existing international social media network has the potential to provide reliable and standardized data streams to support monitoring and decision-making world-wide, in real time, and with limited local resources. The University of Maryland Global COVID Trends and Impact Survey (UMD-CTIS), in partnership with Facebook, invites daily cross-sectional samples from the social media platform9s active users to participate in the survey since launch April 23, 2020. COVID-19 indicators through December 20, 2020, from N=31,142,582 responses representing N=114 countries, weighted for nonresponse and adjusted to basic demographics, were benchmarked with government data. COVID-19-related signals showed similar concordance with reported benchmark case and test positivity. Bonferroni significance and minimal Spearman correlation strength thresholds were met in the majority. Light Gradient Boost machine learning trained on national and pooled global data verified known symptom indicators, and predicted COVID-19 trends similar to other signals. Risk mitigation behavior trends are correlated with, but sometimes lag, risk perception trends. In regions with strained health infrastructure, but active social media users, we show it is possible to define suitable COVID-19 impact trajectories. This syndromic surveillance public health tool is the largest global health survey to date, and, with brief participant engagement, can provide meaningful, timely insights into the COVID-19 pandemic and response in regions under-represented in epidemiological analyses. +
++Anticipating the medium- and long-term trajectory of pathogen emergence has acquired new urgency given the ongoing COVID-19 pandemic. For many human pathogens the burden of disease depends on age and prior exposure. Understanding the intersection between human population demography and transmission dynamics is therefore critical. Here, we develop a realistic age-structured (RAS) mathematical model that integrates demography, social mixing and immunity to establish the suite of possible scenarios of future age-incidence and burden of mortality. With respect to COVID-19, we identify a plausible transition in the age-structure of risks once the disease reaches seasonal endemism, whether assuming long-lasting or brief protective immunity, and across a range of assumptions of relative severity of primary versus subsequent reinfections. We train the model using diverse real-world demographies and age-structured social mixing patterns to bound expectations for changing age-incidence and disease burden. The mathematical framework is flexible and can help tailoring mitigation strategies countries worldwide with varying demographies and social mixing patterns. +
++Purpose: The present study aimed to compare and analyze the sex-specific epidemiological, clinical characteristics, comorbidities, and other information of confirmed COVID-19 patients from the southeast region in Bangladesh for the first time. Methods: 385 lab-confirmed cases were studied out of a total of 2471 tested samples between June 5 and September 10, 2020. RT-PCR was used for COVID-19 identification and SPSS (version 25) for statistical data analysis. Results: We found that male patients were roughly affected compared to females patients (male 74.30% vs. female 25.7%) with an average age of 34.86 +/- 15.442 years, and B (+ve) blood group has been identified as a high-risk factor for COVID-19 infection. Workplace, local market, and bank were signified as sex-specific risk zone (p < 0.001). Pre-existing medical conditions such as diabetes, hypertension, cardiovascular and respiratory diseases were identified among the patients. Less than half of the confirmed COVID-19 cases in the southeast region were asymptomatic (37.73%) and more prevalent among females than males (male vs. female: 36.84% vs. 40.51%, p = 0.001). Conclusions: The findings may help health authorities and the government to take necessary steps for identification and isolation, treatment, prevention, and control of this global pandemic. Keywords: COVID-19, Coronavirus disease, Epidemiological, Clinical features, Asymptomatic, Comorbidities +
+Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients - Condition: Covid19
Interventions: Drug: NTR-441; Drug: Placebo
Sponsor: Neutrolis
Recruiting
COVID-19 Vaccinations With a Sweepstakes - Condition: Covid19
Intervention: Behavioral: Philly Vax Sweepstakes
Sponsors: University of Pennsylvania; Philadelphia Department of Public Health
Active, not recruiting
Covid-19 Virtual Recovery Study - Condition: Covid19
Interventions: Behavioral: Strength RMT; Behavioral: Strength RMT and nasal breathing; Behavioral: Endurance RMT; Behavioral: Endurance RMT and nasal breathing; Behavioral: Low dose RMT
Sponsor: Mayo Clinic
Not yet recruiting
A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adolescents - Condition: Covid19 Vaccine
Interventions: Biological: MVC-COV1901(S protein with adjuvant); Biological: MVC-COV1901(Saline)
Sponsor: Medigen Vaccine Biologics Corp.
Not yet recruiting
Study on Sequential Immunization of Inactivated COVID-19 Vaccine and Recombinant COVID-19 Vaccine (Ad5 Vector) - Condition: COVID-19
Interventions: Biological: Recombinant SARS-CoV-2 Ad5 vectored vaccine; Biological: Inactive SARS-CoV-2 vaccine (Vero cell)
Sponsors: Jiangsu Province Centers for Disease Control and Prevention; CanSino Biologics Inc.
Not yet recruiting
Efficacy of Amantadine Treatment in COVID-19 Patients - Condition: Patients With Moderate or Severe COVID-19
Intervention: Drug: Amantadine
Sponsors: Noblewell; Medical Research Agency (ABM); Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
Recruiting
Covid-19 Patients Management During Home Isolation - Condition: Covid19
Interventions: Procedure: Oxygen therapy and physical therapy; Device: Oxygen therapy
Sponsor: Cairo University
Recruiting
SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Testing Among Utah Community Health Centers - Condition: Covid19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Association for Utah Community Health; Utah Department of Health; National Institutes of Health (NIH)
Recruiting
SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Vaccination Rates Among Utah Community Health Centers - Condition: Covid19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Association for Utah Community Health; Utah Department of Health; National Institutes of Health (NIH)
Recruiting
A Different Use of The Aerosol Box in COVID-19 Patients; Internal Jugular Vein Cannulation - Condition: COVID-19 Pneumonia
Intervention: Procedure: Internal jugular vein cannulation
Sponsor: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
Completed
Chinese Herbal Formula for COVID-19 - Condition: Covid19
Interventions: Drug: mQFPD; Drug: organic brown rice
Sponsor: University of California, San Diego
Not yet recruiting
Remdesivir- Ivermectin Combination Therapy in Severe Covid-19 - Condition: Covid19
Intervention: Drug: Ivermectin
Sponsor: Assiut University
Not yet recruiting
Short Term, High Dose Vitamin D Supplementation in Moderate to Severe COVID-19 Disease - Condition: Covid19
Intervention: Drug: cholecalciferol 6 lakh IU
Sponsor: Postgraduate Institute of Medical Education and Research
Not yet recruiting
Immunogenicity and Safety of an Inactivated COVID-19 Vaccine - Condition: COVID-19
Interventions: Biological: Inactivated COVID-19 Vaccine; Biological: 23-valent pneumococcal polysaccharide vaccine; Biological: Inactivated Hepatitis A Vaccine
Sponsor: Sinovac Research and Development Co., Ltd.
Not yet recruiting
The Role of Chlorhexidine in Minimizing the Viral Load Among COVID-19 Patients - Condition: COVID-19
Intervention: Drug: Chlorhexidine digluconate, povidone iodine
Sponsor: King Abdulaziz University
Not yet recruiting
A bivalent protein targeting glycans and HR1 domain in spike protein potently inhibited infection of SARS-CoV-2 and other human coronaviruses - CONCLUSIONS: Since GL25E showed highly potent and broad-spectrum inhibitory activity against infection of SARS-CoV-2 and its mutants, as well as other HCoVs, it is a promising candidate for further development as a broad-spectrum anti-HCoV therapeutic and prophylactic to treat and prevent COVID-19 and other emerging HCoV diseases.
Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization - The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India^(1-5). It has since then become dominant in some indian regions and UK and further spread to many countries⁶. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), harbouring diverse Spike mutations in the N-terminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2, also termed variant Delta, is believed to spread faster than other…
Multifunctional inhibitors of SARS-CoV-2 by MM/PBSA, essential dynamics, and molecular dynamic investigations - The ongoing COVID-19 pandemic demands a novel approach to combat and identify potential therapeutic targets. The SARS-CoV-2 infection causes a hyperimmune response followed by a spectrum of diseases. Limonoids are a class of triterpenoids known to prevent the release of IL-6, IL-15, IL-1α, IL-1β via TNF and are also known to modulate PI3K/Akt/GSK-3β, JNK1/2, MAPKp38, ERK1/2, and PI3K/Akt/mTOR signaling pathways and could help to avoid viral infection, persistence, and pathogenesis. The present…
AIEgen-loaded nanofibrous membrane as photodynamic/photothermal antimicrobial surface for sunlight-triggered bioprotection - The outbreak of infectious diseases such as COVID-19 causes an urgent need for abundant personal protective equipment (PPE) which leads to a huge shortage of raw materials. Additionally, the inappropriate disposal and sterilization of PPE may result in a high risk of cross-contamination. Therefore, the exploration of antimicrobial materials possessing both microbe interception and self-decontamination effects to develop reusable and easy-to-sterilize PPE is of great importance. Herein, an…
PROTECTIVE ROLE OF CORTISTATIN IN PULMONARY INFLAMMATION AND FIBROSIS - CONCLUSION AND IMPLICATIONS: We identify to cortistatin as an endogenous break of pulmonary inflammation and fibrosis. Deficiency in cortistatin could be a marker of poor-prognosis in inflammatory/fibrotic pulmonary disorders. Cortistatin-based therapies emerge as attractive candidates to treat severe ALI/ARDS, including SARS-Cov-2-associated ARDS.
Luteolin: a blocker of SARS-CoV-2 cell entry based on relaxed complex scheme, molecular dynamics simulation, and metadynamics - Natural products have served human life as medications for centuries. During the outbreak of COVID-19, a number of naturally derived compounds and extracts have been tested or used as potential remedies against COVID-19. Tetradenia riparia extract is one of the plant extracts that have been deployed and claimed to manage and control COVID-19 by some communities in Tanzania and other African countries. The active compounds isolated from T. riparia are known to possess various biological…
Efficacy of tocilizumab in COVID-19: A review of the current evidence - As cases of coronavirus 2019 (COVID-19) keep rising, reported deaths are increasing. Public health measures have been implemented with mixed efficacy. As vaccines are becoming more widely available and accessible globally, treating critically ill COVID-19 patients remains an issue with only dexamethasone found to be therapeutically effective to date. However, trials studying the efficacy of IL-6 inhibitors, namely tocilizumab have been underway with promising results. This paper is a narrative…
Therapeutic potential of phytoconstituents of edible fruits in combating emerging viral infections - Plant-derived bioactive molecules display potential antiviral activity against various viral targets including mode of viral entry and its replication in host cells. Considering the challenges and search for antiviral agents, this review provides substantiated data on chemical constituents of edible fruits with promising antiviral activity. The bioactive constituents like naringenin, mangiferin, α-mangostin, geraniin, punicalagin, and lectins of edible fruits exhibit antiviral effect by…
Inhibition of the 3CL Protease and SARS-CoV-2 Replication by Dalcetrapib - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 3CL protease is a promising target for inhibition of viral replication by interaction with a cysteine residue (Cys145) at its catalytic site. Dalcetrapib exerts its lipid-modulating effect by binding covalently to cysteine 13 of a cholesteryl ester transfer protein. Because 12 free cysteine residues are present in the 3CL protease, we investigated the potential of dalcetrapib to inhibit 3CL protease activity and SARS-CoV-2…
Heparan Sulfate Proteoglycans as Attachment Factor for SARS-CoV-2 - Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing an unprecedented global pandemic demanding the urgent development of therapeutic strategies. Microarray binding experiments, using an extensive heparan sulfate (HS) oligosaccharide library, showed that the receptor binding domain (RBD) of the spike of SARS-CoV-2 can bind HS in a length- and sequence-dependent manner. A hexasaccharide composed of IdoA2S-GlcNS6S repeating units was identified as the minimal binding…
Ramping Up Antimicrobial Peptides Against Severe Acute Respiratory Syndrome Coronavirus-2 - Human-derived antimicrobial peptides (AMPs), such as defensins and cathelicidin LL-37, are members of the innate immune system and play a crucial role in early pulmonary defense against viruses. These AMPs achieve viral inhibition through a variety of mechanisms including, but not limited to, direct binding to virions, binding to and modulating host cell-surface receptors, blocking viral replication, and aggregation of viral particles and indirectly by functioning as chemokines to enhance or…
Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay - The COVID-19 pandemic caused by SARS-CoV-2 is an unprecedentedly significant health threat, prompting the need for rapidly developing antiviral drugs for the treatment. Drug repurposing is currently one of the most tangible options for rapidly developing drugs for emerging and reemerging viruses. In general, drug repurposing starts with virtual screening of approved drugs employing various computational methods. However, the actual hit rate of virtual screening is very low, and most of the…
Antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia - Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of COVID-19 adenoviral vector vaccines^(1-3). VITT resembles heparin-induced thrombocytopenia (HIT) as it is associated with platelet-activating antibodies against platelet factor 4 (PF4)⁴; however, patients with VITT develop thrombocytopenia and thrombosis without heparin exposure. The objective of this study was to determine the binding site on PF4 of antibodies from patients with VITT. Using alanine scanning…
SARS-CoV-2 Nsp3 unique domain SUD interacts with guanine quadruplexes and G4-ligands inhibit this interaction - The multidomain non-structural protein 3 (Nsp3) is the largest protein encoded by coronavirus (CoV) genomes and several regions of this protein are essential for viral replication. Of note, SARS-CoV Nsp3 contains a SARS-Unique Domain (SUD), which can bind Guanine-rich non-canonical nucleic acid structures called G-quadruplexes (G4) and is essential for SARS-CoV replication. We show herein that the SARS-CoV-2 Nsp3 protein also contains a SUD domain that interacts with G4s. Indeed, interactions…
Inhibitory activities of bipyrazoles: a patent review - INTRODUCTION: Bipyrazole is constituted from two pyrazole units either in their fully aromatic or partially hydrogenated forms. Pyrazoles are widely available in pharmaceutical and agrochemical products. Some pyrazoles are essential parts of commercial drugs in the market. This inspired us to collect the pharmacological activities of bipyrazoles that have potential therapeutic behaviours in several biological aspects but none of them were included in commercial drugs.
Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link
SARS-CoV-2 anti-viral therapeutic - - link
A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link
新型冠状病毒B.1.351南非突变株RBD的基因及其应用 - 本发明属于生物技术领域,具体涉及新型冠状病毒B.1.351南非突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.351南非突变株RBD的基因,其核苷酸序列如SEQIDNO.1或SEQIDNO.6所示。本发明通过优化野生型新型冠状病毒南非B.1.351南非突变株RBD的基因序列,并结合筛选确定了相对最佳序列,优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.351南非突变株RBD序列表达效率大幅提高,从而,本发明的新型冠状病毒B.1.351南非突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link
检测新型冠状病毒中和抗体的试剂盒及其应用 - 本发明涉及生物技术领域,具体而言,提供了一种检测新型冠状病毒中和抗体的试剂盒及其应用。本发明提供的检测新型冠状病毒中和抗体试剂盒,具体包括(a)或(b)两种方案:(a)示踪物标记的RBD三聚体抗原,包被在固体支持物上的ACE2,以及,含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液;(b)示踪物标记的ACE2,包被在固体支持物上的RBD三聚体抗原,以及,含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液;其中,RBD三聚体抗原利用二硫键将刺突蛋白的RBD与S2亚基完全交联得到。十二烷基二甲基甜菜碱会显著提高RBD三聚体抗原与新冠中和性抗体结合速度,提升阳性样本平均发光强度,缩短检测时间。 - link
一种检测SARS-CoV-2的引物组合物及其应用 - 本发明涉及一种检测SARS‑CoV‑2的引物组合物及其应用。所述引物组合物包括SEQ ID NO:1~SEQ ID NO:12所示的核酸序列。本发明利用所述引物组合物进行逆转录巢式PCR,并结合Sanger测序,能够快速、准确地获取SARS‑CoV‑2基因信息,从而能够实现快速检测SARS‑CoV‑2以及判断SARS‑CoV‑2突变株,且具备良好的准确性、灵敏度、特异性以及重复性。 - link
一种新冠病毒肺炎重症化预测系统及方法 - 本发明涉及疾病预测技术领域,公开了一种新冠病毒肺炎重症化预测系统及方法,包括以下步骤:步骤一,采集患者血常规信息和用户信息;步骤二,将患者血常规信息按照用户信息进行等级分类;步骤三,将已经等级分类的患者血常规信息与对应等级的标准信息进行比较;步骤四,当患者血常规信息在标准信息范围内则判定患者为轻症患者,当患者血常规信息在标准信息范围外则判定患者为重症患者。本发明能够准确快速地区分轻症和重症。 - link
MEDIDOR DE SATURACION - - link
폐마스크 밀봉 회수기 - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - link
백신 냉각 및 해동 기능을 갖는 백신 보관장치 - 본 발명은 백신 냉각 및 해동 기능을 갖는 백신 보관장치에 관한 것으로, 상, 하부하우징의 제1상, 하부누출방지공간에 냉각물질이 충입된 냉각파이프를 설치하되, 제2상, 하부누출방지공간에 가열물질이 충입된 가열파이프를 설치하여, 구획판부에 의해 구획된 백신냉각공간 및 백신해동공간 각각을 냉각 및 가열하고, 보조도어를 통해 백신냉각공간 내에 수용된 백신을 구획판부의 백신출구도어를 통해 백신해동공간으로 이동시켜, 백신해동공간 내에서 백신을 해동함으로써, 즉시 사용이 가능한 백신을 인출도어를 통해 인출할 수 있다. 본 발명에 따르면, 냉각파이프에 저장된 냉매에 의해 백신냉각공간 내의 온도가 극저온 상태로 변화되고, 극저온 상태를 유지하는 백신냉각공간 내에 백신을 저장하여, 안전하게 보관 할 수 있으며, 백신냉각공간 내의 백신을 백신해동공간 내로 이동시켜, 백신해동공간 내에서 백신을 해동할 수 있고, 이 해동된 백신을 인출도어를 통해 인출한 후 즉시 사용할 수 있어 백신을 해동하는 시간이 단축되며, 보조도어를 통해 백신냉각공간 내의 백신을 백신해동공간으로 이동시켜, 백신이 외기에 노출될 우려가 없으며, 백신냉각공간 내의 백신을 백신해동공간으로 이동시키거나 또는 인출도어를 통해 백신 인출시 정렬장치가 백신을 보조도어 및 인출도어 직하방에 자동 위치시킨다. - link
Why Did the Police Shoot Matthew Zadok Williams? - Outside Atlanta, a mother and five sisters look for answers. - link
What’s Next for the Campaign to Break Up Big Tech? - A judge recently dismissed two antitrust cases against Facebook. But what appeared to be a setback for the effort may actually provide a road map for how it can succeed. - link
What We Need to Learn from the Tragedy in Surfside - It is possible that South Florida, where climate change is a particularly acute problem, is nearing a point at which even the best-constructed buildings are under threat. - link
Eric Adams’s Victory and the Uncertainty of the Biden-Era Democratic Party - Adams won New York City’s mayoral primary by appealing to centrist, working-class voters. But his political vision remains undefined. - link
This July 4th, Can We De-Adapt from the Pandemic and Trump at the Same Time? - Although 2021 is only half over, it has brought about two major restart moments—one in politics and the other in public health. - link
+The brand-new Beyond Chicken tenders taste almost identical to the real thing. +
++If you’ve ever had a Beyond Burger or Impossible Burger, you know that plant-based food companies have figured out how to make fake beef that tastes pretty beefy. Their success is reflected in the fact that many foodies now consider their products not only tolerable but trendy. +
++Yet when it comes to chicken, plant-based meat companies have really struggled to make a convincing substitute. That’s largely because replicating the structure of chicken muscle — which has a fibrous quality, with strands that pull apart — is much harder than creating a ground meat lookalike. Beyond Meat has tried to mimic chicken in the past, releasing chicken strips back in 2012. But reviews were mixed, and the company pulled the product a few years later. +
++Now, Beyond Meat is ready to try again with a new product: Beyond Chicken tenders. Hundreds of restaurants across the US — mostly small regional chains — launched the product on their menus starting July 8 (you can go to this locator to see if it’s available near you). And this time, the company may have finally cracked the code. +
++Their team of 200 scientists examined different plant candidates — soy beans, peas, mung beans, fava beans, and so on — to figure out which would be the best plant to supply the protein in their tenders. They found that when they isolated protein from fava beans, they could use heating, cooling, and pressure to reshape it into a structure that mimics chicken muscle. +
++Fava beans were also able to mimic the taste and even smell of chicken. In the lab, the scientists used an “e-nose” — an electronic nose that sniffs out the aroma molecules that come out of real chicken and then sniffs out the aroma molecules that come from various plants, to find the right match. +
++The result: new faux-chicken tenders that are nearly indistinguishable from the real thing. +
++The breaded tenders work well on their own or as part of a sandwich or wrap, which is how some restaurants are serving them. (You won’t be able to find the tenders in grocery stores yet, but Beyond says it’ll soon expand into hotels, college campuses, and stadiums.) +
++And the taste is only one of the benefits. There are health benefits to be reaped, too: Beyond Chicken tenders have 40 percent less saturated fat than a typical restaurant tender, they have no cholesterol, and they’re made with no antibiotics. (Though, like regular chicken tenders, Beyond’s are high in sodium.) +
++Plus, when you opt for chickenless chicken, you know that you’re reducing the demand for chickens raised in horrible conditions on factory farms. Those giant, industrialized farms also damage the environment and ratchet up the risk of emerging pandemics and antibiotic resistance — so you can feel good knowing you’re not supporting that system. +
++“We call it hedonistic altruism,” Ethan Brown, the founder and CEO of Beyond Meat, told me. “If we can provide a delicious sensory experience for the consumer and they can also feel really great about what they’re doing for the Earth — it’s a win.” +
+ ++Although the tenders are mainly made from fava beans, I honestly wouldn’t have suspected that they come from a plant if I hadn’t known that before I took a bite. They tasted almost identical to real chicken, and the breading on them made them look convincingly chickenesque. +
++When I stripped off the breading to see what was under the hood, I found that the texture inside didn’t 100 percent match chicken (it was a bit denser), though I’d say it was 90 percent of the way there. It replicated the texture of traditional chicken nuggets a bit better than the top competitors in the freezer aisle, like Gardein’s vegan tenders. +
++I actually tried pulling the Beyond Chicken tender apart, and it did have a bit of fibrousness reminiscent of the strands in chicken muscle. Again, not 100 percent true to life, but I only noticed the difference because I was surgically dissecting my lunch. Normally, diners don’t do that — so, I thought, who even cares about these tiny differences? +
++I found myself questioning the whole premise that a faux-chicken product needs to be exactly like chicken. If I have something that’s 90 percent similar to this thing I like to eat, and it’s much better for animals and the environment and human health, why wouldn’t I go for that? Why should I be so fanatically fixated on its metaphysical chickenness? I just care that it tastes good. +
++But I know that some people do care about eating something that tastes exactly like chicken, so I took Beyond Chicken tenders to the toughest food critic I know: my 87-year-old grandmother. She’s been cooking incredible chicken dishes for decades, and I wanted to see if she’d sniff out the difference if I didn’t tell her that what she was being served was not real chicken. So I simply told her I’d brought us a treat to share. After taking a few bites, she said it tasted “very good.” +
++Then I revealed to her that this was not real chicken; it was made from plants. +
++She stared at me for a second. Then she said, “I don’t mind, as long as it tastes like chicken. And it does! It’s a bit heavier, but if you hadn’t said anything, I wouldn’t have noticed.” +
+ ++So far, Beyond Chicken tenders are only available in about 400 restaurant locations. But if more restaurants add the tenders to their menus — and if KFC, after evaluating its 2020 Beyond Fried Chicken trial run, moves forward with a national rollout — it could help us step away from our deeply problematic current system of raising real chickens. +
++About 99 percent of all chickens we eat come from factory farms. These aren’t the idyllic, pastoral farms we’re taught to picture as children, with birds free to wander around in the greenery. Instead, chickens are raised in gigantic, noisy, overcrowded warehouses filled with ammonia fumes. Due to genetic selection for larger size, they grow so fast that their legs can’t support their weight. After six weeks of misery, they’re killed. +
++And as my colleague Kelsey Piper has explained, each year the average American eats about 23 chickens, compared to just over one-tenth of one cow. That’s because chickens are much smaller, producing only a few pounds of meat. Chicken has also become extremely popular; Americans eat twice as much of it now as they did in the 1970s. +
++All this bothers Brown, the Beyond Meat CEO, a lot. +
++“Animal welfare is a really important consideration,” he said. “In terms of just the number of sentient beings — the sheer number of captive beings — chickens are up there. It’s a different thing than beef, for sure.” +
++But plant-based companies are not yet able to mimic chicken in all its forms. Making a breaded tender is one thing — the breading can act as camouflage. Creating a convincing chicken breast is a whole other dream, and Brown suggested we shouldn’t expect it to come true anytime soon. +
++“We have some projects that we consider a holy grail, and chicken breast is one of those. It’s very distinct-looking,” he said. “That’s going to take time.” +
++Meanwhile, the chicken tenders are a good start. +
++The coming battle to expand Supplemental Security Income, explained. +
++In a couple of weeks, the US will start sending monthly checks to the vast majority of American parents. Most other rich countries have policies similar to this (known as a child allowance). If these expanded child tax credit (CTC) checks get to everyone who’s eligible, they could slash child poverty in America by about 40 percent. +
++But it could also be only the first of several improvements to America’s social-safety net. An array of powerful Democrats in Congress, as well as advocates for the elderly and people with disabilities (like AARP), have been championing another major change as part of this fall’s legislative push: boosting Supplemental Security Income (SSI) benefits. +
++SSI is not one of the better-known safety net programs in the US. It was passed into law in 1972 after Richard Nixon tried and failed to get Congress to adopt his “guaranteed annual income” plan, essentially a kind of unconditional basic income that would have given the poorest households in America a guaranteed cash benefit. +
++That plan ran into conservative opposition, but its opponents acceded to two more modest proposals. +
++One was the Earned Income Tax Credit (EITC), which gives working adults (especially those with children) a bigger tax break — and potentially a bigger refund — tied to how much they’ve worked. +
++The other was SSI, meant to help those the EITC didn’t capture: disabled, blind (a different category than “disabled” for legal purposes), and elder Americans living in poverty. +
++Many people in those categories qualify for Social Security payments because they’ve paid into the OASDI (Old-Age, Survivors, and Disability Insurance) program throughout their working lives via payroll tax. +
++But many other people — those under 18, or adults who are never able to work — don’t qualify for Social Security. Even many who do qualify for Social Security still earn a low-enough income to receive additional payments from SSI: About one-third of the 7.8 million SSI recipients are also on Social Security. +
++The point of SSI, in theory, is to make sure that no American who is permanently and totally disabled, blind, or over the age of 65 lives in poverty. +
++In practice, though, the program helps a lot but has yet to meet that goal. +
++In 2021, the maximum SSI benefit for an individual is $9,530.12 per year. The poverty line for a single person is $12,880 — meaning that SSI, at most, brings recipients up to less than three-quarters of the poverty line. +
++It gets worse, though. Let’s say you’re an SSI recipient married to another recipient, which makes you an “eligible couple.” You could both be retirees in your 70s, or disabled/blind people earlier in life. +
++You don’t get to add your benefit amounts together. Instead, you have to share a maximum benefit of $14,293.61, only 50 percent more than the individual benefit. The effect is a really dramatic marriage penalty: Two SSI recipients receive a large income boost if they get divorced, but those who marry take a big cut in benefits. +
++In late May 2020, Joe Biden announced his campaign’s disability policy platform, which included major expansions of SSI benefits. The plan set the maximum benefit at 100 percent of the poverty line, a 35 percent increase in benefits over the status quo. The proposal would also eliminate both the marriage penalty — letting couples keep their full benefits — and the complex “in-kind assistance” provisions that result in reduced SSI checks for some people who, say, live for free in a family member’s home. +
++There’s more. SSI is currently limited to people with assets of less than $2,000, or $3,000 for couples. That means many seniors who have even a small amount of retirement savings, as well as disabled people with nest eggs, aren’t eligible. +
++Biden would more than double the asset limit for individuals and nearly triple it for couples. I’d personally prefer getting rid of the asset test altogether, as it can encourage people to spend every bit of savings they have to qualify for the benefit; that said, raising it is an improvement. +
++Biden has recently faced a strong push from his allies in Congress to include these changes in the huge $6 trillion spending package Democrats plan to pass later this summer or in the fall. +
++Rep. Jamaal Bowman, a freshman congressman from New York, and Ohio Sen. Sherrod Brown are leading the charge, with figures including Senate Budget Committee Chair Bernie Sanders and Finance Committee Chair Ron Wyden on board. +
++The group in April sent a letter to Biden, signed by a total of 18 senators and 33 members of the House, urging him to make expanded SSI a priority. +
++Major parts of the Democratic coalition, like the AFL-CIO union federation, the Consortium for Citizens with Disabilities, and the AARP, are on board. The changes have overwhelming public support — as have other recent programs designed to simply give people money, like the stimulus checks and the previously mentioned CTC checks. +
++And like the CTC checks, these changes could have a major impact on poverty in America. The Urban Institute estimates that the combination of SSI changes and other Social Security reforms Biden has proposed would lift 1.4 million elderly or disabled people out of poverty in 2021. While increasing SSI alone would do less, it would still be a significant step forward for the people impacted. +
++And if SSI improvements happen alongside the child checks, they’d cement Biden’s first term as a period that saw some of the biggest changes to the American social-safety net in decades. +
+The scene sets the table for Florence Pugh to play a bigger role in the Marvel Cinematic Universe. +
++Spoiler alert: This story includes details about the plot and post-credits scene of Black Widow. +
++Can a movie that’s set years before Avengers: Endgame really push the Marvel Cinematic Universe forward? No, but Black Widow’s post-credits scene surely tries. +
++The long-awaited film centered on the Avengers’ Natasha Romanoff — Marvel’s longest-tenured female superhero — is finally in theaters. I liked a lot of things about it, but even if the pandemic hadn’t delayed the film’s release by more than a year, its story would still feel long overdue. +
++Black Widow is a prequel whose chronology in the MCU falls years before Endgame, where the character ultimately dies a dramatic (and controversial) death. Unlike a lot of Marvel’s other solo Avengers films, it doesn’t really advance her individual story forward; instead, it fills in the gaps of a life we’ve previously heard about but rarely seen in the MCU. +
++Still, in the grand tradition of nearly every other Marvel movie to date, Black Widow has a post-credits scene. The studio has long used end-credits scenes to tease future movies and future MCU storylines. Despite Black Widow’s status as a somewhat static “backstory” chapter, its credits scene manages to hint at a possible future storyline and the emergence of a villain we’re just getting to know. It also further cements and strengthens the links between Marvel’s movies and TV series within the MCU. Rather than focusing on Natasha, however, it pivots a bit to tease how Florence Pugh — who plays fellow assassin Yelena — may carry on the title of Black Widow in the MCU’s future. +
++Black Widow’s credits scene opens with Yelena driving down a dirt road with an adorable dog. She finally reaches her destination, which is revealed to be Nat’s gravesite. The headstone is adorned with flowers, indicating Nat’s sacrifice and tenure as an Avenger didn’t go unnoticed. +
++The scene places us in the present day, sometime after Nat’s death in Endgame. That means the last time we saw Yelena in the MCU chronology was right after Civil War and years before Thanos’s invasion in Infinity War, when Yelena and Nat parted ways and Yelena set out to save the many women who’d been brainwashed into becoming Black Widows just like them. +
++Yelena is visiting Natasha’s grave to pay respect to someone who had become a sister to her. Suddenly, she is joined by the Contessa Valentina Allegra de Fontaine (Julia Louis-Dreyfus), who asks Yelena if she wants to avenge Nat’s death. Yelena says yes. Valentina shows Yelena a photo of a man whom she says is responsible for Nat dying. The camera, accompanied by a suspenseful music drop, reveals that the pictured individual is Clint Barton, a.k.a. Hawkeye (Jeremy Renner). That’s when the scene abruptly ends. +
++Technically speaking, Valentina isn’t completely wrong when she tells Yelena that Clint is responsible for Nat’s death. In Endgame, Clint and Natasha were tasked with retrieving the Soul Stone to complete the Infinity Gauntlet and reverse Thanos’s snap. The tricky part is that to obtain the Soul Stone, you need to sacrifice a soul. +
++Both Clint and Nat fought to be the one who sacrificed themselves, but it was Nat — declaring that she should be the one to die, in large part because Clint had a family to look after — who ultimately exchanged her life for the Soul Stone. So, sure, in a very loose interpretation, Clint and his family are the reason Nat is dead. If he didn’t have a family, and if Nat had not been close with them, she might not have been so compelled to throw herself off a cliff and save the world. +
++But from what we know about Valentina in Marvel’s comic books, she’s a nefarious player and mastermind. Also, in her recent appearance on Marvel’s Disney+ TV series The Falcon and The Winter Soldier — which marked her official on-screen introduction to the MCU — she seemed to be planting seeds of doubt and subterfuge in her recruitment of Captain America II, John Walker. +
++Thus, with Valentina not giving Yelena the full story in Black Widow’s credits scene, it appears she is setting up a clash between Yelena and Clint. +
++The inevitable face-off between Yelena and Clint probably won’t happen in one of Marvel’s upcoming movies; the next few titles on the studio’s schedule are The Eternals, Shang Chi, Thor: Love and Thunder, and Doctor Strange and the Multiverse of Madness, none of which will prominently feature Clint or Yelena. Enter Hawkeye, the forthcoming TV series on Disney+ that doesn’t yet have a specific release date but is expected to premiere later in 2021. +
++Few details are known about Hawkeye, except that Renner will reprise his role as the title character and Hailee Steinfeld will play Kate Bishop, a young markswoman who takes on the title of Hawkeye in Marvel’s comic books. +
++Should Yelena show up on Hawkeye and butt heads with Clint and Kate, there may eventually be a time when she learns the full extent of Clint and Nat’s deep friendship. If Yelena comes to realize that Nat loved Clint and his family so much, and that she wanted to do anything she could to help her team, she’d have the complete story rather than the half-truth Valentina told her. +
++Such a reveal would be an opportunity to set up Yelena as part of whatever the next version of the Avengers looks like — and open the door to her (and Pugh’s) future in the MCU. +
++There’s also a potential parallel between the Nat/Yelena and Clint/Kate duos, in that it seems as though Marvel intends to pass on the titles of Black Widow and Hawkeye to new people. In Black Widow, Nat and Yelena acknowledge they are sisters, even if they’re not related by blood. Clint and Kate have sort of an older-brother-younger-sister dynamic in the comic books, and it’s likely the same dynamic will carry over to Hawkeye. There will be a lot of nifty symmetry to future MCU storylines should Pugh and Steinfeld ultimately become the next iterations of Black Widow and Hawkeye, staying true to the characters’ histories and continuing their legacies. +
Wimbledon | Pliskova seeks 1st Grand Slam title, Barty 2nd - Barty’s lone major title so far came on red clay at the 2019 French Open
Sri Lankan cricket team’s data analyst tests positive for COVID-19 - The team’s batting coach Grant Flower had previously contracted the virus.
Politt wins Tour stage 12 as wind denies Cavendish - Germany’s Nils Politt won stage 12 of the Tour de France on Thursday after early winds helped a breakaway build up a convincing lead over the main pa
India’s journey to become great sporting nation will continue: outgoing Sports Minister Rijiju - Outgoing Sports Minister Kiren Rijiju on Thursday said the journey to make India a great sporting nation will continue after Anurag Thakur replaced hi
A shot in the arm for budding racers - TVS Racing adds Rookie category in the One-Make Championship
Is it indiscipline to talk about farmers, Anil Joshi asks Punjab BJP chief - In his two-page reply to a show-cause notice issued by the Punjab BJP for his “anti-party” activities, Mr. Joshi asserted that he always spoke about the party’s interests.
CB take statements of senior staff of CEO office - Probe into complaint that voters’ list in the EC server was illegally removed
Bars reopen as Bevco slashes profit margin - Panel suggests reduction in profit margin on liquor sold to bars from 25% to 13%
Delhi High Court dismisses Chirag Paswan’s plea challenging Speaker’s decision to recognise Paras as LoP - The court refrains from imposing a fine on Paswan.
Adverse impact of Coronavirus | Unable to come out of financial crisis, couple end lives - Two minors left orphans.
Skydivers killed in Swedish plane crash - Eight skydivers and a pilot die in a plane crash close to the runway at Orebro airport.
EU votes for action over Hungary’s anti-LGBT law - The new legislation bans the depiction or promotion of homosexuality and gender change among under-18s.
Spanish ministers clash over campaign to eat less meat - A minister faces pushback from fellow coalition members after urging carnivores to cut down.
German carmakers fined over emissions ‘cartel’ - VW and BMW fined €875m by the European Commission for colluding to restrict emissions cleaning tech.
Euro 2020: England charged by Uefa after ‘laser’ penalty incident - Uefa charges England after a laser pointer is directed at Denmark goalkeeper Kasper Schmeichel during Wednesday’s Euro 2020 semi-final.
Google’s Nest Hub is the best bedside smart display—and sleep tracking helps - Adding sleep tracking bolsters its bedside utility, but the feature could use more depth. - link
Rocket Report: SLS not available for science, OneWeb reaches milestone - “There is great concern about this engine development.” - link
Black Widow review: ScarJo’s sendoff is MCU’s best standalone film yet - Florence Pugh’s scene-stealing turn caps a tremendous MCU mix of action, acting. - link
The Windows 11 insider build is surprisingly unpolished and unfinished - Windows 11 looks to be a decent upgrade, but not one to lose sleep over missing. - link
Morgan Stanley discloses data breach that resulted from Accellion FTA hacks - Financial services firm says data was stolen by exploiting flaws discovered in December. - link
+He is currently assembling his cabinet. +
+ submitted by /u/saturnia2
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+After the plane was airborne, drink orders were taken. The Irishman asked for a whiskey, which was promptly brought and placed before him. +
++The flight attendant then asked the Mormon if he would like a drink. He replied in disgust, “I’d rather be savagely raped by a dozen whores than let liquor touch my lips.” +
++The Irishman then handed his drink back to the attendant and said, “Me, too, I didn’t know we had a choice.” +
+ submitted by /u/Genius_Mate
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+The Canadian politely ignored the American, who, nevertheless started up a conversation. +
++The American snapped his gum and said, “You Canadian folk eat the whole bread?” +
++The Canadian frowned, annoyed with being bothered during his breakfast, and replied, “Of course”. +
++The American blew a huge bubble. "We don’t. In the States, we only eat what’s inside. +
++The crusts we collect in a container, recycle them, transform them into croissants and sell them to Canada." +
++The American had a smirk on his face. The Canadian listened in silence. +
++The American persisted, “D’ya eat jam with your bread?” +
++Sighing, the Canadian replied, “Of course.” +
++Cracking his gum between his teeth, the American said, “we don’t. In the States, we eat fresh fruit for breakfast, then we put all the peels, seeds and the leftovers in containers, recycle them, transform them into jam and sell it to Canada.” +
++The Canadian then asked, “Do you have sex in the States?” +
++The American smiled and said, “Why of course we do.” +
++The Canadian leaned closer to him and asked, “And what do you do with the condoms once you’ve used them?” +
++“We throw them away, of course!” +
++Now it was the Canadian’s turn to smile. +
++"We don’t. In Canada, we put them in a container, recycle them, melt them down into chewing gum and sell them to the United States. Why do you think it’s called Wrigley’s? +
+ submitted by /u/orgasmic2021
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+A: A good start. +
++Q: What do you call 500 triathletes at the bottom of the ocean? +
++A: A bad start. +
+ submitted by /u/Dylanphile
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+Yet they haven’t. I don’t geddit. +
+ submitted by /u/DylanTheG999
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