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+ + + ++Emerging data suggest that the effects of infection with SARS-CoV-2 are far reaching extending beyond those with severe acute disease. Specifically, the presence of persistent symptoms after apparent resolution from COVID-19 have frequently been reported throughout the pandemic by individuals labeled as long-haulers. The purpose of this study was to assess for symptoms at days 0-10 and 61+ among subjects with PCR-confirmed SARS-CoV-2 infection. The UCCORDS dataset was used to identify 1407 records that met inclusion criteria. Symptoms attributable to COVID-19 were extracted from the electronic health record, Symptoms reported over the previous year prior to COVID-19 were excluded, using nonnegative matrix factorization (NMF) followed by graph lasso to assess relationships between symptoms. A model was developed predictive for becoming a long-hauler based on symptoms. 27% reported persistent symptoms after 60 days. Women were more likely to become long- haulers, and all age groups were represented with those aged 50 +/- 20 years comprising 72% of cases. Presenting symptoms included palpitations, chronic rhinitis, dysgeusia, chills, insomnia, hyperhidrosis, anxiety, sore throat, and headache among others. We identified 5 symptom clusters at day 61+: chest pain-cough, dyspnea-cough, anxiety-tachycardia, abdominal pain-nausea, and low back pain-joint pain. Long-haulers represent a very significant public health concern, and there are no guidelines to address their diagnosis and management. Additional studies are urgently needed that focus on the physical, mental, and emotional impact of long-term COVID-19 survivors who become long-haulers. +
++Serosurveillance studies are critical for estimating SARS-CoV-2 transmission and immunity, but interpretation of results is currently limited by poorly defined variability in the performance of antibody assays to detect seroreactivity over time in individuals with different clinical presentations. We measured longitudinal antibody responses to SARS-CoV-2 in plasma samples from a diverse cohort of 128 individuals over 160 days using 14 binding and neutralization assays. For all assays, we found a consistent and strong effect of disease severity on antibody magnitude, with fever, cough, hospitalization, and oxygen requirement explaining much of this variation. We found that binding assays measuring responses to spike protein had consistently higher correlation with neutralization than those measuring responses to nucleocapsid, regardless of assay format and sample timing. However, assays varied substantially with respect to sensitivity during early convalescence and in time to seroreversion. Variations in sensitivity and durability were particularly dramatic for individuals with mild infection, who had consistently lower antibody titers and represent the majority of the infected population, with sensitivities often differing substantially from reported test characteristics (e.g., amongst commercial assays, sensitivity at 6 months ranged from 33% for ARCHITECT IgG to 98% for VITROS Total Ig). Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on the severity of the initial infection, timing relative to infection, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies. +
++Background: Much of the early data on COVID-19 symptomatology was captured in the hospital setting. In a community setting the symptoms most predictive of SARS-CoV-2 positivity may be different. Data from the California sites of a COVID-19 community testing program are presented here. Methods: Prior to being tested, participants in the Baseline COVID-19 Testing Program completed an online screener, in which they self-reported basic demographics and the presence or absence of 10 symptoms. Both positive and negative COVID-19 RT-PCR tests were linked back to the screener data. A multivariable model of positivity was fit using generalized estimating equations, adjusting for month of testing as a fixed effect and accounting for clustering of data within each test site. Results: Among 547,018 first-time tests in California in 2020, positivity rates were 3.4%, 9.9%, and 19.8% for participants with no symptoms, 1 symptom, or 2 or more symptoms at the time of screening, respectively. All ten symptoms were individually associated with higher positivity rates, but only six of ten symptoms were associated with higher positivity when adjusting for other symptoms. Major symptoms with highest predictive value were recent loss of taste or smell, fever, and coughing–with ORs of 3.27, 1.97, and 1.95, respectively. Shortness of breath and vomiting or diarrhea were negatively associated with positivity adjusting for other symptoms and, absent other symptoms, participants with these symptoms did not have significantly higher positivity rates than asymptomatic participants. Conclusions: Recent loss of taste and smell should be elevated to a major symptom along with fever and coughing in public health messaging and in our community approach to testing and surveillance, while mild to moderate shortness of breath should be de-emphasized as a sensitive early predictor of COVID-19 positivity. +
++Background. Treatment of COVID-19 patients with convalescent plasma containing neutralising antibody to SARS-CoV-2 is under investigation as a means of reducing viral loads, ameliorating disease outcomes, and reducing mortality. However, its efficacy might be reduced in those infected with the emerging B.1.1.7 SARS-CoV-2 variant. Here, we report the diverse virological characteristics of UK patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomised controlled trial. Methods. SARS-CoV-2 viral RNA was detected and quantified by real-time PCR in nasopharyngeal swabs obtained from study subjects within 48 hours of admission to intensive care unit. Antibody status was determined by spike-protein ELISA. B.1.1.7 strain was differentiated from other SARS-CoV-2 strains by two novel typing methods detecting the B.1.1.7-associated D1118H mutation with allele-specific probes and by restriction site polymorphism (SfcI). Findings. Of 1260 subjects, 90% were PCR-positive with viral loads in nasopharyngeal swabs ranging from 72 international units [IUs]/ml to 1.7x10^11 IU/ml. Median viral loads were 45-fold higher in those who were seronegative for IgG antibodies (n=314; 28%) compared to seropositives (n=804; 72%), reflecting in part the latter group9s possible later disease stage on enrolment. Frequencies of B.1.1.7 infection increased from early November (<1%) to December 2020 (>60%). Anti-SARS-CoV-2 seronegative individuals infected with wild-type SARS-CoV-2 had significantly higher viral loads than seropositives (medians of 1.2x10^6 and 3.4 x10^4 IU/ml respectively; p=2x10^-9). However, viral load distributions were elevated in both seropositive and seronegative subjects infected with B.1.1.7 (13.4x10^6 and 7.6x10^6 IU/ml; p=0.18). Interpretation. High viral loads in seropositive B.1.1.7-infected subjects are consistent with increased replication capacity and/or less effective clearance by innate or adaptive immune response of B.1.1.7 strain than wild-type. As viral genotype was associated with diverse virological and immunological phenotypes, metrics of viral load, antibody status and infecting strain should be used to define subgroups for analysis of treatment efficacy. +
++Background: Efforts to stem the SARS-CoV-2 pandemic in Canada can benefit from direct understanding of the prevalence, infection fatality rates (IFRs), and information on asymptomatic infection. Methods: We surveyed a representative sample of 19,994 adult Canadians about COVID symptoms and analyzed IgG antibodies against SARS-CoV-2 from self-collected dried blood spots (DBS) in 8,967 adults. A sensitive and specific chemiluminescence ELISA detected IgG to the spike trimer. We compared seroprevalence to deaths to establish IFRs and used mortality data to estimate infection levels in nursing home residents. Results: The best estimate (high specificity) of adult seroprevalence nationally is 1.7%, but as high as 3.5% (high sensitivity) depending on assay cut-offs. The highest prevalence was in Ontario (2.4-3.9%) and in younger adults aged 18-39 years (2.5-4.4%). Based on mortality, we estimated 13-17% of nursing home residents became infected. The first viral wave infected 0.54-1.08 million adult Canadians, half of whom were <40 years old. The IFR outside nursing homes was 0.20-0.40%, but the COVID mortality rate in nursing home residents was >70 times higher than that in comparably-aged adults living in the community. Seropositivity correlated with COVID symptoms, particularly during March. Asymptomatic adults constituted about a quarter of definite seropositives, with a greater proportion in the elderly. Interpretation: Canada had relatively low infection prevalence and low IFRs in the community, but not in nursing homes, during the first viral wave. Self-collected DBS for antibody testing is a practicable strategy to monitor the ongoing second viral wave and, eventually, vaccine-induced immunity among Canadian adults. +
++Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 106 million cases of confirmed infection and more than 2.3 million deaths worldwide as of February 11th 2021. Seroprevalence studies are extremely useful in studying and assessing the epidemiological status in the community and the degree of spread. They help decision makers in implementing or relaxing mitigating measures to contain the disease in addition to other benefits. Objective: To study the seroprevalence rates of SARS-CoV-2 antibodies among healthy blood donors in Jordan, at various points of time as the pandemic evolves in the community. Methods: A total of 1374 blood donor were tested for the SARS-CoV-2 antibodies in 3 groups. The first group of 746 and the second of 348 individuals were tested in June and September of 2020 respectively. The 3rd group of 292 were tested in early February of 2021. We utilized a qualitative assay that uses Electrochemiluminescence method (ECLIA) that has a specificity and sensitivity of 99.8% and 100% respectively. Results: The first 2 groups representing the months of January to September of 2020, where the number of confirmed Covid-19 cases were several hundred to 3000 showed a seroprevalence rate of 0% (95% CI 0.00%, 0.51%). The 3rd group representing late January and early February 2021 when the number of reported confirmed case has reached 100 folds the numbers of September 2020, showed a seroprevalence of 27.4% (95% CI 22.5% and 32.9%). Conclusions: a dramatic rise in seroprevalence of SARS-CoV-2 antibodies was seen among healthy blood donors in Jordan in parallel with wide-spread intracommunity transmission of the disease. This information is useful to assess the degree of herd immunity and provides for better understanding of the pandemic. +
++Aim The objective of this observational study was to investigate the association between SARS-CoV-2 transmission risk, RT-PCR Cycle threshold (Ct) values, and age of infected cases in Danish households. Background The Covid-19 pandemic is one of the most serious global public health threats in recent times. Understanding transmission of SARS-CoV-2 is of utmost importance to be able to respond to outbreaks and take action against the spread of the disease. Viral load is generally thought to correlate with transmission risk. Methods We used comprehensive administrative register data from Denmark, comprising the full population and all SARS-CoV-2 tests (August 25, 2020 to February 10, 2021), to estimate household transmission risk. Results We found that the transmission risk was negatively associated—approximately linear—with the Ct values of the tested primary cases. Also, we found that even for relatively high Ct values, the risk of transmission was not negligible; e.g., for primary cases with a Ct value of 38, we found a transmission risk of 8%. This implies that there is no obvious cut-off for Ct values for risk of transmission. We estimated the transmission risk according to age and found an almost linearly increasing transmission risk with the age of the primary cases for adults (≥20 years) and negatively for children (<20 years). Age had a higher impact than Ct value on the risk of transmission. Conclusions Lower Ct values (indicating higher viral load) are associated with higher risk of SARS-CoV-2 transmission. However, even at high Ct values, transmission occurs. In addition, we found a strong association between age and transmission risk, and this dominated the Ct value association. +
++We analyze data from the Fall 2020 pandemic response efforts at the University of Colorado Boulder (USA), where more than 72,500 saliva samples were tested for SARS-CoV-2 using quantitative RT-PCR. All samples were collected from individuals who reported no symptoms associated with COVID-19 on the day of collection. From these, 1,405 positive cases were identified. The distribution of viral loads within these asymptomatic individuals was indistinguishable from what has been previously reported in symptomatic individuals. Regardless of symptomatic status, approximately 50% of individuals who test positive for SARS-CoV-2 seem to be in non-infectious phases of the disease, based on having low viral loads in a range from which live virus has rarely been isolated. We find that, at any given time, just 2% of individuals carry 90% of the virions circulating within communities, serving as viral super-carriers and possibly also super-spreaders. +
++Importance: With randomized clinical trials ongoing and vaccine still a long distance away, efforts to repurpose old medications used for other diseases provide hope for treatment of COVID−19. Objectives: To examine the risk factors for in−hospital mortality and describe the effectiveness of different treatment strategies in a real−life setting of patients with severe acute respiratory syndrome coronavirus 2 (SARS−CoV−2) pneumonia. Design: Real−life single−center study during the Lombardy COVID−19 outbreak. Setting: Valduce Hospital in Como, Lombardy Region, Italy. Participants: 205 laboratory−confirmed patients presenting with SARS−Cov−2 pneumonia requiring hospitalization. Interventions: All patients received best supportive care and, based on their clinical needs and comorbidities, specific interventions that included the main drugs being tested for repurposing to treat COVID−19, such as hydroxychloroquine, anticoagulation, antiviral drugs, steroids or interleukin−6 pathway inhibitors. Main outcomes and measures: Clinical, laboratory and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in−hospital mortality and compared with current literature data. Results: Univariate analyses for clinical variables showed prognostic significance for age equal or greater than 70 years (estimated 28−days survival: 21.4 vs 67.4%; p<0.0001), presence of 2 or more relevant comorbidities (35.3 vs 61.8%; p=0.0008), ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) less than 200 at presentation (21−days survival: 14.7 vs 52.4%;p<0.0001), high levels of lactate dehydrogenase (LDH) (26.4 vs 65.3%; p=0.0001), and elevated C−reactive protein (CRP) values (25.4 vs 74.9%; p=0.0001), while no statistical significance was found for all the other clinical variables tested. At univariate analysis for the different treatment scheduled, prognostic significance for survival was showed for intermediate or therapeutic-dose anticoagulation (estimated 28−days survival: 37.1 vs 23.4%; p=0.0001), hydroxychloroquine (35.7 vs 27.3%; p=0.0029), early antiviral therapy with lopinavir/ritonavir (60.1 vs 22.4%; p<0.0001), late short−course of steroids (47.9 vs 18.2%; p<0.0001) or tocilizumab therapy (69.4 vs 29.4%; p=0.0059). Multivariable regression confirmed increasing odds of in−hospital death associated with age older than 70 years (odds ratio 3.26, 95% CI 1.81 − 5.86; p<0.0001) and showed a reduction in mortality for patients treated with anticoagulant (−0.37, 0.49 − 0.95; p=0.0273), antiviral (−1.22, 0.16 − 0.54; p<0.0001), or steroids (−0.59, 0.35 − 0.87; p=0.0117) therapy. +
++Background: The SARS-CoV-2 pandemic has led to the development of various vaccines. Real-life data on immune responses elicited in the most vulnerable group of vaccinees over 80 years old is still underrepresented despite the prioritization of the elderly in vaccination campaigns. Methods: We conducted a cohort study with two age groups, young vaccinees below the age of 60 and elderly vaccinees over the age of 80, to compare their antibody responses to the first and second dose of the BNT162b2 COVID-19 vaccination. Results: While the majority of participants in both groups produced specific IgG antibody titers against SARS-CoV-2 spike protein, titers were significantly lower in elderly participants. Although the increment of antibody levels after the second immunization was higher in elderly participants, the absolute mean titer of this group remained lower than the <60 group. After the second vaccination, 31.3 % of the elderly had no detectable neutralizing antibodies in contrast to the younger group, in which only 2.2% had no detectable neutralizing antibodies. Conclusion: Our data suggests that lower frequencies of neutralizing antibodies after BNT162b2 vaccination in the elderly population may require earlier revaccination to ensure strong immunity and protection against infection. +
+Clinical Study in the Treatment of Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: Molixan; Drug: Placebo
Sponsor: Pharma VAM
Not yet recruiting
A Safety and Efficacy Study of Human Monoclonal Antibodies, BRII-196 and BRII-198 for the Treatment of Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: BRII-196 and BRII-198; Drug: Placebo
Sponsor: Brii Biosciences, Inc.
Not yet recruiting
Dose-Ranging Study to Assess the Safety and Efficacy of Melatonin in Outpatients Infected With COVID-19 - Condition: COVID-19
Interventions: Drug: Melatonin; Drug: Placebo
Sponsors: State University of New York at Buffalo; National Center for Advancing Translational Science (NCATS)
Not yet recruiting
A Study to Evaluate the Efficacy and Safety of Brilacidin in Hospitalized Participants With COVID-19 - Condition: COVID-19
Interventions: Drug: Brilacidin; Drug: Placebo; Drug: Standard of Care (SoC)
Sponsor: Innovation Pharmaceuticals, Inc.
Recruiting
Protecting Native Families From COVID-19 - Condition: COVID-19
Interventions: Behavioral: Motivational Interviewing; Behavioral: COVID-19 Symptom Monitoring System; Behavioral: Motivational Interviewing and COVID-19 Symptom Monitoring System; Other: Supportive Services
Sponsor: Johns Hopkins Bloomberg School of Public Health
Not yet recruiting
Safety and Efficacy of Thymic Peptides in the Treatment of Hospitalized COVID-19 Patients in Honduras - Condition: COVID-19
Intervention: Biological: Thymic peptides
Sponsors: Universidad Católica de Honduras; Pontificia Universidad Catolica de Chile
Recruiting
(CBDRA60) to Prevent or Reduce Symptoms of COVID-19 - Condition: COVID-19
Interventions: Dietary Supplement: CBDRA60 supplement; Dietary Supplement: Placebo
Sponsors: Anewsha Therapeutics Inc.; University of Michigan; Biologics Consulting
Not yet recruiting
Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: ATR-002; Drug: Placebo
Sponsor: Atriva Therapeutics GmbH
Not yet recruiting
A Study to Evaluate UB-612 COVID-19 Vaccine in Adolescent, Younger and Elderly Adult Volunteers - Condition: COVID-19
Interventions: Biological: UB-612; Biological: Placebo
Sponsors: United Biomedical Inc., Asia; COVAXX
Recruiting
JS016 (Anti-SARS-CoV-2 Monoclonal Antibody)With Mild and Moderate COVID-19 or SARS-CoV-2 Asymptomatic Infection Subects - Condition: COVID-19
Interventions: Biological: Recombinant Human Anti-SARS-CoV-2 Monoclonal Antibody(25mg/kg;50mg/kg;100mg/kg); Drug: Placebo
Sponsor: Shanghai Junshi Bioscience Co., Ltd.
Recruiting
Study of the Tolerability, Safety, Immunogenicity and Preventive Efficacy of the EpiVacCorona Vaccine for the Prevention of COVID-19 - Condition: COVID-19
Interventions: Biological: EpiVacCorona (EpiVacCorona vaccine based on peptide antigens for the prevention of COVID-19); Other: Placebo (sodium chloride, a 0.9% solution for the preparation of dosage forms for injections)
Sponsor: Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”
Active, not recruiting
Adoptive SARS-CoV-2 Specific T Cell Transfer in Patients at Risk for Severe COVID-19 - Condition: Moderate COVID-19-infection
Interventions: Drug: IMP 1,000 plus SoC; Drug: IMP 5,000 plus SoC; Drug: IMP RP2D plus SoC; Drug: SoC
Sponsors: Universitätsklinikum Köln; ZKS Köln; MMH Institute for Transfusion Medicine; Miltenyi Biomedicine GmbH
Not yet recruiting
A Phase 3 Trial to Determine the Efficacy/Safety of Plitidepsin vs Control in Patients With Moderate COVID-19 Infection - Condition: COVID-19 Infection
Interventions: Drug: Plitidepsin; Drug: Dexamethasone; Drug: Remdesivir
Sponsor: PharmaMar
Not yet recruiting
Study to Evaluate a Single Dose of STI-2020 (COVI-AMG™) in Hospitalized Adults With COVID-19 - Condition: Covid19
Interventions: Biological: COVI-AMG; Drug: Placebo
Sponsor: Sorrento Therapeutics, Inc.
Not yet recruiting
Safety & Efficacy of Low Dose Aspirin / Ivermectin Combination Therapy for Treatment of Covid-19 Patients - Condition: Covid19
Intervention: Drug: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1)
Sponsors: Makerere University; Ministry of Health, Uganda; Mbarara University of Science and Technology; Joint Clinical Research Center
Not yet recruiting
MERS-CoV and SARS-CoV-2 replication can be inhibited by targeting the interaction between the viral spike protein and the nucleocapsid protein - Background: The molecular interactions between viral proteins form the basis of virus production and can be used to develop strategies against virus infection. The interactions of the envelope proteins and the viral RNA-binding nucleocapsid (N) protein are essential for the assembly of coronaviruses including the Middle East respiratory syndrome coronavirus (MERS-CoV). Methods: Using co-immunoprecipitation, immunostaining, and proteomics analysis, we identified a protein interacting with the…
Polyunsaturated omega-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry - The strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based…
Potential neutralizing antibodies discovered for novel corona virus using machine learning - The fast and untraceable virus mutations take lives of thousands of people before the immune system can produce the inhibitory antibody. The recent outbreak of COVID-19 infected and killed thousands of people in the world. Rapid methods in finding peptides or antibody sequences that can inhibit the viral epitopes of SARS-CoV-2 will save the life of thousands. To predict neutralizing antibodies for SARS-CoV-2 in a high-throughput manner, in this paper, we use different machine learning (ML) model…
Flavonoids against the SARS-CoV-2 induced inflammatory storm - The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of…
Design, Synthesis and Biological Evaluation of 2-Aminoquinazolin-4(3H)-one Derivatives as Potential SARS-CoV-2 and MERS-CoV Treatments - Despite the rising threat of fatal coronaviruses, there are no general proven effective antivirals to treat them. 2-Aminoquinazolin-4(3H)-one derivatives were newly designed, synthesized, and investigated to show the inhibitory effects on SARS-CoV-2 and MERS-CoV. Among the synthesized derivatives, 7-chloro-2-((3,5-dichlorophenyl)amino)quinazolin-4(3H)-one (9g) and 2-((3,5-dichlorophenyl)amino)-5-hydroxyquinazolin-4 (3H)-one (11e) showed the most potent anti-SARS-CoV-2 activities (IC(50) < 0.25…
SARS-CoV-2 and other coronaviruses negatively influence mitochondrial quality control: beneficial effects of melatonin - Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities. Results from several studies suggest that CoVs localize in mitochondria and…
Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Lung Diseases: Current Status and Perspectives - Extracellular vesicles (EVs) have emerged as a potential therapy for several diseases. These plasma membrane-derived fragments are released constitutively by virtually all cell types-including mesenchymal stromal cells (MSCs)-under stimulation or following cell-to-cell interaction, which leads to activation or inhibition of distinct signaling pathways. Based on their size, intracellular origin, and secretion pathway, EVs have been grouped into three main populations: exosomes, microvesicles (or…
THE PECULIARITY OF COVID- 19 GENOME AND THE CORONAVIRUS RNA TRANSLATION PROCESS AS APOTENTIAL TARGET FOR ETIOTROPIC MEDICATIONSWITH ADENINE AND OTHER NUCLEOTIDE ANALOGUES (REVIEW) - Despite the multifaceted effects of the medicines provided for COVID-19treatment, the number of the infected and mortality of patients increases which demonstrates the insufficient effectiveness of drugs used to fight coronavirus infections in medical practice, and clearly shows the need to develop new treatment tactics.In this review article are summarized and analyzed the literature data concerning specific features of COVID 19. Particular attention is given to genetic characteristic of this…
Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis - Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed…
Evaluating the Antimicrobial Properties of Commercial Hand Sanitizers - Hand sanitizers have been developed as a convenient means to decontaminate an individual’s hands of bacterial pathogens in situations in which soap and water are not available. Yet to our knowledge, no study has compared the antibacterial efficacy of a large collection of hand sanitizers. Using zone of growth inhibition and kill curve assays, we assessed the performance of 46 commercially available hand sanitizers that were obtained from national chain big-box stores, gasoline stations,…
Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC(50) range, 0.0007-0.35 μg/mL) against live SARS-CoV-2 infection in the golden Syrian hamster model. These HuNAbs inhibit SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding…
Antiviral and immunomodulatory activity of curcumin: A case for prophylactic therapy for COVID-19 - Coronavirus disease-19 (COVID-19), a devastating respiratory illness caused by SARS-associated coronavirus-2 (SARS-CoV-2), has already affected over 64 million people and caused 1.48 million deaths, just 12 months from the first diagnosis. COVID-19 patients develop serious complications, including severe pneumonia, acute respiratory distress syndrome (ARDS), and or multiorgan failure due to exaggerated host immune response following infection. Currently, drugs that were effective against…
Exploring existing drugs: proposing potential compounds in the treatment of COVID-19 - The COVID-19 situation had escalated into an unprecedented global crisis in just a few weeks. On the 30^(th) of January 2020, World Health Organization officially declared the COVID-19 epidemic as a public health emergency of international concern. The confirmed cases were reported to exceed 105,856,046 globally, with the death toll of above 2,311,048, according to the dashboard from Johns Hopkins University on the 7^(th) of February, 2021, though the actual figures may be much higher. Conserved…
Targeting the Main Protease of SARS-CoV-2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors - The main protease of SARS-CoV-2 (Mpro), the causative agent of COVID-19, constitutes a significant drug target. A new fluorogenic substrate was kinetically compared to an internally quenched fluorescent peptide and shown to be ideally suitable for high throughput screening with recombinantly expressed Mpro. Two classes of protease inhibitors, azanitriles and pyridyl esters, were identified, optimized and subjected to in-depth biochemical characterization. Tailored peptides equipped with the…
Targeting the Coronavirus Nucleocapsid Protein through GSK-3 Inhibition - The coronaviruses responsible for severe acute respiratory syndrome (SARS-CoV), COVID-19 (SARS-CoV-2), Middle East respiratory syndrome (MERS-CoV), and other coronavirus infections express a nucleocapsid protein (N) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV by glycogen synthase kinase 3 (GSK-3) is required for its function and inhibition of GSK-3 with lithium impairs N phosphorylation, viral transcription, and replication….
Sars-CoV-2 vaccine antigens - - link
SARS-COV-2 BINDING PROTEINS - - link
Compositions and methods for detecting SARS-CoV-2 spike protein - - link
一种3-羟基丁酰化修饰蛋白质药物及其制备方法和应用 - 本发明涉及医药技术领域,公开了一种3‑羟基丁酰化修饰蛋白质药物(例如抗体)及其制备方法和应用,特别是一种3‑羟基丁酰化修饰抗体及其制备方法和应用。发明人经过大量实验发现,3‑羟基丁酸及其类似物修饰蛋白质药物(例如抗体)后,可以显著提高蛋白质药物的热稳定性、对蛋白酶水解的抗性,降低蛋白质药物的等电点,并显著延长其在受试者体内的半衰期,进而提高其药效。修饰后所得蛋白质药物在科研和临床方面具有广阔的应用前景和较高的商业价值。 - link
新冠病毒重组融合蛋白、其制备方法和应用 - 本发明提供一种新冠病毒重组融合蛋白、其制备方法和应用。本发明通过对新冠病毒S和N重组融合蛋白的基因序列进行设计,选择最优的片段进行整合,再通过人源HEK293细胞系统重组表达融合蛋白,经过纯化后对融合蛋白的分子量、纯度进行检测,最后利用融合蛋白制成新冠病毒抗体胶体金检测试纸条/试剂盒。与单独使用S蛋白或N蛋白制备的胶体金检测试纸条相比,该重组融合蛋白制备的胶体金检测试纸条具有更高的灵敏度和更低的漏检率。此外,本发明提供的新冠病毒重组融合蛋白可广泛应用于不同平台技术的新冠抗体检测试剂盒开发,如胶体金、荧光免疫层析、化学发光和酶联免疫等。 - link
稳定的冠状病毒重组蛋白二聚体及其表达载体 - 本发明公开了稳定的冠状病毒重组蛋白二聚体及其表达载体,冠状病毒重组蛋白,由冠状病毒S蛋白S‑RBD、冠状病毒N蛋白的CTD区N‑CTD和将二者偶联的连接子构成。本发明一些实例的冠状病毒重组蛋白,可以形成并维持稳定的二聚体结构,避免单体S‑RBD降解,有利于提高冠状病毒重组蛋白的免疫原性,有望用于制备检测试剂原料、疫苗、抗体、预防或治疗性药物。本发明一些实例的冠状病毒重组蛋白二聚体,具有很好的免疫原性。在疫苗开发领域具有广阔的应用前景。本发明一些实例的表达载体,易于表达冠状病毒重组蛋白二聚体且表达量高。 - link
SELF-CLEANING AND GERM-KILLING REVOLVING PUBLIC TOILET FOR COVID 19 - - link
一种新冠病毒S1蛋白的灌流生产系统及方法 - 本发明涉及细胞生物学技术领域,提供了一种新冠病毒S1蛋白的灌流生产系统及方法,包括:细胞反应器,用于培养表达S1蛋白的细胞株;灌流系统,包括过滤装置、出液管、回液管和第一循环泵,所述过滤装置的主体内设有孔径为0.1‑0.2μm的中空纤维柱,用于过滤透出液,截留细胞培养液中的S1蛋白;所述出液管的两端分别与所述细胞反应器和所述中空纤维柱的下端相连通;所述回液管的两端分别与所述细胞反应器和所述中空纤维柱的上端相连通;所述第一循环泵设置于所述出液管与所述中空纤维柱相连的管路中。本发明系统投入成本低且S1蛋白产量高。 - link
检测新冠病毒的方法及试剂盒 - 本发明公开了一种检测新冠病毒的方法及试剂盒。其中,该方法包括以下步骤:1)采集样本;2)采用核酸释放剂提取核酸;3)采用LAMP扩增进行检测,其中,核酸释放剂包括:热敏蛋白酶1000U/L~10000U/L、Tris‑HCl 5~50 mmol/L、曲拉通X‑100体积百分比0.05%0.5%和金属离子螯合剂0.10.5mmol/L,其余为无菌水,热敏蛋白酶为≥55℃加热5~10分钟会完全失活的蛋白酶。应用本发明的检测新冠病毒的方法及试剂盒,检测新冠病毒,检测周期短,操作简单方便,检测结果通俗易懂,检测特异性高,检测成本低。 - link
一种新型冠状病毒拉曼光谱数据中心的构建方法 - 本发明公开了一种新型冠状病毒拉曼光谱数据中心的构建方法,该方法包括以下步骤:S1.构建新冠病毒结构蛋白拉曼光谱数据库;S2.构建新冠病毒核酸拉曼光谱数据库;S3.构建新冠病毒颗粒拉曼光谱数据库;S4.构建新冠病毒临床检测样本拉曼光谱数据库;将各新型冠状病毒拉曼光谱数据库存入新型冠状病毒拉曼光谱检测服务器构成新型冠状病毒拉曼光谱数据中心。本发明有效建立了一套完整的新型冠状病毒拉曼光谱数据库,为新冠病毒拉曼检测技术提供可靠的标准数据支撑,有效提高检测结果的准确性及置信度。 - link
South Carolina Republicans Face a Trump-Fuelled Schism - The former President has left the White House, but the battle for the G.O.P. is only getting started. - link
The Wasting of the Evangelical Mind - The peculiarities of how American Christianity took shape help explain believers’ vulnerability to conspiratorial thinking and misinformation. - link
The Russians Protesting Putin in Their Personal Lives - Since Alexey Navalny’s arrest, some Russians are reëvaluating their compromises, questioning whether the price of success—or merely getting by—has become untenable. - link
The Vaccine Resisters - Why do so many people say that they won’t be immunized against COVID-19? - link
What Does National Security Even Mean Anymore? - Talking threats, foreign and domestic, with Mark Milley, the chairman of the Joint Chiefs of Staff. - link
+The animated fantasy is a gorgeous, if generic, vehicle for a great Disney princess. +
++Disney’s latest princess film, Raya and the Last Dragon, delivers a lush, beautifully animated, endearing, and engaging story. It’s funny and well written, with dark, layered themes, memorable characters, a pair of deliciously kickass teen girl rivals, and perhaps the most overtly political messaging Disney has pushed in decades. Plus, it’s a fantasy adventure that promises to bring Disney fans a long-awaited treasure: Raya, the first Southeast Asian Disney princess. +
++But it has drawn its share of skeptics, and for good reason: The film, premiering on Disney+ and in select theaters March 5 (with an accompanying short film, Us Again), is a conundrum. +
++The film’s writers, Qui Nguyen (The Society) and Adele Lim (Crazy Rich Asians) are, respectively, Vietnamese American and Malaysian American, and copious research has gone into Raya to make the film feel true to Southeast Asian viewers. The dragons in Raya are mainly based on Southeast Asian folklore, and the visuals and settings are mainly drawn from the region’s real geography. +
++But the film’s production team has drawn criticism from Southeast Asian viewers for casting East Asian actors in many of its most important roles, rather than Southeast Asian actors. Though the title role went to Kelly Marie Tran, a Disney fan favorite of Vietnamese descent (known for Star Wars), the main cast also includes Awkwafina in the role of the “last dragon,” Daniel Dae Kim as Raya’s father, and Gemma Chan as Raya’s nemesis Namaari. They are respectively, Chinese and Korean American, Korean American, and British Chinese. +
++Voice actors have been fighting to win roles that reflect their ethnicity, a fact that led to early criticism around Raya and its casting. But there is another worry about the use of East Asian actors: The blending of the distinct and varied cultures of Vietnam, Thailand, Malaysia, Singapore, the Philippines, and half a dozen other nations has left Raya and the Last Dragon feeling indistinct and insensitive. +
++Fans of the Airbender/Korra franchise might be reminded of those series and note that they did much of what Raya is trying to do now, better, 15 years ago. Movie buffs may feel like Raya has taken 80 percent of its beats from other animated stories, from The Lion King to The Dark Crystal. But the most disappointing thing about Raya is that Southeast Asian Disney fans may struggle to find any identifiable part of their specific cultures in the film’s gorgeous but messy world-building. +
++Raya (pronounced “RYE-ah”) is set in a fantasy land called Kumandra, a blend of Southeast Asian nations and cultures. The real-world region consists of about a dozen countries, including parts of India and the South Pacific, which between them encompass hundreds of miles, languages, cultures, and islands. In Raya, this diverse part of the planet has been condensed to a group of five loosely defined tribes who aren’t clearly mapped to any specific culture but instead to parts of a dragon: There’s Fang, Talon, Spine, Tail, and Raya’s home, Heart. +
++Centuries ago, Kumandra was a happy land freely cohabited by the five human tribes and dragons, until the land was invaded by a strange monster species called the Druun, who turn everything they touch to stone. It’s not clear what the Druun live on, or how they arose, or how to fully defeat them. They’re essentially a purple-cloud plot device for everything that comes afterward — several centuries of geopolitical strife. The Druun wipe out the dragons, but one, Sisu (Awkwafina) sacrifices herself and uses all her magic to vanquish the Druun threat. With no dragon magic to protect them, the tribes of Kumandra fall into conflict. +
++When we meet Raya, her father, the leader of Heart, is trying diligently to reunite the tribes once and for all by convincing them to trust one another. Raya is still just a young girl, so she’s easy prey for Namaari, the daughter of the visiting Fang leader. They bond over their shared love of dragons and a wish to find Sisu, who, according to legend, was never killed in the Druun war, but instead went into hiding. When Raya entrusts Namaari with a secret, however, Namaari betrays her, setting off a chain of events that leads to the sudden return of the Druun. +
++The resurrected Druun turn masses of people into stone, including Raya’s father. The planet falls out of ecological balance, and the divisions between the remaining tribes grow even more fierce. With no alternative, Raya devotes herself to trying to find the river where Sisu may be hiding, in the hope of getting her help to heal the world. +
++The dragons of this universe draw inspiration from the benevolent magical dragons of Vietnamese folklore, with a design based on the naga folklore of Thailand and other countries. They’re delightful, non-threatening, and non-fire-breathing — colorful serpents who fly, swim, and generally behave like wriggly pets. As voiced by Awkwafina, Sisu is a fun addition to the Disney canon of magical sidekicks; she’s wisecracking but earnest, rambunctious but wise, and her loving nature is a good foil for Raya, who’s vulnerable but much tougher, thanks to Namaari. Meanwhile, Namaari has grown up to lead her home tribe, Fang, but has begun questioning the aggressive direction of her clan. +
++Determined to reunite the tribes as Raya’s father always intended, Raya and Sisu journey to each of the other four lands to try and steal the remaining dragon crystals they each control, in hopes that uniting all the crystals can return the dragons to Kumandra, vanquish the Druun, and bring peace. Predictably, this road trip brings them lots of new friends and enemies. The biggest enemy of all, of course, is Raya’s archnemesis — but if you’re vibing the Airbender-ness of it all, you’ve probably guessed that Namaari may turn out to be the reluctant ally Raya has needed all along. +
++Raya is a gorgeous, accessible film, with engaging characters, a winning heroine, and sumptuous animation from start to finish. It’s a film you’ll want to look at again and again, and its story will hold up fairly well on repeat viewing. As a bonus, Us Again, the short film that accompanies Raya on streaming platforms and in theaters, delivers stunning animation and big-hearted emotions throughout its noisy but wordless seven minutes. Its story of an elderly couple rekindling their relationship through their love of dance pays homage to the grand tradition of movie musicals from Singin’ in the Rain to La La Land, but also feels like an accidental anthem for a vibrant city whose nightlife scenes have dimmed fully during quarantine. You will cry, so be prepared, but Us Again’s dazzling seven minutes alone are worth Raya’s hefty add-on streaming price of nearly $30. +
++For most Disney fans, the main feature will also be worth the price. Yet the blended version of Southeast Asia on display in Raya may leave viewers conflicted about the way the movie flattens all of Southeast Asia into the land of Kumandra. +
++Each of the five tribes in Raya’s fractured homeland has its own distinctive geography and what seems to be an approximation of a distinctive culture. But they aren’t recognizably linked to cultures in our own world — not in the way that (to use what still seems to be the best example of this exercise in US animation) the four tribes of Airbender map identifiably to Inuit, Chinese, Tibetan, and Japanese cultures. +
++Throughout my viewing of Raya, I was confused about what signifiers I was meant to recognize as a viewer; initially, I thought Raya’s tribe, Heart, was meant to be based on Thailand. Then I settled on Indonesia, then on Vietnam; eventually, as the film’s cultural guideposts kept shifting — Thai decor seemed to merge with Cambodian temples, Filipino weaponry, Vietnamese mountains — I gave up. +
++Hollywood’s push for diversity has also brought with it a renewed understanding of the importance of cultural sensitivity, and Disney’s outsized influence means its films draw close scrutiny. Moana ran into controversy in 2016 because of its buffoonish depiction of the Polynesian god Maui, which some found offensive, as well as the inclusion of elements of indigenous cultures that some viewers regarded as racist stereotypes. “The filmmakers cut off manageable chunks of exotica,” argued Maori writer Morgan Godfery, “while refusing to keep faith with actual Polynesian histories and mythologies.” +
++Perhaps because of that backlash, Raya’s creative team doesn’t appear to have engaged existing mythos at all apart from the dragon concept. Unlike most films in the Disney princess pantheon, Raya’s story isn’t taken from any extant cultural source, but comes from the brain of veteran Disney director Bradley Raymond, known mainly for directing sequels like Lion King 3 and Pocahontas 2. Here, he’s credited with generating the story ideas upon which Raya is based. +
++That’s not to say that white men or white creatives — or indeed any of us — aren’t capable of generating meaningful stories about cultures not their own. At a bare minimum, doing so requires respect and research, and Raya’s production did plenty of the latter. In preparation for the film, members of Disney’s production and animation teams reportedly traveled throughout Southeast Asia, making stops in seven countries. In aiming for respectful cultural representation, they created the Raya Southeast Asia Story Trust, an assemblage of various experts including, according to Looper, “a textile expert, linguists (who approved every name in the film), and a visual anthropologist.” +
++But much of this careful attention to detail seems to have been executed mainly as background aesthetic, rather than as key parts of the storyline or the worldbuilding. While the production team includes numerous East Asian and Southeast Asian creators, including writers, animators, technical effects crew, and producers, most of the project decisions ultimately rested with directors Don Hall (Big Hero 6) and Carlos López Estrada (Blindspotting) and their co-directors, Paul Briggs (Big Hero 6) and John Ripa (Moana). +
++The biggest problem, however, is that all of that well-intentioned research seems to have been done for the explicit purpose of flattening Southeast Asia’s diversity, condensing a striking array of distinct cultures into five tribes. Aspects of cultures from other regions are blended in, too. There were numerous times the film’s aesthetics will remind viewers more of Korea and China, and even farther-flung places like Samoa and Central America, than Southeast Asia. Viewers analyzing the trailer have further commented that the film’s temples and architecture are uncharacteristically decor-free, and that the clothing lacks distinctively detailed patterns common in the nations. +
++After the fiasco of 2020’s terrible Mulan remake, in which the film’s East Asian cultural signifiers were put on display but badly mishandled, you might think that a generalized approach is a safer way to go. And initially, I was fully on board with that idea, because I was wooed by Raya’s many other strengths. +
++Raya herself is a wonderful protagonist, easily one of my favorite Disney princesses by a mile, though she’s justifiably drawn many comparisons to the Airbender franchise’s hot-blooded hero, Korra (they even bear a striking visual resemblance). She’s strong, bold, clever, and raids tombs with all the wiles of Indiana Jones. She and Namaari have a satisfying rivalry complete with thrilling fight scenes. The side characters are a mostly forgettable hodgepodge of typical Disney side characters — there’s a scheming team of monkeys and a conniving orphan baby who are all so outlandishly bizarre they cycled around from “horrifying” to “macabre treat” — but Awkwafina is a gem. +
++By the time I was near the end, however, the film’s innumerable borrowed tropes really began to get to me. I started to question the construction of the entire project: How many of the story elements really came from Nguyen and Lim, or from the head of story, Thai American animator Fawn Veerasunthorn? How many from Bradford, or from the six other people who all share story credits with Nguyen and Lim, most of whom are white? +
++Even the score by James Newton Howard, which I initially found lush and ebullient, increasingly sounded like one of his phoned-in action scores, but with added vague chanting in non-specific languages. As the credits rolled, I found myself studying the long list of English names associated with the score’s production, wondering how it would sound to a Southeast Asian audience member. The outro song, usually one of the highlights of any Disney film, is here a forgettable number called “Lead the Way.” It’s written and performed by Jhené Aiko, an artist of partial Japanese heritage who at one point gives up on lyrics and just starts singing “Kumandra, Kumandra” over and over, as if simply naming the film’s setting could clarify anything for us. +
++This all may sound like futile nitpicking, but it really isn’t. Raya’s generic attributes lend the film a vague quality overall. Compared to the memorable localization of Disney films like Frozen, which referenced actual rococo art, or Coco, which fully immersed the audience in Mexican culture, Raya feels thin. Its lack of specificity works against it. +
++Perhaps the biggest tell that Raya isn’t the representation Southeast Asian Disney fans deserve is that many of them won’t actually be able to watch it with the rest of us — because Disney+ is currently only available in three Southeast Asian countries. If there are stronger objections to be made to this film, the people best in a position to make them may not get to see it. +
++And so the film mainly leaves me questioning who Raya’s intended audience is — and whether it was meant to appeal to Southeast Asian viewers. It seems clear that fans deserved a better movie that more fully and overtly embraced their cultures, instead of simply borrowing their beautiful settings for an average fantasy story. +
++
++
+The Biden administration wants a professional, dispassionate process during its Afghanistan review. +
++The Biden administration’s internal debate over the future of US military involvement in the war in Afghanistan over the last several weeks has taken place quietly, largely behind closed doors. +
++But that doesn’t mean it hasn’t been heated. In fact, a previously unreported episode at a recent high-level meeting shows just how fraught these discussions have been as the Biden team tries to figure out how, or even whether, to bring to an end America’s longest-ever war. +
++At a recent National Security Council Principal’s Committee meeting, Cabinet-level officials including Chairman of the Joint Chiefs of Staff Gen. Mark Milley, Secretary of Defense Lloyd Austin, and others gathered as part of the administration’s weekslong review of US policy in Afghanistan. +
++The officials are debating which of three broad options for the 20-year war in Afghanistan Biden should pursue. The first is to adhere to former President Donald Trump’s deal with the Taliban, which would require Biden to withdraw all remaining 2,500 US troops by May 1. The second is to negotiate an extension with the insurgent group, allowing American forces to remain in the country beyond early May. And third is to defy the Trump-Taliban pact altogether and keep fighting in Afghanistan with no stated end date. +
++During the meeting, according to four sources from the White House, Pentagon, and elsewhere familiar with what happened, Milley made an impassioned — and at times “emotional,” according to some — case to consider keeping US troops in the country. +
++Milley, who was the deputy commanding general of US forces in Afghanistan and served three tours in the country, essentially argued that if American forces fully withdraw by May 1, it would open the door for the Taliban to overtake the country, making life worse for millions of Afghans and imperiling US national security goals. +
++Women’s rights “will go back to the Stone Age,” Milley said, according to two of the sources. He argued that it wasn’t worth leaving the country after “all the blood and treasure spent” there over the last two decades. He also added that, in his view, the lack of 2,500 US troops in Afghanistan would make it harder to stem threats from a nuclear-armed Pakistan. +
++“He went on for a while,” said a White House official, “and everyone was sort of like, ‘Whoa.’” The official said Milley’s plea was filled with “a lot more emotion than substance” but that “it wasn’t super logical.” +
++After Milley finished, Secretary of Defense Austin during his turn to speak said he understood that there was a lot of emotion surrounding this issue after two decades of war. But, Austin asserted, “We’re not going to make decisions based on emotion,” two of the sources said. +
++Some in the room took that comment as a direct rebuke of Milley, while others understood the secretary’s remarks as simply saying he wanted the Afghanistan review to proceed in a professional, fact-based manner. +
++In a statement after the story was published, National Security Adviser Jake Sullivan said “I will not ordinarily comment on the private deliberations of Principals Committee meetings. But I reject the characterization provided by anonymous sources of the comments made in the meeting. It’s a movie-style rendering of what was — throughout — a professional, thoughtful, fact-based deliberation.” +
++A Defense Department spokesperson said the Pentagon doesn’t comment on closed-door meetings. But a senior defense official familiar with the exchange told me that Austin was trying to convey that he preferred “a decision-making process that was as dispassionate as possible, and as deliberate and thoughtful and careful as it could be.” +
++This episode may seem at first glance to be nothing more than a brief moment of lively debate about a major policy issue in which passions momentarily ran high. And in some ways, it was just that. +
++But it also provides an important window into why successive US administrations, from Bush to Obama to Trump to Biden, have found ending the US war in Afghanistan so difficult. +
++Four American administration have overseen the conflict, and each wrestled with the same general problem: Whether doing the increasingly popular thing of ending America’s involvement in the war risks all the gains — namely a more secure Kabul and better rights for women and children — that were won in large part due to the service and sacrifice of US and allied forces over the past 20 years. +
++That’s a tough decision to make, especially when most experts believe the lives of millions in Afghanistan would get worse without US troops on the ground. What’s more, terrorist groups like al Qaeda and ISIS operate in that country, and a lack of American forces would make it harder to fight them. +
++That’s partly why Presidents Obama and Trump both vowed to end the war on their watch yet ended up leaving office with at least a few thousand troops still in the country. They were persuaded by military and civilian officials who said the US had less to lose from keeping its forces engaged in the conflict than from leaving it. +
++That was the main message in a congressional report last month from the Afghanistan Study Group, an independent, bipartisan commission of experts co-chaired by retired Marine Gen. Joseph Dunford, former Republican Sen. Kelly Ayotte, and US Institute of Peace President Nancy Lindborg. +
++Yet despite his impassioned plea to continue the fight, Milley himself told a think tank audience in December that the US had only “achieved a modicum of success” in Afghanistan after all this time. +
++“We have been in a condition of strategic stalemate where the government of Afghanistan was never going to militarily defeat the Taliban,” he acknowledged, “and the Taliban, as long as we were supporting the government of Afghanistan, is never going to militarily defeat the regime.” +
++President Joe Biden, who promised to end America’s involvement in the war by the end of his first term, has yet to make a final decision about what to do ahead of the May 1 deadline. Multiple sources say all options remain on the table, including the complete withdrawal one. +
++The Milley-Austin exchange shows just how difficult — and emotionally charged — that decision will ultimately be. +
+March 4 was supposed to be a big day for QAnon. It didn’t happen. +
++A threat against the Capitol that prompted House of Representatives leadership to cancel Thursday’s session thankfully amounted to nothing. +
++Capitol Police warned on Wednesday that they “obtained intelligence that shows a possible plot to breach the Capitol by an unidentified militia group on Thursday, March 4.” That finding was echoed by Rep. Michael McCaul (R-TX), the leading Republican on the homeland security committee, who said on CNN on Wednesday that “President Trump has a responsibility to tell them to stand down. This threat is credible. It’s real. It’s a right-wing militia group.” +
+++Rep. Michael McCaul says fmr. Pres. Trump has a responsibility to tell extremists, who believe Trump will be inaugurated on March 4, and who the FBI say are plotting a possible attack on the US Capitol, to stand down. “This threat is credible. It’s real.” https://t.co/txZq2tbwMH pic.twitter.com/n4X4WbwTIo +
+— The Lead CNN (@TheLeadCNN) March 3, 2021 +
+Trump did not tell anybody to stand down, but thankfully all was quiet anyway around the Capitol on Thursday, where the Senate began debate on the $1.9 trillion Covid-19 relief bill despite the House’s decision to shut down for the day. +
++March 4 is a significant date in QAnon — a cultish, deranged conspiracy theory whose adherents believe Donald Trump is secretly fighting a global child sex trafficking cabal led by prominent Democrats. Vox’s Nicole Narea explains the theory’s fixation with March 4 in all its convoluted detail, but in brief: Some believers held that March 4, which was the date presidents were inaugurated until the 20th Amendment was adopted in 1933, would be when Trump would be inaugurated for another term of office. The Trump International Hotel located just blocks away from the White House even tried to capitalize on the conspiracy theory by raising room rates for the date. +
++But Jared Holt told Vox that he “did not find any of the usual tells we tend to see when online extremism is about to translate into real-world mobilization prior to March 4.” Holt is a resident fellow at DFRLab focused on domestic extremism; he correctly warned in the days leading up to the January 6 insurrection about internet chatter indicating pro-Trump demonstrations that day could spiral out of control. +
++“In recent days, even, many extremist influencers and communities actively discouraged participation in any would-be action on that date,” continued Holt in a Twitter direct message. “Although large mobilization was incredibly unlikely by standard measures, there continued to exist an ever-present risk posed by small groups or individuals who may feel compelled to act on their extremist beliefs.” +
++Holt noted that while the House’s decision to shut down for the day and all the security precautions around the Capitol “may seem like overkill,” the January 6 insurrection that left five dead “is still incredibly fresh on the minds of law enforcement and I’m not surprised that officials are acting with an abundance of caution.” +
++Indeed, law enforcement officials seemed to be trying to avoid a repeat of what happened on January 6, when numerous intelligence memos warning about the threat of violence from Trump supporters who gathered in Washington, DC, to protest the election on the day weren’t sufficient to prevent law enforcement from being overwhelmed by the MAGA mob. +
++While law enforcement officials are being extra careful these days, Republicans who egged on the insurrection by spreading lies about the 2020 election are not. On Thursday, Rep. Michael Waltz (R-FL) and Sen. Josh Hawley (R-MO) — both of whom supported Trump’s efforts to overthrow the election — went on Fox & Friends and argued that despite the active threat at the Capitol, they saw no need for the National Guard’s continued presence. +
++“I think the idea of keeping [the National Guard] there indefinitely, and keeping a barbed wire fence around the Capitol indefinitely is crazy,” Hawley said. +
++++On the day that the House is shut down because of a threat of violence, pro-insurrection Sen. Josh Hawley rails against National Guard troops being stationed at the Capitol pic.twitter.com/LIjTKmzbFU +
+— Aaron Rupar (@atrupar) March 4, 2021 +
+But if Trump-supporting Republicans really wanted to reopen the Capitol, the best thing they could do is denounce the lies and conspiracy theories about the 2020 election that continue to inspire deranged Trump supporters to try and take matters into their own hands. Instead of doing that, however, the Republican Party remains largely unified behind the false notion that Joe Biden’s victory was tainted. +
++While Republicans like Hawley and Waltz see no need for the continued National Guard presence at the Capitol, Capitol Police disagree. On Thursday, the force reportedly requested that the National Guard stay at the Capitol for at least two more months, citing ongoing security concerns. That request came a day after a House hearing where Capitol Police acting Chief Yogananda Pittman told lawmakers that threats against lawmakers have increased nearly 100 percent year over year. +
+Shikha Pandey’s omission a tough call but she is not dropped: Harmanpreet - The Indian women’s team will play five ODIs and three T20Is against South Africa, starting in Lucknow on Sunday
Delhi Capitals co-owner JSW group named as principal sponsor of IPL franchise - Indian Premier League side Delhi Capitals on Friday named its co-owners JSW Group as team’s principal sponsor for a three-year term. As per the agre
Ind vs Eng fourth Test | Rishabh Pant smashes hundred as India seize control from England - Visitors managed to make inroads every time when a partnership seemed to be on the horizon.
Good day for Maruri sisters - Eighth seed Suhitha Maruri beat top seed Sarah Dev 6-3, 6-2 to make the final of the ITF grade-4 junior tennis her on Thursday. In the final, Suhitha
Pooja in semis, Lovlina out - Asian champion Pooja Rani (75kg) entered the semifinals, but two-time World bronze-winner Lovlina Borgohain (69kg) bowed out after a quarterfinal loss
Don’t accept gifts, money from candidates, voters urged - The Youth for Anti-Corruption urged the voters not to accept any gifts and money from candidates during the municipal elections to ensure free and fai
Bandh evokes good response in Srikakulam district - State govt. not trying to stop the privatisation of steel plant, alleges CITU
Akali MLAs evicted amid ruckus in Punjab House - Assembly resolution calls for withdrawal of three Central farm laws
Assam Assembly elections 2021 | BJP snub over nomination revives AGP faction in Assam - With former CM Mahanta denied a ticket, the break-away faction may join the Congress-led alliance
I-T raids on Taapsee, Anurag Kashyap: FM says they were raided in 2013 as well - In comments seen as defending income tax raids on Bollywood actor Taapsee Pannu and filmmaker Anurag Kashyap, Finance Minister Nirmala Sitharaman on
Brexit: EU legal action imminent over UK extension to grace periods - The UK says it will unilaterally extend grace periods for Irish Sea border checks on parcels and agri-foods.
Covid: Italy ‘blocks’ AstraZeneca vaccine shipment to Australia - The bar on shipping 250,000 doses amid a row with the firm is backed by the EU.
Covid-19: Cyprus to welcome vaccinated UK tourists from May - It is not yet clear how visitors will be required to prove they have received both doses of a jab.
Covid-19: Another new variant added to UK watch list - It shares a worrying mutation with the South Africa and Brazil variants of concern.
Coronavirus: Hairdressers reopen in the Netherlands - Hairdressers in the Netherlands have reopened after being shut since December.
Rocket Report: SpaceX explains landing failure, More on New Glenn delays - “The level of detail that we get is remarkable, how good the forecast is.” - link
Chairs Technica: We review two new models from Anda Seat - We liked the Anda Fnatic so much, we’re reviewing two new models as well. - link
Meet Maxwell’s gambling demon—smart enough to quit while it’s ahead - Physicists even demonstrated the basic principle in a nanoscale electronic device. - link
US roads got more dangerous in 2020 even though we stayed at home - Preliminary data puts the death toll at 42,060, with 4.8 million people injured. - link
Valve scraps revamped Artifact, dumps free, unfinished “2.0” version on Steam - Rebuilt game had been in closed beta for one year before Valve pulled the plug today. - link
+They said, “Is this your wife, sir?” Shocked, I answered, “Yes.” +
++They said, “I’m afraid it looks like she’s been hit by a bus.” +
++I said, “I know, but she has a lovely personality.” +
+ submitted by /u/blackshadowed
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+Chewie is short for Chewbacca +
++Ani is short for Anakin Skywalker +
++What is Luke short for? +
++A stormtrooper +
+ submitted by /u/bria9509
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+Therapist: I think you might be getting carried away. +
++Me: NOT WITHOUT A FIGHT I’M NOT!!! +
+ submitted by /u/JadenYuki15
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+An engineer dies and reports to the Pearly Gates. Saint Peter checks his dossier and, not seeing his name there, accidentally sends him to Hell. +
++It doesn’t take long before the engineer becomes rather dissatisfied with the level of comfort in Hell. He soon begins to design and build improvements. Shortly thereafter, Hell has air conditioning, flush toilets and escalators. Needless to say, the engineer is a pretty popular guy. +
++One day, God calls Satan and says with a sneer: “So, how are things in Hell?” +
++Satan replies: “Hey, things are going great. We’ve got air conditioning, flush toilets, and escalators. And there’s no telling what this engineer is going to come up with next.” +
++“What!” God exclaims: “You’ve got an engineer? That’s a mistake – he should never have been sent to Hell… send him to me.” +
++“Not a chance,” Satan replies: “I like having an engineer on the staff, and I’m keeping him!” +
++God insists: “Send him back or I’ll sue.” +
++Satan laughs uproariously and answers: “Yeah, right. And where are you going to get a lawyer?” +
+ submitted by /u/raknor88
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+It was his life savings. +
+ submitted by /u/WarlikeDisco
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