Emergence of SARS-CoV-2 stains harbouring the signature mutations of both A2a and A3 clade -
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+SARS-CoV-2 strains with both high transmissibility and potential to cause asymptomatic infection is expected to gain selective advantage over other circulating strains having either high transmissibility or ability to trigger asymptomatic infection. The D614G mutation in spike glycoprotein, the characteristic mutation A2a clade, has been associated with high transmissibility, whereas the A3 clade specific mutation L37F in NSP6 protein has been linked with asymptomatic infection. In this study, we performed a comprehensive mutational analysis of 3,77,129 SARS-CoV-2 genomes collected during January, 2020 to December, 2020 from all across the world for the presence of D614G and L37F mutations. Out of 3,77,129 SARS-CoV-2 strains analysed, 14, 598 (3.87%) were found to harbour both the D614G and L37F mutations. Majority of these double mutant SARS-CoV-2 strains were identified in Europe (11097) followed by North America (1915), Asia (980), Oceania (242), Africa (219), and South America (145). Geographical root surveillance revealed their first emergence during February-March in all the six continents. Temporal prevalence analysis from February, 2020 to December, 2020 showed a gradual upsurge in their frequencies worldwide, which strongly demonstrated the adaptive selection of these double mutants. Evolutionary analysis depicted that these double mutants emerged as a new clade in the dendrogram (named as A2a/3), and were sub-divided into four distinct clusters (Cluster I, II, III and IV) according to different sets of coexisting mutations. The frequency distribution pattern showed the global predominance of cluster III (41.42%), followed by cluster IV (23.31%), cluster II (21.02%) and cluster I (14.25%). Overall, our study highlighted the emergence of a unique phylogenetic clade encompassing the double-mutant SARS-CoV-2 strains which may provide a fitness advantage during course of virus evolution.
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Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial -
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+Background Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. Methods We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. Results 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Conclusion Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.
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Implementation of an in-house real-time reverse transcription-PCR assay for the rapid detection of the SARS-CoV-2 Marseille-4 variant -
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+Introduction. The SARS-CoV-2 pandemic has been associated with the occurrence since summer 2020 of several viral variants that overlapped or succeeded each other in time. Those of current concern harbor mutations within the spike receptor binding domain (RBD) that may be associated with viral escape to immune responses. In our geographical area a viral variant we named Marseille-4 harbors a S477N substitution in this RBD. Materials and methods. We aimed to implement an in-house one-step real-time reverse transcription-PCR (qPCR) assay with a hydrolysis probe that specifically detects the SARS-CoV-2 Marseille-4 variant. Results. All 6 cDNA samples from Marseille-4 variant strains identified in our institute by genome next-generation sequencing (NGS) tested positive using our Marseille-4 specific qPCR, whereas all 32 cDNA samples from other variants tested negative. In addition, 39/42 (93%) respiratory samples identified by NGS as containing a Marseille-4 variant strain and 0/26 samples identified as containing non-Marseille-4 variant strains were positive. Finally, 1,585/2,889 patients SARS-CoV-2-diagnosed in our institute, 10/277 (3.6%) respiratory samples collected in Algeria, and none of 207 respiratory samples collected in Senegal, Morocco, or Lebanon tested positive using our Marseille-4 specific qPCR. Discussion. Our in-house qPCR system was found reliable to detect specifically the Marseille-4 variant and allowed estimating it is involved in more than half of our SARS-CoV-2 diagnoses since December 2020. Such approach allows the real-time surveillance of SARS-CoV-2 variants, which is warranted to monitor and assess their epidemiological and clinical characterics based on comprehensive sets of data.
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SARS-CoV-2 Transmission Risk from sports Equipment (STRIKE) -
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+OBJECTIVES: To investigate the potential of shared sporting equipment as transmission vectors of SARS-CoV-2 during the reintroduction of sports such as soccer, rugby, cricket, tennis, golf and gymnastics. SETTING: Laboratory based live SARS-CoV-2 virus study. INTERVENTIONS: Ten different types of sporting equipment were inoculated with 40μl droplets containing clinically relevant high and low concentrations of live SARS-CoV-2 virus. Materials were then swabbed at time points relevant to sports (1, 5, 15, 30, 90 minutes). The amount of live SARS-CoV-2 recovered at each time point was enumerated using viral plaque assays, and viral decay and half-life was estimated through fitting linear models to log transformed data from each material. MAIN OUTCOME MEASURE: The primary outcome measure was quantification of retrievable SARS-CoV-2 virus from each piece of equipment at pre-determined time points. RESULTS: At one minute, SARS-CoV-2 virus was recovered in only seven of the ten types of equipment with the low dose inoculum, one at five minutes and none at 15 minutes. Retrievable virus dropped significantly for all materials tested using the high dose inoculum with mean recovery of virus falling to 0.74% at 1 minute, 0.39% at 15 minutes and 0.003% at 90 minutes. Viral recovery, predicted decay, and half-life varied between materials with porous surfaces limiting virus transmission. CONCLUSIONS: This study shows that there is an exponential reduction in SARS-CoV-2 recoverable from a range of sports equipment after a short time period, and virus is less transferrable from materials such as a tennis ball, red cricket ball and cricket glove. Given this rapid loss of viral load and the fact that transmission requires a significant inoculum to be transferred from equipment to the mucous membranes of another individual it seems unlikely that sports equipment is a major cause for transmission of SARS-CoV-2. These findings have important policy implications in the context of the pandemic and may promote other infection control measures in sports to reduce the risk of SARS-CoV-2 transmission and urge sports equipment manufacturers to identify surfaces that may or may not be likely to retain transferable virus.
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Conspiracy theories and their societal effects during the COVID-19 pandemic -
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+During COVID-19, conspiracy theories were intensely discussed in the media. Believing in specific conspiracy theories (i.e., explanations for events based on powerholders’ secret arrangements) as well as the general tendency to believe in conspiracy theories—a so-called conspiracy mentality—have been found to predict cognition and behavior with negative societal effects, such as low institutional trust. Accordingly, believing in conspiracy theories around COVID-19 should work against institutional trust, support of governmental regulations and their adoption, as well as societal engagement (e.g., helping members of risk groups). We tested these predictions in a national random sample, an experimental study, and a longitudinal study (Ntotal = 1,213; all studies preregistered). Indeed, believing in and being confronted with a COVID-19 conspiracy theory decreased institutional trust, support of governmental regulations, adoption of physical distancing, and—to some extent—social engagement. Findings underscore that conspiracy theories have severe societal effects in the context of COVID-19.
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Information Dissemination and the COVID-19 Pandemic: The Relationship between Different Information Sources and Symptoms of Psychopathology -
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+The 2020-2021 COVID-19 pandemic has added to the mental health strain on individuals and groups across the world. Viral mitigation protocols and viral spread affect millions every day, but to widely different degrees. How individuals gather information about the pandemic might have an effect on levels of mental distress in the population. In this cross-sectional and representative study of the adult population of Norway, findings suggest that information gathered through newspapers and social media are the information pathways with the strongest association to symptoms of anxiety, depression and health anxiety with small to medium effect sizes. However, avoiding information about the pandemic had larger effect sizes related to symptoms of psychopathology than acquiring information about the pandemic from any source. The results suggest that to reach those who avoid pandemic news is an important goal, both to ensure the population as a whole gets relevant information regarding current viral mitigation protocols, that may in turn alleviate stress, and thus reduce the likelihood of viral transmission. The spread of pandemic misinformation on social media and the internet must be buffered, and successful interventions against misinformation may affect the mental health of the population.
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Underweighting of rare events in social interactions and its implications to the design of voluntary health applications -
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+Research on small decisions from experience suggests that people often behave as if they underweight rare events and choose the options that are frequently better. In a pandemic, this tendency implies complacency and reckless behavior. Furthermore, behavioral contagion exacerbates this problem. In two pre-registered experiments (Ntotal = 312), we validate these predictions and highlight a potential solution. Groups of participants played a repeated social game in one of two versions. In the basic version, people clearly preferred the dangerous reckless behavior that was better most of the time over the safer responsible behavior. In the augmented version, we gave participants an additional alternative abstracting the use of an application that frequently saves time but can sometimes have high costs. This alternative was stochastically dominated by the option abstracting the responsible choice and was thus normatively “irrelevant” to the decision participants made. Nevertheless, most people chose the new (“irrelevant”) alternative, providing the first clear demonstration of underweighting of rare events in fully described social games. We discuss public policies that can make the responsible use of health applications better most of the time, thus helping them get traction despite being voluntary. In one field demonstration of this idea amid the COVID-19 pandemic, usage rates of a contact tracing application among nursing home employees more than tripled when using the app also started saving them little time on a daily basis, and the high usage rates sustained over at least four weeks.
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Social Inequalities in Mobility During and Following the COVID-19 associated lockdown of the Madrid Metropolitan Area in Spain -
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+Spain has been one of the most affected regions by the COVID-19 worldwide, and Madrid its most affected city. In response to this, the Spanish government enacted a strict lockdown in late March, that was gradually eased until June. We explored differentials in mobility by area-level deprivation in the functional area of Madrid, before, during, and after the COVID-19 lockdown. We used cell phone-derived mobility indicators (% of the population leaving their area) from the National Institute of Statistics (INE), and a composite measure of deprivation from the Spanish Society of Epidemiology (SEE). We computed changes in mobility with respect to pre-pandemic levels, and explored spatial patterns and associations with deprivation. We found that levels of mobility before COVID-19 were slightly higher in areas with lower deprivation. The economic hibernation period resulted in very strong declines in mobility, most acutely in low deprivation areas. These differences weakened during the re-opening, and levels of mobility were similar by deprivation once the lockdown was lifted. Given the existence of important socioeconomic differentials in COVID-19 exposure, it is key to ensure that these interventions do not widen existing social inequalities.
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Mask-wearing and social distancing: Evidence from a video-observational and natural-experimental study of public space behavior during the COVID-19 pandemic -
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+Background: Face masks have been widely employed as a personal protective measure during the COVID-19 pandemic. However, concerns remain that masks create a false sense of security that reduces adherence to other public health measures, including social distancing. Purpose: This paper tested whether mask-wearing was negatively associated with social distancing compliance. Methods: In two studies, we combined video-observational records of public mask-wearing in two Dutch cities with a natural-experimental approach to evaluate the effect of an area-based mask mandate. Results: We found no observational evidence of an association between mask-wearing and social distancing (Study 1: p = .398; Study 2: p = .511), but found a positive link between crowding and social distancing violations (Study 1: p < .001; Study 2: p < .001). Our natural-experimental analysis showed that an area-based mask mandate did not significantly affect social distancing or crowding levels (Study 2: p = .781 and p = .126, respectively). Conclusions: Our results alleviate the concern that mask use reduces social distancing compliance or increases crowding levels. On the other hand, crowding reduction may be a viable strategy to mitigate social distancing violations.
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University Students’ Adherence to the COVID-19-guidelines: A Qualitative Study on Facilitators and Barriers -
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+Objective. This study aims to explore students’ adherence and reasons behind the (non)adherence to the COVID-19-regulations within a university setting. Methods. A total of 33 students participated in on-site and online focus group interviews (k=8). Discussed topics included the general COVID-19-guidelines of the university, including keeping ≥1.5 m distance, staying at home and getting tested when having symptoms, and wearing facemasks. Additionally, education and psychosocial wellbeing in the times of COVID-19 were discussed. We also conducted online interviews with stewards (2 focus group interviews and 1 individual interview) and security/crowd control officials (1 focus group interview) to learn more about students’ (non)adherence behaviors. Results. The findings of this study show that the interviewed students were willing to adhere to the guidelines within the university buildings. They mentioned several facilitators (e.g., the infrastructure of the buildings and staff) and barriers (e.g., being together with friends and difficulties with telling others to follow the regulations) for their compliance behaviors. Some students also stated that they are not afraid of COVID-19 because they are young, while others adhered to the regulations to protect vulnerable people. Conclusion. To create a safe environment within the university and alleviate the spread of the virus, future interventions require targeting the determinants of students’ non-adherence behaviors, such as lower risk perception (e.g., being young and no perceived threat/low vulnerability) and lower self-efficacy (e.g., for keeping distance, to determine symptoms for testing/isolating and to correct others).
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Self-assembling SARS-CoV-2 nanoparticle vaccines targeting the S protein induces protective immunity in mice -
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+The spike (S), a homotrimer glycoprotein, is the most important antigen target in the research and development of SARS-CoV-2 vaccine. There is no doubt that fully simulating the advanced structure of this homotrimer in the subunit vaccine development strategy is the most likely way to improve the immune protective effect of the vaccine. In this study, the preparation strategies of S protein receptor-binding domain (RBD) trimer, S1 region trimer, and ectodomain (ECD) trimer nanoparticles were designed based on ferritin nanoparticle self-assembly technology. The Bombyx mori baculovirus expression system was used to prepare these three nanoparticle vaccines with high expression levels in the silkworm. The immune results of mice show that the nanoparticle vaccine prepared by this strategy can not only induce an immune response by subcutaneous administration but also effective by oral administration. Given the stability of these ferritin-based nanoparticles vaccine, easy-to-use and low-cost oral immunization strategy can make up for the vaccination blind areas caused by the shortage of ultralow-temperature equipment and medical resources in underdeveloped areas. And the oral vaccine is also a very potential candidate to cut off the spread of SARS-CoV-2 in domestic and farmed animals, especially in stray and wild animals.
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SARS-CoV-2 infects brain astrocytes of COVID-19 patients and impairs neuronal viability -
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+COVID-19 patients may exhibit neuropsychiatric and neurological symptoms. Here we found that anxiety and cognitive impairment are manifested by 28-56% of COVID-19 convalescent individuals with mild respiratory symptoms and are associated with altered cerebral cortical thickness. Using an independent cohort, we found histopathological signs of brain damage in 25% of individuals who died of COVID-19. All of the affected brain tissues exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. We also found that neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons and in the biogenesis of neurotransmitters, and elicited a secretory phenotype that reduces neuronal viability. Our data support the model where SARS-CoV-2 reaches the brain, infects astrocytes and consequently leads to neuronal death or dysfunction. These processes are likely to contribute to the structural and functional alterations in the brain of COVID-19 patients.
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Insights on SARS-CoV-2’s Mutations for Evading Human Antibodies: Sacrifice and Survival -
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+Recent mutations on the receptor binding domain (RBD) of the SARS-CoV-2’s spike protein have been manifested as the major cause of the wide and rapid spread of the virus. Especially, the variant B.1.351 in South Africa with the hallmark of triple mutations (N501Y, K417N and E484K) is worrisome. Quickly after the outbreak of this new variant, several studies showed that both N501Y and E484K can enhance the binding between RBD and the human ACE2 receptor. However, the mutation K417N seems to be unfavorable because it removes one interfacial salt-bridge. So far, it is still not well understood why the K417N mutation is selected in the viral evolution. Here, we show that despite the loss in the binding affinity (1.48 kcal/mol) between RBD and ACE2 the K417N mutation abolishes a buried interfacial salt-bridge between RBD and the neutralizing antibody CB6 and thus substantially reduces their binding energy by 9.59 kcal/mol, facilitating the variants to efficiently elude CB6 (as well as many other antibodies). Thus, when proliferating from person to person the virus might have adapted to the human immune system through evasive mutations. Taking into account limited and relevant experimental works in the field, we show that our theoretical predictions are consistent with existing experimental findings. By harnessing the revealed molecular mechanism for variants, it becomes feasible to redesign therapeutic antibodies accordingly to make them more efficacious.
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The local topological free energy of the SARS-CoV-2 Spike protein -
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+The novel coronavirus SARS-CoV-2 infects human cells using a mechanism that involves binding and structural rearrangement of its spike protein. Understanding protein rearrangement and identifying specific residues where mutations affect protein rearrangement has attracted a lot of attention for drug development. We use a mathematical method introduced in (Baldwin2021) to associate a local topological/geometrical free energy along the SARS-CoV-2 spike protein backbone. Our results show that the total local topological free energy of the SARS-CoV-2 spike protein monotonically decreases from pre-to post-fusion and that its distribution along the protein domains is related to their activity in protein rearrangement. By using density functional theory (DFT) calculations with inclusion of solvent effects, we show that high local topological free energy conformations are unstable compared to those of low topological free energy. By comparing to experimental data, we find that the high local topological free energy conformations in the spike protein are associated with mutations which have the largest experimentally observed effect to protein rearrangement.
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Targeting CTP Synthetase 1 to Restore Interferon Induction and Impede Nucleotide Synthesis in SARS-CoV-2 Infection -
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+The newly emerged SARS-CoV-2 caused a global pandemic with astonishing mortality and morbidity. The mechanisms underpinning its highly infectious nature remain poorly understood. We report here that SARS-CoV-2 exploits cellular CTP synthetase 1 (CTPS1) to promote CTP synthesis and suppress interferon (IFN) induction. Screening a SARS-CoV-2 expression library identified ORF7b and ORF8 that suppressed IFN induction via inducing the deamidation of interferon regulatory factor 3 (IRF3). Deamidated IRF3 fails to bind the promoters of classic IRF3-responsible genes, thus muting IFN induction. Conversely, a shRNA-mediated screen focused on cellular glutamine amidotransferases corroborated that CTPS1 deamidates IRF3 to inhibit IFN induction. Functionally, ORF7b and ORF8 activate CTPS1 to promote de novo CTP synthesis while shutting down IFN induction. De novo synthesis of small-molecule inhibitors of CTPS1 enabled CTP depletion and IFN induction in SARS-CoV-2 infection, thus impeding SARS-CoV-2 replication. Our work uncovers a strategy that a viral pathogen couples immune evasion to metabolic activation to fuel viral replication. Inhibition of the cellular CTPS1 offers an attractive means for developing antiviral therapy that would be resistant to SARS-CoV-2 mutation.
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Study to Evaluate the Safety and Efficacy of a Single Dose of STI-2020 (COVI-AMG™) to Treat COVID-19 - Condition: Covid19 Interventions: Biological: COVI-AMG; Drug: Placebo Sponsor: Sorrento Therapeutics, Inc. Not yet recruiting
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Study to Evaluate a Single Dose of STI-2020 (COVI-AMG™) in Adults With Mild COVID-19 Symptoms - Condition: Covid19 Interventions: Biological: COVI-AMG; Drug: Placebo Sponsor: Sorrento Therapeutics, Inc. Not yet recruiting
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Phase III Study of AZD7442 for Treatment of COVID-19 in Outpatient Adults - Condition: COVID-19 Interventions: Drug: AZD7442; Drug: Placebo Sponsor: AstraZeneca Not yet recruiting
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Telerehabilitation in Covid-19 After Hospital Discharge - Condition: Covid19 Intervention: Other: Telerehabilitation intervention Sponsor: Universidad de Granada Not yet recruiting
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TOCILIZUMAB - An Option for Patients With COVID-19 Associated Cytokine Release Syndrome; A Single Center Experience - Condition: Covid19 Intervention: Drug: Tocilizumab Sponsor: FMH College of Medicine and Dentistry Completed
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Convalescent Plasma in the Treatment of Covid-19 - Condition: Covid19 Interventions: Biological: Convalescent plasma from COVID-19 donors; Biological: Placebo Sponsors: Helsinki University Central Hospital; Finnish Red Cross Recruiting
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A Study to Evaluate the Efficacy and Safety of VB-201 in Patients With COVID-19 - Condition: Severe COVID-19 Interventions: Drug: VB-201 + Standard of care; Drug: Standard of care Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics Recruiting
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Efficacy of Nano-Ivermectin Impregnated Masks in Prevention of Covid-19 Among Healthy Contacts and Medical Staff - Condition: Covid-19 Intervention: Other: ivermectin impregnated mask Sponsor: South Valley University Recruiting
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An Outpatient Clinical Trial Using Ivermectin and Doxycycline in COVID-19 Positive Patients at High Risk to Prevent COVID-19 Related Hospitalization - Condition: Covid19 Interventions: Drug: Ivermectin Tablets; Drug: Doxycycline Tablets; Drug: Placebo Sponsor: Max Health, Subsero Health Recruiting
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CPI-006 Plus Standard of Care Versus Placebo Plus Standard of Care in Mild to Moderately Symptomatic Hospitalized Covid-19 Patients - Condition: Covid-19 Interventions: Drug: CPI-006 2 mg/kg + SOC; Drug: CPI-006 1 mg/kg + SOC; Drug: Placebo + SOC Sponsor: Corvus Pharmaceuticals, Inc. Recruiting
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Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients - Condition: Covid19 Intervention: Drug: Ivermectin Sponsor: FMH College of Medicine and Dentistry Completed
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Famotidine vs Placebo for the Treatment of Non-Hospitalized Adults With COVID-19 - Condition: Covid-19 Interventions: Drug: Famotidine; Drug: Placebo Sponsors: Northwell Health; Cold Spring Harbor Laboratory Recruiting
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Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19 - Conditions: Severe Acute Respiratory Syndrome Coronavirus 2; COVID-19 Interventions: Drug: SNG001; Drug: Placebo Sponsor: Synairgen Research Ltd. Recruiting
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COVID-19 and Pregnancy: Placental and Immunological Impacts - Condition: Covid19 Intervention: Other: Specimens specific for the study Sponsor: Hopital Foch Recruiting
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A Study to Evaluate the Efficacy and Safety of Prothione™ Capsules for Mild to Moderate Coronavirus Disease 2019 (COVID-19) - Condition: Coronavirus Disease 2019 (COVID-19) Interventions: Drug: Placebo; Drug: Prothione™ (6g) Sponsor: Prothione, LLC Not yet recruiting
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From PubMed
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Avelumab, a PD-L1 Inhibitor, in Combination with Hypofractionated Radiotherapy and the Abscopal Effect in Relapsed Refractory Multiple Myeloma - CONCLUSION: Avelumab in combination with radiotherapy for patients with RRMM and EMD was associated with very modest systemic clinical benefit; however, patients did benefit as usual from local radiotherapy. Furthermore, the combination was very well tolerated compared with historical RRMM treatment regimens.
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Recent updates in the clinical trials of therapeutic monoclonal antibodies targeting cytokine storm for the management of COVID-19 - Clinical studies have identified a cytokine storm in the third stage of disease progression in critical ill patients with coronavirus disease 2019 (COVID-19). Hence, effectively suppressing the uncontrolled immune response of the host towards the invaded viruses in a cytokine storm is a critical step to prevent the deterioration of patient conditions and decrease the rate of mortality. Therapeutic monoclonal antibodies (mAbs) are found to be effective for the management of acute respiratory…
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The screening and evaluation of potential clinically significant HIV drug combinations against the SARS-CoV-2 virus - Spike glycoprotein is essential for the reproduction of the SARS-CoV-2 virus, and its inhibition using already approved antiviral drugs may open new avenues for treatment of patients with the COVID-19 disease. Because of that we analyzed the inhibition of SARS-CoV-2 spike glycoprotein with FDA-approved antiviral drugs and their double and triple combinations. We used the Vini in silico model of cancer to perform this virtual drug screening, showing HIV drugs to be the most effective. Besides,…
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Recent Advances in Systemic Therapies for Advanced Hepatocellular Carcinoma - PURPOSE OF REVIEW: This paper aims to summarize the data of recently completed and key ongoing clinical trials of systemic agents for advanced hepatocellular carcinoma (aHCC). In particular, the review focuses on ongoing checkpoint inhibitor combination trials and promising studies combining tyrosine kinase inhibitors with checkpoint inhibitors.
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Mechanistic insight into anti-COVID-19 drugs: recent trends and advancements - The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has been established now to be a deadly disease afflicting the whole world with worst consequences on healthcare, economy and day-to-day life activities. Being a communicable disease, which is highly pathogenic in humans, causing cough, throat infection, breathing problems, high fever, muscle pain, and may lead to death in some cases especially those having other comorbid conditions such as heart or kidney problems, and diabetes….
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Delving Into the Origin of Destructive Inflammation in COVID-19: A Betrayal of Natural Host Defense Peptides? - In contrast to other pathogenic agents that directly destroy host cells and tissues, the lethal power of SARS-CoV-2 resides in the over-reactive immune response triggered by this virus. Based on numerous evidences indicating that the lipid composition of host membranes is dramatically affected by COVID-19, and in the fact that our endogenous antimicrobial peptides (AMPs) are sensitive to the membrane composition of pathogenic agents, we propose that such destructive immune response is due to the…
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CSF3 Is a Potential Drug Target for the Treatment of COVID-19 - Coronavirus Disease 2019 (COVID-19) is an acute respiratory infectious disease that appeared at the end of 2019. As of July 2020, the cumulative number of infections and deaths have exceeded 15 million and 630,000, respectively. And new cases are increasing. There are still many difficulties surrounding research on the mechanism and development of therapeutic vaccines. It is urgent to explore the pathogenic mechanism of viruses to help prevent and treat COVID-19. In our study, we downloaded two…
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The computational intervention of macrolide antibiotics in the treatment of COVID-19 - The spike (S) glycoprotein of SARS coronavirus (SARS-CoV-2) and human Angiotensin-converting enzyme 2 (ACE2), are both considered the key factors for the initiation of virus infection. The present work is an effort for a computational target to block the spike proteins (S) and ACE2 receptor proteins with Macrolide antibiotics like Azithromycin, (AZM), Clarithromycin (CLAM) and Erythromycin (ERY) along with RNA-dependent RNA polymerase (RdRp). These compounds were able to block the residues…
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COVID-19 patients often show high-titer non-platelet-activating anti-PF4/heparin IgG antibodies - CONCLUSION: COVID-19 patients often present with strong reactivity in PF4/heparin antigen tests without the presence of platelet-activating antibodies. Diagnosis of HIT requires confirmation of heparin-dependent, platelets activating antibodies to avoid overdiagnosis and overtreatment with non-heparin anticoagulants.
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Novel insights into impacts of the COVID-19 pandemic on aquatic environment of Beijing-Hangzhou Grand Canal in southern Jiangsu region - In 2020, a sudden COVID-19 pandemic unprecedentedly weakened anthropogenic activities and as results minified the pollution discharge to aquatic environment. In this study, the impacts of the COVID-19 pandemic on aquatic environment of the southern Jiangsu (SJ) segment of Beijing-Hangzhou Grand Canal (SJ-BHGC) were explored. Fluorescent component similarity and high-performance size exclusion chromatography analyses indicated that the textile printing and dyeing wastewater might be one of the…
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SARS-CoV-2: From the pathogenesis to potential anti-viral treatments - INTRODUCTION: The world is witnessing the spread of one of the members of Coronaviruses (CoVs) family, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the 21st century. Considering the short time spent after its prevalence, limited information is known about the effect of the virus mechanism on different organs of the body; meanwhile the lack of specific treatment and vaccine for this virus has exposed millions of people to a big challenge.
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Genetic Conservation of SARS-CoV-2 RNA Replication Complex in Globally Circulating Isolates and Recently Emerged Variants from Humans and Minks Suggests Minimal Pre-Existing Resistance to Remdesivir - Remdesivir (RDV) exhibits potent antiviral activity against SARS-CoV-2 and is currently the only drug approved for the treatment of COVID-19. However, little is currently known about the potential for pre-existing resistance to RDV and the possibility of SARS-CoV-2 genetic diversification that might impact RDV efficacy as the virus continue to spread globally. In this study, >90,000 SARS-CoV-2 sequences from globally circulating clinical isolates, including sequences from recently emerged United…
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A Critical Appraisal of the Effects of Anesthetics on Immune-system Modulation in Critically Ill Patients with COVID-19 - PURPOSE: The aim of the present article was to briefly summarize current knowledge about the immunomodulatory effects of general anesthetics and the possible clinical effects of this immunomodulation in patients with COVID-19.
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Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2 - SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued. Here, we report that…
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Nsp1 protein of SARS-CoV-2 disrupts the mRNA export machinery to inhibit host gene expression - The ongoing unprecedented severe acute respiratory syndrome caused by the SARS-CoV-2 outbreak worldwide has highlighted the need for understanding viral-host interactions involved in mechanisms of virulence. Here, we show that the virulence factor Nsp1 protein of SARS-CoV-2 interacts with the host messenger RNA (mRNA) export receptor heterodimer NXF1-NXT1, which is responsible for nuclear export of cellular mRNAs. Nsp1 prevents proper binding of NXF1 to mRNA export adaptors and NXF1 docking at…
A PHARMACEUTICAL COMPOSITION OF NITAZOXANIDE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of a nitazoxanide or its pharmaceutically acceptable salts thereof and an mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the nitazoxanide in the ratio of 0.05% to 66% w/v and the mefloquine in the ratio of 0.05% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of nitazoxanide and mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. - link
METHOD AND APPARATUS FOR ACQUIRING POWER CONSUMPTION IMPACT BASED ON IMPACT OF COVID-19 EPIDEMIC - - link
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一种新冠肺炎CT检测识别定位系统及计算设备 - 本发明涉及图像处理领域，公开了一种新冠肺炎CT检测识别定位系统及计算设备，包括图像采集单元、模块建立单元、新冠肺炎病灶识别单元和新冠肺炎病灶定位单元；图像采集单元采集待识别检测新冠肺炎的CT图像、新冠肺炎CT影像病灶分割训练数据集和新冠CT图像识别训练集；模块建立单元建立U_Net卷积神经网络模型、加入注意力机制的InceptionV3网络和目标检测模型；新冠肺炎病灶识别单元对已分割出病灶的轮廓特征图像进行识别；新冠肺炎病灶定位单元确定病灶在人体肺部的位置。本发明利用U_Net卷积神经网络模型对新冠病灶检测分割，并通过加入注意力机制的网络进行新冠肺炎识别，通过目标检测模型定位病灶在肺部的位置，识别准确率高，计算速度快。 - link
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一种基于磁微粒化学发光的新型冠状病毒抗体检测试剂盒 - 本发明提供一种基于磁微粒化学发光的新型冠状病毒抗体检测试剂盒。所述检测试剂盒包括：链霉亲和素磁微粒、生物素标记的新型冠状病毒抗原、吖啶磺酰胺标记的二抗、样本稀释液和质控品；所述生物素标记的新型冠状病毒抗原包括重组核衣壳蛋白和重组棘突蛋白S1。将待检样本、生物素标记抗原与链霉亲和素磁微粒混合，孵育和洗涤，再加入吖啶磺酰胺标记的抗体，形成磁微粒‑链霉亲和素‑生物素‑抗原‑新型冠状病毒抗体‑二抗复合物，进而检测发光强度实现对待测样品的定性。 - link
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A PHARMACEUTICAL COMPOSITION OF ARTESUNATE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of an artesunate or its pharmaceutically acceptable salts thereof and a mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the artesunate in the ratio of 0.25% to 66% w/v and mefloquine in the ratio of 0.25% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of Artesunate and Mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. The present invention also discloses a method to preparing the pharmaceutical composition comprising of Artesunate and Mefloquine. - link
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Zahnbürstenaufsatz, elektrische Versorgungseinheit einer elektrischen Zahnbürste, elektrische Zahnbürste mit einem Zahnbürstenaufsatz, Zahnbürste sowie Testaufsatz für eine elektrische Zahnbürste -
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Zahnbürstenaufsatz für eine elektrische Zahnbürste (20) umfassend einen Koppelabschnitt (2), über den der Zahnbürstenaufsatz (1) mit einer elektrischen Versorgungseinheit (10) der elektrischen Zahnbürste (20) verbindbar ist und einen Bürstenabschnitt (3), der zur Reinigung der Zähne ausgebildete Reinigungsmittel (3.1) aufweist, dadurch gekennzeichnet, dass an dem Zahnbürstenaufsatz (1) eine Sensoreinheit (4) vorgesehen ist, die dazu ausgebildet ist, selektiv das Vorhandensein eines Virus oder eines Antigen im Speichel eines Nutzers des Zahnbürstenaufsatzes (1) durch Messen zumindest eines virusspezifischen Parameters zu bestimmen.
一种医用可佩戴式防护口鼻的微型气幕系统 - 本发明公开了一种医用可佩戴式防护口鼻的微型气幕系统，包括框柱，框柱一侧开凿有气幕送风口和呼吸用送风口，气幕送风口和呼吸用送风口内分别连接有软管一和软管二，框柱内开凿有水平条缝和垂直条缝，水平条缝与垂直条缝均与气幕送风口相连通，框柱靠近水平条缝的一侧贯穿开凿有出风口，出风口内设有滤网，出风口贯穿框柱的一端连接有高效过滤器，滤网与高效过滤器之间连接有吸气泵，框柱靠近出风口的一侧连接有电池和开关。本发明通过提出一种在口腔处应用洁净空气幕阻挡气溶胶传播的可佩戴装置，可以在口腔类相关诊疗过程，保护医生和周围人的健康，避免引起可能引发的呼吸道疾病交叉感染。 - link
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+ 08 February, 2021
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+Daily-Dose
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Examining the Case Against the Filibuster - In a new book, Adam Jentleson blames government failures on more than a century of Southern obstruction in the Senate. - link
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Joe Biden Is Playing It Cool with Benjamin Netanyahu - The Biden Administration’s support for the Abraham Accords is having unintended consequences for Israel’s Prime Minister. - link
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On Climate, Biden’s Administration Needs to Combat Zombie Trumpism Quickly - And Montana’s Yaak Valley is a good place to start. - link
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Can a Country Control the Virus and Host a Grand Slam? Australia Is Trying - In light of Melbourne’s long stretch of stringent lockdown measures, Australia’s decision to allow more than a thousand people into the country for a tennis tournament has been controversial. - link
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How San Francisco Renamed Its Schools - The president of the San Francisco Board of Education discusses the controversies around reopening and renaming her district’s schools, including questions about how to view the legacies of complex historical figures. - link
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From Vox
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Watch: The Weeknd’s toned-down Super Bowl halftime show was mellow but satisfying -
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+Mike Ehrmann/Getty Images
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+The typically edgy artist went for a lower-key, Covid-safe performance.
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+Prior to his Super Bowl 55 halftime performance in Tampa on Sunday, The Weeknd promised to keep his typically edgy fare much more family-friendly for the game’s millions of viewers. Typically, the fascinating star — his real name is Abel Tesfaye — delivers a heady mix of sex, drugs, and rock and roll through his music, a cocktail of R&B, hip-hop, and classic pop. The Weeknd’s halftime performance was significantly lower-key, but once it started, he had the size-limited crowd at the Raymond James Stadium fully under his thumb, with powerful vocals serving as the main draw.
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+Continuing the Las Vegas theme he began with his music videos for “Heartless” and “Blinding Lights,” The Weeknd opened the halftime show with an ethereal robot choir accompanying him to “Starboy” and “Call Out My Name,” before segueing into a dazzling chorus of “The Hills.” In the background, the set illuminated what might be keywords for a Weeknd performance, as well as for the overall pandemic mood: “touch,” “alone,” and “empty,” among others.
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+Though The Weeknd didn’t don the controversial face bandages he wore when performing at the American Music Awards last November, he one-upped that look for the Super Bowl. This time, in a brightly lit funhouse of golden mirrors, he manifested a whole crowd of face-bandaged doppelgangers, all colliding against the mirrors and each other in a rendition of “Can’t Feel My Face,” enacting the stumbling, drug-fueled stupor of the song’s theme. It was the main taste of the orgiastic cocktail of self-destruction The Weeknd’s performances usually proffer.
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+Should “Las Vegas Plastic Surgery Recovery Unit” be a show on CBS? “CSI: Las Vegas Plastic Surgery Recovery Unit?” We’ll workshop it and get back to you. @theweeknd, call us. #PepsiHalftime#SBLVpic.twitter.com/cNxYIt7wAr
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+The performance was otherwise benign — not only because The Weeknd was performing for a much larger and more all-ages audience than usual, but because Covid-19 safety protocols meant a smaller crowd at the stadium and presumably fewer opportunities for complicated onstage hijinks (or surprise cameos from guest artists). The Weeknd mostly performed solo, backed by an ensemble whose limited choreography — and at one point, violin instrumental — was mostly performed in place. When the bandaged dancers finally showed up again, it was to take over the football field like a surrealist marching band, at first all standing a rigid six feet apart.
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+In the middle, The Weeknd paraded in his now-iconic red sequin jacket, skipping into an intense, bouncy rendition of “Blinding Lights” — the song that arguably won him this Super Bowl gig in the first place.
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+The Weeknd has frequently drawncomparisons to Michael Jackson, one of his biggest artistic influences, and the scene gave off a definite “Thriller vibe,” with the choreography getting progressively more unhinged and erratic. The halftime show ended with The Weeknd walking off the field solo after razing the field of his dopples, who lay as if dead — perhaps felled by the force of The Weeknd’s concert intensity.
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+All in all, even though this was an unlikely halftime show featuring an unlikely performer at an uncertain Super Bowl, it was exactly the halftime show we needed. The Weeknd strode through it with confidence and charm, reminding viewers that even though plenty is different in 2021, the most important things — including the music and the magic of live performance — remain the same.
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Trump’s impeachment trial is imminent. GOP senators are working to cast it as a Democratic plot. -
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+Sen. Ron Johnson, who asked Sunday if the Senate trial is a “diversionary operation,” speaks at Linda Thomas-Greenfield’s confirmation hearing as UN ambassador. | Michael Reynolds/AFP/Getty Images
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+Republicans claim the trial is constitutionally illegitimate. Most scholars disagree.
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+Top Republican senators argued on Sunday that the Senate impeachment trial of former President Donald Trump set to begin this week is not constitutionally legitimate — and one even tried to suggest that Democrats might be to blame for the storming of the US Capitol.
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+The dismissals and distraction tactics suggest that after a brief period of uncertainty about whether to censure Trump, Republicans are poised to present a fairly united front in rejecting the case that Trump should be convicted for his role in inciting the January 6 insurrection.
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+Sen. Ron Johnson (R-WI) argued that 45 Republican senators already believe the Senate trial is “unconstitutional,” when speaking with Fox News’ Maria Bartiromo on Sunday. He was referring to the vote total on the Senate motion brought by Sen. Rand Paul (R-KY) in January to dismiss the impeachment trial on the basis that it’s unconstitutional to hold an impeachment trial for a private citizen. Five Republicans joined the Democrats in rejecting the motion, but every other Republican voted in favor of it. (Many legal scholars believe that such a trial is perfectly constitutional — more on that later.)
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+But Johnson’s subsequent comments on Fox took a more shocking turn — he floated the baseless idea that House Speaker Nancy Pelosi was to blame in some sense for the violent assault on the Capitol.
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+“Is this another diversionary operation? Is this meant to deflect away from potentially what the speaker knew and when she knew it? I don’t know, but I’m suspicious,” Johnson said.
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+Ron Johnson absurdly floats that Nancy Pelosi is somehow responsible for a MAGA mob descending on the Capitol for a deadly insurrection pic.twitter.com/hUi6SydEe1
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+Other senators also attempted to question the legitimacy of the trial. Sen. Bill Cassidy (R-LA) said that the House vote on impeachment was all for show — and resembled the legal process in an authoritarian state.
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+“There was no process. It’s almost like, if it happened in the Soviet Union, you would have called it a show trial,” Cassidy said on NBC’s Meet the Press. “The president wasn’t there, he wasn’t allowed counsel, they didn’t amass evidence, in five hours they kind of judged and boom, he’s impeached,” he said.
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+The House impeachment process, in fact, does not involve a trial; the Senate trial following impeachment does. Trump was invited to testify at his Senate trial, but declined.
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+WATCH: “If it happened in the Soviet Union, you would have called it a show trial,” says @SenBillCassidy of the second impeachment trial of former Pres. Trump. #MTP
Cassidy: “The House did an incredibly poor job of building a case before their impeachment vote.” pic.twitter.com/5Pzlrq3ROA
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+Sen. Lindsey Graham (R-SC) argued on CBS’ Face the Nation that the trial was an “unconstitutional exercise” and that “the outcome is really not in doubt.”
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+He suggested that attempts to sanction Trump’s behavior should instead be dealt with through the conventional legal system. “If you believe he committed a crime, he can be prosecuted like any other citizen; impeachment is a political process,” Graham said.
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+Graham is correct in asserting that the outcome of the trial is in little doubt; 17 Republicans would have to join every member of the Democratic caucus for a conviction to be successful, as a conviction requires two-thirds of the Senate. As was evident Sunday, there appears to be little appetite for such a vote among the GOP.
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+Impeachment, however, is about the prosecution of crimes — specifically, “high crimes and misdemeanors,” according to the Constitution, and Trump’s impeachment trial does not appear to be an “unconstitutional exercise,” as Graham suggested.
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+There are historical examples of officials being tried after leaving office
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+Many Republicans have argued that the Senate trial lacks constitutional legitimacy because Trump has already left office. But scholars and Democratic lawmakers have pointed out that the US Constitution is silent on the issue, and point to previous examples of federal officials, such as judges, being tried even after leaving office.
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+According to the Wall Street Journal, a report from the Congressional Research Service — Congress’s internal research organization — found that “while the matter is open to debate, the weight of scholarly authority agrees that former officials may be impeached and tried.”
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+The CRS report cited the example of Secretary of War William Belknap, who was impeached by the House and tried in the Senate in 1876, though he had already resigned after evidence emerged that he had acted corruptly.
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+Laurence Tribe, a legal scholar at Harvard Law School, wrote in the Washington Post in January that “the clear weight of history, original understanding and congressional practice bolsters the case for concluding that the end of Donald Trump’s presidency would not end his Senate trial.”
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+Tribe wrote that the Constitution’s references to impeachment do not limit impeachment power based on whether an official is holding office. “Nothing in the Constitution suggests that a president who has shown himself to be a deadly threat to our survival as a constitutional republic should be able to run out the clock on our ability to condemn his conduct and to ensure that it can never recur,” he wrote.
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+That isn’t to say there is a consensus on this view. Former federal appeals court judge J. Michael Luttig has argued that the Senate trial would be unconstitutional, and says that he believes only the Supreme Court can make a definitive judgment on the matter.
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+There is still a lot that’s uncertain about the trial
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+A open question is whether any GOP senator will vote to convict Trump, particularly given that not all Republican senators have attempted to undermine the legitimacy of the Senate trial.
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+Sen. Pat Toomey of Pennsylvania — one of the five Republican senators who voted against Paul’s motion — said he believes the process is constitutional on Sunday.
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+“I think it’s clearly constitutional to conduct a Senate trial with respect to an impeachment. In this case the impeachment occurred prior to the president leaving office,” Toomey said on CNN’s State of the Union. “I still think the best outcome would have been for the president to resign. Obviously he chose not to do that.”
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+“I’m going to listen to the arguments on both sides and make the decision that I think is right,” he added.
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+“I think it’s clearly constitutional to conduct a Senate trial with respect to an impeachment,” Republican Sen. Pat Toomey says on fmr. Pres. Trump’s upcoming trial.
+While there is some question about possible Republican conviction votes, Democrats appear far more united on the issue. Sen. Chris Murphy (D-CT) encapsulated Democrats’ argument Sunday, defending the trial as something that’s not only allowed by the Constitution — but demanded by it.
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+“There is clear precedent for the Senate moving forward on impeachment trial once being sent articles, even after an official has left office, and so my analysis here sort of begins and ends with what is my constitutional responsibility,” he said on Fox News Sunday.
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+“Impeachment comes not only with the provision to remove an official from office, but to disqualify them from future office,” Murphy said.
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+Murphy also noted that there remain some big questions about how the trial will be conducted — including if witnesses will be brought in. He argued that since the riot was public, it wasn’t as necessary to call witnesses as it was during Trump’s first Senate impeachment trial, but that “if the House [impeachment] managers want to call witnesses, I think we should allow them to do so.”
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+One broad point of agreement between the two parties is that both Democrats and Republicans want the trial — which begins Tuesday — to be quick. Republicans will favor a short trial as a damage control measure to reduce public discussion of Trump’s behavior. Democrats, on the other hand, have an ambitious legislative agenda and appointee confirmation schedule, and can’t afford to have senators wrapped up in impeachment matters for too long without slowing those down.
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Liz Cheney asks Republicans to reject Trump, after being censured by her state party -
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+Rep. Liz Cheney speaks at the US Capitol in 2019. | Samuel Corum/Getty Images
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+“People have been lied to” about the election, Cheney told Fox News’ Chris Wallace.
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+A day after being censured by her state’s Republican Party, Wyoming Rep. Liz Cheney, the third-ranking Republican in the House of Representatives, went on Fox News to defend her vote to impeach former President Donald Trump — and to argue that the GOP will have lost its way if it doesn’t reject Trump’s brand of politics.
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+“People have been lied to,” Cheney told Chris Wallace on Fox News Sunday when asked about being censured. “The extent to which the president, President Trump, for months leading up to January 6, spread the notion that the election had been stolen or that the election was rigged was a lie. And people need to understand that.”
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+Cheney’s decision to explain her rejection of Trump on a Fox News show suggests she’s not been swayed by weeks of intraparty criticism over her vote, or attempts to topple her from her leadership position — and that she wants to persuade Republican voters that her faction of the party offers a more authentic and sustainable vision for conservatism.
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+Cheney was one of just 10 House Republicans who joined Democrats in impeaching Trump for the charge of incitement of insurrection at the US Capitol in January. And she has been facing the consequences of that vote ever since.
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+After Trump loyalists in the party called for her ouster from party leadership for turning against Trump, House Republicans held a secret ballot vote Wednesday on whether she should retain her No. 3 position among her colleagues.
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+She handily won the vote to remain in her position, 145 to 61, but the share of votes against her was not trivial, and if the vote had been public, experts say it’s quite possible that more lawmakers would’ve objected to her continuing as a leader in order to signal their commitment to Trump to their constituents.
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+Then, on Saturday, Cheney’s state Republican party approved a censure resolution by a vote of 56 to 8. The resolution says that the Wyoming Republican Party won’t raise money for her going forward — and requests that she repay state party donations made to her 2020 campaign.
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+But on Wallace’s show on Sunday, Cheney appeared unfazed, and defended her decision to impeach Trump without hesitation.
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+“Look, I think people all across Wyoming understand and recognize that our most important duty is to the Constitution,” Cheney said. “And as I’ve explained and will continue to explain to supporters all across the state, voters all across the state, the oath that I took to the Constitution compelled me to vote for impeachment, and it doesn’t bend to partisanship, it doesn’t bend to political pressure, it’s the most important oath that we take.”
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+The Wyoming lawmaker said Trump was not only a bad leader for the Republicans to embrace, but also posed an existential threat to the nation.
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+“The single greatest threat to our republic is a president who would put his own self-interest above the Constitution, above the national interest,” Cheney said. “And we’ve had a situation where President Trump claimed for months that the election was stolen, and then apparently set about to do everything he could to steal it himself.”
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+Cheney wants to take the GOP back from Trump. That’s an uphill climb.
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+Cheney’s plea to Fox viewers to turn away from Trump — in which she said she believed the GOP was the party of Ronald Reagan, not QAnon — shows that she’s committed to fighting for the return of an older version of the party.
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+The question is whether she can persuade Republican voters — and fellow lawmakers — that repudiating Trump is wise for the party after a presidency in which he cultivated an extremely devoted following among the party base.
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+For example, a Washington Post-ABC News poll from mid-January found that most Republicans said Trump bore no responsibility for the assault, and nearly half said Republican lawmakers didn’t actually go far enough in supporting the president’s efforts to overturn the election results.
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+According to the survey, about two-thirds of Republican and Republican-leaning participants thought Trump acted and spoke responsibly after the November 3 election.
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+And a new ABC-Ipsos poll, taken February 5 to 6, found that just 15 percent of Republicans support convicting Trump in a Senate impeachment trial and barring him from running for office again.
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+In other words, if Cheney hopes that the storming of the Capitol would be a wake-up call to Republicans about the dangers of backing Trump and his wing of the party, it would appear those hopes are unfounded.
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+Pro-Trump lawmakers have tried to weaponize Cheney’s views against her. In the run-up to the House Republican vote on whether she should retain her leadership, Florida Rep. Matt Gaetz, one of the fiercest pro-Trump voices in the party, held an anti-Cheney rally in her home state and slammed her policy record.
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+“Liz Cheney is a lot like Congress — deeply unpopular and owned by special interests,” he said at the rally. “She’s taken more money from PACs than people. She works for them, not you.”
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+Other lawmakers have also faced sharp pushback for voting for Trump’s impeachment. Rep. Peter Meijer — a freshman Republican from Michigan and the only first-term Republican to buck Trump — faced some angry questions from constituents during his first virtual town hall this week.
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+Meijer said during the event that he believed a majority of Republicans in his district — “maybe a strong majority” — disagreed with his decision to vote for impeachment. But ultimately he stuck by his decision.
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+“What we witnessed at the Capitol — the attempted insurrection, the involvement of a sitting American president propagating the falsehoods that led up to that — required a significant response,” he said. A number of his constituents reportedly disagreed during the town hall, with some saying they planned to work to unseat him over his vote — and a primary challenge to Cheney is underway as well.
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From The Hindu: Sports
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Pak vs SA | Pakistan beats South Africa by 95 runs in second test, wins series - Hasan, who bagged five wickets in the first innings, tormented the Proteas again returning figures of 5-60 and South Africa collapsed to 274 all out after lunch on the last day
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Ind vs Eng, 1st Test Day 4 | Ishant Sharma becomes 3rd Indian pacer to take 300 Test wickets - The Indian fast bowler reached the landmark when he trapped Dan Lawrence with a delivery that swung back sharply before hitting his pads in England’s second innings
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Australian Open | Canadian Andreescu toils to win in first match in 15 months - She faces a second-round matchup against Taiwan’s Hsieh Su-wei
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Australian Open | Thiem eases into second round - Dominic Thiem overcame an early wobble before overpowering Mikhail Kukushkin 7-6(2) 6-2 6-3 to reach the second round of the Australian Open on Monday
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Ind vs Eng, 1st Test Day 4 | Set world record target of 420, India in trouble at 39/1 - With opener Rohit Sharma (12) back in the hut, Shubman Gill (15) and Cheteshwar Pujara (12) will begin the proceedings for India on the fifth and final day.
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From The Hindu: National News
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Rajya Sabha | Modi showers praise on Azad - PM asks other members of the Upper House to follow Congress leader’s example of non-abrasive brand of politics.
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After Prime Minister’s invite, farmer leaders say ready for talks, ask government to choose date - Farmer leader Shiv Kumar Kakka said they are ready for the next round of talks and the government should tell them the date and time of the meeting.
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PM’s address masterclass in political whataboutery and rhetoric: CPI - Stating that Mr. Modi had failed to address any of the issues raised by MPs, Rajya Sabha MP Binoy Viswam questioned his claim that the minimum support price was part of the contentious farm laws.
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TMC reacts to Modi barb, tells him to show ‘Mamta’ to farmers - The ruling TMC in West Bengal on Feb. 7 slammed Prime Minister Narendra Modi for his hard- hitting comments against Chief Minister Mamata Banerjee and
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Watch | What is happening in Uttarakhand? - A video on the sudden flood in the Dhauli Ganga, Rishi Ganga and Alaknanda rivers that has killed at least 15 persons.
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From BBC: Europe
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Covid: Scientists developing vaccine boosters to tackle variants - An early study suggests the AstraZeneca vaccine may be less effective against the South African variant.
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Storm Darcy: Netherlands hit by ‘first major snowstorm in decade’ - A severe cold snap is pushing through northern Europe, bringing snow and gale-force winds.
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Saharan dust: Orange skies and sandy snow in southern Europe - The sky in parts of southern Europe turns an eerie orange as wind brings sand from the Sahara desert.
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Chechnya: Escaped gay men sent back by Russian police - A rights group says the men are in “mortal danger” in Chechnya, where gay people face persecution.
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French couple jailed after boy’s fatal beating revealed accidentally in call - A French couple are jailed after the cause of a toddler’s death is given away in an emergency call.
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From Ars Technica
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Marvel drops action-packed 2-minute Falcon and the Winter Soldier trailer - Anthony Mackie, Sebastian Stan reprise their titular roles in new Phase Four series. - link
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ABL Space tapped to launch the first orbital rocket from Britain - “The ABL system is relatively easy, quick, and cost-effective to deploy.” - link
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As cars get heavier, even small speed differences matter in a crash - A study on speed and crashes has me pining for lightweight cars. - link
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A curious observer’s guide to quantum mechanics, pt. 5: Catching a wave - When it comes to quantum mechanics, confinement is not necessarily bad. - link
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YouTube’s lo-fi music streams are all about the euphoria of less - Lo-fi hip-hop channels have created a community for minimalist escape. - link
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From Jokes Subreddit
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Jack woke up with a huge hangover after attending his company’s Christmas party. He didn’t even remember how he got home from the party. As bad as he was feeling, he wondered if he did something wrong. -
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+Jack had to force himself to open his eyes, and the first thing he saw was a couple of aspirins next to a glass of water on the side table. And, next to them, a single red rose! Jack sat up and saw his clothing in front of him, all clean and pressed. He looked around the room and saw that it was in perfect order, spotlessly clean. So was the rest of the house.
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+He took the aspirins, and cringed when he saw a huge black eye staring back at him in the bathroom mirror. Then he noticed a note hanging on the corner of the mirror written in red with little hearts on it and a kiss mark from his wife in lipstick: “Honey, breakfast is on the stove. I left early to get groceries to make you your favourite dinner tonight. I love you, darling!” He stumbled to the kitchen and sure enough, there was hot breakfast, steaming hot coffee and the morning newspaper. His son was also at the table, eating. Jack asked, “Son, what happened last night?” “Well, you came home after 3 A.M, drunk and out of your mind. You fell over the coffee table and broke it, and then you puked in the hallway, and got that black eye when you ran into the door.” Confused, he asked his son, “So, why is everything in such perfect order and so clean? I have a rose, and breakfast is on the table waiting for me??”
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+His son replied, “Oh THAT! Mum dragged you to the bathroom to clean you up, and when she tried to take your pants off, you screamed, ‘Leave me alone bitch, I’m married!’”
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English to become the official European language -
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+The European Commission has just announced an agreement whereby English will be the official language of the European Union rather than German, which was the other possibility.
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+As part of the negotiations, the British Government conceded that English spelling had some room for improvement and has accepted a 5- year phase-in plan that would become known as “Euro-English”.
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+In the first year, “s” will replace the soft “c”. Sertainly, this will make the sivil servants jump with joy. The hard “c” will be dropped in favour of “k”. This should klear up konfusion, and keyboards kan have one less letter.
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+There will be growing publik enthusiasm in the sekond year when the troublesome “ph” will be replaced with “f”. This will make words like fotograf 20% shorter.
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+In the 3rd year, publik akseptanse of the new spelling kan be expekted to reach the stage where more komplikated changes are possible.
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+Governments will enkourage the removal of double letters which have always ben a deterent to akurate speling.
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+Also, al wil agre that the horibl mes of the silent “e” in the languag is disgrasful and it should go away.
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+By the 4th yer peopl wil be reseptiv to steps such as replasing “th” with “z” and “w” with “v”.
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+During ze fifz yer, ze unesesary “o” kan be dropd from vords kontaining “ou” and after ziz fifz yer, ve vil hav a reil sensi bl riten styl.
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+Zer vil be no mor trubl or difikultis and evrivun vil find it ezi TU understand ech oza. Ze drem of a united urop vil finali kum tru.
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+Und efter ze fifz yer, ve vil al be speking German like zey vunted in ze forst plas.
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+Five surgeons are discussing who makes the best patients to operate on.
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+The first surgeon says, “I like to see accountants on my operating table because when you open them up, everything inside is numbered.”
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+The second responds, “Yeah, but you should try electricians! Everything inside them is color coded.”
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+The third surgeon says, “No, I really think librarians are the best! Everything inside them is in alphabetical order.”
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+The fourth surgeon chimes in, “You know, I like construction workers…Those guys always understand when you have a few parts left over.”
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+But the fifth surgeon shut them all up when he said, “You’re all wrong. Politicians are the easiest to operate on. There’s no guts, no heart, no balls, no brains, and no spine… Plus, the head and the ass are interchangeable!”
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