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+ + + ++Importance The SARS CoV2 alpha variant posed increased risk for COVID19 complications in pregnant women. However, its impact on the maternal humoral response and placental IgG transport remains unclear. Objective To characterize the maternal humoral waning and neonate immunity acquired during the third COVID19 wave in Israel, dominated by the Alpha variant, as compared to earlier Wildtype infections and humoral response to vaccination across gestation. Design Maternal and fetal blood serum were collected at delivery since April 2020 from parturients. Sera IgG and IgM titers were measured using the Milliplex MAP SARS CoV2 Antigen Panel supplemented with additional HA coupled microspheres. Setting A nationwide multicenter cohort study on SARS CoV2 infections and vaccination during pregnancy. Participants Expectant women presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 primary groups. 157 SARS CoV2 positive and 125 fully vaccinated during pregnancy, and 212 unvaccinated noninfected controls matched to the infected group by BMI, maternal age, comorbidities and gestational age. Eligibility criteria included pregnant women without active COVID19 disease, age over 18 years and willingness to provide informed consent. Main Outcomes and Measures Pregnant womens humoral response is dependent on the SARS CoV2 strain. Results The humoral response to infection as detected at birth, showed a gradual and significant decline as the interval between infection or vaccination and delivery increased. Significantly faster decay of antibody titers was found for infections occurring during the third wave compared to earlier infection or vaccination. Cord blood IgG antigens levels correlated with maternal IgG. However, cord IgG HA variance significantly differed in SARS CoV2 infections as compared to the other groups. No sexual dimorphism in IgG transfer was observed. Lastly, high fetal IgM response to SARS CoV2 was detected in 17 neonates, all showing elevated IgM to N suggesting exposure to SARS CoV2 antigens. Conclusions and Relevance Infections occurring during the third wave induced a faster decline in humoral response when compared to Wildtype infections or mRNA BNT162b2 vaccination during pregnancy, consistent with a shift in disease etiology and severity induced by the Alpha variant. Vaccination policies in previously infected pregnant women should consider the timing of exposure along pregnancy as well as the risk of infection to specific variants of concern. +
++Background After a rapid upsurge of COVID-19 cases in Italy during the fall of 2020, the government introduced a three-tiered restriction system aimed at increasing physical distancing. The Ministry of Health, after periodic epidemiological risk assessments, assigned a tier to each of the 21 Italian regions and autonomous provinces (AP). It is still unclear to what extent these different measures altered mixing patterns and how quickly the population adapted their social interactions to continuous changes in restrictions. Methods and findings We conducted a survey between July 2020 and March 2021 to monitor changes in social contact patterns among individuals in the metropolitan city of Milan, Italy, which was hardly hit by the second wave of COVID-19 pandemic. The number of contacts during periods characterized by different levels of restrictions was analyzed through negative binomial regression models and age-specific contact matrices were estimated under the different tiers. Relying on the empirically estimated mixing patterns, we quantified relative changes in SARS-CoV-2 transmission potential associated with the different tiers. As tighter restrictions were implemented during the fall of 2020, a progressive reduction in the mean number of contacts recorded by study participants was observed: from 16.4% under mild restrictions (yellow tier), to 45.6% under strong restrictions (red tier). Higher restrictions levels were also found to increase the relative contribution of contacts occurring within the household. The SARS-CoV-2 reproduction number was estimated to decrease by 18.7% (95%CI: 4.6-30.8), 33.4% (95%CI: 22.7-43.2), and 50.2% (95%CI: 40.9-57.7) under the yellow, orange, and red tiers, respectively. Conclusions Our results give an important quantification of the expected contribution of different restriction levels in shaping social contacts and decreasing the transmission potential of SARS-CoV-2. These estimates can find an operational use in anticipating the effect that the implementation of these tiered restriction can have on SARS-CoV-2 reproduction number under an evolving epidemiological situation. +
++Background: It is not clear whether previous thyroid diseases influence the course and outcomes of COVID-19. The study aims to compare clinical characteristics and outcomes of COVID-19 patients with and without hypothyroidism. Methods: The study is a part of a multicentric cohort of patients with confirmed COVID-19 diagnosis, including data collected from 37 hospitals. Matching for age, sex, number of comorbidities and hospital was performed to select the patients without hypothyroidism for the paired analysis. Results: From 7,762 COVID-19 patients, 526 had previously diagnosed hypothyroidism (50%) and 526 were selected as matched controls. The median age was 70 (interquartile range 59.0-80.0) years-old and 68.3% were females. The prevalence of underlying comorbidities were similar between groups, except for coronary and chronic kidney diseases, that had a higher prevalence in the hypothyroidism group (9.7% vs. 5.7%, p=0.015 and 9.9% vs. 4.8%, p=0.001, respectively). At hospital presentation, patients with hypothyroidism had a lower frequency of respiratory rate > 24 breaths per minute (36.1% vs 42.0%; p=0.050) and need of mechanical ventilation (4.0% vs 7.4%; p=0.016). D-dimer levels were slightly lower in hypothyroid patients (2.3 times higher than the reference value vs 2.9 times higher; p=0.037). In-hospital management was similar between groups, but hospital length-of-stay (8 vs 9 days; p=0.029) and mechanical ventilation requirement (25.4% vs. 33.1%; p=0.006) were lower for patients with hypothyroidism. There was a trend of lower in-hospital mortality in patients with hypothyroidism (22.1% vs. 27.0%; p=0.062). Conclusion: In this large Brazilian COVID-19 Registry, patients with hypothyroidism had a lower requirement of mechanical ventilation, and showed a trend of lower in-hospital mortality. Therefore, hypothyroidism does not seem to be associated with a worse prognosis, and should not be considered among the comorbidities that indicate a risk factor for COVID-19 severity. +
++Introduction: Testing is critical to controlling the COVID-19 pandemic. Antigen-detecting rapid diagnostic tests (Ag-RDTs) that can be used at the point of care have the potential to increase access to COVID 19 testing, particularly in settings with limited laboratory capacity. This systematic review synthesized literature on specific use cases and performance of Ag RDTs for detecting SARS-CoV-2, for the first comprehensive assessment of Ag RDT use in real-world settings. Methods: We searched three databases (PubMed, EMBASE and medRxiv) up to 12 April 2021 for publications on Ag- RDT use for large-scale screening, irrespective of symptoms, and surveillance of COVID-19, excluding studies of only presumptive COVID-19 patients. We tabulated data on the study setting, populations, type of test, diagnostic performance and operational findings. We assessed risk of bias using QUADAS-2 and an adapted tool for prevalence studies. Results: From 4313 citations, 39 studies conducted in asymptomatic and symptomatic adults were included. Study sample sizes varied from 40 to >5 million. Of 39 studies, 37 (94.9%) investigated lateral flow Ag-RDTs and two (5.1%) investigated multiplex sandwich chemiluminescent enzyme immunoassay Ag-RDTs. Six categories of testing (screening/surveillance) initiatives were identified: mass screening (n=13), targeted screening (n=11), healthcare entry testing (n=6), at-home testing (n=4), surveillance (n=4) and prevalence survey (n=1). Across studies, Ag-RDT sensitivity varied from 40% to 100%. Ag-RDTs were noted as convenient, easy-to-use and low cost, with a rapid turnaround time and high user acceptability. Risk of bias was generally low or unclear across the studies. Conclusion: This systematic review demonstrates the use of Ag-RDTs across a wide range of real-world settings for screening and surveillance of COVID-19 in both symptomatic and asymptomatic individuals. Ag-RDTs were overall found to be easy-to-use, low cost and rapid tools, when consideration is given to their implementation and interpretation. The review was funded by FIND, the global alliance for diagnostics. +
++SARS-CoV-2 causes a severe inflammatory syndrome called COVID-19 that primarily affects the lungs leading, in many cases, to bilateral pneumonia, severe dyspnea and in ~5% of the cases, death. The mechanisms through which this occurs are still being elucidated. A strong relationship between COVID-19 progression and autoimmune disorder pathogenesis has been identified as an exacerbated interferon immune response or an inflammatory condition mediated by an increase of pro-inflammatory cytokine production, among other. DNA methylation is known to regulate immune response processes, thus COVID-19 progression might be also conditioned by DNA methylation changes not studied in depth, yet. Thus, here an epigenome-wide DNA methylation analysis combined with DNA genotyping for 101 and 473 SARS-CoV-2 negative and positive lab tested individuals, respectively, from two different clinical centers is presented in order to evaluate the implications of the epigenetic regulation in the course of COVID-19 disease. The results reveal the existence of an epigenome regulation of functional pathways associated with the COVID-19 progression, such as innate interferon responses, hyperactivation of B and T lymphocytes, phagocytosis and innate C-type lectin DC-SIGN. These DNA methylation changes were found to be regulated by genetic loci associated with COVID-19 susceptibility and autoimmune disease. In mild COVID-19 patients hypomethylation of CpGs regulating genes within the AKT signaling pathway, and the hypermethylation of a group of CpGs related to environmental traits regulating IL-6 expression via the transcription factor CEBP, discriminate these individuals from those who develop the most critical outcomes of the disease. Thus, the analysis points out to an environmental contribution that mediated by DNA methylation changes in SARS-CoV-2 positive patients, might be playing a role in triggering the cytokine storm described in the most severe cases. In addition, important differences were found in terms of epigenetic regulation between severe and mild cases when compared with systemic autoimmune diseases. +
++The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) took the world by surprise. Following the first outbreak of COVID-19 in December 2019, several models have been developed to study and understand its transmission dynamics. Although the spread of COVID-19 is being slowed down by vaccination and other interventions, there is still a need to have a clear understanding of the evolution of the pandemic across countries, states and communities. To this end, there is a need to have a clearer picture of the initial spread of the disease in different regions. In this project, we used a simple SEIR model and a Bayesian inference framework to estimate the basic reproduction number of COVID-19 across Africa. Our estimates vary between 1.98 (Sudan) and 9.66 (Mauritius), with a median of 3.67 (90% CrI: 3.31 - 4.12). The estimates provided in this paper will help to inform COVID-19 modeling in the respective countries/regions. +
++Introduction & Objective: Vaccination is one of the most important and effective ways of preventing infectious diseases, and has recently been used in the COVID-19 epidemic and pandemic. The present meta-analysis study aimed to evaluate the effectiveness of COVID-19 vaccines in reducing the incidence of infection, hospitalization, and mortality in observational studies. Materials and Methods: A systematic search was performed independently in Scopus, PubMed, ProQuest, and Google Scholar electronic databases as well as Preprint servers using the keywords under study. The heterogeneity of the studies was assessed using I2 and χ2 statistics, according to which the I2 of > 50% and P-value <0.1 was reported as heterogeneity of the studies. In addition, the Pooled Vaccine Effectiveness (PVE) obtained from the studies was calculated by converting (1- Pooled estimate * 100%) based on the type of outcome. Results: A total of 54 records were included in this meta-analysis. The rate of PVE against SARS-COV 2 infection was about 71% (OR = 0.29, 95% CI: 0.23-0.36) in the first dose and 87% (OR = 0.13, 95% CI: 0.08-0.21) in the second, and the highest effectiveness in the first and second doses was that of BNT162b2 mRNA and combined studies. The PVE versus COVID-19-associated hospitalization was 73% (OR = 0.27, 95% CI: 0.18-0.41) in the first dose and 89% (OR = 0.11, 95% CI: 0.07-0.17) in the second. mRNA-1273 and combined studies in the first dose and ChAdOx1 and mRNA-1273 in the second dose had the highest effectiveness. Regarding the COVID-19-related mortality, PVE was about 28% (HR = 0.39, 95% CI: 0.23-0.45) in the first dose and 89% (HR = 0.11, 95% CI: 0.03-0.43) in the second. Conclusion: The evidence obtained from this study showed that the effectiveness of BNT162b2 mRNA, mRNA-1273, and ChAdOx1 in the first and second doses, and even combined studies were associated with increased effectiveness against SARS-COV2 infection, hospitalization, and death from COVID-19. In addition, considering that the second dose was significantly more efficient than the first one, a booster dose injection could be effective in high-risk individuals. On the other hand, it was important to observe other prevention considerations in the first days after taking the first dose. +
++Background: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking. Methods: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults between May 1 and Nov 2, 2020. Information on 88 potential risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively. Results: 1696 (15.2%) of 11,130 participants were seropositive. Factors independently associated with increased risk included frontline health/care occupation (aOR 1.86, 95% CI 1.49-2.33), international travel (1.22, 1.08-1.37), BMI >30 vs <25 kg/m2 (1.22, 1.05-1.42), Asian/Asian British vs White ethnicity (1.65, 1.10-2.47), and alcohol consumption ≥15 vs 0 units/week (1.26, 1.06-1.49). Light physical exercise associated with decreased risk (0.80, 0.69-0.93, for ≥10 vs 0-4 h/week). Higher titres associated with frontline health/care occupation (aGMR 1.26, 95% CI 1.13-1.41), international travel (1.10, 1.04-1.16), BMI >30 vs <25 kg/m2 (1.09, 1.01-1.17), and Asian/Asian British vs White ethnicity (1.23, 1.03-1.46); these associations were not substantially attenuated by adjustment for disease severity. Conclusions: Higher alcohol consumption and reduced physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between Asian/Asian British ethnic origin and obesity and increased risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, clinical, or behavioural factors investigated. +
++COVID-19 has challenged the world9s public health and led to over 4.5 million deaths. A rapid, sensitive, and cost-effective point-of-care virus detection device is crucial to the control and surveillance of the contagious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Here we demonstrate a solid phase isothermal recombinase polymerase amplification coupled CRISPR-based (spRPA-CRISPR) assay for on-chip multiplexed, sensitive, and visual COVID-19 DNA detection. By targeting the SARS-CoV-2 structure protein encoded genomes, two specific genes were simultaneously detected with the control sample without cross-interaction with other sequences. The endpoint signal can be directly visualized for rapid detection of COVID-19. The amplified target sequences were immobilized on the one-pot device surface and detected using the mixed Cas12a-crRNA collateral cleavage of reporter released fluorescent signal when specific genes were recognized. The system was tested with samples of a broad range of concentrations (20 to 2x105 copies) and showed analytical sensitivity down to 20 copies per reaction. Furthermore, a low-cost LED UV flashlight (~$12) was used to provide a visible SARS-CoV-2 detection signal of the spRPA-CRISPR assay which could be purchased online easily. Thus, our platform provides a sensitive and easy-to-read multiplexed gene detection method with the capacity to specifically identify low concentration genes. Similar CRISPR biosensor chips can support a broad range of applications such as HPV DNA detection, influenza SARS-CoV-2 multiplex detection, and other infectious disease testing assays. +
++Background. Poor immunogenicity and antibody waning were found in vaccinees of CoronaVac. There is lack of randomized controlled trial (RCT) data to compare the immunogenicity and safety of schedules using homologous and heterologous vaccine as a booster dose. Methods. We randomly assigned adults who had received 2 doses of CoronaVac with low antibody response to receive an additional booster dose of either BNT162b2 or CoronaVac. The local and systemic adverse reactions were recorded. Levels of SARS-CoV-2 neutralizing and spike binding antibody in plasma were measured. Findings. At one month after the third dose of vaccine, BNT162b2 vaccines elicited significantly higher surrogate virus neutralizing test (sVNT), spike receptor binding, spike N terminal domain binding, spike S2 domain binding levels than CoronaVac. More participants from the BNT162b2 group reported injection site pain and swelling as well as fatigue and muscle pain than those who received CoronaVac as the third dose. The mean results of the sVNT against the wild type, beta, gamma and delta variants in the BNT162b2 boosted group was 96.83%, 92.29%, 92.51% and 95.33% respectively which were significantly higher than the CoronaVac boosted group (Wild type: 57.75%; Beta: 38.79 %; Gamma: 32.22%; Delta: 48.87%) Conclusion. Our RCT study shows that BNT162b2 booster dose for those people who poorly responded to the previous vaccination of CoronaVac is significantly more immunogenic than a CoronaVac booster. BNT162b2 also elicits higher levels of SARS-CoV-2 specific neutralizing antibodies to different variants of concern. The adverse reactions were only mild and short-lived. +
++Contact tracing is a key component of successful management of COVID-19. Contacts of infected individuals are asked to quarantine, which can significantly slow down (or prevent) community spread. Contact tracing is particularly effective when infections are detected quickly (e.g., through rapid testing), when contacts are traced with high probability, when the initial number of cases is low, and when social distancing and border restrictions are in place. However, the magnitude of the individual contribution of these factors in reducing epidemic spread and the impact of vaccination in determining contact tracing outputs is not fully understood. We present a delayed differential equation model to investigate how vaccine roll-out and the relaxation of social distancing requirements affect contact tracing practises. We provide an analytical criteria to determine the minimal contact tracing efficiency (defined as the the probability of identifying and quarantining contacts of symptomatic individuals) required to keep an outbreak under control, with respect to the contact rate and vaccination status of the population. Additionally, we consider how delays in outbreak detection and increased case importation rates affect the number of contacts to be traced daily. We show that in vaccinated communities a lower contact tracing efficiency is required to avoid uncontrolled epidemic spread, and delayed outbreak detection and relaxation of border restrictions do not lead to a significantly higher risk of overwhelming contact tracing. We find that investing in testing programs, rather than increasing the contact tracing capacity, has a larger impact in determining whether an outbreak will be controllable. This is because early detection activates contact tracing, which will slow, and eventually reverse exponential growth, while the contact tracing capacity is a threshold that will easily become overwhelmed if exponential growth is not curbed. Finally, we evaluate quarantine effectiveness during vaccine roll-out, by considering the proportion of people that will develop an infection while in isolation in relation to the vaccination status of the population and for different viral variants. We show that quarantine effectiveness decreases with increasing proportion of fully vaccinated individuals, and increases in the presence of more transmissible variants. These results suggest that a cost-effective approach during vaccine roll-out is to establish different quarantine rules for vaccinated and unvaccinated individuals, where rules should depend on viral transmissibility. Altogether, our study provides quantitative information for contact tracing downsizing during vaccine roll-out, to guide COVID-19 exit strategies. +
++Drug overdose mortality rates have increased sharply during the COVID-19 pandemic. In recent years, overdose death rates were rising most rapidly among racial/ethnic minority communities. The pandemic has disproportionately affected communities of color in a wide swath of health, social, and economic outcomes. Careful attention is therefore warranted to trends in overdose mortality by race/ethnicity during COVID-19. We calculated total drug overdose death rates per 100,000 population by race/ethnicity for the 1999-2020 time period. We find that Black overdose mortality overtook that of White individuals in 2020 for the first time since 1999. Between 2019 and 2020 Black individuals had the largest percent increase in overdose mortality, of 48.8%, compared to 26.3% among White individuals. In 2020, Black overdose death rates rose to 36.8 per 100,000, representing 16.3% higher than the rate for White individuals for the same period. American Indian and Alaska Native (AI/AN) individuals experienced the highest rate of overdose mortality in 2020, of 41.4 per 100,000, representing 30.8% higher than the rate among White individuals. Our findings suggest that drug overdose mortality is increasingly becoming a racial justice issue in the United States and appears to have been exacerbated by the COVID-19 pandemic. Providing individuals with a safer supply of drugs, closing gaps in access to MOUD and harm reductions services, and ending routine incarceration of individuals with substance use disorders represent urgently needed, evidence-based strategies that can be employed to reduce rising inequalities in overdose. +
+COVID-19 Study of Pharmacokinetics, Safety, Tolerability, and Efficacy of Intravenous Anti-Spike(s) SARS-CoV-2 Monoclonal Antibodies (Casirivimab+Imdevimab) for the Treatment of Pediatric Patients Hospitalized Due to COVID-19 - Condition: COVID-19
Intervention: Drug: casirivimab+imdevimab
Sponsor:
+Regeneron Pharmaceuticals
Not yet recruiting
Immunogenicity and Safety of Heterologous and Homologous Boosting With ChAdOx1-S and CoronaVac or a Formulation of SCB-2019 (COVID-19) - Condition: Covid19
Interventions: Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford- AstraZeneca); Biological: CoronaVac (Sinovac Biotech); Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS- protein Subunit Vaccine (SCB-2019 - Clover)
Sponsors: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation; Instituto Fernandes Figueira
Not yet recruiting
JINZHEN for Treatment of Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: JINZHEN Granules for Oral Solution; Drug: Placebo
Sponsor: Lianyungang Kanion Group, Ltd.
Not yet recruiting
Effectiveness of Using Interactive Consulting System to Enhance Decision Aids of COVID-19 Vaccination - Condition: COVID-19
Intervention: Device: Chatbot
Sponsor: Sun Yat- sen University
Recruiting
Efficacy and Safety of Apixaban in COVID-19 Coagulopathy Patients With Respiratory Severity Under Critical Care - Condition: COVID-19
Intervention: Drug: Apixaban
Sponsors:
+Scotmann Pharmaceuticals; Rawalpindi Medical College
Not yet recruiting
Hypertonic Saline Nasal Irrigation and Gargling (HSNIG) for Suspected COVID-19 in Pakistan - Condition: COVID-19
Intervention: Other: Hypertonic Saline Nasal Irrigation and Gargles (HSNIG)
Sponsors: The Allergy and Asthma Institute, Pakistan; University of Edinburgh
Recruiting
Clinical Validation of Breath Analyser Tests for Diagnosis of COVID-19. - Condition: COVID-19
Intervention: Diagnostic Test: Breath Sample analysis
Sponsor: Tera Group
Recruiting
A Study to Evaluate Safety & Immunogenicity of SARS-CoV-2 DNA Vaccine Delivered Intramuscularly Followed by Electroporation for COVID-19 - Condition: Covid19
Interventions: Biological: SARS-CoV-2 DNA Vaccine; Biological: Matching placebo
Sponsors: The University of Hong Kong; Immuno Cure 3 Limited
Not yet recruiting
Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 Vaccines Delivered by Aerosol - Conditions: COVID-19; SARS-CoV2 Infection
Interventions: Biological: Ad5-triCoV/Mac; Biological: ChAd-triCoV/Mac
Sponsors: McMaster University; Canadian Institutes of Health Research (CIHR)
Not yet recruiting
Homeopathic Treatment of Post-acute COVID-19 Syndrome - Condition: Post-acute Covid-19 Syndrome
Interventions: Drug: Homeopathic Medication; Other: Placebo
Sponsors: Southwest College of Naturopathic Medicine; Samueli Institute for Information Biology
Recruiting
Effect of PBM on Functional Capacity and Fatigability in Post Covid-19 Elderly - Condition: Post Covid-19 Elderly
Interventions: Radiation: photobiomodulation; Other: placebo intervention by photobiomodulation device
Sponsor: Cairo University
Recruiting
Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) Booster Study - Condition: COVID-19 Pandemic
Interventions: Biological: Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01); Biological: Blank Preparation of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01)
Sponsor: Livzon Pharmaceutical Group Inc.
Not yet recruiting
Home-based Brain Stimulation Treatment for Post-acute Sequelae of COVID-19 (PASC) - Condition: Post-Acute Sequelae of COVID-19
Interventions: Device: Active tDCS; Device: Sham tDCS
Sponsor: Massachusetts General Hospital
Not yet recruiting
The Effect Of Music On Compliance Of Patients İn COVİD-19 Intensive Care Unit With CPAP Device - Conditions: COVID-19; COVID-19 Acute Respiratory Distress Syndrome
Intervention: Device: Listening to music with a bluetooth headset to patients receiving CPAP support
Sponsors: SÜMEYYE BİLGİLİ; Ataturk University
Recruiting
The Efficacy of Vitamin D Supplementation in Patients With Severe and Extremely Severe COVID-19 - Condition: SARS-CoV2 Infection
Intervention: Dietary Supplement: Vitamin D (cholecalciferol)
Sponsor: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Recruiting
Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection - The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2’3’-cGAMP associated with STING activation. cGAS…
A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants - The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective…
Auranofin: Past to Present, and repurposing - Auranofin (AF), a gold compound, has been used to treat rheumatoid arthritis (RA) for more than 40 years; however, its mechanism of action remains unknown. We revealed that AF inhibited the induction of proinflammatory proteins and their mRNAs by the inflammatory stimulants, cyclooxygenase-2 and inducible nitric oxide synthase, and their upstream regulator, NF-κB. AF also activated the proteins peroxyredoxin-1, Kelch-like ECH-associated protein 1, and NF-E2-related factor 2, and inhibited…
Methotrexate as a safe immunosuppressive agent during the COVID-19 pandemic - CONCLUSION: The present findings demonstrated that methotrexate does not predispose patients to severe COVID-19; on the contrary, patients taking methotrexate may experience a milder disease, possibly due to their reduced severe inflammatory reactions as a result of inhibited TNFα, lowered IL6, and increased T regulatory cells. According to these findings, methotrexate appears to be a suitable treatment option for patients who need immunosuppressive medications during the COVID-19 pandemic.
An airway organoid-based screen identifies a role for the HIF1alpha-glycolysis axis in SARS-CoV-2 infection - It is urgent to develop disease models to dissect mechanisms regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we derive airway organoids from human pluripotent stem cells (hPSC-AOs). The hPSC-AOs, particularly ciliated-like cells, are permissive to SARS-CoV-2 infection. Using this platform, we perform a high content screen and identify GW6471, which blocks SARS-CoV-2 infection. GW6471 can also block infection of the B.1.351 SARS- CoV-2 variant. RNA…
New tale on LianHuaQingWen: IL6R/IL6/IL6ST complex is a potential target for COVID-19 treatment - LianHuaQingWen (LHQW) improves clinical symptoms and alleviates the severity of COVID-19, but the mechanism is unclear. This study aimed to investigate the potential molecular targets and mechanisms of LHQW in treating COVID-19 using a network pharmacology-based approach and molecular docking analysis. The main active ingredients, therapeutic targets of LHQW, and the pathogenic targets of COVID-19 were screened using the TCMSP, UniProt, STRING, and GeneCards databases. According to the…
Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L - Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is a promising drug target for novel antivirals against SARS-CoV-2. The marine natural product gallinamide A and several synthetic analogues were identified as potent inhibitors of cathepsin L with IC(50) values in the picomolar range. Lead molecules possessed selectivity over other cathepsins and alternative host proteases involved in viral entry. Gallinamide A directly interacted with cathepsin L in cells…
Dasabuvir Inhibits Human Norovirus Infection in Human Intestinal Enteroids - Human noroviruses (HuNoVs) are acute viral gastroenteritis pathogens that affect all age groups, yet no approved vaccines and drugs to treat HuNoV infection are available. In this study, we screened an antiviral compound library to identify compound(s) showing anti-HuNoV activity using a human intestinal enteroid (HIE) culture system in which HuNoVs are able to replicate reproducibly. Dasabuvir (DSB), which has been developed as an anti-hepatitis C virus agent, was found to inhibit HuNoV…
Microbial based natural compounds as potential inhibitors for SARS-CoV-2 Papain-like protease (PLpro): a molecular docking and dynamic simulation study - COVID-19 (Coronavirus disease of 2019) pandemic is one of the largest health threats the planet has faced in recent decades. Efforts are being continuously made to design a viable drug or a vaccine. Several natural and synthetic molecules are under study for their potency to inhibit viral replication. In order to emphasize the importance of microbial-based natural components in antiviral drug discovery, an attempt has been made through this study to find potential inhibitors for SARS-CoV-2…
Rapid inactivation of SARS-CoV-2 with LED irradiation of visible spectrum wavelengths - Difficulty in controlling SARS-CoV-2 transmission made the ability to inactivate viruses in aerosols and fomites to be an important and attractive risk reduction measure. Evidence that light frequencies have the ability to inhibit microorganisms has already been reported by many studies which, however, focused on ultraviolet (UV) wavelengths, which are known to induce potential injury in humans. In the present study, the effect on suspensions of SARS-CoV-2 of a Light Emitting Diode (LED) device…
Potential Dietary Interventions for COVID-19 Infection Based on the Gut-Immune Axis: An Update Review on Bioactive Component of Macronutrients - Recently emerged coronavirus, known as SARS-CoV-2 or Covid-19 is considered as a serious threat for human health. Due to unavailable specific drugs for this virus, there is an urgent need for supportive cares. Epigenetic immune boosting approaches and developing anti-inflammatory agents by gut-associated bioactive macronutrients can be plausible protective cares for COVID-19. Suitable intake of bioactive macronutrients including prebiotics, fatty acids, proteins and branched-chain amino acids…
In silico identification of potential inhibitors against main protease of SARS-CoV-2 6LU7 from Andrographis panniculata via molecular docking, binding energy calculations and molecular dynamics simulation studies - CONCLUSION: In conclusion, findings of the current study suggest that selected diterpenoids were predicted to be the significant phytonutrient-based inhibitor against SARS-CoV-2 6LU7 (M^(pro)). However, preclinical and clinical trials are needed for the further scientific validation before use.
Broad spectrum antiviral nucleosides-Our best hope for the future - The current focus for many researchers has turned to the development of therapeutics that have the potential for serving as broad-spectrum inhibitors that can target numerous viruses, both within a particular family, as well as to span across multiple viral families. This will allow us to build an arsenal of therapeutics that could be used for the next outbreak. In that regard, nucleosides have served as the cornerstone for antiviral therapy for many decades. As detailed herein, many nucleosides…
Hemin as a novel candidate for treating COVID-19 via heme oxygenase-1 induction - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 (COVID-19). More than 143 million cases of COVID-19 have been reported to date, with the global death rate at 2.13%. Currently, there are no licensed therapeutics for controlling SARS-CoV-2 infection. The antiviral effects of heme oxygenase-1 (HO-1), a cytoprotective enzyme that inhibits the inflammatory response and reduces oxidative stress, have been investigated in several viral…
Protease Inhibitors as Promising Weapons against COVID-19: Focus on Repurposing of Drugs used to Treat HIV and HCV Infections - As a part of the efforts to quickly develop pharmaceutical treatments for COVID-19 through repurposing existing drugs, some researchers around the world have combined the recently released crystal structure of SARS-CoV-2 M^(pro) in complex with a covalently bonded inhibitor with virtual screening procedures employing molecular docking approaches. In this context, protease inhibitors (PIs) clinically available and currently used to treat infectious diseases, particularly viral ones, are relevant…
Anti-SARS-CoV-2 antibodies and uses thereof I - - link
Anti-SARS-CoV-2 antibodies and uses thereof II - - link
휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수물 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 약 90% 이며, 건강한 성인이면, 육각수 물은 약 62% 이며, COVID-19 환자, 사고의 부상, 17만개의 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수 물을 평소보다 많이 흡수 하면서 동반 산소부족 상태가 되며, 육각수물 보충 없이 산소 호흡기를 사용하면 심각한 후유증이 발병 할 수 있다.
육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link
+휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 90% 이며, 육각수물은 약 62% 이며, COVID-19, 사고 부상, 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수물을 평소보다 많이 흡수하면서 산소부족 상태가 되며, 육각수 보충 없이 산소호흡기를 사용하면 심각한 후유증이 발병 할 수 있다 육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수물을 62% ~ 80% 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link
用于检测新冠病毒的配对抗体及其应用 - 本发明涉及一种用于检测新冠病毒的配对抗体及其应用,其包括第一检测抗体和第二检测抗体;第一检测抗体具有如SEQ ID NO:1~3所示的轻链互补决定区,以及如SEQ ID NO:4~6所示的重链互补决定区,第二检测抗体具有如SEQ ID NO:7~9所示的轻链互补决定区,以及如SEQ ID NO:10~12所示的重链互补决定区。本发明筛选得到具有上述互补决定区序列的配对抗体,其识别N蛋白的不同表位,且由于两种抗体识别的是N蛋白非核酸结合区域,不会受核酸负电荷干扰,对核酸抗原表现出了兼容性,具有较好的稳定性,同时上述配对抗体具有较高的亲和力,病毒N蛋白检测灵敏度高。 - link
抗KL-6双特异性抗体及基因、重组载体、药物、试剂盒 - 本发明公开了抗KL‑6双特异性抗体或其变体、或其功能性片段,所述抗KL‑6双特异性抗体或其变体、或其功能性片段包括抗PTS域和抗SEA域,所述抗PTS域的重链可变区的CDR1、CDR2和CDR3分别具有SEQ ID NO.1~3所示的氨基酸序列。本发明还提供了基因、重组载体、药物、试剂盒。本发明的抗KL‑6双特异性抗体或其变体、或其功能性片段用于与KL‑6蛋白特异性结合,基因、重组载体用于抗KL‑6双特异性抗体的制备,药物用于治疗KL‑6蛋白引起的相关疾病,试剂盒用于KL‑6蛋白的定量检测。 - link
基于决策树模型与逻辑回归模型组合的感染筛查方法 - 本发明公开了一种基于决策树模型与逻辑回归模型组合的感染筛查方法,其检测操作方便,可提高感染筛查准确性,该方法基于生命体征监护仪实现,生命体征监护仪与远程数据服务平台通信连接,远程数据服务平台依据临床数据进行感染筛查,该方法包括:通过生命体征监护仪检测获取用户临床数据,将临床数据随机划分为训练集、测试集,将训练集均分为两份:训练集A、训练集B,基于训练集A构建决策树模型,同时,对训练集A进行特征选择,将关键特征向量作为已构建的决策树模型的输入,获取新构造特征向量,基于组合特征向量,构造逻辑回归模型,基于决策树模型和逻辑回归模型组合,对测试集进行预测分类,获取分类结果。 - link
病毒中和抗体与非中和抗体联合检测方法、检测卡及应用 - 一种病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用,通过病毒受体结合蛋白夹心法原理检测中和抗体,其为通过提前设置病毒受体结合蛋白和能阻断中和抗体与其结合的作为配体的蛋白所形成的复合物,将靶向受体蛋白的非中和抗体提前捕获,保证后续通过夹心法检测中和抗体的特异性。解决了现有技术中中和抗体检测灵敏度低、特异性差以及不能区分中和抗体与非中和抗体的问题,提供了一种简便、快速、灵敏度高、特异性高的病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用。 - link
扩增△500-532的SARS-CoV-2 Nsp1基因的引物对及其检测方法 - 本发明公开了一种扩增Δ500‑532的SARS‑CoV‑2 Nsp1基因的引物对及其检测方法。引物对的具体序列如SEQ ID NO.1和SEQ ID NO.2所示,其检测方法为:采用引物对对SARS‑CoV‑2 Nsp1基因进行PCR,对PCR产物进行变性退火后,加入T7EI内切酶孵育,再进行PCR扩增,并判断是否存在Δ500‑532的SARS‑CoV‑2 Nsp1基因。本发明可简便快捷的区分出SARS‑CoV‑2 Nsp1基因突变型和野生型。 - link
多肽及其在新型冠状病毒检测中的应用 - 本发明涉及生物医学领域,具体而言,涉及一种多肽及其在新型冠状病毒检测中的应用。所述多肽包括如下部分:S——Linker——N——avi‑tag。通过经过优化的刚性linker序列把S蛋白和N蛋白串联起来,使得这两个蛋白即具备相对独立的空间构象,又增加了许多优势表位,很大程度上提高了灵敏度和信号值;此外,融合蛋白引入Avi‑tag,使得重组蛋白可以通过固定的位点被固相化,降低包被过程所带来的空间位阻的影响。由此,该多肽能够达到很高的灵敏度和特异性,并且不易发生漏检。 - link
Will Supply-Chain Issues Ruin Christmas? - Shortages resulting from the pandemic and Brexit are already causing runs on gifts, turkeys, and puddings. - link
It’s Time for Democrats to Take a Win on Spending - Warts and all, the reconciliation bill would tilt the economy in a greener direction, improve the lives of Americans, and give a boost to Biden. - link
Why Spain Was Long in Denial About Franco—and Still Stands By Columbus - When President Biden proclaimed that Columbus Day would also be Indigenous Peoples’ Day, the right reacted as if the country’s national identity were at stake. - link
The Supreme Court Wonders Where the Texas Abortion Law Might Lead - In order to trample on reproductive rights, S.B. 8 tramples on all rights. - link
The Velvet Underground Eludes Todd Haynes - The long-awaited documentary about the Velvet Underground is very good, but we had reason to expect more. - link
+This month has everything: Eternals, murder, tennis, and Princess Di. +
++It’s no exaggeration to say that this November is the biggest month for movies not just this year, but in several years, thanks to the pandemic. The reason is mostly logistics: Some movies slated to come out a year ago are finally hitting theaters, and with the Oscar eligibility window closing at the end of December, film distributors are rushing to put their most impressive films and performers in the spotlight. And of course, the holidays — a prime moviegoing season — are coming too. +
++So the bounty is impressive, from new MCU installments to the buzziest films from the fall festivals to big, wild-looking period pieces. November will be a great month at the movies, so here are the 14 movies to see. +
++Release date: November 5 +
++The latest big-screen addition to the Marvel Cinematic Universe zooms out — way out. Eternals tells the story of a group of immortal interstellar beings who are sent to earth to protect the planet and its inhabitants from the Deviants, who are their equivalents, but evil. Directed by Chloé Zhao (whose film Nomadland won Best Picture and Best Director at the Oscars earlier this year), Eternals jumps around in time and space, a hugely ambitious epic that never really gels narratively but is worth seeing nonetheless. It’s also got a great cast: Gemma Chan, Richard Madden, Kumail Nanjiani, Barry Keoghan, Lauren Ridloff, Lia McHugh, Brian Tyree Henry, Salma Hayek, and Angelina Jolie play the Eternals. +
++How to watch it: Eternals will premiere in theaters. +
+ ++
++Release date: November 5 +
++Kristen Stewart is Princess Diana in Spencer — or at least, she’s a version of the icon who left a legend in the wake of her tragic 1997 death. Following his imagination-fueled fantasia on Jackie Kennedy in 2016’s Jackie, director Pablo Larrain returns with a similarly speculative dive into the psyche of the famous princess, right as she’s reaching a breaking point. The film follows Diana through the Christmas holidays with the royal family, often filming Stewart in claustrophobic, panicky frames that give Spencer, at times, the feeling of a horror film. It’s a bit less sly about what it’s up to than Jackie was, and suffers from some ploddingly obvious symbolism. But the spell it casts is murky and laced with dread, and it’s hard to shake after the movie ends. +
++How to watch it: Spencer will premiere in theaters. +
++
++Release date: November 10 +
++Rebecca Hall wrote and directed this adaptation of Nella Larsen’s 1929 novel, which is about two childhood friends who encounter one another again in adulthood. Irene (Tessa Thompson), who goes by Reeny, lives with her doctor husband (André Holland) and their children in a stately Harlem house. Clare (Ruth Negga) is married to a racist businessman (Alexander Skarsgård), who has no idea that his wife is not white. The film feels almost dreamlike, evoking a world in which the lines that separate friendship from desire, love from hate, and white from Black are more permeable than you might expect — a world a lot like today’s. +
++How to watch it: Passing, which is playing in limited theaters, begins streaming on Netflix on November 10. +
++
++Release date: November 12 +
++Belfast, Kenneth Branagh’s unabashedly sentimental dip into his youthful memories of strife during the Troubles in Northern Ireland, is really a family drama told from a small boy’s perspective. The boy’s parents (Jamie Dornan and Caitríona Balfe) are Protestant Belfast natives who watch their Catholic neighbors become the target of violence, struggling to keep their family together as they weigh whether their future lies in Belfast with his grandparents (Judi Dench and Ciarán Hinds) or elsewhere. The boy himself, Branagh’s avatar Buddy (Jude Hill), catches glimpses of the big world outside the family’s corner of Belfast on the TV and at the movies. Belfast is in black and white, but Branagh renders whatever they’re watching, from Star Trek and Chitty Chitty Bang Bang to The Man Who Shot Liberty Valance, in color. The stories we watch on screen, Branagh reminds us, are a vibrant reminder to truly live during dark times. +
++How to watch it: Belfast will open in theaters on November 12. +
++
++Release date: November 12 +
++Indelible, gutting, and hopeful, Procession is a documentary unlike anything you’ve seen before. The filmmakers, led by director Robert Greene, reached out to six men in the Kansas City, Missouri, area who were abused as boys by Catholic priests and clergy. Rather than proceeding as an exposé, Procession is a collaborative project in healing, as each of the six men creates and films traumatic memories in a drama therapy-informed quest to … well, what, exactly? That’s what they’re exploring: the meaning of healing, the ways we perform to cope and to crack ourselves open, and the possibilities, such as they are, for redemption. It’s a must-see. +
++How to watch it: Procession will open in limited theaters on November 12 and begin streaming on Netflix on November 19. +
++
++Release date: November 12 +
++Lin-Manuel Miranda steps behind the camera for Tick, Tick… Boom!, a film adaptation of the autobiographical musical by Rent composer Jonathan Larson. Andrew Garfield plays Larson, who is closing in on his 30th birthday and increasingly terrified that he’s running out of time to actually break into the musical theater world. The real Larson wrote Tick, Tick… Boom! a few years before Rent made him famous, and thus only a few years before he died unexpectedly of an undiagnosed heart condition. That backstory makes Tick, Tick… Boom! all the more poignant — and the film adaptation will likely draw in a new generation of fans. +
++How to watch it: Tick, Tick… Boom! will open in limited theaters on November 12 and begin streaming on Netflix on November 19. +
++
++Release date: November 17 +
++Jane Campion’s first film since 2009’s Bright Star is The Power of the Dog, and it is set, despite its New Zealand shooting location, in the American West. For most of its runtime, The Power of the Dog is confined to the big ranch that Phil and George (Benedict Cumberbatch and Jesse Plemons) own and operate. George marries Rose (Kirsten Dunst) and brings her there, along with her waifish teenage son Peter (Kodi Smit-McPhee). Phil despises both of the ranch’s new residents. But people’s exteriors rarely match what they’re capable of inside. The Power of the Dog will keep you guessing as it morphs from a Western to a romance to something deliciously dark, a melodrama with an eerie bite and sweeping, craggy vistas. +
++How to watch it: The Power of the Dog will premiere in theaters on November 17 and begin streaming on Netflix on December 1. +
++
++Release date: November 19 +
++Joaquin Phoenix stars in C’mon C’mon, the sensitive and huge-hearted new movie from Mike Mills (whose last film was 20th Century Women). Phoenix is Johnny, an artist interviewing young people around the US about the future: what they hope for, what they dream of, what they fear. But when his semi-estranged sister (Gaby Hoffmann) suddenly has to attend to an emergency, he ends up caring for his precocious and eccentric 9-year-old nephew Jesse (Woody Norman), and both of them learn a lot from one another. The premise of C’mon C’mon could easily swing into way-too-precious territory, but Mills’s steady hand and feeling for story rhythms, along with Phoenix’s performance, keep the ship on course. The result is a warm and winsome meditation on the ties that bind us. +
++How to watch it: C’mon C’mon will premiere in theaters. +
++
++Release date: November 19 +
++Will Smith stars in King Richard as Richard Williams, the father of tennis superstars Venus Williams (Demi Singleton) and Serena Williams (Saniyya Sidney). Directed by Reinaldo Marcus Green, it’s a biopic centering on Richard’s “unconventional” methods in helping two of his daughters reach the top of their game. It’s just the kind of crowd-pleasing, family-friendly sports movie that tends to do well during the holiday season. While the Williams family was involved with the production, it’s still not totally clear why Richard is at the center (rather than, for instance, both parents, who were equally involved in their daughters’ early careers). But with a cast that also includes Aunjanue Ellis as the girls’ mother Oracene Price and Tony Goldwyn and Jon Bernthal as their coaches, it seems destined for the awards-season stage. +
++How to watch it: King Richard will premiere in theaters and on HBO Max. +
++
++Release date: November 24 +
++Ryusuke Hamaguchi directed and co-wrote the screenplay for Drive My Car, which is based on a Haruki Murakami short story. The film centers on Yūsuke Kafuku (Hidetoshi Nishijima), a theater director who returns home one day to find that his wife Oto (Reika Kirishima), a TV executive, has died. Then time jumps forward, and Kafuku is directing a production of Chekhov’s Uncle Vanya, with each actor performing in their own language. He decides to cast his wife’s lover, Takatsuki (Masaki Okada), in the main role. Through rehearsals and the relationships that develop during the project — including with Misaki (Toko Miura), the quiet young woman hired to drive him to and from the theater — Kafuku starts to understand something that’s nearly ineffable about his past and his future. Drive My Car is a melancholy, meaningful film, occupied with friendships, old wounds, and the task of continuing to live. +
++How to watch it: Drive My Car will premiere in theaters. +
++
++Release date: November 24 +
++Encanto is the animated musical tale of the Madrigals, a Colombian family who all have magical powers and live in an enchanted mountain town. Every member of the family has a singular talent except Mirabel (voiced by Stephanie Beatriz), who is pretty frustrated about this state of affairs. Then, one day, she discovers that her family’s magic may be under threat, and she must go on a journey to save both the magic and her family’s home. With additional voice work from John Leguizamo, María Cecilia Botero, Diane Guerrero, Jessica Darrow, Angie Cepeda, Wilmer Valderrama, Carolina Gaitán, Mauro Castillo, Adassa, Rhenzy Feliz, and Maluma, and songs written by Lin-Manuel Miranda, Encanto seems like the perfect family film for the holiday season. +
++How to watch it: Encanto will premiere in theaters. +
++
++Release date: November 24 +
++Ridley Scott’s second movie this year (the other was The Last Duel) is House of Gucci, starring Adam Driver as Maurizio Gucci, head of the legendary Gucci fashion house, and Lady Gaga as his ex-wife Patrizia Reggiani. The film follows the murder of Gucci in 1995 and the events that took place afterward, and features — among other things — absolutely fabulous costume design. With Jared Leto, Jeremy Irons, Al Pacino, and Salma Hayek (who, incidentally, is married to the current head of Gucci) among the cast and a juicy true-crime story at its core, House of Gucci is certain to be, at minimum, a lot of fun at the movies. +
++How to watch it: House of Gucci will premiere in theaters. +
++
++Release date: November 24 +
++Stephen Karam’s play The Humans won a Tony and was a finalist for the Pulitzer, and it turns out it makes a great movie, too. Karam adapted and directed the film, which stars a terrific cast — Richard Jenkins, Jayne Houdyshell (who reprises her Broadway role), Beanie Feldstein, Amy Schumer, Steven Yeun, and June Squibb — as a family who’ve gathered in one daughter’s rickety new Chinatown apartment for Thanksgiving. Over the course of the evening, conversations start to hint at what’s right about this family and what’s gone very wrong. The film is funny and raw, full of the kinds of things families say to one another at holidays, and Karam’s use of space keeps the adaptation from feeling too much like just a filmed play. It’s haunting, a little hopeful, and very, very honest. +
++How to watch it: The Humans will premiere in theaters. +
++
++Release date: November 26 +
++Paul Thomas Anderson follows up 2017’s Phantom Thread with Licorice Pizza, a romantic coming-of-age story set in 1973 about two young people, played by singer Alana Haim, of the band Haim, and Cooper Hoffman, son of frequent Anderson collaborator Philip Seymour Hoffman. Anderson is famously tight-lipped about the details of his plots before his films premiere, but the trailer for Licorice Pizza set the internet ablaze, in part because of its cast: Tom Waits, Sean Penn, Benny Safdie, Maya Rudolph, Mary Elizabeth Ellis, Ben Stiller, John C. Reilly, Christine Ebersole, and Bradley Cooper in bombastic mode as a film producer named Jon Peters, who may or may not be based on the real guy. And who doesn’t love a drama about the glories and disappointments of first love? +
++How to watch it: Licorice Pizza will open in limited theaters on November 26 and widely on December 22. +
+This lesser-known greenhouse gas will make or break a “decisive decade” for climate change. +
++From his home office in Arizona, Riley Duren was multitasking, telling me about frighteningly powerful greenhouse gases even as he monitored his team’s aircraft. The plane was flying at 20,000 feet to measure methane spewing from wells in the Permian Basin of Texas. An aerial map on his computer screen brought the measurements to life: Dozens of red zones represented otherwise invisible plumes of methane above oil and gas fields. +
++“It’s just like watching a firework show. They’re just popping up all over the place,” said Duren, a University of Arizona scientist who leads the nonprofit Carbon Mapper, which has public and private partners including NASA, the state of California, and the company Planet. +
++In the public conversation about climate change, methane has gotten too little attention for too long. Many people may be unaware that humans have been spewing a greenhouse gas that’s even more potent than carbon dioxide into the atmosphere at a rate not seen in at least 800,000 years. It harms air quality and comes from sources as varied as oil and gas pipelines to landfills and cows. But methane and other greenhouse gases, including hydrofluorocarbons, ozone, nitrogen dioxides, and sulfur oxides, are finally getting the attention they deserve — thanks largely to advances in the science. +
++Until the past few years, methane’s relative obscurity made sense. Carbon dioxide (CO2) is by far the largest contributor to climate change, and it comes from recognizable fossil fuel sources such as car tailpipes, coal smokestacks, and burning gas and oil. The most troubling part is that it sticks around in the atmosphere for hundreds of years, making climate change not just a problem for us now, but generations well into the future. +
++But the world no longer has the luxury of overlooking methane. And at the 26th international climate conference in Glasgow, which runs until November 12, a major new initiative was launched to address methane head-on. More than 100 countries, representing nearly half of global methane pollution levels, committed to a voluntary Global Methane Pledge of reducing levels by at least 30 percent by the end of the decade. President Joe Biden, who is co-leading the initiative with the European Union, announced a suite of regulatory actions that aim to bring the United States in line with that global target. +
++Some of the largest methane polluters, including Russia and China, have not joined the global pledge. It’s just one sign that the world still hasn’t fully heeded scientists’ wake-up calls on methane. +
+ ++Even though methane is not nearly as well understood as carbon dioxide, it’s playing an enormous role in the climate crisis. It’s at least 80 times as effective at trapping heat as carbon dioxide in a 20-year period, but it starts to dissipate in the atmosphere in a matter of years. If this is the “decisive decade” to take action, as the Biden administration has said, then a methane strategy has to be at the center of any policy for tackling global warming. +
++Methane could mean the difference between a rapidly warming planet changing too quickly and drastically for humanity to handle, and buying the planet some much-needed time to get a handle on the longer-term problem of fossil fuels and carbon pollution. +
++Drew Shindell, one of the scientists who raised an early alarm about methane, was studying air pollution in the late 2000s when he found a strange trend. Ground-level ozone, the pollutant that forms hazy smog, was rising in the US — which surprised him after decades of progress under the Clean Air Act. He realized the “relentless growth in methane,” which accelerates the formation of ozone near the ground, was to blame. Ever since, he’s been trying to warn the world not to overlook this dangerous pollutant and its costs to both the climate and human health. +
++Identifying the millions of sources of methane around the globe isn’t so simple. Cattle release methane, and so does decomposing organic material. All the food waste that goes into landfills release methane. And natural gas is almost entirely methane. +
++If you’ve heard politicians call natural gas a “bridge fuel,” what they mean is that natural gas emits less carbon dioxide than coal. It’s wrong to call it clean, because burning methane still releases carbon — and methane that escapes without burning is a powerful warmer. +
+ ++The oil and gas industry has argued that it isn’t to blame for methane pollution, but advocates and scientists have shown otherwise. The Environmental Defense Fund, which has commissioned flights to monitor methane over Texas oil and gas fields, has found that oil fields in the US are leaking 60 percent more methane than the Environmental Protection Agency estimates. University of Michigan scientist Eric Kort found methane spewing from offshore wells at far higher rates than previously understood. The environmental group Earthworks, using expensive, on-the-ground camera equipment, helped track down some sites that were repeat offenders of venting methane into the atmosphere. +
++The scientific papers have mounted: Since 2013, at least 45 scientific papers have highlighted the disproportionate role of oil and gas operations, according to a review by the advocacy group Climate Nexus. Scientists like Duren have also produced vivid images of methane that a layperson can understand, just like the imagery below from April this year. +
++According to Duren, Carbon Mapper has detected over 3,000 methane plumes in the Permian Basin with its airborne surveys, all coming from a range of oil and gas infrastructure, including wells, tank batteries, compressor stations, pipelines, and more. +
++Together, these findings suggest a grim outlook for the minimal progress made so far in tackling carbon pollution: Rising methane pollution effectively erases some of the progress the US has made by cleaning up the coal-fired power sector. +
++Methane has been rapidly climbing since 2007, driven by a mix of agriculture (from East and West Asia, Brazil, and northern Africa) and fossil fuels, specifically from North America. In other words, scientists are confident that humans are the main cause of increasing methane pollution. +
++Still, the data needs to get better. The Biden administration is essentially starting from scratch with proposed EPA rules that require oil companies to monitor and fix their own leaks. The Trump administration wasted critical years by scrapping rules that targeted new wells and set basic standards for self-reporting practices. +
++For the world to tackle methane, countries still have to better understand what sectors and sources it is coming from. Few major economies even measure methane. China has launched a carbon-trading market to tackle carbon dioxide emissions, but has done less to control methane, which comes not just from gas but coal as well. +
++For the first time in August, the IPCC devoted substantial attention to the major role of gases other than CO2. The UN’s sixth assessment of the science of climate change, which finds that the evidence of man-made warming is “unequivocal” and many climate impacts will be irreversible, dedicates a full chapter of the report to “short-lived pollutants” such as methane. One of their most common sources is fossil fuels. +
+ ++Since these gases are such a tiny part of the atmosphere compared to how much carbon dioxide we’re pumping in the air, methane is “always No. 2” in discussions of climate change, said Shindell, who chaired the world’s first United Nations Global Methane Assessment released this year. It’s fallen “between the cracks” in global research thus far, Shindell said. +
++Until now, methane has literally fallen between the cracks: Some of it leaks out of the ground in places like oil fields and permafrost, and scientists are still trying to understand where it all comes from. The IPCC report reflects these uncertainties. The report authors, for example, do not name the dominant source of human-caused methane emissions, whether fossil fuels or agriculture. But what we now know represents one of the greatest evolutions in climate research since the last IPCC assessment came out in 2013. The work of scientists like Duren helps the world understand the biggest culprits of the methane crisis, in the hope that governments and corporations take urgent action. +
++There are other greenhouse gases out there besides CO2 and methane. Nitrogen dioxides, black carbon, and halogenated gases (a category that includes chemicals used for refrigerants, hydrofluorocarbons) are other contributors to climate change. +
++A graphic from the IPCC’s summary for policymakers makes sense of how all these gases interact to add up to at least 1.1 degrees Celsius of average global warming since the 1850s. As the below graphic shows, CO2 and methane make up most of the warming, but other pollutants leave their mark too. Some aerosols from fossil fuels, like sulfur dioxide, actually have a cooling effect (but are dangerous to our lungs). +
+ ++There’s good news and bad news when it comes to the second-worst cause of global warming. +
++First the bad: Methane is rising, and there’s plenty we don’t know about it. Even if we pinpointed the worst offenders in oil and gas, its other sources would still require sweeping societal change, like a reduction in the number of cows raised for food. (There’s been some experimentation with feed for cattle to reduce methane, or more wackily, fart-collecting backpacks for cows). +
++Food waste, which releases methane as it decomposes, is a problem too. Across the world, the richest economies are throwing out half their food. Landfills may be able to capture some of the methane, but that too is an energy-intensive process. +
+ ++That leaves oil, coal, and gas. Coal is the worst offender; it leaches both carbon dioxide as well as methane, making it the number one priority to phase out. Oil production is a big problem too, in part because producers don’t face much regulatory or economic pressure to recapture the extra gas. Even when industry is trying to capture and sell natural gas, producers lose methane throughout its extraction and transportation. It leaks out as producers pipe the gas to compressor stations, process it for shipment, ship it hundreds of miles by pipeline to a refinery, and transport it to the consumer in the form of liquefied natural gas, plastic, petrochemicals, or the gas that lights up ovens in homes and apartments. +
++The whole system is extremely leaky, but the leakiest parts are not totally clear. “It’s just been really hard to put our finger on exactly the source, and be able to attribute it to the granularity that would enable us to solve it,” said Fran Reuland, a researcher on methane in the oil and gas industry at the think tank RMI. “Because it’s happening over such a large area, wrapping your mind around just how much is coming out is one of the main problems.” +
++Another frustrating challenge is that methane emissions fluctuate. Carbon Mapper pieced together a time series of a section of the Permian Basin in the southwestern US, in which the dots correspond with methane emissions. About half the time, Duren estimates, some of the worst offenders may be venting methane directly into the atmosphere to relieve pressure, while the other half probably represent persistent leaks and malfunctions. +
++Environmentalists argue we must transition off coal, gas, and oil as quickly as possible — but stopping the pollution can’t wait for the transition to play out. A coalition of 134 environmental and health groups have rallied around a certain target — cutting 65 percent of the oil and gas industry’s methane pollution by 2025 — and have pressured the Biden administration to adopt the same goal by using existing technology. +
++The gains from containing methane will be critical as the world continues to gamble with its climate. A study from EDF scientists published in the peer-reviewed journal Environmental Research Letters found that tackling methane emissions across multiple sectors, including oil and gas, agriculture, and landfills, can slow the current rate of runaway warming by a staggering 30 percent. One-quarter of one degree Celsius by 2050 might not sound like a lot, but small changes to global averages contain a range of extreme impacts that will worsen across the globe. +
++There’s the good news: The world doesn’t need to wait around for better science. Action is feasible now. +
+ ++When the IPCC report came out on August 9, Lisa DeVille, a member of the Dakota Resource Council who lives on the Fort Berthold Indian Reservation, was encouraged to hear scientists “echoing what most of us can see with our own eyes,” based on what she sees on the front lines of oil production in North Dakota. +
++“The land near my home is crisscrossed with oil and gas pipelines, literally littered with drilling rigs,” DeVille said in a call with reporters. She said her home has been ravaged by unusually high rainfall and flooding, and she and her husband have had to breathe in smoke from wildfires. “I live less than a mile away from well pads that vent and flare methane and choke our atmosphere, making local people like my husband and I sick. This means the land that is part of my identity as an Indigenous woman has been turned into a pollution-filled industrial zone.” +
+ ++Under pressure from climate advocates, the EPA proposed a new set of methane rules in November. Once finalized, the rules would require oil and gas companies to monitor and address methane leaks from existing and future wells, using sensors and regular equipment checks. The administration says the new rule covers 75 percent of all methane emissions in the US. +
++The proposal is just the first step in a long road ahead to seeing serious methane cuts from oil and gas. The regulations may face long delays as the EPA gathers public comment and opponents launch lawsuits. They are also at risk of reversal if a Republican takes the White House in the next two elections. +
++There’s widespread agreement, even from some in the fossil fuel industry, that the place to start is tackling leaks. This will get easier as scientists gather better data about where methane is leaking. From the industry’s perspective, companies are losing product and dollars. For activists, plugging leaks is one step on the road to permanently phasing out gas. +
++For all the industry’s talk of reining in methane leaks, oil companies remain one of the biggest obstacles standing in the way of tougher methane restrictions in the US. An important part of the proposed Build Back Better bill Congress is debating would place a fee on methane emissions, not only ensuring better monitoring for methane but financially swaying oil producers to fix the worst problem areas. The oil industry lobby, the American Petroleum Institute, has formally opposed the measure that counts as one of the most impactful climate policies still on the table in the Build Back Better agenda. +
++The problem that underlies all climate action is that humanity has to trade short-term profit for long-term benefit. Carbon dioxide affects the world for the long haul, and methane is making the crisis significantly worse in the near term. +
+On the plus side, tackling methane and other dangerous pollutants would have an “immediate payoff,” said Global Methane Assessment’s Shindell. It could change our dangerous climate trajectory over the next 30 years. +
++“Every action counts,” said Jane Lubchenco, a senior science adviser to the Biden administration, in an August interview with Vox. “Every avoided tenth of a degree matters.” +
++Fractions of degrees could translate into wild swings in extreme weather, or tipping points we don’t even fully understand. In the effort to prevent climate catastrophe, methane will count tremendously. +
++Update, November 3, 4 pm: This story has been updated to include developments at COP26 and the Biden administration’s announcement that it will regulate methane from new and existing oil and gas operations. +
++Democrats’ Virginia loss and the close New Jersey race may have a common root. +
++Democrats’ loss in Virginia’s governor race and a closer-than-expected contest in New Jersey this week came as a surprise to many. But in retrospect, there was one glaring warning sign: President Joe Biden’s declining approval rating. When presidents have bad approval ratings, their party tends to do poorly in downballot races. +
++In FiveThirtyEight’s average of polls, Biden’s approval is down to 42.9 percent, with his disapproval rating up to 50.7 percent. It’s obviously not good to be nearly 8 points underwater, but with historical context, Biden’s situation looks even worse. +
++For one, Biden’s disapproval rating at this point in his term is higher than all but one president’s since the advent of modern polling. Only Donald Trump’s was higher, by about 6 percentage points, per FiveThirtyEight’s historical numbers. +
++Biden’s approval rating is already lower than Barack Obama’s and Bill Clinton’s were just before their disastrous 2010 and 1994 midterms — Obama’s approval was at 45 percent, and Clinton’s was at 47.2 percent. Democrats lost 63 House of Representatives seats in 2010 and 54 seats in 1994. +
++As for Trump, Biden’s 42.9 percent approval rating right now is only slightly higher than Trump’s 42 percent on the eve of the 2018 midterms, when Republicans lost 40 House seats. +
++The one potential silver lining for Biden is that the trajectory of Trump’s numbers shows that some improvement in the second year is possible, albeit rare. Trump’s approval rating hit its lowest point in 2017 but improved by about 5 points over 2018, which likely helped him avoid an even worse midterm defeat. It is possible that if conditions in the country improve, Biden’s numbers could rebound. +
++Of course, things could also get worse. +
++Biden’s numbers haven’t always been this awful. Like most presidents (Trump excepted), Biden started his term reasonably popular — per FiveThirtyEight’s tracker, his approval rating was about 53 percent and his disapproval was about 36 percent. +
++Also like most presidents, he lost some of that sheen, but as of mid-August things still looked decent for him — 50 percent approval and 43.8 percent disapproval. That’s not so bad for a president in the modern polarized era who won with 51.3 percent of the popular vote. +
++Then things took a turn. In the final two weeks of August, as headlines were dominated by chaos in Afghanistan while Biden was withdrawing troops, the president’s numbers dropped precipitously, and his disapproval rating topped his approval rating for the first time. +
++And things never really got better — indeed, they got worse. The media moved on from Afghanistan, but the rise of the delta variant and renewed economic woes loomed large as summer changed to autumn. Biden’s approval kept dropping, his disapproval kept rising, and his numbers are now at their worst yet. +
++In mid-August, a majority of Americans approved of Biden, and now a majority disapprove of him. In just two and a half months, he lost the country. +
++The timing of Biden’s decline makes it hard to deny that the tumultuous Afghanistan withdrawal played a significant part. But it’s not the whole story. Biden was already trending downward, albeit more slowly, beforehand, and continued trending downward after national attention turned elsewhere. +
++Part of this might be unavoidable — some frustration and backlash against the president are common in advance of the midterm elections — but, again, Biden’s numbers are worse than Clinton’s or Obama’s at this point. While a loss of support for the president may be common, just exactly how much support is lost can vary. +
++One big factor is probably that Americans went from believing, in June, that the end of the pandemic was imminent and economic recovery was here to being rudely awakened by delta and higher prices over the following months. +
++In a recent NBC News national poll, net approval of Biden’s performance on the economy dropped from +9 in April to -17 in October. Net approval of his handling of the pandemic dropped from +42 to +4 during that same span. About half of respondents also gave Biden low marks for “competence.” +
++From Afghanistan to his legislative agenda to the economy to the coronavirus, the narrative has been the same: that Biden is floundering and ineffective. Some of those criticisms are fair; some are blaming him for events out of his control. But to have any hope of averting midterm disaster, that perception has to change. +
++
++
++
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+The crew and the Secret Service were scrambling to launch a boat to go get it, when Biden waved them off, saying, “Never mind boys, I’ll get it.” +
++Then Joe climbed over the side of the yacht, walked on the water to the hat, picked it up, +
++walked back on the water, climbed into the yacht, and handed the Pope his hat. +
++The crew was speechless. The security team and the Pope’s entourage were speechless. No one knew what to say, not even the Pope. +
++But that afternoon, ABC, CBS, NBC, CNN, MSNBC reported: +
++“BIDEN CAN’T SWIM” +
+ submitted by /u/YZXFILE
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+Man 1: No, shark attack. +
+ submitted by /u/AdligaTitlar
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+Screws, nuts, and bolts. +
+ submitted by /u/BookerCatchanSTD
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+As a last present, his parents brought him to Arabia on a trip. While they were walking through a market, little Benny bought a lamp from a vendor. +
++When he arrived home, he rubbed the lamp to clean it, and, to his surprise, a genie popped out in a flash of light. +
++“What is it that you require?”, the genie boomed. “I just want to get better,” little Benny replied. +
++“Very well,” said the genie. “But on one condition: as per the custom of my people, you can never shave your face. If you do, you will be turned into a Persian urn.” +
++Little Benny eagerly agreed, and the genie disappeared. When little Benny went to the doctor again, he was shocked to see that Benny had completely recovered. +
++Years go by. Benny has grown up and gotten married. All this time, he had kept his word, and never shaven once. However, it was beginning to get to him. It was hard to sleep at night because of the heavy beard and the itching. +
++One night, he decides he has had enough and grabs a razor to shave. His wife tries to talk him out of it, but he doesn’t listen. +
++As soon as the razor cuts a single hair, he transforms into a large Persian urn. +
++The moral of the story? A Benny shaved is a Benny urned. +
+ submitted by /u/welltechnically7
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+She heard a strange buzzing noise coming from within. Opening the door, she observed her daughter with a vibrator. +
++Shocked, she asked: ‘what in the world are you doing?’ +
++The daughter replied: ‘Mom, I’m thirty-five years old, unmarried, and this thing is about as close as I’ll ever get to a husband. Please, go away and leave me alone.’ +
++The next day, the girl’s father heard the same buzz coming from the other side of the closed bedroom door. Upon entering the room, he observed his daughter making passionate love to her vibrator. +
++To his query as to what she was doing, the daughter said: ‘Dad I’m thirty-five, unmarried, and this thing is about as close as I’ll ever get to a husband. Please, go away and leave me alone.’ +
++A couple days later, the wife came home from a shopping trip, placed the groceries on the kitchen counter, and heard that buzzing noise coming from, of all places, the living room. She entered that area and observed her husband sitting on the couch, downing a cold beer, and staring at the TV. +
++The vibrator was next to him on the couch, buzzing like crazy. +
++The wife asked: ‘What the heck are you doing?!’ +
++The husband replied: ‘I’m watching football with my son-in-law.’ +
+ submitted by /u/PurrrplePrincess
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