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+ + + ++Background: Migrants in the UK may be at higher risk of SARS-CoV-2 exposure; however, little is known about their risk of COVID-19-related hospitalisation during waves 1-3 of the pandemic. Methods: We analysed secondary care data linked to Virus Watch study data for adults and estimated COVID-19-related hospitalisation incidence rates by migration status. To estimate the total effect of migration status on COVID-19 hospitalisation rates, we ran fixed-effect Poisson regression for wave 1 (01/03/2020-31/08/2020; wildtype), and fixed-effect negative binomial regressions for waves 2 (01/09/2020-31/05/2021; Alpha) and 3 (01/06/2020-31/11/2021; Delta). Results of all models were then meta-analysed. Results: Of 30,276 adults in the analyses, 26,492 (87.5%) were UK-born and 3,784 (12.5%) were migrants. COVID-19-related hospitalisation incidence rates for UK-born and migrant individuals across waves 1-3 were 2.7 [95% CI 2.2-3.2], and 4.6 [3.1-6.7] per 1,000 person-years, respectively. Pooled incidence rate ratios across waves suggested increased rate of COVID-19-related hospitalisation in migrants compared to UK-born individuals in unadjusted 1.68 [1.08-2.60] and adjusted analyses 1.35 [0.71-2.60]. Conclusions: Our findings suggest migration populations in the UK have excess risk of COVID-19-related hospitalisations and underscore the need for more equitable interventions particularly aimed at COVID-19 vaccination uptake among migrants. +
++Abstract Background The impact of the COVID-19 pandemic on the Hispanic population resulted in the almost complete elimination of the longstanding Hispanic mortality advantage relative to the non-Hispanic White population. However, it is unknown how COVID-19 mortality affected the diverse Hispanic sub-populations. Objective We estimate life expectancy at birth in 2019 and 2020 by Hispanic sub-group and explore how changes in age-specific all-cause and COVID-19 mortality affected changes in life expectancy between 2019 and 2020 for each group. Methods We use final 2019 and 2020 mortality data from the National Center for Health Statistics and population estimates based on the 2019 and 2020 American Community Survey. We calculate life tables and apply decomposition techniques to explore the effects of changes in age- and cause-specific mortality on life expectancy. Results Patterns of age- and cause-specific excess deaths and their impact on declines in life expectancy due to the COVID-19 pandemic differed substantially by Hispanic sub-group. Life expectancy losses ranged from 0.6 to 6.7 years among males and 0.6 to 3.6 years among females. Conclusions Our findings highlight the heterogeneous impact of the COVID-19 pandemic within the Hispanic population. Contributions Our findings contribute new information that will assist future research identify the causes of the disproportionately severe impact of the COVID-19 pandemic on the Hispanic population. Our study underscores the importance of population disaggregation in endeavors to identify the multiple pathways by which the pandemic affected the Hispanic population. +
++The coronavirus disease (COVID-19) pandemic resulted in major disruptions to the food service industry and regulatory food inspections. The objective of this study was to conduct an interrupted time series analysis to investigate the impact of the COVID-19 pandemic on food safety inspection trends in Toronto, Canada. Inspection data for restaurants and take-out establishments were obtained from 2017 to 2022 and ordered as a weekly time series. Bayesian segmented regression was conducted to evaluate the impact of the pandemic on weekly infraction and inspection pass rates. On average, a 0.31-point lower weekly infraction rate (95% credible interval [CI]: 0.23, 0.40) and a 2.0% higher probability of passing inspections (95% CI: 1.1%, 3.0%) were predicted in the pandemic period compared to pre-pandemic. Models predicted lower infraction rates and higher pass rates immediately following the pandemic that were regressing back toward pre-pandemic levels in 2022. Seasonal effects were also identified, with infraction rates highest in April and pass rates lowest in August. The COVID-19 pandemic resulted in an initial positive effect on food safety outcomes in restaurants and take-out food establishments in Toronto, but this effect appears to be temporary. Additional research is needed on seasonal and long-term inspection trends post-pandemic. +
++We have developed a CRISPR based assay that can detect the presence of SARS-CoV-2 in RNA extracted from human samples and also predict if it is an Omicron or non-Omicron variant of the virus. This is a nucleic acid amplification-based test (NAAT). The amplification and detection are carried out in two independent steps in this assay. Amplification is done using a standard one-step RT-PCR method. The detection is done using a method that utilizes the trans-cleavage activity of the Cas12a enzyme. We have evaluated the performance of OmiCrisp in more than 80 clinical samples and observed an agreement of 100% with the sequencing results, in labeling SARS-CoV-2 positive samples as Omicron or non-Omicron. OmiCrisp -like platform can be developed quickly and can potentially complement sequencing for quick and rapid tracking of the transmission of new pathogen variants. +
++T cells play key protective but also pathogenic roles in COVID-19. We studied expression of long non-coding RNAs (lncRNAs) in COVID-19 T cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highest MALAT1 expression, amongst CD4+ and CD8+ T cells populations, respectively. We then identified gene signatures that covaried with MALAT1 in single T cells. A significantly higher number of transcripts correlated negatively with MALAT1 than those that correlated. Enriched functional annotations of the MALAT1- anti-correlating gene signature included processes associated with T cell activation such as cell division, oxidative phosphorylation and response to cytokine. The MALAT1 anti-correlating gene signature shared by both CD4+ and CD8+ T cells marked dividing T cells in both lung and blood of COVID-19 patients. Focussing on the tissue, we used an independent patient cohort of post-mortem COVID-19 lung samples and demonstrated that MALAT1 suppression was indeed a marker of MKI67+ proliferating CD8+ T cells. Our results reveal MALAT1 suppression and its associated gene signature are a hallmark of human proliferating T cells. +
++Background Since early in the COVID-19 pandemic, SARS-CoV-2 wastewater concentration has been measured as a surrogate for community prevalence. However, our knowledge remains limited regarding wastewater concentration and effects of the COVID-19 vaccination on overall disease burden as measured by hospitalization rates. Methods We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and spatially linked vaccination and hospitalization data, from April to August 2021. Our susceptible (S), vaccinated (V), variant-specific infected (I1 and I2), recovered (R), and seropositive (T) model (SVI2RT) tracked prevalence longitudinally. This was related to wastewater concentration for a spatial analysis of strain mutation, vaccination effect, and overall hospitalization burden. Findings We found strong linear association between wastewater concentration and estimated community prevalence (r=0.916). Based on the corresponding regression model, the 64% county vaccination rate translated into about 57% decrease in SARS-CoV-2 incidence. During the study period, the estimated effect of SARS-CoV-2 Delta variant emergence was seen as an over 7-fold increase of infection counts, which corresponded to over 12-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration had the strongest correlation (r=0.963) at 1 week lag time. We estimated the community vaccination campaign resulted in about 63% reduction in the number of daily admissions over the study period. This protective effect was counteracted by the emergence of SARS-CoV-2 Delta strain mutation. Interpretation Wastewater samples can be used to estimate the effects of vaccination and hospitalization burden. Our study underscores the importance of continued environmental surveillance post-vaccine and provides a proof of concept for environmental epidemiology monitoring. +
++Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the FDA in late 2020 for adults, approval for young children 6 months to < 5 years of age did not occur until 2022. Understanding real world vaccine effectiveness in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 vaccine effectiveness (VE) against infection among children aged >6 months and adults aged <50 years. Methods: CASCADIA is a four-year community-based prospective study of SARS-CoV-2 VE among adult and pediatric populations aged 6 months to 49 years in Oregon and Washington. At enrollment and regular intervals, participants complete a sociodemographic questionnaire. Individuals may provide a blood sample at enrollment and annually thereafter, with additional, optional blood draws after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by RT-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who report symptoms outside of their weekly swab collection and symptom survey are asked to collect an additional swab. Participants who test positive for SARS-CoV-2 undergo serial swab collection every three days for three weeks. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralization assays. Analysis: Cox regression models will be used to estimate the hazard ratio associated with SARS-CoV-2 vaccination among the pediatric and adult population, controlling for demographic factors and potential confounders, including clustering within households. +
++As the coronavirus (COVID-19) pandemic approaches the three-year mark and the number of confirmed COVID-19 cases now exceeds 100 million cases in the United States and continues to climb, there have been increasing concerns raised over the future public health and economic burden of long COVID including disability and concomitant declines in labor force participation. Only a handful of US studies have explored sociodemographic and socioeconomic characteristics that may put people at risk of long COVID or have investigated the possible mental health and socioeconomic sequelae of long COVID. In this paper, I report findings from the largest multivariable analysis to date using US nationally-representative population-based data on 152,812 adults including 19,871 adults with long COVID to explore key predictors and sequelae of long COVID. An estimated 14.0% of US adults aged 18-84 years (34.55 million adults; 95% CI = 33.63 to 35.47 million adults) and 15.4% of US working-aged adults aged 18-64 years (31.14 million adults; 95% CI = 30.26 to 32.02 million adults) had developed long COVID by November 2022. I identify several sociodemographic and socioeconomic factors as predictors of long COVID including lower household income levels, being Hispanic, female, gay/lesbian or bisexual, and divorced or separated. Even after accounting for such factors, having long COVID was linked to higher risks of recent unemployment, financial hardship, and anxiety and depressive symptomatology, with evidence of dose-response relationships. Overall, an estimated 27.3 million US adults with long COVID were at risk of adverse socioeconomic and health outcomes including anxiety and depression. These preliminary estimates highlight the substantial public health and economic implications of long COVID among Americans and should prompt further inquiry and intervention. +
++Background: As there are limited data on B cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine. Methods: Using overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n=30), WT infected (n=30), delta infected (n=30), omicron infected+vaccinated (n=20) and Sinopharm (BBIBP-CorV) vaccinees (n=30). We then investigated the sensitivity and specificity of these immunodominant regions and analysed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses and bat Sarbecoviruses. We then investigated the kinetics of responses to these regions in those with varying severity of acute COVID-19. Results: We identified four immunodominant regions aa 29-52, aa 155-178, aa 274 to 297 and aa 365 to 388, were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, with WT infected individuals predominantly recognizing aa155 to 178 regions, delta infected individuals and vaccinated+omicron infected individuals predominantly recognizing regions aa 29 to 52 and aa 274 to 294 regions. Sinopharm vaccinees recognized all four regions, with the magnitude of responses significantly lower than other groups. >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses. Conclusions: N-protein specific responses appear to be detectable in over 90% of those who were naturally infected or vaccinated with a whole virus inactivated vaccine, with responses mainly directed against four regions of the protein, which were highly conserved. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines. +
++Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the FDA in late 2020 for adults, approval for young children 6 months to < 5 years of age did not occur until 2022. Understanding real world vaccine effectiveness in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 vaccine effectiveness (VE) against infection among children aged >6 months and adults aged <50 years. Methods: CASCADIA is a four-year community-based prospective study of SARS-CoV-2 VE among adult and pediatric populations aged 6 months to 49 years in Oregon and Washington. At enrollment and regular intervals, participants complete a sociodemographic questionnaire. Individuals may provide a blood sample at enrollment and annually thereafter, with additional, optional blood draws after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by RT-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who report symptoms outside of their weekly swab collection and symptom survey are asked to collect an additional swab. Participants who test positive for SARS-CoV-2 undergo serial swab collection every three days for three weeks. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralization assays. Analysis: Cox regression models will be used to estimate the hazard ratio associated with SARS-CoV-2 vaccination among the pediatric and adult population, controlling for demographic factors and potential confounders, including clustering within households. +
++Background It was found that more than half of the population in Korea had a prior COVID-19 infection. In 2022, most nonpharmaceutical interventions, except mask-wearing indoors, had been lifted. Discussions about easing the indoor mask mandate are ongoing. Methods We developed an age-structured compartmental model that distinguishes vaccination history, prior infection, and medical staff from the rest of the population. Contact patterns among hosts were separated based on age and location. We simulated scenarios with the lifting of the mask mandate all at once or sequentially according to the locations. Furthermore, we investigated the impact of a new variant assuming that it has higher transmissibility and risk of breakthrough infection. Findings We found that the peak size of administered severe patients might not exceed 1,100 when the mask mandate is lifted everywhere, and 800 if the mask mandate only remains in the hospital. If the mask mandate is lifted in a sequence (except hospital), then the peak size of administered severe patients did not exceed 650. Moreover, if the new variant have both of higher transmissibility and immune reduction therefore the effective reproductive number of the new variant is approximately 3 times higher than the current variant, additional interventions may be needed to keep the administered severe patients from exceeding 2,000, which is the critical level we set. Interpretation Our findings showed that the lifting of the mask mandate, except in hospitals, would be applicable more manageable if it is implemented sequentially. Considering a new variant, we found that depending on the population immunity and transmissibility of the variant, wearing masks and other interventions may be necessary for controlling the disease. +
++Introduction: With the global spread of Coronavirus disease (COVID-19) and public health crisis, appropriate allocation of healthcare human resources has been necessitated. Although nursing practice takes up a larger part of medical practice in hospitals, the quantitative assessment of nursing care has not been investigated for human resource allocation in the medical field. The objective of this study to explore the time spent for each nursing intervention, and compared provided amount of nursing intervention between negative pressure isolation wards (NPIWs) and general wards (GWs) provided by COVID-19 hub hospitals. Methods: This research is a time-motion (TM) observational study. Three trained external observers recorded their observations for every minute in 19 different work schedules in 2 NPIWs and 2 general respiratory wards. Observation items were chosen based on the standard operating guidelines of Integrated Nursing and Caring Services developed by the Ministry of Health and Welfare and National Health Insurance Service. The average nursing workload per shift was compared by calculating the sum of the spent time of three nurses staffed in each shift in each ward between two groups. In addition, to compare the amount of directed nursing care for patients between two types of wards, nursing work category was divided into directed and undirected nursing interventions. Results: In the comparison of demographic characteristics of nursing workforce between two groups, there was no statistically significant difference (p>0.05 respectively). In both groups, the most time-consuming nursing work category was recording in three work shifts. The average duration of those work tasks was 312.5 minutes in NPIWs and 307 minutes (per 3 nurses) in GWs, having no significant difference (p>0.05). Of all nurse duties, the second most time-consuming work category was others (including changing to protective clothing) in NPIWs, and medication administration and transfusion in GWs. The mean duration of performing the category for others that include wearing PPE was 308 minutes in NPIWs and 160 minutes (per 3 nurses) in GWs, showing a significant difference (p<0.05). The greater amount of time was taken for hygiene management in isolation wards. Medication administration and transfusion and nursing assessment were more frequently performed in GWs, demonstrating a statistical significance. In the aggregated spent time for all duties including directed and undirected nursing care, the time spent for directed nursing care was 654 minutes longer in GWs than in NPIWs (per 3 nurses) in each work shift, displaying a significant difference. Conclusion: This study provides the quantitative difference in time-consuming nursing works between NPIWs and GWs by direct observation. Recording was the most time-consuming nursing work category in both NPIWs and GWs. Considering nurses in each duty in GWs provided more directed nursing care than nurse in NIPWs, careful considerations are required in allocation of nursing workforce. +
++Growth and aging are fundamental features of animal life. The march from fertilization to oblivion comes in enormous variety: days and hundreds of cells for nematodes, decades and trillions of cells for humans. Since Verhulst (1838) proposed the Logistic Equation (exponential growth with a countervailing linear decline in rate) biologists have searched for ever better density-dependent growth equations, none of which accurately capture the relationship between size and time for real animals. Furthermore, while growth and aging run in parallel, whether the relationship is causal has yet to be determined. Similarly unknown has been the reason behind the exponential Force of Mortality, described by Gompertz in 1825 for all-cause mortality and reported by Levin et al. in 2020 for COVID 19. Here we report that examination in units of numbers of cells, N, Cellular Phylodynamic Analysis, reveals that growth, lifespan, and mortality, are linked to the reduction in the fraction of cells dividing, occurring by a simple expression, the Universal Mitotic Fraction Equation. Lifespan is correlated with an age when fewer than one-in-a-thousand cells are dividing, quantifying the long-appreciated mechanism of aging, the failure of cells to be rejuvenated by dilution with new materials made and DNA repaired at mitosis. These observations provide practical mathematical tools for comprehending and managing the challenges of growth and aging, for such tasks as deciphering COVID-19 lethality and its amelioration by vaccination. +
++Gauging COVID 19 lethality, and how vaccination can reduce that lethality, has been challenging. Here, a new method, Gompertzian Analysis, counting cases and deaths, by age, and displaying them on logarithmic graphs, is outlined, and its first findings presented: FIRST, COVID-19 Gompertzian Lethality (Deaths/Cases) exhibits an ~10,000-fold exponential increase in the chance of death with age, the Gompertzian Force of Mortality, captured by the Gompertz Mortality Equation. SECOND, COVID-19 Pasteurian Infectivity (Cases/Population) occurs at similar rates across ages. THIRD, the same Gompertzian Force of Mortality characterizes other diseases and all-cause mortality, possibly from loss of Mitotic Dilution of toxic compounds due to decline in mitosis. FOURTH, resistance to COVID-19 infectivity and lethality appear to be separate processes. FIFTH, Over the past several years, Gompertzian Lethality, has declined, but not Pasteurian Infectivity. SIXTH, with each variant, Gompertzian Lethality has declined, but not Pasteurian Infectivity. SEVENTH, the unvaccinated have seen a decline in Gompertzian Lethality, less than the vaccinated, ascribable to infection, at the cost of lives lost. EIGHTH, different vaccines have different reductions in Gompertzian Lethality and Pasteurian Infectivity. NINTH, vaccination has reduced Pasteurian Infectivity, but not enough to suppress the pandemic. TENTH, vaccination has reduced Gompertzian Lethality, with sequential vaccination pointing linearly towards zero death after 3 or 4 boosters, without signs of waning. CONCLUSION: Gompertzian Analysis provides new, practical, actionable, information for understanding, and minimizing, the lethal burden of COVID 19 and other diseases. +
++Relaxing social distancing measures and reduced level of influenza over the last two seasons may lead to a winter 2022 influenza wave in England. We used an established model for influenza transmission and vaccination to evaluate the rolled out influenza immunisation programme over October to December 2022. Specifically, we explored how the interplay between pre-season population susceptibility and influenza vaccine efficacy control the timing and the size of a possible winter influenza wave. Our findings suggest that susceptibility affects the timing and the height of a potential influenza wave, with higher susceptibility leading to an earlier and larger influenza wave while vaccine efficacy controls the size of the peak of the influenza wave. With pre-season susceptibility higher than pre-COVID-19 levels, under the planned vaccine programme an early influenza epidemic wave is possible, its size dependent on vaccine effectiveness against the circulating strain. If pre-season susceptibility is low and similar to pre-COVID levels, the planned influenza vaccine programme with an effective vaccine could largely suppress a winter 2022 influenza outbreak in England. +
+Efficacy and Safety of Jaktinib in Patients With COVID-19 Pneumoia - Condition: COVID-19 Pneumonia
Interventions: Drug: Jaktinib; Drug: Placebo
Sponsor: First Affiliated Hospital of Zhejiang University
Not yet recruiting
Effect of a Traditional Chinese Medicine Formulation on COVID-19 Infection - Condition: COVID-19
Interventions: Drug: Traditional Chinese Medicine Formulation; Other: Placebo Treatment
Sponsor: First Affiliated Hospital Xi’an Jiaotong University
Not yet recruiting
Efficacy and Safety of Anti-COVID-19 Antibody SA58 Nasal Spray to Prevent Infection in High-risk Populations - Condition: COVID-19
Intervention: Drug: SA58 Nasal Spray
Sponsor: Sinovac Life Sciences Co., Ltd.
Recruiting
Efficacy and Safety of SA58 Nasal Spray in Close Contact With COVID-19 People - Condition: COVID-19
Interventions: Drug: SA58 Nasal Spray; Drug: Placebo
Sponsors: Sinovac Life Sciences Co., Ltd.; Beijing Ditan Hospital
Recruiting
Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines - Condition: COVID-19
Interventions: Biological: CoronaVac/CoronaVac; Biological: CoronaVac/BNT162b2
Sponsor: Institut Pasteur de Tunis
Completed
Immunogenicity and Safety of COVID-19 Vaccine as a Booster Vaccination in Population Aged 18 Years and Above - Condition: COVID-19
Interventions: Biological: Recombinant SARS-CoV-2 Vaccine (CHO Cell) LYB001; Biological: ZF2001
Sponsors: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.
Not yet recruiting
A Vaccine Booster (GEO-CM04S1) for the Prevention of COVID-19 in Patients With Chronic Lymphocytic Leukemia - Conditions: Chronic Lymphocytic Leukemia; COVID-19 Infection
Interventions: Procedure: Biospecimen Collection; Biological: mRNA COVID-19 Vaccine; Biological: Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1
Sponsors: City of Hope Medical Center; National Cancer Institute (NCI)
Not yet recruiting
Sars-COV-2 Immunity in immunoCOmpromised Populations - Conditions: SARS CoV 2 Infection; COVID-19
Intervention: Diagnostic Test: Humoral immunity
Sponsors: Maria Goossens; Université Libre de Bruxelles; Institute of Tropical Medicine, Belgium; Mensura EDPB; Erasme hospital
Not yet recruiting
Safety, Tolerability and Pharmacokinetic Characteristics Evaluation on GST-HG171 Tablets - Condition: COVID-19
Interventions: Drug: GST-HG171; Drug: placebo of GST-HG171
Sponsor: Fujian Akeylink Biotechnology Co., Ltd.
Recruiting
Benefits of an Aerobic and Strength Rehabilitation Program With Post- SARS-CoV-2 Patients Moderate-severe - Condition: COVID-19
Interventions: Other: Aerobic plus strength group; Other: Aerobic group
Sponsor: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Not yet recruiting
The Effect of Amantadine on Post-COVD-19 Fatigue - Condition: Post-COVID-19 Syndrome
Intervention: Drug: Amantadine
Sponsor: Shahid Beheshti University of Medical Sciences
Not yet recruiting
Enhanced External Counterpulsation to Treat Long COVID Fatigue - Condition: Post-Acute COVID-19 Syndrome
Intervention: Procedure: Enhanced external counterpulsation
Sponsor: Sheba Medical Center
Not yet recruiting
Oral Vitamin D2 for Prevention of COVID-19 - Condition: Healthy Volunteers
Interventions: Drug: Vitamin D2; Other: placebo
Sponsors: Peking University Third Hospital; Beijing Haidian Hospital
Recruiting
Melatonin, Vitamins and Minerals Supplements for the Treatment of Covid-19 and Covid-like Illness - Condition: Influenza -Like Illness
Intervention: Drug: kelavit
Sponsor: Hôpital Universitaire Sahloul
Not yet recruiting
Effectiveness of Rapid Antigen Testing of Students for COVID-19 in Reducing Absences From Schools in Bangladesh - Condition: School Absenteeism
Intervention: Diagnostic Test: Rapid Antigen Testing (RAT) for COVID-19
Sponsors: International Centre for Diarrhoeal Disease Research, Bangladesh; Columbia University
Completed
Huashibaidu formula attenuates sepsis-induced acute lung injury via suppressing cytokine storm: Implications for treatment of COVID-19 - CONCLUSION: The therapeutic mechanism of HSBD against sepsis-induced ALI mainly involved suppressing cytokine storms and relieving inflammatory symptoms by regulating the expression of TLR4/NF-κB and PI3K/Akt. Our study provides a scientific basis for the mechanistic investigation and clinical application of HSBD in the treatment of sepsis and COVID-19.
Xuanfei Baidu Decoction suppresses complement overactivation and ameliorates IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway - CONCLUSION: XFBD suppressed complement overactivation and ameliorated IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway. These data contribute to understanding the mechanisms of XFBD in COVID-19 treatment.
Blue light irradiation exerts anti-viral and anti-inflammatory properties against herpes simplex virus type 1 infection - The aim of this study was to investigate the antiviral and anti-inflammatory functions of blue light (BL) in cutaneous viral infections. Previously, we examined the photo-biogoverning role of 450 nm BL in SARS-CoV-2-infected cells, which showed that photo-energy could inhibit viral activation depending on the number of photons. However, the communication network between photo-energy irradiation and immune cells involved in viral infections has not been clarified. We verified viral activation,…
A vaccine delivery system promotes strong immune responses against SARS-CoV-2 variants - Global COVID-19 pandemics highlight the need of developing vaccines with universal and durable protection against emerging SARS-CoV-2 variants. Here we developed an extended-release vaccine delivery system (GP-diABZI-RBD), consisting the original SARS-CoV-2 WA1 strain receptor-binding domain (RBD) as the antigen and diABZI STING agonist in conjunction with yeast β-glucan particles (GP-diABZI) as the platform. GP-diABZI-RBD could activate STING pathway and inhibit SARS-CoV-2 replication. Compared…
Antiviral role of nanomaterials: a material scientist’s perspective - The present world continues to face unprecedented challenges caused by the COVID-19 pandemic. Collaboration between researchers of multiple disciplines is the need of the hour. There is a need to develop antiviral agents capable of inhibiting viruses and tailoring existing antiviral drugs for efficient delivery to prevent a surge in deaths caused by viruses globally. Biocompatible systems have been designed using nanotechnological principles which showed appreciable results against a wide range…
Fluorogenic reporter enables identification of compounds that inhibit SARS-CoV-2 - The coronavirus SARS-CoV-2 causes the severe disease COVID-19. SARS-CoV-2 infection is initiated by interaction of the viral spike protein and host receptor angiotensin-converting enzyme 2 (ACE2). We report an improved bright and reversible fluorogenic reporter, named SURF (split UnaG-based reversible and fluorogenic protein-protein interaction reporter), that we apply to monitor real-time interactions between spike and ACE2 in living cells. SURF has a large dynamic range with a dark-to-bright…
mascRNA alleviates STING-TBK1 signaling-mediated immune response through promoting ubiquitination of STING - mascRNA (MALAT1-associated small cytoplasmic RNA) is a tRNA-like cytoplasmic small noncoding RNA whose function remains elusive. We previously revealed that this small RNA negatively regulates TLR4/2-triggered proinflammatory response while positively regulates TLR3-induced antiviral response. Here, we investigated whether and how mascRNA influences the stimulator of interferon genes (STING) signaling-triggered immune response. We found that overexpression of mascRNA inhibited the expression of…
Porcine Epidemic Diarrhea Virus nsp13 Protein Downregulates Neonatal Fc Receptor Expression by Causing Promoter Hypermethylation through the NF-κB Signaling Pathway - Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic porcine enteric coronavirus that causes severe watery diarrhea and even death in piglets. The neonatal Fc receptor (FcRn) is the only transport receptor for IgG. FcRn expressed by intestinal epithelial cells can transport IgG from breast milk to piglets to provide immune protection. Previous studies have shown that viral infection affects FcRn expression. In this study, we showed for the first time, to our knowledge, that FcRn…
Identification and semisynthesis of (-)-anisomelic acid as oral agent against SARS-CoV-2 in mice - (-)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC(50) of 1.1 and 4.3 μM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung…
Rapid Resolution of Post-COVID-19 Inflammatory Syndrome in an Adult With Targeted Inhibition of Interleukin-1B - Multisystem inflammatory syndrome (MIS) is a severe inflammatory response that occurs days to weeks following the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). Initially known in children and named MIS-C, recently several cases of MIS in adults have been reported to the Centers for Disease Control and Prevention (CDC), leading to the recognition of a new disease MIS in adults (MIS-A). The current…
Anti-CD73 antibody activates human B cells, enhances humoral responses and induces redistribution of B cells in patients with cancer - CONCLUSIONS: Mupadolimab activates B cells and stimulates the production of antigen specific antibodies. The effects in patients with cancer suggest that activated, CD69^(POS) B cells redistribute to lymphoid tissues. Minor tumor regression was observed in several patients. These results support further investigation of mupadolimab as an immunotherapy for cancer and its potential use as a vaccine adjuvant.
Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19 - Spleen tyrosine kinase (SYK) is a previously unidentified therapeutic target that inhibits neutrophil and macrophage activation in coronavirus disease 2019 (COVID-19). Fostamatinib, a SYK inhibitor, was studied in a phase 2 placebo-controlled randomized clinical trial and was associated with improvements in many secondary end points related to efficacy. Here, we used a multiomic approach to evaluate cellular and soluble immune mediator responses of patients enrolled in this trial. We…
Targeting Spike Glycans to Inhibit SARS-CoV2 Viral Entry - SARS-CoV-2 Spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the Spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety…
Data-driven drug discovery for drug repurposing - To improve the decreased efficiency of drug discovery and development, drug repurposing (also called drug repositioning) has been expected, that it is a strategy for identifying new medical indications for approved, investigational or suspended drugs. Particularly, according to the rapid expansion of medical and life science data and the remarkable technological progress of AI technology in recent years, the approach of computational drug repurposing has been attracted as one of the applications…
Endogenous G-quadruplex-forming RNAs inhibit the activity of SARS-CoV-2 RNA polymerase - Replication of RNA viruses is catalysed by virus-specific polymerases, which can be targets of therapeutic strategies. In this study, we used a selection strategy to identify endogenous RNAs from a transcriptome library derived from lung cells that interact with the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. Some of the selected RNAs weakened the activity of RdRp by forming G-quadruplexes. These results suggest that certain endogenous RNAs, which potentially form G-quadruplexes, can…
Kevin McCarthy Is Not the Only Loser in the House G.O.P.’s Speaker Mess - Notes from a historic debacle on Capitol Hill. - link
The Conservative Who Wants to Bring Down the Supreme Court - The lawyer who wrote Texas’s abortion ban has a bigger project—disempowering the judiciary—that may appeal to liberals, too. - link
The Profound Defiance of Daily Life in Kyiv - In the capital, Ukrainians track the trajectory of Russian missiles on smartphone apps, but refuse to be defeated by fear. - link
Kevin McCarthy’s Hollow Victory Will Have Economic and Political Consequences - If the new House Speaker is to get anything done, he will need to retain the support of far-right extremists. - link
Netanyahu’s Government Takes a Turn Toward Theocracy - The Israeli Prime Minister’s new coalition includes members who would enforce religious prohibitions over democratic liberties. - link
+Meat production is making lifesaving drugs less effective. Where’s the FDA? +
+ ++The US Food and Drug Administration (FDA) knew that America’s meat industry had a drug problem. +
++For decades, evidence had amassed that the widespread use of antibiotics to help chickens, pigs, and cattle grow faster — and survive the crowded conditions of factory farms — was causing bacteria to mutate and develop resistance to antibiotics. By 2009, US agriculture companies were buying up two-thirds of what are termed medically important antibiotics — those used in human medicine. This in turn has made those precious, lifesaving drugs less effective for people. +
++Over time, once easily treatable human infections, like sepsis, urinary tract infections, and tuberculosis, became harder or sometimes impossible to treat. A foundational component of modern medicine was starting to crumble. But it wasn’t until the mid-2010s that the FDA finally took the basic steps of requiring farmers to get veterinary prescriptions for antibiotics and banning the use of antibiotics to make animals grow faster — steps that some European regulators had taken a decade or more prior. +
++Thanks to those two actions alone, sales of medically important antibiotics for livestock plummeted 42 percent from 2015 to 2017. But according to Matthew Wellington of the Public Interest Research Group, the FDA’s reforms went after the low-hanging fruit, and they didn’t go nearly far enough. Now, in a concerning course reversal, antibiotic sales for use in livestock ticked back up 7 percent from 2017 to 2021, per a new FDA report. The chicken industry, which had led the pack in reducing antibiotic use on farms, bought 12 percent more antibiotics in 2021 than in 2020. +
+ ++It’s a sobering turn of events with life-and-death implications. In 2019, antibiotic-resistant bacteria directly killed over 1.2 million people, including 35,000 Americans, and more than 3 million others died from diseases where antibiotic resistance played a role — far more than the global toll of HIV/AIDS or malaria, leading the World Health Organization to call antibiotic resistance “one of the biggest threats to global health, food security, and development today.” +
++Public health advocates want to see the FDA take the threat much more seriously, and often point to Europe as a role model. From 2011 to 2021, antibiotic sales for use in livestock fell by almost half across the European Union, and use per animal is now around half that of the US. Last year, the EU implemented perhaps its most significant reform yet: banning the routine use of antibiotics to prevent disease, reserving their use for only when animals are actually sick. That critical step is expected to slash the continent’s antibiotic use further. +
+ ++It’s unlikely the FDA will follow in Europe’s footsteps any time soon. Asked about an EU-style ban on preventive use of antibiotics, an FDA spokesperson responded, “The laws in the US and our livestock population are not the same as that of the EU or other countries. The FDA’s initiatives to promote judicious use and reduce AMR [antimicrobial resistance] were devised specifically for the US and the conditions we face with the aim of maximizing effectiveness and cooperation of drug sponsors, veterinarians, and animal producers.” +
++The FDA and the US food industry have proven that they can make progress on the issue — but to keep antibiotics working, they need to do a lot more. That will require them to tackle beef and pork, two of the more stubborn and complex sectors of America’s meat system that just can’t seem to quit antibiotics, since doing so could demand substantive changes to how animals are farmed for food. +
++It wasn’t just the FDA’s new rules that caused antibiotic sales for livestock to plunge in a two-year period — Big Chicken played a part too. +
++In the early 2000s, the nation’s fourth-largest chicken producer Perdue Farms began efforts to wean its birds off antibiotics, which it achieved in 2016 by changing chickens’ diets and replacing antibiotics with vaccines and probiotics. At first, chicken raised without antibiotics cost 50 percent more, but the company says it has since been able to all but close the cost differential. +
++In the mid-2010s, while Perdue was making progress, activists leveraged the momentum and successfully convinced McDonald’s to source chicken raised without medically important antibiotics. Tyson Foods, the nation’s largest poultry producer, then committed to reducing antibiotic use, contributing to a “domino effect” in which producers and restaurants made further pledges to reduce antibiotics in poultry, said Wellington. +
++By 2020, a little over half of America’s 9 billion chickens farmed for meat were raised without antibiotics, according to an industry survey. +
++The sea change in chicken production demonstrated it was possible to quickly scale down antibiotics in farming, but it didn’t do much to reduce overall use, as the chicken industry only used 6 percent of antibiotics in agriculture in 2016. And the momentum didn’t spread to other parts of the meat business, like beef and pork, which together account for over 80 percent of medically important antibiotics fed to farmed animals. +
+ ++Some of the lack of progress in beef and pork comes down to the simple fact that pigs and cattle are raised differently than chickens. Chickens are slaughtered at just six or seven weeks old, so the chance they’ll get sick is lower than pigs, who are slaughtered at six months old, or cattle, slaughtered at around three years of age. +
++The chicken industry is also vertically integrated, meaning a company like Tyson or Perdue controls virtually every link in the supply chain, so making big changes like cutting out antibiotics is easier than in the more decentralized supply chain of beef. For example, the typical steer will change hands several times before slaughter, going from a breeder to pasture grazing to a feedlot, all of which make it harder to coordinate an antibiotic-free regimen. In the last few months of their life cattle are also fed a high-grain diet that they aren’t adapted to digest, which increases the chance they’ll develop a liver abscess, a condition that’s prevented with — you guessed it — antibiotics. +
++The pork sector, like poultry, is also vertically integrated, but the industry has largely opposed animal welfare, environmental, and antibiotic reforms. Antibiotics in pig production shot up 25 percent from 2017 to 2021. +
++There’s also no pork or beef giant that’s taken the antibiotic-free leap like Perdue did for chicken. That could change in the years ahead: McDonald’s, the world’s largest beef purchaser, announced at the end of 2022 that it plans to reduce antibiotic use in its beef supply chain. However, the announcement didn’t come with a timeline, which worries advocates like Wellington, and the company has failed to make good on other pledges. +
++Although voluntary change can move the needle, without regulation, industry has little incentive to make the dramatic reductions needed to safeguard antibiotics. While the FDA has prohibited meat producers from using antibiotics to speed up growth— their original purpose in agriculture — some of the antibiotics that promote growth, like tylosin, are still allowed for disease prevention, a loophole that disincentivizes producers from reducing antibiotics, Wellington said: “Our concern has always been that they’re just putting a different name on the same kind of use, which is a problem.” +
+ ++In response to this concern, an FDA spokesperson said, “Veterinarians are on the front lines and as prescribers, they’re in the best position to ensure that both medically important and non-medically important antimicrobials are being used appropriately.” +
++Aside from outright banning the routine use of medically important antibiotics to prevent disease, Wellington said he’d like to see the FDA take three actions: set a target of reducing antibiotic use by 50 percent by the end of 2025 (based on 2010 levels); publish data on antibiotic use, not just sales; and limit the duration of antibiotic courses for farmed animals. +
++An FDA spokesperson said specific reduction targets weren’t possible because the agency doesn’t know how many antibiotics farmers are using: “We cannot effectively monitor antimicrobial use without first putting a system in place for determining [a] baseline and assessing trends over time.” The agency right now only collects sales data, and it’s been exploring a voluntary public-private approach to collect and report real-world use data. +
++Some states haven’t waited on federal regulators: Maryland and California have both restricted the use of antibiotics on farms. +
++Just because it’s difficult to reduce antibiotics in beef and pork production doesn’t mean it’s impossible, as the story of Iowa pig farmers Tim and Deleana Roseland demonstrates. +
++In 2005, they switched from raising pigs in the conventional manner — tightly cramped and fed a steady diet of antibiotics — to raising pigs for Niman Ranch, a higher-welfare meat company now owned by Perdue. That required the Roselands to ditch the routine use of antibiotics. +
++“I was nervous about it at first but as it turned out, it was no big deal whatsoever,” Tim Roseland said. But he added that it wouldn’t have been possible with his old setup: “There’s too much overcrowding, small pens, too many pigs crammed into a little area.” +
++Their newer system gives each pig more space in larger pens, and bedding that they root through and chew on, instead of, when they’re packed into factory farms, chewing on each other. They also give the pigs more vaccines and feed them probiotics. +
++And there’s a lot to learn from the Europeans: Denmark, the continent’s second-largest pork producer, has become the de facto case study in how to wean Big Meat off antibiotics. In the early 1990s, it started phasing out antibiotics in pigs with little impact on the industry. From 1992 to 2008, antibiotic use per pig fell by over 50 percent, and while pig mortality went up in the short term, by 2008 it had dropped back to near-1992 levels. +
+ ++The small country’s transformation wasn’t a matter of rocket science, but a suite of smart management practices: more frequent barn cleaning, better ventilation, later piglet weaning, more space per pig, extra vaccines, and experimenting with feed and additives. +
++All this comes with difficult tradeoffs: antibiotic-free pork costs more and requires more land, which increases its carbon footprint. But we can’t expect to have cheap meat forever without a cost to public health, an uncomfortable truth that’s led many environmental and public health groups to champion a message of “less but better” meat. +
++“I think the fact that Denmark, despite very low antibiotic use since 1995, is still one of the biggest pork exporters in the world, already speaks for itself,” said Francesca Chiara, a director at the University of Minnesota’s Center for Infectious Disease Research and Policy. +
++Given the projected rise of global antibiotic sales for agriculture, Denmark’s example may not be speaking loudly enough. But it’s time we listen — nothing less than the future of human medicine is at stake. +
++
++
+Kim Jong Un’s military plans are raising tensions with the South to new heights. +
++Tensions on the Korean Peninsula are at the highest in years after an unprecedented year of missile launches on the part of North Korea — and a more bellicose posturing from the South Korea’s president, Yoon Suk-yeol. +
++In 2022, North Korea launched at least 95 missiles — more than in any previous year — and shot off another short-range missile New Year’s Day of this year, according to the New York Times. The tests are the product of several factors, including domestic North Korean politics, as well as the rapid and extreme deterioration of diplomatic relations between Kim Jong Un’s regime and the US-South Korea alliance since 2019’s failed summit in Hanoi, Vietnam, between Kim and former President Donald Trump. +
++Since Yoon’s inauguration in May 2022, the South and the US have pursued a tit-for-tat strategy in dealing with the North, pursuing joint military exercises which the North sees as provocative, and even sending unmanned aerial vehicles (UAVs) to Pyongyang after one of the North’s own drones buzzed Seoul, South Korea’s capital. +
++Despite a 2018 resolution between the North and the South prohibiting military hostilities between the two nations, both sides have engaged in increasingly dramatic shows of force over the past several months which, given the lack of diplomatic efforts, could increase the possibility of grave miscalculation and outright conflict on the part of either party. +
++The explicit threats on Kim’s part, as well as the increase in missile tests, point to a North Korea that’s interested in projecting a credible deterrent capacity and to try and manage instability internally. And the South is taking a hard line and projecting its own force — sometimes at odds with the interests of the US, its primary military ally. +
++Given both nations’ vows to increase their military capacity, the possibility of peace on the peninsula seems to be deteriorating by the day. Furthermore, the US — which maintains a force presence in the South — isn’t doing enough to prevent conflict and encourage diplomacy to prevent miscommunication, according to Ankit Panda, the Stanton Senior Fellow in the Nuclear Policy Program at the Carnegie Endowment for International Peace. +
++“The United States should be doing more to express concerns about possible allied defensive plans and postures that might actually increase escalation risks,” which would inevitably implicate the US. +
++Kim announced last week his intention to build “overwhelming military power,” including a focus on producing shorter-range tactical nuclear weapons to target the South, as well as long-range intercontinental ballistic missiles, or ICBMs, capable of reaching the US mainland, among other innovations. Kim’s announcement, and Yoon’s suggestion that the South and the US would hold joint nuclear weapons exercises, have brought the nuclear threat into sharp focus. +
++As Panda told Vox via email, Kim’s policy announcement isn’t exactly new, “but more of a fleshing-out of a fairly well-articulated and constant nuclear strategy.” Kim and his predecessors have always seen the South and the US as their existential adversaries; the new policy announcements and missile testing simply make the North’s nuclear threats more realistic and achievable. “Their intentions haven’t changed: They’re still reserving the right to use nuclear weapons first to deter an attack on their territory,” Panda said. +
++Rather than an ambiguous threat of nuclear firepower, the North is now putting increased energy into tactical nuclear weapons which could be used in a battlefield scenario, or to repel a perceived attack from the South. +
++Increased focus on solid-fuel missiles also indicate the intention to deploy missiles rapidly, since they come pre-fueled and are highly mobile. Developing solid-fuel missiles has been a priority for Kim at least since the the Party’s plenary meeting in January 2021. Kim held a successful ground launch of a solid-fuel rocket motor — which could be used either on an ICBM or a missile launched from a submarine — in December. +
++“They’ve identified solid-propellant ICBMs as a particular focus for this year,” Panda said, specifying that, “we should expect to see flight-testing of large-diameter solid propellant missiles and perhaps even solid propellant ICBMs this year.” +
++Missiles are just the delivery vehicle — and just one aspect of the nuclear threat. The North’s nuclear arsenal also depends on its ability to develop warheads — the missile’s payload. +
++Nuclear weapons development in the North is difficult to track due to the extremely secretive (and illegal) nature of that work, but the missile tests, Kim’s announcements, and satellite imagery help analysts understand how far along the Kim regime is in creating weapons of mass destruction. +
++The North has not staged a nuclear test since September 2017, but experts have told Vox that all signs point to a seventh at any time — and even an eighth soon after, Panda said. +
++Two of the North’s main nuclear sites are Yongbyon Nuclear Research Center, which has a uranium enrichment facility, and Punggye-ri, the country’s only nuclear test site. +
++Yongbyon continues to be operational, Joseph Bermudez, the Korea chair at the Center for Strategic and International Studies told Vox. “We see rail cars coming in and out, we see the razing of several buildings and work on updating other buildings, we see activity in and around the reactors and also in and around the centrifuge plant,” he said, but without thermal imagery, it’s impossible to tell what that activity means. +
++As for Punggye-ri, the testing site, “it’s been basically quiet for the last couple of months,” Bermudez said. However, the US and South Korean governments have indicated they believe a nuclear test could take place “at any time that Kim Jong Un decides to do so,” he said, adding that imagery from earlier in the week “shows tracks in the snow indicating the movement of vehicles.” +
++“We believe that someone is checking on it,” although given the positioning of the facility — one of the entrances is shielded by a steep mountain slope and the angle of the sun — it’s hard to tell who and what’s coming in and out. The North also tends to move equipment and vehicles under cloud cover and in the dark, further obscuring those movements to outside observers. +
++Bermudez assessed that the North is “not only validating missile designs, but probably refining them,” and repeated missile tests indicate “new systems coming online and being distributed to units.” +
++Still, for Kim to use a nuclear missile or stage an invasion of the South would be a death sentence, both for his military and his regime. And the increased missile tests and activity around nuclear facilities can provide only limited information about the North’s actual capabilities. +
++But the fear that a nuclear-capable North Korea instills in its adversaries also serves a purpose; for all the testing and parades, Kim’s nuclear arsenal is further along than it’s ever been, but it’s far from complete. What Kim is showing off may not yet work militarily, “but it certainly has the potential work coercively” Bennett said. +
++Kim likely feels wary of engaging in diplomacy with the US or South Korea because of the spectacular breakdown of peace talks with former President Donald Trump, according to Toby Dalton, co-director of the Nuclear Policy Program at the Carnegie endowment for International Peace told Vox in a previous interview. That process ended in a humiliating failure in Hanoi, Vietnam, when Trump tried to push for full denuclearization in return for an end to the punishing sanctions regime the US has built up over the decades. +
++“[Kim] took some risks in terms of his domestic constituency in terms of pursuing that diplomacy — and then it fell apart and I think he was embarrassed by that,” Dalton said. From the North’s perspective, “they’re not willing to trust South Korea or the US to engage in diplomacy,” he told Vox, and the parties involved aren’t even in agreement about what the outcome of that diplomacy would be. +
++“It’s unsurprising that inter-Korean dynamics are as tense as they are right now,” Panda said. “We’ve seen this pattern play out under previous conservative-led governments in Seoul. That said, the [North’s] weapons development plans would likely have proceeded as they have regardless of the outcome of the 2022 South Korean election.” +
++Internal politics, especially in the North, favor a muscular response — at least in the eyes of Kim and Yoon. +
++In the North, for example, “even the elites are having trouble,” according to Bruce Bennett, a researcher at the RAND Corporation. Some members of leadership and Kim’s inner circle have reportedly been purged; “[Kim’s] been pretty brutal, and it hasn’t just been with the common people — it’s been with the elites, too.” Internal struggles, like consistent fuel and food shortages, pose a serious threat to Kim’s leadership, and in an authoritarian government, the only way to deal with internal struggle is to blame an external enemy. +
++“What does Kim need to manage his internal instability? What he needs is to look powerful,” hence the escalated rhetoric from both him and his sister and advisor, Kim Yo Jong. Testing, threats, and military parades help the elite feel like, “Wow, we’re powerful, [Kim] is a good leader, he’s making us powerful,” Bennett said, easing the pressure on Kim himself. +
++South Korea isn’t facing the same internal issues; it has the backing of the US and a strong military and economy. Public opinion polling indicates that South Koreans may be looking at China — not the North — as their major adversary in the future. Still, Yoon has pursued a “strength for strength” tactic, as opposed to former President Moon Jae-in’s pursuit of concessions and conciliation to reach a negotiated outcome. Though Yoon’s response may assure South Koreans that they’re defended from the North, it doesn’t do much to deter Kim, Bennett said. +
++“[Kim] appears to be trying to divide the US-ROK alliance” in order to isolate the South and demonstrate some form of dominance on the peninsula by explicitly focusing on shorter-range weapons that can only reach the South and ICBMs which would only be useful against the US, Bennett said. +
++Yoon’s claims that the US and the South were discussing joint nuclear exercises are a “good example of where an ally might be getting ahead of where the United States is ready to go,” Panda said. The Biden administration is focused on repairing its relationships with allies after “the atrocious treatment that US allies endured at the hands of the Trump administration,” Panda said — but that approach could backfire. +
++Rather, Biden should be more explicit with regional allies — including Japan, which is pursuing remilitarization after decades of minimal defense spending — about what the US’s limits and intentions are regarding the North. Just as crucially, the US and allies must pursue diplomatic channels to try and reduce the risk of miscommunication and miscalculation while that’s still feasible. +
++“I want to say there’s always room for diplomacy,” Bermudez said, but given the situation, “it seems like that room is very narrow.” +
+A fractured GOP could be good news for Democrats. +
++Rep. Kevin McCarthy has become speaker of the House, but only did so by offering offered a series of concessions that effectively mean his speakership will consistently be under threat from his own caucus. +
++McCarthy’s agreement to weaken the role of the speaker is likely to lead to extreme gridlock within the ranks of the GOP. But it could also present an opening for Democrats. If far-right lawmakers in the GOP follow through on their promises to hold up pivotal spending and debt ceiling legislation, Republicans may well have to rely on Democrats’ help to get any bills across the finish line — a dynamic Democrats could capitalize on. +
++“The deal is, if they want to get stuff done, they’re going to have to work with us,” says Rep. Jim McGovern (D-MA), the top Democrat on the House Rules Committee. “And we’re not going to be a cheap date.” +
++Given Republicans’ narrow 222-person majority, they can’t really pass much if they lose any more than five votes in their own conference. Since conservatives have been vocal about their commitment to blocking key bills, like an increase to the debt ceiling, in order to get the spending cuts they want, Republicans will likely need Democratic votes to keep essential government functions and services running if they want to do so. +
++Additionally, given the number of Freedom Caucus members added to the House Rules Committee, Democrats could theoretically join with the conservatives on the panel to block or slow bills favored by House GOP Leadership. +
++The situation gives Democrats more leverage to put forth their own demands, if Republican leadership is actually interested in getting anything done. Of course, there’s a high chance that they aren’t, a reality Democrats are preparing to confront as well. +
++“I think there is an opportunity,” says Rep. Mark DeSaulnier (D-CA), a member of the Rules Committee. “But it’s just such an unusual time — and it’s so hard for so many of them to reach across the aisle.” +
++Republicans can only lose a handful of votes before any bill falls short of the simple majority it needs to advance, which gives Democrats an opening. +
++In the last decade or so, there have been times when House Republicans have relied on Democratic support when their conference has similarly fractured. In 2011 and 2014, Republican House Speaker John Boehner needed Democratic votes to approve spending bills to fund the government, for example. +
++That same dynamic could play out this term, with Republicans relying on Democratic help to make up for the support they’re missing in their own caucus. “These people who are causing all this nonsense right now — you can’t work with them. They can’t ever get to yes,” said McGovern. +
++Ultimately, House Republicans will need to get a majority to pass bills including an increase to the debt ceiling, spending legislation, the farm bill — which authorizes many Agriculture Department programs — and a defense bill that lays out funding for the military. Were conservative members to withhold their support for such policies, the GOP wouldn’t be able to pass the bills on their own. If they aren’t able to, they risk scenarios like the country defaulting on the national debt and causing an economic crisis, as well as a potentially interminable government shutdown. +
++As Republicans have shown in the past, after the US nearly defaulted on its debt in 2011, and when it went into a shutdown in 2013, members of the party could well be okay with those scenarios playing out. In both those cases, however, House Republicans also garnered significant public backlash for their role in causing these debacles, and eventually passed agreements that were reached with Democratic support. +
++As Vox’s Andrew Prokop noted, however, any Republican attempts to reach across the aisle this term could also prompt blowback from the conservative wing, who may threaten the speaker as a result. As part of his bid to become speaker, McCarthy reportedly offered a rules change that will allow any one Republican to force a vote of “no confidence.” +
++Known as the motion to vacate, this would allow a single member to call a vote on the speaker’s ousting if they weren’t happy with how he was handling a particular bill or issue. Theoretically, a single far-right member could punish any collaboration with Democrats by submitting a motion to vacate, forcing a vote against the speakership. A majority of members would still have to agree to remove him, though. Some Democrats warned that the rule changes McCarthy agreed to in order to become speaker could blunt collaboration for fear of reprisals. +
++“It does feel like they may need to get in the middle more to get anything done. But I’m not sure that giving more weapons to the most extreme folks is going to promote that goal,” Rep. Mary Gay Scanlon (D-PA), a member of the Rules Committee, told Vox. +
++The best case for Democrats is that they’re able to slip a few of their priorities into must-pass legislation. But, as Scanlon alluded to, there’s a worst-case scenario as well: utter gridlock. +
++In addition to the change on the motion to vacate, which could cause GOP leadership to shy away from bipartisan dealmaking, McCarthy’s concessions included adding multiple members of the Freedom Caucus to the Rules Committee, which plays a key role in deciding what bills make it to the floor and what amendments get considered. Should three ultraconservative Republicans be added to that committee, something McCarthy agreed to, they’d be able to delay bills and push more extreme versions of policies. +
++That’s led some Democrats to worry these changes will empower Republicans’ conservative flank to use the panel for obstruction. “We have a small faction basically holding Congress hostage,” Scanlon says. “Many of the rules changes that are being proposed by this kind of extreme faction have the same goal.” +
++Rep. Norma Torres (D-CA), a member of the Rules Committee, notes that conservatives could gum up the process on bills by forcing debate on amendments, whether or not they are germane to the legislation at hand. “It’s impossible to legislate from that perspective,” she said. +
++Interestingly, Democrats could use potential rules changes to their advantage, too, argues Daniel Schuman, a policy expert at the progressive advocacy group Demand Progress. Although Democrats aren’t able to use the motion to vacate in the same way as Republicans, they would be able to offer their own amendments to bills like appropriations legislation if those changes came to fruition. +
++“They’re creating a lot of veto points for legislation, and more opportunities to amend that legislation,” says Schuman. “And those opportunities, in many circumstances, will be available to all members, not just to Republican members.” +
++Additionally, as Prokop explained, the appointments of Freedom Caucus members to the Rules Committee could give Democrats the ability to form unexpected coalitions and throw their weight around. Previously, the Rules Committee had 13 members, nine in the majority and four in the minority. Were McCarthy to use that same breakdown, and give three seats to Freedom Caucus members, there would be nine Republicans, three of whom would be hardline conservatives, along with four Democrats. In that instance, the Democrats and hardline conservatives could theoretically work together to form a seven-person majority. +
++It remains to be seen how likely any kind of bipartisan collaboration would be given how polarized the two parties are. Republicans’ narrow margins, however, could lead to Democrats using their numbers in interesting ways. +
++“The Freedom Caucus could build an alliance with some or all the Democrats, the McCarthy faction could build an alliance with some or all the Democrats, or the McCarthy faction and the Freedom Caucus could build an alliance with each other,” says Schuman. +
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The Netherlands reasserts its supremacy; Indian slide continues -
Hockey World Cup | India has a good chance of reaching semifinals, says Ties Kruize - The Dutchman believes the host has two crucial ingredients for success — a good goalkeeper and PC battery
Djokovic shrugs off injury scare, wins Adelaide title - Djokovic had to save a match and chamionship point at 5-6 in the second set Sunday and was fully stretched by the 22-year-old Korda, son of 1998 Australian Open champion Petr Korda.
Saloon Car racer Kumar dies in crash at the National Car Racing Championship in Chennai -
Suryakumar — the jewel in the crown of India’s white-ball warriors - He does not doubt his ability and that’s the reason for his success in this format; need to maintain this mindset when the pitch is not as helpful, says skipper Hardik
Chances of infection: food safety squad continues aggressive checking in eateries - Nearly 70 shops dealing with food-based business inspected; flash inspections conducted considering the crowd turnout for Kerala State School Kalolsavam
Andhra Pradesh: improve technical knowledge to meet expectations of industry, Waltair DRM tells engineering students -
Best researcher award for Kerala University professor -
Chikkamagaluru police arrest one, recover pistol, live bullets from him -
Teacher arrested under POCSO Act near Tiruvannamalai - He made the girls student stay in classroom after school hours and sexually harassed her
Iranian man held in Germany over suspected chemical attack - Police raided the man’s residence where they say they found toxic chemicals.
Ukraine war: The Christmas ceasefire that wasn’t - Few in Ukraine’s eastern city of Bakhmut expected Russia’s declared truce to be matched with action.
In pictures: Orthodox Christians around the world mark Christmas - Some 200 million people are marking the holiday, one of the most important dates in the faith.
Ukraine war: Western allies to send fighting vehicles to Kyiv - Germany and the US agree to join France in boosting Ukraine’s military capability on the battlefield.
Filippo Bernardini: Italian admits stealing unpublished books - Margaret Atwood, Sally Rooney and Ethan Hawke were all targets of phishing scams.
What Twitter’s 200 million email leak really means - Exposure of email addresses puts pseudonymous users of the social network at risk. - link
Ancient Roman concrete could self-heal thanks to “hot mixing” with quicklime - Mysterious lime clasts, dismissed as defects, turn out to serve a useful purpose. - link
Apple rolls out AI-narrated audiobooks, and it’s probably the start of a trend - “This audiobook features ‘Madison’—a digital voice based on a human narrator.” - link
Google’s split-screen Android Auto revamp is rolling out now - The new panel design fits big screens, wide screens, and small screens. - link
FDA approves new Alzheimer’s treatment despite risks, unclear benefits - The drug’s price has already been set at $26,500 per year. - link
Why Bilbo had to be Male -
++Fun fact: Bilbo Baggins had to be a male in order for the plot of The Hobbit to work. If he was instead female, everything would have fallen apart in the goblin cave. Bilbo would have gone off wandering around in the dark and dreary caverns, found the ring, and seen Gollum fishing like in the original plot, sure. And but then there would be trouble when they were playing riddles in the dark. And this is where everything would break. Because while Bilbo may have gotten lucky and answered the first few riddles, a female Bilbo couldn’t possibly ever win like male Bilbo. I think that, in the end, the problem with female Bilbo playing this riddle in the dark game is quite clear. Sure, she might be clever, but even if she was very lucky, she’d never think to ask “What have I got in my pockets?” Or even if she did, Gollum would have gotten the answer right. Because we all know that women’s clothes don’t have actual pockets. +
++Edit: glad to see so many of you like it! For those of you that don’t like the long version of this joke: TL;DR short version of joke (Spoilers) (Duh!): Why did Bilbo have to be male? Because if Bilbo was a woman, she couldn’t ask “What have I got in my pockets?” +
++Edit 2 (again, joke spoiler): Regarding Women’s Pockets While it is true that women’s clothing can have pockets, it is less likely than men’s clothing, and even if they do have pockets, they are usually small than men’s or just fake pockets. If evidence, there is research easily found online, along with explanations by fashion designers as to why (and plenty of comics/memes). This came up because I was looking for a nice long coat that wasn’t black/brown/gray/khaki, so it had to be women’s, but I’m not crazy enough to get one without pockets! +
++Edit 3, Regarding Those of You Who Find the Joke to be Unfunny: ”Some who have read the book, or at any rate have reviewed it, have found it boring, absurd, or contemptible; and I have no cause to complain, since I have similar opinions of their works, or of the kinds of writing that they evidently prefer.” -J.R.R. Tolkien +
+ submitted by /u/Zognot
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The other night I overheard three very hefty women talking -
++Their accent appeared to be Scottish, so I approached them and asked: “Hello, are you three lassies from Scotland?” +
++One of them angrily screeched: “It’s Wales, Wales you bloody idiot!” +
++So I apologized and replied: “I am so sorry. Are you three whales from Scotland?” +
++And that’s the last thing I remember. +
+ submitted by /u/cyberfugue
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Son, you’re adopted -
++“I Knew it! I want to meet my biological parents.” +
++“We are your biological parents, your adoptive parents will come for you tomorrow.” +
+ submitted by /u/Green_Submarine7965
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What’s the difference between your mom and a refrigerator? -
++A refrigerator doesn’t fart when you take the meat out. +
+ submitted by /u/Barber606
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Im a good man, I give 50% of my money to charity -
++Except when she’s not working I give it to destiny . +
+ submitted by /u/Outrageous-Low-4979
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