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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Childcare burden and changes in fertility desires of mothers during the COVID-19 pandemic</strong> -
<div>
Background: Previous studies have documented a decline in fertility desires following the COVID-19 outbreak, but reasons for this decline are not well understood. This study examined whether greater childcare burden on mothers during the lockdowns and quarantines, COVID-related stress and COVID-19 exposure were associated with a change in desired number of children. Methods: The survey was conducted in Poland in AprilJuly 2021 and completed by 622 non-pregnant mothers without diagnosed infertility. Women were asked whether the COVID-19 pandemic has changed their reproductive plans. Childcare burden was reported during lockdown and quarantines. Results: Almost 30% of mothers reported decrease in their fertility desires because of the pandemic. Associations were observed between childcare responsibilities during the quarantine (but not lockdown) and fertility desires: mothers who solely or mainly took care of their children during the quarantine(s) were more likely to decrease their desired number of children ([adjusted] aOR = 1.91, 95% CI = 1.163.15). Mothers with higher levels of COVID-related stress (aOR = 1.81, 95% CI = 1.482.22) and greater COVID exposure index (aOR = 1.39, 95% CI = 1.121.72) were more likely to decrease their fertility desires. Conclusions: Mothers who bare more childcare responsibilities during quarantine had lower desire to have more children. At the same time, both greater COVID-related stress and exposure were associated with a decreased wish to have children, regardless of the childcare responsibilities during the pandemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/3m9zs/" target="_blank">Childcare burden and changes in fertility desires of mothers during the COVID-19 pandemic</a>
</div></li>
<li><strong>COVID-19 Vaccine Uptake And Its Associated Factors among general population In Basmaia City in Baghdad 2022</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Objective: Vaccination is a vital cornerstone of public health, which has saved countless lives throughout history. Therefore, achieving high vaccination uptake rates is essential for successful vaccination programs. Unfortunately, vaccine uptake has been hindered by deferent factors and challenges. The objective of this study is to assess COVID-19 vaccine uptake and associated factors among the general population. Methods: This study is a descriptive cross-sectional study conducted in Basmaia city, Baghdad from June to October 2022. Data were collected through a semi-structured questionnaire using multi-stage random sampling. Statistical analysis was performed using descriptive statistics, chi-square analysis, Mann-Whitney test, and binary and multivariable logistic regression. Results: the prevalence of COVID-19 vaccine uptake was 70.4%. The most common reason for getting vaccinated was protection from the disease, while fear of side effects and not needing the vaccine were the main reasons for refusal. The study found that gender, age, education level, job title, risk perception, knowledge, and attitude towards the vaccine were significantly associated with COVID-19 vaccine uptake. Males were 2.273 times more likely to get vaccinated than females, and older age groups had higher odds of vaccination than younger age groups. Those with higher education levels were also more likely to receive the vaccine. Participants with higher risk perception, knowledge, and positive attitude towards the vaccine were more likely to get vaccinated. And found that mandatory vaccination policies may negatively impact uptake of subsequent vaccine doses. Conclusion: the study found a high prevalence of COVID-19 vaccine uptake, with gender, age, education level, and job title being significant factors associated with vaccine uptake. Additionally, mandatory vaccination policies may have a negative impact on the uptake of subsequent vaccine doses. Public health efforts should prioritize addressing these factors to increase vaccine uptake.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.07.23288262v1" target="_blank">COVID-19 Vaccine Uptake And Its Associated Factors among general population In Basmaia City in Baghdad 2022</a>
</div></li>
<li><strong>Spatial and Temporal Origin of The Third SARS-Cov-2 Outbreak in Taiwan</strong> -
<div>
Since the first report of SARS-CoV-2 in December 2019, Taiwan has gone through three local outbreaks. Unlike the first two outbreaks, the spatial and temporal origin of the third outbreak (April 20 to November 5, 2021) is still unclear. We assembled and analyzed a data set of more than 6,000 SARS-CoV-2 genomes, including 300 from Taiwan and 5812 related sequences downloaded from GISAID as of 2021/12/08. We found that the third outbreak in Taiwan was caused by a single virus lineage belonging to Alpha (B.1.1.7) strain. This lineage, T-III (the third outbreak in Taiwan), carries a distinct genetic fingerprint, consisting of spike M1237I (S-M1237I) and three silent mutations, C5812T, C15895T, and T27869C. The T-III is closest to the sequences derived from Turkey on February 8, 2021. The estimated age of the most recent common ancestor (TMRCA) of T-III is March 23, 2021 (95% highest posterior density [HPD] February 24 - April 13, 2021), almost one month before the first three confirmed cases on April 20, 2021. The effective population size of the T-III showed approximately 20-fold increase after the onset of the outbreak and reached a plateau in early June 2021. Our results reconcile several unresolved observations, including the occurrence of two infection clusters at the same time without traceable connection and several airline pilots who were PCR negative but serum IgM-/IgG+ for SARS-CoV-2 in late April. Therefore, in contrast to the general notion that the third SARS-CoV-2 outbreak in Taiwan was sparked by two imported cases from USA on April 20, 2021, which, in turn, was caused by the partial relaxation of entry quarantine measures in early April 2021, our comprehensive analyses demonstrated that the outbreak was most likely originated from Europe in February 2021.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.04.498645v3" target="_blank">Spatial and Temporal Origin of The Third SARS-Cov-2 Outbreak in Taiwan</a>
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<li><strong>A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases</strong> -
<div>
Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAM) to pulmonary diseases remains poorly understood due to difficulty in accessing them from human donors and their rapid phenotypic change during in vitro culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies. We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, i.e., Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (GM-CSF, TGF-{beta}, and IL-10) that facilitate the conversion of blood-obtained monocytes to an AM-Like (AML) phenotype and function in tissue culture. Similar to HAM, AML cells are particularly susceptible to both Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study reveals the importance of alveolar space components in the development and maintenance of HAM phenotype and function, and provides a readily accessible model to study HAM in infectious and inflammatory disease processes, as well as therapies and vaccines.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.05.535806v1" target="_blank">A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases</a>
</div></li>
<li><strong>The Rous sarcoma virus Gag polyprotein forms biomolecular condensates driven by intrinsically-disordered regions</strong> -
<div>
Biomolecular condensates (BMCs) play important roles in cellular structures including transcription factories, splicing speckles, and nucleoli. BMCs bring together proteins and other macromolecules, selectively concentrating them so that specific reactions can occur without interference from the surrounding environment. BMCs are often made up of proteins that contain intrinsically disordered regions (IDRs), form phase-separated spherical puncta, form liquid-like droplets that undergo fusion and fission, contain molecules that are mobile, and are disrupted with phase-dissolving drugs such as 1,6-hexanediol. In addition to cellular proteins, many viruses, including influenza A, SARS-CoV-2, and human immunodeficiency virus type 1 (HIV-1) encode proteins that undergo phase separation and rely on BMC formation for replication. In prior studies of the retrovirus Rous sarcoma virus (RSV), we observed that the Gag protein forms discrete spherical puncta in the nucleus, cytoplasm, and at the plasma membrane that co-localize with viral RNA and host factors, raising the possibility that RSV Gag forms BMCs that participate in the virion intracellular assembly pathway. In our current studies, we found that Gag contains IDRs in the N-terminal (MAp2p10) and C-terminal (NC) regions of the protein and fulfills many criteria of BMCs. Although the role of BMC formation in RSV assembly requires further study, our results suggest the biophysical properties of condensates are required for the formation of Gag complexes in the nucleus and the cohesion of these complexes as they traffic through the nuclear pore, into the cytoplasm, and to the plasma membrane, where the final assembly and release of virus particles occurs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.07.536043v1" target="_blank">The Rous sarcoma virus Gag polyprotein forms biomolecular condensates driven by intrinsically-disordered regions</a>
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<li><strong>GATA1 knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation</strong> -
<div>
Human pluripotent stem cell (hPSC)-derived tissues can be used to model diseases and validate targets in cell types that are challenging to harvest and study at scale, such as neutrophils. Neutrophil dysregulation, specifically unbalanced neutrophil extracellular trap (NET) formation, plays a critical role in the prognosis and progression of multiple diseases, including COVID-19. hPSCs can provide a limitless supply of neutrophils (iNeutrophils) to study these processes and discover and validate targets in vitro. However, current iNeutrophil differentiation protocols are inefficient and generate heterogeneous cultures consisting of different granulocytes and precursors, which can confound the study of neutrophil biology. Here, we describe a method to dramatically improve iNeutrophils yield, purity, functionality, and maturity through the deletion of the transcription factor GATA1. GATA1 knockout (KO) iNeutrophils are nearly identical to primary neutrophils in cell surface marker expression, morphology, and host defense functions. Unlike wild type (WT) iNeutrophils, GATA1 KO iNeutrophils generate NETs in response to the physiologic stimulant lipopolysaccharide (LPS), suggesting they could be used as a more accurate model when performing small-molecule screens to find NET inhibitors. Furthermore, through CRSPR/Cas9 deletion of CYBB we demonstrate that GATA1 KO iNeutrophils are a powerful tool in quickly and definitively determining involvement of a given protein in NET formation.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.08.526339v3" target="_blank">GATA1 knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation</a>
</div></li>
<li><strong>A rapid, low cost, and highly sensitive SARS-CoV-2 diagnostic based on whole genome sequencing</strong> -
<div>
Early detection of infection with SARS-CoV-2 is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosis of SARS-CoV-2 infection, dubbed Pathogen-Oriented Low-Cost Assembly &amp; Re-Sequencing (POLAR), that enhances sensitivity by aiming to amplify the entire SARS-CoV-2 genome rather than targeting particular viral loci, as in typical RT-PCR assays. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing and de novo genome assembly. We are able to reliably (&gt;95% accuracy) detect SARS-CoV-2 at concentrations of 84 genome equivalents per milliliter, better than the reported limits of detection of almost all diagnostic methods currently approved by the US Food and Drug Administration. At higher concentrations, we are able to reliably assemble the SARS-CoV-2 genome in the sample, often with no gaps and perfect accuracy. Such genome assemblies enable the spread of the disease to be analyzed much more effectively than would be possible with an ordinary yes/no diagnostic, and can help identify vaccine and drug targets. Finally, we show that POLAR diagnoses on 10 of 10 clinical nasopharyngeal swab samples (half positive, half negative) match those obtained in a CLIA-certified lab using the Center for Disease Controls 2019-Novel Coronavirus test. Using POLAR, a single person can process 192 samples over the course of an 8-hour experiment, at a cost of ~$30/patient, enabling a 24-hour turnaround with sequencing and data analysis time included. Further testing and refinement will likely enable greater enhancements in the sensitivity of the above approach.
</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.04.25.061499v4" target="_blank">A rapid, low cost, and highly sensitive SARS-CoV-2 diagnostic based on whole genome sequencing</a>
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<li><strong>The effect of perceived morbidity and mortality risk on risk-taking and patience</strong> -
<div>
Beyond immediate health consequences, the COVID-19 pandemic has profoundly affected peoples environment. People had to adapt to new circumstances and take into account the risks related to COVID-19 in their everyday decisions. Given the unprecedented circumstances associated with the first wave of the COVID-19 pandemic, we might ask how people adapt to their new environment. In particular, we ask how people form their morbidity and mortality risk perception associated with the virus and whether increased perceived risk affects psychological traits, such as risk-taking and patience. To address these questions, we analyzed data from a large survey conducted during the first wave in France on 5,000 nationally-representative people. We find that people use the public information on COVID-19 deaths in the area where they live to form their perceived morbidity and mortality risk. Using a structural model approach to lift endogeneity concerns, we found that higher perceived morbidity and mortality risk increases risk aversion. We also found that higher perceived morbidity and mortality risk leads to less patience, although this was only observed for high levels of perceived risk.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/u768y/" target="_blank">The effect of perceived morbidity and mortality risk on risk-taking and patience</a>
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<li><strong>Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocol</strong> -
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Background:The coronavirus disease (COVID-19) pandemic has led to an unprecedented public health crisis. Insufficient testing continues to limit the effectiveness of the global response to the COVID-19 pandemic. Molecular testing methods such as reverse transcriptase polymerase chain reaction (RT-PCR) continue to be highly centralized and are a sub-optimal option for population surveillance. Rapid antigen tests (Ag-RDTs) offer multiple benefits including low costs, high flexibility to conduct tests in a wide variety of settings, and faster return of results. Recently, self-test Ag-RDTs (STs) have gained approval in several markets and offer the possibility to expand testing, reaching at-risk populations. While STs have the potential to assist the COVID-19 response, test result integrity, reporting, and appropriate linkage to care continue to hinder the widespread implementation of self-testing programs. Methods:This protocol presents a mixed-methods pragmatic trial (ISRCTN91602092) to better understand the feasibility of self-testing as part of a contact tracing strategy within the Brazilian public health system. Approximately 604 close contacts of 150 index cases testing positive for COVID-19 will be enrolled. Close contacts will be randomized to either serial (daily) self-testing over a 10-day follow-up period or a more traditional approach to contact tracing with a professional Ag-RDT at one time point post-exposure. Usability workshops and focus group discussions will also be conducted. Discussion:This study protocol presents a comprehensive plan to assess the effectiveness, operational feasibility, and stakeholder preferences of a serial self-testing strategy for contact tracing within the Brazilian public health system. Our results will contribute to better understanding of the feasibility of a self-testing strategy within the public sector. Potential risks and limitations are discussed. Our findings will have important implications as governments continue working to mitigate the impact of COVID-19, particularly in the context of where to direct limited resources for testing and healthcare infrastructure.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288207v1" target="_blank">Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocol</a>
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<li><strong>The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein</strong> -
<div>
Coronaviridae is recognized as one of the most rapidly evolving virus family as a consequence of the high genomic nucleotide substitution rates and recombination. The family comprises a large number of enveloped, positive-sense single-stranded RNA viruses, causing an array of diseases of varying severity in animals and humans. To date, seven human coronaviruses (HCoV) have been identified, namely HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1, which are globally circulating in the human population (seasonal HCoV, sHCoV), and the highly pathogenic SARS-CoV, MERS-CoV and SARS-CoV-2. Seasonal HCoV are estimated to contribute to 15-30% of common cold cases in humans; although diseases are generally self-limiting, sHCoV can sometimes cause severe lower respiratory infections, as well as enteric and neurological diseases. No specific treatment is presently available for sHCoV infections. Herein we show that the anti-infective drug nitazoxanide has a potent antiviral activity against three human endemic coronaviruses, the Alpha-coronaviruses HCoV-229E and HCoV-NL63, and the Beta-coronavirus HCoV-OC43 in cell culture with IC50 ranging between 0.05 and 0.15 g/ml and high selectivity indexes. We found that nitazoxanide does not affect HCoV adsorption, entry or uncoating, but acts at postentry level and interferes with the spike glycoprotein maturation, hampering its terminal glycosylation at an endoglycosidase H-sensitive stage. Altogether the results indicate that nitazoxanide, due to its broad-spectrum anti-coronavirus activity, may represent a readily available useful tool in the treatment of seasonal coronavirus infections.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.13.499346v2" target="_blank">The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein</a>
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<li><strong>The role of N-glycosylation in spike antigenicity for the SARS-CoV-2 Gamma variant</strong> -
<div>
The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity towards the viral spike protein, whether acquired from infection or vaccination. Mutations that impact N-glycosylation of spike may be particularly important in influencing antigenicity, but their consequences are difficult to predict. Here, we compare the glycosylation profiles and antigenicity of recombinant viral spike of ancestral Wu-1 and the Gamma strain, which has two additional N-glycosylation sites due to amino acid substitutions in the N-terminal domain (NTD). We found that a mutation at residue 20 from threonine to asparagine within the NTD caused the loss of NTD-specific antibody binding. Glycan site-occupancy analyses revealed that the mutation resulted in N-glycosylation switching to the new sequon at N20 from the native N17 site. Site-specific glycosylation profiles demonstrated distinct glycoform differences between Wu-1, Gamma, and selected NTD variant spike proteins, but these did not affect antibody binding. Finally, we evaluated the specificity of spike proteins against convalescent COVID-19 sera and found reduced cross-reactivity against some mutants, but not Gamma spike compared to Wuhan spike. Our results illustrate the impact of viral divergence on spike glycosylation and SARS-CoV-2 antibody binding profiles.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535004v1" target="_blank">The role of N-glycosylation in spike antigenicity for the SARS-CoV-2 Gamma variant</a>
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<li><strong>Longitudinal study of humoral immunity against SARS-CoV-2 of health professionals in Brazil: the impact of booster dose and reinfection on antibody dynamics</strong> -
<div>
The pandemic caused by SARS-CoV-2 has had a major impact on health systems. Vaccines have been shown to be effective in improving the clinical outcome of COVID-19, but they are not able to fully prevent infection and reinfection, especially that caused by new variants. Here, we tracked for 450 days the humoral immune response and reinfection in 52 healthcare workers from Brazil. Infection and reinfection were confirmed by RT-qPCR, while IgM and IgG antibody levels were monitored by rapid test. Of the 52 participants, 19 (36%) got reinfected during the follow-up period, all presenting mild symptoms. For all participants, IgM levels dropped sharply, with over 47% of them becoming seronegative by the 60th day. For IgG, 90% of the participants became seropositive within the first 30 days of follow-up. IgG antibodies also dropped after this period reaching the lowest level on day 270 (68.5{+/-}72.3, p&lt;0.0001). Booster dose and reinfection increased the levels of both antibodies, with the interaction between them resulting in an increase in IgG levels of 130.3 units. Overall, our data indicate that acquired humoral immunity declines over time and suggests that IgM and IgG antibody levels are not associated with the prevention of reinfection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535504v1" target="_blank">Longitudinal study of humoral immunity against SARS-CoV-2 of health professionals in Brazil: the impact of booster dose and reinfection on antibody dynamics</a>
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<li><strong>Pre-infection neutralizing antibodies, Omicron BA.5 breakthrough infection, and long COVID: a propensity score-matched analysis</strong> -
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Importance Investigating the role of preinfection humoral immunity against Omicron BA.5 infection risk and long COVID development is critical to inform public health guidance. Objective To investigate the association between preinfection immunogenicity after the third vaccine dose and the risks of Omicron BA.5 infection and long coronavirus disease. Design, Setting, and Participants This nested casecontrol analysis was conducted among tertiary hospital staff in Tokyo, Japan who donated blood samples in June 2022 (1 month before Omicron BA.5 dominant wave onset [JulySeptember 2022]) approximately 6 months after receiving the third dose of the historical monovalent coronavirus disease 2019 mRNA vaccine. Exposures Live virusneutralizing antibody titers against Wuhan and Omicron BA.5 (NT50) and antiSARSCoV2 spike protein antibody titers with Abbott (AU/mL) and Roche (U/mL) assays at preinfection. Main Outcomes and Measures Symptomatic SARSCoV2 breakthrough infections during the Omicron BA.5 dominant wave vs. undiagnosed controls matched using a propensity score. Incidence of long COVID (persistent symptoms ≥4 weeks after infection) among breakthrough infection cases. Results Antispike antibody titers were compared between 243 breakthrough infection cases and their matched controls among the 2360 staff members who met the criteria. Neutralizing antibodies in 50 randomly selected matched pairs were measured and compared. Preinfection anti-spike and neutralizing antibody titers were lower in breakthrough cases than in undiagnosed controls. Neutralizing antibody titers against Wuhan and Omicron BA.5 were 64% (95% CI: 4277) and 72% (95% CI: 5383) lower, respectively, in breakthrough cases than in undiagnosed controls. Individuals with previous SARS-CoV-2 infections were more frequent among undiagnosed controls than breakthrough cases (19.3% vs. 4.1%), and their neutralizing antibody titers were higher than those of infectionnaive individuals. Among the breakthrough cases, preinfection antibody titers were not associated with the incidence of long COVID. Conclusions and Relevance Preinfection immunogenicity against SARSCoV2 may play a role in protecting against the Omicron BA.5 infection, but not in preventing long COVID.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288162v1" target="_blank">Pre-infection neutralizing antibodies, Omicron BA.5 breakthrough infection, and long COVID: a propensity score-matched analysis</a>
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<li><strong>Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines in Immunocompromised Individuals: A Systematic Review and Meta-Analysis Using the GRADE Framework</strong> -
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Introduction: Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response following vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) versus BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework. Methods: The systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals ≥18 years of age; outcomes of interest were SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed for randomized and observational studies using the Risk of Bias 2 tool and the Newcastle-Ottawa Scale, respectively. Evidence was evaluated using the GRADE framework. Results: Overall, 22 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR 0.87, 95% CI 0.79-0.96; P=0.0054; I2=61.9%), COVID-19-associated hospitalization (RR 0.83, 95% CI 0.76-0.90; P&lt;0.0001; I2=0%), and COVID-19-associated mortality (RR 0.62, 95% CI 0.43-0.89; P=0.011; I2=0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials and evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies. Conclusion: This GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288195v1" target="_blank">Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines in Immunocompromised Individuals: A Systematic Review and Meta-Analysis Using the GRADE Framework</a>
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<li><strong>Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infectionin Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir</strong> -
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Background: The role of Nirmatrelvir plus ritonavir (NMV-r) in preventing post-acute sequelae of SARS-CoV-2 infection (PASC) is unknown. The objective of this study is to assess the effect of NMV-r in non-hospitalized, vaccinated patients on the occurrence of PASC. Methods: We performed a comparative retrospective cohort study utilizing data from the TriNetX research network, including vaccinated patients ≥18 years old who subsequently developed Covid-19 between December 2021-April 2022. Cohorts were based on NMV-r administration within five days of diagnosis. Based on previously validated broad and narrow definitions, the main outcome was the presence of symptoms associated with PASC. Outcomes were assessed between 30-180 days and 90-180 days after the index Covid-19 infection. Results 1,004 patients remained in each cohort after propensity-score matching. PASC (broad definition) occurred in 425 patients (42%) in the NMV-r cohort, vs. 480 patients (48%) in the control cohort (OR 0.8 CI 0.67-0.96; p=0.01) from 30-180 days and in 273 patients (27%) in the NMV-r cohort, as compared to 347 patients (35%) in the control cohort (OR 0.707, CI 0.59-0.86; p&lt;0.001) from 90-180 days. Narrowly defined PASC was reported in 337 (34%) patients in the NMV-r and 404 (40%) in the control cohort between 30-180 days (OR=0.75, CI 0.62-0.9, p=0.002) and in 221 (22%) in the NMV-r cohort as compared to in 278 (28%) patients in the control cohort (OR=0.7, CI 0.63-0.9, p=0.003) between 90 -180 days. Conclusions NMV-r treatment in non-hospitalized vaccinated patients with Covid-19 was associated with a reduction in the development of symptoms commonly observed with PASC and healthcare utilization.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288196v1" target="_blank">Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infectionin Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Nasal Treatment for COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Optate;   Drug: Placebo<br/><b>Sponsor</b>:   Indiana University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RCT for Yinqiaosan-Maxingganshitang in the Treatment of COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Chinese Herb;   Diagnostic Test: Placebo<br/><b>Sponsor</b>:   Chinese University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants</strong> - <b>Condition</b>:   COVID19 Testing<br/><b>Interventions</b>:   Behavioral: FABI tailored COVID-19 testing pamphlet;   Behavioral: Standard COVID-19 home-based test kit<br/><b>Sponsors</b>:   Texas Womans University;   National Institutes of Health (NIH)<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Complementary Self-help Strategies for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Interventions</b>:   Behavioral: Complementary self-help strategies in addition to treatment as usual;   Other: Treatment as usual<br/><b>Sponsor</b>:   Universität Duisburg-Essen<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized.</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Drug: PF-07817883;   Drug: Placebo<br/><b>Sponsor</b>:   Pfizer<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of a Health Pathway for People With Persistent Symptoms Covid-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Other: usual care and follow-up by a nurse;   Other: Personalized Multifactorial Intervention (IMP)<br/><b>Sponsor</b>:   Centre Hospitalier Universitaire de Saint Etienne<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Interventions</b>:   Other: conventional western medicine treatment;   Drug: Dexamethasone oral tablet;   Other: Traditional Chinese medicine decoction<br/><b>Sponsor</b>:   China-Japan Friendship Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Study on Safety and Effectiveness of Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19.</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Intervention</b>:   Biological: Extracellular Vesicles from Mesenchymal Stem Cells<br/><b>Sponsors</b>:   First Affiliated Hospital of Wenzhou Medical University;   REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inpatient COVID-19 Lollipop Study</strong> - <b>Conditions</b>:   COVID-19;   Diagnostic Test<br/><b>Intervention</b>:   Device: Lollipop<br/><b>Sponsor</b>:   University of Wisconsin, Madison<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: NP-101;   Other: Placebo<br/><b>Sponsor</b>:   Novatek Pharmaceuticals<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Building Resilience During the COVID-19 Pandemic: a Randomized Controlled Trial</strong> - <b>Conditions</b>:   Healthy;   COVID-19;   Distress, Emotional<br/><b>Interventions</b>:   Behavioral: RASMUS Resilience Training;   Behavioral: Progressive Muscle Relaxation<br/><b>Sponsor</b>:   Medical University Innsbruck<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of Testofen Compared to Placebo on Long COVID Symptoms</strong> - <b>Condition</b>:   Long Covid19<br/><b>Interventions</b>:   Drug: Testofen;   Drug: Microcrystalline cellulose<br/><b>Sponsor</b>:   RDC Clinical Pty Ltd<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Care for Veterans Post-COVID</strong> - <b>Condition</b>:   Post-Acute COVID-19 Syndrome<br/><b>Interventions</b>:   Behavioral: Concordant Care Training;   Behavioral: Education Packet Training<br/><b>Sponsor</b>:   VA Office of Research and Development<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety &amp; Immunogenicity of RVM-V001/RVM-V002 or RVMV001+RVMV002 (Co Administered as Separate Injections) in Healthy Individuals</strong> - <b>Conditions</b>:   Infectious Disease;   COVID-19<br/><b>Interventions</b>:   Biological: RVM-V001 30 µg;   Biological: RVM-V002 30 µg;   Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration<br/><b>Sponsor</b>:   RVAC Medicines (US), Inc.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>HH-120 Nasal Spray for Post-exposure Prevention of SARS-CoV-2</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: HH-120 Nasal Spray;   Drug: Placebo<br/><b>Sponsor</b>:   Huahui Health<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neurological damages in COVID-19 patients: Mechanisms and preventive interventions</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, causes coronavirus disease 2019 (COVID-19) which led to neurological damage and increased mortality worldwide in its second and third waves. It is associated with systemic inflammation, myocardial infarction, neurological illness including ischemic strokes (e.g., cardiac and cerebral ischemia), and even death through multi-organ failure. At the early stage, the virus infects the lung epithelial cells and is slowly…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Unexpected Protective Role of Thrombosis in Sepsis-Induced Inflammatory Lung Injury Via Endothelial Alox15</strong> - CONCLUSION: We have demonstrated that moderate levels of thrombosis protect against sepsis-induced inflammatory lung injury via endothelial Alox15. Overexpression of Alox5 inhibits severe pulmonary thrombosis-induced increase of ALI. Thus, activation of ALOX15 signaling represents a promising therapeutic strategy for treatment of ARDS, especially in sub-populations of patients with thrombocytopenia and/or severe pulmonary thrombosis.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Massively Parallel Profiling of RNA-targeting CRISPR-Cas13d</strong> - Type VI CRISPR enzymes cleave target RNAs and are widely used for gene regulation, RNA tracking, and diagnostics. However, a systematic understanding of their RNA binding specificity and cleavage activation is lacking. Here, we describe RNA c hip- h ybridized a ssociation- m apping p latform (RNA-CHAMP), a massively parallel platform that repurposes next-generation DNA sequencing chips to measure the binding affinity for over 10,000 RNA targets containing structural perturbations, mismatches,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immune and ionic mechanisms mediating the effect of dexamethasone in severe COVID-19</strong> - CONCLUSION: Our findings suggest that dexamethasone attenuates inflammatory cytokine release via Kv1.3 suppression, and this mechanism contributes to dexamethasone-mediated immunosuppression in severe COVID-19.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Transporter Inhibition Profile for the Antivirals Tilorone, Quinacrine and Pyronaridine</strong> - Pyronaridine, tilorone and quinacrine are cationic molecules that have in vitro activity against Ebola, SARS-CoV-2 and other viruses. All three molecules have also demonstrated in vivo activity against Ebola in mice, while pyronaridine showed in vivo efficacy against SARS-CoV-2 in mice. We have recently tested these molecules and other antivirals against human organic cation transporters (OCTs) and apical multidrug and toxin extruders (MATEs). Quinacrine was found to be an inhibitor of OCT2,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The therapeutic effect and mechanism of parthenolide in skeletal disease, cancers, and cytokine storm</strong> - Parthenolide (PTL or PAR) was first isolated from Magnolia grandiflora and identified as a small molecule cancer inhibitor. PTL has the chemical structure of C15H20O3 with characteristics of sesquiterpene lactones and exhibits the biological property of inhibiting DNA biosynthesis of cancer cells. In this review, we summarise the recent research progress of medicinal PTL, including the therapeutic effects on skeletal diseases, cancers, and inflammation-induced cytokine storm. Mechanistic…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immune-mediated liver injury following COVID-19 vaccination</strong> - Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination protocols. All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations, e.g., BNT162b2, mRNA-1273, and ChAdOx1-S, can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Happily Distant or Bitter Medicine? The Impact of Social Distancing Preferences, Behavior, and Emotional Costs on Subjective Wellbeing During the Epidemic</strong> - To inhibit the spread of COVID-19 Public health officials stress, and governments often require, restrictions on social interaction (“social distancing”). While the medical benefits are clear, important questions remain about these measures downsides: How bitter is this medicine? Ten large non-probability internet-based surveys between April and November 2020, weighted statistically to reflect the US population in age, education, and religious background and excluding respondents who even…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>5-alpha reductase inhibitors use in prostatic disease and beyond</strong> - 5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Their effect relies on the inhibition of the 5-alpha reductase enzyme which aids in the conversion of testosterone to dihydrotestosterone. 5-ARIs have increasing clinical relevance outside of benign prostatic hyperplasia (BPH). Such development requires clinicians to have an updated review to guide clinical practices. This review details the pharmacology…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions</strong> - SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type, Delta, and Omicron variants. Specifically, heparan sulfate and suramin had enhanced preferential binding for Omicron RBD, and suramin is most potent against the live SARS-CoV-2 Omicron variant…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection</strong> - Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towards…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of a Peptide Sensor Derived from Human ACE2 for Fluorescence Polarization Assays of the SARS-CoV-2 Receptor Binding Domain</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuing emergence of infectious variants have caused a serious pandemic and a global economic slump since 2019. To overcome the situation and prepare for future pandemic-prone diseases, there is a need to establish a convenient diagnostic test that is quickly adaptable to unexpected emergence of virus variants. Here we report a fluorescent peptide sensor 26-Dan and its application to the fluorescence polarization (FP) assay…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparison of a rapid fluorescence immunochromatographic test with an enzyme-linked immunosorbent assay for measurement of SARS-CoV-2 spike protein antibody neutralizing activity</strong> - CONCLUSION: FIC had good qualitative agreement with ELISA in the detection of positive NAbs-RBD(%) and could be an alternative for rapid NAbs-RBD(%) testing.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparison of antibody response to coronavirus disease 2019 vaccination between patients with solid or hematologic cancer patients undergoing chemotherapy</strong> - CONCLUSION: Hematologic cancer patients receiving chemotherapy tended to respond poorly to both COVID-19 mRNA and vector vaccines and had a significantly lower antibody titer compared to those with solid cancers.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A covalent inhibitor targeting the papain-like protease from SARS-CoV-2 inhibits viral replication</strong> - Covalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 have great potential as antivirals, but their non-specific reactivity with thiols has limited their development. In this report, we performed an 8000 molecule electrophile screen against PLpro and identified an α-chloro amide fragment, termed compound 1, which inhibited SARS-CoV-2 replication in cells, and also had low non-specific reactivity with thiols. Compound 1 covalently reacts with the active site cysteine of PLpro,…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inside the Hush-Money Payments That May Decide Trumps Legal Fate</strong> - Years of interviews with potential witnesses provide insights into the Manhattan D.A.s case. - <a href="https://www.newyorker.com/news/news-desk/inside-the-hush-money-payments-that-may-decide-trumps-legal-fate">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How Putin Criminalized Journalism in Russia</strong> - The case of Evan Gershkovich, a Wall Street Journal reporter being held in Moscow on espionage charges, is only the most recent example of the Kremlins crackdown on reporters. - <a href="https://www.newyorker.com/news/our-columnists/how-putin-criminalized-journalism-in-russia">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Same Ole Line Dudes Are Waiting for You</strong> - Donald Trumps arraignment was a circus for the media, but it was just another day at the office for New Yorks professional line sitters. - <a href="https://www.newyorker.com/news/our-local-correspondents/the-same-ole-line-dudes-are-waiting-for-you">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Whats Behind the Fight Between Pope Francis and the Latin Mass Movement?</strong> - The discord has become a stand-in for conflicts over the decline in Catholics participation in Mass, over the progressive orientation of Franciss pontificate, and over Vatican II itself. - <a href="https://www.newyorker.com/news/daily-comment/whats-behind-the-fight-between-pope-francis-and-the-latin-mass-movement">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Fighting for the Right to Come and Go</strong> - In Mexico, return-migrant activists are asserting their “pocha” heritage and working to end legal and cultural exclusion. - <a href="https://www.newyorker.com/news/annals-of-immigration/fighting-for-the-right-to-come-and-go">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>If it doesnt take our jobs, AI could make work better</strong> -
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<img alt="" src="https://cdn.vox-cdn.com/thumbor/MV2N2CDvQr6qMTjUc0yxed_W51I=/240x0:1680x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72164921/V1_Final_Chatgpt.0.jpg"/>
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Paige Vickers for Vox/Jorm Sangsorn/Getty Images
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Whos afraid of ChatGPT? Not these workers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TJKDX4">
A lot of what Conor Grennan does as a dean of students at NYUs Stern School of Business could be done at least in part by bots. Brainstorming and planning are prime examples of tasks that can be easily handled by generative AI tools like ChatGPT.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="etmyRh">
But instead of feeling like he could be replaced by AI, Grennan has become an evangelist of this technology and its potential to make work better. He likens the opportunity to work with AI technology right now to finding material wealth.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DxfUAB">
“It feels like the Gold Rush, like theres a bunch of people getting to California and seeing little flakes of gold in the river,” he told Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ISb6e0">
Some of Grennans new AI-powered workflow is pretty simple. He drops email chains into ChatGPT or Bing or Bard — he uses them all — and asks it to quickly search for details about a student or deliverables he needs to act on. But he admits that using this technology just for menial tasks would be akin to picking up an iPhone just to use its flashlight. He prefers to use AI to research, brainstorm, and learn.
</p>
<div class="c-float-right c-float-hang">
<aside id="AmNtJA">
<q>“It feels like the Gold Rush, like theres a bunch of people getting to California and seeing little flakes of gold in the river”</q>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p47ut0">
For example, Grennan might ask an AI to give him five suggestions of a good place to hold an event for 50 students in lower Manhattan on a Tuesday night, or have it reason through how young people in Ohio could help the climate crisis, or have it explain to him what exactly an API is. He keeps asking and refining the questions until he gets good answers, and hes <a href="https://www.linkedin.com/in/conorgrennan/recent-activity/all/">constantly coming up with</a> new things to ask. Grennan thinks talking with the AI makes him more creative, stokes his sense of wonder, and ultimately makes him better at his job and life.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lYN1PW">
“Instead of the drudgery of Ive been given a task, now Im going to solve that task, its, Ive been given a task. What are different ways of looking at it? How can this improve my life? How can I actually get smarter?’” said Grennan. He was recently granted the additional title of head of generative AI at Stern, and is helping develop an AI initiative for Sterns MBA program so students, faculty, and administrators can become comfortable with AI tools in the workplace.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JM1tSV">
A <a href="https://arxiv.org/pdf/2303.10130.pdf">recent study</a> by the University of Pennsylvania and OpenAI, the makers of ChatGPT and its more advanced successor <a href="https://www.vox.com/2023/3/15/23640640/gpt-4-chatgpt-openai-generative-ai">GPT-4</a> — who have a vested interest in hyping their own technologys capabilities — found that half of workers could have more than half their tasks exposed to large language models, like ChatGPT. Exposure was the highest among high-wage jobs that require degrees and had previously felt relatively safe from the onslaught of technological erasure: financial analysts, web designers, legal researchers, and journalists, among others. While the study said tools like ChatGPT could certainly save those jobs significant time completing tasks, it stopped short of saying those jobs would be fully automated by those technologies. Its likely, however, that it will change them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9w02jY">
While much has been made about AIs potential to destroy our jobs, Grennan and other American workers whose tasks overlap with capabilities of software like ChatGPT are embracing the technology to do away with drudge work, to be more creative, and to level up their skills. Marketers are using it to write better copy; programmers are using it to take on projects that were previously out of their league or read code in unfamiliar languages. And it seems like everyones now using it to summarize or write emails and boilerplate documents.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4yMCYs">
Where some see a threat, these workers see possibility. And they hope their mastery of the tools, coupled with their uniquely human skills, will allow them to stay employed even as artificial intelligence gets more and more clever. Back in January, over <a href="https://www.fishbowlapp.com/insights/70-percent-of-workers-using-chatgpt-at-work-are-not-telling-their-boss/">40 percent</a> of Americans said they were using generative AI technology at work, and that rate has likely gotten higher. At the same time, about <a href="https://docs.cdn.yougov.com/0jv1wfqlmo/results_AI%20Effects%20on%20Job%20Market.pdf">half of Americans</a> think AI could negatively impact the number of jobs in the US.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="i8CtT4">
The truth is we dont know exactly how artificial intelligence technologies will impact work. The fear is that if tools make existing tasks take hours instead of days, employers might hire fewer employees to get the job done or make their work part-time. The hope is that while the new technology could cause some disruption in what people do, it will ultimately lead to more and better work, much like previous technological advancements, such as the personal computer or even the internet, <a href="https://www.theatlantic.com/ideas/archive/2023/01/chatgpt-ai-economy-automation-jobs/672767/">didnt spell the end</a> of white-collar jobs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AixAPi">
For now, we know that Americans whove chosen to deploy this technology at work seem to like it. They certainly dont feel like frogs boiling in a pot.
</p>
<h3 id="eLpX1u">
Goodbye to drudgery?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2dvWLf">
Its important to remember that even the best jobs have parts of them that suck. And those parts are the first ones on which workers are bringing AI to bear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GVa5oG">
Colin McAuliffe, a filmmaker and founder of the production company Zero One Digital Media, has been using the AI software DALL-E to generate images to illustrate business pitch decks. Rather than scroll through pages and pages of stock images, he simply tells the software precisely what he wants — say, a “photograph of a lemon” — and it pops one out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Sme1Ne">
“Its something I hated doing or I would make other people do for me,” he said. “And now I do it myself easily, and its kind of fun.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7qP3b9">
Recently, a client gave him a script that had been written by ChatGPT, and while McAuliffe hasnt had it write scripts yet, he wants to use AI more often to make shooting schedules and plan trips for his company.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="necFq7">
“All that other stuff just takes me away from making videos,” he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WUjkEV">
People say theyre using these tools on tasks they hate, and that allows them to focus on what they love.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JaBrl6">
Vanessa Bowen, a self-employed product designer, used to dread having to come up with the text that would go inside their app prototypes. If something was off, clients would get hung up on the text rather than critiquing the user interface design of the app, and it could derail the whole interaction. Now, Bowen feeds the AI information about the client and the product, and what type of text box theyre trying to fill; then ChatGPT generates that text.
</p>
<div class="c-float-left c-float-hang">
<aside id="1Facv0">
<q>“It would leave us more time to do other things like be more creative or not work so much”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rGOQWU">
“It throws out something simple and concise and takes away some of that cognitive load,” they said. That lets Bowen focus on what they really like doing: designing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1AXNms">
“I find that we are stuck in the mundane activities of the day-to-day that could be automated, which then in turn could free up our whole lives,” they added. “It would leave us more time to do other things like be more creative or not work so much.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dOTYOF">
Its a sentiment white-collar workers expressed over and over again, and its part of why companies like <a href="https://www.vox.com/technology/2023/3/16/23643806/ai-microsoft-word-powerpoint-office-google-artificial-intelligence-chatgpt-automation-jobs-work">Microsoft</a> are leaning into AI so heavily in their workplace tools: Not all work is good work. Soon, Microsoft says workers will be able to ask AI-powered tools to make Excel perform complex equations, to have PowerPoint build presentations, and to summarize Outlook emails — all within seconds and by talking to them like you would a person.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oXOYkF">
Whether that means people will spend that time saved on the parts of their job they really like or whether theyll simply squander those freed-up hours remains to be seen. Its also possible that this technology just enables them to make more unnecessary work for everyone else. Take for example, this <a href="https://marketoonist.com/2023/03/ai-written-ai-read.html">great cartoon</a> where one person uses AI to make a bullet point into a long email, to which the emails reader responds by asking the AI to distill the email into a single bullet point.
</p>
<h3 id="SzBzPb">
Leveling up at work
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NetQLx">
Theres a lot of doom and gloom about what generative AI will mean for computer programmers specifically. Indeed, these tools can often spin up perfectly functional code, using natural language, in an instant, so its fair to wonder what that means for the highly paid people who used to do the same thing more slowly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9aLSiV">
But the software engineers and developers we spoke to preferred to think of the technology as something that enables them to be better at what they do, likening it to having an incredibly smart assistant or intern at their disposal.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cpTfhg">
Victor Boutté, a software engineer and tech lead manager at the video hosting company Wistia, says AI tools like GitHub Copilot make him more productive, by suggesting how to complete code hes started so that he doesnt have to write the whole thing. Boutté, who works remotely, considers AI tools to be a lot like sitting next to a very smart colleague who also happens to have already read through his code and has limitless time for his questions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ywFu4v">
“Im using it essentially as I would another engineer to bounce ideas off of. Its helping me flesh through these ideas more deeply, and the feedback is instant,” he said.
</p>
<div class="c-float-right c-float-hang">
<aside id="n1iYOO">
<q>“It gets the creative wheels spinning about what can I use this kind of tech to build”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qRk2z9">
AI not only helps Boutté code more quickly, but also elevates whats possible for him to code in the first place.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xBEeDf">
“Throughout my career, Ive never seen a technology as advanced as this. And it gets the creative wheels spinning about what can I use this kind of tech to build,” he said. “Its inspiring me.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AH3TRt">
For independent developer and researcher Simon Willison, AI tools allow him to be more ambitious because he spends less time researching how to figure things out. That means he has more time to try out time-intensive projects he might have previously had to pass on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Dljgv0">
Recently, Willison helped his wife with a pottery project. She wanted to see the rate at which a kiln cooled down after being heated in a microwave, in order to estimate its peak temperature while heating. Since she couldnt put the thermometer in the microwave, after taking the kiln out, she would have to check its temperature over the course of the 90 minutes it took to cool. Instead, Willison <a href="https://til.simonwillison.net/googlecloud/video-frame-ocr">asked GPT-4</a> how to break down a video of the thermometer into 10-second JPEG intervals. He then asked it for commands that would read the temperature from the images and chart it over time. Willison is now thinking about how he could help journalists bring such knowledge to problems like analyzing police body camera footage.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nfyf8W">
“Normally, when faced with challenges like this, Id be like, Its gonna take me an hour to figure this out. Just sit down next to the microwave and write the numbers down,” he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VXSHDH">
Even in less technical and more creative areas, workers are finding that generative AI is able to make them better at what they do. In addition to letting humans spend more time on their creative tasks, generative AI is showing off its own kind of creativity — with the right prompts.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xLuj8f">
Michael Kaye, director of brand marketing and communications at the dating app OkCupid, has been asking generative AI to come up with in-app matching questions. OkCupid matches people based on how they answer these questions, so coming up with ones that illuminate whats important to people is incredibly important to how the service functions. At any given time, OKCupid has thousands of these questions available for daters to answer, and Kaye was responsible for creating new ones. For Kaye, this was one of many tasks he does at work, so offloading some of the question creation to AI helped free him up to work on other things. More importantly, he said, the questions that the AI generated — which were based on the simple prompts of “What would you ask on a date?” and “What would you ask on a dating app?” — were actually very good.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0esIIw">
The first 10 AI-generated questions Kaye ended up <a href="https://theblog.okcupid.com/chatgpt-is-the-matchmaker-you-didnt-know-you-needed-1c79f57416a4">adding to the dating service</a> included “How do you balance your own needs with the needs of your partner in a relationship?” “What do you value most in a partner?” and “Are you a morning or night person?” So far, theyve been popular, with users responding to them more than 675,000 times since the end of January.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6lERSz">
“Theyre high-quality, especially given how generic the prompt was,” Kaye said. “They might sound surface-level, but I think those are things that really help connect people.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3gS5P8">
He plans to add more ChatGPT questions using more specific prompts every month this year.
</p>
<h3 id="JEPDc0">
Why AI probably wont take our jobs
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HZ8SG6">
While everyone we spoke to understood that generative AI might be disruptive to some jobs, no one felt it was a real danger to theirs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sHY80B">
A common refrain was a version of a <a href="https://twitter.com/svpino/status/1610984481342771200">tweet</a> from machine learning engineer Santiago Valdarrama that said, “AI will not replace you. A person using AI will.” In other words, they felt that their mastery over generative AI tools would give them a leg up, even if that generative AI made some of what theyre paid to do obsolete.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LxFFvW">
“When I first started using GPT-4, [losing my job] was my first concern. Its very natural to feel threatened by new technology, especially technology thats really good at what you do,” said Stephanie Yamkovenko, a group manager for the digital marketing team at Khan Academy, an education nonprofit that has partnered with GPT-4 maker OpenAI since September.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="77jnqL">
“But as Ive used it more, Ive realized that its going to be a skill thats going to be in high demand for writing and editing in the future,” she added.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z559gV">
Yamkovenko recently was able to work on a much more robust product launch than what her small team normally would have been able to do. She used ChatGPT to write a greater volume of social media copy, which in turn snagged the company 10 times the traffic it would normally get.
</p>
<div class="c-float-left c-float-hang">
<aside id="gbUo1J">
<q>“Its very natural to feel threatened by new technology, especially technology thats really good at what you do”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wvV7lG">
Others were sanguine that their skills, now boosted by their agility with generative AI, are eternally in demand.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n437qS">
Somnath Banerjee, VP of data science at the early-stage investment firm Clear Ventures, said there will always be an abundance of work for engineers like himself. Hes been using AI to code projects more quickly and to feel more confident in his email writing as a non-native speaker.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uFrYqx">
“They will not say, I paid him for two weeks and you did it in two days, because theres always two years of work waiting for you,” he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NamXEN">
None of this, of course, is to say that work will be the same. The acceptance of using tools like ChatGPT will be the first of many changes. Even if they do keep their jobs, what these white-collar workers do and how they do it will likely be different if generative AI technology becomes widely used. That will be a loss to many who like their craft as is.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vGYJqe">
Take, for example, this 3D mobile games artist who <a href="https://www.reddit.com/r/blender/comments/121lhfq/i_lost_everything_that_made_me_love_my_job/">lamented on Reddit</a> recently: “My job is different now since Midjourney v5 came out last week. I am not an artist anymore.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zNClAl">
The poster added, “All I do is prompting, photoshopping and implementing good looking pictures. The reason I [wanted] to be a 3D artist in the first place is gone. I wanted to create form In 3D space, sculpt, create. With my own creativity. With my own hands.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WSABjD">
Those whove embraced generative AI and who are less tied to the specific tasks of their work will likely have an easier time adjusting to a world of work thats changing in front of their fingertips.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ITVS0h">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WykvN4">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xAIqcr">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RBahP2">
</p></li>
<li><strong>How the US ran short on Adderall</strong> -
<figure>
<img alt="An empty prescription bottle." src="https://cdn.vox-cdn.com/thumbor/jWt3YAau8BpoTz1t51RC_BdDGNo=/0x0:3376x2532/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72164889/GettyImages_185278776.0.jpg"/>
<figcaption>
The ADHD drug Adderall is still experiencing a shortage in the US, six months after the FDA first announced the inadequate supply. | Getty Images/iStockphoto
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Limits on the ADHD drugs supply are coming under scrutiny amid an increase in diagnoses and a six-month shortage.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zcNACs">
Six months after the FDA first announced a shortage of <a href="https://www.vox.com/policy-and-politics/23484040/rsv-flu-amoxicillin-tamiflu-abuterol-drug-adderall-shortages">the ADHD drug Adderall</a> and its generic variations, a <a href="https://www.houstonchronicle.com/business/article/ozempic-adderall-albuterol-medication-shortages-17876067.php">steady</a> <a href="https://www.cnn.com/2023/02/23/health/adderall-shortage-adhd/index.html">stream</a> of <a href="https://twitter.com/fordm/status/1638213864494866442">reports</a> shows patients are still struggling to obtain a medication that can be essential for leading a normal and productive life.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rxclMG">
Adderall might seem like just one of many drugs that its been increasingly difficult to get. Drug shortages are becoming <a href="https://www.vox.com/policy-and-politics/23484040/rsv-flu-amoxicillin-tamiflu-abuterol-drug-adderall-shortages#:~:text=According%20to%20a%202022%20report,economics%20of%20the%20pharmaceutical%20market">increasingly common</a> in the United States, and on average, lasting longer. Typically, these shortages are, essentially, a supply chain problem: When one drug company experiences a shortage because of supply problems with raw materials, for example, there is little capacity in the market to make up for that shortfall.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6Qv5hf">
But the explanation for the persistent Adderall shortage is more complicated. While it began with manufacturing problems, the picture has muddied over the past few months. Currently, four different companies are <a href="https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Amphetamine%20Aspartate;%20Amphetamine%20Sulfate;%20Dextroamphetamine%20Saccharate;%20Dextroamphetamine%20Sulfate%20Tablets&amp;st=c&amp;tab=tabs-1">reporting shortages</a> of the drug. Their reasons include a shortage of its active ingredient due in part to the unusual way in which Adderall is regulated, and an increase in demand.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sYdia9">
Drug shortages are almost always the result of too little supply, not too much demand. But while artificial limits on supply are undoubtedly contributing to the shortage, the growing demand for Adderall is unique. As the medical science on ADHD has evolved, doctors now better understand how ADHD manifests at different ages and are better able to identify when a patient may be dealing with the disorder and, therefore, when Adderall or another stimulant medication may be an appropriate treatment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6ZrHWK">
For most medical conditions, an increase in the number of people diagnosed would not create new barriers (other than market constraints) to manufacturing more medications for the people who need treatment. But whats different about ADHD is that the first-line treatment is a stimulant drug with the potential for misuse or addiction — and so its a matter not just for pharmaceutical companies but for law enforcement. The Drug Enforcement Agency has hedged on the side of keeping production of these drugs down to limit the potential for abuse.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mkfW7I">
The fear is that Adderall would follow the same path as opioid painkillers: careless overprescribing would lead to an epidemic of drug addiction — this time, to stimulants.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uEMZnO">
The current shortage is the result of rising demand colliding with restricted supply, with consequences for millions of patients.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mYS3LA">
“People are raising the question, Why is Adderall being put in the same category as the opiates?’” Dr. Max Wiznitzer, who advises the ADHD advocacy group CHADD and practices in the Cleveland area, told me. “Its not where the science is. Theyre so stuck on what it has been, theyre not necessarily asking themselves where the science is pointing now.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IZCjtY">
The Adderall shortage could be an opportunity to change how the country at large views this condition and the medication to treat it. But institutional inertia, and the shadow of the opioid crisis, is standing in the way.
</p>
<h3 id="fq73oh">
How has our understanding of ADHD evolved?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hgcIJ4">
The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000907/">modern scientific understanding of ADHD</a> is commonly associated with George Still, a British pediatrician who in a series of lectures in 1902 described children who were showing symptoms of hyperactivity, impulsivity, and inattention and referred to their condition as a “defect of moral control.” The children were said to suffer from poor academic performance and other behavioral problems.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="P5nR43">
In the following decades, medical sciences understanding of the disorder advanced from blaming “moral defects” to brain damage to understanding that a deficit of certain neurotransmitters, particularly dopamine, contributes to the disorders telltale symptoms.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r3miPI">
“As time went on, we had science tell us, it wasnt that people were doing something wrong,” Wiznitzer said. “It was a product of how their brains were built.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IhhXyB">
As ADHD became more widely accepted as a distinct clinical disorder, rather than a result of poor parenting or a byproduct of another condition, the medical community began investigating more treatments. Ritalin had first been approved by the FDA in the 1950s, but it requires more frequent dosing to have a sustained effect.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UjORMo">
Adderall was approved in 1996 and would soon become the most commonly prescribed treatment for ADHD, though Ritalin and several other drugs remain in use. A few years later, an extended-release version of the drug — intended to be less prone to abuse — was put on the market.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tRfVay">
According to <a href="https://www.cdc.gov/ncbddd/adhd/data.html">the Centers for Disease Control and Prevention (CDC)</a>, approximately 6 million children ages 3 to 17 (about 9.8 percent of children in the United States) have been diagnosed with ADHD as of 2019. Boys are about twice as likely to be diagnosed with the condition as girls.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PleObw">
National surveys have varied in their estimates of how many US adults have ADHD, with figures ranging from 1 to 4 percent, but the trend is consistent: The share who have been diagnosed is <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2753787?utm_source=For_The_Media&amp;utm_medium=referral&amp;utm_campaign=ftm_links&amp;utm_term=110119">going up</a>. <a href="https://news.ohsu.edu/2022/10/13/ohsu-researchers-sharpen-estimate-of-true-percentage-of-people-with-adhd">A new estimate</a> published in 2022 by researchers from the Oregon Health and Science University put the percentage of the total US population with ADHD at 3.5 percent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CDTtO5">
According to IQVIA, a health care data and analytics company, <a href="https://www.axios.com/2022/11/15/adderall-shortage-adhd-diagnosis-prescriptions">about 41.4 million prescriptions for Adderall</a> were dispensed in the US in 2021. Not every prescription is for a unique individual, but those data suggest that millions of Americans are relying on the drug to moderate their ADHD symptoms.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KI30Jn">
But that suddenly became more difficult when, in October 2022, the Adderall shortage began.
</p>
<h3 id="w7L860">
How does the federal government limit Adderall production?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4Oabtw">
The reasons for drug shortages can be difficult to divine. Manufacturers are not mandated to report the reasons for a drug shortage and any public information they do provide can be vague.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0NBgWm">
That has proven true with the Adderall shortage too. However, experts say that the role of the federal government in regulating one of Adderalls active ingredients makes this shortage distinct.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qycdPS">
One of the active ingredients in Adderall is amphetamine, and therefore the drug is regulated as a controlled substance under federal law. Its potential for abuse has long been recognized, with the cliche example being college students taking the drug to help them study. <a href="https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2018.17091048">A 2018 study by federal researchers</a> found that about 5 million Americans misused a prescribed stimulant, of which Adderall is the most common, at least once in the past year; about 400,000 misused stimulant drugs frequently enough to be characterized as having a disorder. (About 2.7 million people in the US <a href="https://www.cdc.gov/dotw/opioid-use-disorder/index.html#:~:text=impairment%20and%20distress.-,A%20diagnosis%20of%20OUD%20is%20based%20on%20specific%20criteria%20such,States%20report%20suffering%20from%20OUD.">report</a> they have an opioid use disorder.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zAxNpe">
To mitigate the potential for abuse, the Drug Enforcement Administration sets production limits for Adderall and its generic competitors. In order to produce the drugs legally, pharmaceutical manufacturers must obtain approval from the government and comply with regulations for the medications manufacturing, distribution, and dispensing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rNsZ0T">
The DEA also sets annual production quotas for Adderall, as with other controlled substances that have recognized medical uses, based on estimates of legitimate medical and scientific needs, as well as the potential for diversion and abuse. However, those quotas are not well understood; while the agency announced in 2019 that it was allowing for more production of Adderall, given the apparent growing need in the patient population, we still dont know exactly how much production has been authorized or the limits set for individual companies.
</p>
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“The DEA gives the companies a set amount of raw material quota to manufacture these products, but we dont know which company gets how much,” said Erin Fox, a pharmacist at the University of Utah and leading expert on US drug shortages. “Some companies say theyre short, but DEA says that they havent used it all, so lots of finger-pointing.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QujDsu">
Indeed, the companies that produce Adderall and its generic version <a href="https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Amphetamine%20Aspartate;%20Amphetamine%20Sulfate;%20Dextroamphetamine%20Saccharate;%20Dextroamphetamine%20Sulfate%20Tablets&amp;st=c&amp;tab=tabs-1">have cited</a> both a shortage of the active ingredients and an increase in demand to explain their ongoing shortages. But another factor, new limits on the dispensing of the drug at US pharmacies, is making the situation worse.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="T2mY54">
In 2022, drug distributors reached a settlement with most states over their role in the proliferation of prescription opioids that helped create an addiction and overdose epidemic. Bloomberg <a href="https://www.bloomberg.com/news/articles/2023-04-03/adderall-shortages-are-made-worse-by-the-opioid-crisis">reported this week</a> that, as part of that settlement, secret limits were placed on the dispensation of controlled substances last July. That has in turn prevented pharmacists from filling the prescription of every patient who comes to their pharmacy with an Adderall order.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AEYAQZ">
According to Bloomberg, in essence, manufacturers are supposed to limit a pharmacys supply of drugs covered by the Controlled Substances Act, which includes opioids as well as stimulants. Pharmacists can only fill a certain number of prescriptions over a set period. But there has been widespread confusion over these rules because the pharmacists themselves dont know what the limits are or when they are approaching them. Sometimes, they wont know their access to Adderall has been cut off until trying to fill a prescription.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RLIwYB">
In theory, that information is hidden to prevent anyone from gaming the system. But in practice, it has made it harder for patients to get access to the medicines they need during a six-month shortage.
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“I understand the intention of this policy is to have control of controlled substances so they dont get abused, but its not working,” Richard Glotzer, an independent pharmacist in Millwood, New York, told Bloomberg. “Theres no reason I should be cut off from ordering these products to dispense to my legitimate patients that need it.”
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Doctors have found workarounds. Certain dosages (such as 7.5mg versus 15) are more plentiful. Some physicians have also opted for immediate-release versions of the drug instead of the extended-release doses that are chiefly in short supply. And for some of those patients, those creative solutions may work. But that may not be true for everybody: Wiznitzer told me that, on the day of our interview, a mother had come into his practice and asked that her child be returned to his older medication, currently still experiencing a shortage, as soon as possible.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nxyhKL">
Some manufacturers report they expect to have production back on track by the end of April or in May. But the fact that a drug depended upon by millions of Americans could, at best, experience more than half a year of shortages has left experts wondering why more couldnt be done to provide relief sooner.
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How can the government make sure Adderall is available to those who need it?
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MvNT9p">
The ongoing shortage has brought the DEAs limits on Adderall production under scrutiny. Though the current shortage was officially recognized in October 2022, the agency did not alter its plans for production quotas in 2023 in <a href="https://www.govinfo.gov/content/pkg/FR-2022-12-02/pdf/2022-26351.pdf">a December 2022 bulletin</a>, to the bafflement of <a href="https://reason.com/2023/03/14/wheres-your-adderall/">some outside observers</a>.
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Maia Szalavitz, a leading commentator on substance abuse issues, suggested in <a href="https://www.nytimes.com/2023/03/25/opinion/adderall-shortage-drug-policy.html">a column published last month in the New York Times</a> that oversight of the drug should be shifted from the DEA, which approaches the issue through a law-enforcement lens, to the Food and Drug Administration. She advocated specifically for increasing production quotas and for revisiting the opioid settlements that have added to the regulatory red tape that may limit legitimate access to the drug for patients who need it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3fiZtk">
These artificial limits on production, however well-intentioned, are at least partly to blame for the persistent shortage of the past six months. Lawmakers are <a href="https://spanberger.house.gov/posts/spanberger-puts-more-pressure-on-dea-to-address-adderall-shortage-following-silence-from-federal-agencies">pressing the DEA</a> to do what it can to alleviate the problem. The solution seems simple — allow more of the drug to be produced — though that also has potential downsides.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kViX57">
Illicit use of prescription stimulants is a real problem. Some of the doctors I spoke to did not want to comment on the record about any changes to federal Adderall regulations, given its sensitive nature. There are <a href="https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2018.17091048">several hundred thousand people</a> in the US who are abusing stimulants like Adderall habitually. Prescription stimulants can be deadly, though they have historically accounted for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606828/">a small percentage of all overdose deaths</a>.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U1hZ2f">
Regulations should reflect the relative risks. “Stimulants like Adderall and Ritalin are nowhere near as addictive or lethal as Fentanyl or other opioids,” Linda Schmidt, a child and adolescent psychiatrist at Oregon Health and Science University, told me.
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The question is how to calibrate government oversight to balance the risks to public health versus the risks to patients who cant access the medications they need. Some experts believe the current system is too overloaded toward preventing abuse, and the current shortage is a consequence of that misalignment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WZRfdi">
It would certainly be possible to monitor for Adderall diversion without subjecting it to the same restrictions as opioids. Wiznitzer pointed out that, under Ohio laws, physicians are required to check the states prescription drug monitoring database once a month for patients who are prescribed opioids, but only once a year for patients who are prescribed stimulants.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IMrlMj">
Most of the policy discussion during the shortage has focused on questions of how to loosen up the supply of Adderall.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p0Xks4">
The other factor driving the shortage, the increase in demand, is more complicated. During the pandemic, it became easier for doctors to prescribe controlled substances without an in-person visit. There have been examples, as <a href="https://www.vox.com/recode/23310326/tiktok-adhd-telehealth-done-adderall">Voxs Sara Morrison previously reported</a>, of “sketchy as hell” startups pushing Adderall on social media sites like TikTok. The DEA has proposed new rules to require an in-person consultation before the prescription of a drug like Adderall.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9CGrfU">
But that plan <a href="https://newrepublic.com/article/171018/biden-telemedicine-adderall-buphenorphine-restrictions">has been criticized</a> by some as putting patients at risk who may rely on telemedicine for legitimate reasons. Wiznitzer pointed out that a virtual visit, in which a doctor can observe a child in their natural habitat, can be more revealing than an office visit.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gevye8">
This law enforcement mindset is at the heart of the critique from Szalavitz and others. The DEA approaches its role in regulating Adderall as primarily one of law enforcement, with the emphasis being placed on preventing abuse as much as possible. That may be an understandable — if misguided, in the eyes of some — legacy of the opioid epidemic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ew0XIP">
“Perhaps in response to its failure to prevent the rise in prescription opioid misuse, the D.E.A. may be trying to avert a repeat crisis by keeping stimulant manufacturing quotas tight,” Szalavitz wrote in the Times.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NW11du">
But the crisis of the past six months has also shown the potential risk of the current approach: In the richest country in the world, desperate patients cant get a medicine they need.
</p></li>
<li><strong>Kelly Link secures her crown as queen of the literary fairy tale</strong> -
<figure>
<img alt="A parchment-colored book cover depicts a broken nutshell. A small black dog sits in one half of the shell, and the word STORIES is superimposed on the other. On the right side of the cover we can see the shadow of pointed cat ears. The top of the cover says WHITE CAT, BLACK DOG, and the bottom says KELLY LINK, FINALIST FOR THE PULITZER PRIZE." src="https://cdn.vox-cdn.com/thumbor/FPAJf6MQnTIGkUIFZ9_EWDiof3Y=/0x226:298x450/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72164822/9780593449950.0.jpeg"/>
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<em>White Cat, Black Dog</em> by Kelly Link. | Random House
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Her latest book, White Cat, Black Dog, is a collection of fairy tales that shimmer with unease.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SmLJRx">
A characteristic of the fairy tale is that it refuses to explain itself. Not for folklore is our modern fretting over magical systems that behave, science-like, in clear and predictable ways, with rules an audience can fathom. Cinderellas slipper is glass because thats what its made out of. There are giants at the end of Jacks beanstalk because thats where they are. Rapunzels hair grows long enough to be used as a ladder because thats what it does.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4BFYQ1">
Kelly Links short stories are fairy tales in part because she does not force them to explain themselves. In Links funny, eerie tales, you talk to a magical grub by putting it into your own mouth because thats how it works. Death requires a house sitter because he does. “The mechanics of how I can speak are really of no great interest,” says a cannabis-farming white cat, “and Im afraid I dont really understand it myself, in any case.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K615cO">
The pot-growing cat is one of the title characters of <a href="https://bookshop.org/p/books/white-cat-black-dog-stories-kelly-link/18600074"><em>White Cat, Black Dog</em></a>, Links latest collection of short stories. Its the fifth anthology Link has published since she put out her debut, <em>Stranger Things Happen</em>, at her own Small Beer Press in 2001, and the first since she became a Pulitzer finalist for 2016 and won a MacArthur “genius” grant <a href="https://www.washingtonpost.com/entertainment/books/short-story-writer-kelly-link-wins-macarthur-genius-grant/2018/10/04/75b53be8-c768-11e8-b1ed-1d2d65b86d0c_story.html">in 2018</a>. <em>White Cat, Black Dog</em> is also the first Link anthology in which each story is explicitly a fairy tale, although the straight-faced incomprehensibility of the magic in her previous stories makes them a good match for the genre, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LC8gmn">
The white cat in question comes from “The White Cats Divorce,” Links take on Madame dAulnoys “The White Cat.” A king — or, in Links case, a tech billionaire — sends his three sons off in search of the smallest and most beautiful dog they can find, assuring them hell name the winner his heir. The youngest son meets a white cat, who sends him home with a nutshell which, on being cracked open, reveals a miniscule dog of supreme beauty. “Certainly, that is a very small dog,” allows Links tech billionaire.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4pFHXc">
Links retelling, though, is not a copy-and-paste of the original with updated job titles. She knows that fairy tales were never really just for children, and she uses their deceptively simple structures to explore decidedly adult concerns. Her billionaire, Peter Thiel-like, longs to become immortal, and to that end marries a succession of increasingly younger wives, swims two miles a day, receives blood transfusions from the young, and dines upon “fish and berries and walnuts as if he were a bear and not a rich man at all.” He sends his sons off on increasingly baroque quests because he finds that their presence is one of the great obstacles to his dream of conquering death: “It is very difficult to remain young when ones children selfishly insist upon growing older,” observes Link.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="f3Imip">
Again and again, Link applies her fairy tales like a nutcracker to our contemporary archetypes, breaking them open and making us shiver with mingled horror and delight at the tiny and unsettling wonders she finds within. The newlywed quest narrative “East of the Sun, West of the Moon,” applied to a couple of middle-aged Upper West Side gay men in “Prince Hat Underground,” becomes a study of the problem of a perennially unfaithful beloved. “The Lady and the Fox” sets the Scottish tale of a fairy knight “Tam Lin” within a wealthy family that delights in adopting strays, and in so doing casts a vexed eye over the part-grateful, part-resentful power dynamics that ensue.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DTReWJ">
Within these half-familiar story forms, Links magic continually disrupts the ideas we think we have a solid grasp on. The worlds she builds are recognizable but fundamentally strange, other, not quite like anything youve ever seen before. When you emerge out of <em>White Cat, Black Dog</em>, the world you left behind doesnt look quite like anything youve seen before either.
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hockey India moves closer to reviving HIL</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2023 | Five sixes bat used by Rinku was KKR captain Ranas</strong> - The left-handed Rinku Singh hammered successive sixes off Yash Dayal from the last five balls of KKRs run chase</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Perks of BCCIs honorary job | First class travel, suite room and $1,000 per day on foreign trips</strong> - The BCCI board has also revised the allowances for the members of its state units who will now get ₹30,000 per day during domestic travel and $400 on foreign travel</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Indian GM Gukesh wins title at World Chess Armageddon Asia &amp; Oceania event</strong> - He won in a field that included former world classical champion Vladimir Kramnik, Daniil Dubov, Yangyi Yu, Vidit Gujrathi and Karthikeyan Murali and Param Maghsoodloo, apart from Nodirbek Abdusattorov</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2023 | Shikhar Dhawan blames batting unit for loss against SRH</strong> - Dhawan slammed a 66-ball 99 not out to carry the Punjab team on his shoulders as the other batters cut a sorry figure after being asked to take first strike</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Centre runs up dues of ₹483 crore on welfare pensions payment to Kerala</strong> - As per information shared by State Finance department in response to an RTI application</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>HAL pays second interim dividend of ₹502.58 crore</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Geographical Indication: post-registration initiatives vital, say top officials of Textiles Committee</strong> - One need to register producers as authorised users, train them to use GI as an instrument for marketing the product, build the brand and logo, says Tapan Kumar Rout</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Countering Rahul Gandhis ₹20,000 crore claim, Adani says $2.6 billion stake sale money came in group firms</strong> - The statement was issued rebutting reports in an international publication, which apparently was the basis of Rahul Gandhis statement late last month questioning</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SC grants Centre 4 weeks to respond to PIL for barring those charged with serious crimes from polls</strong> - A Bench of Justices K. M. Joseph and B. V. Nagarathna also said the Union Government first needed to identify what constituted serious offences</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Who leaked top secret US documents - and why?</strong> - Almost 100 US defence department documents have been leaked - and it is unclear who will benefit.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mikheil Saakashvili: Thousands join mass anti-government rally in Georgia</strong> - The demonstrators are calling for the immediate release of jailed ex-President Mikheil Saakashvili.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Qatargate: Andrea Cozzolinos lawyer speaks to the BBC</strong> - An MEP allegedly took bribes to sway EU lawmakers. His lawyer says prosecutors want to “crack” him.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>French Alps avalanche: Guides among six killed at Armancette glacier</strong> - A wall of snow hit a group near Mont Blanc in south-eastern France.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Vitaly Votanovsky flees Russia after documenting a Wagner cemetery</strong> - How an activist documented Russias war dead by counting graves - and was forced to flee.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Last-gen ultralight laptops are nearly as fast as new models—and much cheaper</strong> - Would you pay 42 percent more for a 7.8 percent productivity boost? - <a href="https://arstechnica.com/?p=1923886">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Musk admits NPR isnt state-affiliated after asking questions he could have Googled</strong> - NPR now labeled “Government Funded” despite getting under 1% of funds from US. - <a href="https://arstechnica.com/?p=1930327">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Black hole is soaring between galaxies, leaving stars in its wake</strong> - A galaxy merger may have set a supermassive black hole free. - <a href="https://arstechnica.com/?p=1930219">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Klaus Teuber made Catan, and it changed the worlds expectations for board games</strong> - One mans quest to re-create ancient exploration opened up new tabletop worlds. - <a href="https://arstechnica.com/?p=1929865">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Were one step closer to reading an octopuss mind</strong> - A recording device and electrodes were implanted in the very flexible cephalopods. - <a href="https://arstechnica.com/?p=1930115">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Ukranian Soldier</strong> - <!-- SC_OFF --></p>
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A Russian general hears someone shouting from the woods - “One Ukranian soldier is better than ten Russian”. The angry general sends ten men to deal with the annoying Ukranian. After a short period of shots and screams, another shout is heard - “One Ukranian is better than a hundred Russians”. The general sends a hundred soldiers, and again none of them come back. Then general hears a third shout - “One ukranian soldier is better than a thousand russians”. Furious, the general sends a thousand men. This time one of his soldiers survives and reports to general - “Sir, its a trap, theres two of them”.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MerfaGlopp"> /u/MerfaGlopp </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12h8exo/the_ukranian_soldier/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12h8exo/the_ukranian_soldier/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I sexually identify as a microwave dinner</strong> - <!-- SC_OFF --></p>
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Im done in five minutes and look nothing like the picture
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/mutilatedxlips"> /u/mutilatedxlips </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12gtnqg/i_sexually_identify_as_a_microwave_dinner/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12gtnqg/i_sexually_identify_as_a_microwave_dinner/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Whats brown and rhymes with snoop?</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Dr Dre
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/theturtlegame"> /u/theturtlegame </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12h1a6h/whats_brown_and_rhymes_with_snoop/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12h1a6h/whats_brown_and_rhymes_with_snoop/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man has his mother-in-law move in with him when she lost her job.</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
About a week later, he returns home from his job and finds her laying on the floor, unconscious. He calls 911, the ambulance comes and takes her off to the hospital.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He calls his wife and tells her she may have to cut her business trip short, but hell keep her posted.
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He gets to the hospital and waits outside the surgery, nervous and pacing. Soon, the doctor comes out and says he has some good news and some bad news.
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“Give me the bad news first, Doc.”
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“Well, your mother-in-law had a massive stroke. Shes lost her ability to speak and can only cackle like a chicken.” The man nods his head.
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“Shes also lost all motor control to her arms and legs, so not only wont she be able to walk, she wont even be able to feed herself. Youll have to feed her baby food for the rest of her life. Every day, three times a day.” Somberly, the man nods, so the doctor continues.
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“Without any motor control, shell also be incontinent, so shell have to wear diapers for the rest of her life. Youll have to clean her and put a new diaper on her several times a day for the rest of her life.”
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The man nods, processing all this information in his brain, then looks to the doctor and asks, " thats some pretty bad news, but you said you had some good news. Whats the good news?"
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“The good news is Im just joking with you: she died.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Swiggy1957"> /u/Swiggy1957 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12hb5lt/a_man_has_his_motherinlaw_move_in_with_him_when/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12hb5lt/a_man_has_his_motherinlaw_move_in_with_him_when/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Wife: Do men wipe after they pee?</strong> - <!-- SC_OFF --></p>
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Aging husband: Yes. Wipe the floor, wipe the rim, wipe the wall…..
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/asiers"> /u/asiers </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12ghs76/wife_do_men_wipe_after_they_pee/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12ghs76/wife_do_men_wipe_after_they_pee/">[comments]</a></span></p></li>
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