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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 data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Deploying wearable sensors for pandemic mitigation</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wearable sensors can continuously and passively detect potential respiratory infections, before or absent symptoms. However, the population-level impact of deploying these devices during pandemics is unclear. We built a compartmental model of Canada9s second COVID-19 wave and simulated wearable sensor deployment scenarios, systematically varying detection algorithm accuracy, uptake, and adherence. With current detection algorithms and 4% uptake, we found that deploying wearable sensors could have averted 9% of second wave SARS-CoV-2 infections, though 29% of this reduction is attributed to incorrectly quarantining uninfected device users. Improving detection specificity and offering confirmatory rapid tests each minimized incorrect quarantines and associated costs. With a sufficiently low false positive rate, increasing uptake and adherence became effective strategies for scaling averted infections. We concluded that wearable sensor deployment can meaningfully contribute to pandemic mitigation; in the case of COVID-19, technology improvements or supporting measures are required to reduce social and economic costs to acceptable levels.
</p>
</div></li>
</ul>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.02.07.22270634v2" target="_blank">Deploying wearable sensors for pandemic mitigation</a>
</div>
<ul>
<li><strong>First cases of infection with the 21L/BA.2 Omicron variant in Marseille, France</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The SARS-CoV-2 21K/BA.1, 21L/BA.2, and BA.3 Omicron variants have recently emerged worldwide. To date, the 21L/BA.2 Omicron variant has remained very minority globally but became predominant in Denmark instead of the 21K/BA.1 variant. Here we describe the first cases diagnosed with this variant in south-eastern France. We identified thirteen cases using variant-specific qPCR and next-generation sequencing between 28/11/2021 and 31/01/2022, the first two cases being diagnosed in travellers returning from Tanzania. Overall, viral genomes displayed a mean (+/-standard deviation) number of 65.9+/-2.5 (range, 61-69) nucleotide substitutions and 31.0+/-8.3 (27-50) nucleotide deletions, resulting in 49.6+/-2.2 (45-52) amino acid substitutions (including 28 in the spike protein) and 12.4+/-1.1 (12-15) amino acid deletions. Phylogeny showed the distribution in three different clusters of these genomes, which were most closely related to genomes from England and South Africa, from Singapore and Nepal, or from France and Denmark. Structural predictions pointed out a significant enlargement and flattening of the 21L/BA.2 N-terminal domain surface compared with that of the 21K/BA.2 Omicron variant, which may facilitate initial viral interactions with lipid rafts. Close surveillance is needed at global, country and center scales to monitor the incidence and clinical outcome of the 21L/BA.2 Omicron variant.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.02.08.22270495v1" target="_blank">First cases of infection with the 21L/BA.2 Omicron variant in Marseille, France</a>
</div></li>
<li><strong>Safety and Efficacy of Preventative COVID Vaccines: The StopCoV Study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: To partially immunize more persons against COVID-19 during a time of limited vaccine availability, Canadian public health officials recommended extending the vaccine dose interval and brand mixing. Impact on the antibody response among the older ambulatory population was unclear. Methods: Decentralized prospective cohort study with self-report of adverse events and collection of dried blood spots. Data is presented for 1193 (93%) of the 911 older (aged &gt;70 years) and 375 younger (30-50 years) recruits. Findings: Local and systemic reactivity rates were high but short-lived, particularly in the younger cohort and with mRNA-1273 vaccine. After a single COVID-19 vaccine, 84% younger but only 46% older participants had positive IgG antibodies to both spike protein and receptor binding domain (RBD) antigens, increasing to 100/98% with the second dose respectively. In multivariable linear regression model, lower normalized IgG RBD antibody ratios two weeks after the second dose were statistically associated with older age, male gender, cancer diagnosis, lower body weight, BNT162b2 relative to mRNA-1273 and longer dose intervals. Antibody ratios in both cohorts declined 12 weeks post second vaccine dose. Interpretation: We report success of a decentralized serology study. Antibody responses were higher in the younger than older cohort and were greater for those with at least one mRNA-1273 dose. The immunity threshold is unknown but correlations between binding and neutralizing antibodies are strongly positive. Trends with time and at breakthrough infection will inform vaccine booster strategies. Funding: Supported by the Public Health Agency of Canada and the University Health Network Foundation.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.02.09.22270734v1" target="_blank">Safety and Efficacy of Preventative COVID Vaccines: The StopCoV Study</a>
</div></li>
<li><strong>Estimating the risk of incident SARS-CoV-2 infection among healthcare workers in quarantine hospitals: the Egyptian example</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In response to the COVID-19 epidemic, Egypt established a unique care model based on quarantine hospitals where only externally-referred confirmed COVID-19 patients were admitted, and healthcare workers resided continuously over 1- to 2-week working shifts. While the COVID-19 risk for HCWs has been widely reported in standard healthcare settings, it has not been evaluated yet in quarantine hospitals. Here, we relied on longitudinal data, including results of routine RT-PCR tests, collected within three quarantine hospitals located in Cairo and Fayoum, Egypt. Using a model-based approach that accounts for the time-since-exposure variation in false-negative rates of RT-PCR tests, we computed the incidence of SARS-CoV-2 infection among HCWs. Over a total follow-up of 6,064 person-days (PD), we estimated an incidence rate (per 100 PD) of 1.05 (95% CrI: 0.58-1.65) at Hospital 1, 1.92 (95% CrI: 0.93-3.28) at Hospital 2 and 7.62 (95% CrI: 3.47-13.70) at Hospital 3. The probability for an HCW to be infected at the end of a shift was 13.7% (95% CrI: 7.8%-20.8%) and 23.8% (95% CrI: 12.2%-37.3%) for a 2-week shift at Hospital 1 and Hospital 2, respectively, which lies within the range of risk levels previously documented in standard healthcare settings, whereas it was &gt;3-fold higher for a 7-day shift at Hospital 2 (42.6%, 95%CrI: 21.9%-64.4%). Our model-based estimates unveil a proportion of undiagnosed infections among HCWs of 46.4% (95% CrI: 18.8%-66.7%), 45.0% (95% CrI: 5.6%-70.8%) and 59.2% (95% CrI: 34.8%-78.8%), for Hosp1 to 3, respectively. The large variation in SARS-CoV-2 incidence we document here suggests that HCWs from quarantine hospitals may face a high occupational risk of infection, but that, with sufficient anticipation and infection control measures, this risk can be brought down to levels similar to those observed in standard healthcare settings.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.21.20248594v3" target="_blank">Estimating the risk of incident SARS-CoV-2 infection among healthcare workers in quarantine hospitals: the Egyptian example</a>
</div></li>
<li><strong>Construction of a new chromosome-scale, long-read reference genome assembly for the Syrian hamster, Mesocricetus auratus</strong> -
<div>
Background: The Syrian hamster (Mesocricetus auratus) has been suggested as a useful mammalian model for a variety of diseases and infections, including infection with respiratory viruses such as SARS-CoV-2. The MesAur1.0 genome assembly was generated in 2013 using whole-genome shotgun sequencing with short-read sequence data. Current more advanced sequencing technologies and assembly methods now permit the generation of near-complete genome assemblies with higher quality and greater continuity. Findings: Here, we report an improved assembly of the M. auratus genome (BCM_Maur_2.0) using Oxford Nanopore Technologies long-read sequencing to produce a chromosome-scale assembly. The total length of the new assembly is 2.46 Gbp, similar to the 2.50 Gbp length of a previous assembly of this genome, MesAur1.0. BCM_Maur_2.0 exhibits significantly improved continuity with a scaffold N50 that is 6.7 times greater than MesAur1.0. Furthermore, 21,616 protein coding genes and 10,459 noncoding genes are annotated in BCM_Maur_2.0 compared to 20,495 protein coding genes and 4,168 noncoding genes in MesAur1.0. This new assembly also improves the unresolved regions as measured by nucleotide ambiguities, where approximately 17.11% of bases in MesAur1.0 were unresolved compared to BCM_Maur_2.0 in which the number of unresolved bases is reduced to 3.00%. Conclusions: Access to a more complete reference genome with improved accuracy and continuity will facilitate more detailed, comprehensive, and meaningful research results for a wide variety of future studies using Syrian hamsters as models. Keywords: Syrian hamster, Mesocricetus auratus, genome, disease model, COVID-19
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.07.05.451071v3" target="_blank">Construction of a new chromosome-scale, long-read reference genome assembly for the Syrian hamster, Mesocricetus auratus</a>
</div></li>
<li><strong>N-acylethanolamine acid amide hydrolase is a novel target for drugs against SARS-CoV-2 and Zika virus</strong> -
<div>
Several compounds have been tested against SARS-CoV-2; at present, COVID-19 treatments decrease the deleterious inflammatory response and acute lung injury. However, the best therapeutic response would be expected by combining anti- inflammatory properties, while concomitantly blocking viral replication. These combined effects should drastically reduce both infection rate and severe complications induced by novel SARS-CoV-2 variants. Therefore, we explored the antiviral potency of a class of anti-inflammatory compounds that inhibit the N-Acylethanolamine acid amidase (NAAA). This enzyme catalyzes the hydrolysis of palmitoylethanolamide (PEA), a bioactive lipid that mediates anti-inflammatory and analgesic activity through the activation of peroxisome proliferator receptor- (PPAR-). Similarly, this pathway is likely to be a significant target to impede viral replication since PPAR- activation leads to dismantling of lipid droplets, where viral replication of Flaviviruses and Coronaviruses occurs.
</div>
<div class="article-link article-html- link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.08.479661v1" target="_blank">N-acylethanolamine acid amide hydrolase is a novel target for drugs against SARS-CoV-2 and Zika virus</a>
</div></li>
<li><strong>SARS-CoV-2 ORF6 disrupts innate immune signalling by inhibiting cellular mRNA export</strong> -
<div>
SARS-CoV-2 is a betacoronavirus and the etiological agent of COVID-19, a devastating infectious disease. Due to its far-reaching effect on human health, there is an urgent and growing need to understand the viral molecular biology of SARS-CoV-2 and its interaction with the host cell. SARS-CoV-2 encodes 9 predicted accessory proteins, which are presumed to be dispensable for in vitro replication, most likely having a role in modulating the host cell environment to aid viral replication. Here we show that the ORF6 accessory protein interacts with cellular Rae1 to inhibit cellular protein production by blocking mRNA export. We utilised cell fractionation coupled with mRNAseq to explore which cellular mRNA species are affected by ORF6 expression and show that ORF6 can inhibit the export of many mRNA including those encoding antiviral factors such as IRF1 and RIG-I. We also show that export of these mRNA is blocked in the context of SARS-CoV-2 infection. Together, our studies identify a novel mechanism by which SARS-CoV-2 can manipulate the host cell environment to supress antiviral responses, providing further understanding to the replication strategies of a virus that has caused an unprecedented global health crisis.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.08.479664v1" target="_blank">SARS-CoV-2 ORF6 disrupts innate immune signalling by inhibiting cellular mRNA export</a>
</div></li>
<li><strong>Auto-Immunoproteomics Analysis of COVID-19 ICU Patients Revealed Increased Levels of Autoantibodies Related to Male Reproductive System</strong> -
<div>
The role of autoantibodies in coronavirus disease (COVID-19) complications is not yet fully understood. The current investigation screened two independent cohorts of 97 COVID-19 patients (Discovery (Disc) cohort from Qatar (n = 49) and Replication (Rep) cohort from New York (n = 48)) utilizing high-throughput KoRectly Expressed (KREX) immunome protein-array technology. Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (P [≤] 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients that served as controls. Both cohorts showed substantial similarities (r2 = 0.73) and exhibited higher autoantibodies responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. KREX analysis of the specific IgG autoantibody responses indicates that the targeted host proteins are supposedly increased in COVID-19 patients. The autoantigen-autoantibody response was cross-validated for SPANXN4 and STK25 proteins using Uniprot BLASTP and sequence alignment tools. SPANXN4 is essential for spermiogenesis and male fertility, which may predict a potential role for this protein in COVID-19 associated male reproductive tract complications and warrants further research.
</div>
<div class="article-link article- html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.09.479669v1" target="_blank">Auto- Immunoproteomics Analysis of COVID-19 ICU Patients Revealed Increased Levels of Autoantibodies Related to Male Reproductive System</a>
</div></li>
<li><strong>Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat</strong> -
<div>
The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a SARS-CoV-2 outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.09.479546v1" target="_blank">Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat</a>
</div></li>
<li><strong>Aerosol Formation During Processing of Potentially Infectious Samples on Roche Immunochemistry Analyzers (cobas e analyzers) and in an End-to-End Laboratory Workflow to Model SARS-CoV-2 Infection Risk for Laboratory Operators</strong> -
<div>
Background: This study assessed formation of potentially infectious aerosols during processing of infectious samples in a real-world laboratory setting, which could then be applied in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This two-part study assessed aerosol formation when using cobas e analyzers only and in an end-to-end laboratory workflow. To estimate aerosol formation, recombinant hepatitis B surface antigen (HBsAg) was used as a surrogate marker for infectious virus particles to evaluate the potential risk of SARS- CoV-2 infection to laboratory operators. Using the HBsAg model, air sampling was performed at different positions around the cobas e analyzers and in four scenarios reflecting critical handling and/or transport locations in an end-to-end laboratory workflow. Aerosol formation of HBsAg was quantified using the Elecsys(R) HBsAg II quant II assay. The model was then applied to a SARS-CoV-2 context using SARS-CoV-2 infection-specific parameters to calculate viral RNA copies. Results: Following application to SARS-CoV-2, the mean HBsAg uptake per hour when recalculated into viral RNA copies was 1.9 viral RNA copies across the cobas e analyzers and 0.87 viral RNA copies across all tested scenarios in an end-to- end laboratory workflow. This corresponds to a maximum aspiration rate of &lt;16 viral RNA copies during an 8-hour shift when using cobas e analyzers and/or in an end-to-end laboratory workflow. Conclusions: The low production of marker- containing aerosol when using cobas e analyzers and in an end-to-end laboratory workflow is consistent with a remote risk of laboratory-acquired SARS-CoV-2 infection for laboratory operators.
</div>
<div class="article-link article-html- link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.08.479519v1" target="_blank">Aerosol Formation During Processing of Potentially Infectious Samples on Roche Immunochemistry Analyzers (cobas e analyzers) and in an End-to-End Laboratory Workflow to Model SARS-CoV-2 Infection Risk for Laboratory Operators</a>
</div></li>
<li><strong>Olverembatinib inhibits SARS-CoV-2-Omicron variant-mediated cytokine release</strong> -
<div>
The Omicron variant has become dominant in the U.S. and around the world. This variant is found to be 2-fold more infectious than the Delta variant, posing a significant threat of severe cases and death. We and others have recently reported that the N-terminus domain (NTD) of the SARS-CoV-2 of various variants is responsible for inducing cytokine release in human PBMCs. Here, we demonstrate that the NTD of the Omicron variant remains highly effective at inducing cytokine release in human PBMCs. Furthermore, we show that Ponatinib and a novel compound, Olverembatinib, are potent Omicron NTD-mediated cytokine release inhibitors. Target profiling revealed that Olverembatinib blocks most of the previously identified kinases responsible for cytokine release. Together, we propose that Ponatinib and Olverembatinib may represent an attractive therapeutic option for treating moderate to severe COVID-19 cases.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.07.479443v1" target="_blank">Olverembatinib inhibits SARS- CoV-2-Omicron variant-mediated cytokine release</a>
</div></li>
<li><strong>The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters</strong> -
<div>
A well-tolerated and cost-effective oral drug that blocks SARS-CoV-2 growth and dissemination would be a major advance in the global effort to reduce COVID-19 morbidity and mortality. Here, we show that the oral FDA-approved drug nitazoxanide (NTZ) significantly inhibits SARS-CoV-2 viral replication and infection in different primate and human cell models including stem cell-derived human alveolar epithelial type 2 cells. Furthermore, NTZ synergizes with remdesivir, and it broadly inhibits growth of SARS-CoV-2 variants B.1.351 (beta), P.1 (gamma), and B.1617.2 (delta) and viral syncytia formation driven by their spike proteins. Strikingly, oral NTZ treatment of Syrian hamsters significantly inhibits SARS-CoV-2-driven weight loss, inflammation, and viral dissemination and syncytia formation in the lungs. These studies show that NTZ is a novel host-directed therapeutic that broadly inhibits SARS-CoV-2 dissemination and pathogenesis in human and hamster physiological models, which supports further testing and optimization of NTZ-based therapy for SARS-CoV-2 infection alone and in combination with antiviral drugs.
</div>
<div class="article-link article- html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.08.479634v1" target="_blank">The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters</a>
</div></li>
<li><strong>Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein</strong> -
<div>
Worldwide SARS-CoV-2 sequencing efforts track emerging mutations in its spike protein, as well as characteristic mutations in other viral proteins. Besides their epidemiological importance, the observed SARS-CoV-2 sequences present an ensemble of viable protein variants, and thereby a source of information on viral protein structure and function. Charting the mutational landscape of the nucleocapsid (N) protein that facilitates viral assembly, we observe variability exceeding that of the spike protein, with more than 86% of residues that can be substituted, on average by 3-4 different amino acids. However, mutations exhibit an uneven distribution that tracks known structural features but also reveals highly protected stretches of unknown function. One of these conserved regions is in the central disordered linker proximal to the N-G215C mutation that has become dominant in the Delta variant, outcompeting G215 variants without further spike or N-protein substitutions. Structural models suggest that the G215C mutation stabilizes conserved transient helices in the disordered linker serving as protein-protein interaction interfaces. Comparing Delta variant N-protein to its ancestral version in biophysical experiments, we find a significantly more compact and less disordered structure. N-G215C exhibits substantially stronger self-association, shifting the unliganded protein from a dimeric to a tetrameric oligomeric state, which leads to enhanced co-assembly with nucleic acids. This suggests that the sequence variability of N-protein is mirrored by high plasticity of N-protein biophysical properties, which we hypothesize can be exploited by SARS-CoV-2 to achieve greater efficiency of viral assembly, and thereby enhanced infectivity.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.08.479556v1" target="_blank">Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein</a>
</div></li>
<li><strong>Designing effective siRNAs to silence structural proteins associated genes of Indian SARS-CoV-2 strains: an in silico approach</strong> -
<div>
Background: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a highly transmissible and pathogenic coronavirus that first emerged in late 2019 and has since triggered a pandemic of acute respiratory disease named “coronavirus disease 2019” (COVID-19), poses a significant threat to all public health institutions in the absence of specific antiviral treatment. Methods: The innate RNA interference (RNAi) pathway, on the other hand, allows for the development of nucleic acid-based antiviral drugs. It is a cellular gene-silencing event in which complementary small interfering RNA (siRNA) molecules cause sequence-specific degradation of target mRNA. Hence, in this current study, the potential of RNAi was utilized to construct siRNA molecules against specific target genes of SARS-CoV-2 structural proteins, such as the envelope protein gene (E), membrane protein gene (M), nucleocapsid phosphoprotein gene (N), and surface glycoprotein gene (S). Results: Conserved sequence from 811 SARS-CoV-2 strains from around India was collected to construct 157 siRNAs that can inactivate E, M, N and S genes. The proposed siRNA molecules possessed sufficient nucleotide-based and other features for effective gene silencing and siRNAs’ targets revealed no significant matches across the whole human genome and hence, siRNAs were found to have no off-target effects on the genome, ruling out the possibility of off-target silencing. Conclusions: Finally, based on GC content, free energy of folding, free energy of binding, melting temperature and molecular docking analysis, 4 effective siRNA molecules were selected for each target gene which is proposed to exert the best action. Our engineered siRNA candidates could be used as a genome-level therapeutic treatment against various sequenced SARS-CoV-2 strains in India. However, future applications will necessitate additional validations in vitro and in vivo animal models.
</div>
<div class="article-link article-html- link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.08.479559v1" target="_blank">Designing effective siRNAs to silence structural proteins associated genes of Indian SARS-CoV-2 strains: an in silico approach</a>
</div></li>
<li><strong>The mechanism of RNA capping by SARS-CoV-2</strong> -
<div>
The SARS-CoV-2 RNA genome contains a 5’-cap that facilitates translation of viral proteins, protection from exonucleases and evasion of the host immune response. How this cap is made is not completely understood. Here, we reconstitute the SARS-CoV-2 7MeGpppA2’-O-Me-RNA cap using virally encoded non-structural proteins (nsps). We show that the kinase-like NiRAN domain of nsp12 transfers RNA to the amino terminus of nsp9, forming a covalent RNA-protein intermediate (a process termed RNAylation). Subsequently, the NiRAN domain transfers RNA to GDP, forming the cap core structure GpppA-RNA. The nsp14 and nsp16 methyltransferases then add methyl groups to form functional cap structures. Structural analyses of the replication-transcription complex bound to nsp9 identified key interactions that mediate the capping reaction. Furthermore, we demonstrate in a reverse genetics system that the N-terminus of nsp9 and the kinase- like active site residues in the NiRAN domain are required for successful SARS-CoV-2 replication. Collectively, our results reveal an unconventional mechanism by which SARS-CoV-2 caps its RNA genome, thus exposing a new target in the development of antivirals to treat COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.07.479471v1" target="_blank">The mechanism of RNA capping by SARS- CoV-2</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>Evaluation of Full Versus Fractional Doses of COVID-19 Vaccines Given as a Booster in Adults in Australia - Mongolia, Indonesia, Australia Coronavirus (MIACoV).</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Tozinameran - Standard dose;   Biological: Tozinameran - fractional dose;   Biological: Elasomeran - standard dose;   Biological: Elasomeran - fractional dose<br/><b>Sponsors</b>:   Murdoch Childrens Research Institute;   Coalition for Epidemic Preparedness Innovations;   PATH;   The Peter Doherty Institute for Infection and Immunity<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>Zofin to Treat COVID-19 Long Haulers</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Zofin;   Other: Placebo<br/><b>Sponsors</b>:  <br/>
Organicell Regenerative Medicine;   Proxima Clinical Research, Inc.<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 Daily Oral Administration of Food Supplement NLC-V in Patients Diagnosed With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Dietary Supplement: NLC-V<br/><b>Sponsor</b>:  <br/>
Todos Medical, Ltd.<br/><b>Completed</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>Fourth COVID-19 Vaccine Dose- mRNA1273</strong> - <b>Condition</b>:   COVID-19 Pandemic<br/><b>Intervention</b>:   Biological: mRNA1273 vaccine<br/><b>Sponsor</b>:   Sheba Medical Center<br/><b>Active, not 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 Design of the Diacerein in Patients With Covid-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Diacerein;   Drug: placebo capsules<br/><b>Sponsors</b>:   University of Campinas, Brazil;   Fundação de Amparo à Pesquisa do Estado de São Paulo<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>HEART Rate Variability Biofeedback in LOng COVID-19 (HEARTLOC)</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Behavioral: Heart Rate Variability Biofeedback (HRV-B)<br/><b>Sponsors</b>:   University of Leeds;   University of Manchester;   Leeds Comunity Healthcare NHS Trust<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 Study to Evaluate the Safety, Tolerability, and Immunogenicity of MVC-COV1901 or MVC-COV1901(Beta) Against COVID-19</strong> - <b>Condition</b>:   COVID-19 Vaccine<br/><b>Interventions</b>:   Biological: MVC-COV1901(Beta);   Biological: MVC- COV1901<br/><b>Sponsor</b>:   Medigen Vaccine Biologics Corp.<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>Fourth BNT162b2 COVID-19 Vaccine Dose</strong> - <b>Condition</b>:   COVID-19 Pandemic<br/><b>Intervention</b>:   Biological: BNT162b2 vaccine<br/><b>Sponsor</b>:   Sheba Medical Center<br/><b>Active, not 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>Effects of Aerobic Exercise in Patients With Post COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Other: High-intensity interval aerobic exercise training;   Other: Control Group<br/><b>Sponsor</b>:   Gazi 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>Evaluate the Efficacy and Safety of TF0023 in Treatments for COVID-19 in Hospitalized Adults</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Intervention</b>:   Drug: TF0023<br/><b>Sponsor</b>:  <br/>
Techfields Inc<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>Immunogenicity and Safety of the SpikoGen COVID-19 Vaccine in Children Aged 5 to &lt;12 Years and 12 to &lt;18 Years Compared With Adults Aged 18 to 40 Years</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Low-dose SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant;   Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant<br/><b>Sponsors</b>:  <br/>
Cinnagen;   Vaxine 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>Safety and Immunogenicity of COVI-VAC as a Booster Dose in Adults Previously Vaccinated Against COVID-19</strong> - <b>Conditions</b>:   COVID-19;   SARS-CoV-2<br/><b>Intervention</b>:   Biological: COVI-VAC<br/><b>Sponsor</b>:  <br/>
Codagenix, Inc<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>Effects of Inspiratory Muscle Training in Patients With Post COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Other: Inspiratory Muscle Training Group;   Other: Control Group<br/><b>Sponsor</b>:   Gazi 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>Short Daily Versus Conventional Hemodialysis for COVID-19 Patients</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Other: Short daily dialysis<br/><b>Sponsor</b>:  <br/>
Shahid Beheshti University of Medical Sciences<br/><b>Completed</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>Ivermectin for Post Exposure Prophylaxis of Covid-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Ivermectin;   Other: Placebo<br/><b>Sponsors</b>:  <br/>
Clinical Research Centre, Malaysia;   Hovid Berhad<br/><b>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>Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro</strong> - The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed…</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>Neutralization against Omicron SARS-CoV-2 from previous non-Omicron infection</strong> - The spread of the Omicron SARS-CoV-2 variant underscores the importance of analyzing the cross-protection from previous non-Omicron infection. We have developed a high-throughput neutralization assay for Omicron SARS-CoV-2 by engineering the Omicron spike gene into an mNeonGreen USA-WA1/2020 SARS-CoV-2 (isolated in January 2020). Using this assay, we determine the neutralization titers (defined as the maximal serum dilution that inhibited 50% of infectious virus) of patient sera collected at 1-…</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>Reconstruction of the unbinding pathways of noncovalent SARS-CoV and SARS-CoV-2 3CLpro inhibitors using unbiased molecular dynamics simulations</strong> - The main protease (3CLpro) is one of the essential components of the SARS-CoVs viral life cycle, which makes it an interesting target for overpowering these viruses. Although many covalent and noncovalent inhibitors have been designed to inhibit this molecular target, none have gained FDA approval as a drug. Because of the high rate of COVID-19 pandemic development, in addition to laboratory research, we require in silico methods to accelerate rational drug design. The unbinding pathways of two…</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>Centrifugal Microfluidic Method for Enrichment and Enzymatic Extraction of Severe Acute Respiratory Syndrome Coronavirus 2 RNA</strong> - The diversification of analytical tools for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is imperative for effective virus surveillance and transmission control worldwide. Development of robust methods for rapid, simple isolation of viral RNA permits more expedient pathogen detection by downstream real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) to minimize stalled containment and enhance treatment efforts. Here, we describe an automatable…</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>Altered motor cortex physiology and dysexecutive syndrome in patients with fatigue and cognitive difficulties after mild COVID-19</strong> - CONCLUSIONS: Patients with fatigue and cognitive difficulties following mild COVID-19 present altered excitability and neurotransmission within M1 and deficits in executive functions and attention.</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 siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant</strong> - The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on long term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We here have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma and Epsilon, at…</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>Association between early initiation of breastfeeding and reduced risk of respiratory infection: Implications for nonseparation of infant and mother in the COVID-19 context</strong> - Early initiation of breastfeeding, within 1 h of birth, is vital for the health of newborns and reduces morbidity and mortality. Secondary analysis of the 2016 Nepal Demographic and Health Survey (DHS) showed that early initiation of breastfeeding significantly reduced the risk of acute respiratory infection (ARI) in children under 2 years. Early initiation of breastfeeding requires maternal proximity. Separation of infant and mother inhibits early initiation of breastfeeding and increases the…</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 randomized, controlled, feasibility study of RD-X19 in subjects with mild-to-moderate COVID-19 in the outpatient setting</strong> - The RD-X19 is an investigational, handheld medical device precisely engineered to emit blue light through the oral cavity to target the oropharynx and surrounding tissues. At doses shown to be non-cytotoxic in an in vitro 3-dimensional human epithelial tissue model, the monochromatic visible light delivered by RD-X19 results in light-initiated expression of immune stimulating cytokines IL-1α and IL-1β, with corresponding inhibition of SARS-CoV-2 replication. A single exposure of 425 nm blue…</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>Risk Factors for COVID-19: Diabetes, Hypertension, and Obesity</strong> - CONCLUSION: Overall, diabetes, hypertension, and obesity seem to negatively affect the clinical course and disease outcome in patients with COVID-19. However, these data need further confirmation by studies with more accurate data registration.</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>Screening of potential inhibitors of COVID-19 with repurposing approach via molecular docking</strong> - SARS-CoV-2 (COVID-19) is the causative organism for a pandemic disease with a high rate of infectivity and mortality. In this study, we aimed to assess the affinity between several available small molecule and proteins, including Abl kinase inhibitors, Janus kinase inhibitor, dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papain-like protease inhibitors, using binding simulation, to test whether they may be effective in inhibiting COVID-19 infection through…</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>Disulfiram inhibits neutrophil extracellular trap formation protecting rodents from acute lung injury and SARS-CoV-2 infection</strong> - Severe acute lung injury has few treatment options and a high mortality rate. Upon injury, neutrophils infiltrate the lungs and form neutrophil extracellular traps (NETs), damaging the lungs and driving an exacerbated immune response. Unfortunately, no drug preventing NET formation has completed clinical development. Here, we report that disulfiram -an FDA-approved drug for alcohol use disorder- dramatically reduced NETs, increased survival, improved blood oxygenation, and reduced lung edema in…</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 Effect of Anti-Chemokine Oral Drug XC8 on Cough Triggered by The Agonists of TRPA1 But Not TRPV1 Channels in Guinea Pigs</strong> - CONCLUSIONS: XC8 acts against cough evoked by the activation of TRPA1 (citric acid/cinnamaldehyde) but not TRPV1 (capsaicin) channels. XC8 inhibits the cough reflex and suppresses the cough potentiation by IFN-γ. XC8 might be of significant therapeutic value for patients suffering from chronic cough associated with inflammation.</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>Structures of the Omicron Spike trimer with ACE2 and an anti-Omicron antibody</strong> - The SARS-CoV-2 Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own or in complex with ACE2 or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein, which change binding epitopes to many current antibodies. In the ACE2 binding site, compensating mutations strengthen RBD binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An…</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>Cytokine Storm and Failed Resolution in COVID-19: Taking a Cue from Multiple Sclerosis</strong> - CONCLUSION: Given the fact that current treatment for COVID-19 is only supportive, global research is aimed at developing safe and effective therapeutic options that can result in a better clinical course in patients with comorbid conditions. Accordingly, taking a cue from our experiences in controlling robust inflammatory response in MS and diabetes by simultaneously inhibiting inflammatory process and stimulating its resolution, combinatorial therapy of metformin and SPM in COVID-19 holds…</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>Anticoronavirus Activity of Water-Soluble Pristine C<sub>60</sub> Fullerenes: In Vitro and In Silico Screenings</strong> - CONCLUSION: Pioneer in vitro study to identify the anticoronavirus activity of water-soluble pristine C(60) fullerenes indicates that they are highly promising for further preclinical studies, since a significant inhibition of the infectious activity of swine coronavirus of transmissible gastroenteritis in BHK-21 cell culture was found. According to molecular modeling results, it was shown that C(60) fullerene can create the stable complexes with 3CLpro and RdRp proteins of SARS-CoV-2…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IDENTIFICATION AND ALARM SYSTEM FOR FACIAL CORONA MASK USING CNN BASED IMAGE PROCESSING</strong> - tThe covid-19 epidemic is the world’s largest wake-up call for people to pay attention to their own and society’s health. One thing to keep in mind is that there is a segment of the population that has been exposed to the covid-19 virus and has generated antibodies without developing any significant illnesses and is continuing to be healthy. This indicates that a significant section of the population, even excluding the elderly, lacks the necessary bodily immunity to combat a Viral infection. As terrible as covid-19 is on a global scale, developing personal health standards and preventative measures for any pathogenic virus as a community would have spared many lives. In’this work, a camera is combined with an image processing system to recognise facial masks, which may be improved in a variety of ways. First and foremost, this method is meant to identify masks on a single person’s face. While this method is efficient in identifying someone has a mask, it does not ensure that they will wear it all of the time. The most effective update for this task is to install a camera with a wide field of view so that many individuals can be seen in the frame, and the faces of those who aren’t wearing markings can be identified, as well as the number of people and the timing. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN346889253">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ANTIMICROBIAL SANITIZING FORMULATION</strong> - An antimicrobial sanitizing formulation, comprising, i) isopropyl alcohol in the range of 0.1%- 80% w/w, ii) an emollient in the range of 0.1%-15% w/w, iii) hydrogen peroxide in the range of 0.1 0.13% w/w, iv) citric acid in the range of 0.1% to 2.0% w/w, v) silver nitrate in the range of 0.1% to 0.5% w/w, and vi) a fragrance imparting agent in the range of 0.1% to 2.0% w/w. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN346888094">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A HEALTH BAND WITH A BIOMETRIC MODULE AND WORKING METHOD THEREOF</strong> - The present invention discloses a health band with a biometric module and method thereof. The assembly includes, but not limited to, a plurality of sensors configured to gather health data associated with a predefined symptom of a medical condition of a user; a memory unit configured to store the data and an interface, which is configured to determine the medical condition using the data;a processing unit configured to execute the application; and a notification facility configured to provide a notification upon receiving from the interface an instruction associated with the notification, wherein the notification is associated with a drug reminder and the like. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN346889061">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RNA 검출 방법</strong> - 본 발명은 RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 특히, 본 발명은 짧은 염기서열의 RNA까지 분석이 가능하면서도 높은 민감도 및 정확도로 정량적 검출까지 가능하여 감염증, 암 등 여러 질환의 진단 용도로도 널리 활용될 수 있다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR346026620">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>黄芩黄酮活性成分及其制剂在制备预防和/或治疗炎症风暴药物中的应用</strong> - 本发明公开了黄芩黄酮活性成分及其制剂在制备预防和/或治疗炎症风暴药物中的应用。所述黄芩黄酮活性成分选自下述至少一种：黄芩素、汉黄芩素和千层纸素A。炎症风暴是一种机体对外界刺激的过度免疫反应和炎症反应，以炎症细胞因子的快速大量释放为特征。炎症风暴可由许多感染或非感染性疾病引起，并与疾病的严重程度和多器官功能障碍综合征的发生密切相关。减少炎症风暴的发生有助于降低器官损伤和减缓疾病进程，尤其对危重症患者的治疗至关重要。本发明发现，黄芩素、汉黄芩素、千层纸素A均具有不同程度抑制小鼠细胞因子风暴的作用。黄芩素能改善炎症风暴引发的肺损伤和炎性细胞浸润。因此黄芩黄酮活性成分可用于制备防治炎症风暴的药物。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN349220813">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种预防和/或治疗炎症风暴的药物组合物及其制剂与应用</strong> - 本发明公开了一种预防和/或治疗炎症风暴的药物组合物、制剂及其应用。该药物组合物，由黄芩素、汉黄芩素和千层纸素A组成，其中，黄芩素、汉黄芩素、千层纸素A的质量比为0.25<sub>1.5：0.5</sub>7：1。本发明提供的自微乳包括下述组分：药物磷脂复合物、油相、乳化剂和助乳化剂；其中，所述药物磷脂复合物由上述药物组合物和磷脂材料复合而成。本发明的实验结果表明在LPS诱导的系统性炎症风暴小鼠模型中，黄芩素、汉黄芩素和千层纸素A的组合物及其自微乳制剂均具有不同程度抑制小鼠细胞因子风暴的作用。本发明为炎症风暴的临床治疗提供了一种安全、有效、经济的解决方案。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN349220821">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>用于核酸检测的微流控芯片及检测方法</strong> - 本发明提供一种用于核酸检测的微流控芯片及检测方法。所述微流控芯片包括依次叠放在一起并相互密封的三层结构，由上至下分别为气道层、中间层和流道层；所述气道层包含两个独立的气道，所述中间层为弹性薄膜，用于控制流道层上微阀的开启和关闭，所述流道层包含四个进样口，两个出样口，四个微阀，一个LAMP反应室、一个CRISPR反应室以及若干条流道，所述微阀通过弹性薄膜与气道层的气道相连，并通过气道层气压的改变来实现微阀的开关，实现不同进样口的顺序进样。本发明将微流控与LAMP扩增技术以及CRISPR检测技术相结合，在单个芯片上实现高灵敏，高特异性的检测病毒核酸。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN349220678">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>REUNION OF PHOTOTHERMAL THERAPY WITH MXENE ADSORBED UREMIC TOXINS AND CYTOKINES: A SHILED FOR COVID-19 PATENTS</strong> - The COVID-19 pandemic has created havoc throughout the world. The disease has proved to be more fatalfor patients having comorbidities like diabetics, lungs and kidney infections, etc. In the case of COVID-19 patientsI having kidney injury, the. removal of uremic toxins from the blood is hindered and there is a rapid surge in the levelj of cytokine hormone resulting in the death of the patient in a short interval of time. To resolve this issue,iI; researchers have examined that the immediate removal of these toxins can improve the condition of the patient to a |greater extent. Studies have also found the presence of SARS CoV-2 viral RNAs in the blood of COVID-19patients, which risks their life as well as impacts the blood transfusion process, especially in the case ofasymptomatic patients. Hence it is required to control the surge of cytokines and uremic toxins as well as disinfectthe blood of the patient from the virus. MXenes, having a foam-like porous structure and hydrophilic negativesurface functionalization have greater adsorption efficiency as well as superior photothermal activity. Utilizingthese properties of MXenes, the MXene membranes can be used in the dialyzer that can help in the efficient andBiuick removal of the uremic toxins, cytokines, and other impurities from the blood. Along with this the greaterTJAdsorption efficiency of MXenes to amino acids result in the trapping of the SARS CoV-2 viruses on the surface J)3&gt;f the MXene. Many researchers as well as the WHO have proved the efficient reduction of the viral copy numbersjjvith the increase of temperature. Hence, followed by the trapping of the viruses, the implementation of"Zphotothermal Therapy can result in the inactivation and denaturation of the viruses and their respective viral RNAsBJlby the produced heat. The same process can be repeated several times to get better results. This whole process canr&gt;oQ-esult in impurity-free and infection-free blood, that can be returned back to the body of the patient or can be!— I Sitilized for the blood transfusion process without any risk of infection.IM - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN346889224">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>基于引物设计和铜纳米簇的SARS-CoV-2德尔塔变异株检测方法</strong> - 本发明公开了一种基于引物设计和铜纳米簇的SARS‑CoV‑2德尔塔变异株检测方法。该方法结合DPO引物和AT引物成功区分了单碱基缺失的SARS‑CoV‑2德尔塔变异株和SARS‑CoV‑2野生菌株。并且DPO引物和AT引物的PCR产物可以作为CuNCs的生成模板，在紫外照射下实现SARS‑CoV‑2德尔塔变异株的可视化检测。本申请利用常规实验条件，借助PCR仪将DPO引物和AT引物结合扩增，使其SARS‑CoV‑2德尔塔变异株检测具有特异性、高灵敏、可视化的优势。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN348141584">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>REDUCING AND STOPPING OXYGEN WASTAGE IN HOSPITAL</strong> - In an aspect, the present invention discloses a system (200) for prevention and reduction of oxygen wastage from oxygen mask (202). The system (200) includes the oxygen mask (202) having straps; a tension sensor (204), the tension sensor being sensitive towards tension produced in the straps as the oxygen gets leakage through sides of the mask (202); a processor configured in alignment with the tension sensor (204); and a buzzer (206) in alignment with processor. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN346042219">link</a></p></li>
</ul>
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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>Russia and China Unveil a Pact Against America and the West</strong> - In a sweeping long-term agreement, Vladimir Putin and Xi Jinping, the two most powerful autocrats, challenge the current political and military order. - <a href="https://www.newyorker.com/news/daily-comment/russia-and-china-unveil-a-pact-against-america-and-the-west">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What Happened After the Chicken-Pox Vaccine?</strong> - In the COVID era, the success of the varicella vaccine in the nineties is staggering to contemplate. - <a href="https://www.newyorker.com/science/elements/what-happened-after-the-chicken-pox-vaccine">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What the January 6th Papers Reveal</strong> - The Supreme Court ruled to give the House Select Committee access to a trove of documents detailing election-negating strategies that Donald Trump and his advisers entertained—including a military seizure of voting machines—but he continues to peddle a counter-narrative in which he’s the victim. - <a href="https://www.newyorker.com/magazine/2022/02/14/what-the-january-6th-papers-reveal">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I Can’t Stop Thinking About This</strong> - On the Internet, where attention is the currency, obsession has become a default register. - <a href="https://www.newyorker.com/culture/infinite-scroll/i-cant-stop-thinking-about-this">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Novel That Teaches Us How to Read Each Other</strong> - Jessica Au’s “Cold Enough for Snow” challenges our assumptions about what it means to uncover our stories—and our selves. - <a href="https://www.newyorker.com/books/page-turner/a-novel-that-teaches-us-how-to-read-each-other">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Is the FDA too cautious?</strong> -
<figure>
<img alt="The FDA logo amid protective face masks, seen in an illustration photo taken in Krakow, Poland,
on January 11, 2022." src="https://cdn.vox-
cdn.com/thumbor/7SqTP48mSToP3K9gCAC2PADyphQ=/198x0:3347x2362/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70492181/GettyImages_1237662188.0.jpg"/>
<figcaption>
The FDA logo amid protective face masks, seen in this illustration photo taken in Krakow, Poland, on January 11, 2022. | Jakub Porzycki/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The pandemic revealed the flaws in the FDA’s risk assessments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="REKo9r">
Nobody is happy with the FDA.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XFInCj">
Almost a year ago, Vox’s Dylan Scott <a href="https://www.vox.com/policy-and-politics/2021/2/8/22272298/fda-covid-19-vaccine-janet-woodcock-josh-
sharfstein">reported</a> that the Food and Drug Administration had been “demoralized and tarnished during the Trump era.” Things haven’t gotten much better for the embattled agency in the months since.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sJnR35">
In December, epidemiologist Michael Mina <a href="https://twitter.com/michaelmina_lab/status/1473515522461511682?s=20">detailed</a> the “frustrating secret” behind why it was so difficult to get rapid tests: The FDA’s “onerous but remarkably useless check boxes,” he wrote, were slowing the approval for different at-home options. Mina explained that the FDA was holding fast to processes that didn’t allow it to consider “the ample data around the world” and was forcing companies to compare rapid tests to lab-run PCRs, preventing hundreds of millions of tests from being purchased by Americans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BXJqdV">
If this type of problem seems familiar, it’s because it is. Throughout the pandemic, the FDA has faced criticism about its seeming inability to adapt its processes for an emergency.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UNb88l">
It’s the sort of tightrope walk you can only watch with your face behind your hands. Act too quickly, miss something, and lives hang in the balance, not to mention Americans’ dwindling faith in institutions. But it’s just as dangerous to act too slowly when approving needed treatments or tests, to be inflexible in the face of new evidence — lives hang in the balance if you do nothing, as well. And time and again, the FDA seems to<strong> </strong>have chosen to fear the dangers of action over inaction.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2axFlG">
In a statement, FDA spokesperson Michael Felberbaum defended the organization’s pandemic response, arguing it ”made the most appropriate and timely decisions regarding the products we regulate using the best available science, with the health and safety of the American public in mind.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iLOgnc">
“Our decision-making must strike a careful balance between the potential risks and benefits of a variety of public health, legal and regulatory considerations,” he said in an email. “These considerations are never as clear-cut as some like to suggest.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rJPt0V">
But critics argue the agency could have moved faster. As Conor Friedersdorf <a href="https://www.theatlantic.com/ideas/archive/2021/08/fda-delays-carry-death-toll/619871/">reported</a> for the Atlantic last summer, when the FDA was considering authorizing Covid-19 vaccines for children ages 5 to 11, it asked<strong> </strong>Pfizer and Moderna to gather more safety data, rather than rely on existing evidence that the vaccines were safe for adults and teenagers. Even<strong> </strong>the American Academy of Pediatrics <a href="https://downloads.aap.org/DOFA/AAP%20Letter%20to%20FDA%20on%20Timeline%20for%20Authorization%20of%20COVID-19%20Vaccine%20for%20Children_08_05_21.pdf">believed the existing evidence was sufficient</a> to grant authorization: “The FDA should strongly consider authorizing these vaccines for children ages 5–11 years based on data from the initial enrolled cohort, which are already available,” they <a href="https://downloads.aap.org/DOFA/AAP%20Letter%20to%20FDA%20on%20Timeline%20for%20Authorization%20of%20COVID-19%20Vaccine%20for%20Children_08_05_21.pdf">wrote in a letter to the agency</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ds8q53">
The delay approving rapid tests followed the same script. As <a href="https://www.propublica.org/article/heres-why-rapid-covid-tests-are-so-expensive-and-hard-to-find">ProPublica’s Lydia DePillis and Eric Umansky</a> found last November, the source of<strong> </strong>the FDA’s delay “appears to be a confounding combination of overzealous regulation and anemic government support.” While tests were approved in other countries that prioritized “accessibility and affordability over perfect accuracy,” the FDA blocked the use of such tests in the United States.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7mTtyS">
It was the same story again when it came to human challenge trials. The FDA <a href="https://www.centerwatch.com/articles/24665-group-urges-challenge-trials-for-covid-19-vaccine-but-fda-and-
ethicists-balk">brushed off the idea</a>, despite thousands of Americans stepping forward early in the pandemic to volunteer to be infected with SARS-CoV-2, the virus that causes Covid-19, to more rapidly study the efficacy of Covid-19 vaccines. Human challenge trials are a controversial approach, but notably, the United Kingdom was willing to <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/worlds-first-covid-human-challenge-trial-found-be-
safe-young-adults-2022-02-02/">approve this research method</a> in February 2021 because of its potential<strong> </strong>to help “<a href="https://www.gov.uk/government/news/worlds-first-coronavirus-human-challenge-study-receives-
ethics-approval-in-the-uk">accelerate</a>” vaccine development.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="k6kSMB">
As months pass and these events pile up, an uneasy question has risen to the forefront: What if the FDA’s failures during the pandemic happen all the time, and most people are just now noticing? If the institution itself is broken, the danger could be far greater than just this moment.
</p>
<h3 id="PBZqKo">
What if the FDA has always been broken?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="36LgZl">
George Mason University economist Alex Tabarrok has been beating this drum since long before Covid-19 was a concern. Tabarrok, a leading libertarian thinker advocating for institutional reform of the FDA, <a href="https://www.nytimes.com/2021/04/01/opinion/covid-vaccine.html">gained traction</a> criticizing America’s pandemic response. Recently, I asked the economist: what if this goes beyond Covid-19?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pqAvNC">
Tabarrok has coined a haunting phrase to describe his concerns with the agency: “The FDA is conservative because when it approves a bad drug, its error is visible, but when it fails to approve good drugs, the dead are buried in an invisible graveyard.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="may0Lu">
In an interview, he pointed me to a 2017 <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=2641547">paper</a> by Leah Isakov, Vahid Montazerhodjat, and Andrew Lo titled “Is the FDA Too Conservative or Too Aggressive?: A Bayesian Decision Analysis of Clinical Trial Design.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wkRy8e">
The paper explores the trade-offs the agency faces between what it calls Type I and Type II errors, or false positives and false negatives, respectively. A false positive would be approving a drug that is either harmful or ineffective, and a false negative would be failing to approve a drug that would be helpful or even potentially lifesaving.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C01Xlt">
Type I errors are much more salient to the FDA than Type II. The agency can drive down the rate of false positives to near zero by being stingy with its approvals — after all, you’ll never approve a drug that harms people if you never approve drugs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K1CdSO">
Optimizing for the appropriate levels of risk in both directions — ensuring important treatments are quickly approved, while also guarding against the approval of dangerous or worthless<strong> </strong>drugs — is an incredibly difficult problem to solve. So how does the FDA score?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GzT7ju">
According to Isakov, Montazerhodjat, and Lo: badly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hevoQB">
They find that the FDA is way too conservative when assessing clinical trials for therapies of “terminal illnesses with no existing therapies such as pancreatic cancer.” These are the areas where you would hope the FDA would be overly willing to approve therapeutics since the risk of death and disability are already high for patients.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gYwNd4">
This paper confirms an anecdote from Henry Miller, a former FDA physician who has detailed the <a href="https://www.fdareview.org/issues/why-the-fda-has-an-incentive-to-delay-the-introduction-of-new-drugs/">flawed incentive structure within the agency</a>:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Fo1GGd">
In the early 1980s, when I headed the team at the FDA that was reviewing the NDA for recombinant human insulin … we were ready to recommend approval a mere four months after the application was submitted (at a time when the average time for NDA review was more than two and a half years). With quintessential bureaucratic reasoning, my supervisor refused to sign off on the approval—even though he agreed that the data provided compelling evidence of the drug’s safety and effectiveness. “If anything goes wrong,” he argued, “think how bad it will look that we approved the drug so quickly.”
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gvsk0n">
In Miller’s telling, the agency was overly sensitive to the possibility of making a Type I (false positive) error — and to safeguard the agency’s reputation, they withheld a drug from the public.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nCPsxh">
On average, starting the timer at when a drug begins pre-clinical testing, <a href="https://www.sciencedirect.com/science/article/pii/S2452302X1600036X">it takes the FDA 12 years to approve a new drug</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aATiJI">
And even as the organization has worked to speed up its processes during the Covid-19 pandemic,<strong> </strong>the agency failed repeatedly on balancing risks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8ylG7n">
According to <a href="https://progress.institute/taking-emergency-use-authorization-seriously/">Institute for Progress senior biosecurity fellow Nikki Teran</a>, the US “requires antigen tests to be 80 percent as sensitive as the gold standard RT-PCR tests.” That means, in theory, that an antigen test in the US “needs to be over 30,000 times more sensitive” than in the UK, where Teran notes there are more than 150 different rapid antigen tests available (<a href="https://twitter.com/michaelmina_lab/status/1473517674156244997">and for complicated reasons</a>, 30,000 times more sensitive in a clinical trial does not actually mean 30,000 times better in real life).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VdRdHo">
<a href="https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-
devices/in-vitro-diagnostics-euas-antigen-diagnostic-tests-sars-cov-2">According to the FDA</a>, as of February 9, just 15 emergency use authorizations have been granted for over-the-counter at-home tests. The agency says there are a few common errors preventing it from authorizing antigen tests, and most boil down to poor data: too few patients tested, not enough proof people know how to use the tests,<strong> </strong>incorrect types of samples, and more.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vM0nxj">
Disregarding Mina’s argument that data does<em> </em>exist, just not in the format the FDA wants, there’s still another thing to consider as the FDA rejects applications: The alternative to a complicated test that doesn’t work well is often no test at all.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SHHUEp">
There are dangerous parallels in history to the current Covid-19 crisis. <a href="https://repository.uchastings.edu/cgi/viewcontent.cgi?article=3178&amp;context=hastings_law_journal">According to Steven Salbu</a>, then an associate professor of business at the University of Texas Austin, “in the late 1980s the FDA adopted a de facto blanket ban on HIV home-testing kits.” Salbu writes that an FDA spokesperson explained this policy by pointing to the potential for “improper drawing of blood samples, the possibility of blood samples being held for long periods of time, and the potential for blood samples to be affected by temperature changes during in-mail transit.”
</p></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GeIGFv">
So the FDA, seeing that there could be problems with the capability for HIV tests to be performed perfectly accurately at home, chose instead to allow no at-home tests to exist. Sounds familiar.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XTmbyz">
<a href="https://www.kff.org/hivaids/fact-sheet/the-hivaids-epidemic-in-the-united-states-the-basics/">According to the Kaiser Family Foundation</a>, more than 700,000 Americans have died from an HIV-related illness.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rArUE4">
“Now, my view is that for people who have AIDS and cancer and heart disease, it’s always an emergency for them,” Tabarrok said. “Right? It’s always been like a pandemic for them. And now, I hope that people will come to appreciate the opportunity cost of more safety of FDA delay and apply this more broadly.”
</p>
<div id="vIsofz">
<blockquote class="twitter-tweet">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" dir="ltr" lang="en">
Yes, the FDA’s sloth like action on rapid antigen tests is part of a history of antipathy, skepticism, and delay towards all home tests. The FDA banned HIV tests for 25 years, tried to regulate pregnancy tests as med devices before courts stopped them, slowed genetic tests etc…
</p>
— Alex Tabarrok (<span class="citation" data-cites="ATabarrok">@ATabarrok</span>) <a href="https://twitter.com/ATabarrok/status/1475141013928771589?ref_src=twsrc%5Etfw">December 26, 2021</a>
</blockquote>
</div>
<h3 id="KFh23Y">
Maybe the FDA’s problem isn’t about risk tolerance
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NKG6Uw">
Scientist and writer Hilda Bastian <a href="https://www.theatlantic.com/science/archive/2021/08/fda-pfizer-
vaccine-full-approval/619870/">disagrees</a> that the FDA was too slow on vaccines. She has pointed out that the agency has moved pretty quickly relative to its normal vaccine authorization process. And that’s not the only thing Bastian finds a little unnerving.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Cqc4iX">
“By the end of the year, Pfizer will have produced an estimated 3 billion doses, the most of any company,” she <a href="https://www.theatlantic.com/science/archive/2021/08/fda-pfizer-vaccine-
full-approval/619870/">wrote</a> in the Atlantic in August 2021. “That lightning-fast progress is awe-inspiring—and a little nerve-racking. … The FDA <em>has</em> to be thorough, especially with the first of a new type of drug with completely new production processes.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="R3fQb2">
A recent controversy over the FDA approval of an Alzheimer’s drug, Aduhelm, showcases the double bind the agency is in.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KfG7if">
As Vox’s Dylan Scott has <a href="https://www.vox.com/policy-and-politics/22547044/new-alzheimers-disease-drug-aducanumab-research-
science">explained</a>, the approval of the drug, which “came over the objections of [FDA’s] own scientific advisers, who cited a lack of evidence for the drug’s effectiveness,” has raised flags that innovation on future Alzheimer’s treatments will decline. Ultimately, Medicare decided to significantly limit which patients could receive the drug — <a href="https://www.nytimes.com/2022/01/11/health/aduhelm-medicare-alzheimers.html">according to the New York Times</a>, officials “concluded that there remain significant doubts about whether the potential benefits of Aduhelm for patients outweigh the safety risks.” (A STAT <a href="https://www.statnews.com/2021/06/29/biogen-fda-alzheimers-drug-approval-
aduhelm-project-onyx/">investigation</a> suggested troublingly close contact between Biogen, the drug manufacturer, and FDA officials.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JqhjCP">
This episode pushes back against the narrative that the FDA is too conservative. Instead, it indicates that the relevant question may not be “how risk-averse is the agency?” but instead, “in what situations has it been willing to take risks?” In the case of Aduhelm’s approval, some have alleged that the agency has been too close to the pharmaceutical industry. But when it came to a worldwide emergency, suddenly an abundance of caution ruled the day.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cudakK">
And maybe, as physician <a href="https://www.theatlantic.com/health/archive/2021/07/americas-drug-approval-system-unsustainable/619422/">Benjamin Mazer suggests</a>, the problem is actually “the long-standing and gradual erosion of the agency’s scientific standards.” Mazer points out that 30 years ago, roughly 40 percent of drugs qualified for a regulatory shortcut, but by 2018, 60 percent of them did.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AevYfC">
Whether the FDA’s caution is confined to its decision-making during the Covid-19 pandemic or if it suffers from a much deeper-rooted illness is still up for debate. At the very least, the scrutiny on the FDA demands a rethinking of whether the agency’s risk tolerance is in line with the nation’s best interests.
</p>
<ul>
<li><strong>Why book banning is back</strong> -
<figure>
<img alt="" src="https://cdn.vox-
cdn.com/thumbor/MftiLA4eyuzTc5xpJAAyMIAla2g=/572x0:5191x3464/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70492167/GettyImages_1350634079.0.jpg"/>
<figcaption>
A display of banned or censored books is featured at Books Inc independent bookstore in Alameda, California, on October 16, 2021. | Smith Collection/Gado/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The fight over books in schools is part of a much bigger struggle, revealing where conservatism is today.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A8TiC1">
If you’ve been following the news recently, you’ve likely seen headlines about an escalating push to ban books in schools across the country.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="I88hlZ">
Be it the removal of the Holocaust graphic novel <em>Maus</em> from <a href="https://www.smithsonianmag.com/smart-news/maus-
becomes-bestseller-after-tennessee-school-ban-180979499/">a Tennessee school district’s eighth-grade curriculum</a> or <a href="https://www.theatlantic.com/books/archive/2022/02/banned-books-list-to-kill-a-mockingbird-
maus/621428/">attempts to yank classics</a> like <em>The Handmaid’s Tale </em>from library shelves, incidents of grassroots (and mostly conservative) pressure against schools to control the materials children can access have seemingly grown in frequency and intensity.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fgPy9S">
According to a new <a href="https://www.usatoday.com/story/news/education/2022/02/05/maus-beloved-banned-book-student/6668059001/?gnt-
cfr=1">American Library Association report,</a> there were 330 “book challenges” in the fall of 2021, an uptick from the same periods in recent years. “Parents, activists, school board officials and lawmakers around the country are challenging books at a pace not seen in decades,” <a href="https://www.nytimes.com/2022/01/30/books/book-ban-us-
schools.html">the New York Times</a> reported last month.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lfyjuf">
Viewed in a broader national context — there are roughly 99,000 public K-12 schools in the US — these numbers are still far too low to describe as a national crisis. But free speech advocates insist the new campaigns are worth paying attention to — and worrying about.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OtfTWD">
The rise of book bans, in their view, is the tip of a deeper iceberg: a growing movement on the right to use the levers of local and state governance to control teachers and push an ideologically slanted vision of what children should learn about American culture, society, and history.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AZqrwq">
“You’re seeing really powerful movements under way to constrain expression. It’s not about discussing ideas objectively. It’s about not discussing them at all,” says Jeffrey Sachs, a professor at Acadia University who tracks free speech in education.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Z5Cgzv">
On the local level, the effort manifests in parent- and activist-led drives to remove books from shelves and curriculums. On the state level, there’s been a push to pass “critical race theory” bans that constrain teachers’ speech and “educational transparency” rules that sometimes go as far as putting teachers on publicly accessible webcams and forcing them to <a href="https://legiscan.com/AZ/text/HB2011/2022">seek parental permission if students try to join LGBTQ clubs</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tbAOGN">
This movement is picking up steam. According to Sachs, every single Republican-controlled state where the legislature is currently in session is considering a new “<a href="https://pen.org/in-higher-education-
new-educational-gag-orders/">educational gag order</a>” bill. Many even target university education, which traditionally enjoys much wider latitude to discuss politically controversial ideas.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FkQHLO">
It’s too early to judge the campaign’s effects yet, but all the activity offers an instructive window into where the energy on the American right is today. A conservative movement that once claimed to stand for limited government is increasingly embracing the coercive use of law to commandeer a culture it fears it has lost.
</p>
<h3 id="wiqIfb">
The local level: book challenges in schools
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YUZfpn">
It is certainly not new to hear conservative parents lamenting that schoolbooks are corrupting their children’s minds. The complaints run along some familiar themes: Writing by leftist radicals will steer youth toward political extremism; literature from LGBTQ authors encourages them to adopt “alternative lifestyles”; books that discuss sex and sexuality push them toward risky behaviors.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qWiApb">
At the local level, citizens can act on these concerns by mounting <a href="https://knowledgequest.aasl.org/book-challenges-coming-soon-to-a-school-
near-you/">“book challenges”</a> — basically, make a case to libraries and public schools that a book should be removed from shelves because it is inappropriate for children. In late January, the school board in St. Louis suburb Wentzville voted to ban Toni Morrison’s <em>The Bluest Eye </em><a href="https://www.stltoday.com/news/local/education/wentzville-
school-board-bans-acclaimed-novel-from-high-school-libraries-over-obscenity-
complaints/article_0aeb99be-466e-5423-b313-25c6556f7157.html">in response to parental challenges</a> targeting the book’s depictions of sexual abuse. In November, the school board in Indian River County, Florida <a href="https://cbs12.com/news/local/indian-river-schools-plan-to-review-content-of-library-books-after-parent-
protests">opted to pull <em>All Boys Aren’t Blue</em></a>, an essay collection by author George Matthew Johnson about his experiences as a queer Black man.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xPxqG1">
According to <a href="https://www.oif.ala.org/oif/harry-
potter-20-years-controversy/">the American Library Association</a> (ALA), the most common arguments in challenges prior to 1999 were about sexual content or obscene language. That year marked the US publication of <em>Harry Potter and the Sorcerer’s Stone</em>, which transformed the censorship scene. The ALA reports that, in each year between 2000 and 2009, <em>Harry Potter</em> books were at the top of the group’s most challenged book list nationwide, primarily because of concerns among Christian parents who believed the books were glorifying witchcraft.
</p>
<figure class="e-image">
<pre><code> &lt;img alt=" " src="https://cdn.vox-</code></pre>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">cdn.com/thumbor/-MSgnmatA6kDywKqkc_pmsV3VJs=/800x0/filters:no_upscale()/cdn.vox- cdn.com/uploads/chorus_asset/file/23230069/GettyImages_51885326.jpg" /&gt; <cite>Justin Sullivan/Getty Images</cite></p>
<pre><code>&lt;figcaption&gt;Copies of Harry Potter books on display at the Clean Well-Lighted Place For Books in San Francisco, </code></pre>
California, on December 21, 2004.
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YWJguX">
Free speech experts say what’s happening now represents an escalation from that period: that there is a new wave of censorship sweeping America’s schools targeting literature relating to race, LGBTQ identity, and sex. <a href="https://www.ala.org/advocacy/bbooks/frequentlychallengedbooks/top10">In 2020</a>, the most recent year the ALA has published data on specific titles, the two most challenged books were Alex Gino’s <em>Melissa</em> (a middle grade book about a trans child, formerly published as <em>George</em>) and Ibram X. Kendi and Jason Reynolds’s <em>Stamped: Racism, Antiracism, and You</em> (a young adult adaptation of Kendi’s research on racism in America).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vxWnUn">
“We used to call it the ‘Red Scare.’ We’re increasingly calling it the ‘Ed Scare,’” says Jonathan Friedman, the director of free expression and education at the anti-censorship group PEN America.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DsEwjG">
Conservative parents aren’t the only ones trying to take books off of shelves. In 2020, the seventh-most challenged book nationwide was Harper Lee’s <em>To Kill a Mockingbird,</em> which (per the ALA summary) was “banned and challenged for racial slurs and their negative effect on students, featuring a ‘white savior’ character, and its perception of the Black experience.” The eighth most challenged book was John Steinbeck’s <em>Of Mice and Men</em>, which contained “racial slurs and racist stereotypes.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HeeI8k">
Moreover, it’s not clear just how widespread the Ed Scare is. The 330 challenges that the ALA reported from September to December of 2021 is an increase relative to the same months in prior years, but still a minuscule number compared to the roughly 99,000 public schools in the country — a case perhaps of media attention and social media virality inflating the threat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O3GpDF">
But Friedman argues that this analysis of the ALA numbers is misleading. For one thing, the figures are most likely an undercount, as teachers and librarians are often afraid of the consequences of reporting censorship campaigns. The current rise of book challenges is also geographically uneven: According to Friedman, challenges are less common in blue states than in red ones. Looking purely at national numbers obscures significant trends toward censorship in certain states and communities.
</p></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VKBkmI">
There’s some evidence to support this claim. An <a href="https://www.nbcnews.com/news/us-news/texas-
books-race-sexuality-schools-rcna13886">NBC investigation in Texas</a>, a state that Friedman points to as the epicenter of the Ed Scare, found a significant uptick in book challenges near major cities:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bQ2qBZ">
Records requests to nearly 100 school districts in the Houston, Dallas, San Antonio, and Austin regions — a small sampling of the state’s 1,250 public school systems — revealed 75 formal requests by parents or community members to ban books from libraries during the first four months of this school year. In comparison, only one library book challenge was filed at those districts during the same time period a year earlier, records show. A handful of the districts reported more challenges this year than in the past two decades combined.
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uo3ZSZ">
To be sure,<strong> </strong>these numbers do not tell us what percentage of these challenges were successful. But the big percentage increase over previous years is strikingly suggestive.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aDkjIB">
To understand what’s happening here, we need to look at the bigger picture of contemporary education politics in America. The intensifying push for book challenges at school districts isn’t happening in a vacuum.
</p>
<h3 id="VIOhuu">
The state level: CRT bans and “transparency”
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="x57aX0">
There is currently a broader move on the American right against what they see as out- of-control “wokeness” in American education. Activist groups like Moms for Liberty, think tanks like the Goldwater Institute, and Republican politicians across the country have all focused considerable resources to push for greater censorship in K-12 schools.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7160t6">
This isn’t to say the school district-level book challenges are being coordinated at a national level; Friedman says many are flaring up on their own. Rather, cues from conservative national media and leaders appear to be inflaming grassroots passions — producing a phenomenon Sachs describes as “three different conservative educational projects … converging.”
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/TVCrfiTIcA19IxxhIH68NI4D_q8=/800x0/filters:no_upscale()/cdn.vox-
cdn.com/uploads/chorus_asset/file/23230116/GettyImages_1236621135.jpg"/> <cite>Robert Gauthier/Los Angeles Times via Getty Images</cite>
<figcaption>
An even mix of proponents and opponents to teaching Critical Race Theory are in attendance as the Placentia Yorba Linda School Board discusses a proposed resolution to ban it from being taught in schools in Yorba Linda, California, on November 16, 2021.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="630N91">
If book bans are the first of these projects, then “critical race theory” bans are the second — and arguably the more significant. In <a href="https://pen.org/steep-rise-gag-orders-many-sloppily-drafted/">a recent report for PEN America</a>, Sachs wrote that more than 120 such bills had been introduced in state legislatures since January 2021. Of these, 12 have passed in 10 different states, and more than 80 remain live in their respective statehouses.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V7TX9x">
Generally speaking, the aim of these bills is to regulate what teachers can do in classrooms. They often prohibit a set of loosely defined concepts related to race from being taught, on occasion specifically singling out certain texts (<a href="https://www.vox.com/identities/2019/8/19/20812238/1619-project-slavery-conservatives"><em>The 1619 Project</em></a> is a common target).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lEV0QX">
Frequently, they aim to prohibit certain kinds of classroom activities <strong>that conservatives have become fixated on, </strong>like “privilege walks,” where students form a line and are asked to take a step forward every time the teacher mentions a form of social advantage that applies to them (setting aside how you feel about them — “privilege walks” <a href="https://nonsite.org/the-first-privilege-
walk/">have their detractors</a> — it’s not clear how prevalent such exercises are in K-12 schools). Sometimes — as in <a href="https://www.npr.org/2021/05/01/992761507/idaho-governor-signs-bill-to-ban-critical-race-theory-in-
schools">Idaho’s bill</a>, the first ban passed in the nation — they merely prevent teachers from “compelling” a student to affirm certain ideas about race.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WFkd8x">
As opposed to book challenges, which are bottom-up censorship with parents and local activists leading the charge across school districts, CRT bans are top-down — state-level rules, often influenced by <a href="https://www.edweek.org/policy-politics/whos-really-driving-critical-race-theory-
legislation-an-investigation/2021/07">model legislation drafted by national conservative groups</a>. Yet while different groups and political actors may be pushing them, both types of campaigns are fueled by the same set of political ideas and circumstances.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FTecry">
Once again, Texas is a clear example of what this looks like in practice.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sdZz23">
Book challenges <a href="https://www.slj.com/?detailStory=anatomy-of-a-challenge-a-book-ban-in-leander-
texas-presaged-a-pattern-of-challenges-nationwide">began gathering steam</a> in school districts in late 2020 and the first half of 2021. In September 2021, the statehouse passed its first critical race theory ban — a bill that required teachers to present “diverse and contending perspectives without giving deference to any one” in any discussion of “currently controversial issues of public policy or social affairs.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xoiMOr">
This loose language has had predictably perverse consequences. One school district leader <a href="https://www.nbcnews.com/news/us-news/southlake-
texas-holocaust-books-schools-rcna2965">told teachers that</a> “if you have a book on the Holocaust” in your classroom library, “you [make sure to] have one that has an opposing, that has other perspectives.” That the Texas law does not have explicit provisions on classroom libraries illustrates the problem: The broad wording, characteristic of many of these bills nationwide, sows fear and overreaction among teachers, librarians, and administrators.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AMJbq3">
<a href="https://www.npr.org/2021/10/28/1050013664/texas-lawmaker-matt-krause-launches-inquiry-into-850-books">In October 2021</a>, Republican state Rep. Matt Krause sent a letter to school districts detailing <a href="https://static.texastribune.org/media/files/94fee7ff93eff9609f141433e41f8ae1/krausebooklist.pdf?_ga=2.1442677.55668335.1637592201-763113133.1637254734">a list of 850 books</a> that he believed “might make students feel discomfort, guilt, anguish, or any other form of psychological distress because of their race or sex.” Examples include Ta-Nehisi Coates’s <em>Between the World and Me</em>, an <a href="https://www.amazon.com/Are-All-Born-Free-
Declaration/dp/1847806635/ref=asc_df_1847806635/?tag=hyprod-20&amp;linkCode=df0&amp;hvadid=255976817970&amp;hvpos=&amp;hvnetw=g&amp;hvrand=11084700176436396394&amp;hvpone=&amp;hvptwo=&amp;hvqmt=&amp;hvdev=c&amp;hvdvcmdl=&amp;hvlocint=&amp;hvlocphy=9061285&amp;hvtargid=pla-556811882860&amp;psc=1">Amnesty International adaption</a> of the UN Declaration of Human Rights, and a picture book titled “<em>Pink is a Girl Color” … and other silly things people say.</em> Krause’s letter <a href="https://www.wfaa.com/article/news/education/granbury-isd-pulls-over-100-library-books-for-
review/287-fc1cb585-71a4-48be-98ac-158fe4fa185b#:~:text=The%20district%20began%20removing%20books%20from%20shelves%20earlier%20this%20month.&amp;text=GRANBURY%2C%20Texas%20%E2%80%94%20On%20Thursday%2C,from%20shelves%20earlier%20this%20month.">appears to have successfully prompted</a> several book removals in Texas schools.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4hB9gx">
In November 2021, Gov.  Greg Abbott (R) <a href="https://gov.texas.gov/news/post/governor-abbott-directs-tea-tslac-sboe-to-shield-children-from-
pornography-inappropriate-content-in-texas-public-schools">ordered</a> the Texas Education Agency, the Texas State Library and Archives Commission, and the Texas State Board of Education to “immediately develop statewide standards to prevent the presence of pornography and other obscene content in Texas public schools.” While that may seem anodyne, many saw it as coded language targeting literature that contained frank discussion of sexuality or LGBTQ identity.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KY1qJn">
“The fact that this is labeled as pornography is misleading,” Brandon Rottinghaus, a political scientist at the University of Houston, told <a href="https://spectrumlocalnews.com/tx/south-texas-el-
paso/news/2021/11/03/educators-react-to-abbott-letter-on--pornographic--books">Spectrum News Austin</a>. “It’s clear that this is politically motivated.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Q8DeDe">
Finally, in December 2021, the statehouse passed yet another<em> </em>CRT ban. The new bill <a href="https://www.texastribune.org/2021/12/02/texas-critical-race-theory-law/">did not fix the vagueness</a> in the first one that gave rise to an educator both-sidesing the Holocaust, but did contain new regulations on curriculum (like an explicit ban on requiring that students read <em>The 1619 Project</em>).
</p>
<figure class="e-image">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><img alt=" " src="https://cdn.vox-cdn.com/thumbor/az-
gi6rR2bA1vnRVpT_6uzvznH0=/800x0/filters:no_upscale()/cdn.vox-
cdn.com/uploads/chorus_asset/file/23230131/GettyImages_1353852323.jpg"/> <cite>Spencer Platt/Getty Images</cite></p>
<figcaption>
“The 1619 Project: A New Origin Story” is displayed at a New York City bookstore on November 17, 2021.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8yiMUx">
And it’s not just Texas. Such efforts are under way across the country, with ambitious Republican politicians in states ranging from <a href="https://www.businessinsider.com/glenn-youngkin-
launches-tipline-report-teachers-2022-1">Virginia</a> to <a href="https://www.usatoday.com/story/news/education/2022/01/19/florida-bill-could-restrict-lessons-on-discrimination-at-
school/6583928001/">Florida</a> to <a href="https://www.nytimes.com/2022/02/07/opinion/culture/maus-tennessee-book-
bans.html">Tennessee</a> trying to capitalize on the political energy surrounding the Ed Scare. Their efforts appear to be escalating.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CN8f4S">
Recently, <a href="https://pen.org/steep-rise-gag-orders-many-sloppily-drafted/">Sachs has begun tracking</a> a third prong of this campaign — so-called “educational transparency” provisions being proposed in 2022 legislative sessions. The phrase “educational transparency” is a clever stroke — who’s against transparency? And many of the transparency provisions, including an influential model <a href="https://web.archive.org/web/20210706205724/https://goldwaterinstitute.org/wp-content/uploads/2021/05/Academic-
Transparency-Act.pdf">written by the Goldwater Institute</a>, merely require schools to post their readings on publicly accessible websites.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VVvyI7">
But some, Sachs writes, are more egregiously panoptic:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kKcQbR">
In Florida, one lawmaker recently introduced legislation that would allow parents to <a href="https://cbsaustin.com/news/nation-world/bill-could-install-video-cameras-in-florida-classrooms">scrutinize video recordings</a> of their children’s classrooms for signs of “critical race theory.” Another in Mississippi wants to <a href="https://www.supertalk.fm/mississippi-representative-wants-cameras-in-public-school-classrooms/">stream them live</a> over the internet. And at least two bills in Missouri propose letting members of <a href="https://legiscan.com/MO/text/SB645/id/2453210/Missouri-2022-SB645-Introduced.pdf">the public</a> <a href="https://legiscan.com/MO/text/HB2189/id/2464797">attend</a> teachers’ professional development workshops.
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZCh9qy">
One especially disturbing bill, Arizona’s HB 2011, goes even further. It amends the state’s law requiring parental permission for sex education to cover student participation in LGBTQ clubs. Schools now must “seek consent” from parents if a student attempts to join a club “involving sexuality, gender or gender identity”; it also requires that schools provide the group’s charter to parents as part of the permission process.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SBfzLt">
“The transparency bills are designed to surveil or monitor, almost in a Big Brother sense, what goes on in a school,” Sachs tells me. “It’s about surveilling these people in a way that makes them vulnerable to bullying and censorship.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rje8P1">
<a href="https://www.newyorker.com/news/annals-of-inquiry/how-a-conservative-activist-
invented-the-conflict-over-critical-race-theory">Christopher Rufo</a>, a fellow at the conservative Manhattan Institute, made this strategy explicit in <a href="https://twitter.com/realchrisrufo/status/1479515716822781952">a series of tweets</a> explaining his support that affirms Sachs’s concerns. “With curriculum transparency, every parent in the country can become an investigative reporter,” Rufo wrote.
</p>
<h3 id="CakiCk">
The national level: The right’s illiberal turn
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VxSNKs">
Stephani Bercu is a parent in the Leander Independent School District, a suburban district outside of Austin home to <a href="https://www.schoollibraryjournal.com/?detailStory=anatomy-of-a-challenge-a-book-ban-
in-leander-texas-presaged-a-pattern-of-challenges-nationwide">one of the earliest skirmishes</a> in the current Texas book-banning offensive. In December 2021, after a year-long process, the Leander Independent School District <a href="https://www.kut.org/education/2021-12-03/leander-isd-pulls-11-books-from-curriculum-after-year-long-
review">officially removed 11 books</a> from lists of acceptable material in optional student reading clubs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iYAsNa">
According to Bercu, what she sees as a fight over free expression in Leander started earlier than most people think. She dates it back to the summer of 2019, when a local library announced that it would host Drag Queen Story Hour, an event where drag queens read books to children.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GMG45j">
The event incensed local conservatives, creating so much controversy that the Leander library ended its sponsorship of the event altogether. A local progressive church rented out the library room to host the event on its own dime, even changing it to “Family Pride and Story Time” to come across more tamely.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bNokXn">
This didn’t appease critics; when the event was held, <a href="https://www.youtube.com/watch?v=3d0emQmwFpM&amp;t=23s">roughly 275 protesters and counterprotesters</a> showed up outside the library, even <a href="https://www.bitchute.com/video/K53MWqhjLW3h/">attracting coverage</a> from the right-wing, conspiracy theory-promoting site InfoWars. In August, the Leander City Council effectively banned the event by <a href="https://www.kvue.com/article/news/local/drag-queen-story-time-officially-over-after-leander-ends-
library-room-rentals/269-7b8bc54c-6567-4e3a-b896-9888e3d1a96f">prohibiting the library from renting out rooms in general</a> (on grounds that the security costs for holding Family Pride and Story Time amidst protest were too high).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KoCBeb">
Bercu sees the ultimate success of the campaign as the beginning of a wider effort to control free expression in Leander. “[This is] where I think it starts for our city,” she told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="npT9YO">
What happened in Leander that summer was in some ways preordained. Earlier that year, in May, Catholic conservative writer Sohrab Ahmari came across a Facebook ad for a Drag Queen Story Hour in Sacramento. “This is demonic,” a <a href="https://www.nytimes.com/2019/06/07/opinion/conservatives-culture-trump.html">clearly furious Ahmari tweeted</a>. “To hell with liberal order.”
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-
cdn.com/thumbor/hy1IxJTfhXvEGz_z-JmhMn9bCQA=/800x0/filters:no_upscale()/cdn.vox-
cdn.com/uploads/chorus_asset/file/23230163/GettyImages_1152686555.jpg"/> <cite>Frederic J. Brown/AFP via Getty Images</cite>
<figcaption>
Drag queens Athena Kills, center, and Scalene Onixxx arrive to awaiting adults and children for Drag Queen Story Hour at Cellar Door Books in Riverside, California, on June 22, 2019.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eusp91">
This rage powered <a href="https://www.firstthings.com/web-exclusives/2019/05/against-david-
french-ism">a subsequent essay by Ahmari</a> in the Christian magazine First Things, railing against what he saw as an unwillingness among cultural conservatives to use the law to establish their values. “Progressives understand that culture war means discrediting their opponents and weakening or destroying their institutions. Conservatives should approach the culture war with a similar realism,” Ahmari wrote.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sky1wr">
What that looked like, in practice, was seen in Leander just weeks later.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vhivzU">
Today, Ahmari’s essay is seen as one of the foundational texts for what’s called the “post-liberals” or <a href="https://newrepublic.com/article/164408/young-intellectuals-illiberal-
revolution-conservatism">“New Right”</a> — a loose ideological group of conservatives who believe in the aggressive use of government to crush liberal influence over culture. <a href="https://www.vox.com/policy-and-
politics/2021/11/19/22787269/conservatives-america-chris-rufo-patrick-deneen">Leading proponents of educational censorship</a>, like Rufo, often fall into this camp.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B2X8ZP">
This brand of conservative sees itself as standing athwart a liberal elite monoculture, where Hollywood, academia, and even Silicon Valley collude to push the country in an increasingly liberal direction. Its vehemence is driven by what the movement views as decades of political defeats on cultural issues from abortion to gay marriage.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KbOKLr">
Much like book challenges, this New Right is not entirely new. It’s a manifestation of a crusading zeal<strong> </strong>for culture war that’s always been a part of the conservative movement but became dominant in the Trump era.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NbZTvf">
But the resurgence of book banning on the right can feel a little discordant with conservatism’s other fixation: cancel culture.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5rxJb2">
To take an example in the realm of education, many conservatives for years have bemoaned the state of free speech on college campuses, alleging that professors and left-wing students shout down any right-wing viewpoints. In this conversation, they pose as champions of open discussion, even gaining support for some liberals.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OPgVoM">
There are profound differences in scale and scope between the campus speech wars and the ant-CRT campaign. The former tend to be unconnected eruptions on different campuses, events that are <a href="https://www.niskanencenter.org/the-campus-free-speech-crisis-ended-last-year/">often overblown</a> by a media fixated on elite colleges. The latter is an honest-to-goodness push to enact laws designed to censor teachers and restructure curricula along right-wing ideological lines (and influenced by model legislation from conservative organizations). That some on the right are existentially concerned about the former, while actively supportive of the latter, is revealing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WmFUeV">
Though they mainly target K-12 schools, anti-CRT laws may also end up presenting a <a href="https://pen.org/in-higher-education-new-educational-gag-orders/">significant long-term threat to campus free expression</a>. Some are worded broadly enough to restrict faculty rights; at Iowa State University, for example, the administration instructed professors that the state’s CRT law <a href="https://www.thefire.org/doubling-
down-iowa-state-again-insists-new-critical-race-theory-law-applies-to-its-faculty-and-classes/">applies in classrooms</a>. According to Sachs, roughly 40 new bills currently contain provisions that apply to higher education.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OMphlv">
Whether this becomes a major problem for universities remains to be seen. More broadly, it’s not yet clear how effective the right’s new push to control education will be.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="goqsRg">
The book-banning campaigns, while objectionable, are hardly as widespread as liberals and free speech advocates sometimes seem to suggest. Most of the state-level CRT bans have only recently come into effect, making it too early to measure their impact on classrooms. It’s possible that requiring teachers to put reading lists on a website will not actually harm them, and that the more clearly objectionable rules pushed under the guise of “transparency” never become law.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FPML9d">
But what’s undeniable is that the use of law to reverse progressive cultural victories has gained new purchase on the right. And education is the domain where they’re trying to show proof of concept.
</p>
<ul>
<li><strong>Why the Olympic monobob event is only for women</strong> -
<figure>
<img alt="" src="https://cdn.vox-
cdn.com/thumbor/KjE0Ms95BO69lYp8BXht-G7ysq8=/240x0:1680x1080/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70489730/VDC_XES_016_monobob_CLEAN.0.jpg"/>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
What the monobob does and doesn’t do for gender equality.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hOR0DN">
Bobsledding (or bobsleighing) is one of the oldest Olympic sports, dating back to the very first Winter Games in 1924. Back then, women were barred from competing in nearly every event except <a href="https://www.britannica.com/event/Chamonix-1924-Olympic-Winter-Games">figure skating</a>. Of the 250 athletes that arrived for the first Winter Olympics, only 11 were women.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UpBjoe">
Times have changed. The 2022 Winter Olympics in Beijing is considered the most gender-balanced to date, with female athletes making up <a href="https://olympics.com/ioc/news/women-at-the-olympic-winter-games-beijing-2022-all-you-need-to-know">45 percent of the roster</a>. But sexist regulations and outdated “science” still creep in. Who could forget the 2021 Tokyo Olympics, when the <a href="https://www.nytimes.com/2021/07/20/sports/norway-beach-handball-team.html?smid=tw-share">Norwegian handball team was fined</a> for refusing to wear bikinis? Or questionable testosterone tests that <a href="https://www.bbc.com/news/world-africa-57748135">barred female sprinters from competing</a> in an event?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AWrbeW">
As recently as 2008, the Winter Olympics was riddled with controversy over gender inclusion issues; female aerial skiers <a href="https://olympics.nbcsports.com/2022/01/17/ski-jumping-olympics-usa-women/">sued the Vancouver Organizing Committee</a> over alleged discrimination. In 2005, the president of the International Ski Federation stated that ski jumping “<a href="http://content.time.com/time/specials/packages/article/0,28804,1963484_1963490_1963447,00.html">seems not to be appropriate for ladies from a medical point of view</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lMQ9gT">
Uteruses, am I right?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RiRKJf">
As for bobsledding, it wasn’t <a href="https://olympics.com/en/beijing-2022/sports/bobsleigh/">until 2002</a> that female athletes were invited to participate in the Games, but only in a single event: the two-woman bob. Since 1932, men have had two events (the two-man and four-man bob). In 2022, a new all-women bobsledding event was introduced: the monobob, a single-woman sled. But is it actually leveling the playing field? Maybe, but not entirely in the way you might think.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rUJSNY">
Further reading:
</p>
<ul>
<li id="ZnG05v">
Read more about the <a href="https://www.ibsf.org/images/federation/Rules_and_Regulations/2021_International_Rules_BOBSLEIGH.pdf">rules and regulations</a> and <a href="https://www.ibsf.org/en/our-sports/bobsleigh-history">history of bobsledding</a> from the IBSF.
</li>
<li id="IaloVl">
Learn more about the <a href="https://www.ibsf.org/en/tracks">different tracks around the world</a>.
</li>
<li id="GRcxzy">
The Lake Placid Museum is a great place <a href="https://www.lakeplacidnews.com/news/local-news/2013/12/09/lake-placid-artifacts-celebrate-sliding-sports-
heroes/">to read about more specific history</a> for sliding sports.
</li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qIPPgS">
You can find this video and the entire library of <a href="https://www.youtube.com/channel/UCLXo7UDZvByw2ixzpQCufnA"><strong>Vox’s videos on YouTube</strong></a>.
</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>Ataash, Beastia and Chancellor impress</strong> - Ataash, Beastia and Chancellor impressed when the horses were exercised here on Thursday (Feb. 10) morning.Inner sand:600m: Silver Steps (Zeeshan), C</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>COVID-19 hits Indian Open golf yet again, cancelled for third year running</strong> - The tournament was first conducted in 1964 and has been held every year since then.</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>ESPNcricinfo awards | Rishabh Pant wins ‘Test Batting Award’, Kane Williamson is ‘Captain of Year’</strong> - The Test bowling award went to Kyle Jamieson for his 5 for 31, which helped New Zealand become the first World Test champions.</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>India vs West Indies third ODI | Dynamic India aim to polish off West Indies</strong> - Rohit-Dravid combo’s willingness to experiment stands vindicated</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>Someone else took credit for decisions I took in Australia: Rahane</strong> - Rahane remains confident of making a comeback into India’s Test squad</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>Rajya Sabha member Jose K. Mani calls for setting up a tribunal for wildlife accidents</strong> - The Wildlife (Protection) Act, 1972 has failed in preventing wildlife raids on human settlements, he says</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>Uttarakhand Assembly elections | PM Modi’s ED, CBI do not scare me: Rahul Gandhi</strong> - “I don’t listen to him because I am not afraid of him or his CBI and ED,” the former Congress president said in an election rally in Uttarakhand</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>Special relationship with Afghan people, UNSC resolution to continue to guide Afghan policy: India</strong> - Minister of State for External Affairs V Muraleedharan said this in Rajya Sabha</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 allows ED to rely on forensic auditors’ report for charge sheet against Unitech ex-promoters</strong> - The top court allowed Sanjay and Ajay Chandra, currently lodged in Mumbai jails, to have video conference meetings.</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>Man arrested for duping job-seekers in Cuddalore</strong> - The Cuddalore District Crime Branch police on Thursday arrested a 38-year-old man on charges of cheating job aspirants of lakhs of rupees by promising</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 tensions: Russia begins military drills with Belarus</strong> - The US has called the 10-day drills an “escalatory” action amid tensions over Ukraine.</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>How suicide became the hidden toll of the war in Ukraine</strong> - A deep stigma around suicide in Ukraine is standing in the way of saving soldiers’ lives.</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>Freedom Convoy: Paris protest banned by police ahead of arrival</strong> - Paris police are taking no chances ahead of a Canada-inspired blockade to protest at Covid measures.</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>Russian gallery security guard accused of drawing eyes on painting</strong> - The painting was sent for restoration after the Russian guard allegedly drew eyes on it.</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>Salah Abdeslam: Paris attacks defendant denies killing anyone</strong> - Salah Abdeslam claims he chose at the last moment not to blow himself up during the Paris attacks.</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>May the 25th be with you: Obi-Wan Kenobi poster, premiere date revealed</strong> - May 25 premiere date coincides with 45th anniversary of <em>A New Hope</em>’s release. - <a href="https://arstechnica.com/?p=1833004">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nintendo Direct headlined by Mario Kart 8’s 48 new upcoming racetracks</strong> - Switch surprises: <em>Portal</em>, <em>No Man’s Sky</em>, <em>Earthbound</em>, <em>Mario Strikers</em>, <em>Live-A- Live</em>… whew! - <a href="https://arstechnica.com/?p=1832901">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>As states drop masking, CDC stands by guidance: “We are not there yet”</strong> - “Our hospitalizations are still high, our death rates are still high,” CDC director cautioned. - <a href="https://arstechnica.com/?p=1832961">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Vodafone Portugal struggles to restore service following cyberattack</strong> - Ambulance and emergency services are among those suffering from “deliberate” hack. - <a href="https://arstechnica.com/?p=1832923">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Police arrest Mesa County clerk who promoted Trump’s false election claims</strong> - Tina Peters was filmed kicking leg toward officer and likely faces charges. - <a href="https://arstechnica.com/?p=1832918">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><strong>A man wanted to literally die with his $$$, so he trusted a third of his money to a Priest, a third to a Doctor, and a third to his Lawyer to bury him with it when he died.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After his death, at the man’s funeral the priest whispered to his dead body and placed a bag in his coffin. The doctor then proceeded to whisper to the body and placed a bag in there as well. Then the lawyer went and dropped off a bag and moved on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
As they were carpooling back from the funeral the lawyer asked what the priest whispered. The priest — with tears in his eyes — said that he had to confess he spent some of the money on an orphanage so that some hungry kids would not starve and that he feels bad for what he had done, but that he had no choice. The doctor then admits that he too had to let him know that one of his patients needed a surgery that he alone could not do, that he spent some of the money to save the person’s life. The lawyer looks at them with scorn and says, “how could you? You have betrayed a man’s last and dying request!” The doctor and priest look at the lawyer and asks, “so your bag had all the money he entrusted you with?” To which he replies, “damn right, I wrote the check for the full amount, not a penny less!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/sightalignment"> /u/sightalignment </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/sozbj4/a_man_wanted_to_literally_die_with_his_so_he/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/sozbj4/a_man_wanted_to_literally_die_with_his_so_he/">[comments]</a></span></p></li>
<li><strong>A rabbit is hopping through the woods. Hop! Hop! Hop! When he comes upon a giraffe. Now, this giraffe is about to smoke some weed. The rabbit looks up at the giraffe and say, “Giraffe, don’t smoke weed! Weed is a drug and drugs are bad, come running with me through the forest!”</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The giraffe looks at the weed, then looks at the rabbit, then back at the weed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The giraffe tossed his blunt aside and they go running through the forest together. Run! Run! Run! Hop! Hop! Hopping along.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Soon they come to a clearing with a sheep.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
This sheep is about to shoot up heroin.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The rabbit says to the sheep, “Mr Sheep, don’t do heroin! Heroin is a drug and drugs are bad for you! Come running with us through the forest!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The sheep looks at the heroin, then looks at the rabbit, then back at the heroin.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The sheep tossed his needle aside and they go running through the forest together.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Run! Run! Run! Hop! Hop! Hopping along.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Soon they come to a clearing and in this clearing is a tiger.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Now, this tiger is about to drink a can of beer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The rabbit looks at the tiger and says, “Mr Tiger, don’t drink beer! Alcohol is a drug and drugs are bad for you! Come running with us through the forest!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The tiger looks at his beer, looks at the rabbit and back his beer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He takes a claw and cracks open the beer and proceeds to carefully place it down beside him.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He gets up and walks over to the rabbit, lifts up a paw and starts mauling the shit out of the rabbit!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The giraffe and sheep are in shock.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
And they scream, “Dude, what the fuck!? He was just trying to help you!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The tiger turns to them and growls, "Every time that fucking rabbit does cocaine, I end up running through the fucking forest!
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/somt29/a_rabbit_is_hopping_through_the_woods_hop_hop_hop/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/somt29/a_rabbit_is_hopping_through_the_woods_hop_hop_hop/">[comments]</a></span></p></li>
<li><strong>Widow at the funeral</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Sam died and left $50,000 in his will for an elaborate funeral.<br/> As the last attenders left, Sam’s wife, Rose, turned to her oldest friend, Sadie, and said: “Well, I’m sure Sam would be pleased.”
</p>
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“I’m sure you’re right” replied Sadie, who leaned in close and lowered her voice to a whisper: “tell me, how much did it really cost?”<br/> “All of it” said Rose. “50,000.”
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“No!” Sadie exclaimed “I mean, it was very nice, but really…….$50,000?”
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Rose nodded. “The funeral was $6500. I donated $500 to the church for the priest services. The food and drinks for another $500. And the rest went towards the memorial stone.”<br/> Sadie computed quickly: “$42,500 for a memorial stone? Exactly how big is it?”<br/> “Seven and a half carats.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/hokka4"> /u/hokka4 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/soqwve/widow_at_the_funeral/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/soqwve/widow_at_the_funeral/">[comments]</a></span></p></li>
<li><strong>Whats the difference between a politician and a hooker?</strong> - <!-- SC_OFF -->
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A hooker will stop fucking you once you run out of money.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Cautious_Reaction_36"> /u/Cautious_Reaction_36 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/som97x/whats_the_difference_between_a_politician_and_a/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/som97x/whats_the_difference_between_a_politician_and_a/">[comments]</a></span></p></li>
<li><strong>Jeff Bezos only got divorced because</strong> - <!-- SC_OFF -->
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he realized his marriage was a union.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/soutiens"> /u/soutiens </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/sojllk/jeff_bezos_only_got_divorced_because/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/sojllk/jeff_bezos_only_got_divorced_because/">[comments]</a></span></p></li>
</ul>
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