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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Robust immunogenicity of a third BNT162b2 vaccination against SARS-CoV-2 Omicron variant in a naive New Zealand cohort</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The ability of a third dose of the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine to stimulate immune responses against subvariants, including Omicron BA.1, has not been assessed in New Zealand populations. Unlike many overseas populations, New Zealanders were largely infection naive at the time they were boosted. This adult cohort of 298 participants, oversampled for at-risk populations, was composed of 29% Māori and 28% Pacific peoples, with 40% of the population aged 55+. A significant proportion of the cohort was obese and presented with at least one comorbidity. Sera were collected 28 days and 6 months post second vaccination and 28 days post third vaccination. SARS-CoV-2 anti-S IgG titres and neutralising capacity using surrogate viral neutralisation assays against variants of concern, including Omicron BA.1, were investigated. The incidence of SARS-CoV-2 infection, within our cohort, prior to third vaccination was very low (&lt;6%). This study found a third vaccine significantly increased the mean SARS-CoV-2 anti-S IgG titres, for every demographic subgroup, by a minimum of 1.5-fold compared to titres after two doses. Diabetic participants experienced a greater increase (~4-fold) in antibody titres after their third vaccination, compared to non-diabetics (increase of ~2-fold). This corrected for the deficiency in antibody titres within diabetic participants which was observed following two doses. A third dose also induced a neutralising response against Omicron variant BA.1, which was absent after two doses. This neutralising response improved regardless of age, BMI, ethnicity, or diabetes status. Participants aged &gt;75 years consistently had the lowest SARS-CoV-2 anti-S IgG titres at each timepoint, however experienced the greatest improvement after three doses compared to younger participants. This study shows that in the absence of prior SARS-CoV-2 infection, a third Pfizer-BioNTech BNT162b2 vaccine enhances immunogenicity, including against Omicron BA.1, in a cohort representative of at-risk groups in the adult New Zealand population.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.30.23287981v1" target="_blank">Robust immunogenicity of a third BNT162b2 vaccination against SARS-CoV-2 Omicron variant in a naive New Zealand cohort</a>
</div></li>
<li><strong>Blood biomarkers-defined subgroups show heterogeneity in post-acute COVID-19 syndrome: a rationale for precision medicine.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Acute COVID-19 can cause a post-infectious syndrome in a significant percentage of patients, with multifacted and long lasting symptoms. We hypothesized that this Post-Acute COVID syndrome (PASC) could result from various underlying causes, which may compromise the demonstration of efficacy for treatments evaluated on cohorts of heterogeneous patients. To assess the feasibility of stratifying or characterizing subgroups of post-COVID-19 patients consistent with different indications in a precision medicine perspective, we tested serum biomarkers in a pilot cross-sectional study of patients with neuro-cognitive symptoms from the Northwestern University post-COVID-19 clinic (Chicago,USA). Patient health status was evaluated with the use of standardized PROMIS questionnaires and underwent validated cognitive tests with the NIH Toolbox. Serum biomarkers were chosen as proteins known to be involved in the pathogenic features of a neuro-inflammatory disease, i.e., multiple sclerosis, with a final selection of the most discriminant ones. A multi-isotypes serology against SARS-CoV-2 spike and nucleocapsid antigens was performed to allow detailed analyses of the humoral immune status. Despite the limited numbers of this feasibility study, results showed that clinical data could not differentiate PASC patients with persisting neuro-cognitive impairment, while three major PASC subgroups were identified with serum biomarkers according to the presence or absence of the HERV-W ENV soluble protein combined with neurofilaments light chains and, to a lesser extent, with elevated levels of IL-6. SARS-CoV-2 serological results in PASC compared to healthy controls also revealed a significant increase of anti-Spike and/or Nucleocapsid IgM, IgA and, unexpectedly, IgE. For IgG, a significant difference was observed with Nucleocapsid only since anti-Spike IgG titers were normally elevated in vaccinated controls. This multi-Ig isotypes serology may provide additional information on the infectious and immunological status of individual patients and should be considered in face of a potential viral persistence in some individuals. Altogether the results show the feasibility of using serum biomarkers to discriminate relevant subgroups or individual patients for precision medicine indications in post-COVID syndromes. This pilot study paves the way to further exploring biological assays for the definition of subtypes of PASC, also called long COVID, useful for the choice of relevant therapeutic strategies.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.31.23288003v1" target="_blank">Blood biomarkers-defined subgroups show heterogeneity in post-acute COVID-19 syndrome: a rationale for precision medicine.</a>
</div></li>
<li><strong>Covid-19 and post-acute sick leave: a hybrid register and questionnaire study in the adult Danish population</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Long covid follows 10-20% of first-time SARS-CoV-2 infections, but the societal burden of long covid and risk factors for the condition are not well-understood. Here, we report findings about self-reported sick leave and risk factors thereof from a hybrid survey and register study, which included 37,482 RT-PCR confirmed SARS-CoV-2 cases and 51,336 test-negative controls who were tested during the index and alpha waves. An additional 33 individuals per 1000 took substantial sick leave following acute infection compared to persons with no known history of infection, where substantial sick leave was defined as &gt;1 month of sick leave within the period 1-9 months after the RT-PCR test date. Being female, ≥50 years, and having certain pre-existing conditions such as fibromyalgia increased risks for taking substantial sick leave. Further research exploring this heterogeneity is urgently needed and may provide important evidence for more targeted preventative strategies.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.31.23288004v1" target="_blank">Covid-19 and post-acute sick leave: a hybrid register and questionnaire study in the adult Danish population</a>
</div></li>
<li><strong>miRNA binding pressure channels evolution of SARS-CoV-2 genomes</strong> -
<div>
In somatic cells, microRNAs (miRNAs) bind to the genomes of RNA viruses and influence their translation and replication. Here we demonstrate that a significant number of miRNA binding sites locate in the NSP4 region of the SARS-CoV-2 genome, and the intestinal human miRNAs exert evolutionary pressure on this region. Notably, in infected cells, NSP4 promotes the formation of double-membrane vesicles, which serve as the scaffolds for replication-transcriptional complexes and protect viral RNA from intracellular destruction. In three years of selection, the loss of many miRNA binding sites, in particular, those within the NSP4, has shaped the SARS-CoV-2 genomes to promote the descendants of the BA.2 variants as the dominant strains and define current momentum of the pandemics.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.31.535057v1" target="_blank">miRNA binding pressure channels evolution of SARS-CoV-2 genomes</a>
</div></li>
<li><strong>Mechanistic investigation of SARS-CoV-2 Omicron variant spike mutants via full quantum mechanical modeling</strong> -
<div>
Ab initio quantum mechanical models can characterize and predict intermolecular binding, but only recently have models including more than a few hundred atoms gained traction. Here, we simulate ~13,000 atoms to predict and characterize binding of SARS-CoV-2 spike variants to the human receptor ACE2 (hACE2). We compare four spike variants in our analysis: Wuhan, Omicron, and two Omicron-based variants. To assess binding, we mechanistically characterize the energetic contribution of each amino acid involved, and predict the effect of select single point mutations. We validate our computational predictions experimentally by comparing binding efficacy of spike variants to cells expressing hACE2. We argue that this computational model, QM-CR, can identify mutations critical for intermolecular interactions and inform the engineering of high-specificity interactors.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.12.01.470748v2" target="_blank">Mechanistic investigation of SARS-CoV-2 Omicron variant spike mutants via full quantum mechanical modeling</a>
</div></li>
<li><strong>Trends in serotype distribution and disease severity in adults hospitalised with Streptococcus pneumoniae infection in Bristol and Bath: a retrospective cohort study, 2006-2022</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<b>Background</b> Paediatric pneumococcal conjugate vaccination (PCV) has reduced adult PCV-serotype disease: PCV7 has greater indirect effects than PCV13. Ongoing surveillance is required to evaluate current vaccine usage and inform future vaccine deployment, particularly with respiratory infection epidemiology changing following SARS-CoV-2 emergence. <b>Methods and Findings</b> A retrospective cohort study, all adults &gt;16 years admitted to three UK hospitals, 2006-2022, with pneumococcal disease. Medical records were reviewed for each clinical episode and serotype data were obtained from the UK Health Security Agency national reference laboratory. We identified 1,501 (40.3%) cases of invasive pneumococcal disease (IPD) with known serotype, 134 (3.6%) IPD cases without serotype data, and 2,084 (56.0%) non-IPD cases, which are typically missed in national surveillance. Disease incidence increased progressively from 2006-2020, followed by a sudden decline after COVID-19 emergence and then a gradual increase to pre-pandemic levels. Paediatric PCV7 introduction reduced adult PCV7 serotype IPD from 29.4% [24.1-35.4] of IPD in 2006-09 to 7.0% [3.7-12.7] in 2021-22. PCV13 introduction also decreased adult vaccine serotype IPD, but considerable residual adult disease remains, causing 34.3% [28.6-40.4] of IPD in 2006-09 and 21.7% [15.5-29.6] 9 in 2021-22, respectively. Serotype replacement diminished the benefits of PCV introduction: PCV20-13 and non-PCV serotypes represented 27.0% [21.9-32.9] and 9.3% [6.3-13.5] of disease in 2006-2009, and 39.5% [31.5-48.2] and 31.8% [24.4-40.2] in 2021-2022, respectively. Serotype shifts have resulted in increasing disease caused by serotype 3 and 8, and the re-emergence of serotype 19F and 19A. These serotype shifts occurred as clinical disease severity changed, and whilst the COVID-19 pandemic disrupted disease severity trends, these have now largely reverted to previous trajectories. Patient age trended upwards and although CURB65 severity decreased there were increased ICU admission rates. Overall, inpatient mortality decreased and hospitalisation duration remained stable. <b>Conclusions</b> After 17 years of PCV use, residual pneumococcal disease due to the vaccine serotypes among hospitalised adults remains. The sharp decline in pneumococcal disease during the COVID-19 pandemic has now reversed, with increasing cases due to vaccine serotypes, especially serotype 3. Around 68.2% of cases in 2022 were potentially covered by the recently licensed 20-valent PCV.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.30.23287917v1" target="_blank">Trends in serotype distribution and disease severity in adults hospitalised with Streptococcus pneumoniae infection in Bristol and Bath: a retrospective cohort study, 2006-2022</a>
</div></li>
<li><strong>The Unexpected Protective Role of Thrombosis in Sepsis-Induced Inflammatory Lung Injury Via Endothelial Alox15</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background. Patients with sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) commonly suffer from severe pulmonary thrombosis, but clinical trials of anti-coagulant therapies in sepsis and ARDS patients have failed. ARDS patients with thrombocytopenia also exhibit increased mortality, and widespread pulmonary thrombosis is often seen in coronavirus disease 2019 (COVID-19) ARDS patients. Methods. Employing different amounts of microbeads to induce various levels of pulmonary thrombosis. Acute lung injury was induced by either lipopolysaccharide i.p. or cecal ligation and puncture. Endothelial cell (EC)-targeted nanoparticle coupled with CDH5 promoter was employed to delivery plasmid DNA expressing the CRISPR/Cas9 system for EC-specific gene knockout or expressing Alox15 for EC-specific overexpression. Additionally, thrombocytopenia was induced by genetic depletion of platelets using DTRPf4Cre mice by breeding Pf4Cre mice into the genetic background of DTR mice. Results. We show that while severe pulmonary thrombosis or thrombocytopenia augments sepsis-induced ALI, the induction of mild pulmonary thrombosis conversely reduces endothelial cell (EC) apoptosis, ALI, and mortality via sustained expression of endothelial arachidonate 15-lipoxygenase (Alox15). Endothelial Alox15 knockout via EC-targeted nanoparticle delivery of CRISPR/Cas9 plasmid DNA in adult mice abolished the protective impact of mild lung thrombosis. Conversely, overexpression of endothelial Alox15 inhibited the increases in ALI caused by severe pulmonary thrombosis. The clinical relevance of the findings was validated by the observation of reduced ALOX15-expressing ECs in lung autopsy samples of ARDS patients. Additionally, restoration of pulmonary thrombosis in thrombocytopenic mice also normalized endotoxemia-induced ALI. Conclusion. We have demonstrated that moderate levels of thrombosis protect against sepsis-induced inflammatory lung injury via endothelial Alox15. Overexpression of Alox5 inhibits severe pulmonary thrombosis-induced increase of ALI. Thus, activation of ALOX15 signaling represents a promising therapeutic strategy for treatment of ARDS, especially in sub-populations of patients with thrombocytopenia and/or severe pulmonary thrombosis.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.29.23287934v1" target="_blank">The Unexpected Protective Role of Thrombosis in Sepsis-Induced Inflammatory Lung Injury Via Endothelial Alox15</a>
</div></li>
<li><strong>Disparities in Mortality Associated with Acute Myocardial Infarction and COVID-19 in the United States: A Nationwide Analysis</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The impact of the COVID-19 pandemic on potential racial disparities in acute myocardial infarction (AMI) management and outcomes is unclear. We examined AMI patient management and outcomes during the pandemic9s initial nine months, comparing COVID-19 and non-COVID-19 cases. Methods: We identified all patients hospitalized for AMI in 2020 using the National Inpatient Sample (NIS), identifying those with or without concurrent COVID-19. Logistic and linear regression was used for analyses of associations, with adjustment for potential confounders. Results: Patients with both AMI and COVID-19 had higher in-hospital mortality rates (aOR 3.19, 95% CI 2.63-3.88), mechanical ventilation (aOR 1.90, 95% CI 1.54-2.33), and hemodialysis (aOR 1.38, 95% CI 1.05-1.89) compared to those without COVID-19. Black and Asian/Pacific Islander patients had higher in-hospital mortality than White patients, (aOR 2.13, 95% CI 1.35-3.59) and (aOR 3.41, 95% CI 1.5-8.37). Moreover, Black, Hispanic, and Asian/Pacific Islander patients had higher odds of initiating hemodialysis, (aOR 5.48, 95% CI 2.13-14.1), (aOR 2.99, 95% CI 1.13-7.97), and (aOR 7.84, 95% CI 1.55-39.5) and were less likely to receive PCI for AMI, (aOR 0.71, 95% CI 0.67-0.74), (aOR 0.81, 95% CI 0.77-0.86), and (aOR 0.82, 95% CI 0.75-0.90). Additionally, Black patients had a lower likelihood of undergoing CABG surgery for AMI (aOR 0.55, 95% CI 0.49-0.61). Conclusion: Our study revealed increased mortality and complications in COVID-19 patients with AMI, highlighting significant racial disparities. Urgent measures addressing healthcare disparities, such as enhancing access and promoting culturally sensitive care, are needed to improve health equity.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.30.23287987v1" target="_blank">Disparities in Mortality Associated with Acute Myocardial Infarction and COVID-19 in the United States: A Nationwide Analysis</a>
</div></li>
<li><strong>The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The associations between longitudinal dynamics and the breadth of SARS-CoV-2 neutralizing antibody response with various Long COVID (LC) phenotypes prior to vaccination are not known. The capacity of antibodies to cross neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms. Methods: We measured longitudinal neutralizing and cross-neutralizing antibody responses to pre- and post-SARS-CoV-2 Omicron variants in participants infected during the early waves of the COVID-19 pandemic, prior to wide-spread rollout of SARS-CoV-2 vaccines. Cross sectional regression models adjusted for various clinical covariates and longitudinal mixed effects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms in general, as well as LC phenotypes. Results: We identified several novel relationships between SARS-CoV-2 antibody neutralization and the presence of LC symptoms. Specifically, we show that, although neutralizing antibody responses to the original, infecting strain of SARS-CoV-2 were not associated with LC in cross-sectional analyses, cross-neutralization ID50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of LC and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with LC phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants. Conclusions: Our findings suggest that relationships between various immune responses and LC are likely complex but may involve the breadth of antibody neutralization responses.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.30.23287923v1" target="_blank">The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms</a>
</div></li>
<li><strong>S:D614G and S:H655Y are gateway mutations that act epistatically to promote SARS-CoV-2 variant fitness</strong> -
<div>
SARS-CoV-2 variants bearing complex combinations of mutations have been associated with increased transmissibility, COVID-19 severity, and immune escape. S:D614G may have facilitated emergence of such variants since they appeared after S:D614G had gone to fixation. To test this hypothesis, Spike sequences from an immunocompromised individual with prolonged infection, and from the major SARS-CoV-2 variants of concern, were reverted to the ancestral S:D614. In all cases, infectivity of the revertants was compromised. Rare SARS-CoV-2 lineages that lack S:D614G were identified and the infectivity of these was dependent upon S:Q613H or S:H655Y. Notably, Gamma and Omicron variants possess both S:D614G and S:H655Y, each of which contributed to infectivity of these variants. All three mutations, S:Q613H, S:D614G, and S:H655Y, stabilized Spike on virions, consistent with selection of these mutations by a common molecular mechanism. Among sarbecoviruses, S:Q613H, S:D614G, and S:H655Y are only detected in SARS-CoV-2, which uniquely possesses a polybasic S1/S2 cleavage site. Results of genetic and biochemical experiments here demonstrated that S:D614G and S:H655Y are likely adaptations to the cleavage site. CryoEM revealed that both mutations shift the Spike receptor binding domain towards the open conformation required for ACE2-binding and Spikes bearing either S:D614G or S:H655Y spontaneously mimic the smFRET signal that ACE2 induces in the parental molecule. Data from these orthogonal experiments demonstrate that S:D614G and S:H655Y are convergent adaptations to the polybasic S1/S2 cleavage site, which stabilize S1 on the virion in the open RBD conformation that is on-pathway for target cell fusion, and thereby act epistatically to promote the fitness of variants bearing complex combinations of clinically significant mutations.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.30.535005v1" target="_blank">S:D614G and S:H655Y are gateway mutations that act epistatically to promote SARS-CoV-2 variant fitness</a>
</div></li>
<li><strong>Determinants of species-specific utilization of ACE2 by human and animal coronaviruses</strong> -
<div>
Utilization of human ACE2 allowed several bat coronaviruses (CoVs), including the causative agent of COVID-19, to infect humans either directly or via intermediate hosts. Here, we analyzed the ability of Spike proteins from 24 human or animal CoVs to use ACE2 receptors across nine reservoir, potential intermediate and human hosts. We show that overall SARS-CoV-2 Omicron variants evolved more efficient ACE2 usage but mutation of R493Q in BA.5 Spike disrupts utilization of ACE2 from Greater horseshoe bats. Spikes from most CoVs showed species-specific differences in ACE2 usage, partly due to variations in ACE2 residues 31, 41 or 354. Mutation of T403R allowed the RaTG13 bat CoV Spike to use all ACE2 orthologs analysed for viral entry. Sera from COVID-19 vaccinated individuals neutralized the Spike proteins of a range of bat Sarbecoviruses. Our results define determinants of ACE2 receptor usage of diverse CoVs and suggest that COVID-19 vaccination may protect against future zoonoses of SARS-CoV-related bat viruses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.31.535059v1" target="_blank">Determinants of species-specific utilization of ACE2 by human and animal coronaviruses</a>
</div></li>
<li><strong>Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia</strong> -
<div>
The COVID-19 pandemic continues to be a health crisis with major unmet medical needs. The early responses from airway epithelial cells, the first target of the virus regulating the progression towards severe disease, are not fully understood. Primary human air-liquid interface cultures representing the broncho-alveolar epithelia were used to study the kinetics and dynamics of SARS-CoV-2 variants infection. The infection measured by nucleoprotein expression, was a late event appearing between day 4-6 post infection for Wuhan-like virus. Other variants demonstrated increasingly accelerated timelines of infection. All variants triggered similar transcriptional signatures, an early inflammatory/immune signature preceding a late type I/III IFN, but differences in the quality and kinetics were found, consistent with the timing of nucleoprotein expression. Response to virus was spatially organized: CSF3 expression in basal cells and CCL20 in apical cells. Thus, SARS-CoV-2 virus triggers specific responses modulated over time to engage different arms of immune response.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.30.534980v1" target="_blank">Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia</a>
</div></li>
<li><strong>Explicit Modelling of Antibody Levels for Infectious Disease Simulations in the Context of SARS-CoV-2</strong> -
<div>
Measurable levels of immunoglobulin G antibodies develop after infections with and vaccinations against SARS-CoV-2. These antibodies are temporarily dynamic; due to waning, antibody levels will drop below detection thresholds over time. As a result, epidemiological studies could underestimate population protection, given that antibodies are a marker for protective immunity. During the COVID-19 pandemic, multiple models predicting infection dynamics were used by policymakers to plan public health policies. Explicitly integrating antibody and waning effects into the models is crucial for reliable calculations of individual infection risk. However, only few approaches have been suggested that explicitly treat these effects. This paper presents a methodology that explicitly models antibody levels and the resulting protection against infection for individuals within an agent-based model. This approach can be integrated in general frameworks, allowing complex population studies with explicit antibody and waning effects. We demonstrate the usefulness of our model in two use cases.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.31.535072v1" target="_blank">Explicit Modelling of Antibody Levels for Infectious Disease Simulations in the Context of SARS-CoV-2</a>
</div></li>
<li><strong>Risk averse reproduction numbers improve resurgence detection</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The effective reproduction number R is a prominent statistic for inferring the transmissibility of infectious diseases and effectiveness of interventions. R purportedly provides an easy-to-interpret threshold for deducing whether an epidemic will grow (R&gt;1) or decline (R&lt;1). We posit that this interpretation can be misleading and statistically overconfident when applied to infections accumulated from groups featuring heterogeneous dynamics. These groups may be delineated by geography, infectiousness or sociodemographic factors. In these settings, R implicitly weights the dynamics of the groups by their number of circulating infections. We find that this weighting can cause delayed detection of outbreak resurgence and premature signalling of epidemic control because it underrepresents the risks from highly transmissible groups. Applying E-optimal experimental design theory, we develop a weighting algorithm to minimise these issues, yielding the risk averse reproduction number E. Using simulations, analytic approaches and real-world COVID-19 data stratified at the city and district level, we show that E meaningfully summarises transmission dynamics across groups, balancing bias from the averaging underlying R with variance from directly using local group estimates. An E&gt;1generates timely resurgence signals (upweighting risky groups), while an E&lt;1ensures local outbreaks are under control. We propose E as an alternative to R for informing policy and assessing transmissibility at large scales (e.g., state-wide or nationally), where R is commonly computed but well-mixed or homogeneity assumptions break down.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.31.22279450v3" target="_blank">Risk averse reproduction numbers improve resurgence detection</a>
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<li><strong>What is stopping us to get vaccinated? The role of optimism-pessimism, information sources, trust, conspiracy theories, and fear in the willingness to get vaccinated</strong> -
<div>
The aim of this study was to check the role of optimism-pessimism, information sources, trust in information sources, and conspiracy theories regarding COVID-19 vaccines in the willingness to get vaccinated. The convenience sample was used (N = 2291) from Serbia. Instruments were used in this study: The Life Orientation Test-Revised; information sources and trust in information sources; fears regarding COVID-19; items on conspiracy theories on COVID-19 vaccines, and items measuring willingness to get vaccinated. SEM confirms the role of optimism-pessimism in COVID-19-related feelings, the relation between trust in information sources and the information gathered from them, the role of information in the fear for oneself and close to others, the negative role of conspiracy and the positive role of fear in vaccination intention.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/rzqx2/" target="_blank">What is stopping us to get vaccinated? The role of optimism-pessimism, information sources, trust, conspiracy theories, and fear in the willingness to get vaccinated</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 Safety &amp; Efficacy of MIR 19 ® Inhalation Solution in Patients With Mild COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: MIR 19 ®;   Combination Product: Standard therapy<br/><b>Sponsor</b>:   National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia<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>LACTYFERRIN™ Forte and ZINC Defense™ and Standard of Care (SOC) vs SOC in the Treatment of Non-hospitalized Patients With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Sesderma LACTYFERRIN™ Forte and Sesderma ZINC Defense™;   Drug: Placebo<br/><b>Sponsors</b>:   Jose David Suarez, MD;   Sesderma S.L.;   Westchester General Hospital Inc. DBA Keralty Hospital Miami;   MGM Technology 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>MP0420 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: MP0420;   Drug: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Molecular Partners AG;   University of Minnesota<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>AZD7442 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: AZD7442;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   AstraZeneca;   University of Minnesota<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>VIR-7831 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: VIR-7831;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Vir Biotechnology, Inc.;   GlaxoSmithKline;   University of Minnesota<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>PF-07304814 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: PF-07304814;   Drug: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Pfizer;   University of Minnesota<br/><b>Suspended</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>BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: BRII-196;   Biological: BRII-198;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Brii Biosciences Limited;   University of Minnesota<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>LY3819253 (LY-CoV555) for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: LY3819253;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Eli Lilly and Company;   University of Minnesota<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>RCT for Yinqiaosan-Maxingganshitang in the Treatment of COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Chinese Herb;   Diagnostic Test: Placebo<br/><b>Sponsor</b>:   Chinese University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of a Health Pathway for People With Persistent Symptoms Covid-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Other: usual care and follow-up by a nurse;   Other: Personalized Multifactorial Intervention (IMP)<br/><b>Sponsor</b>:   Centre Hospitalier Universitaire de Saint Etienne<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Study on Safety and Effectiveness of Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19.</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Intervention</b>:   Biological: Extracellular Vesicles from Mesenchymal Stem Cells<br/><b>Sponsor</b>:   First Affiliated Hospital of Wenzhou Medical University<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>Teletechnology-assisted Home-based Exercise Program for Severe COVID-19</strong> - <b>Conditions</b>:   COVID-19;   Telerehabilitation<br/><b>Intervention</b>:   Behavioral: Teletechnology-assisted home-based pulmonary rehabilitation<br/><b>Sponsor</b>:   National Taiwan University Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: NP-101;   Other: Placebo<br/><b>Sponsor</b>:   Novatek Pharmaceuticals<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cluster-Randomized Trial of Air Filtration and Ventilation to Reduce Covid19 Spread in Homes</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Device: Filtration Fan;   Behavioral: Safe-home pamphlet;   Behavioral: Mid-week phone call<br/><b>Sponsor</b>:   Stanford University<br/><b>Enrolling by invitation</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>Zinc Supplementation Impact in Acute COVID-19 Clinical Outcomes</strong> - <b>Conditions</b>:   Zinc Deficiency;   Sars-CoV-2 Infection<br/><b>Intervention</b>:   Dietary Supplement: Zinc Acetate<br/><b>Sponsors</b>:   Parc de Salut Mar;   Universitat Pompeu Fabra<br/><b>Completed</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>Defibrotide mitigates endothelial cell injury induced by plasmas from patients with COVID-19 and related vasculopathies</strong> - CONCLUSION: Our data, in the context of a recent clinical trial in severe COVID-19, suggest benefits to further exploration of defibrotide and these pathways in COVID-19 and related endotheliopathies.</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>Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19</strong> - CONCLUSION: In patients with severe COVID-19, garadacimab did not confer a clinical benefit over placebo. Transient aPTT prolongation and suppressed FXIIa-mKA showed target engagement of garadacimab that was not associated with bleeding events even with concomitant anticoagulant use. The safety profile of garadacimab was consistent with previous studies in patients with hereditary angioedema.</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 Potential Effect of Dapsone on the Inflammatory Reactions in Covid-19: Staggering view</strong> - Severe SARS-CoV-2 infection is linked with an overstated immune response with the succeeding release of pro-inflammatory cytokines and progression of the cytokine storm. In addition, severe SARS-CoV-2 infection is associated with the development of oxidative stress and coagulopathy. Dapsone (DPS) is a bacteriostatic antibiotic that has a potent anti-inflammatory effect. Thus, this mini-review aimed to elucidate the potential role of DPS in mitigating inflammatory disorders in Covid-19 patients….</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>Hyper-inflammation and complement in COVID-19</strong> - COVID-19 is a complex disease manifesting in a broad severity spectrum and involving distinct organs and systems. Hyperinflammation, including complement over-activation, has a pivotal role in severe COVID-19 pathobiology, stimulating the inflammatory response, causing microangiopathy, platelet-neutrophil activation, and hypercoagulability. SARS-CoV-2 can directly activate the complement system by the classic, alternative, and lectin pathways, and infected cells can produce intracellular…</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>Susceptibility of SARS COV-2 nucleocapsid and spike proteins to reactive oxygen species and role in inflammation</strong> - Chemiluminescence was used to test the susceptibility of the SARS-CoV-2 N and S proteins to oxidation by reactive oxygen species (ROS) at pH7.4 and pH8.5. The Fenton’s system generates various ROS (H(2)O(2), ·OH, -OH, ·OOH). All proteins were found to significantly suppress oxidation (the viral proteins exhibited 25-60% effect compared to albumin). In the second system, H(2)O(2)was used both as a strong oxidant and as a ROS. A similar effect was observed (30-70%); N protein approached the effect…</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>Antimycotic effect of 3-phenyllactic acid produced by probiotic bacterial isolates against Covid-19 associated mucormycosis causing fungi</strong> - The Covid-19 associated mucormycosis (CAM) is an emerging disease affecting immunocompromised patients. Prevention of such infections using probiotics and their metabolites persist as effective therapeutic agents. Therefore, the present study emphasizes on assessment of their efficacy and safety. Samples from different sources like human milk, honey bee intestine, toddy, and dairy milk were collected, screened and characterized for potential probiotic lactic acid bacteria (LAB) and their…</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>Two Resveratrol Oligomers Inhibit Cathepsin L Activity to Suppress SARS-CoV-2 Entry</strong> - Cell entry of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) depends on specific host cell proteases, which are the key targets for preventing and treating viral infections. Herein, we describe miyabenol C and trans-ε-viniferin, two resveratrol oligomers that specifically inhibit SARS-CoV-2 entry by targeting host protease cathepsin L. Several cell-based assays were used to demonstrate the effect of resveratrol oligomers, and their target was identified via screening of antiviral…</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>Amuvatinib Blocks SARS-CoV-2 Infection at the Entry Step of the Viral Life Cycle</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2 propagation is mediated by the protein interaction between viral proteins and host cells. Tyrosine kinase has been implicated in viral replication, and hence, it has become a target for developing antiviral drugs. We have previously reported that receptor tyrosine kinase inhibitor blocks the replication of hepatitis C virus (HCV). In the present study, we…</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>Investigating the potential of natural compounds as novel inhibitors of SARS-CoV-2 RdRP using computational approaches</strong> - COVID-19 is a highly contagious disease caused by SARS-CoV-2. Currently, no vaccines or antiviral treatments are available to combat this deadly virus; however, precautions and some repurposed medicines are available to contain COVID-19. RNA-dependent RNA polymerase (RdRP) plays an important role in the replication or transcription of viral mechanisms. Approved antiviral drug such as Remdesivir has shown inhibitory activity against SARS-CoV-2 RdRP. The purpose of this study was to carry out a…</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>Multifaceted involvements of Paneth cells in various diseases within intestine and systemically</strong> - Serving as the guardians of small intestine, Paneth cells (PCs) play an important role in intestinal homeostasis maintenance. Although PCs uniquely exist in intestine under homeostasis, the dysfunction of PCs is involved in various diseases not only in intestine but also in extraintestinal organs, suggesting the systemic importance of PCs. The mechanisms under the participation of PCs in these diseases are multiple as well. The involvements of PCs are mostly characterized by limiting intestinal…</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>Synthesis, molecular docking, and binding Gibbs free energy calculation of β-nitrostyrene derivatives: Potential inhibitors of SARS-CoV-2 3CL protease</strong> - The outbreak of novel coronavirus disease 2019 (COVID-19), caused by the novel coronavirus (SARS-CoV-2), has had a significant impact on human health and the economic development. SARS-CoV-2 3CL protease (3CLpro) is highly conserved and plays a key role in mediating the transcription of virus replication. It is an ideal target for the design and screening of anti-coronavirus drugs. In this work, seven β-nitrostyrene derivatives were synthesized by Henry reaction and β-dehydration reaction, and…</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>Engineering Nanomolar Potent Protein-based Inhibitors for Papain-like Protease Guided by Residue Correlation Network</strong> - We developed a rational protocol with a minimal number of mutated residues to create highly potent and selective protein-based inhibitors. Guided by an interaction and dihedral correlation network of ubiquitin (Ub) and MERS coronaviral papain-like protease (PLpro) complex, our designed ubiquitin variant (UbV) with 3 mutated residues (A46F, K48E, and E64Y) resulted in a ~3,500-fold increase in functional inhibition as compared with the wildtype Ub (wtUb). Further optimization with C-terminal R74N…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals</strong> - The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to public health. Besides humans, SARS-CoV-2 can infect several animal species. Highly sensitive and specific diagnostic reagents and assays are urgently needed for rapid detection and implementation of strategies for prevention and control of the infection in animals. In this study, we initially developed a panel of monoclonal antibodies (mAbs) against SARS-CoV-2 nucleocapsid (N)…</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>Cell Surface Nucleocapsid Protein Expression: A Betacoronavirus Immunomodulatory Strategy</strong> - We recently reported that SARS-CoV-2 Nucleocapsid (N) protein is abundantly expressed on the surface of both infected and neighboring uninfected cells, where it enables activation of Fc receptor-bearing immune cells with anti-N antibodies (Abs) and inhibits leukocyte chemotaxis by binding chemokines (CHKs). Here, we extend these findings to N from the seasonal human coronavirus (HCoV)-OC43, which is also robustly expressed on the surface of infected and non-infected cells by binding…</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>Totally-green cellulosic fiber with prominent sustained antibacterial and antiviral properties for potential use in spunlaced non-woven fabric production</strong> - The worldwide spread of COVID-19 has put a higher requirement for personal medical protective clothing, developing protective clothing with sustained antibacterial and antiviral performance is the priority for safe and sustaining application. For this purpose, we develop a novel cellulose based material with sustained antibacterial and antiviral properties. In the proposed method, the chitosan oligosaccharide (COS) was subjected to a guanylation reaction with dicyandiamide in the presence of…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Donald Trump Is Indicted and Threatens the Rule of Law: An American Tragedy, Act III</strong> - The indictment of the former President by a Manhattan grand jury begins a perilous new phase in the Trump saga. - <a href="https://www.newyorker.com/news/daily-comment/an-american-tragedy-act-iii">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Unimaginable Horror of Evan Gershkovich’s Arrest in Moscow</strong> - It’s painful and surreal to write these words: Evan Gershkovich, a reporter for the Wall Street Journal, is being held by Russian authorities on espionage charges. - <a href="https://www.newyorker.com/news/daily-comment/the-unimaginable-horror-of-a-friends-arrest-in-moscow">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Wait for the Trump Indictment Is Finally Over</strong> - A press stakeout of Manhattan’s Criminal Courthouse dwindled down to a single cameraman. Then the news that a grand jury had voted to indict the former President arrived. - <a href="https://www.newyorker.com/news/our-local-correspondents/the-wait-for-the-trump-indictment-is-finally-over">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What’s the Point of Reading Writing by Humans?</strong> - Maybe one day journalism could be replaced with an immense surveillance state with a GPT-4 plug-in. Why would we want that? - <a href="https://www.newyorker.com/news/our-columnists/whats-the-point-of-reading-writing-by-humans">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Has Modi Pushed Indian Democracy Past Its Breaking Point?</strong> - With the media and judiciary already under attack, the Prime Minister’s main opponent was just banned from Parliament. - <a href="https://www.newyorker.com/news/q-and-a/has-modi-pushed-indian-democracy-past-its-breaking-point">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>How the relentless drive for optimization made baseball impossible to watch</strong> -
<figure>
<img alt="Swing and a miss." src="https://cdn.vox-cdn.com/thumbor/h9K7PINM_QadtOlvM4yiItdSiYU=/200x0:3400x2400/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72137063/GettyImages_1243964215.0.jpg"/>
<figcaption>
Philadelphia Phillies left fielder Kyle Schwarber strikes out on a pitch from Atlanta Braves relief pitcher Raisel Iglesias during Game 2 of the NLDS between the Atlanta Braves and the Philadelphia Phillies on October 12, 2022, at Truist Park in Atlanta. | Icon Sportswire via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The unlikely similarity between modern baseball and the AI boom.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fgV85s">
Here’s a question for major league baseball’s opening weekend: What does Philadelphia Phillies left fielder Kyle Schwarber have in common with artificial intelligence?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HHuo10">
At first glance, not much. Schwarber — who has the rough physical dimensions of a human keg of beer — is best known for hitting the baseball really, really far when he hits it. Counting the regular season and postseasons, he hit a National League-leading 52 regular and postseason home runs last year — <a href="https://rotowear.com/products/kyles-schwarbombs-shirt">Schwarbombs</a>, as Philly fans like to call them — including one against San Diego in the National League Championship Series that <a href="https://www.mlb.com/video/kyle-schwarber-homers-1-on-a-fly-ball-to-right-field-u53kjh">may have been able to achieve orbital flight</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Q9wuBd">
GPT-4 is capable of doing many things, but <a href="https://www.baseballamerica.com/stories/kyle-schwarbers-home-run-inspires-awe-amazement-in-phillies-nlcs-game-1-win/#:~:text=Schwarber's%20home%20run%20off%20Yu,119.7%20mph%2C%20according%20to%20Statcast.">mashing a baseball 119.7 mph for a total of 488 feet</a>, as Schwarber did against San Diego’s Yu Darvish, is not currently one of them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HYl6ty">
But viewed another way — and I say this as a lifelong Phillies fan — Schwarber is the roly-poly human incarnation of an out-of-control AI. He’s Skynet madly <a href="https://www.slugger.com/en-us/explore/baseball/kyle-schwarber">swinging a 31-ounce Louisville Slugger</a>. He’s HAL from <em>2001</em> in <a href="https://www.nbcsports.com/philadelphia/phillies/kyle-schwarbers-custom-home-run-derby-kicks-are-masterpiece">custom Home Run Derby cleats</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="s50lXb">
And he must be stopped.
</p>
<h3 id="TD3DG5">
The relentless pursuit of optimization
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VtP7Ue">
Allow me to explain.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fl1m2P">
In 2022, counting the regular season and the postseason,<strong> </strong>Schwarber <a href="https://www.baseball-reference.com/players/s/schwaky01.shtml">had 743 plate appearances</a>. Along with those 52 home runs, he walked 101 times and struck out a truly mind-boggling 218 times. That means that almost exactly 50 percent of the time Schwarber came to the plate, he achieved one of baseball’s “<a href="https://www.mlb.com/glossary/idioms/three-true-outcomes">three true outcomes</a>”: a strikeout, a walk, or a home run.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dTajWV">
A true outcome means that the ball isn’t put in play and no member of the defense is involved beyond the pitcher throwing the ball and the catcher attempting to catch it. That means no fielder trying to make a Gold Glove play on a batted ball. It means no speedy runner trying to go first to home on a ball hit in the gap.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KMO2dc">
The three true outcomes are baseball at its most bloodlessly — and boringly — efficient. And over the past 20 years or so, efficiency as represented by the three true outcomes is precisely the direction baseball has been headed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="utbXes">
On the defensive side, that has meant teams loading up on pitchers capable of throwing the ball really, really hard, in search of strikeouts. A ball put in play, after all, could fall for a hit. The average four-seam fastball last year <a href="https://apnews.com/article/mlb-sports-baseball-rob-manfred-8bf105d6dd6431a0201a4544f37b2362">was 93.9 mph</a>, up from 93.1 mph in 2015, the first year such data was collected.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QCmHWE">
It used to be that only <a href="https://bleacherreport.com/articles/808985-mlb-the-28-hardest-throwers-in-baseball-history">freaks of nature like Nolan Ryan</a> could hit triple digits on the radar gun, yet last year there were 3,356 pitches <a href="https://apnews.com/article/mlb-sports-baseball-rob-manfred-8bf105d6dd6431a0201a4544f37b2362">thrown at 100 mph or higher</a> — nearly twice as many as the year before, and far and away the most in baseball history.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qyGtUm">
On the offensive side, the emphasis is on the other two outcomes: walks and home runs. I never believed it when my Little League manager used to tell me that “a walk is as good as a hit” — kids like to swing the bat — but that’s now gospel in the majors, especially if that walk is followed up by the next batter hitting it out of the park for a multi-run homer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PsW5tW">
With pitchers throwing harder than ever, just making contact is difficult enough, so batters have tried to compensate by focusing on <a href="https://www.bruinsportsanalytics.com/post/launch-angle#:~:text=While%20the%20true%20%E2%80%9Cideal%E2%80%9D%20launch,between%2015%20and%2020%20degrees.">raising the launch angle generated by their swings</a>, increasing the chance that when they do put wood to ball, it has the lift to leave the park. Schwarber’s titanic shot off Darvish, for instance, had a <a href="https://www.sportingnews.com/us/mlb/news/kyle-schwarber-home-runs-schwarbomb-phillies-2022/kyhdcahth1n71akxt2mtvkwd">launch angle of 25 degrees</a>, well above the league average, which is higher than it used to be.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XLJXqV">
The downsides of taking all those Ruthian uppercuts, especially if you’re facing a guy throwing 100-mph gas, is that much of the time you will swing and miss. That means <a href="https://www.baseballamerica.com/stories/home-runs-strikeouts-and-low-averages-are-trending-throughout-baseball/#:~:text=While%20MLB's%20strikeout%20rate%20has,2014%20to%2021.0%25%20in%202021.">lots of strikeouts</a> and considerably <a href="https://www.foxsports.com.au/baseball/baseball-news-2022-mlb-problems-changes-to-the-baseballs-stats-strikeouts-no-small-ball-how-to-fix-rob-manfred/news-story/18fb94347df1110942f2193d64063216">fewer balls put into play in the field</a>. In addition, the recent adoption of <a href="https://www.si.com/mlb/2022/04/26/shifts-increasing-the-opener">advanced defensive positioning</a> has meant that managers are moving fielders before the pitch to where they think a hitter is most likely to put the ball, what’s known as a shift.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2VM4FH">
No batter in the National League <a href="https://www.nbcsports.com/philadelphia/phillies/kyle-schwarber-mlb-defensive-shift-banned">faced the shift more often last season</a> than Schwarber, who would often see three infielders on the right side — where a left-handed power hitter like him pulls the ball — with a second baseman essentially playing shallow right field. Those tactics meant that even when hitters like Schwarber made solid, non-home-run contact, they were less likely to result in a hit. Partially as a result, league-wide batting average <a href="https://www.espn.com/mlb/story/_/id/35631564/2023-mlb-rule-changes-pitch-clock-end-shift-bigger-bases">fell to .243 last year</a>, the lowest since 1968, while the humble base hit is practically an endangered species.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="co2vmn">
The result is a game that is highly efficient and highly boring, with lots of strikeouts and way fewer hits, punctuated by the occasional burst of dingers. Just look at last year’s World Series, which featured Schwarber’s Phillies against the Houston Astros. Game 3 <a href="https://www.baseball-reference.com/boxes/PHI/PHI202211010.shtml">saw</a> the Phillies win 7-0, with all seven runs coming on five homers, including one by Schwarber. And then came Game 4, when the Phillies became <a href="https://www.cbssports.com/mlb/news/world-series-no-hitter-four-astros-pitchers-combine-to-blank-phillies-in-second-fall-classic-no-no-ever/live/">only the second team in baseball history to be no-hit</a> in the World Series, with an incredible 14 strikeouts.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="d8LemE">
Yes, as a Phillies fan, it was considerably more fun to watch the glorified home run derby that was Game 3 than seeing them be no-hit the next night. But even in their win, the Phils struck out 11 times. All in all, the Fall Classic, baseball’s crown jewel, mostly involved watching pitchers throw the ball really hard, batters swinging really hard (and generally missing), and everyone else pretty much just standing around.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1ziv2j">
The upshot is that the most efficient, effective way to win baseball — a strategy basically every team is pursuing — happens to have produced as a side effect the most boring kind of baseball to watch, as evidenced by <a href="https://sites.lsa.umich.edu/mje/2022/12/20/is-baseball-a-dying-sport/#:~:text=Even%20the%20World%20Series%2C%20the,year%20(Gough%2C%202022).">declining ratings and attendance</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MPG0uI">
In the relentless pursuit of optimization, baseball may be killing itself.
</p>
<h3 id="TaVD3A">
Unaligned on the diamond
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rg3CtV">
So what does this have to do with AI? It helps to go back two decades to the Moneyball Oakland A’s and their general manager Billy Beane, the <a href="https://terminator.fandom.com/wiki/Miles_Dyson">Miles Dyson</a> of baseball’s Skynet situation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8oibLS">
The A’s had a problem: They were broke. (As Beane, played by Brad Pitt, put it in the movie <em>Moneyball</em>: “There are rich teams and there are poor teams. Then there’s fifty feet of crap, and then there’s us.”) Unable to compete with rich teams like the Yankees for free agents, Beane had to compensate by using statistical analysis derived from the work of <a href="https://www.npr.org/2011/09/26/140813409/the-man-behind-the-moneyball-sabermetrics">maverick figures like the statistician Bill James</a><strong> </strong>to identify players who were undervalued for their actual production.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qoMM1S">
This meant going against the conventional wisdom, which valued players for things like speed and batting average, and pursuing players who could reliably get on base any way possible, as this scene from the film shows:
</p>
<div id="Vhw4LF">
<div style="width: 100%; height: 0; padding-bottom: 56.25%;">
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gIaMpk">
The surprising success of the Moneyball A’s helped speed a league-wide revolution in using advanced statistical models in baseball. Out were <a href="https://batflipsandnerds.com/2018/11/03/analytics-and-its-effects-on-the-mlb-the-stolen-base/">traditional numbers like stolen bases</a> (the risk of getting thrown out and losing one of the 27 outs a team has in a game was higher than the reward of advancing a base). In were <a href="https://library.fangraphs.com/offense/obp/">stats like on-base percentage</a> (which measures the most important thing a batter can do — not make an out, whether through a hit, a walk, or getting hit by a pitch).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UJcRlj">
Rosters were constructed in the front office and teams were managed in the field with an eye toward maximizing the three true outcomes. No one broke any rules. (If anything, baseball became cleaner in the 2000s and 2010s, as performance-enhancing drugs were phased out). The problem was that the most efficient way to win baseball games under the rules as they existed turned out to be highly inefficient for the purpose of entertaining the spectators and TV audiences who make major league baseball major. (Not incidentally, Beane didn’t watch his teams play. He feared that the act of spectating <a href="https://www.businessinsider.com/billy-beane-doesnt-watch-games-2014-9">would lead to a “visceral reaction”</a> that might outweigh his Moneyball rationality.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j4IibG">
In the world of artificial intelligence, this is an example of “misalignment.” Through highly detailed rules, which now <a href="https://img.mlbstatic.com/mlb-images/image/upload/mlb/atcjzj9j7wrgvsm8wnjq.pdf">run to 191 pages</a>, the creators of baseball tried to construct a game that would be entertaining — meaning action, running, excitement. Think Wille Mays making an <a href="https://www.youtube.com/watch?v=7bLt2xKaNH0">over-the-shoulder catch</a> in the World Series or Rickey Henderson <a href="https://bleacherreport.com/articles/430984-stealing-home-or-why-babe-ruth-is-a-better-thief-than-rickey-henderson">stealing home</a>. That was their goal.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3iP3Ej">
But the goal of the teams that play baseball is to use the rules to win games. Excitement doesn’t factor into it. Which is more or less how you end up with the 2022 Phillies, a team explicitly built to hit a bunch of home runs while also <a href="https://www.crossingbroad.com/2022/11/the-phillies-set-a-world-series-record-for-strikeouts.html">setting a record for the most strikeouts in a World Series</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="t01JFB">
We’ve seen this <a href="https://vkrakovna.wordpress.com/2018/04/02/specification-gaming-examples-in-ai/">happen repeatedly in artificial intelligence</a>, especially in games. One AI that was <a href="https://openai.com/research/faulty-reward-functions">trained to play a boat racing game</a> learned that the most efficient way to score the most points wasn’t to win the race — which is what the designers and presumably most humans would aim to do — but instead to drive around repeatedly in a circle, hitting a handful of targets over and over. This was not fun to watch — seeing the boat mindlessly spinning around and around reminded me of watching Game 4 of the World Series — but that didn’t matter to the AI. What mattered was racking up points by any legal means necessary.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PCkn85">
To its credit, baseball is trying to fix its alignment problem by changing some of the rules to encourage more hits and more action. So this season, extreme defensive shifts of the sort faced by Schwarber <a href="https://www.nytimes.com/2022/09/09/sports/baseball/mlb-bans-shift.html">are outlawed</a> — two infielders have to be on either side of second base when the pitch is thrown, and infielders won’t be allowed to start in the outfield.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Fj3uJS">
Baseball has also added a pitch clock of 15 seconds per pitch (20 seconds when a runner is on), which should both speed up the game and tilt some of the advantage back toward the batter. And bases themselves were increased in size from 15 sq. ft. to 18, partially in the hopes of encouraging more stolen bases. (There were just <a href="https://www.baseball-almanac.com/hitting/hisb3.shtml">2,487 stolen bases last year</a>, down from 3,264 three decades ago.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZcXh29">
Will it work? Through spring training, games <a href="https://www.nytimes.com/2023/03/27/sports/baseball/rob-manfred-mlb-new-rules.html">have been shorter, stolen bases have gone up</a>, and slightly more balls put in play <a href="https://www.cbssports.com/mlb/news/impact-of-mlbs-new-rules-shorter-games-more-steals-and-higher-averages-with-pitch-clock-shift-ban-in-place/">are going for hits</a>. That may not be enough to save baseball — few disciplines, after all, are as relentless in their <a href="https://www.theatlantic.com/newsletters/archive/2022/10/sabermetrics-analytics-ruined-baseball-sports-music-film/671924/">pursuit of optimization as professional sports</a>, and players like Schwarber will ultimately be judged on their stats and their win-loss records, not how entertaining their playing style is.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="txc2EF">
But at least baseball is taking proactive steps to nudge their sport in the direction that fans might actually enjoy. On Opening Day, the average length of a game <a href="https://www.cbssports.com/mlb/news/mlb-opening-day-overreactions-adley-rutschman-for-mvp-another-60-homer-year-for-aaron-judge-same-ol-angels/">was down, while stolen base attempts were up</a>. As for Schwarber, he <a href="https://www.mlb.com/gameday/phillies-vs-rangers/2023/03/30/718779/final/box">went 0-5 in an offense-heavy 11-7 loss</a> to the Texas Rangers, striking out twice for a three-true-outcome rate of 40 percent. Which I guess counts as improvement, albeit not the sort that any Phillies fan is likely to applaud.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LszGr9">
As humanity faces down large language models that can throw the equivalent of 100 mph or more, it’s worth being very, very careful about the rules and the goals we program them with — lest we end up in an eternal no-hitter.
</p></li>
<li><strong>How to tell when an investigation is politicized</strong> -
<figure>
<img alt="People gather outside of a Manhattan courthouse as the nation waits for the possibility of an indictment against former president Donald Trump by the Manhattan District Attorney Alvin Bragg’s office on March 21, 2023 in New York City." src="https://cdn.vox-cdn.com/thumbor/Z_0TNE3sh62f8cZXD0L7XLVq-ds=/113x0:1936x1367/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72136993/GettyImages_1249028799.0.jpg"/>
<figcaption>
People gathered outside a Manhattan courthouse on March 21, 2023 in New York City. | Spencer Platt/Getty
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A simple theory of when probes can be described as politicized — and whether the Manhattan DA’s case against Trump qualifies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZlP5z4">
As someone who’s been covering investigations into leading political figures for the past decade, I’ve thought a lot about the <a href="https://www.vox.com/2020/8/28/21358181/trump-barr-justice-department-second-term-agenda">politicization of the rule of law</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eRvyN0">
On the one hand, politicians shouldn’t be above the law — if they commit crimes, and there’s evidence to show that, they should be charged.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7wRxuO">
But on the other hand, criminal law shouldn’t be weaponized for political reasons against the opposing party’s enemies. When that happens in other countries, we generally view it as a sign of dysfunction or corruption.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dWA8L0">
So how do we know whether that’s happening?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sZt7iS">
Often, it’s harder than it may seem. Avid political partisans are very good at talking themselves into justifications for why their enemies are obviously criminals who deserve to be locked up, while their allies are clearly being unfairly persecuted with weak cases.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="okYOEi">
But I’ve come to think that prosecutions and investigations that can fairly be characterized as politicized tend to share several of the following traits:
</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U2lypj">
They’re fishing expeditions — starting focused on one topic, and sprawling very far afield, often lasting years.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ReikEV">
They focus on obscure or technical matters.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UsHZRJ">
They feature novel legal theories.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="948Qiw">
They resemble few previous prosecutions.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JnLnn6">
Investigators are internally divided on the case’s strength.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jK0Ttk">
They involve scrutiny and an investment of resources that would not have been put on anyone else.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Rfcpyr">
Those in charge of them have obvious political motives.
</li>
</ul>
<div class="c-float-right">
<div id="ONrwDx">
<div>
</div>
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ORXe02">
The more politicized an investigation is, the more the end purpose seems to be to “get” a particular political figure, with the exact crimes at issue being a matter of secondary importance.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QpnKPB">
Many of these traits were evident in the <a href="https://www.vox.com/2020/8/28/21358181/trump-barr-justice-department-second-term-agenda">investigations Trump tried to order</a> into his political opponents during his presidency. Many were also present in investigations into Bill Clinton in the 1990s, which started as the <a href="https://www.vox.com/2015/4/13/8397309/hillary-clinton-whitewater">“Whitewater” investigation</a> and sprawled outward.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="045JUe">
And they also all fit what’s been reported about Manhattan District Attorney Alvin Bragg’s investigation and prosecution of Donald Trump.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fvq8Jt">
This indictment hasn’t yet been unsealed, so perhaps there’s something in it to change this assessment — but what we know so far does not exactly suggest this was an apolitical effort.
</p>
<h3 id="3Lmg0D">
Why the Manhattan DA’s probe looks politicized (but other Trump investigations do not)
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zwb0fV">
I’ll start by saying I’m not particularly inclined to defend Donald Trump as a sterling adherent to the rule of law.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mC8ztu">
The <a href="https://www.vox.com/policy-and-politics/23518814/trump-investigations-jack-smith-january-6-classified">investigations into him</a> — special counsel Jack Smith’s federal probes into Trump’s attempt to overturn Biden’s election win and his classified documents at Mar-a-Lago, as well as the <a href="https://www.nytimes.com/2023/02/16/us/politics/fani-willis-trump-investigation.html">Georgia probe</a> into whether Trump tried to steal the election there — seem well-founded. Guess what? If you try to steal the election, you should be rigorously investigated and charged if the evidence and law merit it. But Alvin Bragg got there first.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZrKI6k">
Another caveat is that we don’t yet know the details of Bragg’s indictment — perhaps it will be rock-solid, convincing, and put many concerns to rest. But a <a href="https://www.vox.com/policy-and-politics/2023/1/31/23579526/trump-indictment-grand-jury-stormy-daniels-felony">whole lot has been reported</a> about the background of the investigation itself — and much of it doesn’t look great.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0XfDZR">
<strong>Is it a fishing expedition?</strong> Arguably — it’s certainly been a <a href="https://www.vox.com/policy-and-politics/2023/1/31/23579526/trump-indictment-grand-jury-stormy-daniels-felony">tangled tale</a>. The previous DA, Cyrus Vance Jr., opened the case back in 2019 to focus on hush money payments made to Stormy Daniels. Vance then put that aside and spent years probing the Trump Organization’s business practices, specifically regarding real estate valuation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nYK6tn">
To try and make that case, he pressured Trump Organization Chief Financial Officer Allen Weisselberg to flip on Trump by <a href="https://www.vox.com/22555751/allen-weisselberg-indictment-trump-grand-larceny">charging him</a> (and the company) with tax fraud related to fringe benefits Weisselberg had received. Then, when Bragg took over as DA last year, he wasn’t impressed by the real estate valuation case and put a hold on it, spurring two prosecutors <a href="https://www.vox.com/2022/2/23/22947946/trump-prosecutors-new-york-bragg">to resign in protest</a>. Bragg then returned to the hush money payments and indicted Trump based on that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eOF7eA">
<strong>Does it focus on an obscure or technical matter?</strong> The charges reportedly pertain to New York business records law — and specifically about whether the Trump Organization’s repayments to Michael Cohen for $130,000 in hush money he’d paid Stormy Daniels were inappropriately logged as legal expenses. Obviously, a lot of people with opinions about this indictment, including me, have never given New York business records law a second thought before. The<strong> </strong>more small-scale charges like this after a long investigation seem, the more they suggest prosecutors landed on them because they tried to make a bigger case that didn’t pan out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XiHb7E">
<strong>Does it feature novel legal theories?</strong> It may, in part. The business records law violation appears pretty open and shut. However, Bragg has <a href="https://www.nytimes.com/2023/01/30/nyregion/trump-stormy-daniels-grand-jury.html">reportedly</a> wanted to charge it as a felony rather than a misdemeanor, and can only do so if the records were falsified to cover up another crime.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wji6Ve">
Federal prosecutors investigated the hush money as a violation of federal campaign finance law, but Bragg is a state prosecutor tasked with enforcing state law, and he <a href="https://www.nytimes.com/2023/01/30/nyregion/trump-stormy-daniels-grand-jury.html">reportedly </a>explored several possibilities of crimes he could assert to justify the felony charge.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TQpbi5">
We don’t yet know what Bragg eventually decided. But the <a href="https://www.nytimes.com/2023/03/09/nyregion/trump-potential-criminal-charges-bragg.html">New York Times’s assessment</a> a few weeks before the indictment came down was that “the case against the former president hinges on an untested and therefore risky legal theory involving a complex interplay of laws, all amounting to a low-level felony.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9hQMJJ">
<strong>Does it resemble previous prosecutions?</strong> It’s unclear. Even the assertion that hush money payments violate the law at all — specifically, that they violate federal campaign finance law — is hotly debated. The closest precedent may be that Democratic politician John Edwards <a href="https://www.justice.gov/opa/pr/former-senator-and-presidential-candidate-john-edwards-charged-alleged-role-scheme-violate">was indicted in 2011</a> with charges of violating campaign finance laws in connection with payments made to Rielle Hunter (whom he’d had an affair and fathered a child with), but he <a href="https://abcnews.go.com/Politics/trump-hush-money-case-compared-democrat-john-edwards/story?id=98053273">was acquitted</a> on one count and the jury couldn’t reach a verdict on several others.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LkDbkA">
<strong>Are investigators internally divided on the case’s strength?</strong> Yes. This has been an unusually leaky investigation, with acrimony between members of the prosecution team frequently spilling into public view.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4GYeYK">
As mentioned, Bragg wasn’t impressed by the real estate valuation case that lead prosecutor Mark Pomerantz had been building, and Pomerantz resigned and wrote a book complaining about Bragg. This led others on the team to complain about Pomerantz to <a href="https://nymag.com/intelligencer/2023/02/mark-pomerantzs-revealing-fight-with-alvin-bragg-over-trump.html?utm_source=tw">Ankush Khardori of New York Magazine</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Lj4WLb">
One regular sticking point is Michael Cohen’s usefulness as a witness. Federal prosecutors looked into the hush money too, as recently as early 2021, and according to CNN legal analyst Elie Honig’s recent book <a href="https://www.amazon.com/Untouchable-How-Powerful-People-Away/dp/0063241501?ots=1&amp;slotNum=2&amp;imprToken=54c39c33-2f6e-3adf-eea&amp;ascsubtag=%5B%5Dvx%5Bp%5D23343567%5Bt%5Dw%5Bd%5DD"><em>Untouchable</em></a>, they had mixed opinions about the case and ended up taking a pass.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xyvt2M">
<strong>Does it involve scrutiny and an investment of resources that would not have been put on anyone else?</strong> It’s hard for me to imagine that this years-long investment of resources into this topic would be brought against anyone other than Trump.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B3qPux">
<strong>Do those bringing the case have obvious political motives?</strong> Bragg is an elected Democrat who, if he runs for another term, would be running in Democratic New York City. When he initially put the brakes on Vance’s investigation, <a href="https://www.vox.com/2022/2/23/22947946/trump-prosecutors-new-york-bragg">he faced intense backlash</a> from progressives who thought he was letting Trump off the hook. So, yes, he has a motive to get back on progressives’ good side.
</p>
<h3 id="11Favn">
Defending democracy and the rule of law?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VCOBCs">
Now, there is a difference between the politicized cases Trump wanted to bring against his political enemies, and this current situation, which is: Many liberals believe Donald Trump is a grave threat to democracy. (And I think they’re correct.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E6Tj5t">
The right has long tried to portray Trump as the victim of endless witch hunts from investigators. And of course, Republicans managed to convince themselves Hillary Clinton was tremendously dangerous for American democracy, too (remember the <a href="https://www.vox.com/2016/9/12/12862434/flight-93-election">“Flight 93 election</a>?”).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZLqcee">
But again, Trump did go to extraordinary lengths to try and steal the 2020 election, which really should end all talk of him as some kind of unfairly persecuted innocent. A second Trump term, should he win, <a href="https://www.vox.com/2020/8/28/21358181/trump-barr-justice-department-second-term-agenda">would probably also be</a> quite dangerous for the rule of law.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="81bu7V">
Many liberals who have been hoping and arguing for Trump’s indictment seem to have this justification in mind, even if few will say it explicitly. In 2021, when it looked like Bragg’s predecessor, Vance, might bring charges, he was <a href="https://www.newyorker.com/magazine/2021/03/22/can-cyrus-vance-jr-nail-trump">profiled in the New Yorker</a>, and the former president’s niece Mary Trump weighed in. “It’s incredibly urgent that Vance prosecutes Donald now,” she said, because the Republican Party certainly wasn’t going to stop him.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pspnzb">
Per this mindset, it would be naive to have academic concerns about politicization of the rule of law, when the nation’s continuing existence as a democracy is at stake. Find some crimes, and lock him up!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fCh3lu">
Maybe it will work — <a href="https://poll.qu.edu/poll-release?releaseid=3870">polls</a> <a href="https://www.reuters.com/world/us/americans-see-trump-investigation-political-also-believable-reutersipsos-2023-03-21/">show</a> that though most Americans say they think Bragg has political motives, most also think the investigation is significant and should disqualify Trump for office.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hTeMkL">
Or maybe this prosecution will backfire, spurring Republican voters to rally around him and easing his path to the GOP nomination, and making our country’s divisions even worse.<strong> </strong>We’ll find out soon enough.
</p></li>
<li><strong>Elon Musk wants to fill your Twitter feed with paid accounts</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/T7pOfNsHpmIASY2KGi2_-fJr1Mg=/322x0:3878x2667/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72133667/1246506636.0.jpg"/>
<figcaption>
Elon Musk outside court in San Francisco in January 2023. | Marlena Sloss/Bloomberg via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It’s a broken version of the digital town square.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cxH0Qr">
When Elon Musk took over Twitter, he said he wanted to protect its place as a “digital town square,” where ideas from all corners of the internet could flourish. But soon, if you want your voice to really be heard in the town square, you’ll need to pay.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="X802Ri">
Earlier this week, Musk tweeted that, starting <a href="https://twitter.com/elonmusk/status/1640502698549075972?s=20">April 15</a>, Twitter will only recommend content from paid accounts in the For You tab, the first screen users see when they open the app.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EnyrSO">
This means that if you don’t start paying <a href="https://www.vox.com/recode/2022/11/4/23438917/twitter-verifications-blue-check-elon-musk">$8 a month for Twitter’s subscription plan, Twitter Blue,</a> you’ll have a harder time getting your tweets seen by the masses. For people viewing but not posting on Twitter, you’ll be seeing a lot more content from paid accounts, which currently make up only <a href="https://www.theinformation.com/articles/musks-twitter-has-just-180-000-u-s-subscribers-two-months-after-launch">0.2 percent of all users</a>. After Twitter users started complaining about the new plan, Elon <a href="https://twitter.com/elonmusk/status/1640800519894736896">clarified</a> that people you follow will also show up in the For You feed. Plus, if users don’t like the For You feed, they can switch to the Following feed, which ranks tweets chronologically.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Iz3sfG">
But the main point still stands: Musk wants to fill your Twitter feed with a higher ratio of paid accounts, and is pressuring more free users to pay for what was once considered a given.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VgUqBb">
This move is the next step in Musk’s plan to try to get more people to subscribe to Twitter Blue. Musk says that on April 1 he’ll <a href="https://techcrunch.com/2023/03/23/twitter-will-kill-legacy-blue-checks-on-april-1/">remove “legacy” verification checkmarks from notable accounts</a> that had them for free, including news organizations, politicians, and researchers. On Friday, some <a href="https://www.axios.com/2023/03/31/twitter-verification-white-house-biden-check-mark">major accounts like the White House</a> and <a href="https://twitter.com/KingJames/status/1641836984195743749">LeBron James</a> said they would not be paying for a checkmark — not a good sign for the impending rollout. <a href="https://twitter.com/WilliamShatner/status/1640706670509846528?s=20">Many are concerned</a> that it could become even easier for public figures who don’t pay for a checkmark to be impersonated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uGXMUo">
The checkmark part of Musk’s plan <a href="https://www.vox.com/recode/2022/11/4/23438917/twitter-verifications-blue-check-elon-musk">has received a lot of attention</a> — in part because it involves famous people — but it’s the changes to Twitter’s feed that are potentially just as, if not more, impactful.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fLIzRy">
That’s because Musk is changing the incentives to Twitter’s core product, its recommendation algorithms, to an extent that it could potentially fill the average user’s experience with lower-quality content.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Avc57V">
“The notion that by virtue of being willing to pay $8 a month means that you are a higher-quality account or worthy of being verified is a really reductive analysis,” said Jason Goldman, a VP of product at Twitter from 2007 to 2010. “There’s plenty of people who are complete trolls and are looking to just get attention for ridiculous behavior for whom $8 a month is a pittance to pay.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Upiu3E">
In his explanation of the upcoming feed change, Musk said that Twitter has to charge users to make sure people aren’t actually spam bots. But there’s a simpler reason that’s also driving this push: Twitter needs to make more money. The company, <a href="https://www.theguardian.com/technology/2023/mar/26/elon-musk-twitter-value-leaked-memo-less-than-half-paid">which is now valued at half</a> of what it was when Musk bought it, is <a href="https://www.vox.com/technology/2023/3/23/23651151/twitter-advertisers-elon-musk-brands-revenue-fleeing">still bleeding advertisers</a> that are put off by Musk’s antics. Not enough people have subscribed to Twitter Blue: There are only about 180,000 subscribers, <a href="https://www.theinformation.com/articles/musks-twitter-has-just-180-000-u-s-subscribers-two-months-after-launch?rc=eh9iin">according to the Information</a>. They bring in roughly $28 million in annual revenue, less than 1 percent of the $3 billion Musk aimed to make in 2022. Now, in an effort to get more people to sign up for Twitter Blue, Musk is essentially threatening to make using the app harder for Twitter users who don’t pay.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="g7g6MF">
Moreover, the fact that Musk is seriously proposing turning your Twitter homepage into a place where you don’t see tweets from the users you care about and only see the people who spent money shows how much he’s willing to compromise the basic utility of the app. He’s pushing an extreme version of an <a href="https://www.vox.com/recode/2023/2/21/23609375/meta-verified-twitter-blue-checkmark-badge-instagram-facebook">increasingly popular “pay-to-play”</a> model for social media, one that goes against some of the basic ideas that made apps like Twitter popular in the first place.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wu8oXH">
Early signs that people are buying into Musk’s vision for social media are not looking good.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zQhwFm">
First of all, the company is already planning major exceptions: Twitter’s top 500 advertisers and 10,000 most-followed organizations keep to their checkmarks for free, according to a <a href="https://www.nytimes.com/2023/03/30/technology/elon-musk-ftc-chair.html">recent report in the New York Times</a>. That eliminates a major pool of potential customers that Twitter may have wisely realized were not going to pay.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Olu52U">
Some of the largest newsrooms in the country, like the New York Times, the Los Angeles Times, and Politico,<em> </em>have said they <a href="https://twitter.com/oliverdarcy/status/1641460482480504832">will not be buying a Twitter Blue verification</a> for their company accounts (a one-year subscription for a company costs $12,000), nor do they intend to subsidize individual reporters’ subscriptions. In its rationale, the LA Times said that “verification no longer establishes authority or credibility.” A few celebrities, like Seinfeld star <a href="https://www.huffpost.com/entry/jason-alexander-twitter_n_6423e024e4b0a10577baa1ae">Jason Alexander</a>, <a href="https://twitter.com/WilliamShatner/status/1640706675295543302">William Shatner</a>, and <a href="https://twitter.com/FINALLEVEL/status/1641173898053009411">Ice-T</a> have recently joined other actors, writers, and comedians who <a href="https://twitter.com/StephenKing/status/1587042605627490304?ref_src=twsrc%5Etfw%7Ctwcamp%5Etweetembed%7Ctwterm%5E1587312517679878144%7Ctwgr%5Edfc9ca59f560b0ca49db06a858a4789a5d4642cf%7Ctwcon%5Es2_&amp;ref_url=https%3A%2F%2Fwww.9news.com.au%2Ftechnology%2Felon-musk-twitter-blue-tick-charge-stephen-king-lynda-carter-and-other-celebrities-threaten-to-leave%2Fb7c2eaae-81a6-41eb-95ae-7fd3fb2f977c">previously threatened</a> to leave if Musk took away their checkmark. If more famous people refuse to buy Twitter verification and subsequently find less value in Twitter, they could leave for other platforms.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hsrxkb">
Meanwhile, Twitter’s <a href="https://www.vox.com/technology/2023/2/16/23603155/elon-musk-twitter-worse-degrading-quality-glitches-superbowl-boost-feed">technical quality has been degrading</a> since Musk took over. Features have been more frequently buggy, the site has had embarrassing outages, and source code <a href="https://www.nytimes.com/2023/03/26/technology/twitter-source-code-leak.html">has been leaked online</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7Ge5L7">
“I think [changes to the For You feed and verification] are only going to expedite that decline and demise of a platform that is really in its death rattle right now,” said social media consultant Matt Navarra.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qSRJgz">
Even though Musk acquired Twitter to democratize it from the hands of elite users, in many ways his actions are doing the opposite.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ycp4or">
A major part of social media’s appeal in the past two decades of its existence is the idea that anyone, from anywhere, at any time, could go viral — for better or worse. And in turn, users see the most compelling, “engagement”-worthy media. Companies like Meta, TikTok, and YouTube are in the business of carefully fine-tuning algorithms that recommend the content they know we’ll want to click, whether that’s cat videos, political debates, or beauty tutorials. A major part of Twitter’s appeal was about seeing random interactions between powerful people and everyday citizens, like someone seeing a tweet from a senator, replying to it, and actually getting a reply back.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="m0YG0l">
If Musk starts making it harder for an average user to stumble on and participate in viral exchanges, he’s taking away from the basic democratic promise of social media.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L2E0S0">
Already, under Musk’s leadership, Twitter has been promoting certain content according to the whims of the company’s new owner. Twitter has recently boosted <a href="https://www.platformer.news/p/yes-elon-musk-created-a-special-system">Musk’s own tweets</a>, and for months it has boosted those of certain people the company designated as VIPs, like LeBron James, Ben Shapiro, and (somewhat surprisingly, since she’s a known foe of Musk) Rep. Alexandria Ocasio Cortez, <a href="https://www.platformer.news/p/the-secret-list-of-twitter-vips-getting">according to recent reports in Platformer</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UxwgLX">
It’s important to note here that there’s a good chance Musk will not go through with this, given his track record of missing deadlines for major changes at Twitter. In the few months since he took over, Musk has promised to share revenue with creators (<a href="https://www.theverge.com/2023/3/3/23623927/twitter-blue-ad-revenue-one-month-missing">hasn’t happened</a>) and <a href="https://bgr.com/tech/elon-musk-says-twitter-will-open-source-its-recommendation-code-on-march-31/">to make Twitter’s recommendation algorithm open source</a> (delayed). He’s <a href="https://www.axios.com/2022/11/09/twitter-official-label-select-verified-accounts">warned</a> for months that Twitter will remove blue checkmarks, but he hasn’t actually done it yet.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GxAWXj">
The chance that Musk changes his mind is even higher considering that his key deadline to rid “elites” of their blue checkmarks is literally on April Fools’ Day.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nhJLoc">
Regardless of whether Musk executes his plans, he is to some extent doing what many social media platforms have often done in private: tinker with secretive algorithms and give special treatment to high-profile users. TikTok was found to be <a href="https://www.theverge.com/2023/1/20/23564242/tiktok-heating-view-boosts-creators-businesses">“heating” certain VIP user content</a>, showing it more in people’s For You feeds. Facebook and Instagram have let <a href="https://www.wsj.com/articles/facebook-files-xcheck-zuckerberg-elite-rules-11631541353">celebrities</a> get away with breaking the company’s policies. The two apps, which are owned by Meta, also recently started charging users for verification and some basic services like access to customer support.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cskwvN">
But even if these companies give certain users benefits over others, they’re doing it within reason. Musk is pushing pay-to-play to the extreme. If he goes too far, celebrities and the everyday users who follow them could leave Twitter in a mass exodus. So far, though, they haven’t. Twitter’s biggest benefit is that there is <a href="https://www.vox.com/recode/2022/12/6/23496363/twitter-mastodon-hive-musk-replacement">no good Twitter alternative</a>. The most viable contender, Mastodon, while popular with some journalists, hasn’t reached nearly the same level of mainstream appeal as Twitter.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2NXykk">
Regardless, if Musk wants Twitter Blue to succeed, he’ll need to get celebrities and everyday people not just to stay on Twitter, but to pay for an $8-a-month subscription service.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xKC898">
We’ll see if his plan to turn Twitter into a for-sale popularity contest will work.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UXYGqb">
<em><strong>Update, March 31, 5 pm ET:</strong></em><em> This story has been updated with new details about celebrities reacting to Twitter’s planned changes.</em>
</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>IPL 2023 | Kolkata Knight Riders elect to bowl against Punjab Kings</strong> - For KKR, Afghanistan player Rahmanullah Gurbaz is making his IPL debut.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2023: SRH vs RR | Up against Hyderabad, Rajasthan keen to recreate last year magic</strong> - Over the years, the Royals have built the reputation of being gritty opponents that do not surrender an inch of their territory.</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>Australian GP 2023 | Verstappen takes pole position for Red Bull, ahead of Mercedes 2-3</strong> - Twice world champion Fernando Alonso will start fourth on the grid ahead of fifth-placed Carlos Sainz</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2023 | ‘Impact player’ rule makes captain’s job tough: Hardik Pandya</strong> - Chennai captain Mahendra Singh Dhoni said the team should have set a bigger target</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2023 | If Ruturaj continues the way he is batting, he will do wonders for Indian cricket: Hardik</strong> - Ruturaj Gaikwad’s classy knock of 92 off just 50 balls took Chennai Super Kings to 178 for 7</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>Paddy farmers disillusioned as Supplyco sets restrictions in procurement</strong> - Paddy procurement from farmers limited to five acres and that too only 2,200 kg paddy per acre, say farmers. Officials say the issues related to procurement will be sorted out.</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>Jails overcrowded, courts should ensure that trials are taken up and concluded speedily: SC</strong> - A bench of Justices S. Ravindra Bhat and Dipankar Datta made the observation while enlarging a man accused under the Narcotic Drugs and Psychotropic Substances Act on bail</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>Andhra Pradesh: Technological changes will provide many opportunities for students, says VSP General Manager</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PM Modi flags off Bhopal-Delhi Vande Bharat train</strong> - The Vande Bharat Express will run between Rani Kamlapati and Hazrat Nizamuddin</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>Raja Singh booked for ‘hate speech’ in Ram Navami Shobha Yatra</strong> - Police book a case based on videos of clash between two groups near Charminar that were shared on social media</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>Russia assumes UN Security Council presidency despite Ukrainian anger</strong> - Ukraine’s foreign minister said Russia leading the UN Security Council is “the worst joke ever”.</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>‘I’m still alive’ jokes Pope as he leaves hospital</strong> - The 86-year-old was admitted to Gemelli Hospital in Rome on Wednesday with breathing difficulties.</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>Andrew Tate and Tristan Tate moved to house arrest</strong> - The Tates and two associates are moved to house arrest following a ruling by a Romanian judge.</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>ChatGPT banned in Italy over privacy concerns</strong> - The country’s data-protection regulator has serious privacy concerns over the technology.</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>King Charles at Hamburg memorial for Allied wartime air raids</strong> - King Charles laid a wreath remembering those who died in Allied wartime bombing raids on Hamburg.</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>Nvidia’s GameStream is dead. Sunshine and Moonlight are great replacements.</strong> - What started as a hackathon project is now a full-fledged streaming platform. - <a href="https://arstechnica.com/?p=1906410">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>As glaciers retreat, new streams for salmon</strong> - Insects move in, alders and willows spring up, and spawning fish arrive in thousands. - <a href="https://arstechnica.com/?p=1928383">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hackers exploit WordPress plugin flaw that gives full control of millions of sites</strong> - Elementor Pro fixed the vulnerability, but not everyone has installed the patch. - <a href="https://arstechnica.com/?p=1928488">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Twitter posts the code it claims determines which tweets people see, and why</strong> - Posted algorithm code includes “is_democrat,” “is_republican,” and “is_elon.” - <a href="https://arstechnica.com/?p=1928420">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>GM kills more than CarPlay support, it kills choice</strong> - The software-driven vehicle is supposed to be a place of choice. - <a href="https://arstechnica.com/?p=1928486">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What word means the same thing with several letters added?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Mailbox
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/geminirich"> /u/geminirich </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/128c57k/what_word_means_the_same_thing_with_several/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/128c57k/what_word_means_the_same_thing_with_several/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Whenever I get a stack of resumes on my desk at work, I always pick half at random and throw them out</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Don’t need unlucky people working in my department.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/EvilChefReturns"> /u/EvilChefReturns </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/127v8oe/whenever_i_get_a_stack_of_resumes_on_my_desk_at/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/127v8oe/whenever_i_get_a_stack_of_resumes_on_my_desk_at/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why should you never brush your teeth with your left hand?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Because a toothbrush works better.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Stationary-Event"> /u/Stationary-Event </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/128874h/why_should_you_never_brush_your_teeth_with_your/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/128874h/why_should_you_never_brush_your_teeth_with_your/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Doctor: I’m sorry, but I had to remove your colon.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Me Why?
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/madazzahatter"> /u/madazzahatter </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/128hxf0/doctor_im_sorry_but_i_had_to_remove_your_colon/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/128hxf0/doctor_im_sorry_but_i_had_to_remove_your_colon/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My doctor told me that I had a healthy prostate.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I was deeply touched.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/1963Jan"> /u/1963Jan </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/127ly3k/my_doctor_told_me_that_i_had_a_healthy_prostate/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/127ly3k/my_doctor_told_me_that_i_had_a_healthy_prostate/">[comments]</a></span></p></li>
</ul>
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