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<title>03 April, 2023</title>
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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>Rethinking Remdesivir for COVID-19: A Bayesian Reanalysis of Trial Findings</strong> -
<div>
Background: Following testing in clinical trials, the use of remdesivir for treatment of COVID-19 has been authorized for use in parts of the world, including the USA and Europe. Early authorizations were largely based on results from two clinical trials. A third study published by Wang et al. was underpowered and deemed inconclusive. Although regulators have shown an interest in interpreting the Wang et al. study, under a frequentist framework it is difficult to determine if the non-significant finding was caused by a lack of power or by the absence of an effect. Bayesian hypothesis testing does allow for quantification of evidence in favor of the absence of an effect. Findings: Results of our Bayesian reanalysis of the three trials show ambiguous evidence for the primary outcome of clinical improvement and moderate evidence against the secondary outcome of decreased mortality rate. Additional analyses of three studies published after initial marketing approval support these findings. Conclusions: We recommend that regulatory bodies take all available evidence into account for endorsement decisions. A Bayesian approach can be beneficial, in particular in case of statistically non-significant results. This is especially pressing when limited clinical efficacy data is available.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/metaarxiv/2kam7/" target="_blank">Rethinking Remdesivir for COVID-19: A Bayesian Reanalysis of Trial Findings</a>
</div></li>
<li><strong>A high-throughput multiplex array for antigen-specific serology with automated analysis.</strong> -
<div>
The utility of high-throughput systems to evaluate antigen-specific Ab has been highlighted by the SARS-CoV-2 pandemic. Pathogen specific antibody levels are often used to assess protection following vaccination and, in the case of novel pathogens, an indication of prior exposure. Several platforms exist to visualize antigen-specific Ab, however most are not quantitative and difficult to scale for population levels studies. Additionally, the sensitivity across platforms differs making direct comparisons between studies difficult. Cytometric Bead Arrays are an attractive platform for antigen-specific Ab measurements as they allow antibodies reactive against several antigens and of several isotypes to be performed simultaneously. Additionally, cytometric arrays exhibit a high sensitivity and can be designed to provide quantitative measurements. Using commercially available particles, a biotin-Streptavidin loading strategy, and the inclusion of indirect standards, we describe here a flexible system that can be modified to include a variety of antigens. We generated two arrays, one focused on b-Coronavirus antigens and one focused on Influenza. To support the high throughput capacity of this system, we developed a suit of automated tools to process raw data into antigen-reactive IgM, IgA, and IgG. We describe quality control requirements, assay performance, and normalizations to accurately quantitate antigen specific Ig.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.29.534777v1" target="_blank">A high-throughput multiplex array for antigen-specific serology with automated analysis.</a>
</div></li>
<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>
</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>CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury</strong> - In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers…</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 synergistic effect of Cu-MOF nanoparticles and immunomodulatory agent on SARS-CoV-2 inhibition</strong> - In this work, HKUST-1 and Cu-BDC nanoparticles were used as delivery systems for the early anti-COVID-19 drug, hydroxychloroquine. The antiviral MOF/drug combinations significantly reduced the infectivity of SARS-CoV-2, which can be attributed to the nanometric size of the carriers, the presence of copper in the MOF nodes, and the semi-controlled release of the drug.</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>G4-binding drugs, chlorpromazine and prochlorperazine, repurposed against COVID-19 infection in hamsters</strong> - The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants underline the need for novel and widely accessible therapeutics. G-quadruplexes (G4s) are nucleic acid secondary structures known to affect many cellular processes including viral replication and transcription. We identified heretofore not reported G4s with remarkably low mutation frequency across &gt;5 million SARS-CoV-2 genomes. The G4…</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>Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice</strong> - The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) variants has been associated with the transmission and pathogenicity of COVID-19. Therefore, exploring the optimal immunisation strategy to improve the broad-spectrum cross-protection ability of COVID-19 vaccines is of great significance. Herein, we assessed different heterologous prime-boost strategies with chimpanzee adenovirus vector-based COVID-19 vaccines plus Wuhan-Hu-1 (WH-1) strain (AdW)…</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>Channel activity of SARS-CoV-2 viroporin ORF3a inhibited by adamantanes and phenolic plant metabolites</strong> - SARS-CoV-2 has been responsible for the major worldwide pandemic of COVID-19. Despite the enormous success of vaccination campaigns, virus infections are still prevalent and effective antiviral therapies are urgently needed. Viroporins are essential for virus replication and release, and are thus promising therapeutic targets. Here, we studied the expression and function of recombinant ORF3a viroporin of SARS-CoV-2 using a combination of cell viability assays and patch-clamp electrophysiology….</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 Famotidine on COVID-19: Killing Virus or Opposing ARDS?</strong> - Since the first detection of SARS-CoV-2 in China, COVID-19 (Corona Virus Disease 2019) has taken the lives of more than six million people. Although some antivirals seem proper for treatment, the investigation of finding the best therapeutic approach for COVID-19 is still continuing. Some observational research showed that famotidine has promising effects in addition to its acid-suppressing characteristics in the treatment of COVID-19. The definite viricidal effect of famotidine is not…</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 inhibitory and inducing effects of ritonavir on hepatic and intestinal CYP3A and other drug-handling proteins</strong> - Ritonavir, originally developed as HIV protease inhibitor, is widely used as a booster in several HIV pharmacotherapy regimens and more recently in Covid-19 treatment (e.g., Paxlovid). Its boosting capacity is due to the highly potent irreversible inhibition of the cytochrome P450 (CYP) 3 A enzyme, thereby enhancing the plasma exposure to coadministered drugs metabolized by CYP3A. Typically used booster doses of ritonavir are 100-200 mg once or twice daily. This review aims to address several…</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>Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022</strong> - CONCLUSIONS: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent 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>Potential medicinal plants to combat viral infections: A way forward to environmental biotechnology</strong> - The viral diseases encouraged scientific community to evaluate the natural antiviral bioactive components rather than protease inhibitors, harmful organic molecules or nucleic acid analogues. For this purpose, medicinal plants have been gaining tremendous importance in the field of attenuating the various kinds of infectious and non-infectious diseases. Most of the commonly used medicines contains the bioactive components/phytoconstituents that are generally extracted from medicinal plants….</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>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 pH 7.4 and pH 8.5. 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…</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>
</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>Paul Vallas’s Cops-and-Crime Campaign to Run Chicago</strong> - In a recent poll, nearly two-thirds of the city’s residents reported feeling unsafe. The mayoral runoff presents two starkly different visions for how to move forward. - <a href="https://www.newyorker.com/news/the-political-scene/paul-vallas-brandon-johnson-chicago-mayoral-runoff">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>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Why fear of crime more than crime itself is holding back America’s downtowns</strong> -
<figure>
<img alt="Police officers standing in front of police cars and behind caution tape." src="https://cdn.vox-cdn.com/thumbor/SLoIIWeeUVdOxCIlXyosnBwR3ls=/0x0:4369x3277/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72142063/GettyImages_1419978920.0.jpg"/>
<figcaption>
Police gather at the scene of a shooting in Alphabet City in lower Manhattan on September 1, 2022, in New York City | Spencer Platt/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
People are scared of urban centers. They shouldn’t be.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0w0DDn">
Three years after the start of the Covid-19 pandemic emptied them, America’s downtowns are still hurting. White-collar workers are only back in their offices <a href="https://www.kastle.com/safety-wellness/getting-america-back-to-work/">about half the time</a> — and far less on Monday or Friday. Many businesses that service those workers <a href="https://www.washingtonpost.com/dc-md-va/2022/05/24/dc-businesses-downtown-pandemic-suburbs/">have closed up shop</a>. Between 2019 and 2022, office rents in Manhattan fell about 14 percent, <a href="https://www.axios.com/2023/03/22/remote-work-wf-office-rents-decline">according to recent reporting from Axios.</a> In San Francisco, office rents are down by more than twice that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XKNtuZ">
There’s an obvious explanation for this crisis: Many white-collar workers simply no longer need to commute to their offices, assuming their company even <a href="https://www.bloomberg.com/graphics/2022-remote-work-is-killing-manhattan-commercial-real-estate-market/">still leases one</a>. But there is another major factor that doesn’t get nearly as much recognition: crime.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CWwswy">
“The No. 1 barrier that we heard from people was that fear of crime was what was preventing them from going downtown, particularly within the central business district itself and on their commutes there,” said Hanna Love, senior research associate at the think tank Brookings Institution.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U5VG8y">
Love is working with a team at Brookings that is studying the health and future of American downtowns. She shared their <a href="https://www.brookings.edu/research/the-geography-of-crime-in-four-u-s-cities-perceptions-and-reality/">findings</a> with <a href="https://www.vox.com/today-explained-podcast"><em>Today, Explained</em></a>, Vox’s daily news radio show and podcast, for its new series on the future of cities post-pandemic: “<a href="https://podcasts.apple.com/us/podcast/city-limits-beware-the-doom-loop/id1346207297?i=1000604682913">City Limits</a>.” (I’m a producer and reporter for <em>Today, Explained</em> and the lead producer on this series.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RR9kWs">
Anyone paying attention to big-city politics right now is probably aware of the salience of crime as an issue. Paul Vallas, one of two candidates in Chicago’s early April mayoral runoff, is running an unabashed <a href="https://chicago.suntimes.com/city-hall/2022/12/12/23505791/paul-vallas-public-safety-plan-chicago-police-department-mayoral-candidate">law-and-order campaign</a> in a city where car thefts doubled between <a href="https://www.wbez.org/stories/chicago-sees-fewer-shootings-in-2022-but-still-feels-unsafe/6a14e601-f5dc-4aad-8027-f39a6fac8d87">2021 and last year</a>. In Philadelphia, <a href="https://www.everyvoice-everyvote.org/WhatPhillyWants">89 percent of respondents to a recent survey</a> ahead of that city’s mayoral election in November said “crime” should be the top priority for elected officials. And in Washington, DC, President Joe Biden recently abandoned his commitment to DC home rule by refusing to veto a Republican measure to <a href="https://www.vox.com/today-explained-podcast/2023/3/11/23634087/dc-crime-bill-congress-overrule-biden-no-veto">block the city’s proposed updated criminal code over concerns that it was soft on crime</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gVClbk">
“Things can happen anywhere, anytime,” Allison McDonald, a Chicagoan who lives just outside of downtown, told a <em>Today, Explained</em> freelance producer. “[It] used to feel more pocketed … you kind of knew where to stay away. Now it just happens anywhere, any time of the day. The carjackings. The street crime. It’s just way worse.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G3Fnyl">
Except here’s the thing: While crime has risen since the pandemic in most US cities, it’s not spiking in downtowns.
</p>
<h3 id="GlmQYU">
Tl;dr: Crime is up, but not up much downtown
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1ryQFO">
That’s what Love and her colleagues found when they crunched the data. She and her team have spent the last few months collecting statistics and conducting about 100 interviews with office workers, small business owners, and other folks in New York, Philadelphia, Seattle, and Chicago — four cities <a href="https://downtownrecovery.com/dashboards/recovery_ranking.html">where the downtown business districts have been slow to recover</a>. They then broke out data for violent crime and property crime for each of those cities’ downtowns.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iuINJg">
Homicides spiked nationwide in the early part of the pandemic, before leveling off and then declining slightly between 2021 and 2022. Violent crime more broadly — a category that includes rape and aggravated assault — trended up in each city between 2019 and 2022, to varying degrees. Chicago saw a 5 percent increase in violent crime during that time, Philadelphia saw a 1 percent increase, New York saw a 26 percent increase, and Seattle saw a 22 percent increase.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AxTx69">
Property crime — a category that includes offenses like larceny and car break-ins — saw a sharper uptick in all four cities. Philadelphia saw city-wide property crime increase by 17 percent, New York 38 percent, Seattle 17 percent, and Chicago 36 percent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2cUtGx">
But here’s the twist: in all four of those cities, the share of all property crimes happening downtown remained relatively stable or declined.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oztevf">
Violent crime downtown also stayed relatively stable, declining by 2 percent in Seattle, ticking up by 1 percent in Chicago and Philadelphia, and by 2 percent in New York City.
</p>
<figure class="e-image">
<img alt="Chart of violent crime" src="https://cdn.vox-cdn.com/thumbor/Vn7A2pWLbQ9KOhnERA0FlYYv240=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24548237/Brookings_figure_4.png"/> <cite>Courtesy of Brookings Institution</cite>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bdDTqw">
So downtowns were some of the safest places to be in these cities pre-pandemic. And, by the end of last year, they still were. That fact, though, makes small upticks in crime numbers more perceptible, Love said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yAgS65">
“People aren’t necessarily thinking about citywide statistics when they’re thinking about how they want to feel safe,” Love told <em>Today, Explained</em> co-host Sean Rameswaram. “People are hearing about people getting shot. People are talking to their friends … there is this mismatch in perceptions and reality, but it still matters because people are still afraid.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="78Xilb">
Violent crime has long been <a href="https://ajph.aphapublications.org/doi/10.2105/AJPH.2021.306540">concentrated in low-income Black and Latino neighborhoods</a> that have also been marked by segregation, discrimination, and disinvestment. But crimes in those areas, Love said, tend to get less media attention than those that occur downtown.
</p>
<h3 id="bBYZ3K">
Conflating crime and “disorder”
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rATclT">
What else could be behind the mismatch between crime data<em> </em>and crime vibes<em>? </em>One theory that came up again and again is that city residents and visitors are, to some extent, conflating actual violent crime with broader indications of urban disorder.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DwUCI8">
“There are several visible signs of disorder that are not necessarily related to crime that are causing people to feel that cities have become unsafe,” Henry Grabar, an urban affairs reporter at Slate, told Rameswaram. “I’m thinking of things like homelessness, drug use, empty streets, and lack of people … that’s causing them to think that cities have become more dangerous places than perhaps they are.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mOYKC2">
Homelessness is a good example. In New York, Chicago, and Philly, according to data analyzed by the Brookings team, the homeless population actually fell by more than 20 percent between 2019 and 2022. Seattle was the outlier: King County, which contains Seattle, saw its homeless population grow by 19 percent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dRazxV">
But despite the fact that the homeless population fell by quite a bit in most of those cities during the pandemic, the vast majority of interviewees Brookings spoke to believed the number of homeless people in their city had spiked and that the unhoused were contributing to the crime problem.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FxTn32">
“Across the board, the visibility of unsheltered homelessness has increased in downtowns because there’s less street activity. So people are seeing or noticing more unsheltered people and they are feeling unsafe because of that,” Love said. “That doesn’t necessarily line up with what the statistics tell us, which is that people who are experiencing homelessness are more likely to be victims of crime than to perpetrate them.”
</p>
<h3 id="uuqDBp">
Tackling the perception of crime downtown
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KknvaJ">
So what can a mayor or other elected official do to make people feel as safe as they actually are downtown?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rHfYyP">
Tackling this perception was the explicit goal of “Broken Windows”-style policing. The strategy, laid out in a <a href="https://www.theatlantic.com/magazine/archive/1982/03/broken-windows/304465/">1982 Atlantic essay</a> and adopted most prominently by New York City in the 1990s, argued that police should aggressively enforce low-level offenses like public urination and graffiti, both because that <a href="https://slate.com/business/2023/03/rising-crime-broken-windows-policing-revisited.html">type of crime makes people afraid</a> and because it creates a sense of impunity where more serious crime can flourish.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KMfP0f">
Broken Windows may have made some people feel safer, but, through its cornerstone policy of stop-and-frisk, it also led to countless Black and Latino city residents being targeted by police in dehumanizing and legally dubious stops. In Philadelphia in 2009, police made more than 260,000 stops, more than any other police department in the country, <a href="https://www.krlawphila.com/10-years-later-an-update-on-the-bailey-litigation/">according to an American Civil Liberties Union report</a>. Close to half of those stops were made without showing any reasonable suspicion.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7vPtDD">
And the actual impact of the Broken Windows policy on crime is still <a href="https://www.vox.com/2015/1/13/7536797/nypd-slowdown-arrests">debated</a>. Serious <a href="https://www.washingtonpost.com/nation/2020/02/27/bloomberg-said-stop-frisk-decreased-crime-data-suggests-it-wasnt-major-factor-cutting-felonies/">crimes fell in New York City throughout the 2000s</a> — and kept falling after NYC’s stop-and-frisk policy was declared unconstitutional in 2013.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="66DlAl">
Grabar argues that the best way to address the perception problem is to get more bodies back into downtown on a regular basis. It’s a notion first articulated as “<a href="https://slate.com/business/2023/03/rising-crime-broken-windows-policing-revisited.html">Eyes on the Street”</a> by the famous urbanist Jane Jacobs: the idea being that healthy communities naturally enforce shared social norms. But that requires numbers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CDYzL1">
And therein lies the problem. People don’t want to go downtown because they’re worried. But the best way to make people feel safe again downtown … is to have more people there. The best way to square that circle, Grabar suggests, is that downtowns should try and attract residents instead. That means converting offices to residences and building new housing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="flkQrz">
City leaders in <a href="https://www.nyc.gov/office-of-the-mayor/news/907-22/mayor-adams-governor-hochul-release-making-new-york-work-everyone-action-plan#/0">New York </a>and <a href="https://chicago.suntimes.com/city-hall/2023/1/12/23552497/lasalle-street-residential-housing-grants-approved-city-council-finance-committee">Chicago</a> are on board: They’re pushing plans to encourage office-to-residential conversion. And in Seattle, the planning department <a href="https://www.seattle.gov/opcd/office-to-residential/requirements">is offering a $10,000 prize</a> to teams of property owners and designers that submit plans to convert downtown office buildings to residences.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9JUGI3">
“I don’t think I’m telling city leaders anything they don’t know. It’s just that I don’t think they quite grasp the urgency of it, because if you don’t get people downtown, if you don’t make those streets feel full and lively and vibrant again, then people will leave and they will stop coming,” Grabar said. “And then you get this sort of doom loop of empty streets and a feeling of insecurity and disinvestment in public services and so on. So adding housing downtown is a big way of bringing people back and making the streets feel safe.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5Zga5h">
The renaissance in American cities that began in the 1990s and lasted up until the pandemic arrived depended on bringing crime down and making people feel safer. The challenge for city leaders in this remote-work era is to once again find success on both of these fronts, but without resorting to the punitive tactics of their forebears.
</p></li>
<li><strong>Why all your friends are sending you voice notes</strong> -
<figure>
<img alt="A person holds a phone in front of them and speaks into it. A messaging app is seen on the screen." src="https://cdn.vox-cdn.com/thumbor/BKGgSvQkYybYV06WuwZoneb6Xik=/267x0:4608x3256/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72141978/GettyImages_1038822404.0.jpg"/>
<figcaption>
Voice notes — or voice messages — are growing in popularity with some users. | Lino Mirgeler/picture alliance via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Phone call? Lol. Voice note? Sure.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3RA032">
In a world where we’re <a href="https://www.bbc.com/worklife/article/20210129-how-texting-makes-stress-worse">overloaded</a> with texts, <a href="https://www.thecut.com/article/psychologists-explain-your-phone-anxiety.html">anxiety-ridden</a> about phone calls, and <a href="https://www.psychiatrictimes.com/view/psychological-exploration-zoom-fatigue">fatigued</a> by video chats, many people are turning to another form of communication: voice messages.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vCRARY">
Voice messages, sometimes called “voice notes” or “voice texts,” are short audio recordings people send to each other (not to be confused with voicemail) and a built-in feature in popular messaging apps like WhatsApp, iMessage, and Telegram.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RzBuOT">
Maybe you’ve noticed: Lately, they’re popping up in more group chats and one-on-one conversations. 62 percent of Americans say they’ve sent a voice message, and around 30 percent communicate this way weekly, daily, or multiple times a day, according to a random sample poll of 1,000 US adults by YouGov run for Vox. Younger people are using voice messaging even more, with some 43 percent of 18- to 29-year-olds who responded to the survey saying that they use the feature at least weekly. WhatsApp said last year that over <a href="https://blog.whatsapp.com/making-voice-messages-better">7 billion voice messages </a>are sent on the app every day. Some are even communicating more with voice messages than texts, according to WhatsApp’s head of consumer product, Zafir Khan.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FniKVN">
“I use voice messages every single day,” Kennedy Dierks, a 21-year-old student at Seton Hall University in New Jersey, told me. “I find it to be a lot more personal than a text.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="41EUeT">
Dierks said voice messages have exploded in popularity on her college campus in the past year. As an example, she said she recently used the feature to give a friend the rundown about a date she’d just gone on, because it was easier to “hash it out” than via text. More broadly, voice memos are popular because they allow people to share the richness that comes with voice communication, like tone, mood, and humor — without the pressure of inconveniencing someone with a phone call.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OrASbH">
“It gives me anxiety to think I’m going to catch someone at a bad time with a call,” said Hannah Ayla, a 30-year-old graphic designer in Tampa, Florida, who says voice messages “saved her relationships” when she was dealing with chronic pain in her arm and unable to text.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3TDdoa">
There are downsides to voice messages, though. They can be tedious to listen to if they’re too long or rambling, which can happen a lot. And it’s hard to discreetly send a voice note if you’re in a meeting or at work.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yz79Qp">
“I respect the fact that most people are like, ‘I don’t want to have to stop and listen to you talk for three minutes or whatever. I just want to have a back-and-forth conversation,’” said social media consultant Matt Navarra, who is a power user of WhatsApp voice messages. “It can be quite annoying that you are monopolizing their time.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vixruU">
In my experience, I use voice notes to keep in touch with friends who live overseas in vastly different time zones. With voice messages, I can give them meaningful updates about what’s new in my life without overwhelming them with multiple-paragraph-long texts. I find it to be a more thoughtful form of communication. Although it can take longer for me to listen to a two-minute audio clip than skim through a text, with audio messages there’s less pressure to respond right away, allowing me to really listen to what my friends are saying and respond when I have time to share a deep response.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ujmnnS">
Voice messages give us some of the emotional depth and nuance that’s missing from bite-size texts that compress our feelings. The fact that people are embracing a relatively new, more expressive messaging format for talking to each other may reflect a deeper phenomenon: our desire to strengthen relationships as the horrors of the pandemic gradually recede and we emerge from a period of <a href="https://www.vox.com/2020/3/12/21173938/coronavirus-covid-19-social-distancing-elderly-epidemic-isolation-quarantine">social isolation</a> and <a href="https://today.yougov.com/topics/society/articles-reports/2021/04/01/yougov-personality-study-2021">loneliness</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N8fJj5">
I spoke with several avid voice message users, and dug into the research behind voice versus text communication, to better understand why people are embracing voice messages and how they’re shaping our relationships.
</p>
<h3 id="6iKxH8">
The science of voice messaging
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SD96EQ">
There’s scientific rationale for why people prefer voice messages to texts in some situations: We can understand each other better when we actually listen.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CwCFzo">
Research has shown that by hearing someone’s voice, even for a matter of seconds, people can pick up on what’s called “paralinguistic cues,” which we don’t have over text. Those cues — like someone speaking a little more loudly when they’re excited — help people convey their intended message, especially when it comes to communicating complex emotions like sarcasm or humor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9w5292">
Even though paralinguistic cues can be subtle, they’re “humanizing” reminders that whoever you’re listening to “is a thoughtful, feeling person,” said Juliana Schroeder, a professor at UC Berkeley’s Haas School of Business.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OTFlAs">
Schroeder’s research has shown that not only are people more likely to have “empathic accuracy,” or a better understanding of the mental state a person is in when they hear instead of read what they’re saying, but they seem to find the person more sharp and relatable, too. When people listen to someone speak rather than read their writing, they perceive them as more “mentally capable” — meaning reasonable, emotional, and likable — Schroeder’s <a href="http://faculty.haas.berkeley.edu/jschroeder/Publications/SchroederKardasEpley%20Humanizing%20Voice%20Psych%20Science.pdf">study found</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3Mogx5">
In one experiment, people with liberal views who were exposed to a person espousing conservative political views had a less negative perception of the communicator when they listened to them talking, compared to when they read a transcript of the exact same audio.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="634INa">
On a more personal level, the research findings match what I’ve been hearing about why people like voice messages. Several people told me that they use voice messages to express complex feelings that can become muddled over text: like checking in with someone who you’re worried may be upset with you, or, conversely, showing someone that you’re actually not upset (we’ve all panicked over receiving an inscrutable “k” or “that’s fine” text). In essence, voice messages can help clarify miscommunications.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h7LSyU">
“Sometimes in friendships, there’s a compulsion to apologize for something the other person might not even be bothered by,” said Ashley Alderton, who lives in the San Francisco Bay Area and uses voice texts a lot. “If you’re trying to reassure somebody, it’s so much easier to do that with your voice because you can show warmth.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IoCz9z">
More than just warmth, there’s a sense of authenticity with voice messages that’s harder to achieve with text.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="m66Xik">
For example, Ayla said that when she had to cancel last minute on a date due to suddenly getting booked for surgery, she sent a voice note instead of a text.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xlv91N">
If she texted him, “it would sound really fake,” she said. It’s a good thing she didn’t, Ayla said, because her date (who is now her boyfriend), said he probably wouldn’t have believed her if he didn’t hear her explain the situation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ONdKck">
There’s another big reason some people are more personal in audio messages than in texts: It feels more private. On iMessage, audio messages disappear by default after two minutes, giving them an ephemeral nature. Of course, if someone wanted to, they could save the audio and send it around — so that feeling of privacy may be a false sense of security — but it’s still why some people said they felt more comfortable sharing personal details via voice message.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BD9TbI">
Adding to the more unfiltered vibe of audio messages is the fact that many people send them right away without second-guessing what they’re saying. On both WhatsApp and iMessage, by default, voice messages are sent instantaneously. While both apps give you the option to listen to your message before sending and rerecord if you want, it’s a lot easier to just send one off without thinking about it — a harder task to do with texts.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ElQx90">
“I just lift my finger and let go,” said Ayla, explaining the simple push-and-record mechanism for sending an audio message. “If I re-listened, I would never send one.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dKGi7R">
Many people who send voice notes said they did so because it simply takes less effort than crafting a text, especially for more off-the-cuff conversations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7IKtTH">
“If I’m talking about something that’s really stupid, like if we’re talking about reality TV drama or just some sort of silly story, that would take way more time to write out than it would to rattle on,” Alderton told me.
</p>
<h3 id="Ey9ltp">
An international equalizer
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="euzHEl">
While voice messages seem to be catching on more now in the US, they have long been popular internationally, particularly on WhatsApp, which has had the feature since 2013.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1euUoW">
Voice messages are “an equalizer because not every language is easy to type,” said WhatsApp’s Khan, who uses the feature to keep in touch with relatives in Pakistan whom he can speak with — but not read and write to — in Urdu. In the YouGov poll of 1,000 American users, about 13 percent said they use voice messaging specifically to overcome language barriers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7GidTi">
Voice messaging is also more popular in some parts of the world than others because “in some cultures, people seem to naturally gravitate toward voice,” said Khan. It’s particularly popular, for example, with WhatsApp users in Latin America and West Africa.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j0giij">
Gloria Felicia, a 27-year-old San Francisco-based tech entrepreneur and startup adviser for Spero Studios, said that with her family in Indonesia, voice messages aren’t as common.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AXcQH2">
“It’s almost rude for them to send voice messages,” said Felicia. “But in China, I know for a lot of my friends, voice messaging is an everyday thing. … Even in a personal relationship, like a boyfriend-girlfriend situation, I know people who almost never text each other. They just reply to each other’s voice notes throughout the day.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mD3G8C">
Part of voice messages’ international appeal may be because it’s been a core feature of WhatsApp, which historically has had a much bigger user base outside the US (although recently, it’s been growing the <a href="https://www.fool.com/investing/2022/11/26/the-next-major-pillar-for-meta-isnt-the-metaverse/">fastest in North America</a>). The Meta-owned app is the most popular messaging app in countries like India and Brazil.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZZ9hdu">
In many countries, “it’s not uncommon for us to see some users who communicate primarily with voice messages even more than text,” Khan said. “We want to be an app that’s flexible enough to allow people to communicate in a way that works best for them.”
</p>
<h3 id="o23W25">
Just a fad or a meaningful shift?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4N9pUt">
It’s clear why people like voice messages. But are they actually improving our relationships in a meaningful way? And will they come and go as other fads in audio have (remember <a href="https://www.vox.com/the-goods/22276715/clubhouse-invite-only-audio-app-explained">Clubhouse</a>)?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eZgb5T">
Several studies have shown that people feel more socially bonded when communicating via phone call rather than text-based communication. We don’t know whether those findings hold to voice messages, which, unlike phone calls, are “asynchronous,” meaning that you aren’t talking to the other person at the same time, according to Amit Kumar, a professor of marketing and psychology at UT Austin who <a href="https://news.utexas.edu/2020/09/11/phone-calls-create-stronger-bonds-than-text-based-communications/">conducted research</a> on the topic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pKoVIA">
When I video-called Kumar recently, he explained the upsides: “As we’re having this conversation, I see you nodding when I’m saying things, and you can interject with questions … and I can respond in real time.” The back-and-forth creates social bonding in phone and video calls, but that bonding may not be as strong with voice messages.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="axP5w9">
They can also be less convenient than texting because it takes longer to listen to them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="J7wKBu">
That’s why voice notes aren’t for everyone. Navarra said that some people don’t want to be bothered by listening to voice notes, which he says have much more benefits for the sender than the receiver.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0dUer4">
“It’s quite a self-serving communication style,” he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ICRgTq">
WhatsApp’s Khan acknowledged that voice messages can be “more cumbersome to listen to than text” and said that’s why the app rolled out features to help make voice messages more convenient for people who don’t have the time to listen, like faster playback speeds. The company is also testing auto transcription for voice messages — which could help people take in voice messages more quickly but also would take away some of their personal appeal.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JIfRB3">
Even with these features designed for convenience, voice messages can still be more time-consuming (at least for the receiver) than texting, and don’t have the same benefits of “synchronous” communication like a phone call or in-person chat, researchers say.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qH5WLt">
“I find it curious that people would choose to use this technology,” said Jeffrey Hall, a professor of communication studies at the University of Kansas, “because in some ways it introduces inefficiencies of communication.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ann66B">
But with voice messages, the trade-off is part of the point. Voice messages will never replace the efficiency of a text or the real-time connection of a phone call. Voice messages are a compromise between those two mediums.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JefTHP">
At a time when there are seemingly endless ways to communicate, it’s meaningful that people are choosing voice messages at all. It suggests that people — especially young people — are taking more ownership of their daily communication habits. They’re not just defaulting to texts, calls, or video chats, but instead experimenting with new ways to talk that feel more natural to them. For that reason, my bet is voice messages are here to stay — even if that means it’ll become more normal to spend 15 minutes listening to voice notes detailing my friends’ disastrous first dates.
</p></li>
<li><strong>What if the government had decent customer service?</strong> -
<figure>
<img alt="A woman at a table under a sign that reads “Employment Center” sits and fills out a form with her head in one hand." src="https://cdn.vox-cdn.com/thumbor/GsjbSYLcsxoZIlTUqUU9cpW29b4=/167x0:2596x1822/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72141918/85281529.0.jpg"/>
<figcaption>
A woman applies for food stamps at the Yolo County Department of Employment &amp; Social Services in West Sacramento, California. | Justin Sullivan/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A new experiment suggests that “navigators” could make accessing government services much easier.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uMICyd">
When one thinks about America’s housing system, the phrase “easy to use” does not ordinarily come to mind. Buying a house or even just leasing an apartment usually requires thousands in upfront costs, application fees, credit checks, and more. And if you’re applying for affordable housing, the situation is worse. Cities often make applicants jump through ridiculous hoops to even apply for a scarce number of affordable units. In Washington, DC, <a href="https://twitter.com/MaxGhenis/status/1633192505612148741">applicants have to complete an orientation course</a> and then manually enter individual lotteries for each home they’re applying for.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xMVGyB">
Recipients of housing choice vouchers (better known as <a href="https://www.cbpp.org/research/housing/the-housing-choice-voucher-program">“Section 8” vouchers</a> after the portion of a 1937 federal law authorizing them) have it worst of all. Not only do landlords often discriminate against them, but local housing authorities are underfunded and, once on a waitlist, <a href="https://www.cbpp.org/research/housing/families-wait-years-for-housing-vouchers-due-to-inadequate-funding">applicants wait years on average to actually get a voucher</a>. Many housing authorities have <a href="https://nlihc.org/sites/default/files/HousingSpotlight_6-1_int.pdf">closed their waitlists</a>, so if you suddenly hit hard times and need assistance, you’re out of luck. You literally cannot apply.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yd719P">
But a collaboration between a team of social scientists and two housing authorities in Seattle suggests things don’t have to be this bleak. The program, called <a href="https://www.povertyactionlab.org/page/creating-moves-opportunity">Creating Moves to Opportunity</a> (CMTO), seeks to help Section 8 recipients in the Seattle area find housing in areas where children grow up to make high incomes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WmwMII">
Some of these researchers had <a href="https://opportunityinsights.org/paper/the-opportunity-atlas/">earlier found</a> that opportunity (measured as the share of poor kids who wind up in a higher income bracket as adults) varied widely not just from city to city, but from city block to city block. Their hope was to direct recipients to the blocks whose children have historically prospered as adults.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G07Ro3">
The first results from the initiative came out in 2019 — you can read a <a href="https://www.vox.com/future-perfect/2019/8/4/20726427/raj-chetty-segregation-moving-opportunity-seattle-experiment">story I wrote about it then</a>. Results were promising: The program dramatically increased the share of voucher recipients who moved to high-opportunity neighborhoods. Now, the <a href="https://opportunityinsights.org/wp-content/uploads/2019/08/cmto_paper.pdf">researchers have come out with new results</a>, and with several years of data, they not only confirm that the program spurs moves to high-opportunity zones, but they explain why it works.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2NP4SD">
The short answer: navigators. CMTO did not simply give voucher recipients information about high-opportunity neighborhoods and then leave them to their own devices. It paired them with “housing navigators,” professional administrators who could help them navigate applying for units and talk to landlords to help leases go through. The help made an enormous difference — for the most recent paper, the researchers experimented with giving some applicants only information and others a fuller package. The group without help was much less likely to move to a high-opportunity neighborhood.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mfh6UA">
Raj Chetty, William A. Ackman professor of economics at Harvard and one of the researchers driving this project, told me that standard economic theory wouldn’t predict navigators making this much of a difference. It makes sense that simply getting information would change people’s behaviors, but it’s less clear why having a guide would. Standard economic models assume people act rationally given the information they have, and it seems like learning that a certain neighborhood produces good outcomes for their children should be enough. You shouldn’t need more than the information.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1yOCBc">
For non-economists, though, this conclusion seems quite intuitive. Seattle voucher recipients got good customer service from a government agency — and just as it does nearly everywhere else, that turned out to matter a great deal.
</p>
<h3 id="YE2KCg">
How you create moves to opportunities
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IofTLO">
The navigators at the center of the intervention come in two flavors: family navigators, who work with Section 8 families to help in their housing search; and housing navigators, who meet with landlords in high-opportunity neighborhoods and dispel any negative impressions they might have about the Section 8 program and about tenants who might have criminal records or poor credit. Both are contracted through a local nonprofit, the <a href="http://interimicda.org/">Interim Community Development Association</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fSjPle">
Nikkie Manlapaz, a working mom who found a home through this program, told me back in 2019 that the navigators were absolutely essential. She said that in previous housing searches, she relied on “what I heard from friends and on Craigslist. I tried Apartments.com, but it was just basically calling the places on your own, looking at the places on your own, applying and just waiting, and usually the answer’s no.” Thanks to Section 8, she already had the money. But what she needed was an easier process.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eISVb3">
Manlapaz said that after she told her navigator she wanted to live in the Northgate, an opportunity neighborhood in northern Seattle, her navigator called to tell her about any vacancies. When she picked one she liked, “they pretty much took care of the rest. I gave them my information, they gave my information to the leasing office, they applied for me, and they helped with the first month’s rent and the renter’s insurance for a year.” In some ways, this is what wealthy people get when they pay for rental brokers or elite real estate agents, whose fees might be high but who can remove some drudgery and uncertainty from the process.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ss9R7u">
What we’ve learned since 2019 is that this kind of navigation is exactly why the program works. As part of the follow-up study, the authors (Chetty, Peter Bergman, Stefanie DeLuca, Nathaniel Hendren, Lawrence Katz, and Christopher Palmer) split the experiment into three arms, testing three different programs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Vd8yNA">
One group only got information about high-opportunity areas and some short-term financial assistance to help them move; this is the “light” intervention group. The “medium” group got some limited support from navigators, plus information and financial backing. The “heavy” intervention group got the full navigator experience. A control group received a voucher and no additional information or financial support.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qlht3y">
The results were unequivocal: Families getting the heavy treatment were vastly more likely to move to a high-opportunity area. In the control group, which got no information or assistance, 12.5 percent of families moved to high-opportunity areas. The light intervention increased that share by 8.9 percentage points, but this change wasn’t statistically significant. The medium intervention increased the share moving to a high-opportunity neighborhood to 26.3 percent, a more-than doubling, enough to be statistically significant.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MjSWog">
But the full treatment increased the share to 53.3 percent — most participants were now moving to high-opportunity areas. It was by far the most effective form of intervention.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nqtPrh">
It was also the most expensive, but even so it hardly breaks the bank: it cost $3,060 per family, compared to $1,001 for the medium intervention and $705 for the light one. Chetty notes that this doesn’t include the fact that some high-opportunity neighborhoods had costlier rents, which meant Section 8’s monthly subsidy costs increased. Over the average life of a voucher (seven years), the program cost and additional rent costs add up to a 17.2 percent increase in the voucher’s total cost for the housing authority.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r4co7b">
Not every housing authority would have to pay that much, though. “There are plenty of opportunity bargains, [neighborhoods] that are not more expensive, where we think kids would do equally as well,” Chetty says. It’s possible that a housing authority could decline to increase subsidies for high-cost areas, wind up only paying $3,060 per family, and still be able to place lots of families in these “bargain” areas.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lwDHNK">
Either way, the money seems more than worth it. An <a href="https://scholar.harvard.edu/files/lkatz/files/chk_aer_mto_0416.pdf">earlier paper by Chetty, Hendren, and Katz</a>, analyzing a large-scale experiment run by the Department of Housing and Urban Development in the 1990s, found that children living in voucher housing who were placed in low-poverty neighborhoods by the experiment saw their earnings rise by 31 percent in their mid-20s, relative to recipients who didn’t move. That’s a huge payoff, and easily adds up to more than $3,000 per person in benefits. College attendance is higher, and single parenthood less common, among adults whose families received the voucher; they’re likelier to live in low-poverty neighborhoods as adults too.
</p>
<h3 id="G96P7K">
I’ve been waiting for a guide to come and take me by the hand
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c76isI">
After the 2019 paper, Chetty says, some of his peers in economics were dismissive of the results. But, he notes, “that turns out not to be what’s going on. If you give people information, and even cash, that doesn’t do it.” What does do it is the navigators: an actual hands-on process helping people navigate the frictions of applying for housing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2IHVDX">
If that explanation is foreign to some economists modeling rational actors, it’s totally familiar in sociology, where it’s de rigueur to note that people’s behavior is shaped by stigma, institutional behaviors and attitudes, and their own bandwidth for making decisions. Stefanie DeLuca at Johns Hopkins, a prominent sociologist, is a co-author on the new paper and leads a team of 50 interviewers who wound up talking to 119 different families who were part of the experiment. The hope was to give some qualitative sense of what the program was like for participants: what it helped with, what limitations it had.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3j2FTW">
“The opening invitation to the interviews is ‘tell me the story of your life,’ and then eventually we move to the phase where they sign up for CMTO and we say ‘tell me about CMTO,’” DeLuca explains. “What was jumping out from that initial question,” she recalls, was “the emotional communication aspect of it. Families were feeling really relieved, supported, optimistic, more confident.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="k8GTvh">
Many participants, she recalled, reported “experiences that make them quite pessimistic” with housing in the past. In the paper, she quotes a member of the control group, Arya, who bemoans that during her most recent visit to a prospective apartment, she couldn’t even “get somebody to meet me there that might just sit there with me … to explain the paperwork.” By comparison, Tina, a mom who did receive CMTO help, reported, “Wow, this program, like they’re with you at all times, they help you, they’re there to guide you.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2kP4HE">
The navigators’ work was wide-ranging. They could act as emotional support, reassuring applicants that the process was going well and they’d succeed in finding a place. They could act as coaches, helping applicants put together “rental resumés” to win over landlords. They often served as intermediaries who could handle tricky or testy communications with landlords.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MyxlA8">
Honestly, the best comparison that comes through in the paper is to a concierge at a hotel. The navigators offered similarly comprehensive help to their clients, the kind of help that government rarely extends to citizens. And that, ultimately, was the most powerful part of the intervention for getting people to lease in high-opportunity areas, the main goal the whole time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VV0x4A">
It’s a lesson that could have surprisingly far-reaching implications. There aren’t concierges for most government services. If you’re struggling, programs like food stamps/SNAP and Medicaid often enroll you online with no actual person helping out. State human services departments are usually understaffed and ill-equipped to walk people through applications, support them on job searches, and generally “navigate” through the process the way the Seattle navigators did. We <a href="https://www.vox.com/future-perfect/2023/3/10/23632910/poverty-official-supplemental-relative-absolute-measure-desmond">spend a whole lot of money on social programs</a>, but they don’t do as much as they could because of the difficulty of access. <a href="https://www.fns.usda.gov/usamap">One in five people eligible for food stamps doesn’t get them</a>, and in a number of states like California and North Carolina, 30 percent don’t get them. Some of that is due to the difficulty of signing up and maintaining benefits.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9xzEJJ">
The CMTO results suggest that a concierge model might be worth trying on programs like these as well. People need monetary support, of course. But sometimes they need emotional and logistical support too.
</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>Serie A | Leao strikes twice as AC Milan humiliate Napoli 4-0</strong> - AC Milan have 51 points in the Serie A, one ahead of fourth-placed Inter Milan, and are four behind second-placed Lazio. Napoli are 20 points clear at the top.</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: DC vs GT | Lack of quality in Indian pace attack, poor bench strength may trouble Delhi against Gujarat</strong> - The defending champions have all their bases covered while the hosts are looking like an outfit that is bereft of a Plan 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>England women switch to blue shorts after period concerns</strong> - The issue of women athletes wearing white clothing was also brought up at last year’s Wimbledon tennis championships when female players spoke about the anxiety of being forced to wear white on their period</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 women cricketers get hefty pay rise</strong> - Payments for professional women will rise 66% under a new five-year deal between Cricket Australia and the Australian Cricketers’ Association.</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 | RCB do play consistent cricket, it’s just about staying focused: Virat Kohli</strong> - MI skipper Rohit Sharma rued that they were 30-40 runs short on this track and also blamed the bowlers for failing to execute the plan</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>Security forces arrest NSCN (K) militant who escaped from jail after killing guard</strong> - The State Police had announced a cash prize of ₹1 lakh each for information about the two militants who escaped from jail</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>Kore hospital using Ozaki technique for heart surgeries</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>Delhi HC cautions against frivolous, motivated PILs</strong> - The HC reiterated a Supreme Court observation that the judiciary needs to see whether “behind the beautiful veil of public interest an ugly private malice, vested interest and/or publicity-seeking is not lurking…”</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>Notification for Uttar Pradesh urban local body polls after govt finalises reservation: State Election Commission</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>LSGD to launch second phase of Thozhil Sabha initiative</strong> -</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>Darya Trepova: Russia releases tape of suspect in cafe killing of Vladlen Tatarsky</strong> - In a video likely filmed under duress, Darya Trepova says she handed over a statuette that blew up.</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>Finland to join Nato military alliance on Tuesday</strong> - The move was prompted by Russia’s invasion of Ukraine and comes after Turkey lifted its veto.</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>Bakhmut: Wagner raises Russian flag but Ukraine fights on</strong> - The stunt was dismissed by Ukraine, which said its army still holds the embattled eastern city.</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>Kosovo ex-president Hashim Thaci pleads not guilty to war crimes</strong> - The trial of ex-guerrilla commander turned politician Hashim Thaci opens in The Hague.</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>Sanna Marin defeated by Finland’s conservatives in tight race</strong> - After a dramatic three-way race, Petteri Orpo claims victory in Finland’s election.</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>A passenger aircraft that flies around the world at Mach 9? Sure, why not</strong> - “How much does the world change if you can get anywhere in an hour?” - <a href="https://arstechnica.com/?p=1928356">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Stable Diffusion copyright lawsuits could be a legal earthquake for AI</strong> - Experts say generative AI is in uncharted legal waters. - <a href="https://arstechnica.com/?p=1928010">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The 2023 Hyundai Ioniq 6: A streamlined look equals serious range</strong> - After so many electric crossovers, it’s refreshing to see another sedan. - <a href="https://arstechnica.com/?p=1928423">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Space archaeologists are charting humanity’s furthest frontier</strong> - An innovative research project delivers new evidence about how people live on the ISS. - <a href="https://arstechnica.com/?p=1928443">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SpaceX moves Starship to launch site, and liftoff could be just days away</strong> - No fooling—Starship rolled back to the launch pad on April 1. - <a href="https://arstechnica.com/?p=1928548">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>I think we should stop turning normal names like “Karen” into slurs</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It’s a real Dick move.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/chokobaby"> /u/chokobaby </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12a3ugu/i_think_we_should_stop_turning_normal_names_like/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12a3ugu/i_think_we_should_stop_turning_normal_names_like/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A madam opened the door to her brothel….</strong> - <!-- SC_OFF --></p>
<div class="md">
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…..to see a rather dignified, well-dressed, good-looking man in his late forties or early fifties. “Can I help you?” she asked. “I want to see Natalie.” the man replied. “Sir, Natalie is one of our most expensive ladies. Perhaps you would prefer someone else?” “No. I must see Natalie.” Just then Natalie appeared and announced to the man that she charged $1,000 a visit. Without hesitation, the man pulled out ten 100 dollar bills and gave them to Natalie, and they went upstairs.
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After an hour, the man calmly left. The next night, the same man appeared again, demanding to see Natalie. Natalie explained that no one had ever come back rwo nights in a row (too expensive) and she didn’t give discounts. The price was still $1,000. Again the man peeled off ten $100 bills, gave them to Natalie, and they went upstairs. After an hour, he left.
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The following night the man was there again. Everyone was astounded that he had come for a third consecutive night. But he paid Natalie the $1,000 and they went upstairs. After their session Natalie said, “No one has ever used me three nights in a row. Where are you from?” The man replied, “South Carolina.” “Really! I have family in South Carolina.” “I know. Your father died. I’m your sister’s attorney and she asked me to give you your $3,000 inheritance.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Tugger_Case"> /u/Tugger_Case </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/129vlxb/a_madam_opened_the_door_to_her_brothel/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/129vlxb/a_madam_opened_the_door_to_her_brothel/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What did one tampon say to the other tampon?</strong> - <!-- SC_OFF --></p>
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Nothing. They’re both stuck up c*nts.
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Edit: I know I can say ‘cunt’ on Reddit without consequence; I was being courteous.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Response-Cheap"> /u/Response-Cheap </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/129k040/what_did_one_tampon_say_to_the_other_tampon/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/129k040/what_did_one_tampon_say_to_the_other_tampon/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>This is my first joke. Be nice!</strong> - <!-- SC_OFF --></p>
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A doctor says grimly to a patient, “You are a very sick man. You’ve been diagnosed with covid, monkey pox, swine flu, Ebola, and bubonic plague all at the same time.”
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“Is there anything that can be done to help me?” asks the patient.
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“Amazingly, there is,” says the doctor. “First, we’ll put you in a private room where you’ll have everything you need to be as relaxed and comfortable as possible. Next, we’ll put you on a diet of pancakes and flounder.”
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“Okay…” says the patient, “But why pancakes and flounder?”
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“Because,” the doctor says, “That’s the only food we can slide under your door!”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Openly_Canadian_74"> /u/Openly_Canadian_74 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/129xlkn/this_is_my_first_joke_be_nice/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/129xlkn/this_is_my_first_joke_be_nice/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hookers don’t fart</strong> - <!-- SC_OFF --></p>
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They let out little prosti-toots.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/peterbeater76"> /u/peterbeater76 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/129vog7/hookers_dont_fart/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/129vog7/hookers_dont_fart/">[comments]</a></span></p></li>
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