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<title>04 February, 2023</title>
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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>Epidemic patterns of emerging variants with dynamical social distancing</strong> -
<div>
Motivated by the emergence of new variants during the COVID-19 pandemic, we consider an epidemiological model of disease transmission dynamics, where novel strains appear by mutations of the virus. In the considered scenarios, disease prevalence in the population is modulated by social distancing. We study the various patterns that are generated under different assumptions of cross-immunity. If recovery from a given strain provides immunity against all previous strains, but not against more novel strains, then we observe a very regular sequential pattern of strain replacement where newer strains predominate over older strains. However, if protection upon recovery holds only against that particular strain and none of the others, we find much more complicated dynamics with potential recurrence of earlier strains, and co-circulation of various strains. We compare the observed patterns with genomic analysis we have seen during the COVID-19 pandemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.03.526970v1" target="_blank">Epidemic patterns of emerging variants with dynamical social distancing</a>
</div></li>
<li><strong>Omicron’s Intrinsic Gene-Gene Interactions Jumped Away from Earlier SARS-CoV-2 Variants and Gene Homologs between Humans and Animals</strong> -
<div>
Omicron and its subvariants have become the predominant SARS-CoV-2 variants worldwide. The Omicron’s basic reproduction number (R0) has been close to 20 or higher. However, it is not known what caused such an extremely high R0. This work aims to find an explanation for such high R0 Omicron infection. We found that Omicron’s intrinsic gene-gene interactions jumped away from earlier SARS-CoV-2 variants which can be fully described by a miniature set of genes reported in our earlier work. We found that the gene PTAFR (Platelet Activating Factor Receptor) is highly correlated with Omicron variants, and so is the gene CCNI (Cyclin I), which is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog. The combination of PTAFR and CCNI can lead to a 100% accuracy of differentiating Omicron COVID-19 infection and COVID-19 negative. We hypothesize that Omicron variants were potentially jumped from COVID-19-infected animals back to humans. In addition, there are also several other two-gene interactions that lead to 100% accuracy. Such observations can explain Omicron’s fast-spread reproduction capability as either of those two-gene interactions can lead to COVID-19 infection, i.e., multiplication of R0s leads to a much higher R0. At the genomic level, PTAFR, CCNI, and several other genes identified in this work rise to Omicron druggable targets and antiviral drugs besides the existing antiviral drugs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.01.526736v1" target="_blank">Omicron’s Intrinsic Gene-Gene Interactions Jumped Away from Earlier SARS-CoV-2 Variants and Gene Homologs between Humans and Animals</a>
</div></li>
<li><strong>Data-driven User Model Development of a Conversational AI Chatbot to provide Assistance to Unemployed People during the COVID-19 Pandemic</strong> -
<div>
The COVID-19 pandemic triggered lockdowns all over the world, leading to unprecedented job losses. In the US, this resulted in many first time unemployment benefits filers struggled to navigate the benefits information provided by federal and state websites. We developed BEBO (Benefits Bot) to address these pain points and to provide appropriate and timely information. This paper explains the data-driven user model that was developed to create a user-centric conversational AI chatbot.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/thqf5/" target="_blank">Data-driven User Model Development of a Conversational AI Chatbot to provide Assistance to Unemployed People during the COVID-19 Pandemic</a>
</div></li>
<li><strong>Molecular Epidemiology and Diversity of SARS-CoV-2 in Ethiopia, 2020-2022</strong> -
<div>
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Ethiopia is the second most populous country in Africa and the sixth most affected by COVID-19 on the continent. Despite having experienced five infection waves, &gt;499 000 cases, and ~7 500 COVID-19-related deaths as of January 2023, there is still no detailed genomic epidemiological report on the introduction and spread of SARS-CoV-2 in Ethiopia. In this study, we reconstructed and elucidated the COVID-19 epidemic dynamics. Specifically, we investigated the introduction, local transmission, ongoing evolution, and spread of SARS-CoV-2 during the first four infection waves using 353 high-quality near-whole genomes sampled in Ethiopia. Our results show that whereas viral introductions seeded the first wave, subsequent waves were seeded by local transmission. The B.1.480 lineage emerged in the first wave and notably remained in circulation even after the emergence of the Alpha variant. The B.1.480 was out-competed by the Delta variant. Notably, Ethiopia lack of local sequencing capacity was further limited by sporadic, uneven, and insufficient sampling that limited the incorporation of genomic epidemiology in the epidemic public health response in Ethiopia. These results highlight Ethiopia role in SARS-CoV-2 dissemination and the urgent need for balanced, near-real-time genomic sequencing.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.30.23285174v2" target="_blank">Molecular Epidemiology and Diversity of SARS-CoV-2 in Ethiopia, 2020-2022</a>
</div></li>
<li><strong>Mechanisms of SARS-CoV-2 Inactivation using UVC Laser Radiation</strong> -
<div>
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has had a tremendous impact on humanity. Prevention of transmission by disinfection of surfaces and aerosols through a chemical-free method is highly desirable. Ultraviolet C (UVC) light is uniquely positioned to achieve inactivation of pathogens. We report the inactivation of SARS-CoV-2 virus by UVC radiation and explore its mechanisms. A dose of 50mJ/cm2 using a UVC laser at 266nm achieved an inactivation efficiency of 99.89%, whilst infectious virions were undetectable at 75mJ/cm2 indicating &gt;99.99% inactivation. Infection by SARS-CoV-2 involves viral entry mediated by the spike glycoprotein (S), and viral reproduction, reliant on translation of its genome. We demonstrate that UVC radiation damages ribonucleic acid (RNA) and provide in-depth characterisation of UVC-induced damage of the S protein. We find that UVC severely impacts the ability of the SARS-CoV- 2 spike protein to bind human angiotensin-converting enzyme 2 (hACE2) and this correlates with loss of native protein conformation and aromatic amino acid integrity. This report has important implications for the design and development of rapid and effective disinfection systems against the SARS-CoV-2 virus and other pathogens.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.03.526944v1" target="_blank">Mechanisms of SARS-CoV-2 Inactivation using UVC Laser Radiation</a>
</div></li>
<li><strong>Impact of the COVID-19 restrictions on the epidemiology of Cryptosporidium spp. in England and Wales, 2015-2021. A time-series analysis</strong> -
<div>
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<b>Background</b> In England and Wales, cryptosporidiosis cases peak in spring and autumn, usually associated with zoonotic and environmental exposures (<i>Cryptosporidium parvum</i>, spring/autumn) and with overseas travel and water-based activities (<i>Cryptosporidium hominis</i>, autumn). Restrictions to control the COVID-19 pandemic prevented social mixing and access to swimming pools and restaurants for many months. Foreign travel from the UK also reduced by 74% in 2020. However, these restrictions potentially increased environmental exposures as people sought alternative countryside activities locally. To inform and strengthen surveillance programmes, we investigated the impact of COVID-19 restrictions on the epidemiology of <i>C. hominis</i> and <i>C. parvum cases</i>. <b>Methods</b><i>Cryptosporidium</i>-positive stools, with case demographic data, are referred routinely for genotyping to the national Cryptosporidium Reference Unit (CRU). Cases were extracted from the CRU database (01 January 2015 to 31 December 2021). We defined two periods for pre- and post-COVID-19 restrictions implementation corresponding to the first UK-wide lockdown on 23 March 2020: pre-restrictions between week 1, 2015 and week 12, 2020, and post restrictions-implementation between week 13, 2020 and week 52, 2021. We conducted an interrupted time-series analysis, assessing differences in <i>C. parvum</i> and <i>C. hominis</i> incidence, trends and periodicity between these periods using negative binomial regression with linear-splines and interactions. <b>Results</b> There were 21,304 cases between 01 January 2015 and 31 December 2021 (<i>C. parvum</i> = 12,246; <i>C. hominis</i> = 9,058). Post restrictions-implementation incidence of <i>C. hominis</i> dropped by 97.5% (95%CI: 95.4%-98.6%; p&lt;0.001). The decreasing incidence-trend observed pre-restrictions (IRR=0.9976; 95%CI: 0.9969-0.9982; p&lt;0.001) was not observed post restrictions-implementation (IRR=1.0081; 95%CI: 0.9978-1.0186; p=0.128) due to lack of cases. No periodicity change was observed post restrictions-implementation. Where recorded, 22% of <i>C. hominis</i> cases had travelled abroad. There was also a strong social gradient, with those who lived in deprived areas experiencing a higher proportion of cases. This gradient did not exist post restrictions-implementation, but the effect was exacerbated for the most deprived: 27.2% of cases from the most deprived decile compared to 12.7% in the pre-restrictions period. For <i>C. parvum</i>, post restrictions-implementation incidence fell by 49.0% (95%CI: 38.4%-58.3%; p&lt;0.001). There was no pre-restrictions incidence-trend (IRR=1.0003; 95%CI: 0.9997-1.0009; p=0.322) but a slight increasing incidence-trend existed post restrictions-implementation (IRR=1.0071; 95%CI: 1.0038-1.0104; p&lt;0.001). A periodicity change was observed for <i>C. parvum</i> post restrictions-implementation, peaking one week earlier in spring and two weeks later in autumn. Where recorded, 8% of <i>C. parvum</i> cases had travelled abroad. The social gradient observed for <i>C. parvum</i> was inverse to that for <i>C. hominis</i>, and was stable pre-restrictions and post restrictions-implementation. <b>Conclusion</b><i>C. hominis</i> cases were almost entirely arrested post restrictions-implementation, reinforcing that foreign travel is a major driver of seeding infections. Increased hand-hygiene, reduced social mixing, limited access to swimming pools and limited foreign travel affected incidence of most gastrointestinal (GI) pathogens, including <i>Cryptosporidium</i>, in the same period. <i>C. parvum</i> incidence fell sharply but recovered throughout the post restrictions-implementation period, back to pre-restrictions levels by the end of 2021; this is consistent with relaxation of restrictions, reduced compliance and increased countryside use. The effect on our results of changes in health-seeking behaviours, healthcare access and diagnostic laboratory practices post restrictions-implementation is uncertain, but it is likely that access to GPs and specimen referral rate to CRU decreased. Future exceedance reporting for <i>C. hominis</i> should exclude the post restrictions-implementation period but retain it for <i>C. parvum</i> (except the first six weeks post restrictions-implementation where the incidence fell sharply). Advice on infection prevention and control should be improved for people with GI symptoms, including returning travellers, to ensure hand hygiene and appropriate swimming pool avoidance.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.26.22280357v3" target="_blank">Impact of the COVID-19 restrictions on the epidemiology of Cryptosporidium spp. in England and Wales, 2015-2021. A time-series analysis</a>
</div></li>
<li><strong>A pattern shift in SARS-CoV-2 Omicron variant transmission after the city lockdown–observational study based upon daily reported addresses of infected cases</strong> -
<div>
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Background Varied degrees of lockdown have been imposed for dozens of jurisdictions upon facing the SARS-CoV-2 epidemics during the past two years. Areal lockdown has been demonstrated effective to reduce the morbility and mortality of COVID-19. Even after the strict lockdown the peak of infection will appear around 9-25 days (median 18 days) thereafter. A wave of Omicron variant (BA.2 and BA.2.2) outbreak was seen from March to May 2022, in Shanghai, a megacity in China mainland. Aim To understand the sources of infection cases from outside or inside the isolated locations before and after the strict city lockdown. Methods The attributable addresses of SARS-CoV-2 infection were reported daily as well as the infected cases from March 18th, 2022 on through government website, which was publicly accessible. The address data and infected cases were collected until May 29th, 2022. The location (longitude and latitude) of these addresses were retrieved and the pattern of repeatedly reported addresses were analyzed. A tool of simple and meso-scale point-based (location-based) chronological graph was used to visualize and analyze the interactions of these locations. Results From March 18th to May 29th 2022, 173,350 items representing 35,743 unique addresses and 636,279 infected cases were released. The infection cases peaked 16 days after the city lockdown and were highly clustered in much crowded districts. The proportion of repeatedly reported locations of the previous day increased from around 20% before lockdown to greater than 40% in the plateau and remained at this level for up to one third (20/62) of the lockdown phase. This significantly increased proportion of intra-address infection indicated a pattern shift from inter-addresses to intra-address (D=0.2954, p&lt;0.0001), which might perpetuate to the growth of infection cases. Based upon the day-to-day nearest neighbour transmission assumption the connections between some frequently repeated locations might be complex and heterogeneous. Interpretation During the strict areal isolation the intra-address infection may contribute significantly to infected cases of SARS-CoV-2 Omicron variant, the infection might have easily spilled over the boundary of family(with averaged family size of 2.3-3.1 people and family were required stay-at-home compulsively). This significant inter-addresses to intra-address pattern shift necessitated the understanding of intra-location transmission routes and corresponding interventions. Areal isolation and close off with homogeneous assumption inside and outside the isolated areas should be modified and the quantifing of the elevated risk for previously less exposed but much vulnerable sub-population was in pressing need.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.02.22279556v2" target="_blank">A pattern shift in SARS-CoV-2 Omicron variant transmission after the city lockdown–observational study based upon daily reported addresses of infected cases</a>
</div></li>
<li><strong>Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.</strong> -
<div>
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Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine - either heterologous (PHH-1V group) or homologous (BNT162b2 group) - in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p&lt;0.0001), 1.31 (p=0.0007) and 0.86 (p=0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p&lt;0.0001), 0.65 (p&lt;0.0001) and 0.56 (p=0.003) for the Beta variant; 1.01 (p=0.92), 0.88 (p=0.11) and 0.52 (p=0.0003) for the Delta variant; and 0.59 (p=&lt;0.0001), 0.66 (p&lt;0.0001) and 0.57 (p=0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p=0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.05.22277210v4" target="_blank">Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.</a>
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<li><strong>CITY LEADERSHIP IN PARA-DIPLOMACY: DRIVERS OF JAKARTA’S INTERNATIONAL ENGAGEMENT IN ADDRESSING COVID-19 PANDEMIC</strong> -
<div>
The outbreak of COVID-19 pandemic has impacted all the world’s aspects, including the interactions among governments. While some either chose to be conflicting with others or overlooked the pandemic, the rest attempted to collaborate in addressing the new global threat. Mega-cities in many countries were the most suffering regions due to the enormous virus confirmed cases, deaths, and economic declines, intertwining with other urban issues. As the largest city in Southeast Asia and in Indonesia, Jakarta also experienced the unprecedented crisis. However, apart from the efforts to tackle the crisis at home, the city showed its international engagement in addressing the issue together with other world’s cities as its para-diplomacy. This research aimed to answer the driving factors encouraging the city for such engagement. This research employed the qualitive method with a descriptive analysis and the city leadership theory proposed by Rapoport, Acuto and Grcheva. This research found that the Jakarta’s international engagement in addressing the pandemic as the city leadership action was driven by the role of city leader, decentralization and global city networking, and the regional COVID-19 policies and internet representing three elements in the theory: actor, structures, and tools. This paper argues that cities within the global city networking have demonstrated their stronger role during the pandemic, providing opportunity for nation branding by regional initiatives in handling the pandemic in addition to state foreign policy. As cities have been more consolidated within the networks, seeing the city leadership in responding to global issues merits attentions among scholars.
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🖺 Full Text HTML: <a href="https://osf.io/6f3j5/" target="_blank">CITY LEADERSHIP IN PARA-DIPLOMACY: DRIVERS OF JAKARTA’S INTERNATIONAL ENGAGEMENT IN ADDRESSING COVID-19 PANDEMIC</a>
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<li><strong>Lung viral infection modelling in a bioengineered whole-organ</strong> -
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Lung infections are one of the leading causes of death worldwide, and this situation has been exacerbated by the emergence of COVID-19. Pre-clinical modelling of viral infections has relied on cell cultures that lack 3D structure and the context of lung extracellular matrices. Here, we propose a bioreactor-based, whole-organ lung model of viral infection. The bioreactor takes advantage of an automated system to achieve efficient decellularization of a whole rat lung, and recellularization of the scaffold using primary human bronchial cells. Automatization allowed for the dynamic culture of airway epithelial cells in a breathing-mimicking setup that led to an even distribution of lung epithelial cells throughout the distal regions. In the sealed bioreactor system, we demonstrate proof-of-concept for viral infection with the engineered lung by infecting primary human airway epithelial cells. Moreover, to assess the possibility of drug screening in this model, we demonstrate the efficacy of the broad-spectrum antiviral Remdesivir. This whole-organ scale lung infection model represents a step towards modelling viral infection of human cells in a 3D context, providing a powerful tool to investigate the mechanisms of the early stages of pathogenic infections and the development of effective treatment strategies for respiratory diseases.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.01.526441v1" target="_blank">Lung viral infection modelling in a bioengineered whole-organ</a>
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<li><strong>sciCSR infers B cell state transition and predicts class-switch recombination dynamics using single-cell transcriptomic data</strong> -
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Class-switch recombination (CSR) is an integral part of B cell maturation. Steady-state analyses of isotype distribution (e.g. B cell receptor [BCR] repertoire analysis of snapshots during an immune response) do not directly measure CSR dynamics, which is crucial in understanding how B cell maturation is regulated across time. We present sciCSR (pronounced ‘scissor’, single-cell inference of class switch recombination), a computational pipeline which analyses CSR events and dynamics of B cells from single-cell RNA-sequencing (scRNA-seq) experiments. sciCSR re-analyses transcriptomic sequence alignments to differentiate productive heavy-chain immunoglobulin transcripts from germline “sterile” transcripts. From a snapshot of B cell scRNA-seq data, a Markov state model is built by the pipeline to infer the dynamics and direction of CSR. Applying sciCSR on SARS-CoV-2 vaccination time-course scRNA-seq data, we observe that sciCSR predicts, using data from an earlier timepoint in the collected time-course, the isotype distribution of BCR repertoires of subsequent timepoints with high accuracy (cosine similarity approximately 0.9). sciCSR also recapitulates CSR patterns in mouse models where B cell maturation was perturbed using gene knockouts. sciCSR infers cell state transitions using processes specific to B cells, identifies transitions which are often missed by conventional RNA velocity analyses, and can reveal insights into the regulation of CSR and the dynamics of B cell maturation during an immune response.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.02.526789v1" target="_blank">sciCSR infers B cell state transition and predicts class-switch recombination dynamics using single-cell transcriptomic data</a>
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<li><strong>Development of a mobile laboratory system in hydrogen fuel cell buses and evaluation of the performance for COVID-19</strong> -
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Introduction: We newly designed and developed two types of hydrogen fuel cell (HFC) buses (motorcoach type and minibus type) with a mobile laboratory system. Feasibility studies have been performed for mobile laboratory testing, especially for the laboratory performance of COVID-19 RT-PCR (PCR). Methods: We evaluated the driving range capability, PCR sample size capacity, turn-around time (TAT), and analytical performance for the detection of SARS-CoV-2. Saliva samples were used for the current research and the analytical performance was compared with reference PCR. Results: The estimated driving range and sample size capacity were 432 km and 3,258 samples, respectively for the HFC motorcoach and 313 km and 2,146 samples for the HFC minibus, respectively. For the TAT, the median time between the sample submission and the completion of PCR were 86 min for the motorcoach and 76 min for the minibus, and the median time between sample submission and the electronic reporting of the result to each visitor were 182 min for the motorcoach and 194 min for the minibus. A secondary analysis of 1,574 HFC mobile laboratory testing samples was conducted and all negative samples were negative by reference PCR. Furthermore, all positive samples were confirmed as positive by reference PCR or other molecular examinations. Conclusion: We confirmed the feasibility of HFC mobile laboratory systems for achieving the rapid reporting of highly accurate PCR results.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.30.23285220v1" target="_blank">Development of a mobile laboratory system in hydrogen fuel cell buses and evaluation of the performance for COVID-19</a>
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<li><strong>Associations between reported healthcare disruption due to COVID-19 and avoidable hospitalisation: Evidence from seven linked longitudinal studies for England</strong> -
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Background: Health services across the UK struggled to cope during the COVID-19 pandemic. Many treatments were postponed or cancelled, although the impact was mitigated by new models of delivery. While the scale of disruption has been studied, much less is known about if this disruption impacted health outcomes. The aim of our paper is to examine whether there is an association between individuals experiencing disrupted access to healthcare during the pandemic and risk of an avoidable hospitalisation. Methods: We used individual-level data for England from seven longitudinal cohort studies linked to electronic health records from NHS Digital (n = 29 276) within the UK Longitudinal Linkage Collaboration trusted research environment. Avoidable hospitalisations were defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions (1st March 2020 to 25th August 2022). Self-reported measures of whether people had experienced disruption during the pandemic to appointments (e.g., visiting their GP or an outpatient department), procedures (e.g., surgery, cancer treatment) or medications were used as our exposures. Logistic regression models examined associations. Results: 35% of people experienced some form of disrupted access to healthcare. Those whose access was disrupted were at increased risk of any (Odds Ratio (OR) = 1.80, 95% Confidence Intervals (CIs) = 1.34-2.41), acute (OR = 1.68, CIs = 1.13-2.53) and chronic (OR = 1.93, CIs = 1.40-2.64) ambulatory care sensitive hospital admissions. There were positive associations between disrupted access to appointments and procedures to measures of avoidable hospitalisations as well. Conclusions: Our study presents novel evidence from linked individual-level data showing that people whose access to healthcare was disrupted were more likely to have an avoidable or potentially preventable hospitalisation. Our findings highlight the need to increase healthcare investment to tackle the short- and long-term implications of the pandemic beyond directly dealing with SARS-CoV-2 infections.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.01.23285333v1" target="_blank">Associations between reported healthcare disruption due to COVID-19 and avoidable hospitalisation: Evidence from seven linked longitudinal studies for England</a>
</div></li>
<li><strong>Immunogenicity of the BA.1 and BA.4/5 Bivalent Boosts: A Brief Report of Preliminary Results from the COVAIL Randomized Clinical Trial</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The emergence of Omicron subvariants and waning immunity to initial vaccine regimens led to the authorization of updated SARS-CoV-2 bivalent vaccines containing wildtype with either Omicron BA.1 or BA.4/5. Here, we compare early serologic responses from a randomized clinical trial of a second boost with either the Pfizer/BioNTech BNT162b2 (30 mcg dose) Wildtype/Omicron BA.1 or Wildtype/Omicron BA.4/5 vaccines against homologous and heterologous strains including contemporary Omicron subvariants BQ.1.1 and XBB.1.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.31.23285306v1" target="_blank">Immunogenicity of the BA.1 and BA.4/5 Bivalent Boosts: A Brief Report of Preliminary Results from the COVAIL Randomized Clinical Trial</a>
</div></li>
<li><strong>Discovering SARS-CoV-2 neoepitopes and the associated TCR-pMHC recognition mechanisms by combining single-cell sequencing, deep learning, and molecular dynamics simulation techniques</strong> -
<div>
The molecular mechanisms underlying the recognition of epitopes by T cell receptors (TCRs) are critical for activating T cell immune responses and rationally designing TCR-based therapeutics. Single-cell sequencing techniques vastly boost the accumulation of TCR sequences, while the limitation of available TCR-pMHC structures hampers further investigations. In this study, we proposed a comprehensive strategy that incorporates structural information and single-cell sequencing data to investigate the epitope-recognition mechanisms of TCRs. By antigen specificity clustering, we mapped the epitope sequences between epitope-known and epitope unknown TCRs from COVID-19 patients. One reported SARS-CoV-2 epitope, NQKLIANQF (S919-927), was identified for a TCR expressed by 614 T cells (TCR-614). Epitope screening also identified a potential cross-reactive epitope, KLKTLVATA (NSP31790-1798), for a TCR expressed by 204 T cells (TCR-204). According to the molecular dynamics (MD) simulations, we revealed the detailed epitope-recognition mechanisms for both TCRs. The structural motifs responsible for epitope recognition revealed by the MD simulations are consistent with the sequential features recognized by the sequence-based clustering method. This strategy will facilitate the discovery and optimization of TCR-based therapeutics. In addition, the comprehensive strategy can also promote the development of cancer vaccines in virtue of the ability to discover neoepitopes and epitope-recognition mechanisms.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.02.526761v1" target="_blank">Discovering SARS-CoV-2 neoepitopes and the associated TCR-pMHC recognition mechanisms by combining single-cell sequencing, deep learning, and molecular dynamics simulation techniques</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>Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br/><b>Sponsors</b>:   Wuhan BravoVax Co., Ltd.;   National University Hospital, Singapore;   Shanghai BravoBio Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Plitidepsin<br/><b>Sponsor</b>:   PharmaMar<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>Evaluation of Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Corfluvec component 1 low dose;   Biological: Corfluvec component 2 low dose;   Biological: Corfluvec component 1 high dose;   Biological: Corfluvec component 2 high dose;   Biological: Corfluvec low dose;   Biological: Corfluvec high dose;   Biological: Placebo<br/><b>Sponsors</b>:   Tatyana Zubkova;   MDP-CRO, LLC;   St. Petersburg State Pavlov Medical University<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>COVID-19 Self-testing Study</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Behavioral: SMARTest mobile app for COVID-19 self-testing<br/><b>Sponsor</b>:   Columbia 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>A Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Azvudine;   Drug: Nirmatrelvir-Ritonavir<br/><b>Sponsors</b>:   Shandong Provincial Hospital;   Central hospital Affiliated to Shandong First Medical University;   The Second Affiliated Hospital of Shandong First Medical University;   The Affiliated Hospital Of Southwest Medical University;   Gansu Provincial 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>Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Intervention</b>:   Radiation: Low-Dose Radiation Therapy<br/><b>Sponsors</b>:   Jiangsu Cancer Institute &amp; Hospital;   Nanjing Chest Hospital;   The Affiliated BenQ Hospital of Nanjing Medical University;   Central South University;   Zhongda 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>Tetrandrine Tablets Used in Hospitalized Adults With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Tetrandrine<br/><b>Sponsor</b>:   Peking University Third 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>INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Device: HIGH FREQUENCY CHEST WALL OSCILLATION<br/><b>Sponsor</b>:   Cairo University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Megadose Vitamin C in Severe and Critical Ill COVID-19 Patients.</strong> - <b>Conditions</b>:   Vitamin C;   COVID-19 Pneumonia<br/><b>Interventions</b>:   Drug: Vitamin C;   Drug: Placebo<br/><b>Sponsor</b>:   Zhujiang Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Difference Between Non-invasive High-frequency Oscillatory Ventilation and Non-invasive Continuous Airway Pressure Ventilation in COVID-19 With Acute Hypoxemia</strong> - <b>Conditions</b>:   COVID-19 Pneumonia;   Non-invasive Ventilation<br/><b>Interventions</b>:   Device: Non-invasive high-frequency oscillatory ventilation;   Device: Non-invasive continuous positive airway pressure ventilation<br/><b>Sponsor</b>:   Guangzhou Institute of Respiratory Disease<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>COVID-19 Molecular OTC At Home Test</strong> - <b>Condition</b>:   COVID-19 Pandemic<br/><b>Intervention</b>:   Diagnostic Test: Diagnostic Test: IN Vitro<br/><b>Sponsor</b>:   3EO Health<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>Randomized-controlled Trial of Immunoadsorption (IA) in Patients With Chronic Fatigue Syndrome (CFS) Including Patients With Post-COVID-19 CFS (PACS-CFS)</strong> - <b>Condition</b>:   ME/CSF Including CFS Related to Post-acute COVID-19 Syndrome (PACS)<br/><b>Intervention</b>:   Device: Immunoadsorption<br/><b>Sponsor</b>:   Charite University, Berlin, Germany<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>Phase II/III Immunogenicity and Safety Study of the AVX/COVID-12 Vaccine Against COVID-19 Applied as a Booster.</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Biological: AVX-COVID/12;   Biological: ChAdOx-1-S[recombinant]<br/><b>Sponsors</b>:   Laboratorio Avi-Mex, S.A. de C.V.;   National Council of Science and Technology, Mexico;   Instituto Nacional de Enfermedades Respiratorias<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>Brain-Training Treatment for Long COVID in Older Adults</strong> - <b>Condition</b>:   Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>:   Other: NeuroFlex (computerized gamified tasks)<br/><b>Sponsor</b>:   UConn Health<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>Phase 2/Phase 3 Study To Evaluate The Efficacy And Safety Of Ramatroban Along With The Standard Of Care In Subjects Hospitalized For COVID Pneumonia</strong> - <b>Conditions</b>:   COVID-19 Pneumonia;   COVID-19 Respiratory Infection<br/><b>Interventions</b>:   Drug: Ramatroban;   Drug: Placebo<br/><b>Sponsors</b>:   KARE Biosciences;   JSS Medical Research Inc.;   Biomedical Advanced Research and Development Authority;   Open Philanthropy;   Charak Laboratories India Pvt. Ltd;   Charak Foundation;   BioLink Life Sciences, Inc.<br/><b>Recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation</strong> - The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a severe global health crisis; its structural protein envelope (E) is critical for viral entry, budding, production, and induction of pathology which makes it a potential target for therapeutics against COVID-19. Here, we find that the E3 ligase RNF5 interacts with and catalyzes ubiquitination of E on the 63rd lysine, leading to its degradation by 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>SSRIs differentially modulate the effects of pro-inflammatory stimulation on hippocampal plasticity and memory via sigma 1 receptors and neurosteroids</strong> - Certain selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory effects in preclinical models, and recent clinical studies suggest that fluvoxamine can prevent deterioration in patients with COVID-19, possibly through activating sigma 1 receptors (S1Rs). Here we examined potential mechanisms contributing to these effects of fluvoxamine and other SSRIs using a well-characterized model of pro-inflammatory stress in rat hippocampal slices. When hippocampal slices are exposed acutely…</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>Inhibition of IL-6 signaling prevents serum-induced umbilical cord artery dysfunction from severe COVID-19 patients</strong> - Coronavirus disease 2019 (COVID-19) infection has a negative impact on the cytokine profile of pregnant women. Increased levels of pro-inflammatory cytokines seem to be correlated with the severity of the disease, in addition to predisposing to miscarriage or premature birth. Pro-inflammatory cytokines increase the generation of reactive oxygen species (ROS). It is unclear how interleukin-6 (IL-6) found in the circulation of severe COVID-19 patients might affect gestational health, particularly…</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>Emerging role of microRNAs and long non-coding RNAs in COVID-19 with implications to therapeutics</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which is commonly known as COVID-19 (COronaVIrus Disease 2019) has creeped into the human population taking tolls of life and causing tremendous economic crisis. It is indeed crucial to gain knowledge about their characteristics and interactions with human host cells. It has been shown that the majority of our genome consists of non-coding RNAs. Non-coding RNAs including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs)…</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>Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection</strong> - Although the COVID-19 pandemic began over three years ago, the virus responsible for the disease, SARS-CoV-2, continues to infect people across the globe. As such, there remains a critical need for development of novel therapeutics against SARS-CoV-2. One technology that has remained relatively unexplored in COVID-19 is the use of antisense oligonucleotides (ASOs)-short single-stranded nucleic acids that bind to target RNA transcripts to modulate their expression. In this study, ASOs targeted…</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>Dantrolene and ryanodine receptors in COVID-19:The daunting taskand neglected warden</strong> - Dantrolene (DTN) is a ryanodine receptor (RyR) antagonist that inhibits Ca^(2+) release from stores in the sarcoplasmic reticulum. DTN is mainly used in the management of malignant hyperthermia. RyRs are highly expressed in immune cells and are involved in different viral infections, including SARS-CoV-2, since Ca^(2+) is necessary for viral replication, maturation, and release. DTN can inhibit the proliferation of SARS-CoV-2, indicating its potential role in reducing entry and pathogenesis of…</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>Modular Metal-Quinone Networks with Tunable Architecture and Functionality</strong> - Nanostructured materials with tunable structures and functionality are of interest in diverse areas. Herein, metal ions are coordinated with quinones via metal-acetylacetone coordination bonds to generate a class of structurally tunable, universally adhesive, superhydrophilic, and pH-degradable materials. A library of metal-quinone networks (MQNs) is produced from five model quinone ligands paired with nine metal ions, leading to particles, tubes, capsules, and films. Importantly, MQNs show…</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>Weathering and degradation of polylactic acid masks in a simulated environment in the context of the COVID-19 pandemic and their effects on the growth of winter grazing ryegrass</strong> - The COVID-19 pandemic has led to explosive growth in the production and consumption of disposable medical masks, which has caused new global environmental problems due to the improper disposal of these masks and lack of effective mask recycling methods. To reduce the environmental load caused by the inability of synthetic plastics to degrade, polylactic acid (PLA) masks, as a biodegradable environmentally friendly plastic, may become a solution. This study simulated the actual degradation…</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>Family functioning of families experiencing intensive care and the specific impact of the COVID-19 pandemic: A grounded theory study</strong> - CONCLUSION: There is awareness about the love that exists within the family. A willing to supporting each other in the family even if the critical illness made the family anxious and afraid.</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>Inhibiting the Deubiquitinase UCHL1 Reduces SARS-CoV-2 Viral Uptake by ACE2</strong> - COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) remains a significant public health burden with limited treatment options. Many beta-coronaviruses, including SARS-CoV-2, gain entry to host cells through interaction of SARS-CoV-2 Spike (S) protein with membrane-bound angiotensin-converting enzyme 2 (ACE2). Given its necessity for SARS-CoV-2 infection, ACE2 represents a potential therapeutic target in COVID-19. However, early attempts…</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>Siglec-9 Restrains Antibody-Dependent Natural Killer Cell Cytotoxicity against SARS-CoV-2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the immunological profiles of natural killer (NK) cells. However, whether NK antiviral functions are impaired during severe coronavirus disease 2019 (COVID-19) and what host factors modulate these functions remain unclear. We found that NK cells from hospitalized COVID-19 patients degranulate less against SARS-CoV-2 antigen-expressing cells (in direct cytolytic and antibody-dependent cell cytotoxicity [ADCC] assays)…</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>Discovery of Isojacareubin as a covalent inhibitor of SARS-CoV-2 main protease using structural and experimental approaches</strong> - The ongoing pandemic with the emergence of immune evasion potential and particularly the current omicron sub variants intensified the situation further. Although vaccine are available but the immune evasion capabilities of the recent variants demand further efficient therapeutic choices to control the SARS-CoV-2 pandemic. Hence, considering the necessity of the small molecule inhibitor we target the main protease (3CLpro) which is an appealing target for the development of anti-viral drugs…</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 hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron <em>in vivo</em></strong> - The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron…</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>High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors</strong> - The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^(pro)) and papain like protease (PL^(pro)), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^(pro) inhibitors and 205 PL^(pro) inhibitors with low nmol/l activity of the best hits….</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>Kaempferol has potential anti-coronavirus disease 2019 (COVID-19) targets based on bioinformatics analyses and pharmacological effects on endotoxin-induced cytokine storm</strong> - COVID-19 has infected 272 million patients and caused 5.33 million deaths around the world, and it remains the main global threat. Previous studies revealed that Chinese traditional medicine is an effective treatment for COVID-19 infection. This study aims to reveal the pharmacological effects of kaempferol, which is the active component of Radix Bupleuri and Tripterygii Radix, and potential mechanisms for the treatment of COVID-19. Here, we employed the bioinformatics methods to filter the…</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>The Ukraine Crackup in the G.O.P.</strong> - Republicans aren’t united with one another, never mind with Joe Biden. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/the-ukraine-crackup-in-the-gop">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Is Donald Trump Losing His Mojo?</strong> - The former President’s political and legal challenges are mounting, even as some polls indicate that he still has a lot of support among Republicans. - <a href="https://www.newyorker.com/news/our-columnists/is-donald-trump-losing-his-mojo">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What Ron Klain Learned in the White House</strong> - Joe Biden’s exiting chief of staff is a case study in the slow accumulation of expertise. - <a href="https://www.newyorker.com/news/daily-comment/what-ron-klain-learned-in-the-white-house">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The World the 747 Didn’t Predict</strong> - Boeing’s iconic jumbo jet was prophesied as a “weapon of peace.” It leaves the world a smaller place. And still a war-torn one, too. - <a href="https://www.newyorker.com/news/dispatch/the-world-the-747-didnt-predict">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Are Republicans Ready to Move On from Donald Trump?</strong> - A former loyalist contemplates the former President’s flaws—and the G.O.P.’s willingness to ignore them. - <a href="https://www.newyorker.com/news/q-and-a/are-republicans-ready-to-move-on-from-donald-trump">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Why Bad Bunny’s Un Verano Sin Ti is such a big deal</strong> -
<figure>
<img alt="Bad Bunny sits in a beach chair onstage with an open cooler and other props around him, wearing an all-yellow suit and sneakers. Lighting that mimics being underwater patterns the stage, with a vibrant pink-and-purple sunset reflecting in clouds projected behind it. " src="https://cdn.vox-cdn.com/thumbor/_H2l8skkPgqJCXxyxj-q240Bc84=/141x0:3448x2480/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/71939943/1429278485.0.jpg"/>
<figcaption>
Bad Bunny onstage during a performance on his World’s Hottest Tour, on September 30, 2022, in Inglewood, California. | Kevin Winter/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Grammy nominated artist is making Latinx music mainstream, while expanding what it can be.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WBtQok">
Once again, Bad Bunny is breaking records. His latest album, <a href="https://open.spotify.com/album/3RQQmkQEvNCY4prGKE6oc5"><em>Un Verano Sin Ti</em></a>, is the first Spanish-language album to ever receive a Grammy nomination for Album of the Year. The feat in and of itself is huge — acknowledging the sheer growth and dominance of Latin music in the American mainstream in the last decade, regardless of whether he wins Sunday night.
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It’s a nomination well deserved, after what can only be described as a blockbuster year for the Latin trap artist. Bad Bunny kicked off 2022 wrapping up a stadium tour for his previous album, followed straightaway by launching <em>Un Verano Sin Ti </em>with a sold-out world tour. He then co-starred alongside Brad Pitt in <a href="https://www.vox.com/culture/23290611/bullet-train-review-pitt-cameos-spoilers"><em>Bullet Train</em></a><em>,</em> and won a <a href="https://www.cbsnews.com/news/bad-bunny-artist-of-the-year-2022-video-music-awards-mtv/">Video Music Award</a>, becoming the first non-English language performer to become Artist of the Year. He accepted his award moments after smooching a male and female dancer during a livestream performance of his song “Tití Me Preguntó” at Yankee Stadium.
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“I always knew that I could become a huge artist without changing my culture, my slang, and my language,” he told the audience in Spanish. “I am Benito Antonio Martínez Ocasio, from Puerto Rico to the world.”
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Generating more than <a href="https://www.billboard.com/music/chart-beat/2022-us-year-end-music-report-luminate-top-album-bad-bunny-un-verano-sin-ti-1235196736/">4 billion US streams across several platforms last year,</a> <em>Un Verano Sin Ti</em> (A Summer Without You) was arguably the biggest album of the year. Globally, that’s true, too, <a href="https://newsroom.spotify.com/2022-11-30/the-top-songs-artists-podcasts-and-listening-trends-of-2022/">according to Spotify</a>. The ambitious album boasts 23 tracks, spanning electronic dance and reggaetón, dembow and indie pop. It’s <a href="https://www.youtube.com/watch?v=Cr8K88UcO0s&amp;ab_channel=BadBunny">banger</a>, after <a href="https://www.youtube.com/watch?v=a5rlgE6dcBY&amp;list=OLAK5uy_l3rT1z1t11Pn6CugxRd3ZxQQOpWGqzUMU&amp;index=2&amp;ab_channel=BadBunny">banger</a>, after <a href="https://www.youtube.com/watch?v=VBiNZcH27Y8&amp;list=OLAK5uy_l3rT1z1t11Pn6CugxRd3ZxQQOpWGqzUMU&amp;index=17&amp;ab_channel=BadBunny">banger</a>. There’s a reason it catapulted Bad Bunny to global stardom after years of steady, genre-defying work: the vibes are immaculate. It feels like getting ready for a party on a hot August night, after spending all day toasting on the beach. You can feel it even if you don’t entirely understand what Bad Bunny’s singing about (depending on the song: heartbreak and partying, <a href="https://www.lanacion.com.ar/estados-unidos/andrea-la-cancion-de-bad-bunny-que-cuenta-el-femicidio-que-paralizo-a-puerto-rico-nid10052022/">gender violence</a>, or <a href="https://www.vox.com/future-perfect/2022/10/10/23391700/puerto-rico-hurricane-recovery-colonialism-debt">Puerto Rico’s political problems</a>).
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But the album wasn’t nominated for a Grammy because it has the right energy (although that’s certainly a part of it). <em>Un Verano Sin Ti </em>is a historic heavyweight — it refuses to pull punches or dumb itself down for English listeners. As Bad Bunny has declared in the past, <a href="https://www.npr.org/2020/03/02/811180499/bad-bunny-review-yhlqmdlg-yo-hago-lo-que-me-da-la-gana-la-dificil">he’s going to do whatever he wants</a>. That goes for sticking to Spanish, as well as rejecting the <a href="https://www.them.us/story/bad-bunny-rolling-stone-interview">misogyny and homophobia</a> that’s rife within reggaetón and Latin trap. His unapologetic politics, sonically experimental approach to genre, and dedication to making music for <a href="https://www.vox.com/culture/23292674/bad-bunny-el-choli-concert-puerto-rico-politics-luma-gentrification">Puerto Ricans and Puerto Ricans alone</a> defied cultural norms. At first, it made him generationally divisive. Now, his music is popular internationally <em>because</em> he has playfully transgressed against the crutch of machismo and the burdens of the American imagination — in a way no other Latin artist has been able to achieve.
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“These political and feminist narratives split him from the rest of the pack, making him a more palatable artist for global consumption because he’s not necessarily pigeonholed like all the other reggaetón artists,” said Carlos Chirinos, director of the <a href="https://steinhardt.nyu.edu/people/carlos-chirinos">NYU Music and Social Change Lab</a>. “He stands out.”
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Who is Bad Bunny, explained
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Bad Bunny’s rise to stardom is folkloric in the way that most modern musicians these days are: he got his start on <a href="https://soundcloud.com/badbunny15">SoundCloud</a>. Growing up in the projects in the Almirante Sur barrio of Vega Baja, Benito was very much a child of the late ’90s and early 2000s, witnessing the crossover of reggaetón into American markets courtesy of Daddy Yankee’s iconic “<a href="https://www.youtube.com/watch?v=CCF1_jI8Prk&amp;ab_channel=DaddyYankee">Gasolina</a>” and the <a href="https://www.billboard.com/music/latin/latin-trap-brief-history-ozuna-bad-bunny-de-la-ghetto-7933904/">birth of Latin trap</a> into the 2010s. Being in the periphery informed his fluid style, which had started to form by the time he started college at the University of Puerto Rico at Arecibo, where he studied communications. He dropped “<a href="https://soundcloud.com/badbunny15/diles">Diles</a>” — the sexy trap track that <a href="https://www.thefader.com/2018/08/28/bad-bunny-cover-story-conejo-malo-interview">grabbed the attention</a> of record label Hear This Music — in 2016 while he bagged groceries at ECONO.
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His first few songs and features, “<a href="https://www.youtube.com/watch?v=ws00k_lIQ9U&amp;ab_channel=BadBunny">Soy Peor</a>,” “<a href="https://www.youtube.com/watch?v=tSrTEpRp_2g&amp;ab_channel=UrbanoVideosTV">Te Boté (Remix)</a>,” and “<a href="https://www.youtube.com/watch?v=xTlNMmZKwpA&amp;ab_channel=CardiB">I Like It</a>” acquainted both Spanish and English-language audiences to his heady, slurred vocals. He racked up even more features, <a href="https://www.vice.com/en/article/439mjj/bad-bunny-releases-debut-album-x100pre">ditched his label</a>, and finally released his debut album in 2018: <em>X 100Pre </em>(“Por Siempre” or “Forever”). It’s a bombastic entry in conversation with the rest of the diaspora, with tinges of hip hop, reggaetón, dembow, and even a little pop punk. (Latin trap, of course, is a direct progeny of <a href="https://www.atlantamagazine.com/list/20-reasons-why-atlanta-americas-music-capital/we-are-trap/">Atlanta’s trap music scene</a>.) <em>X 100Pre</em>’s<em> </em>raw <a href="https://www.youtube.com/watch?v=Fp22B_1Mct8&amp;ab_channel=BadBunny-Topic">melancholia</a> superimposed over dreamy drone synths also flirts with <a href="https://www.youtube.com/watch?v=kPg3M4C9N9w&amp;ab_channel=BadBunny">tradition before spinning it on its head</a>.
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In doing so, Bad Bunny became perfectly positioned to be a trailblazer in Latin trap. Not only is his music offering an emotional and technical complexity to the genre, he successfully brings English-language artists (Diplo, Drake) into Spanish, instead of the other way around. It doesn’t hurt that Benito opts to sing about loneliness and centering female pleasure in a deeply relatable way that braggadocio alone couldn’t support. It makes for perfect Gen Z and young millennial bait.
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Given Latin trap’s vulgar lyrics around sex and drugs, it’s not always easy, radio-friendly listening. Reggaetón, too, is still pretty sexual, but it’s <a href="https://genius.com/J-balvin-safari-lyrics">softened</a> a bit since moving out of the underground and into the international spotlight. Both genres, however, have treated women horribly with <a href="https://www.huffpost.com/entry/this-artists-sexist-and-misogynist_b_13519334">objectification</a>, disdain, and sometimes even violence. (It’d be remiss to not mention the women reggaetón artists, like <a href="https://www.okayplayer.com/music/ivy-queen-reggaeton-history.html">Ivy Queen</a>, who challenged sexism and highlighted the <a href="https://latinamericanpost.com/38225-feminism-and-reggaeton-contradiction-or-reality">contradictions</a> within urbano music.)
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But Bad Bunny is among the first men to embrace a more progressive approach in Latin trap. In <em>X 100Pre</em>, he’s rocking <a href="https://www.youtube.com/watch?v=bcHTl9h7TWI&amp;ab_channel=BadBunny">nail polish</a> and crooning about <a href="https://www.elitedaily.com/p/what-do-the-solo-de-mi-lyrics-mean-bad-bunnys-latest-hit-song-is-all-about-self-love-15726961">how women belong to no one</a>. Most of his songs remain sexual and explicit, but challenging to the norms present. His style of gender presentation and defiant music became a source of controversy within Latin media, making him especially controversial among older people. He didn’t start his career with such a feminist and quasi-queer perspective, but his growth is parallel with the political bubblings in Puerto Rico over the years.
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“What we’re seeing is the evolution of an artist as he’s growing up with us,” said <a href="https://twitter.com/vanessajdiaz">Vanessa Díaz</a>, a Chicano/a studies professor at Loyola Marymount University. She’s currently teaching a <a href="https://www.badbunnysyllabus.com/">class on Bad Bunny</a> and political resistance in Puerto Rico. “What’s so appealing about him is his refusal to accommodate. It’s not as if he’s out there saying, ‘I’m an out queer man.’ He’s not identifying as such. But we are getting an openness, a flexibility, a fluidity. I don’t think that it’s about shock value. It’s actually about the refusal to be confined.”
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Come 2019, Bad Bunny is much more active politically. He’s moved past broad, feel-good proclamations that American audiences tend to expect from musicians. At his core, Puerto Rico is what’s important to him. The island, post-Hurricane Maria, had become mired in another political scandal. Gov. Ricky Rosselló’s Telegram <a href="https://theamericanonews.com/2020/07/28/verano-del-19-the-15-days-that-ended-rossellos-government/">group chat leaked</a>, revealing his disdain for hurricane victims and sparking protests across the island. Bad Bunny was one of the <a href="https://www.forbes.com/sites/andreabossi/2019/12/26/how-bad-bunny-influenced-puerto-ricos-2019-movement-ricky-renuncia/?sh=35e4708a4b5d">few Puerto Rican celebrities</a> who were in the streets. He released a song with Residente and iLe — “<a href="https://www.npr.org/2019/07/28/746089844/a-puerto-rico-protest-song-afilando-los-cuchillos">Afilando Los Cuchillos</a>” or “Sharpening The Knives” — calling for the governor’s resignation. Rosselló stepped down within 15 days. Soon after, Bad Bunny began speaking out against <a href="https://people.com/music/bad-bunny-makes-statement-about-trans-woman-killing-tonight-show/">femicides and transphobia</a><strong> </strong>that plague Puerto Rico.
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<img alt=" " src="https://cdn.vox-cdn.com/thumbor/Fxr-QLIy9d65t1SDo-VdKQQi0M8=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24408144/1157222224.jpg"/> <cite>Eric Rojas/AFP via Getty Images</cite>
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Bad Bunny waves a Puerto Rico flag as he takes part of a national strike demanding Gov. Ricardo Rossello’s resignation, in San Juan, Puerto Rico, in 2019.
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“There was a particular audience consuming this and it was divided along generational lines,” said Jorell Meléndez-Badillo, a Caribbean historian at the University of Wisconsin-Madison, who is penning an article for the <a href="https://twitter.com/jorellmelendezb/status/1608511310463111170">Bad Bunny Enigma</a>, an academic journal analyzing the star. <em>“</em>It’s really interesting how Bad Bunny became this global superstar while in conversation with things that were happening in the archipelago. He was basically making music for people in the archipelago, referencing things that only Puerto Ricans would understand.”
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Then Bad Bunny does something absolutely phenomenal: drop three albums in a year. And not just any year. Just before lockdowns in early 2020, Benito released <a href="https://www.youtube.com/watch?v=KywzeIM45FA&amp;list=PLDUEjoBVMbh_c0UZDAueaYhiopUqr4mUd&amp;ab_channel=BadBunny-Topic"><em>YHLQMDLG</em></a> (A Spanish acronym for “I do whatever I want”). It’s a garage-y, nostalgic ode to early reggaetón and hip hop with powerhouse features from Daddy Yankee, Anuel AA, Arcángel, and more. In May, Bad Bunny followed up with <em>Las que no iban a salir</em>, a compilation album of unreleased songs as well as ones written during quarantine. Finally, he dropped <a href="https://www.youtube.com/watch?v=f5omY8jVrSM&amp;list=PLRW7iEDD9RDQBBft2zmdpdcznIOyDw_n2&amp;ab_channel=BadBunny"><em>El Último Tour Del Mundo</em></a><em>,</em> a Latin trap-rock baby.
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The songs from <em>YHLQMDLG </em>and <em>El Último Tour </em>are stronger conceptually than his first album, reflecting that political and personal growth. “<a href="https://www.youtube.com/watch?v=GtSRKwDCaZM&amp;ab_channel=BadBunny">Yo Perreo Sola</a>” — an anthem for women everywhere telling men to fuck off when they’re dancing — features Benito in drag with body prosthetics, to much <a href="https://www.albionpleiad.com/2020/04/opinion-yo-perreo-sola-the-underlying-messages-in-bad-bunnys-newly-released-song-and-music-video/">acclaim</a> and <a href="https://digitalcommons.usf.edu/cgi/viewcontent.cgi?article=10325&amp;context=etd">controversy</a>. “<a href="https://www.youtube.com/watch?v=ctutQRq76bU&amp;ab_channel=BadBunny">Maldita Pobreza</a>” chronicles the struggle of wanting to shower your lover with expensive gifts, but not being able to. <em>El Último Tour </em>became the <a href="https://www.billboard.com/pro/bad-bunny-el-ultimo-tour-del-mundo-billboard-200-number-one/">first all-Spanish album</a> to debut at No. 1 on the Billboard 200.
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“Bad Bunny is one of those phenomena that contributes to changing culture because it challenges stereotypes,” Chirinos, the NYU music professor, said. “It creates a body of work that’s genius in the way he raps, the way he sings. It’s also the simplicity of his music. His music is very elaborate in terms of production, his performance is very simple — that’s why people connect with it so much.”
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The strategic brilliance of <em>Un Verano Sin Ti </em>
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Everyone loves a summer album, and 2022’s <em>Un Verano Sin Ti </em>proves it on an international scale. Right as travel became a more viable option globally in early May, Bad Bunny drops <em>Un Verano Sin Ti</em> with immersive 360-degree visualizers on YouTube. The first track, “<a href="https://www.youtube.com/watch?v=p38WgakuYDo&amp;ab_channel=BadBunny">Moscow Mule</a>,” opens with gulls cawing, atmospheric synths, and an undeniably tropical beat. You know instantly this album is going to be played on beaches everywhere.
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From the infectious electronic mambo of “<a href="https://www.youtube.com/watch?v=a5rlgE6dcBY&amp;ab_channel=BadBunny">Después de la Playa</a>” to the breathy bittersweetness and indie pop sensibilities of “<a href="https://www.youtube.com/watch?v=VBiNZcH27Y8&amp;ab_channel=BadBunny">Otro Atardecer</a>,” there’s something for everyone. If you couldn’t gel with Bad Bunny before, it’d be hard to find something you couldn’t vibe with on the 23-track album. It bridged the generational gap that eluded him before. “You know, I was a bit resistant to Bad Bunny — I’m an old Latino man,” said Chirinos. “At the very beginning, I was like, ‘I don’t know. I don’t get this guy.’ I didn’t know why people were so crazy about him until I listened to <em>Un Verano Sin Ti</em>. It became my number one album last year by far. There are some songs that I think are some of the best songs not just on the album, but ever.”
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The album, easily, is a love letter to the music of the Caribbean. It pulls from bachata, bomba, merengue, dembow, reggae, cumbia, and bossa nova with electricity. It features reggaetón greats like Tony Dize and Plan B’s Chencho Corleone while also advancing the next generation of Latinx music makers, like The Marías, Buscabulla, and Bomba Estereo. (Bad Bunny probably could have put more effort in featuring Afro-Latinos, given how heavy their influence is here.) The breadth of genre and interplay in <em>Un Verano Sin Ti </em>was sonically familiar globally — after all, who hasn’t felt the irresistible tug of bachata drums, begging you to dance?
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“You can hear the Dominican Republic, the Lesser Antilles, and of course, Puerto Rico,” Meléndez-Badillo said. “Although he is paying a tribute or an homage to the Caribbean, particularly summers in the Caribbean, it’s a record that did not have a particular listening audience. That is why it made it such a huge deal when it came out.”
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<img alt="Bad Bunny, wearing large white-framed sunglasses and a patterned yellow outfit with large purple hearts, sings into a microphone. " src="https://cdn.vox-cdn.com/thumbor/PaEoQ0K3qzHx8O-11l4a0RlUSKk=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24408156/1429278303.jpg"/> <cite>Kevin Winter/Getty Images</cite>
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Bad Bunny performs onstage in September 2022 in Inglewood, California.
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It’s a funny paradox: <em>Un Verano Sin Ti</em> is simultaneously Bad Bunny’s most global album and his most Puerto Rican. While the music clearly brings in influences from elsewhere that can attract listeners from around the globe, lyrically Bad Bunny is singing to the specifics of the Puerto Rican experience. In “<a href="https://www.youtube.com/watch?v=gjvTQTGogUM&amp;ab_channel=BadBunny">Andrea</a>,” he sings alongside Buscabulla’s Raquel Berríos about a woman who wants to live her life free from societal pressure. The album’s star song, though, is “<a href="https://www.youtube.com/watch?v=QdQEljUMCEM&amp;ab_channel=BadBunny">El Apagón</a>,” a lively EDM track where Benito champions the beauty of Puerto Rico and <a href="https://gizmodo.com/bad-bunny-el-apagon-puerto-rico-blackouts-1848923170">critiques the gentrification</a> and <a href="https://www.vox.com/future-perfect/2022/10/10/23391700/puerto-rico-hurricane-recovery-colonialism-debt">regular blackouts</a> happening on the island. “I don’t want to leave / let them go,” sings Gabriela Berlingeri (Benito’s partner) in Spanish. “This is my beach / this is my sun / this my land / this is me.”
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Authenticity like that can’t be manufactured. The music video for “El Apagón” could have been a cute little dance number, but is instead a <a href="https://www.youtube.com/watch?v=1TCX_Aqzoo4&amp;ab_channel=BadBunny">22-minute documentary</a> explaining the context behind the song. When he launched his sold-out world tour, Bad Bunny started in Puerto Rico with affordable tickets and streamed the first of three nights on public television. No matter where you were, it was a <a href="https://www.vox.com/culture/23292674/bad-bunny-el-choli-concert-puerto-rico-politics-luma-gentrification">massive party</a>.
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“He is making music for the people of Puerto Rico, and if other people enjoy it, then wonderful,” Díaz, the professor teaching a course on Bad Bunny, said. “But the music is for them. And guess what? Other people <em>have </em>enjoyed it. It’s this really beautiful example of the fact that you can create for a particular people, you can create for your nation, you can create with this particular kind of purpose. You can deal with it or not. And everyone is dealing with it and loving it.”
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The rise and rise of Latin music
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Bad Bunny does not need the American Grammys. For all intents and purposes, he is already at the top of the charts, has a burgeoning <a href="https://variety.com/2022/film/news/el-muerto-marvel-sony-1235240517/">film career</a>, and moonlights as <a href="https://www.wwe.com/superstars/bad-bunny">a WWE wrestler</a> when he finds the time. His two tours last year combine for the <a href="https://www.billboard.com/pro/bad-bunny-2022-concerts-earn-record-breaking-435-million/">highest gross earnings</a> for an artist in a calendar year at a slick $435 million. And he’ll be headlining at Coachella this year. He will be fine whether or not he wins. But what <em>Un Verano Sin Ti</em> means for the future of music consumption cannot be ignored.
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If Luis Fonsi’s “<a href="https://www.vox.com/culture/2017/8/18/16112710/despacito-biggest-song-of-2017-bieber-fonsi-daddy-yankee">Despacito</a>” remix with Justin Bieber and Daddy Yankee cracked open the nutshell of American markets, <em>Un Verano Sin Ti </em>might absolutely pulverize it. “Despacito” was the first Spanish-language song to be nominated for Song and Record of the Year in 2018, but lost to <a href="https://www.billboard.com/music/awards/despacito-grammys-loss-song-record-of-the-year-2018-snub-meaning-voters-8096867/">Bruno Mars on both counts</a>. You might be thinking: Okay, who cares, the Latin Pop and Latin Urban categories are there, too. But language shouldn’t be siloed, when you can sing any song in any language. If Shakira sang “Hips Don’t Lie” in Spanish, she wouldn’t have been nominated for <a href="https://www.grammy.com/artists/shakira/17393">Best Pop Collaboration</a> in the 00s. It’s historic that Bad Bunny’s album has the honor of going up against Beyoncé.
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The nomination also signals a readiness and openness for American audiences to embrace non-English music. We’re already seeing this happen with <a href="https://www.youtube.com/watch?v=JWESLtAKKlU">Pharrell singing in Spanish</a> and the proliferation of K-pop with BTS (although K-pop stars do tend to incorporate English). Bad Bunny sticking with Spanish is exciting, and indicative of a cultural shift. “We might start seeing other folks who are artists who don’t speak or don’t want to speak English in their music getting huge at this global level,” Díaz said. “He’s setting a completely new precedent that actually is going to change the trajectory of global music.”
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According to data from <a href="https://www.billboard.com/music/chart-beat/2022-us-year-end-music-report-luminate-top-album-bad-bunny-un-verano-sin-ti-1235196736/">music tracker Luminate</a>, consumption of Latin music grew by 28 percent in 2022, and Bad Bunny’s responsible for the top four albums in the genre. That’s only expected to grow as Latinx populations grow in the next few decades, says Chirinos. Latin genres are spreading far and wide, with streaming only increasing the possibilities in genre fusion and exploration.
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“Reggaetón is becoming, in a way, a dominant pop music format, or a format that many international artists would probably choose to use because it appeals to international audiences,” Chirinos said. “Streaming is opening the doors that were perhaps closed before in Latin America. Right now, one of the largest markets for streaming music consumption is Mexico. Another one is Brazil. And these are markets poised to grow. It’s an appealing idea for the music industry, looking at Latin America as well as Africa, as the emerging markets for music consumption. That’s where young people are being born.”
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Latin music or culture can’t be ignored in a world where Bad Bunny is a superstar, which is true regardless of how the Grammys shake out. He’s an artist who’s helping to explode the reach of his genres, while simultaneously exploding what the genres have to offer. That kind of expansion, it can’t be denied.
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“We can’t take that for granted or underestimate the long-term cultural value of the moment,” Díaz said. “All of these things create this really important cultural opening. On a Puerto Rican level, on an American level, on a global level.”
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<li><strong>Why we loved Everything Everywhere All at Once — and why we hope it wins the Oscar</strong> -
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Michelle Yeoh with hot dog fingers in <em>Everything Everywhere All at Once.</em> | A24
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Our panel of experts discusses whether last year’s surprise breakout can win it all on Hollywood’s big night.
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<em>Everything Everywhere All at Once</em>, from the directing duo known as the “Daniels” (Daniel Kwan and Daniel Scheinert), has turned out to be one of 2022’s biggest success stories. It’s a quirky, non-franchise film with a wholly original plot about a Chinese immigrant mother who owns a laundromat with her husband, has a tense relationship with her daughter, and is hurtled into a fantastical plan to destroy the multiverse. Not your typical Oscar fare.
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It has netted a whopping 11 Oscar nominations, and two of its stars — Ke Huy Quan and Michelle Yeoh — have been feted all awards season. Could this little film that became a sensation have a chance on Hollywood’s big night?
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To discuss why the film was such a success, why it tugged at audiences’ heartstrings, and what it would mean if it won Best Picture, we gathered Vox culture reporters Alissa Wilkinson, Alex Abad-Santos, and Aja Romano, along with politics reporter Li Zhou, for a discussion around a (virtual) roundtable.
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<strong>Alissa Wilkinson:</strong> <em>Everything Everywhere All at Once</em> (EEAAO) turned out to be a bona fide sensation, and I confess I was a little surprised. Maybe I’m just brain-poisoned from years of seeing only franchise films top the charts, but I thought this kooky, frenetic, big-hearted, wild-imagination film might be too much for audiences. Yet it really turned out to be the little movie that could. It opened modestly and never really <em>exploded</em>, but it played in <a href="https://www.boxofficemojo.com/release/rl3861218049/?ref_=bo_tt_gr_1">theaters for months</a> (which most movies don’t get to do these days) and ended up making a very healthy amount of money: over $70 million in the US, and over $100 million worldwide, the magic number that turns a movie from a “modest success” to a hit. All that with a modest budget of around $25 million, and without a Marvel star or preexisting IP in sight. And those numbers tell a story — in this case, that the main ingredient in its success was word-of-mouth buzz.
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People who saw it liked it, and they grabbed their friends by the shoulders and yelled, “You too must see this!” and went back a second and maybe a third time to see it again. That’s the way movies used to be, but few get that chance anymore. So I want to ask: In your estimation, what accounts for that success? What about it grabbed people enough that they had to grab their friends? What’s the secret sauce? Why did you see it?
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<strong>Alex Abad-Santos:</strong> Throughout EEAAO’s theatrical run, one of the big explanations of why it was doing so well was <a href="https://www.google.com/search?q=everything+everywhere+all+at+once+word+of+mouth&amp;oq=everything+everywhere+all+at+once+word+of+mouth&amp;aqs=chrome.0.0i512j0i390l5.5363j0j7&amp;sourceid=chrome&amp;ie=UTF-8">word of mouth</a> — basically that people who saw the movie went and told everyone how great it was. The funny thing about that is that this movie is impossible to explain. No amount of description — alternate timelines, jumps, existential crises, moms, hot dog fingers, butt plugs, etc. — could ever accurately describe what’s happening at any given moment during this maximalist fantasia. And if you tried to describe all those things, I don’t think that would sell the movie.
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I think what I ended up doing was that I would tell someone, “Go see this movie.” Then that person sees it, and you can finally talk to them about how absolutely bonkers everything is. You can say, “THE ROCKS!” and the other person will say, “THE ROCKS!” and then you both say, “THE ROCKS!” and it’s like speaking a secret language, which I think all points to how the Daniels, Michelle Yeoh, Stephanie Hsu, and that incredible cast pulled it off.
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<strong>Aja Romano: </strong>When we think about the <em>why</em>, I think there are a couple of factors. One is the sheer popular appeal of a movie produced by the guys behind <em>Stranger Things</em>, made by the guys who did the<a href="https://www.youtube.com/watch?v=HMUDVMiITOU"> “Turn Down For What” video</a>, with a cast that includes a martial arts movie legend, a horror scream queen, and an ‘80s action movie child star. It’s a storyline about a multiverse with an entire subplot dedicated to homaging <em>Ratatouille</em>. This film’s geek cred is almost as stuffed and randomized as its plot.
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But the other thing is that the film’s utter absurdism functions like a yell in response to the present age. We live in an era where our foremost Black rapper is a <a href="https://www.vox.com/culture/23400851/kanye-west-antisemitism-hitler-praise">white supremacist</a>, where <a href="https://www.nytimes.com/2022/04/22/us/florida-rejected-textbooks.html">Florida bans math books</a> for teaching kids about their feelings, where chatbots are <a href="https://knowyourmeme.com/news/person-tweets-ai-generated-hot-girls-and-claims-its-so-over-but-real-human-hot-girls-arent-so-sure">learning to generate</a> gigantic-chested fake girls with missing fingers and extra eyelids. Reality seems more overwhelmingly surreal by the day, so why not make a movie that combats existential despair using positive absurdism, where Jamie Lee Curtis may have hot dogs for hands. Even people with hot dogs for hands can have epic multiverse-spanning love stories, and that’s beautiful.
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Because the other thing about this movie is not just that it got incredible word-of-mouth, but that everyone also told you to bring tissues: that this was not just a fun, zany, chaotic brain-buster of a movie, but one that would shred your heart in the best way.
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<strong>Li Zhou: </strong>Yes! It’s that combination of tenderness and spectacle that ultimately got me. The quiet moments that the film sets up between its main characters including Evelyn (Michelle Yeoh) and Waymond (Ke Huy Quan) amid the literal chaos that everyone has alluded to, are such an artful contrast and respite.
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The now-iconic line about laundry and taxes, for example, is so emblematic of how the movie is part pandemonium and part raw emotion. In the end, EEAAO has got cooking raccoons, martial arts battles, and BDSM interludes, as well as this mushy and warmhearted core that’s captivating in its own right.
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<strong>Alissa:</strong> Among the movie’s many virtues — and we all agree, it has many — is the way it deals with some potentially thorny or tricky subjects in the form of a multi-universe melodrama/comedy. It’s about <a href="https://www.vox.com/culture/23025832/everything-everywhere-all-at-once-parental-apology-fantasy-turning-red">parents saying they’re sorry</a>, about <a href="https://www.vox.com/culture/23024945/everything-everywhere-all-at-once-multiverse-explained-quantum-physicist">quantum physics</a>, about regretting your past, about depression and anxiety, and about the experience of a family in which the parents are Asian immigrants and the daughter was raised in America. Which of these — or any other — struck a chord with you as you watched? And how well do you think the movie handled them?
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<strong>Alex:</strong> Being that my parents immigrated to America in the ’80s and I’m a first-generation Asian American who just happens to be a flagrant homosexual who loves Michelle Yeoh (ever since <em>Crouching Tiger</em>), there were moments in this movie that hit close to home. Like, yes, a scene about how difficult it is for immigrant parents to fully understand their kids’ lives (and vice versa) is going to strike a nerve! At the same time, Yeoh’s Evelyn and Hsu’s Joy felt like distinct characters with unique journeys that I wanted to see more of and was refreshed by.
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I do find it wickedly funny that a few years ago, the buzz was about <em>Crazy Rich Asians</em> and what its success meant for Asian American representation in Hollywood movies. At the time, I tepidly <a href="https://www.vox.com/2018/12/21/18141213/crazy-rich-asians-success">joked</a> that hopefully we would get to the point where Asian people didn’t have to be rich or glamorous to warrant a movie being made about them, that maybe true equality and representation would mean that “crazy poor Asians” would get to have stories too. And, well, <a href="https://www.vox.com/culture/2020/2/9/21122561/oscars-2020-parasite-best-picture"><em>Parasite</em> won Best Picture in 2020</a>, and three years later we have a story about a depressed Asian American immigrant mom and her existentially crisis-afflicted daughter in the running for another top award.
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<strong>Aja:</strong> A lot has been written about Joy’s monster as a metaphor for her depression, and I think the movie handled that so well, but it was Evelyn’s anxiety that also really spoke to me, personally — she had this sense of feeling overwhelmed with every small thing she had to do just to get through daily living. With Joy, my feeling was closer to, “Is she depressed or just living in 2022?”
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But also the dynamic between them was so rich and painfully real — the barbs they exchanged landed every time. Certainly every queer kid can relate to the horror of one’s parents trying to mitigate the way they introduce their significant other to relatives who might be less than charitable. The deep hurt and tension laced throughout those scenes was a stellar example of how this movie shows you its taut intergenerational conflicts without spelling them out. Such disparate 2022 movies as <a href="https://www.vox.com/culture/22981394/turning-red-reviews-controversy-reactions-parents"><em>Turning Red</em></a> and the horror film <a href="https://www.vox.com/culture/23500334/2022-horror-movies-x-pearl-barbarian-umma-old-people"><em>Umma</em></a> also prominently featured Asian diaspora protagonists working through a lot of trauma as immigrants and reconciling with their parents across generational and cultural conflicts. As with both of those films, I found this one extremely universally relatable on all these fronts.
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<img alt="A woman with a googly eye stuck to her forehead holds a handsome younger man in glasses by the hair and seems to be speaking into his ear. They both seem to have recently been through a tussle, and they’re in an office building." src="https://cdn.vox-cdn.com/thumbor/CF56e5a0HOoN_Gr8rv3O9vBjd5s=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24407532/ee2.jpg"/> <cite>A24</cite>
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Harry Shum Jr. and Michelle Yeoh in <em>Everything Everywhere All at Once.</em>
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<strong>Li:</strong> To Alex’s point, the fact that this film, and multiple others that have garnered acclaim in recent years, like <em>Minari</em>, are about the stories of different Asian American families without relying on dated tropes or the qualifier of being “crazy rich” is pretty moving and feels significant.
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And I especially loved how Yeoh described this film in her Golden Globes speech as centering a “very ordinary immigrant Asian woman, mother, daughter, who was trying to do her audit.”
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One of the relationships that stood out to me in the movie was also the one between Evelyn and her father, who’s referred to as Gong Gong (James Hong). As a child of immigrants, I’ve definitely witnessed the fracturing between different generations of family members that can be part of the immigrant experience, and the film does a really admirable job capturing the enduring nature of that pain. Relatedly, I thought James Hong’s performance — in addition to those of the other leads — was phenomenal and should be getting more hype.
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<strong>Alissa: </strong>There’s one other big part of this movie that seems hot right now: Like many a recent blockbuster (we are looking at you, MCU), it’s about the multiverse. More specifically, it uses the idea of many universes coexisting to plumb something that feels very true about love, relationships, regret, and empathy.
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It’s interesting to me to see multiverse concepts employed in this manner — it’s a little like what actually does happen in the MCU, but instead of being focused on the action, it’s focused on the emotion. Why do you think this concept resonates so much with filmmakers and audiences right now?
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<strong>Aja: </strong>I think it goes back to that feeling of being overwhelmed that I spoke of earlier. Reality is just <em>so much</em> lately, and it’s partly in response to that feeling that we’ve seen an increase in a kind of performative nihilism — everything from edgelord meme culture to shitposting to <a href="https://www.vox.com/2017/1/23/14354840/silicon-valley-billionaires-prepping-survive-underground-bunkers-new-yorker">billionaire bunkers</a> and <a href="https://www.hawaiipublicradio.org/the-conversation/2021-12-30/what-is-covid-fatalism-and-how-can-you-avoid-getting-stuck-in-that-mindset">covid fatalism</a>. We see that reflected in the film: Joy’s — er, Jobu Tupaki’s reason for trying to destroy the multiverse is that “nothing matters.”
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And when you’re faced with that kind of argument, the only possible answer a hopeful human being can really provide, if we want to not be crushed beneath the weight of the alternate possibility, is: “No, everything matters.”
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What better way to show that than through a multiverse where everything, every act and choice, even tiny gestures of humanity or inhumanity, has a ripple effect — not just across lives but across dimensions? Everything, everywhere, all at once, matters.
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Stephanie Hsu in <em>Everything Everywhere All at Once.</em>
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<strong>Alex: </strong>I have to agree with Aja. One of the more popular refrains of the last few years is that we are all living in the stupidest timeline. And we do! There are so many heinously daft things happening in all of our lives right now that sometimes you cannot help but laugh at it all! The hope and possibility that there’s a version of me living a better, more fun, more hilarious life than me right now is such a joy to think about, and I think that — in large part — is what makes the movie feel so nourishing.
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<strong>Li:</strong> One of the other functions of the multiverse that felt particularly special in<em> Everything Everywhere All at Once</em> is how this concept enabled the actors to take on different versions of their characters. The toggling back and forth between the various Waymonds, Evelyns, Joys, and Gong Gongs was both impressive to witness and an approach that was constantly pushing the audience to reconsider its perception of various characters.
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The contrast between Alpha Waymond and Regular Waymond, for instance, offered this really interesting commentary on masculinity, and how the value of kindness, playfulness, and optimism, is often overlooked.
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<strong>Alissa: </strong>So now I guess it’s time to address the googly-eyed rock in the room: Can this movie win Best Picture? I vacillate wildly between thinking it’s a slam-dunk and a long shot. Maybe it’s both. And if you don’t care to venture a guess at the mind of the Academy, what would it mean for a movie like this to win at the Oscars?
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<strong>Alex:</strong> I have a tip that gives me peace of mind, and it is that awards don’t matter. These awards don’t reward quality or ingenuity or feats! They’re mostly popularity contests and the result of who <a href="https://www.vox.com/culture/23581369/andrea-riseborough-oscar-nomination-controversy-2023">campaigned the best</a>! And I usually stick to that worldview unless, of course, something (the 2009 movie <em>An Education</em>) or someone (Rihanna, Beyoncé, Carly Rae Jepsen) I deeply admire wins, because then, of course, awards do matter and the correct person or movie or album won!
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In this case, I think EEAAO has enough things that the Academy likes — a story about America, an under-appreciated star lead in Michelle Yeoh, a great Jamie Lee Curtis performance, etc. — that it can win. I feel like the real story is Yeoh’s shot at Best Actress, as it will be the Academy’s chance to play a part in a feel-good story about feeling seen and people finally recognizing Yeoh’s talent. But again, we don’t need the Oscars to tell us that Yeoh always brings a dignity and sparkling thrill to every character she plays.
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<strong>Aja: </strong>I do think Ke Huy Quan is almost certainly a lock for Supporting Actor, and it seems like his comeback story is destined to be one of the more storied Hollywood glow-ups. If Michelle Yeoh wins, it will be a welcome sign of the Academy’s ongoing shift toward a broader appreciation of a diversity of experience and range of talent; it would be a huge feat to pull off a win over Cate Blanchett in the year of <a href="https://www.vox.com/culture/23385471/tar-review-cate-blanchett-field"><em>Tár</em></a>, but if anyone can do it, it’s Yeoh.
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<strong>Li: </strong>There is something kind of delightful to think about how this incredibly imaginative — and at times truly wild — film could win in an awards show that’s been known for being pretty stuffy in the past.
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I’m also keeping a close eye on the long-overdue acting awards, while echoing the caveat that Yeoh and Quan don’t need any such recognition to validate their incredible performances. My secret hope is that the actors would perhaps go even further in calling Hollywood out if they win, though fully admire just how gracious they were at the Globes and beyond.
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<strong>Alissa: </strong>I couldn’t agree more. I’ve been lucky enough to hear Quan give several speeches (including at the awards gala for my own critics’ group awards!) and he fits the comeback narrative perfectly — and on top of it, it would be a delight to see him win. But mostly, I’d take an <em>Everything Everywhere All at Once</em> win as a sign that something — taste, proclivities, signs of what’s “best” — has shifted in the Academy along with the <a href="https://www.vox.com/22332389/oscars-academy-diversity-membership-2021">demographic changes</a>.
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Whatever the case, though, when I get down about the state of Hollywood (and I do, pretty often), I look at movies like this one as a sign of hope. Even if it wasn’t your favorite film of the year — and it wasn’t for me! — it’s a warm-hearted burst of creativity that’s not quite like anything the business usually churns out, and I’m so glad to see it make it into awards conversations. Like these!
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Everything Everywhere All at Once <em>has returned to theaters in advance of the Oscars. It’s also available to stream on Paramount+ or rent or purchase on digital platforms.</em>
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<li><strong>The trials of Elon Musk</strong> -
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Elon Musk leaving court in San Francisco, California on February 3, 2023. | <a class="ql-link" href="https://www.gettyimages.com/search/photographer?photographer=Bloomberg" target="_blank">Bloomberg</a>/Contributor
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A jury found the Tesla CEO not liable in a shareholder lawsuit, but the case revealed a lot about Musk’s refusal to back down.
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Elon Musk and Tesla were found not liable for investors’ losses after Musk tweeted in 2018 that funding had been secured to take Tesla private, in a class-action lawsuit that was much watched because of its high-profile defendant. It marked the <a href="https://www.axios.com/2022/11/16/elon-musk-compensation-package">second time in recent months</a> that Musk appeared in court to defend himself as CEO of Tesla, at a time when the company’s investors have increasingly <a href="https://www.wsj.com/articles/tesla-investors-voice-concern-over-elon-musks-focus-on-twitter-11670948786">expressed concerns about Musk’s leadership</a>.
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The verdict proved yet another twist in a months-long public debate about the billionaire’s impetuous, often contentious behavior, especially <a href="https://www.vox.com/the-goods/2022/11/28/23473239/elon-musk-twitter-ceo-leadership">on Twitter</a>. The trial, in the end, revealed as much about how he views his Twitter habits as it did about how he ran the EV company.
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For the past several weeks, Musk has defended himself against the lawsuit over a <a href="https://twitter.com/elonmusk/status/1026872652290379776">tweet</a> he posted on August 7, 2018: “Am considering taking Tesla private at $420. Funding secured.” The stock price, which had hovered <a href="https://www.bloomberg.com/graphics/2018-teslas-crazy-day/">above $340</a> when the markets opened that day, swung up as shareholders envisioned a tidy profit when the buyout was complete. A little more than a week later, when Musk said going private was a no-go in a <a href="https://www.nytimes.com/2018/08/16/business/elon-musk-interview-tesla.html">New York Times interview</a>, the price fell.
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Shareholders quickly <a href="https://www.teslasecuritieslitigation2018.com/admin/api/connectedapps.cms.extensions/asset?id=0dba38e0-bb1f-4819-a425-2f9638780ffa&amp;languageId=1033&amp;inline=true">sued Musk, Tesla, and company directors</a> for securities fraud, alleging that Musk had known his tweets were false and that they had cost them billions of dollars. The lawsuit alleged that Musk had not discussed a specific $420-per-share price with would-be buyers. During the trial, which began in the Northern District of California on January 17, Musk and Tesla argued that the tweets had not been false, merely incomprehensive — and that Musk, at the time, had fully believed investors that would fund the move would pull through.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xXlvKs">
A nine-person jury in a California courtroom reached the verdict in just a few hours. The jury had been asked to find whether Musk and Tesla managed to prove their claims separately. If any of the defendants were found liable, they also would have had to determine how much Tesla’s stock price had been artificially inflated on each day between August 7 and August 17. In the end, jurors determined neither the mercurial billionaire nor the electric car company owed investors a dime.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wuM8X7">
The 2018 tweet had already proven troublesome for Musk and Tesla. The Securities and Exchange Commission sued Musk for <a href="https://www.sec.gov/news/press-release/2018-226">securities fraud</a> in connection with the missive in 2018; he and Tesla settled and were ordered to pay a $40 million penalty, and Musk was required to step down as chair of the Tesla board for three years. His SEC settlement didn’t just come with a monetary penalty — he agreed that his tweets about Tesla would be internally reviewed going forward. Musk, who has treated the <a href="https://www.reuters.com/technology/musk-says-us-sec-bastards-forced-settlement-over-tesla-tweets-2022-04-14/">SEC with contempt</a>, says he was coerced into agreeing to this particular leash. Last year, his lawyer wrote in a court filing that the order existed to “chill his exercise of First Amendment rights.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Z3q18E">
The lead plaintiff representing shareholders was Glen Littleton, a 71-year-old Missouri investor who says he bought Tesla stock after the “funding secured” tweet under the belief that the price would go up. But when the take-private didn’t happen, Littleton argued, he <a href="https://www.reuters.com/article/us-otc-tesla/tesla-class-action-judge-is-reconsidering-lead-plaintiff-in-fraud-case-idUSKBN1OG296">lost millions</a>. An expert witness for the plaintiffs estimated that Tesla investors — not just those who bought or sold Tesla securities between August 7 and August 17 — lost <a href="https://www.bloomberg.com/news/articles/2023-01-31/tesla-investors-lost-12-billion-after-musk-tweet-jury-told#xj4y7vzkg">$12 billion</a> in the 10 days between the tweet and the revelation that the deal would not be taking place. The lawsuit sought damages reported to be in the billions. The plaintiffs argued not only that Elon Musk was liable for making fraudulent tweets, but that Tesla as well as its then-board directors (a group that includes Musk’s brother Kimbal and James Murdoch, son of Fox News media mogul Rupert) were also liable for failing to stop Musk from disseminating false information that harmed shareholders.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NsNZrl">
The lawsuit was a test of whether Musk would be held accountable for making statements that potentially impact markets on Twitter — a platform he now owns, which he has championed for its importance as a free speech haven. After the verdict, Musk <a href="https://twitter.com/elonmusk/status/1621653950947799042">tweeted</a>, “Thank goodness, the wisdom of the people has prevailed!”
</p>
<h3 id="COrPhC">
“Funding secured” — or was it?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fu28V2">
During his <a href="https://www.washingtonpost.com/technology/2023/01/23/elon-musk-tesla-trial/">multi-day court testimony,</a> Musk maintained that what he had tweeted had been the truth, and that he had essentially been thrown under the bus by Saudi Arabia’s Public Investment Fund (PIF), which he said was prepared to provide funding for a buyout. The deal was all but inked, he argued, when he tweeted in August 2018 that the only <a href="https://twitter.com/elonmusk/status/1026914941004001280">remaining hurdle was a shareholder vote</a>. He also <a href="https://www.ft.com/content/f64e3214-f94f-462b-90a4-e9d35d7143da">told the court</a> that he wanted to get ahead of a <a href="https://www.ft.com/content/42ca6c42-a79e-11e8-926a-7342fe5e173f">Financial Times article</a> reporting that the Saudi fund would acquire a <a href="https://www.bloomberg.com/news/articles/2023-01-24/key-takeaways-from-musk-s-third-day-of-testimony-in-fraud-trial">3 to 5 percent stake in Tesla</a>. Deepak Ahuja, former chief financial officer at Tesla, <a href="https://www.bloomberg.com/news/articles/2023-01-25/tesla-ex-cfo-says-timing-of-musk-s-go-private-tweet-wasn-t-ideal">testified</a> that both he and Musk believed the Saudi PIF would fund the entire buyout. “If they say they’re going to do something, they do it,” Musk <a href="https://www.bloomberg.com/news/articles/2023-01-23/key-takeaways-from-musk-s-second-day-of-testimony-in-fraud-trial">said</a> in court. The PIF, he argued, had backed out of the deal.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2hs5eT">
Part of Musk’s defense was also that what’s said on Twitter is often taken with a grain of salt. His argument was that people who read his “funding secured” tweet would have understood the context of the medium — “that this is a very brief statement on Twitter that can’t be fully explained [and that] nobody believes what they read on Twitter exactly,” explained Ann Lipton, a law professor at Tulane University.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Nbme47">
“Just because I tweet something doesn’t mean people believe it or act accordingly,” Musk — new CEO of Twitter, longtime CEO of Tesla and SpaceX — told the courtroom in late January. His testimony downplayed the reach and power his words have on the site that he paid $44 billion to own, where he has over 127 million followers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vzwzwm">
In the SEC’s 2018 complaint against Musk, the agency contended that he hadn’t specifically discussed price with potential investors. In court, Musk said that though there was no written agreement, he didn’t need one to be confident about funding. When asked whether he had set a specific price with the Saudi representatives, Musk said he had not. A court <a href="https://storage.courtlistener.com/recap/gov.uscourts.cand.330489/gov.uscourts.cand.330489.403.0.pdf">motion</a> filed in April 2022 revealed that Musk had one conversation with the Saudi PIF before the August 7 tweet. Making the case even more difficult to parse, the governor of the Saudi fund, Yasir Al-Rumayyan, <a href="https://www.bloomberg.com/news/articles/2023-01-12/saudi-pif-seeks-to-block-subpoena-in-musk-s-tesla-fraud-case">refused to testify</a> in the case. Musk’s lawyers attempted to subpoena him, but the PIF’s lawyers argued that Al-Rumayyan isn’t legally obligated to testify in the California court.
</p>
<h3 id="sFFBjA">
Musk tweeted, and Tesla prices shot up
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BDXCv2">
Musk and his legal team argued that it is hard to say whether his tweets had caused wild swings in Tesla’s stock value, because market behavior can be “<a href="https://news.yahoo.com/the-tweets-are-truthful-elon-musk-takes-witness-stand-to-defend-2018-tesla-tweet-223444555.html">counterintuitive</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="90giD0">
A report prepared by one of the plaintiffs’ expert witnesses, economic consultant Michael Hartzmark, noted that Tesla’s value shot up by almost 11 percent on August 7, the day of the “funding secured” tweet. Hartzmark’s report said that this was an abnormal return of statistical significance. A day after the <a href="https://www.nytimes.com/2018/08/16/business/elon-musk-interview-tesla.html">Times interview</a> with Musk, on August 17, Tesla’s closing price was just under 9 percent lower than the previous day’s close. Third-party analysts have also observed that immediately after Musk’s tweet, Tesla’s trading volume <a href="https://www.cnbc.com/2023/01/20/elon-musk-defends-tweets-in-securities-fraud-trial-in-san-francisco.html">increased tenfold</a> — and trading was temporarily halted.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UBPwCy">
“If these investors purchased the stock at a price that was too high, which eventually did come back down in the near term, and then sold, then that purchase was made on false information,” said Josh White, a Vanderbilt University finance professor and former SEC economist.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kNklQy">
Experts, however, told Vox that it was extremely unusual for a class-action securities case to go to trial. When it does, it’s usually because the plaintiffs’ case is extremely weak and the defendant is confident they can win — otherwise, companies almost always settle. The fact that Musk and Tesla chose to take their chances in court is itself remarkable.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZrqdMe">
“I’m sure he has many reasons for going to trial — although it’s really, really rare,” said David Rosenfeld, a securities law professor at Northern Illinois University. But being able to defend his 2018 tweets was likely one major benefit. “He’s using this, basically, as a public forum to vindicate himself.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JlZrde">
And Musk has insisted the information in this case was legitimate. “The tweets are truthful,” he said in his testimony, contending that he was merely unable to be comprehensive in his tweets given the character limit.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AAvlpL">
Musk’s lawyer, Alex Spiro, argued that the tweets contained only “<a href="https://www.reuters.com/legal/tesla-shareholders-lay-out-arguments-funding-secured-fraud-trial-2023-01-18/">technical inaccuracies</a>.”
</p>
<h3 id="x8pWAc">
What does “technically inaccurate” mean?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BiQYII">
A slightly more credible argument, Lipton told Vox, was that any inaccuracies in Musk’s tweets didn’t really matter.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1pATfk">
Before the trial began, the court had already ruled that Musk’s August 7 tweets were false and made recklessly. This was important, because in a fraud case, the plaintiff has to show either that the defendant intentionally committed fraud or that they acted recklessly. It was a leg up for the plaintiffs in this case that the jury was instructed to accept as fact that Musk had tweeted falsely and recklessly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YxZN6q">
“Musk’s chief defense is ‘All right, it might have been technically false but spiritually true,’” said Lipton. And the plaintiffs weren’t attempting to prove whether Musk’s tweets were false — the court had already established that they were — but that what the tweets misstated was directly tied to the shareholders’ losses. The defense’s argument is that “the undisclosed facts — that is, what the market did not know about this arrangement — were immaterial,” explained Lipton. They would have lost money anyway, or so the argument goes.
</p>
<h3 id="Wv5BTw">
<strong>Tesla investors to CEO: Please stop tweeting</strong>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nkqTTD">
A central facet of the trial wasn’t just the “funding secured” tweet, but Musk’s well-documented habit of tweeting impulsively and without restraint. Plaintiffs’ lawyers argued that his past Twitter statements have revealed information that should not have been public, affected markets, and harmed shareholders. Several Tesla shareholders and others involved with the company testified that they had attempted to get him to <a href="https://apnews.com/article/elon-musk-technology-business-99cef10941f150a5023b1d8c7992c122">stop tweeting</a> (requests that he <a href="https://www.theverge.com/2023/1/20/23564629/elon-musk-twitter-testimony-securities-fraud-trial">ignored</a>).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="txs1dl">
His manner of communicating brusquely became evident during his testimony, too. He occasionally gave <a href="https://apnews.com/article/elon-musk-spacex-twitter-inc-technology-san-francisco-d40110071eb0c546e393f86cf912207a">defiant answers</a> to the plaintiffs’ lawyers, resisting offering a yes or a no. At times his responses were stricken from the court record for being irrelevant or inappropriate. Nicholas Porritt, a lawyer for the plaintiffs, for example, asked whether Musk would agree that he had lost money for an investor who had bought Tesla stock on August 8 believing in the truth of Musk’s tweets, only for the price to fall when it was revealed that funding wasn’t secured.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EPRW38">
“Your question contains falsehoods,” Musk <a href="https://www.bloomberg.com/news/live-blog/2023-01-20/elon-musk-securities-trial?cursorId=63D0322E68900000">replied</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gzYxs4">
Musk has made it abundantly clear that he believes his personal Twitter account is a place where he should be able to express himself freely. Musk’s MO on Twitter often blurs the line between earnestness and shitposting. At times, what he says on the site is to be taken seriously — it’s a direct line of communication between Musk and anyone who wants to keep up with him and his companies. He shares updates and <a href="https://twitter.com/elonmusk/status/1591092334007287809">rebuts</a> <a href="https://twitter.com/elonmusk/status/1598755659499044879">news reports</a> via Twitter. More recently, Musk has extolled Twitter’s ability to be a better source of news than “<a href="https://twitter.com/elonmusk/status/1593160857588232192">old-school media</a>” with <a href="https://twitter.com/elonmusk/status/1585292083610279936">less bias</a>. “Twitter is arguably already the least wrong source of truth on the Internet, but we obviously still have a long way to go,” Musk <a href="https://twitter.com/elonmusk/status/1616179085507702785">tweeted</a> recently.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SEouJD">
Yet Musk also sometimes insists that his own tweets shouldn’t be taken at face value. In a <a href="https://www.latimes.com/business/story/2019-12-10/elon-musk-tweets-tesla">defamation lawsuit</a> in which a diver involved in the 2018 Thai cave rescue sued Musk for calling him a “pedo guy” on Twitter, his lawyers argued that Twitter is hyperbolic and no reasonable person would rely on it as a source of facts.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YcrA4x">
Shades of that argument appeared in this trial as well,<strong> </strong>highlighting Musk’s tricky, tangled relationship with the social media site, where he’s been a prolific tweeter for more than a decade, and where he has <a href="https://www.vox.com/the-goods/2022/11/28/23473239/elon-musk-twitter-ceo-leadership">sowed chaos</a> over the past several months through mass firings and haphazard changes that have led to an exodus of advertisers and a rise in hate speech. On the one hand, Twitter has provided a handy platform for Musk to share his views and news about his companies; his off-the-cuff Twitter persona helped <a href="https://www.vox.com/recode/2022/10/28/23426922/elon-musk-army-fandom-former-fans-twitter-ceo">grow his fan base</a>, which has bolstered Tesla’s popularity and stock value. On the other hand, Musk’s habit of impulsive tweeting keeps landing him in hot water.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8Wd8WR">
Despite these legal troubles, Musk has continued to tweet.
</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>Agnostic and Imperial Blue please</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>Mad Love and Justin impress</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>Australia can win, India more vulnerable at home this time: Greg Chappell</strong> - “India are more vulnerable at home than they have been for some time due to injuries to key players,” said former India coach Greg Chappell</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>Dipa Karmakar handed 21-month ban after failing dope test</strong> - Dipa Karmakar’s ban period will, however, end on July 10, 2023 as it was counted from the day (October 11, 2011) the sample was collected</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>Sri Ramakrishna Cricket Trust girls dominate</strong> -</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>Cong. complains to RC against Mayor</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>Insight Award for Madhu Ambat</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>Action against criminals within police force: DGP</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>Midday meal: DDPI visits Akshaya Patra kitchen</strong> - Meals were supplied to 145 government and aided schools in Mysuru city by the Akshaya Patra Foundation; 18,900 were fed under noon-meal scheme</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>Palakkad IIT holds Open House Day</strong> - 1,150 students from various schools and colleges in Kerala and Tamil Nadu visited the IIT campus on the first day of the two-day Open House, which also coincided with IIT’s techno-cultural festival titled ‘Petrichor’ 2023</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: US to provide long-range missiles in latest aid package</strong> - The fresh aid worth $2.2bn (£1.83bn) includes rockets capable of striking parts of occupied Crimea.</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>Ukraine war: On the front line with engineers working to fix stricken power grid</strong> - The BBC watches engineers and technicians as they race to repair damage across the country.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Andrew Tate: Influencer threatened workers with violence, victim claims</strong> - The alleged victim claims Andrew Tate forced workers to raise €10,000 a month on social media platforms.</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>Paco Rabanne: Celebrated designer dies aged 88</strong> - Paco Rabanne, best known for his perfumes and fashion designs, dies at his home in France.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pope and archbishop on historic peace mission to South Sudan</strong> - The holy men hope to heal South Sudan, the world’s newest nation, overcoming a brutal civil war.</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>Freak infection with an eradicated form of polio shows virus’ craftiness</strong> - Without wastewater sampling, the eradicated virus could have easily spread. - <a href="https://arstechnica.com/?p=1915106">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Musk beats fraud charges; jury rejects investor claims in “funding secured” case</strong> - Musk lawyer claimed investors were “gambling and looking for lawsuits as insurance.” - <a href="https://arstechnica.com/?p=1915085">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why would the Chinese government be flying a large stratospheric balloon?</strong> - It is possible that the balloon’s flight termination system failed. - <a href="https://arstechnica.com/?p=1914963">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Microsoft alleges attacks on French magazine came from Iranian-backed group</strong> - Leaked personal data of Charlie Hebdo customers puts them at risk from extremists. - <a href="https://arstechnica.com/?p=1915010">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SEC gets $35 million settlement in Activision misconduct disclosure case</strong> - Government says company also violated whistleblower protection laws. - <a href="https://arstechnica.com/?p=1915026">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>Why is Metallica the safest band to listen to in an airport?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Because they haven’t set off a metal detector since 1989.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MrNumber3IsMe"> /u/MrNumber3IsMe </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/10swdjv/why_is_metallica_the_safest_band_to_listen_to_in/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/10swdjv/why_is_metallica_the_safest_band_to_listen_to_in/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What does 007’s doorbell sounds like?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Dong. Ding Dong
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/SnowyMooncake"> /u/SnowyMooncake </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/10slv6m/what_does_007s_doorbell_sounds_like/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/10slv6m/what_does_007s_doorbell_sounds_like/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I now identify as invisible</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Although I was born visible, I am now trans-parent. My pronouns are who/where
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Valiric999"> /u/Valiric999 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/10t3uxr/i_now_identify_as_invisible/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/10t3uxr/i_now_identify_as_invisible/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>She married and had 13 children. Her husband died…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She married again and had 7 more children.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Again, her husband died.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
But, she remarried and this time had 5 more children.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She finally died after having 25 children.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Standing before her coffin, the preacher prayed for her.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He thanked the Lord for this very loving woman and said,’ Lord, they’re finally together.’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
One mourner leaned over and quietly asked her friend,’ Do you think he means her first, second, or third husband? ’
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The friend replied, ’ I think he means her legs.’
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/ThomasKatt"> /u/ThomasKatt </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/10sli85/she_married_and_had_13_children_her_husband_died/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/10sli85/she_married_and_had_13_children_her_husband_died/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man calls quantum IT support and complains that his quantum computer isn’t working.</strong> - <!-- SC_OFF --></p>
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Quantum IT support: “Have you tried turning it off and on at the same time?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/alexmojaki"> /u/alexmojaki </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/10suf8r/a_man_calls_quantum_it_support_and_complains_that/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/10suf8r/a_man_calls_quantum_it_support_and_complains_that/">[comments]</a></span></p></li>
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