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<title>17 April, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Longitudinal sequencing and variant detection of SARS-CoV-2 across Southern California wastewater from April 2020 - August 2021</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wastewater based epidemiology (WBE) is a useful method to detect pathogen prevalence and may serve to effectively monitor diseases at a broad scale. WBE has been used throughout the COVID-19 pandemic to track localized and population-level disease burden through the quantification of SARS-CoV-2 RNA present in wastewater. Aside from case load estimation, WBE is being used to assay viral genomic diversity and the emergence of potential SARS-CoV-2 variants. Here, we present a study in which we sequenced RNA extracted from sewage influent samples obtained from eight wastewater treatment plants representing 16 million people in Southern California over April 2020 - August 2021. We sequenced SARS-CoV-2 with two methods: Illumina Respiratory Virus Enrichment and metatranscriptomic sequencing (N = 269), and QIAseq SARS-CoV-2 tiled amplicon sequencing (N = 95). We were able to classify SARS-CoV-2 reads into lineages and sublineages that approximated several named variants across a full year, and we identified a diversity of single nucleotide variants (SNVs) of which many are putatively novel SNVs, and SNVs of unknown potential function and prevalence. Through our retrospective study, we also show that several sublineages of SARS-CoV-2 were detected in wastewater up to several months before clinical detection, which may assist in the prediction of future Variants of Concern. Lastly, we show that sublineage diversity was similar between wastewater treatment plants across Southern California, and that diversity changed by sampling month indicating that WBE is effective across megaregions. As the COVID-19 pandemic moves to new phases, and additional SARS-CoV-2 variants emerge, the ongoing monitoring of wastewater is important to understand local and population-level dynamics of the virus. Our study shows the potential of WBE to detect SARS-CoV-2 variants throughout Southern California9s wastewater and track the diversity of viral SNVs and strains in urban and suburban locations. These results will aid in our ability to monitor the evolutionary potential of SARS-CoV-2 and help understand circulating SNVs to further combat COVID-19.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.14.23288559v1" target="_blank">Longitudinal sequencing and variant detection of SARS-CoV-2 across Southern California wastewater from April 2020 - August 2021</a>
</div></li>
<li><strong>Unsupervised Machine Learning Unveil Easily Identifiable Subphenotypes of COVID-19 With Differing Disease Trajectories</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Given the clinical heterogeneity of COVID-19 infection, we hypothesize the existence of subphenotypes based on early inflammatory responses that are associated with mortality and additional complications. Methods: For this cross-sectional study, we extracted electronic health data from adults hospitalized patients between March 1, 2020 and May 5, 2021, with confirmed primary diagnosis of COVID-19 across five Johns Hopkins Hospitals. We obtained all electronic health records from the first 24h of the patient9s hospitalization. Mortality was the primary endpoint explored while myocardial infarction (MI), pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, delirium, length of stay (LOS), ICU admission and intubation status were secondary outcomes of interest. First, we employed clustering analysis to identify COVID-19 subphenotypes on admission with only biomarker data and assigned each patient to a subphenotype. We then performed Chi-Squared and Mann-Whitney-U tests to examine associations between COVID-19 subphenotype assignment and outcomes. In addition, correlations between subphenotype and pre-existing comorbidities were measured using Chi-Squared analysis. Results: A total of 7076 patients were included. Analysis revealed three distinct subgroups by level of inflammation: hypoinflammatory, intermediate, and hyperinflammatory subphenotypes. More than 25% of patients in the hyperinflammatory subphenotype died compared to less than 3% hypoinflammatory subphenotype (p&lt;0.05). Additional analysis found statistically significant increases in the rate of MI, DVT, PE, stroke, delirium and ICU admission as well as LOS in the hyperinflammatory subphenotype. Conclusion: We identify three distinct inflammatory subphenotypes that predict a range of outcomes, including mortality, MI, DVT, PE, stroke, delirium, ICU admission and LOS. The three subphenotypes are easily identifiable and may aid in clinical decision making.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.07.23288152v1" target="_blank">Unsupervised Machine Learning Unveil Easily Identifiable Subphenotypes of COVID-19 With Differing Disease Trajectories</a>
</div></li>
<li><strong>Long-term effects of extreme smoke exposure on COVID-19: A cohort study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In early 2014, the Hazelwood coalmine fire covered the regional Australian town of Morwell in smoke and ash for 45 days. One of the fire9s by-products, PM<sub>2.5</sub>, has been linked higher rates of COVID-19 infection to increased expression of the ACE2 receptor, which the COVID-19 virus uses to infect cells throughout the body. However, it is unclear whether the effect persists for years after exposure. In this study, we surveyed a cohort established prior to the pandemic to determine whether PM<sub>2.5</sub> from the coalmine fire increased long-term vulnerability to COVID-19 infection and severe disease. In late 2022, 612 members of the Hazelwood Health Study9s adult cohort, established in 2016/17, participated in a follow-up survey including standardised items to capture COVID-19 infections, hospitalisations, and vaccinations. Associations were evaluated in crude and adjusted logistic regression models, applying statistical weighting for survey response and multiple imputation to account for missing data, with sensitivity analyses to test the robustness of results. A total of 271 (44%) participants self-reported or met symptom criteria for at least one COVID-19 infection. All models found a positive association, with odds of infection increasing by between 4-21% for every standard deviation (12.3μg/m3) increase in mine fire-related PM<sub>2.5</sub> exposure. However, this was not statistically significant in any model. There were insufficient hospitalisations to examine severity (n=7; 1%). The findings were inconclusive in ruling out an effect of PM<sub>2.5</sub> exposure from coalmine fire on long-term vulnerability to COVID-19 infection. Given the positive association that was robust to modelling variations as well as evidence for a causal mechanism, it would be prudent to treat PM<sub>2.5</sub> from fire events as a risk factor for long-term COVID-19 vulnerability until more evidence accumulates.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.12.23288500v1" target="_blank">Long-term effects of extreme smoke exposure on COVID-19: A cohort study</a>
</div></li>
<li><strong>Ethnic inequalities among NHS staff in England - workplace experiences during the COVID-19 pandemic</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Objectives. To determine how workplace experiences of NHS staff varied by ethnic group during the COVID-19 pandemic and examine how these experiences are associated with mental and physical health at the time of the study. Methods. An online Inequalities Survey was conducted by the TIDES study (Tackling Inequalities and Discrimination Experiences in health Services) in collaboration with NHS CHECK. This Inequalities Survey collected measures relating to workplace experiences (such as personal protective equipment (PPE), risk assessments, redeployments, and discrimination) as well as mental health, and physical health from NHS staff working in the 18 trusts participating with the NHS CHECK study between February and October 2021 (N=4622). Results. Regression analysis revealed that staff from Black and Mixed/Other ethnic groups had greater odds of experiencing workplace harassment (adjusted odds ratio (AOR) = 2.43 [1.56-3.78] and 2.38 [1.12-5.07], respectively) and discrimination (AOR = 4.36 [2.73-6.96], and 3.94 [1.67-9.33], respectively) compared to White British staff. Staff from black ethnic groups also had greater odds than White British staff of reporting PPE unavailability (AOR = 2.16 [1.16-4.00]). Such workplace experiences were associated with negative physical and mental health outcomes, though this association varied by ethnicity. Conversely, understanding employment rights around redeployment, being informed about, and having the ability to inform redeployment decisions were associated with lower odds of poor health outcomes. Conclusions. Structural changes to the way staff from ethnically minoritised groups are supported, and how their complaints are addressed by leaders within the NHS are urgently required to address racism and inequalities in the NHS. Policy implications. Maintaining transparency and implementing effective mechanisms for addressing poor working conditions, harassment, and discrimination is crucial in the NHS. This can be achieved through appointing a designated staff member, establishing a tracking system, and training HR managers in identifying and handling reports of racial discrimination. Incorporating diversity and inclusion considerations into professional development activities and providing staff with opportunities to actively participate in decision-making can also benefit their health. The NHS Workforce Race Equality Standard may need to broaden its scope to assess race equality effectively.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.13.23288481v1" target="_blank">Ethnic inequalities among NHS staff in England - workplace experiences during the COVID-19 pandemic</a>
</div></li>
<li><strong>Time to get attention: The effect of temporal values on health, income and happiness</strong> -
<div>
We study the effect of people’s temporal values (habits of attending to past or future events) on their health, labour market performance and happiness. Participants’ (N=1177) data were initially collected in 2016 and then again in a follow-up study in 2020-2021. We find that habitually more attending to the future is negatively associated with diseases (heart attack; high cholesterol; diabetes; high-blood pressure; Covid19), but positively with health-related behaviour (eating vegetables and fruit; less smoking), health status (e.g., healthy weight; long life expectancy), income, hourly wage, financial satisfaction and happiness. Furthermore, such temporal values predict participants’ future situation of these aspects of well-being in 2020-2021, even after controlling for the 2016 baseline situation, IQ, self-control, patience, risk aversion and demographic information. Given that habitually attending to the past is likely to lead people to give less priority to the future compared to the past, we propose a temporal values and well-being hypothesis: Temporal values have consequences for people’s planning and behaviour, thus influencing individuals’ concurrent and longitudinal overall well-being. Our findings have strong implications for theories of time perception, measurements of temporal values, and for a better understanding of factors that influence people’s health, income, and happiness.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/7k4ct/" target="_blank">Time to get attention: The effect of temporal values on health, income and happiness</a>
</div></li>
<li><strong>Gender Responsivity of Family Planning Cadres in Family Resilience Counseling during the Covid-19 Pandemic in Ajibarang Subdistrict</strong> -
<div>
The Covid-19 pandemic has decreased resilience, particularly the socio-psychological aspects of many families, including the Ajibarang Subdistrict. This can be seen from the many cases of domestic violence and child marriage occurring in this part of the Banyumas Regency. In order not to continue, this condition needs to be prevented immediately through counseling activities that are appropriate in material and right on target, for both women and men. In other words, counseling must be gender-responsive. In this case, Family Planning Cadres in the village and RW levels play a vital role in helping family planning counselors take preventive measures. Therefore, it would be interesting to study the gender responsivities of family planning counselors. This study aimed to gather information about (1) the phenomenon of family resilience in their area and (2) the gender responsivity of family resilience counseling conducted in the subdistrict. By applying a descriptive qualitative approach, this study gathered data through questionnaires and direct discussions. The data were analyzed using interactive methods. The results showed that during the Covid-19 pandemic, there were a large number of divorced and married children. While counseling was provided to address this issue, the target clients were mostly females. Among the many reasons, cadres only partially understood the concept of gender and never attended training for gender-perspective counseling.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/d3eak/" target="_blank">Gender Responsivity of Family Planning Cadres in Family Resilience Counseling during the Covid-19 Pandemic in Ajibarang Subdistrict</a>
</div></li>
<li><strong>Determination of the factors responsible for host tropism of SARS-CoV-2-related bat coronaviruses</strong> -
<div>
Differences in host ACE2 genes may affect the host range of SARS-CoV-2-related coronaviruses (SC2r-CoVs) and further determine the tropism of host ACE2 for the infection receptor. However, the factor(s) responsible for determining the host tropism of SC2r-CoVs, which may in part be determined by the tropism of host ACE2 usage, remains unclear. Here, we use the pseudoviruses with the spike proteins of two Laotian SC2r-CoVs, BANAL-20-236 and BANAL-20-52, and the cells expressing ACE2 proteins of eight different Rhinolophus bat species, and show that these two spikes have different tropisms for Rhinolophus bat ACE2. Through structural analysis and cell culture experiments, we demonstrate that this tropism is determined by residue 493 of the spike and residues 31 and 35 of ACE2. Our results suggest that SC2r-CoVs exhibit differential ACE2 tropism, which may be driven by adaptation to different Rhinolophus bat ACE2 proteins.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.13.536832v1" target="_blank">Determination of the factors responsible for host tropism of SARS-CoV-2-related bat coronaviruses</a>
</div></li>
<li><strong>A scoping review on the use and acceptability of preprints</strong> -
<div>
Background: Preprints are open and accessible scientific manuscript or report that has not been submitted to a peer reviewed journal. The value and importance of preprints has grown since its contribution during the public health emergency of the COVID-19 pandemic. Funders and publishers are establishing their position on the use of preprints, in grant applications and publishing models. However, the evidence supporting the use and acceptability of preprints varies across funders, publishers, and researchers. The purpose of this scoping review was to explore the current evidence on the use and acceptability of preprints by publishers, funders, and the research community throughout the research lifecycle. Methods: A scoping review was undertaken with no study or language limits. The search strategy was limited to the last five years (2017-2022) to capture changes influenced by COVID-19 (e.g., accelerated use and role of preprints in research). The review included international literature, including grey literature, and two databases were searched: Scopus and Web of Science (24 August 2022). Results: 379 titles and abstracts and 193 full text articles were assessed for eligibility. Ninety-eight articles met eligibility criteria and were included for full extraction. For barriers and challenges, 26 statements were grouped under four main themes (e.g., volume/growth of publications, quality assurance/trustworthiness, risks associated to credibility, and validation). For benefits and value, 34 statements were grouped under six themes (e.g., openness/transparency, increased visibility/credibility, open review process, open research, democratic process/systems, increased productivity/opportunities). Conclusions: Preprints provide opportunities for rapid dissemination but there is a need for clear policies and guidance from journals, publishers, and funders. Cautionary measures are needed to maintain the quality and value of preprints, paying particular attention to how findings are translated to the public. More research is needed to address some of the uncertainties addressed in this review.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/nug4p/" target="_blank">A scoping review on the use and acceptability of preprints</a>
</div></li>
<li><strong>The balance of risks and benefits in the COVID-19 “vaccine hesitancy” literature: An umbrella review</strong> -
<div>
Background: “Vaccine hesitancy” (VH) has been described as a “threat to global health”, especially in the COVID-19 era. Research on VH indicates that the concerns of vaccine recipients with the balance of risks and benefits of COVID-19 vaccination, which involve safety and effectiveness considerations (hereafter “safety concerns”), are a leading driver of VH. However, what explains these concerns is underexplored. Goal: We conducted a qualitative umbrella review following PRISMA guidelines and informed by a critical perspective to examine how the safety concerns of COVID-19 vaccine recipients are addressed in the VH literature. Methods: We searched PubMed, the Epistemonikos COVID-19 platform (COVID-19 L. OVE), and the WHO Global Research on COVID-19 Database. We included 49 refereed reviews examining VH in any population involved with COVID-19 vaccination decisions for themselves or as caretakers, with no methodological, quality, temporal, or geographic restrictions, and were published in English, excluding those that authors did not identify as “systematic”. Two reviewers completed article screening and data extraction and synthesis. Thematic synthesis was used to identify themes and frequencies were calculated to assess the strength of support for themes. Disagreements were resolved through full team discussion. The protocol was registered with PROSPERO (ID CRD42022351489) and partially funded by a SSHRC grant (# 435-2022-0959). Findings: All reviews assumed that VH was a major barrier to ending the COVID-19 crisis. With vaccines assumed to be “safe and effective”, recipients’ safety concerns were downplayed. Evidence incompatible with “VH-as-a-problem”, whenever mentioned, was dismissed as “misinformation”. Informed consent was either not discussed or was presented as a potential threat to “vaccine confidence”. We observed no differences regardless of study population, methodology, or other study characteristics. Limitations are discussed. Conclusions: Neglecting or dismissing vaccine recipients’ safety concerns contributes to the problem that research on COVID-19 VH purports to address. It also undermines the implementation of informed consent, critical to ethical medical and public health research, policy, and practice. The scant attention to bioethical considerations in current COVID-19 VH research is concerning.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/r9xs7/" target="_blank">The balance of risks and benefits in the COVID-19 “vaccine hesitancy” literature: An umbrella review</a>
</div></li>
<li><strong>SARS-CoV-2 NSP5 Antagonizes MHC II Expression by Subverting Histone Deacetylase 2</strong> -
<div>
SARS-CoV-2 interferes with antigen presentation by downregulating MHC II on antigen presenting cells, but the mechanism mediating this process is unelucidated. Herein, analysis of protein and gene expression in human antigen presenting cells reveals that MHC II is downregulated by the SARS-CoV-2 main protease, NSP5. This suppression of MHC II expression occurs via decreased expression of the MHC II regulatory protein CIITA. This downregulation of CIITA is independent of NSP5’s proteolytic activity, and rather, NSP5 delivers HDAC2 to the CIITA promoter via an IRF3-dependent mechanism. Here, HDAC2 deacetylates and inactivates the CIITA promoter. This loss of CIITA expression prevents further expression of MHC II, with this suppression alleviated by ectopic expression of CIITA or knockdown of HDAC2. These results identify a mechanism by which SARS-CoV-2 can limit MHC II expression, thereby delaying or weakening the subsequent adaptive immune response.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.528032v2" target="_blank">SARS-CoV-2 NSP5 Antagonizes MHC II Expression by Subverting Histone Deacetylase 2</a>
</div></li>
<li><strong>The airborne transmission of viruses causes tight transmission bottlenecks</strong> -
<div>
The transmission bottleneck describes the number of viral particles that found an infection in a new host. Previous studies have used genome sequence data to suggest that transmission bottlenecks for influenza and SARS-CoV-2 involve few viral particles, but the general principles underlying these bottlenecks are not fully understood. Here we show that, across a broad range of circumstances, tight transmission bottlenecks arise as a consequence of the physical process underlying airborne viral transmission. We use a mathematical model to describe the process of infectious particles being emitted by an infected individual and inhaled by others nearby. The extent to which exposure to particles translates into infection is determined by an effective viral load, which is calculated as a function of the epidemiological parameter R0. Across multiple scenarios, including those present at a superspreading event, our model suggests that the great majority of transmission bottlenecks involve few viral particles, with a high proportion of infections being caused by a single viral particle. Our results provide a physical explanation for previous inferences of bottleneck size and predict that tight transmission bottlenecks prevail more generally in respiratory virus transmission.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.14.536864v1" target="_blank">The airborne transmission of viruses causes tight transmission bottlenecks</a>
</div></li>
<li><strong>SARS-CoV-2 selectively induces the expression of unproductive splicing isoforms of interferon, class I MHC and splicing machinery genes</strong> -
<div>
Splicing is a highly conserved, intricate mechanism intimately linked to transcription elongation, serving as a pivotal regulator of gene expression. Alternative splicing may generate specific transcripts incapable of undergoing translation into proteins, designated as unproductive. A plethora of respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), strategically manipulate the host’s splicing machinery to circumvent antiviral responses. During the infection, SARS-CoV-2 effectively suppresses interferon (IFN) expression, leading to B cell and CD8+ T cell leukopenia, while simultaneously increasing the presence of macrophages and neutrophils in patients with severe COVID-19. In this study, we integrated publicly available omics datasets to systematically analyze transcripts at the isoform level and delineate the nascent-peptide translatome landscapes of SARS-CoV-2-infected human cells. Our findings reveal a hitherto uncharacterized mechanism whereby SARS-CoV-2 infection induces the predominant expression of unproductive splicing isoforms in key IFN signaling genes, interferon-stimulated genes (ISGs), class I MHC genes, and splicing machinery genes, including IRF7, OAS3, HLA-B, and HNRNPH1. In stark contrast, cytokine and chemokine genes, such as IL6, CXCL8, and TNF, predominantly express productive (protein-coding) splicing isoforms in response to SARS-CoV-2 infection. We postulate that SARS-CoV-2 employs a previously unreported tactic of exploiting the host splicing machinery to bolster viral replication and subvert the immune response by selectively upregulating unproductive splicing isoforms from antigen presentation and antiviral response genes. Our study sheds new light on the molecular interplay between SARS-CoV-2 and the host immune system, offering a foundation for the development of novel therapeutic strategies to combat COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.12.536671v1" target="_blank">SARS-CoV-2 selectively induces the expression of unproductive splicing isoforms of interferon, class I MHC and splicing machinery genes</a>
</div></li>
<li><strong>The impact of COVID-19 lockdown on postpartum mothers in London, England: An online focus group study</strong> -
<div>
Aims: The postpartum/postnatal period is widely acknowledged as a time when mothers require greater levels of support from multiple sources. However, stay-at-home orders commonly known as “lockdown” deployed in some countries to limit COVID-19 transmission reduced access to support. In England, many postpartum mothers navigated household isolation under intensive mothering and expert parenting culture. Examining the impact of lockdown may reveal strengths and weaknesses in current policy and practice, revealing opportunities to improve maternal experience and wellbeing. Subject and Methods: We conducted an online focus group involving 20 mothers living in London, England, with “lockdown babies,” following up on our earlier survey on social support and maternal wellbeing. We thematically analysed focus group transcripts, and identified key themes around Lockdown Experience and Determinants of Lockdown Experience. Results: Participants raised some positives of lockdown, including fostering connections and protection from external expectations, but also raised many negatives, including social isolation, institutional abandonment, and intense relationships within the household. Potential reasons behind variations in lockdown experience include physical environments, timing of birth, and number of children. Our findings reflect how current systems may be “trapping” some families into the male-breadwinner/female-caregiver family model, while intensive mothering and expert parenting culture may be increasing maternal stress and undermining responsive mothering. Conclusions: Facilitating partners to stay at home during the postpartum period and establishing peer/community support instead of reliance on professionals may promote positive postpartum maternal experience and wellbeing.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/r7enw/" target="_blank">The impact of COVID-19 lockdown on postpartum mothers in London, England: An online focus group study</a>
</div></li>
<li><strong>Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model</strong> -
<div>
Maternal antibodies (matAbs) protect against a myriad of pathogens early in life; however, these antibodies can also inhibit de novo immune responses against some vaccine platforms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) matAbs are efficiently transferred during pregnancy and protect infants against subsequent SARS-CoV-2 infections. It is unknown if matAbs inhibit immune responses elicited by different types of SARS-CoV-2 vaccines. Here, we established a mouse model to determine if SARS-CoV-2 spike-specific matAbs inhibit immune responses elicited by recombinant protein and nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccines. We found that SARS-CoV-2 mRNA-LNP vaccines elicited robust de novo antibody responses in mouse pups in the presence of matAbs. Recombinant protein vaccines were also able to circumvent the inhibitory effects of matAbs when adjuvants were co-administered. While additional studies need to be completed in humans, our studies raise the possibility that mRNA-LNP-based and adjuvanted protein-based SARS-CoV-2 vaccines have the potential to be effective when delivered very early in life.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.12.536590v1" target="_blank">Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model</a>
</div></li>
<li><strong>SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition</strong> -
<div>
A significant proportion of patients with SARS-CoV-2 infection develop lingering symptoms for months, even years after their infection, a condition now known as Post-COVID Condition (PCC). The underlying pathophysiology of PCC is not known. The wide spectrum of symptoms encompassing various organ systems and the detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be associated with aberrant immune response to the viral antigens. Here, we studied the antibody and B cell responses to the spike protein and the RBD domain in PCC patients who experienced mild COVID-19 disease during the early stages of COVID-19 pandemic in the pre-vaccination era. Our results suggest that the immune responses to the spike antigen may be altered in those who develop PCC.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.13.535896v1" target="_blank">SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition</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>Effectiveness and Safety of Quinine Sulfate as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia ( DEAL-COVID19 )</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Standard of Care + Quinine Sulfate;   Drug: Standard of Care<br/><b>Sponsors</b>:   Universitas Padjadjaran;   National Research and Innovation Agency of Indonesia;   Prodia Diacro Laboratories P.T.<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>Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Exosomes in Treating Chronic Cough After COVID-19</strong> - <b>Condition</b>:   Long COVID-19 Syndrome<br/><b>Intervention</b>:   Biological: MSC-derived exosomes<br/><b>Sponsors</b>:   Huazhong University of Science and Technology;   REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19</strong> - <b>Condition</b>:   Omicron Variant of COVID-19<br/><b>Intervention</b>:   Drug: Nirmatrelvir/Ritonavir<br/><b>Sponsor</b>:   Xiangao Jiang<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Nasal Treatment for COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Optate;   Drug: Placebo<br/><b>Sponsor</b>:   Indiana University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To Evaluate the Safety and Efficacy of Meplazumab in Treatment of COVID-19 Sequelae</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Meplazumab for injection;   Other: Normal saline<br/><b>Sponsor</b>:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Adult COVID-19 Patients With Comorbidities</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Ropeginterferon alfa-2b;   Procedure: SOC<br/><b>Sponsor</b>:   National Taiwan University Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: SCB-2019/Clover;   Biological: AstraZeneca/Fiocruz;   Biological: Pfizer/Wyeth<br/><b>Sponsors</b>:   D’Or Institute for Research and Education;   Bill and Melinda Gates Foundation<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>Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants</strong> - <b>Condition</b>:   COVID19 Testing<br/><b>Interventions</b>:   Behavioral: FABI tailored COVID-19 testing pamphlet;   Behavioral: Standard COVID-19 home-based test kit<br/><b>Sponsors</b>:   Texas Woman’s University;   National Institutes of Health (NIH)<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Complementary Self-help Strategies for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Interventions</b>:   Behavioral: Complementary self-help strategies in addition to treatment as usual;   Other: Treatment as usual<br/><b>Sponsor</b>:   Universität Duisburg-Essen<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized.</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Drug: PF-07817883;   Drug: Placebo<br/><b>Sponsor</b>:   Pfizer<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Interventions</b>:   Other: conventional western medicine treatment;   Drug: Dexamethasone oral tablet;   Other: Traditional Chinese medicine decoction<br/><b>Sponsor</b>:   China-Japan Friendship Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inpatient COVID-19 Lollipop Study</strong> - <b>Conditions</b>:   COVID-19;   Diagnostic Test<br/><b>Intervention</b>:   Device: Lollipop<br/><b>Sponsor</b>:   University of Wisconsin, Madison<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Intervention</b>:   Dietary Supplement: PS23 heat-treated<br/><b>Sponsors</b>:   Mackay Memorial Hospital;   Bened Biomedical Co., Ltd.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploring the Effect of Video Interventions on Intentions for Continued COVID-19 Vaccination</strong> - <b>Conditions</b>:   Vaccine Refusal;   COVID-19<br/><b>Interventions</b>:   Behavioral: Informational Video;   Behavioral: Altruistic Video;   Behavioral: Individualistic Video<br/><b>Sponsor</b>:   Sir Mortimer B. Davis - Jewish General 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>Building Resilience During the COVID-19 Pandemic: a Randomized Controlled Trial</strong> - <b>Conditions</b>:   Healthy;   COVID-19;   Distress, Emotional<br/><b>Interventions</b>:   Behavioral: RASMUS Resilience Training;   Behavioral: Progressive Muscle Relaxation<br/><b>Sponsor</b>:   Medical University Innsbruck<br/><b>Recruiting</b></p></li>
</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>Development of a novel angiotensin converting enzyme 2 stimulator with broad implications in SARS-CoV2 and type 1 diabetes</strong> - Angiotensin-converting enzyme 2 (ACE2) is protective in cardiovascular disease, lung injury and diabetes yet paradoxically underlies our susceptibility to SARs-CoV2 infection and the fatal heart and lung disease it can induce. Furthermore, diabetic patients have chronic, systemic inflammation and altered ACE2 expression resulting in increased risk of severe COVID-19 and the associated mortality. A drug that could increase ACE2 activity and inhibit cellular uptake of severe acute respiratory…</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>Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5’ untranslated region</strong> - One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) in their genomes. These conserved RNA structures are often essential for viral replication, transcription, or translation. In this report, we discovered and optimized a new coumarin derivative C30 that binds to a four-way RNA helix called SL5 in the 5’ UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a novel sequencing-based method namely cgSHAPE-seq, in which the acylating chemical…</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>Human Surfactant Protein A Alleviates SARS-CoV-2 Infectivity in Human Lung Epithelial Cells</strong> - SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins. This study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity. The interactions…</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>Role of C-Reactive Protein in Kidney Diseases</strong> - BACKGROUND: C-reactive protein (CRP) is an acute-phase protein and has been found to be a risk factor for acute kidney injury (AKI) and chronic kidney diseases (CKD). However, the role and mechanisms of CRP in AKI and CKD remain largely unclear.</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>An updated review on phytochemistry and molecular targets of <em>Withania somnifera (L.)</em> Dunal (Ashwagandha)</strong> - Withania somnifera (L.) Dunal belongs to the nightshade family Solanaceae and is commonly known as Ashwagandha. It is pharmacologically a significant medicinal plant of the Indian sub-continent, used in Ayurvedic and indigenous systems of medicine for more than 3,000 years. It is a rich reservoir of pharmaceutically bioactive constituents known as withanolides (a group of 300 naturally occurring C-28 steroidal lactones with an ergostane-based skeleton). Most of the biological activities of W….</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>Octyl gallate targeting the 3C-like protease exhibits highly efficient antiviral activity against swine enteric coronavirus PEDV</strong> - Infection with porcine epidemic diarrhea virus (PEDV) causes severe watery diarrhea in newborn piglets, leading to substantial financial losses for the swine industry. In this study, we screened small molecule drugs targeting 3 C-like protease (3CLpro) by molecular docking, and further evaluated the antiviral activity of the screened drugs against PEDV. Results showed that octyl gallate (OG), a widely used food additive, exhibited strong binding affinity with the 3CLpro active sites of PEDV….</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>SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine receptors</strong> - Virus entry into animal cells is initiated by attachment to target macromolecules located on host cells. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) trimeric spike glycoprotein targets host angiotensin converting enzyme 2 to gain cellular access. The SARS-CoV-2 glycoprotein contains a neurotoxin-like region that has sequence similarities to the rabies virus and the human immunodeficiency virus glycoproteins, as well as to snake neurotoxins, which interact with nicotinic…</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>Pathological angiogenesis: mechanisms and therapeutic strategies</strong> - In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, and coalescent angiogenesis, as well as vessel co-option, vasculogenic mimicry and lymphangiogenesis, underlie the formation of new vasculature. In many pathological conditions, such as cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A universal fluorescence polarization high throughput screening assay to target the SAM-binding sites of SARS-CoV-2 and other viral methyltransferases</strong> - AbstractSARS-CoV-2 has caused a global pandemic with significant humanity and economic loss since 2020. Currently, only limited options are available to treat SARS-CoV-2 infections for vulnerable populations. In this study, we report a universal fluorescence polarization (FP)-based high throughput screening (HTS) assay for SAM-dependent viral methyltransferases (MTases), using a fluorescent SAM-analog, FL-NAH. We performed the assay against a reference MTase, NSP14, an essential enzyme for…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis, cytotoxicity, and pharmacokinetic evaluations of niclosamide analogs for anti-SARS-CoV-2</strong> - Niclosamide, an oral anthelmintic drug, could inhibit SARS-CoV-2 virus replication through autophagy induction, but high cytotoxicity and poor oral bioavailability limited its application. Twenty-three niclosamide analogs were designed and synthesized, of which compound 21 was found to exhibit the best anti-SARS-CoV-2 efficacy (EC(50) = 1.00 μM for 24 h), lower cytotoxicity (CC(50) = 4.73 μM for 48 h), better pharmacokinetic, and it was also well tolerated in the sub-acute toxicity study in…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Characterization of the induction kinetics and antiviral functions of IRF1, ISG15 and ISG20 in cells infected with gammacoronavirus avian infectious bronchitis virus</strong> - Coronavirus infection induces a variety of cellular antiviral responses either dependent on or independent of type I interferons (IFNs). Our previous studies using Affymetrix microarray and transcriptomic analysis revealed the differential induction of three IFN-stimulated genes (ISGs), IRF1, ISG15 and ISG20, by gammacoronavirus infectious bronchitis virus (IBV) infection of IFN-deficient Vero cells and IFN-competent, p53-defcient H1299 cells, respectively. In this report, the induction kinetics…</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>In-silico approaches for identification of compounds inhibiting SARS-CoV-2 3CL protease</strong> - The world has witnessed of many pandemic waves of SARS-CoV-2. However, the incidence of SARS-CoV-2 infection has now declined but the novel variant and responsible cases has been observed globally. Most of the world population has received the vaccinations, but the immune response against COVID-19 is not long-lasting, which may cause new outbreaks. A highly efficient pharmaceutical molecule is desperately needed in these circumstances. In the present study, a potent natural compound that could…</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>AI-Driven Discovery of SARS-CoV-2 Main Protease Fragment-like Inhibitors with Antiviral Activity <em>In Vitro</em></strong> - SARS-CoV-2 is the causative agent of COVID-19 and is responsible for the current global pandemic. The viral genome contains 5 major open reading frames of which the largest ORF1ab codes for two polyproteins, pp1ab and pp1a, which are subsequently cleaved into 16 nonstructural proteins (nsp) by two viral cysteine proteases encoded within the polyproteins. The main protease (Mpro, nsp5) cleaves the majority of the nsp’s, making it essential for viral replication and has been successfully 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>Inhaled Lipid Nanoparticles Alleviate Established Pulmonary Fibrosis</strong> - Pulmonary fibrosis, a sequela of lung injury resulting from severe infection such as severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) infection, is a kind of life-threatening lung disease with limited therapeutic options. Herein, inhalable liposomes encapsulating metformin, a first-line antidiabetic drug that has been reported to effectively reverse pulmonary fibrosis by modulating multiple metabolic pathways, and nintedanib, a well-known antifibrotic drug that has been widely…</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>Molecular insights into the inhibition mechanism of harringtonine against essential proteins associated with SARS-CoV-2 entry</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently posed a serious threat to global public health. Harringtonine (HT), as a small-molecule antagonist, has antiviral activity against a variety of viruses. There is evidence that HT can inhibit the SARS-CoV-2 entry into host cells by blocking the Spike protein and transmembrane protease serine 2 (TMPRSS2). However, the molecular mechanism underlying the inhibition effect of HT is largely elusive. Here, docking and all-atom…</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 Privacy-Minded Social Network at the Center of the Classified-Document Leak</strong> - A young National Guardsman posted hundreds of secret government files to a private Discord group. Then they sat there for months unnoticed. - <a href="https://www.newyorker.com/culture/infinite-scroll/the-privacy-minded-social-network-at-the-center-of-the-classified-document-leak">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bob Lee’s Murder and San Francisco’s So-Called Crime Epidemic</strong> - The killing of a tech executive reveals the cycle of outrage that puts enormous pressure on progressive district attorneys. - <a href="https://www.newyorker.com/news/our-columnists/bob-lees-murder-and-san-franciscos-so-called-crime-epidemic">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>All Gaffes Are Not Created Equal: Biden vs. the Almighty Trump</strong> - On a week when the 2024 contrast could not be clearer. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/all-gaffes-are-not-created-equal-biden-vs-the-almighty-trump">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What’s Behind the Bipartisan Attack on TikTok?</strong> - A hundred and fifty million Americans are on TikTok. Evan Osnos and Chris Stokel-Walker discuss why politicians are so keen to ban the app. Plus, Broadway’s new comedy of white wokeness. - <a href="https://www.newyorker.com/podcast/the-new-yorker-radio-hour/whats-behind-the-bipartisan-attack-on-tiktok">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Is the Trump Indictment a “Legal Embarrassment”?</strong> - Analysts have argued that the case, which was put down by previous prosecutors, sets a dangerous precedent in American politics. That might be naïve. - <a href="https://www.newyorker.com/news/q-and-a/is-the-trump-indictment-a-legal-embarrassment">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Star Wars has a Baby Yoda problem</strong> -
<figure>
<img alt="A shot from the TV show The Mandalorian shows three Mandalorian fighters in their distinctive helmets and armor, with a variety of weapons." src="https://cdn.vox-cdn.com/thumbor/m1iVH4bABRH7-RF6RqAQpj36iIk=/182x0:2323x1606/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72187218/the_mandalorian_3_83ed1862.0.jpg"/>
<figcaption>
<em>The Mandalorian</em>’s third season has been rocky. | Disney
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Mandalorian was the answer to all of Star Wars’ problems — until it embodied them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dT7a4H">
One could argue that season three of <em>The Mandalorian</em> went off the rails before it ever debuted. Prior to the season’s release, another Disney+ series, <em>The Book of Boba Fett</em>, featured an entire stealth plot arc of <em>The Mandalorian</em> that served to connect the timeline of the show’s previous season with the one about to be released. Without watching it, the first episode of season three felt like a jarring reset. And even with it, the episode glossed over continuity and gave rise to <a href="https://www.hollywoodreporter.com/tv/tv-news/the-mandalorian-season-3-fan-backlash-1235369277/">what has become</a> the series’ biggest question: What is this show even about?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oEDSVp">
It’s a query that reflects a larger one within the <em>Star Wars</em> universe. On the back of this year’s Celebration, <em>Star Wars</em>’ annual fan/industry convention, and the confirmation of <a href="https://www.polygon.com/23673145/star-wars-new-movies-directors-announcement-celebration">three new <em>Star Wars</em> films</a>, the franchise’s flagship TV show stands at something of a crossroads. It seems to be caught between Lucasfilm’s attempts to learn from the mistakes of its controversial latest trilogy and avoid succumbing to the “<a href="https://collider.com/solo-turns-star-wars-into-the-mcu/">MCU-ification</a>” of its own IP.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="T2HQj3">
<em>The Mandalorian</em> has burned through a lot of goodwill as it meanders its way through season three, and with next week’s finale approaching, it could take a lot more than a cute green baby puppet to convince fans the franchise as a whole isn’t still spinning its wheels.
</p>
<h3 id="sVVM1C">
<em>The Mandalorian</em> seemed like the solution to <em>Star Wars</em>’ problems. Instead, it’s perpetuating them.
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JoDCg4">
It’s no secret that Lucasfilm has struggled ever since the tremendous backlash to, well, everything about its recent cinema revival. First, 2015’s <a href="https://www.vox.com/2015/12/17/10383876/star-wars-episode-vii-the-force-awakens-review"><em>The Force Awakens</em></a> drew an endless barrage of criticism from right-wing fans angry at the film’s trio of diverse main characters. This clamor paved the way for a <a href="https://www.vox.com/culture/2019/12/27/21034725/star-wars-the-rise-of-skywalker-last-jedi-j-j-abrams-rian-johnson">philosophical bait-and-switch</a> between Rian Johnson’s <a href="https://www.vox.com/culture/2018/1/12/16834684/the-last-jedi-lost-its-nerve"><em>The Last Jedi</em></a> — which was, despite being critically beloved, <a href="https://www.vox.com/culture/2017/12/18/16791844/star-wars-last-jedi-backlash-controversy">even more controversial</a> than its predecessor — and the subsequent <em>Rise of Skywalker. </em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EfvotV">
J.J. Abrams’ trilogy close-out <a href="https://www.vox.com/culture/2019/12/18/21021188/star-wars-rise-of-skywalker-review-no-spoilers">jettisoned so much</a> of Johnson’s more subversive ethos that it arguably drew more outrage than any of the other films — and a walloping <a href="https://deadline.com/2020/04/star-wars-rise-of-skywalker-movie-profit-2019-lowest-for-lucasfilm-1202915179/">profit drop</a> at the box office. The angry right-wing fans were joined by many left-wing fans, who were angry that the trilogy essentially used a Black male character, John Boyega’s Finn, as a fake-out for <a href="https://www.vox.com/2015/12/28/10672628/star-wars-force-awakens-rey-mary-sue">a white woman</a>, Rey (Daisy Ridley), ultimately <a href="https://ew.com/movies/john-boyega-vs-rise-of-skywalker/">giving him little to do at all</a>. The final film also courted backlash for the decision to write Finn’s intended love interest, Kelly Tran’s character Rose Tico, <a href="https://www.vox.com/2019/12/30/21042843/kelly-marie-tran-rise-of-skywalker-screentime">nearly out of the final film</a> completely, after the actress endured endless harassment from fans. As a bonus, no one seemed to like <a href="https://www.vox.com/culture/2019/12/19/21028496/star-wars-the-rise-of-skywalker-spoilers-episode-9-reys-parents">the resolution</a> to Rey’s storyline either. The movie even spawned <a href="https://www.vox.com/2020/1/6/21046788/release-the-jj-cut-what-is-the-jj-cut-real-explained">an entire fandom conspiracy theory</a> that there was another, better, purer film out there.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rDSo9G">
This complex squabbling over <em>Star Wars</em> identity politics <a href="https://variety.com/2023/film/news/star-wars-kevin-feige-patty-jenkins-movies-shelved-1235545774/">effectively derailed the entire franchise</a>, throwing numerous planned spinoff films into stasis, as they had promised the kind of fresh takes on <em>Star Wars</em> that came out of the first two films. The final film was an attempt to walk back everything that had made a certain type of fan mad, only to blunder into <a href="https://www.vox.com/2019/12/18/21028290/star-wars-rise-of-skywalker-early-reviews-bad">pleasing no one</a>. As Emily St. James <a href="https://www.vox.com/culture/2019/12/21/21030578/star-wars-the-rise-of-skywalker-bad-episode-9-disappointing-problems">wrote</a> for Vox, “The film’s ecology is destroyed early on, as it attempts to serve multiple masters — corporate, fan, and otherwise. It lurches from scene to scene without any finesse. It almost feels like a trip through several enclosed <em>Star Wars</em> habitats that offer a quick glimpse at some of your favorite characters and locations, while never finding a way to make those habitats share the same ecosystem.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z2BcSY">
That criticism may sound awfully familiar to fans of <em>The Mandalorian</em>. For its first two seasons, <em>The Mandalorian</em> seemed to be the spark and the glue the franchise needed to revitalize itself — a fun, streamlined little show with an uncontroversial lead that <a href="https://www.vox.com/culture/21534638/the-mandalorian-disney-plus-explained-do-i-need-to-watch-star-wars-baby-yoda">drew general audiences in</a> with a commitment to atmosphere, good CGI, and, of course, <a href="https://www.vox.com/culture/2019/11/23/20972511/baby-yoda-meme-the-mandalorian-gif-star-wars">Baby Yoda</a>. Soon, however, critics noticed that the show was not only <a href="https://www.vox.com/culture/2019/11/12/20961484/mandalorian-star-wars-disney-plus-review-pedro-pascal">thin on plot and characterization</a> but that it increasingly relied on big, social-media-ready sequences to drive its momentum, with <a href="https://www.vox.com/culture/22195506/the-mandalorian-season-2-finale-recap-the-rescue-luke-skywalker-baby-yoda">little connective tissue</a> in or around such moments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wEynRL">
The complaint that <em>Star Wars</em> is trying to do too much at once has become especially prominent through <em>The Mandalorian</em>’s third season, which sees titular Mandalorian Din Djarin (Pablo Pascal) abruptly reunited with his adopted son, Grogu (the frankly appalling real name of Baby Yoda). This, despite the fact that the narrative journey of the second season was for Grogu to leave Din’s care and train with other potential Jedi like himself.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gi7mvI">
Externally, the reason for this reunification is obvious: Baby Yoda is too much of a marketing coup to go without. Internally, the reason for this reunification gets explained, sort of, not in <em>The Mandalorian</em>, but <a href="https://www.forbes.com/sites/paultassi/2023/03/01/why-is-grogu-back-with-the-mandalorian-you-missed-something-very-stupid/?sh=234ac5021133">over three episodes</a> of <em>The Book of Boba Fett</em>, another breakout series meant to capitalize on the renewed energy provided by <em>The Mandalorian</em>. But despite the popularity of the character Boba Fett himself, <em>The Book of Boba Fett</em> <a href="https://www.rottentomatoes.com/tv/the_book_of_boba_fett/s01">drew widespread criticism</a> for being less a coherent narrative than a collection of cool <em>Star Wars</em> action figures with no ideas. It turns out Boba Fett himself is a terrible character to build a whole story around; while he may be popular, there’s just not that much to him, which could be why the writers ultimately turned the show’s back half into a <em>Mandalorian</em> installment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4J6L8k">
That Boba Fett got his own show at all speaks to the increased emphasis on commercialization and fan service that keeps getting in the way of the franchise’s attempts to move forward. <em>The Mandalorian</em> continually falls prey to this, and season three’s unsatisfied viewers have grown increasingly rowdy over it. Each episode has drawn ire for waylaying the main plot and getting fixated on side characters and quests that seem to have little meaning in the scheme of things. While season one was largely made up of such <em>Trek</em>-y one-offs, those felt fun and fresh because those missions served to build our understanding of the show’s main characters and establish the sociopolitical landscape of the show’s timeline.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SBX8vX">
Now, however, none of those early episodes seem to matter much. In season three, the <em>Star Wars</em> universe and the complex geopolitical dynamics between different worlds and politics are an excuse for flashy starship battles. Despite disconnecting from all that worldbuilding, season three keeps meandering its way around the galaxy at the expense of its own big plot. In only eight episodes, season three has had to: “redeem” Din Djarin as a Mandalorian (since he took his helmet off, long story), unite two mutually antagonistic Mandalorian factions, establish Bo-Katan (Katee Sackhoff) as their leader, organize a return to planet Mandalore, build up a confrontation between the Mandalorians and Empire loyalist Moff Gideon (Giancarlo Esposito), and actually show that confrontation. It could also have bothered to show us Baby Yoda growing into an actual Jedi force to be reckoned with, especially since it stinted the show’s viewers on all his cool Jedi training.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n5e3WB">
Instead, season three keeps falling back on more made-for-TikTok set pieces. Multiple episodes seem to have had little narrative purpose other than to present cool cameos and viral moments for viewers. Episode six, for example, was an <a href="https://www.leisurebyte.com/the-mandalorian-season-3-episode-6-reactions/">instant hit</a> on social media due to cameos from Lizzo, Jack Black, and Christopher Lloyd. But it proved <a href="https://screenrant.com/the-mandalorian-season-3-episode-6-jack-black-lizzo-cameos-reaction/">one of the most divisive</a> episodes yet, probably because outside of ensuring that a limited edition<em> Star Wars</em> Lizzo Funko Pop will be coming soon to a Comic-Con near you, it’s unclear if there were any narrative stakes at all.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fupsZ7">
<em>Mandalorian</em> is <em>Star Wars</em>’ flagship streaming series. If its showrunners, the ever-inventive Jon Favreau (<em>Iron Man</em>) and <em>Star Wars</em> master builder Dave Filoni, are flagging this much, do the studio’s other streaming series even stand a chance?
</p>
<h3 id="aiwe8L">
Lucasfilm jettisoned the <em>Star Wars</em> Extended Universe only to give us … the <em>Star Wars</em> extended universe
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XThWzd">
<em>Star Wars</em>’ pivot to streaming has produced franchise installments that vary widely in quality. <em>The Mandalorian</em> is beloved, but <em>Boba Fett</em> and 2021’s offering, <em>Obi-Wan Kenobi</em>, each drew criticism for sidelining their titular characters. (<em>Obi-Wan</em> also predictably drew racist backlash for having a Black actor in a lead role, and then <a href="https://www.npr.org/2022/06/02/1102509719/star-wars-obi-wan-kenobi-moses-ingram-racist-messages-disney">more backlash directed at Disney</a> for remaining largely silent while yet another <em>Star Wars</em> actor of color endured harassment.) <em>Andor</em>, 2022’s <a href="https://www.theverge.com/23475256/andor-season-one-finale-review-star-wars-disney-plus">critical coup de grace</a>, seemed to contain all of the promise of the <em>Star Wars</em> universe in a drama that was both invigorating and unforgiving.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WuYRPR">
But <em>Andor</em> was a double-edged sword: by committing to a point of view and being unapologetic about its thesis that <a href="https://www.vox.com/culture/23509857/andor-disney-star-wars-evil-empire">the Empire was an evil police state</a> (a far more <a href="https://screenrant.com/star-wars-reasons-galactic-empire-darth-vader-actually-good-guys/">controversial</a> take than it should be!), it highlighted how shallow most of Lucasfilm’s other offerings have been.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IatkpL">
Some of the reasons for this variance may be about avoiding the fandom meltdowns that happened over the last film trilogy’s storytelling efforts. Fans already knew how <em>Andor</em>’s titular character, Cassian Andor (Diego Luna) would end up (he’s also in 2016’s <a href="https://www.vox.com/culture/2016/12/13/13928900/rogue-one-review-star-wars"><em>Rogue One</em></a>). Since Andor himself was a relatively low-stakes character in the <em>Star Wars</em> universe, the show was able to <a href="https://www.polygon.com/reviews/23473565/andor-season-1-review">take storytelling risks</a> that it couldn’t with a new character like Mando to whom fans are increasingly attached, or to an OG like Obi-Wan or Boba Fett.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YGgZQw">
But part of the issue also seems to be structural. It’s not just that the studio keeps making lackluster franchise installments, but that, increasingly, it expects fans to consume all of that content and understand how it all fits together. For many fans, that’s an unfair expectation, an assumption of trust that the franchise hasn’t actually earned over the years. It’s also just logistically difficult; few people, for example, have the time to watch 100+ episodes of <em>Clone Wars</em> just to understand the backstory behind a three-minute scene in <em>The Mandalorian</em>. It’s unclear whether a critical mass of <em>Star Wars</em> fans even watched <em>Boba Fett</em> at all, let alone knew they were supposed to watch three episodes of <em>Boba Fett</em> to get the <em>Mandalorian</em> arc they needed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DoVgL6">
When the highly anticipated <em>Ahsoka</em> appears later this year, it, too, will tie into both <em>The Mandalorian</em> and <em>Boba Fett</em>. So will the untitled film that Filoni is directing, which is intended to serve as a wrap-up on all three of these series. While that’s not inherently bad — spin-offs happen, they’re fine! — what <em>has</em> got viewers antsy is the way this structure has increasingly become built into the franchise. The Marvel formula of turning every show and film into an explicit set-up for the next show and film <a href="https://www.vox.com/culture/23612887/ant-man-quantumania-marvel-flop-era">isn’t even working for Marvel anymore</a>. And despite the hype around the upcoming films, <em>Star Wars</em> fans are <a href="https://wegotthiscovered.com/movies/star-wars-is-officially-going-full-blown-mcu-and-a-lot-of-people-arent-happy-about-it/">openly uneasy</a> about the promise of more overlapping tie-ins.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Junrzs">
After all, it wasn’t that long ago that <em>Star Wars</em> not only tried to quash this kind of endlessly spiraling franchise expansion, but explicitly excluded it from the revamped <em>Star Wars</em> universe. In 2014, in order to make room for <em>The Force Awakens</em>, <a href="https://www.dailydot.com/parsec/star-wars-expanded-universe-not-canon/">Lucasfilm announced</a> that the <em>Star Wars</em> Expanded Universe (EU) — the decades of lore-filled <em>Star Wars</em> media from tie-in novels to comics to board games, a staggering compendium reportedly featuring <a href="https://www.sciencealert.com/data-scientists-map-every-important-character-in-the-star-wars-universe">over 20,000 characters</a> — would no longer be considered part of the official <em>Star Wars</em> canon. Not only that, but no new stories in those worlds would be forthcoming; the studio instead transformed the EU into a giant archive called “Star Wars Legends.” Fans are still <a href="https://www.reddit.com/r/CharacterRant/comments/rvwu27/star_wars_why_disney_removing_the_expanded/">mad</a> and <a href="https://www.themarysue.com/why-i-still-miss-the-star-wars-expanded-universe/">sad</a> about this decision to this day.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pGyxFG">
Rather than fully abandon the EU, however, the current franchise promptly began cherry-picking, or perhaps more accurately, flinging entire handfuls of the old EU <a href="https://screenrant.com/star-wars-legends-disney-canon/#the-clone-wars-is-inspired-by-the-legends-multimedia-project">back into the new canon universe</a>. The most high-profile upcoming storylines, like that of Ahsoka Tano and popular villain Grand Admiral Thrawn, are straight out of the Expanded Universe, and there’s <a href="https://www.ign.com/articles/star-wars-is-dave-filoni-making-an-heir-to-the-empire-movie">rampant speculation</a> that more direct adaptations of EU stories are on the way. If the franchise reined in the EU because it was too unwieldy to begin with, it hasn’t exactly solved its own problem.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gIurNx">
This also speaks to something of an overall franchise identity crisis. Most mainstream <em>Star Wars</em> fans — the kinds of casual fans whose interest you need to cultivate and keep — likely associate <em>Star Wars</em> with a handful of beloved legacy characters and a few new ones thrown in. They’re not tucked away in a forum somewhere opining the loss of, for example, Mara Jade and Ben Skywalker to the new <em>Star Wars</em> canon. Yet that’s also kind of a problem when the studio increasingly expects fans to not only know who EU characters are (for example, Ahsoka Tano) but care about them before their storylines are even underway.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cfDT05">
Is the return on that investment worth it? This is a franchise, after all, where the worldbuilding vacillates between carefully crafted narratives built over years and <a href="https://screenrant.com/obi-wan-kenobi-home-planet-stewjon-george-lucas-joke/">haphazard whimsy</a> — all of which could be tossed aside all over again. When you have the biggest series in the <em>Star Wars </em>oeuvre more or less phoning it in, as fans have accused <em>Mandalorian</em> of doing all season, there’s not much incentive to commit to learning the lore.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vwLIgJ">
This is the ultimate problem <em>Star Wars</em> needs to solve: Will it commit to deepened characterization and worldbuilding, to making the <em>Star Wars</em> universe feel connected and lived-in, even for casual fans? Or will it instead continue to coast on the consumerist appeal of gimmicks like Baby Yoda?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7lPrXr">
When the <em>Star Wars</em> universe is Baby Yodas all the way down, then what?
</p></li>
<li><strong>Why Democrats’ best Trump indictment attack may be none at all</strong> -
<figure>
<img alt="Donald Trump speaks at a wooden podium with a “Trump” campaign sign on it, two large American flags hanging behind him." src="https://cdn.vox-cdn.com/thumbor/prYCQq3e8bwenVfN9hA3OKIZx-I=/343x0:4796x3340/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72187167/1250783613.0.jpg"/>
<figcaption>
Donald Trump gives a speech at his Mar-a-Lago estate in Florida after being arraigned in New York City. | Anadolu Agency via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Republicans are handing Democrats a strategy to deal with Trump. Will they accept it?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ip7z6G">
Many Democrats were <a href="https://thehill.com/homenews/house/3926841-democrats-hail-republicans-blast-trump-indictment/">quick to condemn</a> former President Donald Trump over news of his <a href="https://www.vox.com/politics/2023/3/30/23663972/trump-indicted-grand-jury-what-happens-next">indictment and arraignment in New York</a>. But in the week since, the party’s largely been quiet about Trump’s legal issues.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qCENPt">
That’s because as tempting as it might seem for Democrats to seize on the former president’s arraignment — <a href="https://www.vox.com/politics/2023/4/4/23664866/donald-trump-indictment-alvin-bragg-jack-smith-stormy-daniels-new-york-georgia">or even potential indictments to come</a> — the party has more to gain by speaking to voters’ worries about kitchen table issues, like gas prices, health care, and inflation, than by touching Trump’s legal troubles.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xb9Azy">
“Legal stories produce a lot of oxygen,” James Carville, the longtime Democratic political consultant and campaign strategist, told me. “This story does not need Democratic politicians and pundits to feed the fire. This fire is raging. Go start another fire.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VclcbN">
If the indictment fire is raging, that’s in large part thanks to Trump himself. Two weeks after news of the indictment broke, Trump’s still trying to make his indictment page-one news, especially to conservative and Republican audiences. He’s given a speech from his Mar-a-Lago home, run digital ads hyping (<a href="https://fwiwnewsletter.substack.com/p/trumps-online-indictment-windfall">and raising money off of</a>) his indictment, and sat down for a primetime interview with Fox News to try to spin these charges into positive political capital.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LkqeCK">
But he’s had mixed success so far. While he’s succeeded in rallying much of the Republican Party’s elite around him, big national stories that cater to the Democratic platform have retaken the national spotlight from him: mass shootings in <a href="https://www.vox.com/politics/2023/3/27/23658533/nashville-school-shooting-covenant-school">Tennessee</a> and <a href="https://www.vox.com/politics/2023/4/10/23677156/louisville-shooting-kentucky-active-shooter-police">Kentucky</a>, the expulsion and reinstatement of <a href="https://www.vox.com/politics/2023/4/10/23677366/tennessee-republicans-expelled-justin-jones-justin-pearson">two Tennessee lawmakers</a> who led gun control protests in Nashville, and conflicting rulings by federal judges over the future of the abortion pill <a href="https://www.vox.com/politics/2023/4/10/23677544/democrats-abortion-pill-ruling-law-mifepristone-misoprostol">mifepristone</a> have refocused voters’ attention on perennial social issues that go beyond Trump.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AJDjmO">
The return to prominence of these issues gives Democrats another opportunity to address the issues that helped them win in 2022: gun safety, abortion access, and democratic values.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CV4cGF">
At the same time, Trump’s efforts create a unique, tempting opportunity for President Joe Biden and Democratic candidates down-ballot: running a campaign against a candidate who has been charged with crimes, and a party that’s seemed to have largely decided those charges don’t matter.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JmIoit">
Some grassroots Democrats might want their leaders to emphasize and capitalize on this fact. But political strategists and Democratic party mainstays told me the better political strategy might be to let Republicans twist themselves into knots trying to defend Trump. While Republican candidates rush to defend their leader, <a href="https://www.vox.com/policy-and-politics/2023/2/10/23594319/joe-biden-2024-presidential-campaign-election">Democrats can instead talk up their accomplishments</a>, continue their defense of Social Security and Medicare, and offer a hopeful agenda for four more years of Biden and a renewed Democratic Congress.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XJwA2m">
“In the entire [presidential] primary that’s going to happen, let the Republicans wreck each other. I think that’s the best strategy for Democrats,” Joe Trippi, the Democratic strategist who was Howard Dean’s campaign manager in 2004 and a senior adviser to John Edwards during his presidential campaign in 2007, told me. “It’s the same contrast that worked for Biden in 2020 and worked for the party to avoid a massive red wave in 2022. There’s no way this ends well for Republicans.”
</p>
<h3 id="4zEv5p">
Trump and Republicans are already doing Democrats’ work for them
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="P6LIYy">
Trump is making sure that as many Americans as possible know that he is at the center of a criminal investigation and trial. He and his allies had been <a href="https://time.com/6268116/trump-indictment-details-drama/">meticulously planning the spectacle</a> of his arraignment after news of it leaked, and his trip from Florida to New York generated the kind of <a href="https://www.washingtonpost.com/politics/2023/04/04/analysis-trump-indictment/">media circus</a> the country hasn’t seen since Trump was in office himself.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4GE1FB">
There was plenty of speculation in the lead-up to Trump’s arraignment on just what kind of <a href="https://www.vox.com/politics/2023/3/25/23652166/trump-indictment-2024-election-grand-jury-bragg">political effect an indictment might have on Trump’s primary chances</a>. Many bet that it would help him in the short term and hurt him in the long term, and polling since then shows that at least the former is true.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vE9Eez">
Trump was right in betting that being charged with crimes would inspire a rally-around-the-flag effect. Plenty of his potential primary challengers and scores of Republican lawmakers and politicians have defended him, while his <a href="https://fivethirtyeight.com/features/trumps-indictment-might-be-making-him-more-popular-among-republicans/">support among the Republican base seems to have grown</a>: he’s opened up a wide gap in support with Florida Gov. Ron DeSantis, the potential challenger seen as the biggest primary threat to Trump, <a href="https://morningconsult.com/2024-gop-primary-election-tracker/">according to recent Morning Consult polling</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZN8PvT">
But that’s coming at an expense: A majority of Americans think he acted illegally and see the charges brought against him as serious, according to an <a href="https://www.ipsos.com/en-us/news-polls/Half-of-Americans-say-Trump-charges-are-serious">ABC News/Ipsos poll taken last week</a>. Half of Americans think he should have been charged with a crime, and Trump is losing support among independent voters, a majority of whom now agree that Trump should’ve been charged with a crime.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WP8LP3">
Those numbers suggest that Democrats don’t really need to make an effort to try to frame the indictment and ongoing investigations in a negative light: Republicans are already doing that work for them, bringing it up often and using conspiratorial language that only seems to be resonating with the most conservative, MAGA-friendly kind of American.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U7oYMY">
“There will be 100 percent knowledge that he’s indicted,” Carville said. “There’s not a soul that won’t know, and you can go into the deepest part of Appalachia and they will know that he was indicted.”
</p>
<h3 id="mYPa4f">
There’s not a ton of upside in Democrats talking about the indictment
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N5Elnu">
The White House, and the president, have been handling the news the same way they’ve handled a lot of politically contentious topics: choosing not to comment, and simply ignoring Trump.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AAd63v">
That White House strategy might be replicated on the trail when Biden begins to formally campaign for reelection. He and congressional Democrats have plenty to talk about: <a href="https://www.vox.com/politics/2023/3/22/23652041/federal-reserve-interest-rates-jerome-powell">improving inflation</a>, <a href="https://www.vox.com/2023/4/7/23674305/jobs-report-labor-market-economy-recession">low unemployment</a>, an array of <a href="https://www.vox.com/policy-and-politics/2023/2/10/23594319/joe-biden-2024-presidential-campaign-election">bipartisan accomplishments</a>, and Republican moves against <a href="https://www.vox.com/policy/2023/3/17/23639685/insurance-health-care-medicare-advantage-enrollment-growth">entitlement spending</a> and <a href="https://www.vox.com/policy/2023/4/5/23668272/florida-abortion-desantis-republicans-six-weeks-gop">abortion rights</a> in the states. The indictment simply falls under the umbrella of character flaws and shady behavior that Donald Trump is already known for, Trippi, who advised the campaign of John Edwards, another indicted former presidential candidate, said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZtTYz2">
“It’s the chaos of Trump and the MAGA base of their party, contrasting with Joe Biden and Democrats passing things like the bipartisan infrastructure bill,” he said. “I agree with Biden saying he’s not going to comment on the indictment. Just let it play out.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BR1RAv">
Kurt Bardella, a Democratic strategist and former Republican adviser, meanwhile, said candidates shouldn’t go out of their way to broach Trump’s indictment, unless doing so helps in their individual races. To ignore the charges completely “is implausible,” he told me. “The best way to manage that is to make everything about a contrast, and just hammer home the point that Republicans are on the side of the criminal while the Democrats are trying to actually get shit done.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="khVdRZ">
Democrats running in competitive House and Senate contests in the coming year should be especially selective in how they engage with Trump’s indictment, Kristen Hawn, a Democratic political consultant who works with swing district Democrats, told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TACC2m">
“When you really look at these candidates, my advice on this is that you just don’t take the bait,” she said. “I don’t see too much upside in proactively messaging, certainly not changing your campaign in any way. People still want to hear their representatives talk about things that are important to them.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AiBYrq">
Those issues are the perennial ones: preserving health care coverage for people with preexisting conditions, lowering drug prices, getting the price of food and utilities down, and preserving access to abortion. “Those are the things that people care about. The thing that keeps them up at night is not the indictment of Donald Trump,” she said. “Those members who are going to determine who holds the majority, at least in the House, would be smart to just continue on that path and not get distracted by all of this Trump stuff. There’s a chance that you alienate some voters by doing that.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jQRRia">
Hawn’s point about potentially alienating voters has some historical precedent with indictments. One of the more recent high-profile campaigns against a candidate under indictment happened just four years ago, when Ammar Campa-Najjar, a progressive Latino, Arab American activist, and former Obama staffer, challenged former Republican Rep. Duncan Hunter during the 2018 midterms. Hunter had been at the center of <a href="https://www.sandiegouniontribune.com/news/politics/sd-me-gop-hunter-20180208-story.html">plenty of scandals</a>, but the accusations that he and his wife misused hundreds of thousands of dollars in campaign funds and attempted to cover their tracks led to a <a href="https://www.vox.com/2018/8/21/17766338/duncan-hunter-campaign-fraud-indictment-campa-najjar">federal investigation and indictment</a> a few months before Election Day.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WJivCn">
The district, California’s 50th, had voted for Trump by double digits, and was rated by political experts as a solidly Republican seat. But the indictment, and the anti-Trump anger sweeping the country in that year’s blue wave, made Campa-Najjar’s challenge more serious. He zeroed in on the indictment to try to go after Hunter’s character and chip away at his Republican support, and made tremendous inroads, but ultimately lost by just <a href="https://www.nytimes.com/elections/results/california-house-district-50">3 percentage points.</a>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YqOa46">
“The thing that I would redo in my race is not doubling down on talking about the indictment, because it was already factored in and priced in,” Campa-Najjar told me recently. “People had made up their minds about it. I didn’t need to educate anybody else about it. Everyone knew about it, and there was no way to frame it differently.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MBWDRO">
There were other issues to talk about in that contest, just like Democrats have plenty to talk about beyond Trump and his follies, and talking too much about Trump’s indictment risks missing opportunities to persuade undecided and independent voters, he said: “It’s really important for those undecided voters, whether they’re independents or disenfranchised voters who were just turned off from politics, to educate those undecided voters, but not on the issue of the indictment. It’s on the issue of articulating what the president has done, and his historic victories.”
</p></li>
<li><strong>The 100-year-old-mistake that’s reshaping the American West</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/rZFrHma33PJWDF5pvVVKOF_ehxs=/240x0:1680x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72187160/WyattHersey_Vox_cover_final.0.jpg"/>
<figcaption>
Wyatt Hersey for Vox
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
What happens if the Colorado River keeps drying up?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uXxf63">
You may have heard this before: The Colorado River, which supplies drinking water to seven states in the US and two in Mexico, is the lifeblood of the American West and beyond. It’s drying up at an alarming rate, threatening cities, industries, agriculture, and energy sources. As it shrinks, rich ecosystems across its 1,450 miles are also disappearing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0bQrqG">
In this issue of the Highlight, Vox’s reporters across the science, health, climate, and Future Perfect teams explore the interconnected causes of this crisis, the startling consequences that are already reshaping life in this important region of the world, and the difficult tradeoffs we may need to accept to avert disaster.
</p>
<hr class="p-entry-hr" id="mBBqLq"/>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/3hZn6L9MzUJKeupeAiUOvckpryA=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24561088/Vox_lede1_final.jpg"/> <cite>Wyatt Hersey for Vox</cite>
</figure>
<h3 id="vstK5I">
<a href="https://www.vox.com/the-highlight/23670139/colorado-river-drought-lake-mead"><strong>The worst-case scenario for drought on the Colorado River</strong></a>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AmpoZ5">
One in eight Americans depend on a river that’s disappearing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Bh9ebg">
<em>By Umair Irfan</em>
</p>
<hr class="p-entry-hr" id="8Vwj4F"/>
<figure class="e-image">
<img alt="A man in jeans and a checked short-sleeved shirt kneels next to a long row of mounded soil, where small green plants are growing." src="https://cdn.vox-cdn.com/thumbor/_zdjf_XaweXV6p3hidTzRA-ybtE=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24564616/John_Boelts_showing_me_soil_moisture_in_farm_of_harper_s_melon.jpg"/> <cite>Benji Jones/Vox</cite>
</figure>
<h3 id="abZQyd">
<strong>You — yes, you — are going to pay for the century-old mistake that’s draining the Colorado River </strong><em><strong>(Coming Tuesday)</strong></em>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RGE4N6">
A huge amount of US food is grown in the desert using water from a river that’s drying up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="udK1Ak">
<em>By Benji Jones</em>
</p>
<hr class="p-entry-hr" id="ExLOAS"/>
<figure class="e-image">
<img alt="An illustration of a cow drinking from a stream." src="https://cdn.vox-cdn.com/thumbor/9Up50poXNoEmewDa5hilzp9mrI4=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24558268/Vox_WyattHersey_WaterCrisis.jpg"/> <cite>Wyatt Hersey for Vox</cite>
</figure>
<h3 id="ahfXGw">
<strong>Let’s talk about the biggest cause of the West’s water crisis </strong><em><strong>(Coming Wednesday)</strong></em>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NbVwTw">
The Colorado River is going dry … to feed cows.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NvKVAA">
<em>By Kenny Torrella</em>
</p>
<hr class="p-entry-hr" id="DALUys"/>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/ZX2mmMxb0tubwXsAZfO0s8K_giw=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24567216/MVP_VOX_LEDE_VALLEY_FEVER.jpg"/> <cite>Millie von Platen for Vox</cite>
</figure>
<h3 id="vRZoEc">
<strong>The devil lurking in the dust (</strong><em><strong>Coming Thursday)</strong></em>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9ojKUX">
How extreme weather is driving a deadly fungus further into the American West
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qb0MwP">
<em>By Keren Landman</em>
</p>
<hr class="p-entry-hr" id="tzGWGn"/>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/1b5A9ZuRhdKCK0vJ3FA1haN2FPw=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24566168/MVP_VOX_NEW_LEDE_1.jpg"/> <cite>Millie von Platen for Vox</cite>
</figure>
<h3 id="tGkViQ">
<strong>These 8 species depend on the Colorado River. What happens as it dries up? </strong><em><strong>(Coming Friday)</strong></em>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PtIbuL">
Wildlife needs water, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uk6LGA">
<em>By Benji Jones</em>
</p>
<hr class="p-entry-hr" id="XQiqm6"/>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jW6hDf">
<strong>CREDITS</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="otp9Bk">
<strong>Editors: </strong>Sam Oltman, Brian Resnick, Adam Clark Estes, Bryan Walsh <br/><strong>Copy editors/fact-checkers:</strong> Elizabeth Crane, Kim Eggleston, Tanya Pai, Caitlin PenzeyMoog<br/><strong>Additional fact-checking: </strong>Anouck Dussaud, Sophie Hurwitz<br/><strong>Art direction: </strong>Dion Lee<br/><strong>Audience:</strong> Gabriela Fernandez, Shira Tarlo, Agnes Mazur<br/><strong>Production/project editors:</strong> Lauren Katz, Nathan Hall
</p>
<div id="nOfMPX">
</div>
<div id="G4D8gf">
<div id="money_pixel_page_level_exception">
</div></div></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>Indian archers get Olympic gold medallist Korean coach before World Cup</strong> - This is the first time after the 2014 Asian Games that India have hired a foreign coach</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>Chennai to host Asian Champions Trophy in August</strong> - The 2007 Asia Cup was the last time an International hockey tournament was held in the city</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Premier League | Title race tightens after Arsenal stumbles; Man United moves to 3rd</strong> - Even after dropping four points in two games, Arsenal remains four points clear of Manchester City having played a game more. But the two teams go head-to-head on April 26</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>Bagnaia dominates Grand Prix of the Americas MotoGP sprint</strong> - Alex Rins on the Honda-LCR took second with Jorge Martin on another Ducati in third</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>Karunaratne, Mendis take Sri Lanka to 386-4 vs. Ireland</strong> - Captain Dimuth Karunaratne and Kusal Mendis have scored centuries and shared a record partnership for the second wicket to give Sri Lanka an imposing 386-4 at stumps on the opening day of the first cricket test</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>AIADMK for proper maintenance of feeding rooms in public places</strong> - Such feeding rooms were set up during the then Chief Minister Jayalalithaa’s tenure, says MLA Arunmothithevan</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>If govt not protecting soldiers, it doesn’t have right to be in power: Pawar on Satya Pal Malik’s allegations</strong> - The NCP chief said the responsibility of protecting soldiers of the country lies with the government</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>Milma stresses need to step up internal production of milk</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>Why It Matters | Andhra rock questions conditions for life 2M years ago</strong> - Scientists estimated the temperature and composition of a shallow inland sea from dolomite deposits in Andhra Pradesh.</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>Ambasamudram custodial torture | Victims depose before IAS officer Amudha</strong> - The People’s Watch advocates protested the presence of Special Branch police inside the taluk office where the inquiry is going on</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>Vladimir Kara-Murza: Russian opposition figure jailed for 25 years</strong> - Vladimir Kara-Murza says the harsh sentence shows he is “doing everything right”.</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>EU rejects Ukraine grain bans by Poland and Hungary</strong> - The two countries say the measures are necessary to protect their farming sectors from cheap imports.</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>Germans split as last three nuclear power stations go off grid</strong> - More than 60 years of nuclear power comes to an end, but many Germans are unhappy.</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>Eurovision 2023: Stars of this year’s song contest perform at final pre-party</strong> - ‘We don’t want this to end,’ singers tell the BBC as they perform for fans ahead of May’s finale.</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>France pension reforms: Macron signs pension age rise to 64 into law</strong> - President Macron makes the unpopular reforms law despite widespread protests in Paris and other cities.</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>Watch live: SpaceX to attempt a test flight of its Starship launch system</strong> - No human alive has ever seen a rocket this powerful take flight. - <a href="https://arstechnica.com/?p=1932092">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>iSIM vs eSIM vs SIM: The constantly shrinking ways carriers ID your phone</strong> - The death of physical SIM cards is quickly approaching. These are the alternatives. - <a href="https://arstechnica.com/?p=1925668">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>This adorable sloth briefly stole the spotlight during JUICE launch</strong> - Nicknamed “Jerry” by Netizens, it’s not the first encounter between nature and rockets. - <a href="https://arstechnica.com/?p=1932157">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dealmaster: Best cheap office chair deals</strong> - The ergonomic, affordable alternatives to Herman Miller and Steelcase chairs. - <a href="https://arstechnica.com/?p=1931867">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SCOTUS preserves access to abortion pill—for 5 days</strong> - It’s unclear how the high court will ultimately rule on the matter. - <a href="https://arstechnica.com/?p=1932127">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>A circus performer is driving home after a long day of training, when he is pulled over by a police officer for a broken light.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The officer looks in the car and sees a collection of knives in the backseat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Sir,” he says, “Why do you have all those knives?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“They’re for my juggling act,” the circus performer replies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I don’t believe you,” says the cop. “Prove it.” So the performer gets out of his car and begins juggling the knives flawlessly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Just at that moment, a car with two guys in it drives by. “Wow,” says one to the other. “I’m glad I quit drinking. These new sobriety tests are hard.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/CroakyPyrex"> /u/CroakyPyrex </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12p14ah/a_circus_performer_is_driving_home_after_a_long/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12p14ah/a_circus_performer_is_driving_home_after_a_long/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I think my neighbour is stalking me. I caught her Googling my name. At least I think she was…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The focus on my telescope is a little shaky.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Gil-Gandel"> /u/Gil-Gandel </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12p5m0b/i_think_my_neighbour_is_stalking_me_i_caught_her/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12p5m0b/i_think_my_neighbour_is_stalking_me_i_caught_her/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I decided to put together a support group for erectile dysfunction</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It was a big flop and nobody came.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Arkvoodle42"> /u/Arkvoodle42 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12omt3n/i_decided_to_put_together_a_support_group_for/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12omt3n/i_decided_to_put_together_a_support_group_for/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Osama bin Laden dies.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He immediately goes to hell, where the devil is waiting for him.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I don’t know what to do here,” says the devil. "You are on my list, but I have no room for you.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
You definitely have to stay here, so I’ll tell you what I’m going to do: I’ve got a couple of folks here who weren’t quite as bad as you.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I’ll let one of them go, but you have to take their place. I’ll even let YOU decide who leaves."
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Osama bin Laden thought that sounded pretty good, so the devil opened the first room. In it was Manuel Noriega and a large pool of water. He kept diving in and surfacing empty-handed. Over and over and over. Such was his fate in hell.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“No,” said Osama bin Laden, “I don’t think so. I’m not a good swimmer and I don’t think I could do that all day long.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The devil led him to the next room. In it was Ayatollah Khomeini with a sledgehammer and a room full of rocks. All he did was swing that hammer, time after time after time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“No, I’ve got this problem with my shoulder. I would be in constant agony if all I could do was break rocks all day,” commented Osama bin Laden.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The devil opened a third door. In it, Osama bin Laden saw Bill Clinton, lying on the floor with his arms staked over his head, and his legs staked in a spread-eagle pose. Bent over him was Monica Lewinsky, doing what she does best.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Osama bin Laden took this in disbelief and finally said, “Yeah, I can handle this.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The devil smiled and said, “OK, Monica, you’re free to go.”
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Mahmood551"> /u/Mahmood551 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12omu9u/osama_bin_laden_dies/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12omu9u/osama_bin_laden_dies/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man on his retirement, purchased a house situated near a high school. He spent the first few weeks of his retirement in peace, then the new school year began. One afternoon early into the first semester, three young boys came down the street, beating merrily on every bin they passed.</strong> - <!-- SC_OFF --></p>
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They did this the following day and the day’s after that, for a week, until the man decided it was time to take some action.
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The next afternoon, he walked out to meet the boys as they banged their way down the street.
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Stopping them, he said, “You kids are a lot of fun. In fact, I used to do the same thing when I was your age. Would you do me a favor? I would give you each a dollar, if you promise to come around and do your thing.”
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The boys were more than happy to accept this and continued to bang the bins.
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After a few days, the man came out to meet them with a sad smile, and said, “This recession really is putting a dent in my income. From now on, I will pay you each 50 cents to continue.”
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The boys were unimpressed by this, but continued to do the same afternoon activities.
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A few days later, the man approached them again and said, “Look, the recession has again reduced my income, so from now on, I am afraid I can only pay you 25 cents each.”
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The leader then exclaims angrily, “That’s it? If you really think we are going to waste our time banging the bins for 25 cents each, you must be a fool. No way that’s going to happen. We quit.”
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The man then enjoyed peace and serenity for the rest of his days.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12oo7ks/a_man_on_his_retirement_purchased_a_house/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12oo7ks/a_man_on_his_retirement_purchased_a_house/">[comments]</a></span></p></li>
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