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<title>14 March, 2024</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Engineered Migrasomes: A Robust, Thermally Stable Vaccination Platform</strong> -
<div>
The burgeoning abilities of pathogens and tumor cells to evade immune responses underscore the urgent need for innovative vaccination platforms based on a variety of biological mechanisms. The current logistical challenges associated with cold-chain (i.e. low-temperature) transportation particularly impacts access to vaccines in the global south. We recently discovered organelles called migrasomes, and herein we investigate the potential of migrasomes as an alternative vaccination platform. Their inherent stability and their enrichment with immune-modulating molecules make migrasomes promising candidates, but their low yield presents a hurdle. We address this problem through our engineered migrasome-like vesicles (eMigrasomes), which emulate the biophysical attributes of natural migrasomes with substantially improved yield. We show that eMigrasomes loaded with a model antigen elicit potent antibody responses and maintain stability at room temperature. We demonstrate that eMigrasomes bearing the SARS-CoV-2 Spike protein induce robust humoral protection against the virus. Our study demonstrates the potential of eMigrasome-based vaccines as a unique, robust, and accessible alternative to traditional methods.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.13.584850v1" target="_blank">Engineered Migrasomes: A Robust, Thermally Stable Vaccination Platform</a>
</div></li>
<li><strong>CircRNA-Pro: A Novel Toolkit for High-Precision Detection of Differentially Expressed Circular RNAs and Translatable Circular RNAs</strong> -
<div>
With the increasing discovery of circular RNAs (circRNAs) and their critical roles in gene regulation and disease progression, there is a growing need for more accurate and efficient tools for circRNAs research. In response, we have developed an integrated software suite specifically for circRNAs. This all-in-one tool specializes in detecting differentially expressed circRNAs, including those with the potential to be translated into proteins, and allows for comparing against relevant databases, thereby enabling comprehensive circRNA profiling and annotation. To enhance the accuracy in detecting differentially expressed circRNAs, we incorporated three different software algorithms and cross-validated their results through mutual verification. Additionally, this toolkit improves the effectiveness in identifying translatable circRNAs by optimizing Ribo-seq alignment and verifying against public circRNA databases. The performance of circRNA-pro has been evaluated through its application to public RNA-seq and Ribo-seq datasets on breast cancer and SARS-CoV-2 infected cells, and the results obtained have been validated against previous literature and databases. Overall, our integrated toolkit provides a reliable workflow for circRNA research, facilitating insights into their diverse roles across life sciences.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.13.584785v1" target="_blank">CircRNA-Pro: A Novel Toolkit for High-Precision Detection of Differentially Expressed Circular RNAs and Translatable Circular RNAs</a>
</div></li>
<li><strong>Mutability and hypermutation antagonize immunoglobulin codon optimality</strong> -
<div>
The efficacy of polyclonal antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation (SHM). These processes arose in early jawed vertebrates; however, little is known about how immunoglobulin diversity, mutability, and hypermutation have evolved in tandem with another more ubiquitous feature of protein-coding DNA - codon optimality. Here, we explore these relationships through analysis of germline IG genes, natural V(D)J repertoires, serum VH usage, and monoclonal antibody (mAb) expression, each through the lens of multiple optimality metrics. Strikingly, proteomic serum IgG sequencing showed that germline IGHV codon optimality positively correlated with VH representation after influenza vaccination, and in vitro, codon deoptimization of mAbs with synonymous amino acid sequences caused consistent expression loss. Germline V genes exhibit a range of codon optimality that is maintained by functionality, and inversely related to mutability. SHM caused a load-dependent deoptimization of IGH VDJ repertoires within human tonsils, bone marrow, and lymph nodes (including SARS-CoV-2-specific clones from mRNA vaccinees), influenza-infected mice, and zebrafish. Comparison of natural mutation profiles to true random suggests the presence of selective pressures that constrain deoptimization. These findings shed light on immunoglobulin evolution, providing unanticipated insights into the antagonistic relationship between variable region diversification, codon optimality, and antibody secretion; ultimately, the need for diversity takes precedence over that for the most efficient expression of the antibody repertoire.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.13.584690v1" target="_blank">Mutability and hypermutation antagonize immunoglobulin codon optimality</a>
</div></li>
<li><strong>Understanding Young Caring in the UK Pre- and Post-COVID-19: Prevalence, Correlates, and Insights from Three UK Longitudinal Surveys</strong> -
<div>
Background. Despite increasing awareness of young carers in recent years, there remains a significant gap in our understanding of both the prevalence and the characteristics of young carers. Our study aims to address this gap by examining the impact of the COVID-19 pandemic on the prevalence and characteristics of young carers. Methods. This research utilised data from three UK longitudinal surveys: the UK Household Longitudinal Study (UKHLS), the COVID Social Mobility and Opportunities (COSMO) study, and the Millennium Cohort Study (MCS). We focused on adolescents aged 16-18, and examined two pre-COVID (UKHLS and MCS) and two post-COVID (UKHLS and COSMO) samples. Results. The prevalence of young carers increased from 8.0% pre-COVID to 9.8-11.9% since COVID. Young carers were more commonly found in single-parent and socioeconomically disadvantaged households, with a higher prevalence of young carers in homes where parents were out of paid employment or held lower educational qualifications. Young carers were also more likely to reside in deprived areas. Most young carers engaged in low-intensity caring (&lt; 10 hours/week), but post-COVID there was an increase in high-intensity caring (10+ hours/week), predominantly assumed by young female carers. The primary recipients of care were parents, followed by grandparents and siblings, with no change in the care recipient type since COVID. Conclusion. This study showed an increase in the prevalence of young carers, particularly those providing high-intensity care, since the onset of the COVID pandemic. Further, young carers were more likely to come from socioeconomically disadvantaged households and areas. Given the potential impacts that young caring can have on young peoples’ lives, it is imperative that support for young carers is increased, particularly for those facing multiple disadvantages. In tandem, services that support adult health and social care need to play a key role in identifying young carers.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/65k2m/" target="_blank">Understanding Young Caring in the UK Pre- and Post-COVID-19: Prevalence, Correlates, and Insights from Three UK Longitudinal Surveys</a>
</div></li>
<li><strong>Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. Methods This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-&lt;5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10μg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. Results The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3μg BNT162b2, no sex differences were noted, but after a first dose of 5 or 10μg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p&lt;0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p&lt;0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p&lt;0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. Conclusions Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies. (German Clinical Trials Register ID: DRKS00028759).
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.08.24303999v1" target="_blank">Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study</a>
</div></li>
<li><strong>Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variant JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study</strong> -
<div>
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A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. During the study period (November 2022-January 2024), 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p=0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p=0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Day-28 mortality of JN.1-infected patients was 14.6%.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.11.24304075v1" target="_blank">Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variant JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study</a>
</div></li>
<li><strong>EpidemicKabu a new method to identify epidemic waves and their peaks and valleys</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
INTRODUCTION: The dynamical behavior of epidemic curves is an oscillation between a very low and very high number of incident cases throughout the time. These oscillations are commonly called waves of the epidemic curve. The concept of epidemic waves lacks a consensual definition and a simple methodology that can be used for many diseases. OBJECTIVE: We describe in this study the EpidemicKabu method to identify the start and the end of past epidemic waves but also their peaks and valleys. METHOD: The methodology is divided into processing of the curve, waves detection, and peaks and valleys delimitation. For processing the curve, a Gaussian kernel was used to diminish the noise and to smooth the curve. The first and second derivatives of the curve were used for the detection of waves, delimitation of peaks and valleys. The methodology was derived into the open access library. The method was tested using COVID-19 daily cases reported between 2020 and 2022 for different countries. After detection of waves, we made some measures related to the size of the waves for those countries. RESULTS: The results of the method were the dates of start and end of waves, peaks, and valleys. The dates are displayed on graphs and added as a new column in a dataset. We found that Belgium was the country recording the highest ratio of incident cases per 100 people by day in a wave. CONCLUSION: The EpidemicKabu method is simple, easy to use, and very useful in estimating epidemic waves. The methodology requires expert judgment in order to set a parameter that could only have three possible values.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.11.24304124v1" target="_blank">EpidemicKabu a new method to identify epidemic waves and their peaks and valleys</a>
</div></li>
<li><strong>The PRIME-NL study: evaluating a complex healthcare intervention for people with Parkinson’s disease in a dynamic environment</strong> -
<div>
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Background: An innovative, integrative care model for people with Parkinson (PRIME Parkinson) has gradually been implemented in a selected region of the Netherlands since 2021. A prospective evaluation of this model (PRIME-NL study) was initiated in parallel, spanning the year prior to implementation (baseline) and the implementation period. Following publication of the original study protocol, the COVID-19 crisis delayed implementation of the full PRIME Parkinson care model by two years and hampered the recruitment of study participants. Objective: To describe which methodological adjustments were made to the study protocol because of these developments. Methods: We compare various outcomes between a region where PRIME Parkinson care was implemented (innovation region) versus the rest of the Netherlands (usual care region). We use healthcare claims data of virtually all people with Parkinson in the Netherlands and annual questionnaires in a representative subsample of 984 people with Parkinson, 566 caregivers and 192 healthcare professionals. Four major methodological adjustments had to be made since publication of the original protocol. First, we extended the evaluation period by two years. Second, we incorporated annual process measures of the stage of implementation of the new care model. Third, we introduced a real-time iterative feedback loop of interim results to relevant stakeholders. Fourth, we updated the statistical analysis plan. Discussion: This manuscript provides transparency in how the design and analyses of the evaluation study had to be adapted to control for external influences in a dynamic environment, including eruption of the COVID-19 crisis. Our solutions could serve as a template for evaluating other complex healthcare interventions in a dynamic environment.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.11.24304097v1" target="_blank">The PRIME-NL study: evaluating a complex healthcare intervention for people with Parkinson’s disease in a dynamic environment</a>
</div></li>
<li><strong>The association between prolonged SARS-CoV-2 symptoms and work outcomes</strong> -
<div>
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While the early effects of the COVID-19 pandemic on the United States labor market are well-established, less is known about the long-term impact of SARS-CoV-2 infection and Long COVID on employment. To address this gap, we analyzed self-reported data from a prospective, national cohort study to estimate the effects of SARS-CoV-2 symptoms at three months post-infection on missed workdays and return to work. The analysis included 2,939 adults in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) study who tested positive for their initial SARS-CoV-2 infection at the time of enrollment, were employed before the pandemic, and completed a baseline and three-month electronic survey. At three months post-infection, 40.8% of participants reported at least one SARS-CoV-2 symptom and 9.6% of participants reported five or more SARS-CoV-2 symptoms. When asked about missed work due to their SARS-CoV-2 infection at three months, 7.1% of participants reported missing &gt;=10 workdays and 13.9% of participants reported not returning to work since their infection. At three months, participants with &gt;=5 symptoms had a higher adjusted odds ratio (aOR) of missing &gt;=10 workdays (2.96, 95% CI 1.81-4.83) and not returning to work (2.44, 95% CI 1.58-3.76) compared to those with no symptoms. Prolonged SARS-CoV-2 symptoms were common, affecting 4-in-10 participants at three-months post-infection, and were associated with increased odds of work loss, most pronounced among adults with &gt;=5 symptoms at three months. Despite the end of the Federal COVID-19 Public Health Emergency and efforts to “return to normal”, policymakers must consider the clinical and economic implications of the COVID-19 pandemic on people’s employment status and work absenteeism, particularly as data characterizing the numerous health and well-being impacts of Long COVID continue to emerge. Improved understanding of risk factors for lost work time may guide efforts to support people in returning to work.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.10.24304054v1" target="_blank">The association between prolonged SARS-CoV-2 symptoms and work outcomes</a>
</div></li>
<li><strong>Tight Fit of the SIR Dynamic Epidemic Model to Daily Cases of COVID-19 Reported During the 2021-2022 Omicron Surge in New York City: A Novel Approach</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
We describe a novel approach to recovering the underlying parameters of the SIR dynamic epidemic model from observed data on case incidence. We formulate a discrete-time approximation to the original continuous-time model and search for the parameter vector that minimizes the standard least squares criterion function. We show that the gradient vector and matrix of second-order derivatives of the criterion function with respect to the parameters adhere to their own systems of difference equations and thus can be exactly calculated iteratively. Applying our new approach, we estimated a four-parameter SIR model from data on daily reported cases of COVID-19 during the SARS-CoV-2 Omicron/BA.1 surge of December 2021 - March 2022 in New York City. The estimated SIR model showed a tight fit to the observed data, but less so when we excluded residual cases attributable to the Delta variant during the initial upswing of the wave in December. Our analyses of both the real-world COVID-19 data and simulated case incidence data revealed an important problem of weak parameter identification. While our methods permitted separate estimation of the infection transmission parameter and the infection persistence parameter, only a linear combination of these two key parameters could be estimated with precision. The SIR model appears to be an adequate reduced-form description of the Omicron surge, but it is not necessarily the correct structural model. Prior information above and beyond case incidence data may be required to sharply identify the parameters and thus distinguish between alternative epidemic models.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.13.23287177v3" target="_blank">Tight Fit of the SIR Dynamic Epidemic Model to Daily Cases of COVID-19 Reported During the 2021-2022 Omicron Surge in New York City: A Novel Approach</a>
</div></li>
<li><strong>Into the Unknown - Conceptualizing Citizens’ Experiences of Uncertainty in Citizen-state Interactions</strong> -
<div>
It is often argued that uncertainty is an inherent characteristic of citizen‒state interactions. It is therefore hardly surprising that many scholars of street-level bureaucracy have studied how frontline workers cope with and make discretionary decisions under uncertain conditions. However, citizens’ experiences of uncertainty have received limited attention in the street-level bureaucracy literature. This article argues that understanding citizens’ experiences of uncertainty is highly relevant because experiences of uncertainty are likely to affect mental wellbeing of individuals negatively. The article seeks to address this gap by building a conceptual framework for understanding and analyzing citizens’ experiences with uncertainty in state–citizen interactions based on theoretical insights from the existing literature and in-depth qualitative analysis of 20 narrative interviews with former COVID-19 patients and their relatives concerning their encounter with health authorities. The article proposes a conceptual framework that distinguishes between epistemic uncertainty and moral uncertainty. Epistemic uncertainty concerns uncertainty about empirical facts or knowledge. Moral uncertainty concerns uncertainty about values due to conflicting or competing norms and values. The article illustrates how these forms of uncertainty may arise before, during, and after citizens’ interaction with frontline workers.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/96pjt/" target="_blank">Into the Unknown - Conceptualizing Citizens’ Experiences of Uncertainty in Citizen-state Interactions</a>
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<li><strong>Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages</strong> -
<div>
Motivation: Charged amino acid residues on the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to influence its binding to different cell surface receptors, its non-specific electrostatic interactions with the environment, and its structural stability and conformation. It is therefore important to obtain a good understanding of amino acid mutations that affect the total charge on the spike protein which have arisen across different SARS-CoV-2 lineages during the course of the virus’ evolution. Results: We analyse the change in the number of ionizable amino acids and the corresponding total charge on the spike proteins of almost 2200 SARS-CoV-2 lineages that have emerged over the span of the pandemic. Our results show that the previously observed trend toward an increase in the positive charge on the spike protein of SARS-CoV-2 variants of concern has essentially stopped with the emergence of the early omicron variants. Furthermore, recently emerged lineages show a greater diversity in terms of their composition of ionizable amino acids. We also demonstrate that the patterns of change in the number of ionizable amino acids on the spike protein are characteristic of related lineages within the broader clade division of the SARS-CoV-2 phylogenetic tree. Due to the ubiquity of electrostatic interactions in the biological environment, our findings are relevant for a broad range of studies dealing with the structural stability of SARS-CoV-2 and its interactions with the environment. Availability: The data underlying the article are available in the online Supplementary Material.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.21.563433v2" target="_blank">Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages</a>
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<li><strong>SARS-CoV-2 methyltransferase nsp10-16 in complex with natural and drug-like purine analogs for guiding structure-based drug discovery</strong> -
<div>
Non-structural protein 10 (nsp10) and non-structural protein 16 (nsp16) are part of the RNA synthesis complex, which is crucial for the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nsp16 exhibits 2-O-methyltransferase activity during viral messenger RNA capping and is active in a heterodimeric complex with enzymatically inactive nsp10. It has been shown that inactivation of the nsp10-16 protein complex interferes severely with viral replication, making it a highly promising drug target. As information on ligands binding to the nsp10-16 complex (nsp10-16) is still scarce, we screened the active site for potential binding of drug-like and fragment-like compounds using X-ray crystallography. The screened set of 244 compounds consists of derivatives of the natural substrate S-adenosyl methionine (SAM) and adenine derivatives, of which some have been described previously as methyltransferase inhibitors and nsp16 binders. A docking study guided the selection of many of these compounds. Here we report structures of binders to the SAM site of nsp10-16 and for two of them, toyocamycin and sangivamycin, we present additional crystal structures in the presence of a second substrate, Cap0-analog/Cap0-RNA. The identified hits were tested for binding to nsp10-16 in solution and antiviral activity in cell culture. Our data provide important structural information on various molecules that bind to the SAM substrate site which can be used as novel starting points for selective methyltransferase inhibitor designs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.13.583470v1" target="_blank">SARS-CoV-2 methyltransferase nsp10-16 in complex with natural and drug-like purine analogs for guiding structure-based drug discovery</a>
</div></li>
<li><strong>Changes in the senescence profile and immune checkpoints in HIV-infected individuals after COVID-19</strong> -
<div>
Background: Both SARS-CoV-2 and HIV infection exhibit alterations in the senescence profile and immune checkpoint (IC) molecules. However, the midterm impact of SARS-CoV-2 on these profiles in people with HIV (PWH) remains unclear. This study aimed to evaluate differences in plasma biomarker levels related to ICs, the senescence-associated secretory phenotype (SASP), and pro- and anti-inflammatory cytokines in PWH following recovery from SARS-CoV-2 infection. Methods: We conducted a cross-sectional study of 95 PWH receiving antiretroviral therapy, stratified by SARS-CoV-2 infection status: a) 48 previously infected (HIV/SARS) and b) 47 controls without previous infection (HIV). Plasma biomarkers (n=44) were assessed using Procartaplex Multiplex Immunoassays. Differences were analyzed using a generalized linear model adjusted for sex and ethnicity and corrected for the false discovery rate. Significant values were defined as an adjusted arithmetic mean ratio [≥]1.2 or [≤]0.8 and a qvalue&lt;0.1. Spearman correlation evaluated relationships between plasma biomarkers (significant correlations, rho[≥]0.3 and q value&lt;0.1). Results: The median age of the PWH was 45 years, and 80% were men. All SARS-CoV-2-infected PWH experienced symptomatic infection; 83.3% had mild symptomatic infection, and sample collection occurred at a median of 12 weeks postdiagnosis. The HIV/SARS group showed higher levels of ICs (CD80, PDCD1LG2, CD276, PDCD1, CD47, HAVCR2, TIMD4, TNFRSF9, TNFRSF18, and TNFRSF14), SASP (LTA, CXCL8, and IL13), and inflammatory plasma biomarkers (IL4, IL12B, IL17A, CCL3, CCL4, and INF1A) than did the HIV group. Conclusions: SARS-CoV-2 infection in PWH causes significant midterm disruptions in plasma ICs and inflammatory cytokine levels, highlighting SASP-related factors, which could be risk factors for the emergence of complications in PWH.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.12.584682v1" target="_blank">Changes in the senescence profile and immune checkpoints in HIV-infected individuals after COVID-19</a>
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<li><strong>Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice</strong> -
<div>
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in severe disease often characterised by a 'cytokine storm' and the associated acute respiratory distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout the course of infection. Although blood biomarkers of severe disease are well studied, less well understood are the inflammatory signatures in lung tissues associated with mild disease or silent infections, wherein infection and inflammation are rapidly resolved leading to sequelae-free recovery. Herein we described RNA-Seq and histological analyses of lungs over time in an omicron BA.1/K18-hACE2 mouse infection model, which displays these latter features. Although robust infection was evident at 2 days post infection (dpi), viral RNA was largely cleared by 10 dpi. Acute inflammatory signatures showed a slightly different pattern of cytokine signatures compared with severe infection models, but where much diminished 30 dpi and absent by 66 dpi. Cellular deconvolution identified significantly increased abundance scores for a number of anti-inflammatory pro-resolution cell types at 5/10 dpi. These included type II innate lymphoid cells, T regulatory cells, and interstitial macrophages. Genes whose expression trended downwards over 2 - 66 dpi included biomarkers of severe disease and were associated with 'cytokine storm' pathways. Genes whose expression trended upward during this period were associated with recovery of ciliated cells, AT2 to AT1 transition, reticular fibroblasts and innate lymphoid cells, indicating a return to homeostasis. Very few differentially expressed host genes were identified at 66 dpi, suggesting near complete recovery. The parallels between mild or subclinical infections in humans and those observed in this BA.1/K18-hACE2 mouse model are discussed.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.12.584739v1" target="_blank">Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice</a>
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<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>Home-Based Circuit Training in Overweight/Obese Older Adult Patients With Knee Osteoarthritis and Type 2 Diabetes</strong> - <b>Conditions</b>: Aerobic Exercise; Strength Training; Glycemic Control; Blood Pressure; Oxidative Stress; Metabolic Syndrome <br/><b>Interventions</b>: Behavioral: 12-week home-based circuit training (HBCT); Behavioral: Standard of care (CONT) <br/><b>Sponsors</b>: Princess Nourah Bint Abdulrahman University <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>RECOVER-AUTONOMIC Platform Protocol</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG + Coordinated Care; Drug: IVIG Placebo + Coordinated Care; Drug: Ivabradine + Coordinated Care; Drug: Ivabradine Placebo + Coordinated Care; Drug: IVIG + Usual Care; Drug: IVIG Placebo + Usual Care; Drug: Ivabradine + Usual Care; Drug: Ivabradine Placebo + Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SVF for Treating Pulmonary Fibrosis Post COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis <br/><b>Interventions</b>: Biological: Autologous adipose-derived SVF IV administration <br/><b>Sponsors</b>: Michael H Carstens; Ministerio de Salud de Nicaragua; Wake Forest University; National Autonomous University of Nicaragua <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>RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine)</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: Ivabradine; Drug: Ivabradine Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)</strong> - <b>Conditions</b>: Long COVID; Long Coronavirus Disease 2019 (Covid19); Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG (intravenous immunoglobulin); Drug: IVIG Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <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>Understanding Adaptive Immune Response After COVID-19 Vaccination Boosters to Improve Vaccination Strategies in Vulnerable Groups.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Other: Analisys of cellular response and humoral response to SARS-CoV-2 vaccine booster doses <br/><b>Sponsors</b>: IRCCS Sacro Cuore Don Calabria di Negrar <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>COVIDVaxStories: Randomized Trial to Reduce COVID-19 Vaccine Hesitancy in Populations of Color</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Storytelling; Behavioral: Learn More (Active Comparator) <br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp &amp; Dohme LLC <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>An E-health Psychoeducation for People With Bipolar Disorders</strong> - <b>Conditions</b>: Bipolar Disorder; Psychoeducation; COVID-19 Pandemic <br/><b>Interventions</b>: Other: e-health psychoeducation <br/><b>Sponsors</b>: University of Cagliari; Alessandra Perra <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>Sulfureous Water Therapy in Viral Respiratory Diseases</strong> - <b>Conditions</b>: Long-COVID; Post COVID-19 Condition; Chronic COVID-19 Syndrome; Post Acute Sequelae of COVID-19 <br/><b>Interventions</b>: Other: Inhalation of Sulfurous Thermal Water; Other: Inhalation of Sterile Distilled non-pyrogenic Water <br/><b>Sponsors</b>: University of Roma La Sapienza; Università degli studi di Roma Foro Italico; Queen Mary University of London; Bios Prevention Srl <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>Phase 3 Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine and Influenza Combination Vaccine</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection <br/><b>Sponsors</b>: Novavax <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection.</strong> - <b>Conditions</b>: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection <br/><b>Interventions</b>: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo) <br/><b>Sponsors</b>: Sheng-Teng Huang <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>SHEN211 Tablets for the Treatment of Mild and Moderate Novel Corona Virus Infections (COVID-19)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets <br/><b>Sponsors</b>: JKT Biopharma Co., Ltd. <br/><b>Not yet 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>Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel</strong> - Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neutralization of SARS-CoV-2 and Intranasal Protection of Mice with a nanoCLAMP Antibody Mimetic</strong> - Intranasal treatment, combined with vaccination, has the potential to slow mutational evolution of viruses by reducing transmission and replication. Here, we illustrate the development of a SARS-CoV-2 receptor-binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope-binding nanoCLAMP, P2609. The resulting multimerized nanoCLAMP P2712 had…</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 cell-free assays for COVID-19 serosurvey</strong> - Serosurveys to monitor immunity toward COVID-19 in the population are primarily performed using an ELISA to screen samples for SARS-CoV-2 antibodies, followed by confirmation by a virus neutralization test, which is considered the Gold Standard. However, virus neutralization test may not be feasible for some laboratories because of the requirement for specific facilities and trained personnel. In an attempt to address this limitation, we evaluated three cell-free methods as potential…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The risk of acute infections in new users of antidepressants: An observational cohort study</strong> - CONCLUSIONS: Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.</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>Overlaid Lateral Flow Immunoassay for the Simultaneous Detection of Two Variant-Specific SARS-CoV-2 Neutralizing Antibodies</strong> - COVID-19 vaccines have been provided to the general public to build immunity since the 2019 coronavirus pandemic. Once vaccinated, SARS-CoV-2 neutralizing antibodies (NAbs-COVID-19) are needed for excellent protection against COVID-19. However, monitoring NAbs-COVID-19 is complicated and requires hospital visits. Moreover, the resulting NAbs-COVID-19 are effective against different strains of COVID-19 depending on the type of vaccine received. Here, an overlaid lateral flow immunoassay (O-LFIA)…</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 orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations</strong> - Inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^(pro)) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function against these mutants are thus urgently needed. We hypothesized that the covalent hepatitis C virus protease…</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>Repurposing of Plant-based Antiviral Molecules for the Treatment of COVID-19</strong> - COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context,…</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>Protective effect and mechanism of Qingfei Paidu decoction on myocardial damage mediated by influenza viruses</strong> - Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear. Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Decoding HiPSC-CM’s Response to SARS-CoV-2: mapping the molecular landscape of cardiac injury</strong> - CONCLUSION: SARS-CoV-2 infection in hiPSC-CMs is fundamentally mediated via mitochondrial dysfunction. Therapeutic interventions targeting mitochondrial dysfunction may alleviate the cardiovascular complications associated with SARS-CoV-2 infection.</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>Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CL(Pro) and PL(Pro)) by Molecular Docking and Dynamic Simulation Studies</strong> - We provide promising computational (in silico) data on phytochemicals (compounds 1-10) from Arabian Peninsula medicinal plants as strong binders, targeting 3-chymotrypsin-like protease (3CL^(Pro)) and papain-like proteases (PL^(Pro)) of SARS-CoV-2. Compounds 1-10 followed the Lipinski rules of five (RO5) and ADMET analysis, exhibiting drug-like characters. Non-covalent (reversible) docking of compounds 1-10 demonstrated their binding with the catalytic dyad (CYS145 and HIS41) of 3CL^(Pro) 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>Inhibitory Efficacy of Main Components of Scutellaria baicalensis on the Interaction between Spike Protein of SARS-CoV-2 and Human Angiotensin-Converting Enzyme II</strong> - Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against…</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>Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2</strong> - Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction becomes a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) 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>Licorice extract inhibits porcine epidemic diarrhea virus in vitro and in vivo</strong> - Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and even death in piglets, resulting in significant economic losses to the pig industry. Because of the ongoing mutation of PEDV, there might be variations between the vaccine strain and the prevailing strain, causing the vaccine to not offer full protection against different PEDV variant strains. Therefore, it is necessary to develop anti-PEDV drugs to compensate for vaccines. This study confirmed the anti-PEDV effect of licorice…</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>Neutrophil proteases are protective against SARS-CoV-2 by degrading the spike protein and dampening virus-mediated inflammation</strong> - Studies on severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have highlighted the crucial role of host proteases for viral replication and the immune response. The serine proteases furin and TMPRSS2 and lysosomal cysteine proteases were shown to facilitate virus entry by limited proteolytic processing of the spike (S) protein. While neutrophils are recruited to the lungs during COVID-19 pneumonia, little is known about the role of the neutrophil serine proteases (NSPs) cathepsin…</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>ACE2 acts as a novel regulator of TMPRSS2-catalyzed proteolytic activation of influenza A virus in airway cells</strong> - The transmembrane serine protease 2 (TMPRSS2) activates the outer structural proteins of a number of respiratory viruses including influenza A virus (IAV), parainfluenza viruses, and various coronaviruses for membrane fusion. Previous studies showed that TMPRSS2 interacts with the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), a cell surface protein that serves as an entry receptor for some coronaviruses. Here, by using protease activity assays, we determine that ACE2 increases the…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Explicitly Redistributive Budget for an Election Year</strong> - Joe Biden wants to expand the social safety net and reduce the deficit by raising taxes on the top two per cent and particularly the top 0.01 per cent. - <a href="https://www.newyorker.com/news/our-columnists/an-explicitly-redistributive-budget-for-an-election-year">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Have the Liberal Arts Gone Conservative?</strong> - The classical-education movement seeks to fundamentally reorient schooling in America. Its emphasis on morality and civics has also primed it for partisan takeover. - <a href="https://www.newyorker.com/magazine/2024/03/18/have-the-liberal-arts-gone-conservative">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Percival Everett Can’t Say What His Novels Mean</strong> - The author of “Erasure” is renowned for his satires of genre, identity, and America. But his great target may be language itself. - <a href="https://www.newyorker.com/magazine/2024/03/18/percival-everett-profile">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Open-Air Prison for ISIS Supporters—and Victims</strong> - Since the Islamic State fell, tens of thousands of people—many of them children—have been herded into Al-Hol, a giant fenced-in camp in Syria, and effectively given life sentences. - <a href="https://www.newyorker.com/magazine/2024/03/18/the-open-air-prison-for-isis-supporters-and-victims">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Among the A.I. Doomsayers</strong> - Some people think machine intelligence will transform humanity for the better. Others fear it may destroy us. Who will decide our fate? - <a href="https://www.newyorker.com/magazine/2024/03/18/among-the-ai-doomsayers">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Why the </strong>** does everyone swear all the ******* time?** -
<figure>
<img alt="An illustration of two brightly colored young people with bangs covering their eyes are talking to one another and using casual hand gestures. The speech bubbles surrounding them read “F@%k!,” “S#%t!,” “*%*!,” and “#@nt.”" src="https://cdn.vox-cdn.com/thumbor/YiDz7B_rhh51-4US5Cb3d0FFK64=/240x0:1680x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73206239/_5.0.jpg"/>
<figcaption>
Brian Scagnelli for Vox
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Curse words shift a lot over time. They’re in the middle of a big shift right now.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OqSXya">
One may as well begin with all the “cunts.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GmMYBC">
Over the past few years, my social media feeds have gradually filled up with people (largely American cis white women in their 30s) congratulating themselves on “serving cunt.” <a href="https://www.vox.com/culture/24074113/bayonetta-office-siren-tiny-reading-glasses-trend-tiktok-sexy-librarian">Cunty little librarian glasses</a> are all the rage. “Can a historian tell me why, as a society, we got less cunt?” <a href="https://www.tiktok.com/@cray/video/7321100854017248554">demanded a viral TikTok</a> in February that compared candy-colored Y2K technology with sleek post-iPhone contemporary tech. “QUIZ: Are They Really Serving Cunt or Do You Just Like Saying That?” <a href="https://reductress.com/post/quiz-are-they-really-serving-cunt-or-do-you-just-like-saying-that/">asked Reductress in December</a>. “Cunty (cunt, cunt, cunt, cunt),” sings Beyoncé in “PURE/HONEY.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oQ1fbF">
Yet about a decade ago, most of the people I knew considered the word to be nearly unspeakable outside of <a href="https://www.youtube.com/watch?v=oFi2YJ7YLR4">ribald British cinema</a>. It was so offensive, so shocking, that we called it “the c-word.” We suggested it was <a href="https://www.reddit.com/r/AskAnAmerican/comments/7gm4pi/how_offensive_is_the_word_cnt_to_you_my_american/">one of the most offensive words in American English</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KP2LZq">
“Cunt” is only the latest in a series of previously unspeakable words that have over time become trendy to say. “Fuck” is now in such widespread use that it’s come to seem a little antiquated that you still can’t say it on network <a href="https://www.vox.com/tv">television</a>. (Remember those “<a href="https://www.youtube.com/watch?v=Tj_0zcOlb4M">what the fork?</a>” ads for <em>The Good Place</em>?) And TV long ago gave up on trying to ban phrases like “ass” and “pissed off,” although they were once considered so obscene <a href="https://www.famous-trials.com/lennybruce/556-home">Lenny Bruce was arrested for using them</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ng5N0y">
In the face of all these dirty words, a person might be forgiven for asking: Why the fuck are people swearing so goddamn much these days?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W0u2AC">
It’s hard to prove, says Michael Adams, author of <a href="https://bookshop.org/p/books/in-praise-of-profanity-michael-adams/11993624?ean=9780199337583"><em>In Praise of Profanity</em></a>, that people actually are swearing more than they used to. “That’s for a number of methodological reasons,” he explains. For one thing, while people swear a lot on social media, it’s hard to show that social media users are a representative sample of the population. For another, we don’t have a real sense of how much people swore 50 years ago, as they unforesightfully failed to keep detailed records.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UkJWLt">
But if people aren’t swearing <em>more</em> than they used to, it does seem to be the case that they are swearing <em>differently</em> than they used to. “The specific words that are judged to be profane change over time,” says Benjamin Bergen, a professor of cognitive science and the author of <a href="https://bookshop.org/p/books/what-the-f-what-swearing-reveals-about-our-language-our-brains-and-ourselves-benjamin-k-bergen/12401993?ean=9781541617209"><em>What the F: What Swearing Reveals About Our Language, Our Brains, and Ourselves</em></a>. “We’re currently experiencing a lot of flux in exactly how offensive particular words are judged to be.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9wWPc8">
To understand how swear words change over time, it’s time for a brief history lesson.
</p>
<h3 id="DQLUXz">
One of the harshest medieval swears you could say was “zounds.”
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4W7ucA">
In medieval England, lots of the four-letter words we use to talk about bodies and sex were considered normal descriptive language. In her book <a href="https://bookshop.org/p/books/holy-sh-t-a-brief-history-of-swearing-melissa-mohr/7854674?ean=9780190491680"><em>Holy Sh*t: A Brief History of Swearing</em></a>, Melissa Mohr notes that both London and Oxford boasted medieval streets called Grope-cunt Lane (where the brothels were). By a medieval country pond, Mohr writes, “There would’ve been a shiterow in there fishing, a windfucker flying above, arse-smart and cuntehoare hugging the edges of the pond, and pissabed amongst the grass.” (Those are, in today’s sadly unvivid terminology, the birds heron and kestrel; and the plants water pepper, horehound, and dandelions.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="s4NcN1">
“They were kind of direct words for certain things that you wouldn’t necessarily say if you had an audience with the king, but they didn’t have any extraordinary power,” Mohr told Vox. “They appeared in schoolbooks.”
</p>
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What people considered obscene in medieval England was religious swearing. A word like “zounds,” from “Christ’s wounds,” could be genuinely shocking, which is why even today, our vocabulary for talking about profanity is religiously inflected. We talk about oaths and swearing and cursing because in the Middle Ages, to invoke God out loud meant that God was going to pay attention to whatever you were promising. When you said, “God damnit,” you were swearing before God, and he might damn you to hell if you didn’t deliver.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VlbVmX">
Mohr argues that bodily words were unremarkable in the Middle Ages because we had so little privacy from one another’s bodies. In a time of shared bedrooms and no indoor plumbing, defecation and sex happened more or less openly, and there was little point in being delicate about it with your language.
</p>
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As the world grew more private, however, starting in the 15th century, bodily words grew steadily more taboo. By the 19th century, Victorians had begun to describe pants as “unmentionables.” Religious oaths were losing their edge in the post-Enlightenment age, but “fuck” and its ilk were by now plenty shocking enough to fill the vacuum.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ANb51P">
Now, “fuck” seems to have become a lot less shocking than it used to be.
</p>
<h3 id="LdWjRd">
Over the past few decades, the f-word has grown steadily less offensive
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vrl4Uu">
Bergen thinks that we’re seeing a generational shift in what kinds of words are considered offensive. “Folks who are maybe 40 or older tend to think of profanity as including words that describe bodily functions and sex,” he says. “In more recent survey data, younger Americans tend to judge those words as far less offensive than older Americans do, to the point where the word ‘shit’ shows up for most people as not even in the top 50 most offensive words. For folks 25 and younger, ‘fuck’ is not in the top 20.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RqT3bf">
Bergen says the “grandmother” of these surveys is <a href="https://link.springer.com/content/pdf/10.3758/BRM.40.4.1065.pdf">one performed by Kristin Janschewitz at UCLA in 2008</a>. Janschewitz gave her subjects a list of 460 words and asked them to rate each one for taboo and offense, along with a few other factors. In the final tally, “fuck” is fifth on the list of most taboo words, but it doesn’t appear in the top 10 list of most offensive. In other words, it’s a word college students know you’re not supposed to say, but that most of them aren’t particularly bothered by hearing. Bergen gives a version of the same survey to 100 undergraduates every year, and he says “fuck” is only trending more and more strongly out of the offensive category over time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9UQPuH">
Profanity as we know it today evolves, spreads, and flourishes within subcultures, especially the subcultures of minority groups. “They are places where you have very clear in–versus-out group relations, and oftentimes where you find close social bonds and high degrees of emotionality,” says Berger. “That’s where you get the most interestingly creative profanity, and it’s the most profanity overall.”
</p>
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You can signal your membership within a marginalized subgroup by using the profanity people within that group have reclaimed for themselves (which is why, as <a href="https://www.vox.com/media">Fox News</a> is always pointing out with deep outrage, it is okay for Black people to use the n-word but not white people). Most of the exciting and interesting slang in American English comes from subcultures, and profanity is no exception. Even the military, which gave us “SNAFU” and “clusterfuck,” can function as a linguistic subculture with its own colorful innovations on the f-word.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7tLlDv">
The queer community has historically tended to play with profanity with particular abandon, dirty words about sex and bodies being of particular interest to a group marginalized for their sexual preferences. “Serving cunt,” that fashionable phrase, comes from the drag scene, and gradually made its way toward the mainstream from there.
</p>
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“What was once restricted to the drag community and understood to be a marker of that community’s identity now ends up seeping into mainstream culture through media like <em>RuPaul’s Drag Race</em>,” says Adams. “And then before you know it, people are using words they don’t know where they come from. They don’t know what they signify to the people who they mattered to first. They develop meanings or people start using them in ways that don’t really correspond to their subgroup origins. In some ways, that’s just the history of language.”
</p>
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A lot has to happen, though, for “serving cunt” to go from <em>Paris Is Burning</em> to the <a href="https://www.vox.com/twitter">Twitter</a> account of a cis straight white woman. There are a few different theories as to why sex and body words have become less taboo over time. One possible factor is the rise of social media, where people write for a wide audience as informally as they talk to their close friends in private.
</p>
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“It used to be that the only media you could consume was highly edited,” says Bergen. “With social media, all of a sudden now we have direct access to people’s informal language. If we have access to people’s informal communication and it includes more profanity, that just means we’re going to be exposed to more of it and that’s going to normalize it, and so people have become inured.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ChToz9">
Covid has its role to play, too. In the post-lockdown work-from-home era, swearing in the workplace seems to have begun trending up. In 2022, <a href="https://sentieo.docsend.com/view/nx9xk6e8fpc6hrqz">the office software company Sentieo reported that from 2020 to 2021</a>, the incidence of expletives in conference call transcripts jumped from 104 to 166. (Their sample size is limited to calls made using their software, so let’s not consider this a formal study.) “Business formality,” Sentieo noted in its analysis of the trend, “is on its way out.” It seems to be harder for people to keep their language office-friendly when they’re dialing into Zoom meetings from their couches — and as public profanity becomes more common, the division between office language and private language comes to seem more and more artificial.
</p>
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There’s also the issue of the rise of Donald Trump, who <a href="https://www.nytimes.com/2019/05/19/us/politics/trump-language.html">the New York Times once dubbed “the profanity president.”</a> Trump swears frequently, publicly, and gleefully (“shithole countries,” “I fired his ass,” “grab ’em by the pussy,” etc.) and his supporters love him for it. They consider Trump’s swearing to be part of his authenticity, proof that he really is one of them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="obW40k">
In apparent answer, rank-and-file politicians have begun to swear with public abandon. <a href="https://thehill.com/blogs/in-the-know/in-the-know/457732-f-bombs-away-why-lawmakers-are-cursing-now-more-than-ever/">A 2019 analysis from GovPredict</a> found that politicians posted curse words on Twitter fewer than 200 times in 2016. In 2018, however, politicians tweeted curses over 2,500 times.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ahSh8H">
“They realized that there was some power in the electorate that Trump had identified,” says Adams of the rise of political swearing. “It made these politicians seem more normal.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xJF5E2">
The swearing politicians included those who at the time were actively seeking the Democratic nomination for president. After a mass shooting in 2019, <a href="https://www.thewrap.com/beto-orourke-donald-trump-politics-of-profanity/">Beto O’Rourke released a campaign T-shirt that said</a> “This is f<em>cked up. This is f</em>cked up. This is f<em>cked up. This is f</em>cked up. This is f<em>cked up. This is f</em>cked up,” and then, in smaller type, “End gun violence now.” He began a press conference with the line, “Members of the press: What the fuck?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AV5T0E">
“Profanity is not the f-bomb,” <a href="https://www.thewrap.com/beto-orourke-donald-trump-politics-of-profanity/">O’Rourke said on MSNBC</a> of his frequent campaign trail swearing. “What’s profane is a 17-month-old baby being shot in the face.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oJ3nBr">
O’Rourke’s line here points to one of the big cultural shifts that has accompanied the fall of “fuck” as a word of great obscenity. As a country, we have gone through decades of social change centered around the idea of making our sexual culture less shame-based. We have birth control now. The sexual revolution has come and gone. The whole shift has been so successful that we’re now seeing the beginnings of a backlash to the pro-casual sex culture, with the right having successfully taken down <em>Roe</em> and freely <a href="https://www.nbcnews.com/tech/internet/birth-control-side-effects-influencers-danger-rcna90492">admitting they plan to come for contraceptives next</a>. In some ways, it’s easier to say “fuck” than it is to actually do the deed in the US right now — but the changes the sexual revolution made to our culture are still there in the language. By now, we have all read lots of books and heard speeches about how bodies and sex aren’t filthy, and what’s really filthy is violence.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GqsBQv">
Which perhaps is why today, the words in the English language that are considered truly unspeakable are words that are held to enact or symbolize violence.
</p>
<h3 id="yjJVXZ">
The unspeakable words of today are the slurs
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aXuYAc">
“Fuck” isn’t that offensive to millennials and Gen Z, but slurs are. In Janschewitz’s study, the n-word is found to be the most offensive and most taboo of all the words on her list. It’s so taboo that it’s against Vox style to spell the word out under most circumstances.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7Qe6tV">
“I think you see a lot of intentional education of kids describing the ways in which slurs and other terms of abuse can be harmful, and I don’t think that’s a thing that really was discussed in the ’80s or ’90s around kids,” says Bergen. “You see it internalized by younger folks and Gen Z and so on, to the point where they take it on themselves to educate older people about their attitudes towards slurs.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3Unl2e">
Mohr points out that when religious and sexual swears were still shocking, racial epithets mostly weren’t. “When they made <em>Gone With the Wind</em> in 1939, they made such a big deal about putting ‘damn’ in there,” she says. “But <a href="https://www.npr.org/2014/09/14/347987062/from-casting-to-cutting-the-n-word-the-making-of-gone-with-the-wind">the n-word was just going to be in there like it was totally fine</a> until some of the Black actors objected. Societal consciousness of that as a potential slur only happened quite recently in the bigger scheme of things.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Hzz3pk">
In this context, the oddity of “cunt” becomes a little clearer. “Cunt” is unusual because it is both a bodily expletive and a gendered slur. <a href="https://theconversation.com/theyre-serving-what-how-the-c-word-went-from-camp-to-internet-mainstream-210214">After decades evolving in the drag ball scene</a>, it’s ripe for reclamation, but it’s also almost unspeakable, ranked six on Janschewitz’s list of taboo words. That makes it potentially hurtful, but it also makes it exceptionally exciting to say. It is that rare thing: a word about sex and bodies that still has the power to shock.
</p></li>
<li><strong>Is Justin Timberlake the pop star anyone wants?</strong> -
<figure>
<img alt="Justin Timberlake wearing a tuxedo." src="https://cdn.vox-cdn.com/thumbor/A_xRNVGZcSStz1MZt0qjyXxmbQQ=/459x0:7798x5504/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73206199/GettyImages_2075763170.0.jpg"/>
<figcaption>
Justin Timberlake attending the 2024 Vanity Fair Oscar Party on March 10, 2024. | Lionel Hahn/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A new kind of masculinity is dominating music — leaving little room for yesterday’s pop idol.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ioYsQd">
In the year 2024, the name Justin Timberlake comes with a lot of baggage.
</p>
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His Super Bowl halftime show performance <a href="https://youtu.be/v6xUgawDQB0?feature=shared">six years ago</a> — which coincided with the release of his last album, <a href="https://www.vox.com/culture/2018/2/2/16947136/justin-timberlake-man-of-the-woods-white-masculinity"><em>Man of the Woods</em></a> — kicked off a serious round of discourse about his 2004 halftime show performance and the <a href="https://www.vox.com/culture/22739035/janet-jackson-wardrobe-malfunction-controversy-explainer-sexuality-damita-jo">wardrobe malfunction</a> that tanked Janet Jackson’s career while leaving Timberlake unscathed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vQpXKE">
Then there was the way he handled his highly publicized 2002 breakup with <a href="https://www.vox.com/culture/23814154/britney-spears-fans-conspiracy-theories-conservatorship">Britney Spears</a>, feeding into the sexist commentary surrounding her — the details of which resurfaced in the <a href="https://www.vox.com/culture/22276585/framing-britney-spears-us-weekly-perez-hilton-daniel-ramos">2021 documentary <em>Framing Britney Spears</em></a>. In Spears’s 2023 memoir, <em>The Woman In Me</em>, she revealed <a href="https://www.vulture.com/2023/10/britney-spears-book-the-woman-in-me-justin-timberlake.html">more embarrassing revelations</a> about Timberlake, further igniting fiery discussions about his privilege as a white man in an industry that unfairly punishes his Black and female counterparts. There have been cries of appropriation and of infidelity.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZlnPkZ">
Now, after years away from the spotlight (<a href="https://www.nytimes.com/2021/02/12/arts/music/justin-timberlake-statement-britney-spears.html">and one Instagram apology</a>), Timberlake is releasing a new album titled <em>Everything I Thought It Was</em>.<em> </em>So far, its lead single (“Selfish”) and promotional track (“Drown”) point to a more mellow, R&amp;B-lite direction for the singer — with the exception of the gospel-flavored song “Sanctified,” which <a href="https://www.youtube.com/watch?v=E3ZoiIC7Sfk">previewed on <em>Saturday Night Live</em></a>. And the <a href="https://www.tiktok.com/@justintimberlake/video/7339580778508078378?lang=en">album’s artwork</a>, influenced by 1971’s <em>Willy Wonka and the Chocolate Factory</em> and Federico Fellini’s masterpiece <em>8 ½</em>, hints at an emphasis on visuals.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vroq8K">
It seems as though Timberlake is ready to reclaim his title as the millennial king of pop. But in a culture that is now seeking to reckon with the sins of the ’90s and early aughts, can he rise above being viewed as a cultural misstep? Or is a decline in relevance the only natural trajectory for an objectionable, 43-year-old white dude in our current pop landscape where “sensitive” male artists like Bad Bunny and Harry Styles reign supreme?
</p>
<h3 id="niIDYV">
Justin Timberlake’s “bad boy” image always had an expiration date
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7BJpnO">
Justin Timberlake’s current image — <a href="https://twitter.com/DmvMusicPlug/status/1538545684030361600?s=20">dancing on stage in khakis</a> and <a href="https://www.youtube.com/watch?v=97SPDxM3Ezw">promoting songs for the <em>Trolls</em> soundtrack</a> — is a far cry from the version the singer put forth after breaking out of NSYNC.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9T6QY7">
By the time of his 2002 solo debut, <em>Justified</em>, Timberlake had begun to shed his boy-band identity and embrace an edgier posture in his music and <a href="https://www.rollingstone.com/music/music-news/justin-timberlake-the-bachelor-244039/">romantic life</a>. Like many white pop stars in the early aughts, he also experimented with street fashion, cornrows, and other Black aesthetics. In <em>The Woman in Me, </em>Spears<em> </em><a href="https://ew.com/ginuwine-responds-justin-timberlake-fo-shiz-britney-spears-memoir-8413544">alleged</a> a cringey interaction between Timberlake and R&amp;B singer Ginuwine that signaled a desire for Blackness. Ultimately, his iteration of a “bad boy” read as manufactured and relatively safe. As Pitchfork contributor Julianne Escobedo Shepherd explains, “His masculinity was couched in a nonthreatening, boy-next-door persona that relied immensely on his whiteness, even as he was drawing on Black music and collaborating with Black musicians.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gwhDIq">
Timberlake’s affinity for Black music and soulful vocal styling is <a href="https://www.usatoday.com/story/life/music/2013/04/09/justin-timberlake-shares-childhood-obsession-grammy-moment/2068491/">often attributed</a> to his Southern Baptist roots — he performed in his church choir — or his upbringing in Memphis, Tennessee, a breeding ground for soul and rock ’n’ roll. As a member of NSYNC, he dabbled in a commercialized form of pseudo-R&amp;B. But his work on <em>Justified </em>was the start of his gaining acceptance in Black spaces and establishing decades-long relationships with producers like Timbaland and Pharrell Williams. Unlike the marginalized artists he was often trying to emulate, his whiteness afforded him an appearance of innocence and goodwill in the public eye that could easily be weaponized.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wAjLz0">
“He was very effective at using his boy-band past and white, blond, blue-eyed looks to shore up the general victim narrative that was central to his early career,” Escobedo Shepherd says. It was the tactic he used in the 2002 video for his hit single “Cry Me a River,” in which he not-so-subtly indicts Spears as a cheater while placing himself in the role of a guy who has revenge sex in his ex’s home and continues to stalk her afterward.
</p>
<figure class="e-image">
<img alt="Justin Timberlake in a white sweater and Britney Spears in a black dress smile while leaning into each other." src="https://cdn.vox-cdn.com/thumbor/oa1ccSSq77npIoVlQjo2nrlmYNY=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25334614/GettyImages_76235991.jpg"/> <cite>Kevin Mazur/WireImage</cite>
<figcaption>
Justin Timberlake and Britney Spears at the MTV Movie Awards on June 3, 2000.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TaOrh3">
“Justin Timberlake was <em>the man</em> in the early 2000s,” says Kelli Williams, co-host of the podcast <em>Beyond the Blinds</em>. “He broke up with Britney. He’s dating Alyssa Milano. He’s [rumored to be] dating Scarlett Johansson. But it’s like what Jennifer Aniston said about Brad Pitt: There’s a <a href="https://www.vanityfair.com/news/2005/09/aniston200509">sensitivity chip</a> missing.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OOcfBq">
That lack of sensitivity would only really be interrogated years later. Many <a href="https://www.rollingstone.com/music/music-features/justin-timberlake-the-new-king-of-pop-233648/">critical analyses</a> at the time were focused on Timberlake’s unique stardom in an era otherwise flooded with rappers and aging male rockstars. Some music writers were excited to name him the <a href="https://nymag.com/arts/popmusic/reviews/20314/">heir to Michael Jackson and Prince</a> for his impressive vocal range, slick dance moves, and proficiency performing Black music, while others were still <a href="https://slate.com/culture/2003/08/why-are-pop-critics-so-afraid-of-justin-timberlake.html">figuring out</a> whether he was a hack.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wCeu4T">
Following the Grammy-winning <em>Justified</em> and a <a href="https://ew.com/article/2006/04/21/justin-timberlake-movie-star/">detour into acting</a>, he amped up his persona as a sex symbol with the more experimental 2006 album <em>FutureSex/LoveSounds</em>. The record saw Timberlake play with structure — incorporating reprises and interludes — as well as different genres, including funk and techno, and some annoying beatboxing. Critics were impressed, or at least awed, by his boldness and what they saw as his ingenuity as an artist.
</p>
<div class="c-float-right">
<aside id="XHtc2w">
<q>“It’s like what Jennifer Aniston said about Brad Pitt: There’s a sensitivity chip missing”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YneC97">
Timberlake would retreat to Hollywood again after his sophomore album. In the early 2010s, he booked roles in a series of buzzy movies. In <em>The Social Network, </em>he gave a deliciously dirtbaggy portrayal of Napster founder Sean Parker; in <em>Friends With Benefits</em> and <em>In Time,</em> he was positioned as the sexy leading man. He also appeared on <em>Saturday Night Live </em>numerous times, showcasing himself as a charismatic, well-rounded talent. When he returned to music in 2013 with the first half of the double album <em>The 20/20 Experience</em>, he seemed to have attained some self-awareness about the unsavory reputation he had gained as a younger man. “I don’t want people to think I’m a self-obsessed sex machine,” he told<em> </em><a href="https://www.gq-magazine.co.uk/article/justin-timberlake-interview-2006">British GQ</a> in 2012.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KZVqR2">
His third record saw a softer, more romantic side of Timberlake, with sultry serenades that reflected his personal life, including his marriage to actress Jessica Biel. His newfound maturity was best represented in the album’s blockbuster single “Mirrors,” which — despite its <a href="https://slate.com/culture/2013/02/justin-timberlake-new-song-mirrors-is-this-the-most-narcissistic-love-song-of-all-time.html">arguably narcissistic lyrics</a> — signified his commitment to monogamy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bpOTJU">
Unfortunately for Timberlake, he would experience a significant fall from grace in the following years, both as an artist and as a <a href="https://www.cnn.com/2019/12/05/entertainment/justin-timberlake-apologizes-jessica-biel-intl-scli/index.html">wife guy</a>.
</p>
<h3 id="xJQCeY">
In the 2010s, Timberlake’s complicated relationship with Black culture finally caught up to him
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hy9Nfx">
Timberlake’s relationship to Black music has long been polarizing, an object of criticism for some and a sign of credibility to others. Throughout his career, Black organizations like the BET Networks and the NAACP have nominated him for awards and welcomed him at ceremonies. He’s gotten props from legendary Black artists, including Stevie Wonder, who praised him for having “absorbed a lot of different kinds of music” in a <a href="https://time100.time.com/2013/04/18/time-100/slide/justin-timberlake/">Time 100 tribute</a>. Despite being embraced by the rap and R&amp;B worlds, though, he’s found himself at the center of heated discussions about cultural appropriation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6mPy5U">
The strange landscape of pop music in the 2010s generated many of these online conversations. At the time, white rappers like Macklemore and Iggy Azalea were dominating the charts, and singers like Katy Perry and Madonna <a href="https://www.billboard.com/music/music-news/pop-star-ladies-wearing-grills-madonna-miley-beyonce-more-show-off-5915737/">were donning hood aesthetics</a>, which some labeled as appropriation. During and following his <em>20/20 Experience </em>era, Timberlake was receiving that <a href="https://colorlines.com/article/justin-timberlake-making-money-black-music-reader-forum/">criticism</a><a href="https://www.theroot.com/have-blacks-forgiven-justin-timberlake-1790895595">, too</a> — and some critics, <a href="https://pitchfork.com/news/66500-vic-mensa-calls-out-justin-timberlake-for-benefiting-from-using-black-culture/">including rapper Vic Mensa</a>, called out his silence around the <a href="https://www.vox.com/race">Black Lives Matter</a> movement. In 2016, Timberlake drew more heat after he <a href="https://pitchfork.com/news/66418-justin-timberlake-apologizes-for-bet-awards-tweet-controversy/">responded condescendingly</a> on Twitter to a Black journalist who accused him of “appropriating [Black] culture.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KUK8LB">
Just a year and a half later, Timberlake <a href="https://www.buzzfeednews.com/article/annehelenpetersen/go-west-white-man">caused a stir</a> with the announcement of his country-inspired fifth album, <em>Man of the Woods</em>. At first glance, it appeared that Timberlake was abandoning his signature urban sound to appeal to a broader (and whiter) fanbase. Ultimately, as Northwestern University professor and author Lauren Michele Jackson <a href="https://www.vulture.com/2018/01/exploring-justin-timberlakes-relationship-to-black-music.html">wrote for Vulture</a> in 2018, the frenzy over his perceived genre switch wasn’t really warranted. In an interview with Vox, Jackson says the eclectic album was “very in line with Timberlake’s amalgamative tendencies.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VoWMjS">
She says that his aesthetic pivot felt pointed in the eyes of critics due to our tense political climate: “The charge [against Timberlake] was inauthenticity. Funny enough, that is the same charge belatedly brought against his performing in the genre that yielded his fame in the first place.”
</p>
<div>
<aside id="wgbFaY">
<q>The sex appeal that felt so crucial to Timberlake’s image seemed to have entirely dissipated</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0Sbhdb">
Nevertheless, the critical <a href="https://pitchfork.com/reviews/albums/justin-timberlake-man-of-the-woods/">reception</a> to <em>Man of the Woods</em> was <a href="https://www.esquire.com/entertainment/music/a15962375/justin-timberlake-man-of-the-woods-review/">mixed</a> at best, and the album lacked the inescapable bangers he had produced in the past. Timberlake’s title as pop’s reigning king suddenly felt dubious. At one time, his pushing of racial boundaries in his music had made him a virtuoso. But in hindsight, it made him seem like a fraud. The year after he released <em>Man of the Woods</em>, Timberlake’s marriage also saw trouble after he was caught holding hands with his co-star in the film <em>Palmer</em>, Alisha Wainwright, leading him to <a href="https://www.usatoday.com/story/entertainment/celebrities/2019/12/04/justin-timberlake-apologizes-family-his-lapse-judgment/2614997001/">release an apology</a>. Meanwhile, the reappraisals of his relationships to both Jackson and Spears added extra precarity to his crumbling reputation. Could he ever return to music in an acceptable form?
</p>
<h3 id="XvCetO">
Is Justin Timberlake irrelevant in 2024, or does his stardom just look different?
</h3>
<figure class="e-image">
<img alt="Timberlake gestures to the audience while the other members of the band stand by." src="https://cdn.vox-cdn.com/thumbor/2z-hvPP3gl7s3Df8Q4HyIM1fDvE=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25334580/GettyImages_1677226784.jpg"/> <cite>Mike Coppola/Getty Images for MTV</cite>
<figcaption>
Joey Fatone, Lance Bass, Justin Timberlake, JC Chasez, and Chris Kirkpatrick of NSYNC onstage at the MTV Video Music Awards on September 12, 2023.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZEcQUF">
In June 2022, a <a href="https://x.com/DmvMusicPlug/status/1538545684030361600?s=20">viral video</a> of Timberlake doing the Beat Ya Feet dance — some fast and fancy footwork <a href="https://www.kqed.org/arts/13879679/dont-mute-dc-how-go-go-music-inspires-the-beat-ya-feet-dance-movement">created</a> by Black Washington, DC, teens in the ’90s — at Pharrell Williams’s Something in the Water Festival seemed to indicate that his next music venture would be an uphill battle for several reasons. Not only were the once-revered dancer’s moves labeled awkward, but social media also got a kick out of his paternal appearance — his khakis and patterned button-up made him look like a middle-aged dad at a cookout.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UsPpFS">
The sex appeal that felt so crucial to Timberlake’s image in the early 2000s <a href="https://www.youtube.com/watch?v=P0e8koQYA6s">seemed</a> to have entirely <a href="https://www.youtube.com/watch?v=ru0K8uYEZWw">dissipated</a> in his post-<em>Trolls</em> era. The reaction was less about his actual looks and more about how expectations for the way male pop musicians present themselves have changed. In a New York Times piece, writer Lindsay Zoladz <a href="https://www.nytimes.com/2022/12/27/arts/music/pop-men-harry-styles-jack-harlow-bad-bunny.html">pointed</a> to a trend of younger male pop stars like Bad Bunny, Harry Styles, Lil Nas X, and even rapper Jack Harlow embracing a gender-bending, “softboi” brand of masculinity — something Timberlake hasn’t attempted. On the red carpet, he sticks to his refined, GQ-in-2012 style; onstage, well, you saw those khakis.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FisKFH">
Most important, though, is Timberlake’s new music. “Selfish,” the lead single from <em>Everything I Thought It Was</em>, had a lukewarm reception, debuting at No. 19 on the Billboard Hot 100. The song itself was ultimately overshadowed by Britney Spears’s fan army, which trolled Timberlake by streaming her 2011 song of the same name — at one point, Spears’s “Selfish” <a href="https://www.billboard.com/music/chart-beat/britney-spears-justin-timberlake-selfish-sales-trending-up-1235594534/">beat Timberlake’s</a> on the iTunes charts. Fab drama aside, the midtempo, R&amp;B-tinged single, which <a href="https://www.thedailybeast.com/justin-timberlakes-selfish-comeback-is-missing-something">drew comparisons</a> to Nick Jonas’s “Jealous,” sounded shockingly generic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="az4qhv">
The lyrical content of “Selfish” felt bland and distanced as well, given the turmoil that has defined his career and personal life recently. Host of the <em>Pop Pantheon</em> podcast DJ Louie XIV says that the singer struggles to balance his showmanship with younger listeners’ desire for intimacy. He points to Timberlake’s contemporary Beyoncé as someone who’s married their theatricality with a “sense of deep, personal revelation that speaks to the demands of the moment.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p996ga">
“Everything is much more driven by intimacy and relatability, a feeling that you know your stars of choice and that they are accessible to you and share your concerns,” he says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XnNWBd">
It’s probably not a coincidence then that one of the biggest male artists at the moment, <a href="https://www.vox.com/culture/23785854/drake-rap-21-savage-for-all-the-dogs-its-all-a-blur-tour-poetry">Drake</a>, built off a chart-topping career by lamenting his love life and anxieties — no matter how childish — as a public figure. Pop superstars Styles and Ed Sheeran have also found success using diaristic lyrics. And the latest male sensation in the pop sphere, indie-folk singer <a href="https://www.vox.com/culture/23920808/noah-kahan-vermont-dial-drunk-stick-season-tiktok">Noah Kahan</a>, has seemingly captivated Gen Z, in part, by singing about and advocating <a href="https://www.vox.com/mental-health">mental health</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MCOos7">
Still, the announcement of Timberlake’s Forget Tomorrow World Tour has been met with high demand, <a href="https://www.livenationentertainment.com/2024/02/justin-timberlake-announces-first-shows-on-second-leg-of-highly-successful-the-forget-tomorrow-world-tour-following-21-sold-out-shows-and-over-350000-tickets-sold-thus-far/">selling out in multiple venues</a> and requiring additional dates. A search of the artist’s name on <a href="https://www.vox.com/tiktok">TikTok</a> still shows <a href="https://www.tiktok.com/@90snsync/video/7271707794074553643?q=nsync%20justin&amp;t=1709933265487">accounts</a> that are <a href="https://www.tiktok.com/@thenerdsawaken/video/7328572776087080238?lang=en">thirsting</a> over the musician and fans who are <a href="https://www.tiktok.com/@littlehoneyvee_/video/7329017136280505642?q=justin%20timberlake%20snl%20&amp;t=1709933730263">responding eagerly</a> to his latest <em>Saturday Night Live</em> performance and reunion with NSYNC. Timberlake can still count on the collaboration with his former boy band for engagement.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Q3iW9J">
“Nostalgia is the best drug out there right now,” says Williams. “I think the only way for Justin to really get into the public’s good graces is to work with NSYNC. I don’t think NSYNC is beneath him, but it makes him look humble that, after all these years, he can go back to his roots.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BV2qex">
Whether or not Timberlake can compete on the charts with the Harry Styleses of the world may not be a concern for his die-hard fans. For listeners who grew up alongside him, there’s a level of amusement in watching someone mature and navigate a new stage of their life, even if it’s a little awkward. While Timberlake’s “dad” era may be cringe to some, it’s offered him an air of innocence that he’s struggled to maintain publicly — and ultimately may never fully get back.
</p></li>
<li><strong>Who is the British royal family willing to protect?</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/JTF6IHAlMKfDAYa7wsADtbWbAfY=/244x0:4732x3366/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73206185/1243292742.0.jpg"/>
<figcaption>
From left to right, Princess Catherine; Prince William; Prince Harry; and Meghan, Duchess of Sussex, greet well-wishers outside Windsor Castle on September 10, 2022, after the death of Queen Elizabeth II. | Mark Kerrison/In Pictures via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Kategate, briefly explained.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="flDwZH">
Have you heard the news? <a href="https://www.vox.com/culture/24087565/princess-kate-middleton-disappearance-rumors-explained-abdominal-surgery-kensington-palace">Princess Catherine of Wales, formerly Kate Middleton, seems to be missing</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UFSBXf">
Kate hasn’t been seen in public since several weeks before she reportedly underwent abdominal surgery, a fact that first made the internet alarmed and then, later, very amused.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="w9r7yQ">
Over the past week, a series of highly questionable photos of Kate have made their way to the public, culminating in <a href="https://www.vox.com/culture/24098724/kate-middleton-editing-photo-explained">one picture that was so heavily and amateurishly Photoshopped</a> that multiple photo agencies, including the AP and Reuters, issued a kill notice for it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cSRtuU">
The Palace appears to be trying in a very hamfisted way to cover something up. Instead, they only fueled the internet’s appetite for gossip. The story has crossed from the group chats of royal watchers into the mainstream media. Even <a href="https://twitter.com/CarmenGranddau1/status/1767828446237839572?s=20">Colbert’s on it</a> as of Tuesday night.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tWMTPk">
That’s because this surreal saga is about more than any one illness, any one photograph, or even any one princess.
</p>
<aside id="1DLROg">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6rrgYG">
The <a href="https://www.vox.com/british-royal-family">British royal family</a> theoretically has a sophisticated apparatus in place to manage their reputations and the reputation of the throne. So for them to bungle a story as badly as they have bungled this one is fascinating.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YWfQxT">
What’s perhaps most fascinating about it is that they seem to have messed up in the first place in an attempt to protect Kate and her privacy — which raises all sorts of questions about whom the British throne is willing to protect, and whom they throw to the wolves instead.
</p>
<h3 id="ejzI4F">
A brief timeline of what we know about Kate’s whereabouts
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nMGzM8">
The last time <a href="https://www.harpersbazaar.com/celebrity/latest/a46227698/kate-middleton-royal-blue-christmas-day-church-service-prince-william-kids/">Kate was seen in public</a> was on Christmas, attending church with her family. Here’s what has happened since — and how each move has in turn kicked off more conspiracy theorizing:
</p>
<ul>
<li id="LaYBhw">
<strong>January 17:</strong> <a href="https://www.royal.uk/news-and-activity/2024-01-17/a-statement-from-kensington-palace">Kensington Palace announces</a> that Kate entered the hospital the day before for planned abdominal surgery. The statement adds that she is “unlikely” to resume her public duties until Easter, which falls this year on March 31.
</li>
<li id="W8TAaQ">
<strong>January 27:</strong> <a href="https://twitter.com/KensingtonRoyal/status/1751938452721996034">Kensington Palace announces</a> that Kate has returned home to finish recovering. No photos exist of her leaving the hospital or heading home. Royal watchers begin to take note, pointing out that Kate historically has posed for photos in full makeup and heels <a href="https://www.townandcountrymag.com/society/tradition/a19674665/kate-middleton-post-birth-appearance-differences-comparison/">within hours of giving birth to all three of her children</a>.
</li>
<li id="8v2SBk">
<strong>March 4:</strong> A paparazzi agency publishes <a href="https://www.etonline.com/see-kate-middleton-for-the-first-time-since-hospitalization-for-abdominal-surgery-pic-220894">a grainy photo of Kate and her mother, Carol Middleton, driving around Windsor Castle</a>. Watchers begin speculating about Kate Middleton body doubles.
</li>
<li id="vf9wRJ">
<strong>March 10:</strong> On Mother’s Day in the UK, <a href="https://www.vox.com/culture/24098724/kate-middleton-editing-photo-explained">Kensington Palace releases a photograph of Kate with her arms around her children</a>. Within hours, international photo agencies conclude that the photo has been manipulated and issue a kill notice for it.
</li>
<li id="uPzN5p">
<strong>March 11: </strong><a href="https://twitter.com/KensingtonRoyal/status/1767135566645092616">Kate and Prince William’s X account posts an apology</a> for the doctored image, signing it C for Catherine and saying, “Like many amateur photographers, I do occasionally experiment with editing.” The same day, <a href="https://people.com/kate-middleton-leaves-windsor-prince-william-private-appointment-hours-after-mothers-day-photo-apology-8607277">paparazzi publish a photo</a> in which the hair and ear of a brunette woman can be seen in a car with Prince William. The photo agency identifies the woman as Kate; royal watchers are skeptical.
</li>
</ul>
<h3 id="Xk9V5w">
This whole controversy says a lot about the monarchy’s priorities
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VH7EWl">
The royal family appears to be trying very clumsily to cover up something that has to do with Kate and her medical condition. Part of why the story has gone viral in the first place is that in the past, that’s reportedly not something they were willing to do for Meghan Markle.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nqQRPi">
Since Meghan and Harry’s engagement in 2017, Kate and Meghan have been used as each other’s foils in the press. Meghan tends to be positioned as either<a href="https://www.dailymail.co.uk/home/you/article-4155700/Kate-v-Meghan-wears-cool-crown.html"> more progressive, glamorous, and exciting</a>; or more <a href="https://www.buzzfeednews.com/article/ellievhall/meghan-markle-kate-middleton-double-standards-royal">whiny, demanding, and attention-seeking</a>. Kate tends to be positioned as either <a href="https://www.dailymail.co.uk/home/you/article-4155700/Kate-v-Meghan-wears-cool-crown.html">more conservative, dowdy, and traditional</a>; or more <a href="https://www.buzzfeednews.com/article/ellievhall/meghan-markle-kate-middleton-double-standards-royal">respectable, royal, and maternal</a>. Neither of them is ever quite allowed to exist outside the shadow of the other.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cWz9kH">
So, <a href="https://www.niemanlab.org/2024/03/this-is-just-weird-buzzfeed-news-former-royals-reporter-on-kate-middleton-palace-press-and-distrust-in-the-media/?utm_source=substack&amp;utm_medium=email">Meghan fans demanded</a> as Kate’s disappearance began to extend toward scandal, why is the royal family ready to make sacrifices for Kate that they would not make for Meghan?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S9Spf9">
In <a href="https://www.vox.com/culture/23502170/netflix-harry-meghan-review">their Netflix docuseries <em>Harry &amp; Meghan</em></a>, the Sussexes discuss all the ways in which Meghan asked for help and privacy with her <a href="https://www.vox.com/health-care">health care</a> and all the ways the royal family declined to assist her.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ArGxWO">
According to Meghan, she wanted to choose the hospital where she would give birth to her child and do the customary photoshoot at the castle rather than just outside the hospital, immediately postpartum. <a href="https://www.marieclaire.com/celebrity/a34462275/prince-william-meghan-markle-in-labor-with-archie-announcement/">William reportedly considered the move a “prima donna maneuver,”</a> and the British press covered the news with outrage. When Meghan began to struggle with suicidal ideation, she says she was told that she could not go to a therapist, as doing so would bring scandal to the family.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EvTzsw">
It’s tempting to see this situation through a US lens and conclude that the discrepancy exists because Kate is whiter and better behaved than Meghan is. And it’s certainly fair to say that those factors play a role here.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gLG8dk">
But with the royals, it’s all about precedence. If the royal family is really treating Kate with more forbearance than they did Meghan, that’s because Kate is next in line to be Queen of England, and she’s married to the future King. Meghan, married to the proverbial spare, was most likely not afforded such courtesies because the family had decided she wasn’t close enough to the crown to bother.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Dlz3Ar">
Like all stories about British royalty, this is a story about power and how power protects itself.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yH5b6A">
<em>This story appeared originally in </em><a href="https://www.vox.com/today-explained-podcast"><em><strong>Today, Explained</strong></em></a><em>, Vox’s flagship daily newsletter. </em><a href="https://www.vox.com/pages/today-explained-newsletter-signup"><em><strong>Sign up here for future editions</strong></em></a><em>.</em>
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ravindra becomes youngest recipient of Sir Richard Hadlee Medal</strong> - At 24, Ravindra is the youngest winner in the award’s history</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>Fifty-two entries for 47th MMSC South India Rally</strong> -</p></li>
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<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kurnool MP Sanjeev Kumar joins TDP</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>A trickle of defections to BJP discomfits Congress ahead of PM Modi’s Kerala visit on March 15</strong> - Latest Congress deserters to BJP in Kerala include Padmini Thomas who is a 1982 Asian Games medalist and Arjuna Award winner and former municipal counsellor Thampanoor Satheesh</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>Indian Naval Symphonic Band regales audience in Tiruchi</strong> - A band of 35 talented musicians of the Eastern Naval Command played carnatic fusion, popular English and Tamil songs besides the Tri-Services song to thunderous applause</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>Telangana government plans to enforce ECBC effectively in association with LiFE Mission, BEE</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>Drug seizure case | Tamil Nadu government files defamation against Edappadi Palaniswami, Annamalai for comments against CM Stalin</strong> - The complaints were filed before the Principal Sessions Court by the City Public Prosecutor G. Devarajan on behalf of the State government</p></li>
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<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rosenberg: Russia’s stage-managed election</strong> - In Borovsk, Steve Rosenberg looks at the Russia Putin wants you to see - and Russia in reality.</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>60 migrants die as boat sinks in Med, survivors say</strong> - Shipwreck survivors tell rescuers they had set sail from Libya a week earlier.</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>Dutch anti-Islam populist Wilders abandons PM bid</strong> - His party won a dramatic victory in the 2023 elections, but talks on forming a coalition continue.</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>Atletico beat Inter on penalties to reach last eight</strong> - Atletico Madrid dramatically beat Inter Milan on penalties to reach the Champions League quarter-finals and eliminate last season’s runners-up.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Denmark to start conscripting women for first time</strong> - The Scandinavian nation also wants to raise the service time for men and women, and boost defence spending.</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>2024 Lincoln Nautilus first drive: a sea change for Lincoln’s middle-child</strong> - The Nautilus might just be enough to finally get people into Lincoln dealers. - <a href="https://arstechnica.com/?p=2010079">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The 2025 Porsche Panamera perfectly balances luxury ride and great handling</strong> - There’s clever new air suspension and a much bigger battery for the PHEV variant. - <a href="https://arstechnica.com/?p=2009599">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SpaceX has a license to launch Starship—this time it might fly at dawn</strong> - The launch window opens before sunrise Thursday at SpaceX’s launch site in Texas. - <a href="https://arstechnica.com/?p=2009349">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Death by neti pot: Why you shouldn’t use tap water to clean your sinuses</strong> - An alarming number of Americans think tap water is sterile—it’s definitely not. - <a href="https://arstechnica.com/?p=2010041">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bitcoin Fog operator convicted of laundering $400M in bitcoins on darknet</strong> - Roman Sterlingov will appeal, denouncing DOJ’s crypto-tracing techniques. - <a href="https://arstechnica.com/?p=2010017">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>An old one, but I was reminded of the Magic Dildo today.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
While on a visit to the sex shop, a young woman named Lisa came across a product advertised as the Magic Dildo.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She brought the item to the shopkeeper to ask about it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Ah yes”, he said, “this one is voice activated. You just put the batteries in, and say the words ‘Magic Dildo-‘ and wherever you want it to go!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Quite intrigued, Lisa paid for the Magic Dildo and brought it home to her small apartment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Inserting the batteries, she felt silly holding a voice activated dildo, so as a test, she quietly stated: “Magic Dildo, the bed”.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Magic Dildo shot up onto the air and flew across the room, landing softly on the bed with a gentle whir.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The young woman excitedly removed her clothes, got on the bed with her new toy and whispered “Magic Dildo- my pussy.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Magic Dildo gave a whir and slid effortlessly inside, vibrating and pulsating. Lisa moaned with pleasure as the Magic Dildo hit all the right spots.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After a few minutes of pure bliss, Lisa came with an orgasm that shook the entire bed. Toes curled and screaming in ecstasy, she felt the Magic Dildo’s whirring intensify.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wave after wave and orgasm after orgasm left Lisa screaming and drenched with sweat and other fluids. She wanted to stop but realized she couldn’t get a grip on the Magic Dildo to pull it out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Magic Dildo STOP! MAGIC DILDO NO MORE!” The Magic Dildo wasn’t listening.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Lisa struggled to get somewhat dressed, and crawled back to her car. orgasming over and over again she drove as best she could back to the sex shop for help, but her erratic driving caught the attention of a traffic cop, who pulled her over.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Please!” She screamed before the officer could even say a word, “I am not drunk! I have a Magic Dildo, I can’t get it out!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The policeman laughed, “Magic Dildo- My Ass”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/mercuryandcyanide"> /u/mercuryandcyanide </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1be0t5g/an_old_one_but_i_was_reminded_of_the_magic_dildo/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1be0t5g/an_old_one_but_i_was_reminded_of_the_magic_dildo/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>4 mothers talk about how succesfull their kids are…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The first one starts. “My little boy is a really succesfull doctor. He and his girlfriend will go on a 1 month vacation in Europe next week.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The second mother goes: “Thats nothing. My boy is a succesfull lawyer and just bought his girlfriend a new Aston Martin.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The third mother goes: " Thats still nothing, my boy is a very good banker and he bought his girlfriend a new beachhouse last month and he let her choose all the furniture with no limits."
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Full of expectation they look at the last mother.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She sighs and goes: “Sadly my girl just works at a bar and keeps relationships with multiple men at a time. But they give her a lot of gifts.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In this moment, a beautifull girl pulls up to them in an new Aston Martin. She lets down the window and starts talking to the last mother.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
" Hey mum nice seeing you. I just wanted to ask if could you please take care of the beachhouse next month? I still expect a lot of furniture deliveries and I’ll be on vacation to Europe for the whole month."
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/InitiativeExcellent"> /u/InitiativeExcellent </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1behzyj/4_mothers_talk_about_how_succesfull_their_kids_are/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1behzyj/4_mothers_talk_about_how_succesfull_their_kids_are/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A bus stops and two Italian men get on.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A bus stops and two Italian men get on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They sit down and engage in a conversation. The lady sitting behind them ignores them at first, but her attention is caught when she hears one of the men say the following:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Emma come first. Den I come. Den two asses come together. I come once-a-more. Two asses, they come together again. I come again and pee twice. Then I come one lasta time.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“You foul-mouthed idiot. In this country we don’t talk about our sex lives in public!” yelled the shocked lady.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Hey, coola down lady,” said the man. “Who talkin’ abouta sexa? I’m a justa tellin’ my frienda how to spella ‘Mississippi’.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/mildads"> /u/mildads </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1befzb1/a_bus_stops_and_two_italian_men_get_on/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1befzb1/a_bus_stops_and_two_italian_men_get_on/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I told my wife, “I think Worcestershire Sauce is my favourite condiment.”</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Her: Why?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Me: It’s..hard to say.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/porichoygupto"> /u/porichoygupto </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1beb9jc/i_told_my_wife_i_think_worcestershire_sauce_is_my/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1beb9jc/i_told_my_wife_i_think_worcestershire_sauce_is_my/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What do you get when you cross a virgin with a board game?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
No fucking clue.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/KairuSmairukon"> /u/KairuSmairukon </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1be598f/what_do_you_get_when_you_cross_a_virgin_with_a/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1be598f/what_do_you_get_when_you_cross_a_virgin_with_a/">[comments]</a></span></p></li>
</ul>
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