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<title>19 May, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2</strong> -
<div>
Proline is widely known as the only proteogenic amino acid with a secondary amine. In addition to its crucial role in protein structure, the secondary amino acid modulates neurotransmission and regulates the kinetics of signaling proteins. To understand the structural basis of proline import, we solved the structure of the proline transporter SIT1 in complex with the COVID-19 viral receptor ACE2 by cryo-electron microscopy. The structure of pipecolate-bound SIT1 reveals the specific sequence requirements for proline transport in the SLC6 family and how this protein excludes amino acids with extended side chains. By comparing apo and substrate-bound SIT1 states, we also identify the structural changes which link substrate release and opening of the cytoplasmic gate, and provide an explanation for how a missense mutation in the transporter causes iminoglycinuria.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.17.541173v1" target="_blank">Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2</a>
</div></li>
<li><strong>Marginated aberrant red blood cells induce pathologic vascular stress fluctuations in a computational model of hematologic disorders</strong> -
<div>
Red blood cell (RBC) disorders affect billions worldwide. While alterations in the physical properties of aberrant RBCs and associated hemodynamic changes are readily observed, in conditions such as sickle cell disease and iron deficiency, RBC disorders can also be associated with vascular dysfunction. The mechanisms of vasculopathy in those diseases remain unclear and scant research has explored whether biophysical alterations of RBCs can directly affect vascular function. Here we hypothesize that the purely physical interactions between aberrant RBCs and endothelial cells, due to the margination of stiff aberrant RBCs, play a key role in this phenomenon for a range of disorders. This hypothesis is tested by direct simulations of a cellular scale computational model of blood flow in sickle cell disease, iron deficiency anemia, COVID-19, and spherocytosis. We characterize cell distributions for normal and aberrant RBC mixtures in straight and curved tubes, the latter to address issues of geometric complexity that arise in the microcirculation. In all cases aberrant RBCs strongly localize near the vessel walls (margination) due to contrasts in cell size, shape, and deformability from the normal cells. In the curved channel, the distribution of marginated cells is very heterogeneous, indicating a key role for vascular geometry. Finally, we characterize the shear stresses on the vessel walls; consistent with our hypothesis, the marginated aberrant cells generate large transient stress fluctuations due to the high velocity gradients induced by their near-wall motions. The anomalous stress fluctuations experienced by endothelial cells may be responsible for the observed vascular inflammation.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.541016v1" target="_blank">Marginated aberrant red blood cells induce pathologic vascular stress fluctuations in a computational model of hematologic disorders</a>
</div></li>
<li><strong>CParty: Conditional partition function for density-2RNA pseudoknots</strong> -
<div>
RNA molecules fold into biologically important functional structures. Efficient dynamic programming RNA (secondary) structure prediction algorithms restrict the the search space to evade NP-hardness of general pseudoknot prediction. While such prediction algorithms can be extended to provide a stochastic view on RNA ensembles, they are either limited to pseudoknot-free structures or extremely complex. To overcome this dilemma, we follow the hierarchical folding hypothesis, i.e. the bio-physically well-motivated assumption that non-crossing structures fold relatively fast prior to the formation of pseudoknot interactions. Thus, we efficiently compute the conditional partition function (CPF) given a non-crossing structure G for a subset of pseudoknotted stuctures i.e. density-2 structures G {cup} G' for non-crossing disjoint G'. Notably, this enables sampling from the hierarchical distribution P (G'|G). As our main contribution, we devise the algorithm CParty, which transfers the dynamic programming scheme of HFold to a partition function variant by for the first time de-ambiguating its decomposition of density-2 structures. Compared to the only other available pseudoknot partition function algorithm, which covers simple pseudoknots, our method covers a much larger structure class; at the same time, it is significantly more efficient (reducing the time as well as the space complexity by a quadratic factor). Summarizing, we provide a highly efficient (cubic time) algorithm for the stochastic analysis of pseudoknotted RNAs, which enables novel applications. For example, we discuss how the CPF for a pseudoknotted therapeutic target in SARS-CoV-2 provides insights into RNA structure formation kinetic paths.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.541023v1" target="_blank">CParty: Conditional partition function for density-2RNA pseudoknots</a>
</div></li>
<li><strong>Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Abstract Background: The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods: Using a bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL) and disability in 1082 severely and critically patients with COVID-19 between December 8, 2022 and February 9, 2023 in Shanghai, China. The final 60-day follow-up was completed on April 10, 2023. Results: Among 1082 patients (mean age, 78.0 years), 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval, 0.24-0.79]) and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 0.44-1.14]) compared with the control. IL-6 receptor antagonist, Baricitinib, and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR &gt;0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06-2.50]), and glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71-2.16]). Paxlovid, Azvudine and therapeutic anticoagulation showed significant reduction in disability (p&lt;0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in resource-limited scenario. Treatment with IL-6 receptor antagonist, Baricitinib, and a-thymosin also had high probabilities of benefit of improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine and therapeutic anticoagulation could significantly reduce disability at day 60. Keyword: COVID-19; Azvudine; Paxlovid; Interleukin-6 receptor antagonist; Baricitinib, α-thymosin, Intravenous immunoglobulin
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.10.23289325v3" target="_blank">Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China</a>
</div></li>
<li><strong>Delineating a ‘15-Minute City’: An Agent-based Modeling Approach to Estimate the Size of Local Communities</strong> -
<div>
With progressively increased people living in cities, and lately the global COVID-19 outbreak, human mobility within cities has changed. Coinciding with this change, is the recent uptake of the ‘15-Minute City’ idea in urban planning around the world. One of the hallmarks of this idea is to create a high quality of life within a city via an acceptable travel distance (i.e., 15 minutes). However, a definitive benchmark for defining a ‘15-Minute City’ has yet to be agreed upon due to the heterogeneous character of urban morphologies worldwide. To shed light on this issue, we develop an agent-based model named ‘D-FMCities’ utilizing realistic street networks and points-of-interest, in this instance the borough of Queens in New York City as a test case. Through our modeling we grow diverse communities from the bottom up and estimate the size of such local communities to delineate 15-minute cities. Our findings suggest that the model could be helpful to detect the flexibility of defining the extent of a ‘15-minute city’ and consequently support uncovering the underlying factors that may affect its various definitions and diverse sizes throughout the world.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/p7fdz/" target="_blank">Delineating a ‘15-Minute City’: An Agent-based Modeling Approach to Estimate the Size of Local Communities</a>
</div></li>
<li><strong>Promoting Urban Farming for Creating Sustainable Cities in Nepal</strong> -
<div>
This paper responds to the research question, “can urban farming in Nepal help create sustainable cities?” Especially after the COVID-19 pandemic, urban residents have begun to realize that food transported from long distances is not always reliable. Urban farming can help produce fresh food locally and help urban residents become self-reliant by engaging in healthy eating habits and practicing sustainable agricultural techniques in food-desert areas, while creating a positive impact on the environment through regenerative agricultural methods. In doing so, urban farms can help the growers save on food expenditures and even earn some additional income, while also improving air quality and minimizing the effects of urban heat islands. This practice also helps reduce greenhouse gases through plant carbon use efficiency (CUE), as vegetation carbon dynamics (VCD) can be adjusted while supporting the circular economy. As urban lands command higher prices than agricultural land, urban farming usually happens on residential yards, roofs, balconies, community gardens, and dedicated areas in public parks. Rainwater harvesting and redirecting can help irrigate urban farms, which can be part of rain gardens. The national census of 2021 identified that 66% of Nepal’s population lives in urban areas. However, the World Bank (2018) showed that only 21 of Nepal’s population was projected to live in urban areas in 2021. It is not debatable that the urbanization process in Nepal is on the rise. Thus, urban agriculture can play an important role in supplementing residents’ food needs. Many cities in Nepal have already successfully adapted to urban farming wherein residents grow food on their building sites, balconies, and rooftop, often growing plants in pots, vases, and other types of containers. The UN-Habitat, with the support of the European Union and local agencies, published a rooftop farming training manual (2014), showing the feasibility of urban farming in Nepal. This paper discusses how public-private partnership (PPP) can promote urban agriculture and make the process more effective and attractive to urban-farming households. It also analyzes how a PPP approach also facilitates the use of better technology, advisory support, and use of research extension activities. This paper draws on a literature review, uses remote-sensing imagery data and data from National Census Nepal 2021, and the authors’ professional experiences related to best practices in the areas to analyze the benefits and challenges related to urban farming both in Nepal and Arizona, USA. The paper provides recommendations for Nepali cities to maximize the benefit provided by urban farming.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/xz4t7/" target="_blank">Promoting Urban Farming for Creating Sustainable Cities in Nepal</a>
</div></li>
<li><strong>Minority Communities United Against COVID-19: It Takes a Village</strong> -
<div>
COVID-19 has illuminated how racial inequities across multiple institutions in the United States have converged and resulted in profound and lasting negative impacts on people and communities of color. Disparities in the treatment of Native (Indigenous) Americans, African (Black) Americans, and Latinx individuals in the United States concomitant with health disparities more prevalent in these populations have resulted in COVID-19 death rates that have been consistently higher than that of white counterparts and at rates that are significantly higher than their percentage of the population. While reports have focused have necessarily focused on the despair in these communities and the disparities in case and death rates, we report on the historical resilience of these communities and how this has been used to mobilize interventions in these communities that have served to mitigate the negative impact of COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/3zm7w/" target="_blank">Minority Communities United Against COVID-19: It Takes a Village</a>
</div></li>
<li><strong>Longitudinal analysis of memory T follicular helper cells and antibody response following CoronaVac vaccination</strong> -
<div>
The inactivated vaccine CoronaVac is one of the most widely used COVID-19 vaccines globally. However, the longitudinal evolution of the immune response induced by CoronaVac remains elusive compared to other vaccine platforms. Here, we recruited 88 healthy individuals that received 3 doses of CoronaVac vaccine. We longitudinally evaluated their polyclonal and antigen-specific CD4+ T cells and neutralizing antibody response after receiving each dose of vaccine for over 300 days. Both the 2nd and 3rd dose of vaccination induced robust spike-specific neutralizing antibodies, with a 3rd vaccine further increased the overall magnitude of antibody response, and neutralization against Omicron sub-lineages B.1.1.529, BA.2, BA.4/BA.5 and BA.2.75.2. Spike-specific CD4+ T cell and circulating T follicular helper (cTFH) cells were markedly increased by the 2nd and 3rd dose of CoronaVac vaccine, accompanied with altered composition of functional cTFH cell subsets with distinct effector and memory potential. Additionally, cTFH cells are positively correlated with neutralizing antibody titers. Our results suggest that CoronaVac vaccine-induced spike-specific T cells are capable of supporting humoral immunity for long-term immune protection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.541033v1" target="_blank">Longitudinal analysis of memory T follicular helper cells and antibody response following CoronaVac vaccination</a>
</div></li>
<li><strong>SARS-CoV-2 infection leads to Tau pathological signature in neurons</strong> -
<div>
Background: The coronavirus disease 19 (COVID-19) has represented an issue for global health since its outbreak in March 2020. It is now evident that the SARS-CoV-2 infection results in a wide range of long-term neurological symptoms and is worryingly associated with the aggravation of Alzheimer's disease. Little is known about the molecular basis of these manifestations. Methods: Several SARS-CoV-2 strain variants were used to infect SH-SY5Y neuroblastoma cells and K18-hACE C57BL/6J mice. The Tau phosphorylation profile and aggregation propensity upon infection were investigated using immunoblot and immunofluorescence on cellular extracts, subcellular fractions, and brain tissue. The viral proteins Spike, Nucleocapsid, and Membrane were overexpressed in SH-SY5Y cells and the direct effect on Tau phosphorylation was checked using immunoblot experiments. Results: Upon infection, Tau is phosphorylated at several pathological epitopes associated with Alzheimer's disease and other tauopathies. Moreover, this event increases Tau's propensity to form insoluble aggregates and alters its subcellular localization. Conclusions: Our data support the evidence that SARS-CoV-2 infection in the Central Nervous System triggers downstream effects altering Tau function, eventually leading to the impairment of neuronal function.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.17.541098v1" target="_blank">SARS-CoV-2 infection leads to Tau pathological signature in neurons</a>
</div></li>
<li><strong>Tracing the origin of SARS-CoV-2 Omicron-like Spike sequences detected in wastewater</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The origin of divergent SARS-CoV-2 spike sequences found in wastewater, but not in clinical surveillance, remains unclear. These cryptic wastewater sequences have harbored many of the same mutations that later emerged in Omicron lineages. We first detected a cryptic lineage in municipal wastewater in Wisconsin in January 2022. Named the Wisconsin Lineage, we sought to determine the geographic origin of this virus and characterize its persistence and evolution over time. Methods: We systematically sampled maintenance holes to trace the origin of the Wisconsin Lineage. We sequenced spike RBD domains, and where possible, whole viral genomes, to characterize the evolution of this lineage over the 13 consecutive months that it was detectable. Findings: The persistence of the Wisconsin Lineage signal allowed us to trace it from a central wastewater plant to a single facility, with a high concentration of viral RNA. The viral sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in Wisconsin at low levels from October 2020 to February 2021, while mutations in the spike gene resembled those subsequently found in Omicron variants. Interpretation: We propose that prolonged detection of the Wisconsin Lineage in wastewater represents persistent shedding of SARS-CoV-2 from an infected individual, with ongoing within-host viral evolution leading to an ancestral B.1.234 virus accumulating Omicron-like mutations. Funding: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention (CDC), National Institute on Drug Abuse (NIDA), and the Center for Research on Influenza Pathogenesis and Transmission.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.28.22281553v2" target="_blank">Tracing the origin of SARS-CoV-2 Omicron-like Spike sequences detected in wastewater</a>
</div></li>
<li><strong>Detection of SARS-CoV-2 B.1.1.529 (Omicron) variant by SYBR Green‑based RT‑qPCR</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The COVID-19 pandemic is unceasingly spreading across the globe, and recently a highly transmissible Omicron SARS-CoV-2 variant (B.1.1.529) has been discovered in South Africa and Botswana. Rapid identification of this variant is essential for pandemic assessment and containment. However, variant identification is mainly being performed using expensive and time-consuming genomic sequencing. Methods and results: In this study we propose an alternative RT-qPCR approach for the detection of the Omicron BA.1 variant using a low-cost and rapid SYBR Green method. We have designed specific primers to confirm the deletion mutations in the spike (S ∆143-145) and the nucleocapsid (N ∆31-33) which are characteristics of this variant. For the evaluation, we used 120 clinical samples from patients with PCR-confirmed SARS-CoV-2 infections, and displaying an S-gene target failure (SGTF) when using TaqPath COVID-19 kit (Thermo Fisher Scientific, Waltham, USA) that included the ORF1ab, S, and N gene targets. Our results showed that all the 120 samples harbored S ∆143-145 and N ∆31-33, which was further confirmed by Whole genome sequencing (WGS) of 4 samples thereby validating our SYBR Green-based protocol. Conclusions: This protocol can be easily implemented to rapidly confirm the diagnosis of the Omicron BA.1 variant in COVID-19 patients and prevent its spread among populations, especially in countries with high prevalence of SGTF profile.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.16.23289717v1" target="_blank">Detection of SARS-CoV-2 B.1.1.529 (Omicron) variant by SYBR Green‑based RT‑qPCR</a>
</div></li>
<li><strong>Examining outpatients’ hand hygiene behaviour and its relation to other infection prevention measures.</strong> -
<div>
Background: The increasing demand for outpatient care is associated with a higher risk of infection transmission in these settings. However, there is limited research on infection prevention and control practices in ambulatory clinics, and none focuses on patients. Aim: Consequently, this study aims to examine outpatients’ hand hygiene behaviours, their determinants, and their associations with other infection prevention measures during the COVID-19 pandemic. Methods: We observed the hand hygiene behaviour of patients in one outpatient clinic and surveyed outpatients in five clinics about their hand hygiene practice in outpatient facilities. A questionnaire based on the Theoretical Domains Framework (TDF) was used to examine predictors of the behaviour. Moreover, patients indicated their compliance with COVID-19 infection prevention measures, vaccination status, disease risk perception, and vaccine hesitancy. Findings: Observed hand hygiene rates among 618 patients were low (12.8%), while 67.3% of the 300 surveyed patients indicated sanitising their hands upon entering the clinic. The TDF domains memory, attention, and decision processes, and emotions significantly predicted both current (today’s) and general hand hygiene behaviour in outpatient clinics. Hand hygiene behaviour and compliance with COVID-19 infection prevention showed a positive association; however, no significant connection was found with patients’ vaccination status, suggesting different behavioural motivators. Conclusion: Hand hygiene among outpatients should be improved through interventions focusing on helping patients remember to clean their hands. More research on infection prevention in outpatient facilities is needed to ensure patient safety.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/wrzfa/" target="_blank">Examining outpatients’ hand hygiene behaviour and its relation to other infection prevention measures.</a>
</div></li>
<li><strong>Single-cycle SARS-CoV-2 vaccine elicits high protection and sterilizing immunity in hamsters</strong> -
<div>
Vaccines have been central in ending the COVID-19 pandemic, but newly emerging SARS-CoV-2 variants increasingly escape first-generation vaccine protection. To fill this gap, live particle-based vaccines mimicking natural infection aim at protecting against a broader spectrum of virus variants. We designed "single-cycle SARS-CoV-2 viruses" (SCVs) that lack essential viral genes, possess superior immune-modulatory features and provide an excellent safety profile in the Syrian hamster model. Full protection of all intranasally vaccinated animals was achieved against an autologous challenge with SARS-CoV-2 virus using an Envelope-gene-deleted vaccine candidate. By deleting key immune-downregulating genes, sterilizing immunity was achieved with an advanced candidate without virus spread to contact animals. Hence, SCVs have the potential to induce a broad and durable protection against COVID-19 superior to a natural infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.17.541127v1" target="_blank">Single-cycle SARS-CoV-2 vaccine elicits high protection and sterilizing immunity in hamsters</a>
</div></li>
<li><strong>Discovery of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro)</strong> -
<div>
Papain-like protease (PLpro) is a viral protease found in some coronaviruses, including SARS-CoV-2, the virus that causes COVID -19, and is a target for antiviral drug development. Inhibition of PLpro activity could potentially limit viral replication, making it an attractive target for antiviral drug development. This work describes the discovery of novel allosteric residues of SARS-CoV-2 PLpro that can be targeted with antiviral drugs. First, a computational analysis was performed to identify potential druggable pockets on the surface of SARS-CoV-2 PLpro. The computational analysis predicted three druggable pockets that span the surface of PLpro and are located at the interface of its four domains. Pocket 1 is located at the interface between the Ub1 and thumb domains, pocket 2 is at the interface between the thumb, finger, and palm domains, and pocket 3 is at the interface between the finger and palm domains. Targeted alanine mutagenesis of selected residues with important structural interactions revealed that 12 of 23 allosteric residues (D12, Y71, Y83, Q122, Q133, R140, T277, S278, S212, Y213, K254, and Y305) are essential for maintaining a catalytically active and thermodynamically stable PLpro. This work provides experimental confirmation of essential contacts in the allosteric sites of PLpro that could be targeted with non-competitive inhibitors as novel therapeutics against COVID -19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.540953v1" target="_blank">Discovery of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro)</a>
</div></li>
<li><strong>Defining distinct RNA-protein interactomes of SARS-CoV-2 genomic and subgenomic RNAs</strong> -
<div>
Host RNA binding proteins recognize viral RNA and play key roles in virus replication and antiviral defense mechanisms. SARS-CoV-2 generates a series of tiered subgenomic RNAs (sgRNAs), each encoding distinct viral protein(s) that regulate different aspects of viral replication. Here, for the first time, we demonstrate the successful isolation of SARS-CoV-2 genomic RNA and three distinct sgRNAs (N, S, and ORF8) from a single population of infected cells and characterize their protein interactomes. Over 500 protein interactors (including 260 previously unknown) were identified as associated with one or more target RNA at either of two time points. These included protein interactors unique to a single RNA pool and others present in multiple pools, highlighting our ability to discriminate between distinct viral RNA interactomes despite high sequence similarity. The interactomes indicated viral associations with cell response pathways including regulation of cytoplasmic ribonucleoprotein granules and posttranscriptional gene silencing. We validated the significance of five protein interactors predicted to exhibit antiviral activity (APOBEC3F, TRIM71, PPP1CC, LIN28B, and MSI2) using siRNA knockdowns, with each knockdown yielding increases in viral production. This study describes new technology for studying SARS-CoV-2 and reveals a wealth of new viral RNA-associated host factors of potential functional significance to infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.15.540806v1" target="_blank">Defining distinct RNA-protein interactomes of SARS-CoV-2 genomic and subgenomic RNAs</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Glucocorticoid<br/><b>Sponsor</b>:   Huashan Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Investigation of the Effect on Cognitive Skills of COVID-19 Survivors</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Other: green walking and intelligence gam<br/><b>Sponsors</b>:   Bayburt University;   Karadeniz Technical 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>Conducting Clinical Trials of the Medicine “Rutan Tablets 0.1g” No. 10 in the Complex Therapy of COVID-19</strong> - <b>Condition</b>:   Patients With COVID-19<br/><b>Interventions</b>:   Drug: The drug “Rutan 0.1”.;   Other: Basic treatment<br/><b>Sponsor</b>:   Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<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>Arginine Replacement Therapy in COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Arginine Hydrochloride<br/><b>Sponsor</b>:   Emory University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Intramuscularly administered Ad5-nCoV vaccine;   Biological: Aerosolized Ad5-nCoV;   Biological: DelNS1-2019-nCoV-RBD-OPT1;   Biological: SYS6006<br/><b>Sponsor</b>:   Jiangsu Province Centers for Disease Control and Prevention<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>Studying the Efficiency of the Natural Preparation Rutan in Children in the Treatment of COVID-19, ARVI</strong> - <b>Condition</b>:   COVID-19 Respiratory Infection<br/><b>Interventions</b>:   Drug: Rutan 25 mg;   Other: Control group<br/><b>Sponsor</b>:   Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment</strong> - <b>Condition</b>:   Post COVID-19 Cognitive Impairment<br/><b>Interventions</b>:   Device: Vielight Neuro RX Gamma active device;   Device: Vielight Neuro RX Gamma sham device<br/><b>Sponsor</b>:   Vielight Inc.<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>PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway</strong> - <b>Conditions</b>:   Post COVID-19 Condition, Unspecified;   SARS-CoV2 Infection;   COVID-19<br/><b>Interventions</b>:   Drug: Nirmatrelvir/ritonavir;   Drug: Placebo<br/><b>Sponsors</b>:   Haukeland University Hospital;   University of Bergen<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>Use of a Hypochlorous Acid Spray Solution in the Treatment of COVID-19 Patients : COVICONTROL Study .</strong> - <b>Condition</b>:   SARS CoV 2 Infection<br/><b>Interventions</b>:   Other: Spray with Hypochlorous Acid Group;   Other: Spray with Placebo Group<br/><b>Sponsor</b>:   University of Monastir<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>Role of Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and Immunoglobulin G Response</strong> - <b>Condition</b>:   COVID-19 Respiratory Infection<br/><b>Intervention</b>:   Combination Product: Vitamin-D<br/><b>Sponsor</b>:   Sulaimany Polytechnic 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>Telerehabilitation Program and Detraining in Patients With Post-COVID-19 Sequelae</strong> - <b>Condition</b>:   COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>:   Other: Telerehabilitation program<br/><b>Sponsor</b>:   Campus docent Sant Joan de Déu-Universitat de Barcelona<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>COVID-19 Vaccine Uptake Amongst Underserved Populations in East London</strong> - <b>Conditions</b>:   COVID-19;   Influenza;   Vaccination Refusal<br/><b>Intervention</b>:   Device: Patient Engagement tool<br/><b>Sponsors</b>:   Queen Mary University of London;   Social Action for Health<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>REVERSE-Long COVID-19 With Baricitinib Pilot Study</strong> - <b>Condition</b>:   Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>:   Drug: Baricitinib 4 MG<br/><b>Sponsors</b>:   Vanderbilt University Medical Center;   Emory University;   University of California, San Francisco;   University of Minnesota;   Vanderbilt University;   Yale University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Tolerability and Immunogenicity of Alveavax-v1.2, a BA.2/Omicron-optimized, DNA Vaccine for COVID-19 Prevention</strong> - <b>Condition</b>:   Sars-CoV-2 Infection<br/><b>Interventions</b>:   Drug: Alveavax-v1.2;   Drug: Janssen Ad26.COV2.S<br/><b>Sponsor</b>:   Alvea Holdings, LLC<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>Post Covid-19 Dysautonomia Rehabilitation Randomized Controlled Trial</strong> - <b>Conditions</b>:   Post-Acute COVID-19 Syndrome;   Dysautonomia<br/><b>Interventions</b>:   Procedure: Rehabilitation;   Procedure: Standard of Care<br/><b>Sponsors</b>:   Evangelismos Hospital;   National and Kapodistrian University of Athens;   LONG COVID GREECE;   414 Military Hospital of Special Diseases<br/><b>Recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Optimization of urban emergency support material distribution under major public health emergencies based on improved sparrow search algorithm</strong> - The outbreak of major public health emergencies such as the coronavirus epidemic has put forward new requirements for urban emergency management procedures. Accuracy and effective distribution model of emergency support materials, as an effective tool to inhibit the deterioration of the public health sector, have gradually become a research hotspot. The distribution of urban emergency support devices, under the secondary supply chain structure of “material transfer center-demand point,” which…</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>Passive swab versus grab sampling for detection of SARS-CoV-2 markers in wastewater</strong> - Early detection of the COVID-19 virus, SARS-CoV-2, is key to mitigating the spread of new outbreaks. Data from individual testing is increasingly difficult to obtain as people conduct non-reported home tests, defer tests due to logistics or attitudes, or ignore testing altogether. Wastewater based epidemiology is an alternative method for surveilling a community while maintaining individual anonymity; however, a problem is that SARS-CoV-2 markers in wastewater varies throughout the day….</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>Oxalic acid blocked the binding of spike protein from SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variants to human angiotensin-converting enzymes 2</strong> - An epidemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Moreover, the emergence of SARS-CoV-2 variants of concern, such as Delta and Omicron, has seriously challenged the application of current therapeutics including vaccination and drugs. Relying on interaction of spike protein with receptor angiotensin-converting enzymes 2 (ACE2), SARS-CoV-2 successfully invades to the host cells, which indicates a…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antifungal Activity and Potential Action Mechanism of Allicin against Trichosporon asahii</strong> - Trichosporon asahii is an emerging opportunistic pathogen that causes potentially fatal disseminated trichosporonosis. The global prevalence of coronavirus disease 2019 (COVID-19) poses an increasing fungal infection burden caused by T. asahii. Allicin is the main biologically active component with broad-spectrum antimicrobial activity in garlic. In this study, we performed an in-depth analysis of the antifungal characteristics of allicin against T. asahii based on physiological, cytological,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Nucleocapsid Protein Is a Potential Therapeutic Target for Anticoronavirus Drug Discovery</strong> - SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, is a highly contagious positive-sense RNA virus. Its explosive community spread and the emergence of new mutant strains have created palpable anxiety even in vaccinated people. The lack of effective anticoronavirus therapeutics continues to be a major global health concern, especially due to the high evolution rate of SARS-CoV-2. The nucleocapsid protein (N protein) of SARS-CoV-2 is highly conserved and involved in diverse processes 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>Six-month immune responses to mRNA-1273 Vaccine in cART-treated late presenter people living with HIV according to previous SARS-CoV-2 Infection</strong> - CONCLUSIONS: Altogether, these findings support the need for additional vaccine doses in PLWH with a history of advanced immune depression and poor immune recovery on effective cART.</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><em>In silico</em> design of miniprotein to inhibit SARS-CoV-2 variant Omicron spike protein</strong> - Omicron is a novel variant of SARS-CoV-2 that is currently spreading globally as the dominant strain. The virus first enters the host cell through the receptor binding domain (RBD) of the spike protein by interacting with the angiotensin-converting enzyme 2 (ACE2). Thus, the RBD protein is an ideal target for the design of drugs against the Omicron variant. Here, we designed several miniprotein inhibitors in silico to combat the SARS-CoV-2 Omicron variant using single- and double-point mutation…</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>Conformal Hydrogel-Skin Coating on a Microfluidic Channel through Microstamping Transfer of the Masking Layer</strong> - Poly(dimethylsiloxane) (PDMS) is used in microfluidics owing to its biocompatibility and simple fabrication. However, its intrinsic hydrophobicity and biofouling inhibit its microfluidic applications. Conformal hydrogel-skin coating for PDMS microchannels, involving the microstamping transfer of the masking layer, is reported herein. A selective uniform hydrogel layer with a thickness of ∼1 μm was coated in diverse PDMS microchannels with a resolution of ∼3 μm, maintaining its structure 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>The C-terminal 32-mer fragment of hemoglobin alpha is an amyloidogenic peptide with antimicrobial properties</strong> - Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111-142). The non-fibrillar peptide has…</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>Challenges and Progress in Designing Broad-Spectrum Vaccines Against Rapidly Mutating Viruses</strong> - Viruses evolve to evade prior immunity, causing significant disease burden. Vaccine effectiveness deteriorates as pathogens mutate, requiring redesign. This is a problem that has grown worse due to population increase, global travel, and farming practices. Thus, there is significant interest in developing broad-spectrum vaccines that mitigate disease severity and ideally inhibit disease transmission without requiring frequent updates. Even in cases where vaccines against rapidly mutating…</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>Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies</strong> - CONCLUSION: These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of 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>Discovery of dual S-RBD/NRP1-targeting peptides: structure-based virtual screening, synthesis, biological evaluation, and molecular dynamics simulation studies</strong> - Both receptor-binding domain in spike protein (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human neuropilin-1 (NRP1) are important in the virus entry, and their concomitant inhibition may become a potential strategy against the SARS-CoV-2 infection. Herein, five novel dual S-RBD/NRP1-targeting peptides with nanomolar binding affinities were identified by structure-based virtual screening. Particularly, RN-4 was found to be the most promising peptide targeting S-RBD…</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>Compounds from myrtle flowers as antibacterial agents and SARS-CoV-2 inhibitors: <em>In-vitro</em> and molecular docking studies</strong> - Plants and their related phytochemicals play a key role in the treatment of bacterial and viral infections, which inspire scientists to design and develop more efficient drugs starting from the phytochemical active scaffold. This work aims to characterize the chemical compounds of Myrtus communis essential oil (EO) from Algeria and to evaluate its in vitro antibacterial effect, as well as the in silico anti-SARS-CoV-2 activity. The chemical profile of hydrodistilled EO from myrtle flowers was…</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>Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines</strong> - CONCLUSION: KTRs’ humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of &gt;10 years.</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>Interactive network pharmacology and electrochemical analysis reveals electron transport-mediating characteristics of Chinese medicine formula Jing Guan Fang</strong> - BACKGROUND: Jing Guan Fang (JGF) is an anti-COVID-19 Chinese Medicine decoction comprised of five medicinal herbs to possess anti-inflammatory and antiviral properties for treatment. This study aims to electrochemically decipher the anti-coronavirus activity of JGF and show that microbial fuel cells may serve as a platform for screening efficacious herbal medicines and providing scientific bases for the mechanism of action (MOA) of TCMs.</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>Don’t Believe Donald Trump: A Failure to Raise the Debt Ceiling Would Be Disastrous</strong> - The ex-President’s intervention has made a fraught situation even more complicated. - <a href="https://www.newyorker.com/news/our-columnists/dont-believe-donald-trump-a-failure-to-raise-the-debt-ceiling-would-be-disastrous">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Vanishing Acts of Vladimir Putin</strong> - One of the seeming paradoxes of the Russian President is the degree to which he is at once a unitary micromanager and an absent, aloof, and often indecisive leader. - <a href="https://www.newyorker.com/news/daily-comment/the-vanishing-acts-of-vladimir-putin">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Salmon in the Sky</strong> - A painted plane that flew the Alaskan coast. - <a href="https://www.newyorker.com/news/afterword/the-salmon-in-the-sky">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>“Debt-Limit Terror” Is No Way to Run a Superpower</strong> - On the latest round of the Republicans’ dangerous game. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/debt-limit-terror-is-no-way-to-run-a-superpower">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why Erdoğan Prevailed in a Battle of Competing Turkish Nationalisms</strong> - As the country heads to a Presidential runoff, will the aftermath of a devastating earthquake hold more sway than old narratives of grievance? - <a href="https://www.newyorker.com/news/q-and-a/why-erdogan-prevailed-in-a-battle-of-competing-turkish-nationalisms">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>More mammograms are a good thing … right?</strong> -
<figure>
<img alt="A finger pointing to a spot on a mammography scan of a breast." src="https://cdn.vox-cdn.com/thumbor/Aq37UeVUOg5DHbwa43m6arlNo-k=/441x0:1881x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72295060/Vox_1238822195.0.jpg"/>
<figcaption>
Michael Hanschke/picture alliance via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The new breast cancer screening recommendations for women over 40 are surprisingly fraught.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5Yzox5">
On May 9, the US Preventive Services Task Force (USPSTF) released a <a href="https://www.uspreventiveservicestaskforce.org/uspstf/public-comments-and-nominations/opportunity-for-public-comment">draft</a> of their new guidelines on who should be screened for breast cancer. The biggest change: recommending that women with average breast cancer risk start getting mammograms every two years beginning at 40, <a href="https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-screening">instead of starting at age 50.</a>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o7VsBX">
According to the recommendation’s authors, the <a href="https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/breast-cancer-screening-adults#bcei-recommendation-title-area">reasons</a> for the change included a noticeable increase in breast cancer cases among women in their 40s between 2015 and 2019, as well as a higher likelihood of late cancer diagnoses — and of dying due to breast cancer — among Black women in particular.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yphKpL">
“The most important thing for women to know is to begin screening at the age of 40, because it just might save your life,” said USPSTF chair Carol Mangione in a <a href="https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/breast-cancer-screening-adults">video</a> on the USPSTF website.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B6Ast7">
But a number of experts say it’s not that simple. For a test so often touted as lifesaving, there’s a surprising <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582264/">lack</a><a href="https://theconversation.com/routine-mammograms-do-not-save-lives-the-research-is-clear-84110"> of</a><a href="https://pubmed.ncbi.nlm.nih.gov/34703006/"> consensus</a> about how much mammography actually prolongs lives, and whether the unnecessary medical care mammograms sometimes lead to is worth their benefits.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kzrn0h">
Breast cancer causes more than <a href="https://www.cdc.gov/cancer/breast/basic_info/index.htm#:~:text=Each%20year%20in%20the%20United,What%20Is%20Breast%20Cancer%3F">42,000 deaths</a> in the US each year, and <a href="https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/2022-2024-breast-cancer-fact-figures-acs.pdf">about 40 percent</a> more Black women die due to breast cancer than do white women. The <a href="https://www.bcrf.org/blog/black-women-and-breast-cancer-why-disparities-persist-and-how-end-them/">causes of this disparity</a> are complex — and recommending more mammograms to all Americans as the solution comes with increased physical, emotional, and economic costs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p5QvkB">
Will they be worth it? Let’s get realistic about what these recommendations can and can’t do.
</p>
<h3 id="erWW2e">
The new recommendations can increase rates of breast cancer diagnosis and treatment — which is both good and bad
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="469T4Q">
The USPSTF’s recommendations offer guidance on how to use mammograms for screening average-risk people. That’s worth keeping in mind for a couple of reasons. First, higher-risk people — like those with family histories of breast cancer — <a href="https://www.cancer.org/cancer/types/breast-cancer/screening-tests-and-early-detection/american-cancer-society-recommendations-for-the-early-detection-of-breast-cancer.html">may need to be screened differently</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="liZ8tO">
Additionally, not every mammogram that gets done is for screening: These recommendations do not apply to, for example, someone who detects a lump in their breast. (In that scenario, because the person has a symptom before they get the test, the mammogram is a diagnostic test — and the <a href="https://www.nationalbreastcancer.org/diagnostic-mammogram/#:~:text=A%20mammogram%20is%20an%20x,physician%20to%20check%20the%20tissue.">procedure</a> and <a href="https://www.michigan.gov/mdhhs/-/media/Project/Websites/mdhhs/Keeping-Michigan-Healthy/CancerDocuments/BC3NP/Clinical/BC3NPBCFUAlgorithmsPY01.pdf?rev=4716e92c93e94616897ac6565c018fcf&amp;hash=B3422E7F6B2F0584D7C3C1D3977655D3">what follows</a> are a little different.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2iLsGp">
When screening tests work, they find medical problems early, before people have any indication that they might have that problem. Mammograms can do this, flagging tiny changes associated with <a href="https://www.nationalbreastcancer.org/types-of-breast-cancer/">many types of breast cancer</a>. Some breast cancers are slow-moving while others grow quickly; some are treatment-responsive and others are resistant to treatment; some readily invade other tissues and others resolve on their own. Mammograms can help spot them all.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pG9eRD">
But they can also detect lots of breast changes that <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790523">aren’t actually abnormal</a>, like benign texture differences in the breast tissue called <a href="https://my.clevelandclinic.org/health/symptoms/22080-fibrocystic-breasts">fibrocystic changes</a>. Trouble is, they’re not great at distinguishing what’s harmful from what’s benign. For that reason, abnormal mammograms are generally followed by a cascade of <a href="https://www.michigan.gov/mdhhs/-/media/Project/Websites/mdhhs/Keeping-Michigan-Healthy/CancerDocuments/BC3NP/Clinical/BC3NPBCFUAlgorithmsPY01.pdf?rev=4716e92c93e94616897ac6565c018fcf&amp;hash=B3422E7F6B2F0584D7C3C1D3977655D3">other evaluations</a> to help determine what’s going on, depending on what they’ve found.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U4BnX7">
Increasing the number of mammograms people get can increase the number of abnormalities that get diagnosed and will lead to more follow-up ultrasounds, biopsies, and other procedures. It can also increase the number of people getting treated for conditions judged to be cancerous, with a range of surgeries, chemotherapies, and radiation treatments.
</p>
<h3 id="Rug1qt">
But how much more premature breast cancer death can all this added care prevent? That’s not a simple question to answer.
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Hm91bL">
The thing about breast cancer is that most types are so slow-moving and so responsive to therapy that even if people don’t get breast cancer treatment until they first notice a lump, they’re still <a href="https://moffitt.org/cancers/invasive-ductal-carcinoma/diagnosis/stages/">highly likely</a> to survive the cancer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sec-3">
Yes, diagnosis in early stages of these cancers leads to <a href="https://www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-survival-rates.html">better outcomes</a> than late-stage diagnoses — but those early stages last a while, with the median time around <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011255/">10 years</a> altogether.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yPrWpq">
(About <a href="https://www.cancer.org/cancer/types/breast-cancer/about/types-of-breast-cancer/triple-negative.html">one in 10</a> breast cancers diagnosed in the US are very aggressive and resistant to treatment, and they usually move too quickly to be caught by a mammogram done only once every two years.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4SdR4H">
That means that for people who are vigilant about changes in their bodies and have decent access to health care, the value-add of mammograms over simply being aware of your body is actually pretty small.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="t9qU3M">
“The better we get able to treat a disease, the less important it becomes to find it,” said <a href="https://csph.brighamandwomens.org/theplus_team_member/welch-gilbert/">Gilbert Welch</a>, a senior researcher at Brigham and Women’s Hospital in Boston who studies cancer overdiagnosis. In other words, when we find treatments that work at many different stages of disease, the benefits of early diagnosis shrink dramatically. For breast cancer, that treatment is the anti-hormonal therapies that emerged in the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2566956/">1990s</a> and dramatically changed breast cancer survival rates.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bJJ7F3">
A recent <a href="https://lowninstitute.org/earlier-screening-for-breast-cancer-benefits-and-harms/">analysis</a> by the Lown Institute, a nonprofit health care think tank, highlighted some key USPSTF figures, which show the limits of mammograms in a helpful way.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9FT1un">
The analysis imagines a world without screening mammograms, in which women seek evaluation for breast cancer only when they notice a breast lump or other concerning symptoms. According to <a href="https://www.uspreventiveservicestaskforce.org/uspstf/document/draft-modeling-report/breast-cancer-screening-adults">the USPSTF’s models</a>, about 28 out of every 1,000 women in this world would die from breast cancer at some point in their lives.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cInpxy">
Then, let’s look at what the previous guidelines — recommending regular mammograms starting at age 50 — can accomplish. If all women adhered to those guidelines, then seven of those breast cancer deaths would be prevented.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uwmyoF">
However, the USPSTF estimates those mammograms would also result in 1,021 false-positive mammograms and<strong> </strong>148 biopsies that turn out to be benign. It would also lead to 10 cases of overdiagnosis — that is, treatment of a cancer that never would have harmed them to begin with.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LPn9u6">
That’s bad. False-positive mammograms are associated with <a href="https://bmjopen.bmj.com/content/13/4/e072188.long">psychological consequences</a>, such as anxiety and sleep issues, that persist for years afterward. And the unnecessary surgeries, medications, and radiotherapies that follow breast cancer overdiagnosis cost the US an estimated <a href="https://pubmed.ncbi.nlm.nih.gov/25847639/">$4 billion a year</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="plDMhy">
Now, what can we expect under the new guidelines, with the mammogram age starting at 40? The USPSTF projects that would save an additional two of those 1,000 women from a breast cancer death (technically, one and a half; the authors rounded up). But significant added harms would come with all of those extra positive mammograms: This scenario leads to an additional 62 benign biopsies and two additional overdiagnosed cases.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FuOHmm">
What all of this means is that<strong> </strong>the new recommendations can potentially lead to a lot of unnecessary, and potentially harmful, care. To some people, those trade-offs, even if they harm hundreds of people, are worth saving even one extra life.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="43YoRV">
What complicates things even further is that these are calculations set in the ideal world of a statistical model. The complexity of the real world leads to some changes in the math, especially for Black women.
</p>
<h3 id="vOzY9x">
The new recommendations can give Black women in particular an on-ramp to breast cancer care — but they can’t map the rest of the route
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8zYIlV">
These models assume that every one of these 1,000 hypothetical women is equally watchful and attentive to changes in their bodies, and seek medical evaluation and care when they notice something’s off. They also assume that each has equal access to a medical system that provides the same quality of care to all of them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UMNfnI">
But we know that latter part isn’t the American reality. Decades of economic and residential segregation mean Black Americans are <a href="https://tcf.org/content/report/racism-inequality-health-care-african-americans/">more likely to be uninsured</a> and to live in areas without readily available health care providers and facilities. Furthermore, the legacy of medical racism translates to <a href="https://www.commonwealthfund.org/publications/newsletter-article/2021/jan/medical-mistrust-among-black-americans#:~:text=Medical%20Mistrust%20and%20Its%20Impacts,it's%20worse%20among%20Black%20Americans.&amp;text=In%20an%20October%202020%20poll,percent%20say%20they%20distrust%20it.">high levels of distrust</a> in medical providers among Black Americans. And Black women with breast cancer receive <a href="https://pubmed.ncbi.nlm.nih.gov/14531494/">lower doses</a> of breast cancer chemotherapy compared with white women.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rwyEQ6">
As a result, even if Black women notice breast changes that may be associated with cancer, they may be less likely to seek and receive evaluation for those changes, and to get appropriate care when they do.<strong> </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1AAG2v">
That delay means many Black women only start treatment <a href="https://pubmed.ncbi.nlm.nih.gov/17101943/">in the later stages</a> of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789230/">disease</a>, once the cancer is more likely to have spread beyond their breasts. These kinds of treatment differences explain, at least in part, why<strong> </strong>even Black women with treatable breast cancers have <a href="https://ascopubs.org/doi/full/10.1200/JCO.2017.73.7932">worse outcomes</a> than do women of other racial and ethnic groups.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HZsKb9">
Black women also more often have the rarer, particularly aggressive <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604720/">triple-negative breast cancers</a>, so named because their cells don’t carry any of the three targets at which the most effective treatments take aim. These cancers, which make up around <a href="https://www.frontiersin.org/articles/10.3389/fmolb.2022.836417">20 percent</a> of all US breast cancers and have <a href="https://seer.cancer.gov/statistics-network/explorer/application.html?site=55&amp;data_type=4&amp;graph_type=5&amp;compareBy=subtype&amp;chk_subtype_622=622&amp;chk_subtype_623=623&amp;chk_subtype_620=620&amp;chk_subtype_621=621&amp;series=9&amp;sex=3&amp;race=1&amp;age_range=1&amp;stage=101&amp;advopt_precision=1&amp;advopt_show_ci=on&amp;hdn_view=0&amp;advopt_show_apc=on&amp;advopt_display=2#resultsRegion0">lower survival rates</a> than other types, are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744285/">at least twice as likely</a> to be diagnosed in Black women than in white women, especially <a href="https://pubmed.ncbi.nlm.nih.gov/36895969/">at younger ages</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4emKUw">
The role of mammograms in improving these cancers’ outcomes is unclear: Triple-negative breast cancers are generally <a href="https://www.annalsofoncology.org/article/S0923-7534(19)37639-2/fulltext">harder to see and progress far more quickly</a> than other cancer types, making them hard to catch at early stages by a test done only every one or two years. Although magnetic resonance imaging (MRI) is better at diagnosing these cancers, its <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178936/">cost and resource demands</a> are barriers to using it as a population-wide screening tool.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wApDY8">
The more common and more treatable breast cancers are where the new recommendations could potentially help by giving Black women an on-ramp to earlier cancer care. In this sense, regularly scheduled mammograms — which are <a href="https://www.verywellhealth.com/find-free-or-low-cost-mammograms-429861">covered by all US insurance plans</a> and are often available free for uninsured people — could make an end-run around some of the many reasons women might let a breast lump go unevaluated for years.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NY8Rep">
Because routine mammograms could help improve access to care among Black women with treatable cancers who’d otherwise lack a treatment entry point, this group could have more to gain than lose from getting more mammograms. In USPSTF’s models, the number of Black women’s lives saved by routine mammograms was slightly higher than in the general population, no matter at what age they started.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lxbJCy">
What the recommendations don’t (and can’t) do is plot out a route for after the on-ramp.
</p>
<h3 id="oYWl3L">
More mammograms aren’t the solution to the biggest problems in breast cancer
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aqfabA">
The USPSTF didn’t restrict its new recommendations to Black women alone: It recommended it for all women. That also means more mammograms for women who have already effectively maxed out the benefit they could get from the screening test. In that group, the recommendation will likely lead to more benign biopsies, more overdiagnoses, and more harm.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r56vxX">
Some researchers have <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2803948">suggested</a> starting screening mammograms at different ages in different racial and ethnic groups based on these considerations. However, the USPSTF opted not to do that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TZ1Q4q">
USPSTF member and internist John Wong told Vox in an email that rising rates of breast cancer among younger women of all racial and ethnic backgrounds provoked the choice. Younger women stand to have more years of life saved when a mammogram diagnoses a breast cancer in them than in an older person, he said. “Fundamentally, with more women being diagnosed at younger ages, each life that is saved from dying of breast cancer means even more years that women have to live after a diagnosis,” he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="39Mu8Y">
That’s true — if the early diagnosis is what saved their life. But it’s possible these younger women would’ve survived the same duration even with a later diagnosis.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pIdMTI">
<a href="https://lowninstitute.org/staff/shannon-brownlee/">Shannon Brownlee</a>, a special adviser to Lown’s president, said the new recommendations mean “exposing a large population of women to overdiagnosis and overtreatment — which is harmful, we know that — in order to fix the fact that poor women and Black women have poor access to health care.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7PfaJ0">
Furthermore, they don’t actually fix the health care access disparities at the root of the problem, she said, because they do nothing to address barriers to getting timely care for cancers identified during those screenings.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gh5igK">
“Maybe it’ll help some women who really didn’t have access” to health care, she said, “but they still don’t have access: You can get your mammogram now for free, but then you can’t get treated because your insurance isn’t adequate.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="62eLAm">
It “just seems like a really dumb way to fix that problem,” she said. “This is really a travesty. Frankly, I think it’s going to harm a lot of women.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y80ReF">
Instead of increasing the number of mammograms, it would be far more beneficial to research and identify the environmental, genetic, and other potential causes of triple-negative breast cancers that create added risk for Black women, said Brownlee.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0wdOUH">
Also critical, she said, is addressing racial inequities in health care access.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8zwVcn">
Many studies have documented how differences in environment, insurance coverage, and treatment likely <a href="https://www.bcrf.org/blog/black-women-and-breast-cancer-why-disparities-persist-and-how-end-them/">contribute to breast cancer mortality inequities</a> and<a href="https://www.pbs.org/newshour/show/data-shows-massive-disparity-in-excess-deaths-among-black-americans"> also drive</a> Black Americans’ <a href="https://jamanetwork.com/journals/jama/article-abstract/2804822">dramatically worse mortality</a> more broadly. Fixing these inequities is generationally important work that urgently demands the attention of American policymakers, scholars, and health care institutions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1Zhkfg">
But more mammograms won’t solve these problems, said Welch. “You can’t screen your way out of health disparities.”
</p>
<h3 id="hVUMTL">
What’s a person with breasts to do?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8n2tfD">
The new recommendations are still just in draft form and will be open for public comment through <a href="https://uspreventiveservicestaskforce.org/uspstf/announcements/public-comment-draft-recommendation-statement-draft-evidence-review-and-draft-modeling-report-screening-breast-cancer">June 5</a>. But things might not get much clearer even once they’re finalized. Meanwhile, what’s a woman with average breast-cancer risk to do?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3tKG9R">
Welch urges viewing the recommendations in a bigger context. “No one should think this is the most important thing they do for their health,” he said. Instead, people should do “what their grandmother would have told them 40 years ago: Eat your fruits and vegetables, go play outside, run around, find things that give your life meaning, exercise.” he said. “And don’t smoke. Whatever you do, don’t smoke.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="t3yiV9">
Even if you opt out of mammograms, being aware of your body and seeking care for early warning signs and for other general preventive care makes sense. (The USPSTF officially <a href="https://www.uspreventiveservicestaskforce.org/home/getfilebytoken/zESNSGqmKFpJWqNb573WXC">recommended against</a> breast self-exams in 2009, but some research suggests the practice <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4179105/">still has value</a>, especially in <a href="https://www.sciencedirect.com/science/article/abs/pii/S0002961009003560">high-risk groups</a>, like those with personal or family breast cancer histories or who carry certain genetic mutations.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rS38bo">
It’s understandable if, even knowing all of this, some people still want regular screening mammograms.<strong> </strong>If he had to write the mammography guidelines, Welch would tell people that getting a mammogram is a choice. Although women who notice a breast lump should seek care immediately, viewing their breasts as ticking time bombs can itself create a sense of unwellness, he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VwIQRQ">
“You develop a new problem, come see the doctor,” said Welch. “But this whole question of to what extent you should see your body as a laboratory, you need to be testing it every other day — I think that’s a recipe for a sick society.”
</p></li>
<li><strong>What a debt default could mean for America’s superpower status</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/iyjmHiQZpGTAMExCExsuwQdAL_g=/0x0:4929x3697/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72295002/1483917249.0.jpg"/>
<figcaption>
US Treasury Secretary Janet Yellen listens during an open session of a Financial Stability Oversight Council meeting at the Department of the Treasury on April 21, 2023, in Washington, DC.  | Alex Wong/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The showdown will cause a global crisis — and that has real implications for US influence.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mROrdI">
In case you haven’t heard, the United States is in the middle of a <a href="https://www.vox.com/policy/2023/5/6/23707949/debt-ceiling-crisis-budget-deal-questions">perilous debt-ceiling showdown</a>. <a href="https://www.vox.com/congress">Congress</a> needs to expand the amount of <a href="https://www.vox.com/money">money</a> the US can legally<strong> </strong>borrow, but <a href="https://www.vox.com/politics/2023/5/16/23724602/debt-ceiling-negotiations-house-republicans">Republicans</a> and the Biden White House can’t agree on the terms.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D1mRUv">
That is pushing America closer and closer to the <a href="https://www.vox.com/policy/2023/5/6/23707949/debt-ceiling-crisis-budget-deal-questions">date of default</a>, which means America won’t be able to pay its bills. That would, as you’ve also probably heard, cause economic pandemonium in the United States, but also abroad, potentially triggering a global financial crisis and recession.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TieoEj">
Sounds bad — because it is. The US political dysfunction will engulf the rest of the world because America anchors the global financial system. US Treasury bonds and the dollar have traditionally been seen as risk-free. If the US defaults, they won’t be that reliable any longer — but that readjustment can’t happen overnight, either.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JdUkzQ">
The US is already starting to look like a much more chaotic bet. And if America defaults, that could accelerate and<strong> </strong>have profound implications for the United States’s global influence. US power and geopolitical leverage have very much to do with its financial dominance. It’s how the US can wield sanctions to <a href="https://www.vox.com/22968949/russia-sanctions-swift-economy-mcdonalds">punish Russia for its Ukraine invasion</a>, or <a href="https://armscontrolcenter.org/fact-sheet-north-korea-sanctions/">North Korea for its nuclear weapons program. </a>Suddenly, the world looks very different if, say, central banks start buying up more reserves of euros or Chinese renminbi.
</p>
<aside id="BZiewU">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hOoCYB">
To be clear, the world is nowhere near that yet, but as Marcus Noland, executive vice president and director of studies at the Peterson Institute for International Economics said, a US default “gives that process a nice shove.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6Zf8XD">
Vox spoke with Noland about what we’re actually talking about when we talk about a US debt default causing a global crisis, and what some of the longer-term implications of that might be for America and the rest of the world.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rgiAlW">
The conversation, edited and condensed for length and clarity, is below.
</p>
<hr class="p-entry-hr" id="HA4dDr"/>
<h4 id="5JbhlL">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="I3Hc1Q">
When we talk about a possible US default, we often say some version of it could cause a <a href="https://www.whitehouse.gov/cea/written-materials/2021/10/06/life-after-default/">“global financial crisis.”</a> What does that mean?
</p>
<h4 id="0TUKDw">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mfg0FP">
US Treasury bonds act as a kind of risk-free benchmark on which many, many, many, many, many other financial transactions around the world are based, so that your mortgage, or commercial real estate — all sorts of transactions — are linked, ultimately, to the prices for US Treasury bonds, and the interest rates that are implied by those prices.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HRrAvm">
It can get way beyond just things like mortgages or commercial real estate interest rates, but other kinds of transactions as well. This could be in all kinds of financial markets, and it’s not limited to the United States. There are markets around the world that ultimately are benchmarked against this standard of a risk-free asset.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tFR4o1">
If that market freezes up and there are no longer transactions [around US Treasury bonds], and those prices are no longer observable, or the markets become so thin and fragmentary that the prices become highly unstable and erratic, that will cascade into other markets. Not only will the US Treasury market itself be affected, but all these other markets that are ultimately linked to it are affected as well.
</p>
<h4 id="y2k2y7">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8swZw5">
So the value of other contracts is pinned to the value of the US Treasury bond?
</p>
<h4 id="ozYNp4">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WNP2g4">
There may be a contract in which the interest rate on this particular contract is some margin above a specific US Treasury issuance. If that US Treasury issuance essentially no longer exists, if there’s no price, then that [other] contract basically has no price.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qLYwZr">
Once the market for US Treasuries freezes up, then that will have a cascading effect, within the United States, but globally as well, as other financial contracts that are ultimately linked to that risk-free benchmark can no longer function, either.
</p>
<h4 id="Y7Pjhe">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S1cnDT">
Essentially, it takes this standard that everyone is using, and it just throws it completely out of whack because you don’t have a fixed point to compare it to — so you don’t even know what you’re supposed to be paying.
</p>
<h4 id="nhVqWK">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1FQn0k">
Exactly, exactly. You lose that fixed point. That’s a good way of putting it. It would be sort of like if Greenwich Mean Time disappeared. You wouldn’t even know what time it was because everything is measured against Greenwich Mean Time.
</p>
<h4 id="6TrJMy">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rYhwua">
Outside of the United States, are there countries or markets or industries that are particularly vulnerable if that were to happen?
</p>
<aside id="vCL5nk">
<div>
</div>
</aside>
<h4 id="RYr0go">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VieWJZ">
I’ve mentioned, obviously, things like housing, commercial real estate here in the United States, but essentially, anybody who holds US Treasuries would be at risk. And that includes foreign central banks, that includes foreign financial intermediaries or American intermediaries that sell services to foreigners based on US Treasuries, or securities that are benchmarked off of US Treasuries. Think of pension funds. Think of banks. I mean, it would be taking the cornerstone out of the entire modern <a href="https://www.vox.com/business-and-finance">finance</a> global financial system.
</p>
<h4 id="7Pd3rz">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="htEWBc">
It sounds like immediate chaos. What might happen next?
</p>
<h4 id="UIS02T">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dLWPxX">
I honestly don’t know what large holders of US Treasuries would do. For example, foreign central banks. You can imagine an alternative system in which bonds issued by the European Central Bank, or bonds issued by the Bank of England, or other major central banks around the world, could start to form that new set of benchmarks. And you could essentially reconstruct contracts, linking them to those instruments as kind of the risk-free benchmark. But there’s a reason why the dollar is, and US Treasuries are, the benchmark, and not the euro and bonds issued by the European Central Bank or the Bank of England or something. In some long-run sense, they might play an equivalent role, but they don’t play that role today.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aj8pVM">
It’s not like there are no alternatives to the dollar-based system. But the dollar and US Treasuries are the dominant vehicles for this function in the international financial system.
</p>
<h4 id="Nw2yzn">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="u2isML">
Even if the US does not default, this showdown is coming closer to the edge — and may be a feature, not a bug, of our political system. How do you think that is influencing how the rest of the world thinks about US Treasury bonds and the dollar in the longer term?
</p>
<h4 id="cryBbK">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xdYAOS">
The dollar can play a variety of roles, and US Treasuries play a variety of roles. The use of the dollar and US Treasury securities as central bank reserves has been declining over time, but it’s still by far the largest. It accounts for <a href="https://crsreports.congress.gov/product/pdf/IF/IF11707">about 60 percent of global central bank reserves</a>, and no other currency comes close. <a href="https://www.imf.org/en/Blogs/Articles/2021/05/05/blog-us-dollar-share-of-global-foreign-exchange-reserves-drops-to-25-year-low">The euro is in second [at about 20 percent]</a>. And then I think after that, everything else is in single digits. So there’s already a trend away from the dollar, but it’s a slow-moving trend.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VHejDd">
Likewise, it’s hard to get data on trade invoicing. But the International Monetary Fund and other groups have tried to collect such data. It appears that the dollar is the predominant currency used in international trade. The Chinese are denominating a lot of their trade in renminbi. <a href="https://www.thenationalnews.com/business/2023/04/05/chinas-yuan-gains-traction-as-international-trade-settlement-currency/">So that is already rising</a>, and that process is further along. The use of non-dollar currencies for trade invoicing has moved along further than for central bank reserves.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ssj8lZ">
And then you can look at things like: How is it used in portfolio investment around the world? In this situation, of course, people are going to be moving away from the dollar. The question is, how rapidly and to what other alternatives?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FEF25A">
Periodically, there has been a thought that some other currency might challenge the US dollar for supremacy. Back in the late 1980s, people thought maybe it would be the Japanese yen. But the Japanese didn’t want to do the things that would be necessary to make the yen more widely used around the world. So that moment passed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4uvHLi">
Then the euro was created in 1999. People thought the euro could be an alternative to the dollar. But this was an untested central bank that was governed by a whole group of countries. That’s not the same thing as the US Treasury and the US Federal Reserve. And so while the euro has gained use in all sorts of ways, it has not supplanted the dollar.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8W7hVg">
Now the interest is with the Chinese renminbi. Here, the story gets more interesting because <a href="https://www.vox.com/china">China</a> is a non-Western country with a set of diplomatic interests and political values that seem to be quite distinct from those held in the United States and the West more broadly. It is thought that the rise of China and the potential use of the renminbi could present a greater political challenge to the United States, which leads to your interest in sanctions and foreign policy.
</p>
<h4 id="fHwLUF">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qLzG11">
Yep, let’s talk sanctions.
</p>
<h4 id="sWS4H7">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HYnna0">
Because the dollar is the dominant currency, that has implications for United States foreign policy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KZgzUn">
The US can use its control over dollar deposits in the United States as a direct lever for sanctions, as we have done in the case of <a href="https://www.vox.com/22968949/russia-sanctions-swift-economy-mcdonalds">Russia and its invasion of Ukraine.</a>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jdGK2Y">
[The US] can also use the vast and lucrative US financial market as a lever to gain compliance with economic sanctions. For example, in the 2000s, <a href="https://home.treasury.gov/news/press-releases/js2720">the United States sanctioned a small bank in Macao called Banco Delta Asia,</a> which was a small, obscure bank, but it turned out it was one of only two banks that North Korea used. When the US put sanctions on Banco Delta Asia and got the Macanese authorities to freeze North Korean holdings in the bank, it crippled North Korean international exchange. Ultimately, the Macanese authorities and the People’s Bank of China were willing to go along with this because they took a look around and they said — obviously, I’m making these numbers up for illustrative purposes — “you know, we’re doing $10,000 worth of business with the North Koreans. We’re doing $10 billion worth of business with the United States. We’re going to do the commercially prudent thing and throw this troublesome small customer overboard to maintain access to the US market.” The centrality of the dollar and the size of the US financial markets gives leverage in that regard.
</p>
<aside id="RWXbxd">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C4bnIG">
The final way is — and I’m going to use an example with respect to North Korea — when you’re doing dollar transactions, those dollar transactions pass through banks in the United States, and through the US Federal Reserve System. And so we can watch what you’re doing. We can block transactions. We can use all that data, we have to suss out what front companies may be operating to do illicit transactions that we don’t want to happen. When it comes to North Korea and, say, missile proliferation or their nuclear program, we can use our information on dollar transactions to figure out who the front companies are and how they’re linked, and then we can go after them in terms of trying to impede these transactions that we want to stop.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C0yYL6">
If you have a rise in the renminbi and have the development of alternative messaging systems to SWIFT and those transactions — especially if you have a central bank digital currency, the e-Chinese yuan, and those transactions are going through the People’s Bank of China, they’re not going through the New York Fed, then we can’t see them. And so now, if you’re the North Koreans, and you want to do some nuclear program work or missile proliferation, you can run your transactions through Chinese banks in Chinese currency and never use the dollar, it never enters the American radar system. And so if you’re in the United States, and you want to impede these activities, the rise of the renminbi as an alternative to the dollar can really impede the effectiveness of US sanctions activities.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bIJODl">
For all three of those reasons, an erosion of the status of the US dollar and the centrality of the dollar or dominance of the dollar will lessen the ability of the United States to carry out certain forms of economic or financial diplomacy or sanctions policy.
</p>
<h4 id="7Hktn3">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="66BFC7">
How does the <a href="https://www.vox.com/2023/5/9/23715753/debt-ceiling-limit-default-deal-crisis">debt ceiling</a> showdown tie into that, exactly?
</p>
<h4 id="kNtvoO">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LlkYK7">
There’s this massive loss of confidence in the dollar, and massive reappraisal of the riskiness of the United States, and you’re looking around for alternatives.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hLcY1M">
Now I want to make clear, the renminbi is not going to immediately replace the dollar. The Chinese have capital controls. Their internal financial markets are large, but they’re relatively unsophisticated. If you were a foreign investor, you cannot hedge and swap risk in China like you can in New York. Finally, the issue of lack of constraint on executive authority — maybe we don’t have enough executive authority here — but they have excessive amounts. You might be a little concerned about putting yourself at the whim of Xi Jinping.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a4UZ6k">
So it’s not like the renminbi is immediately going to replace the dollar. But this is more like a self-inflicted thing by the United States, which then encourages people to start looking around for alternatives.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4DnErK">
The most likely ones will be the euro and the renminbi. In the long run, we may end up in a situation, such as some people argue we existed in prior to the First World War, where you have multiple currencies all kind of existing together. There’s not a single dominant currency. You could imagine, eventually, in however many years, the dollar, the euro, and the renminbi kind of playing a similar role in the 21st century.
</p>
<h4 id="WncWkE">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h7syCv">
So it’s not like this will happen overnight, but these debt showdowns, and the possibility of default, may accelerate that decline of the dollar’s dominance.
</p>
<aside id="FvHCZx">
<div>
</div>
</aside>
<h4 id="h9Hz6D">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JtcoqU">
Exactly. It gives that process a nice shove.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iRn2EC">
What it will do in China is — China, like I said, they have capital controls; their markets aren’t as well developed as ours are; they have an executive that doesn’t have a lot of constraints on his behavior. But China may say to themselves, “This is presenting us with an opportunity. If we start to get rid of the capital controls, if we develop more sophisticated markets, if we tie the executive’s hands more, we may make the renminbi more attractive to others.” So it might also elicit a kind of response within China that would help propel or facilitate the internationalization of the Chinese yuan.
</p>
<h4 id="vDhVs3">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tkRPos">
But I wonder, is a global financial market where different currencies have more parity necessarily a bad thing?
</p>
<h4 id="1oaG1e">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8BrcJB">
No. That’s the world that existed, basically, at the end of the 19th century, in the first stage of globalization, and it seemed to work okay. But it means that the US would have less power and influence.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hybHfG">
In a pure economic sense, no: You can have a multi-currency world. The fact that we have vast increases in electronic capabilities and development of digital currencies will reduce the transaction cost of moving from one currency to another. There might be some efficiency gain from having a single currency, but there’s not going to be huge efficiency loss from having several currencies operating in that way.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="k8A4m1">
The big change would be the loss of US geopolitical influence.
</p>
<h4 id="sIWc9n">
Jen Kirby
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D0k8ap">
Is there anything else about a potential US debt default that you wanted to flag?
</p>
<h4 id="WvYkJA">
Marcus Noland
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mGoGv1">
I mean, everybody loses.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5Si5gG">
Low-income countries will be vulnerable because a lot of them borrow in dollars, but everybody will be vulnerable. If you want to bring it home to Americans, you could disrupt their pension systems and pension payments and their mortgage and everything else. And then the foreign policy aspect is the US is advantaged by the centrality of the dollar and our Federal Reserve System in global finance. If that starts to disappear, then our ability to use financial sanctions for things like dealing with North Korea start to erode as well.
</p></li>
<li><strong>How the Disney villain disappeared</strong> -
<figure>
<img alt="Ursula in “The Little Mermaid”: A sea witch, aka a woman with an octopus body and human head with a short spiky haircut." src="https://cdn.vox-cdn.com/thumbor/-X38BAOIcLgWRufDM-dzg4HdgXQ=/94x0:1830x1302/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72294920/Screen_Shot_2023_05_08_at_4.28.30_PM.0.png"/>
<figcaption>
The original 1989 Ursula (voiced by Pat Carroll) in all her glory. | © 1989 Walt Disney Studios. All rights reserved.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The live-action Little Mermaid is a reminder of what movies like Encanto and Frozen II don’t have: a bad guy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="59KDwu">
When <a href="https://www.vox.com/disney">Disney</a>’s live-action remake of <em>The</em> <em>Little Mermaid</em> is released on May 26, audiences will finally get to see Melissa McCarthy’s take on one of the most iconic villains of all time: Ursula. The sea-witch octopus, originally voiced by Pat Carroll and modeled after drag queen Divine, is the epitome of a classic Disney baddie: unabashedly evil and self-serving, with a campy anthem to boot. But with a new version of this character back on our screens, you might realize that it’s been quite some time since Disney has produced an antagonist as brazenly wicked as Ursula. That kind of unbridled villainy has become a relic of sorts in the animation studio’s latest original storytelling, which might have you wondering: Where are all the bad guys?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O32wwj">
Once a staple of Disney’s animated features, particularly musicals, villains have slowly been phased out in favor of stories like <em>Frozen II</em> or <em>Encanto</em> that focus more on our hero’s inner conflict with themselves. Rather than face off against an evil archetype working toward their downfall, our current generation of heroes are fighting their own demons, acting as their own foils, and having to overcome their own mistakes.
</p>
<aside id="urDdWE">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aBOEtn">
The change marks one of the starkest shifts in the history of Disney fairytales, perhaps second only to the switch from 2D animation to CGI. For over half a century, the villain had loomed large in these stories, beginning with the Evil Queen in the first-ever animated feature, <em>Snow White and the Seven Dwarfs</em>. Cinderella’s Stepmother, Captain Hook, and Maleficent soon followed during the Golden Age, and eventually, when the “Disney Renaissance” began in 1989, villains like Ursula, Jafar, and Scar continued the tradition.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dCkNxp">
It’s classic storytelling, with each playing a key role in driving the plot and furthering the character development of our hero. Whether it be locking them away in a tower, stealing their voice, or trying to kill them in a power grab, these characters set the ball in motion and serve as a tangible figure to defeat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TfsSzr">
But as of late, those archetypes have gradually faded away. While <em>The Princess and the Frog</em> (2009) and <em>Tangled</em> (2010) gave us Dr. Facilier and Mother Gothel respectively, we haven’t seen a traditional villain since 2013. Even in that case — Hans from <em>Frozen</em> — the villain pales in comparison to the conflict that Elsa has with her own powers. That theme continued in the film’s sequel, where Elsa struggled to find where she and those powers belonged. Similarly, in 2016’s <em>Moana</em>, the title character sets out on an adventurous ocean quest of self-discovery. And most recently, in 2021’s <em>Encanto</em>, Mirabel’s main conflict is her desire for approval and purpose within her magical family as she fights to restore their fading powers.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/F7IcVzselb8DJmATs89Wji_75M4=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24642398/ENCANTO_ONLINE_USE_490.0_074.60_0104.jpg"/> <cite>Disney</cite>
<figcaption>
In <em>Encanto</em>, Mirabel doesn’t have a traditional foe, just her own longing for approval.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BzvIs6">
But why exactly did this change come about? Disney’s storytelling patterns have always evolved over time, but typically that evolution has been guided by (and can be traced back to) previous successes and failures.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FNuMm6">
For example, when <em>The Little Mermaid</em> revitalized the studio’s flailing animation department in 1989, the company doubled down on fairytales and the songwriting team of Howard Ashman and Alan Menken — resulting in <em>Beauty and the Beast</em> and <em>Aladdin</em>. It also began the still-active trope of an “I Want” song, in which the main character sings about their desires early in the film, with “Part of Your World.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zLt7RJ">
More recently, when disappointing box office numbers for <em>The Princess and the Frog</em> were blamed on the title deterring boys, <em>Rapunzel</em>’s title was changed to the more gender-neutral <em>Tangled</em>, and the successful adjective trend of course continued with <em>Frozen</em>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wxVZxU">
So what was it that could have inspired this move away from the traditional hero vs. villain format?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VBLcSi">
If there’s anything in the world of animation that could have spurred such a seismic shift, it’s <a href="https://www.vox.com/culture/2019/6/27/18715845/pixar-movies-rankings">Pixar</a>. From its origins producing the first ever CGI animated feature with 1995’s <em>Toy Story</em>, the studio (now a subsidiary of Disney) completely reimagined the genre — both in terms of its animation style, and the kinds of stories they were telling. Pixar’s themes, premises, and characters broke convention time after time, and the studio even veered into Disney’s lane by trying its hand at a princess movie with <em>Brave</em>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="usf4V8">
The success of Pixar’s films likely gave filmmakers permission to draw outside the lines, and reimagine what a Disney animated feature could be. This new, broader path, which led Disney to acclaimed films like <a href="https://www.vox.com/culture/2016/11/22/13713820/moana-review-disney-dwayne-johnson-lin-manuel-miranda"><em>Moana</em></a> and <a href="https://www.vox.com/culture/22894837/we-dont-talk-about-bruno-billboard-tik-tok-structure-music"><em>Encanto</em></a>, proved commercially and critically successful, and resulted in groundbreaking new stories told in exciting new ways. And at times, that meant no villains.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DwRjth">
But <em>Frozen II</em>, which had a more mixed reception in 2019, demonstrates some of the pitfalls that can come along with this new approach. In the film, Elsa is led by a mysterious voice on a journey of self-discovery to protect her kingdom from a curse. If it sounds a bit abstract, that’s because it is. The docuseries <em>Into the Unknown: Making Frozen II</em> follows the last year of the film’s production, and the challenges that the creative team faced in crafting a clear narrative. With only months to go until the film’s release date, they were still unsure of who the voice was that was calling Elsa, and feedback from repeated test screenings highlighted the story’s lack of clarity. In this case, fighting the abstract concept of “the elements” paired with the internal journey of finding one’s place proved very difficult to clearly depict on screen. It’s in an instance like this, where the story becomes muddled, that the value of having a villain is really seen.
</p>
<aside id="huulEN">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="b2z2kN">
While a traditional good guy vs. bad guy dynamic might seem simpler and less nuanced than complicated heroes facing complex internal battles, oftentimes both approaches are doing the same thing. A villain is at their best when their presence is facilitating our hero’s inner journey and eventual growth — and doing so in an active, cinematic way.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="StwZB0">
Take <em>The Little Mermaid</em> for example. Much like <em>Moana</em> or <em>Frozen</em>, that movie is about a character grappling with balancing their love of family with their desire to leave them behind for something more. The difference is the inclusion of Ursula, who facilitates that journey and thus helps depict it in a very linear and active way. With Ursula there to push Ariel in a certain direction, her grappling becomes a dialogue instead of a monologue. “Life’s full of tough choices<em>,</em> <em>innit</em>?” Ursula famously says, before kicking off the film’s plot by forcing Ariel to make that tough choice.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DDgZlk">
The role villains like Ursula play is invaluable, whether it be as surrogates for our hero’s own inner demons, foils to their big plans, or fun, campy fools that we love to see defeated. Not to mention that villains come with great accessories: a showstopper like “Poor Unfortunate Souls,” poisoned produce, or a comedic sidekick like Iago — all of which are more entertaining than a vague, mysterious curse.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mddbVW">
For now, we can look to the slew of live-action remakes to remind us what we’re missing. Those films, along with the success of retellings like <em>Cruella</em> and <em>Maleficent</em>, should also garner hope that the studio hasn’t lost sight of the value villains can hold.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vTwNLe">
But until these live-action attempts inspire a return to form on the animation front, those classic villains continue to be missing in action. To <a href="https://www.youtube.com/watch?v=0KUb4bWbyEQ">borrow a phrase</a>: “You’ll find that nowadays / I’ve mended all my ways / repented, seen the light, and made the switch<em>.” </em>But will that switch stick? When <em>The Little Mermaid</em> ushered in the return of fairy tales for the first time since 1959’s <em>Sleeping Beauty</em>, it proved that a return to form is always possible for the House of Mouse. And soon enough, an iconic animated villain might come our way again. Who knows? Maybe someone at Disney is sketching a pair of sinister, villainous eyebrows as we speak.
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Aruna Quadri leads foreign players line-up; Sharath, Sathiyan and Manika key attractions among Indians</strong> - Fourth season of the Ultimate Table Tennis League is scheduled to be held at the Balewadi Sports Complex in Pune from July 13 to 30</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>Talented Yashasvi Jaiswal has learnt art of conversion from chase-master Virat Kohli: Sehwag</strong> - Former India cricketer Virender Sehwag lauded the young Mumbaikar for taking a leaf out of legendary Virat Kohli’s book as he looks to convert the fifties into hundreds</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>WTC final: India vs Australia | Ponting feels India should have Suryakumar Yadav in squad, backs Kishan to provide X factor</strong> - The former Australian captain Ricky Ponting feels Australia have a slight upper hand going into the title clash.</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>BCCI set to ratify its POSH policy and form World Cup Working Group at SGM</strong> - The Working Group for the ODI World Cup will comprise BCCI president, secretary, treasurer along with acting CEO and other senior officials.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2023: KKR vs LSG | Listless Kolkata hoping against hope, Lucknow eyes play-off berth</strong> - On momentum too, LSG look far superior to a struggling KKR who have struggled to get into the act at their home den.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>WFI chief to hold rally in Ayodhya on June 5 amid wrestlers’ protest</strong> - Supporters including representatives from Rajput organisations have vowed to stand by him alleging that the WFI chief was being harassed due to his caste affiliation; till now, Brij Bhushan Sharan Singh has evaded any action</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>APEAPCET-2023 concludes for engineering stream in Andhra Pradesh</strong> - Out of 2,38,180 registered students, 2,24,724 take the test, say officials</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>Bharat Biotech’s partner says Covaxin not commercially viable in North America</strong> - Ocugen’s decision comes after U.S. FDA backs bivalent vaccines 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>DVAC launches fresh probe into highways contracts</strong> - Road projects executed during the AIADMK regime come under scrutiny</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>India fully prepared, committed to protecting its sovereignty &amp; dignity: PM Modi amid eastern Ladakh border row</strong> - In an interview with Japanese publication Nikkei Asia, PM Modi said, “the future development of the India-China relationship can only be based on mutual respect, mutual sensitivity and mutual interests”</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Taking steps to tackle the mental scars of conflict</strong> - The psychological effects of Russia’s invasion are starting to show in Ukraine, at the front and at home.</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>West Ham players confront AZ Alkmaar fans after ‘awful scenes’ as family section attacked</strong> - West Ham players confront AZ Alkmaar fans who attacked an area in which friends and family are watching the match.</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>G7: New sanctions will make sure Russia pays a price, Sunak says</strong> - Rishi Sunak says he hopes other countries follow the UK and bring in new sanctions against Russia.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Russia launches ninth wave of missile attacks on Kyiv this month</strong> - All missiles over the capital were shot down, but falling debris caused some damage, Ukraine says.</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>Italy floods leave 13 dead and force 13,000 from their homes</strong> - More bodies are found after almost every river flooded between the coast and Bologna.</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>Ars Frontiers is Monday, May 22: Top minds talk AI, mRNA, and TikTok bans</strong> - Everyone is invited to our (free!) event, streaming live this coming Monday! - <a href="https://arstechnica.com/?p=1937010">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rocket Report: Canada places premium on a spaceport, Lueders heads to Starbase</strong> - “I fell to my knees, sobbing, from witnessing such an incredible feat.” - <a href="https://arstechnica.com/?p=1940052">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dealmaster: Save on Dell XPS 15, smartwatches, and more</strong> - Summer is here, but that shouldn’t keep you from your cable management project. - <a href="https://arstechnica.com/?p=1940097">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potentially millions of Android TVs and phones come with malware preinstalled</strong> - The bane of low-cost Android devices is showing no signs of going away. - <a href="https://arstechnica.com/?p=1940400">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RSV vaccine to protect infants gets green light from FDA advisors</strong> - Faint data signal of possible increased risk of premature birth caused some concern. - <a href="https://arstechnica.com/?p=1940392">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>Female masturbation is like preparing coffee.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
You can grind your beans by hand, but it’s easier and faster to just use a machine.
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/FunnyGoNow"> /u/FunnyGoNow </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/13la8ms/female_masturbation_is_like_preparing_coffee/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/13la8ms/female_masturbation_is_like_preparing_coffee/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What is the difference between iron man and aluminium man ?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Iron man stops the bad guys, aluminium man just foils their plans.
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/InboxInviteNeeded"> /u/InboxInviteNeeded </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/13ljnbq/what_is_the_difference_between_iron_man_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/13ljnbq/what_is_the_difference_between_iron_man_and/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can we ban “yo momma” jokes from this sub? They’re old, stupid and have been done by literally everyone hundreds of times..</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Just like yo mamma
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/HelpingHandsUs"> /u/HelpingHandsUs </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/13law49/can_we_ban_yo_momma_jokes_from_this_sub_theyre/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/13law49/can_we_ban_yo_momma_jokes_from_this_sub_theyre/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I just passed my drug test…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
My dealer has some explaining to do!
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/AnnoyingOldGuy"> /u/AnnoyingOldGuy </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/13lm5kd/i_just_passed_my_drug_test/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/13lm5kd/i_just_passed_my_drug_test/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I know a woman who has been married 3 times and is still a virgin</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Her first husband was a psychologist and all he ever wanted to do was talk about it. Her second husband was a gynecologist and all he ever wanted to do was look at it. Her third husband was a gourmet and all he wanted to do was eat it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The good news is that I just heard she is getting remarried. This time she is going to marry a lawyer that way she knows she will get screwed.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/setherooo9"> /u/setherooo9 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/13lhvjc/i_know_a_woman_who_has_been_married_3_times_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/13lhvjc/i_know_a_woman_who_has_been_married_3_times_and/">[comments]</a></span></p></li>
</ul>
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