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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>An outbreak of SARS-CoV-2 with high mortality in mink (Neovison vison) on multiple Utah farms</strong> -
<div>
The breadth of animal hosts that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may serve as reservoirs for continued viral transmission are not known entirely. In August 2020, an outbreak of SARS-CoV-2 occurred in multiple mink farms in Utah and was associated with high mink mortality and rapid viral transmission between animals. The outbreak’s epidemiology, pathology, molecular characterization, and tissue distribution of virus within infected mink is provided. Infection of mink was likely by reverse zoonosis. Once established, infection spread rapidly between independently housed animals and farms, and caused severe respiratory disease and death. Clinical signs were most notably sudden death, anorexia, and increased respiratory effort. Gross pathology examination revealed severe pulmonary congestion and edema. Microscopically there was pulmonary edema with moderate vasculitis, perivasculitis, and fibrinous interstitial pneumonia. Reverse transcriptase polymerase chain reaction (RT-PCR) of tissues collected at necropsy demonstrated the presence of SARS-CoV-2 viral RNA in multiple organs including nasal turbinates, lung, tracheobronchial lymph node, epithelial surfaces, and others. Whole genome sequencing from multiple mink was consistent with published SARS-CoV-2 genomes with few polymorphisms. The Utah mink SARS-CoV-2 strain fell into Clade GH, which is unique among mink and other animal strains sequenced to date and did not share other spike RBD mutations Y453F and F486L found in mink. Localization of viral RNA by in situ hybridization revealed a more localized infection, particularly of the upper respiratory tract. Mink in the outbreak reported herein had high levels of virus in the upper respiratory tract associated with mink-to-mink transmission in a confined housing environment and were particularly susceptible to disease and death due to SARS-CoV-2 infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.09.447754v1" target="_blank">An outbreak of SARS-CoV-2 with high mortality in mink (Neovison vison) on multiple Utah farms</a>
</div></li>
<li><strong>Estimating the direct Covid-19 disability-adjusted life years impact on the Malta population for the first full year</strong> -
<div>
Background Disability-adjusted life years (DALYs) combine the impact of morbidity and mortality, allowing for comprehensive comparisons of the population health impact of diseases, injuries, and risk factors. The aim of this paper was to estimate the DALYs due to Covid-19 in Malta (March 2020-21) and investigate its impact in relation to other causes of disease and injury, at a population level. Methods Mortality and weekly hospital admission reported data were used to calculate the DALYs, based on the European Burden of Disease Network consensus Covid-19 model. Covid-19 infection durations of 14 days was considered. Sensitivity analyses for different morbidity scenarios, including post-acute consequences were presented. Estimates were for March 2020-21. Results An estimated 70,421 people were infected (with and without symptoms) by Covid-19 in Malta (March 2020-21), out of which 1,636 required hospitalisation and 331 deaths, contributing to 5,478 DALYs. These DALYs positioned Covid-19 as the fourth leading cause of disease and injury in Malta. Mortality contributed to 95% of DALYs, while post-acute consequences contributed to 60% of morbidity. Conclusion Covid-19 over a period of one year has impacted substantially the population health in Malta. Post-acute consequences are the leading morbidity factors that require urgent targeted action to ensure timely multidisciplinary care. It is recommended that DALY estimations in 2021 and beyond are calculated to assess the impact of vaccine roll-out and emergence of new variants on population health.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/8gdrs/" target="_blank">Estimating the direct Covid-19 disability-adjusted life years impact on the Malta population for the first full year</a>
</div></li>
<li><strong>Overcoming Supply Chain Disruptions During Pandemics by Utilizing Found Hardware for Open Source Gentle Ventilation</strong> -
<div>
The COVID-19 pandemic created temporary shortages of medical equipment like ventilators throughout the world. Recent medical research also indicates a gentle ventilation may be more appropriate for many patients. This article details the design of an open source gentle ventilator (gentle-vent) framework that can be used in periods of scarcity when no other options are available. The system utilizes a wide range of commonly available components that are combined using basic electronics skills to achieve the desired end product. The firmware is programed in the Arduino IDE using any Arduino compatible microcontroller. The main function of the gentle-vent is to generate a calibrated pressure wave at the pump to provide support to the patient’s breathing. Each gentle-vent permutation was tested using a DIY manometer as it could be done in the field in low-resource settings. These measurements were also verified with an open source VentMon. All permutations were able to accurately hold a desired setpoint for at least 2 hours. The most rudimentary implementation using found mechanical components and perf-board costs less than $20. The results indicate that an open source approach can be used to make breathing support accessible in most contexts.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/wd5s2/" target="_blank">Overcoming Supply Chain Disruptions During Pandemics by Utilizing Found Hardware for Open Source Gentle Ventilation</a>
</div></li>
<li><strong>The Impact of Personality and Situational Factors on Perceived Stress: An Investigation During COVID-19 Pandemic</strong> -
<div>
The study investigates the relationship between personality and situational factors on perceived stress level during the global COVID-19 pandemic. Analysis of data collected from people across different territories confirms the association between personality traits and perceived stress level. Furthermore, the paper shows that people are experiencing moderate stress, which is affected by where they are residing, whether their personal finance is at risk, and their usage of social media during the pandemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/5rzts/" target="_blank">The Impact of Personality and Situational Factors on Perceived Stress: An Investigation During COVID-19 Pandemic</a>
</div></li>
<li><strong>Country-wide genomic surveillance of SARS-CoV-2 strains</strong> -
<div>
Genomic surveillance has enabled the identification of several SARS-CoV-2 variants, allowing the formulation of appropriate public health policies. However, surveillance could be made more effective. We have determined that the time taken from strain collection to genome submission for over 1.7 million SARS-CoV-2 strains available at GISAID. We find that strain-wise, time lag in this process ranges from one day to over a year. Country-wise, the UK has taken a median of 16 days (for 417,287 genomes), India took 57 days (for 15,614 genomes), whereas Qatar spent 289 days (for 2298 genomes). We strongly emphasize that along with increasing the number of genomes of COVID-19 positive cases sequenced, their accelerated submission to GISAID should also be strongly encouraged and facilitated. This will enable researchers across the globe to track the spreading of variants in a timely manner; analyse their biology, epidemiology, and re-emerging infections; and define effective public health policies.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.08.447365v1" target="_blank">Country-wide genomic surveillance of SARS-CoV-2 strains</a>
</div></li>
<li><strong>Neutralizing antibodies elicited by the Ad26.COV2.S COVID-19 vaccine show reduced activity against 501Y.V2 (B.1.351), despite protection against severe disease by this variant.</strong> -
<div>
The emergence of SARS-CoV-2 variants, such as 501Y.V2, with immune evasion mutations in the spike has resulted in reduced efficacy of several COVID-19 vaccines. However, the efficacy of the Ad26.COV2.S vaccine, when tested in South Africa after the emergence of 501Y.V2, was not adversely impacted. We therefore assessed the binding and neutralization capacity of n=120 South African sera (from Day 29, post-vaccination) from the Janssen phase 3 study, Ensemble. Spike binding assays using both the Wuhan-1 D614G and 501Y.V2 Spikes showed high levels of cross-reactivity. In contrast, in a subset of 27 sera, we observed significantly reduced neutralization of 501Y.V2 compared to Wuhan-1 D614G, with 22/27 (82%) of sera showing no detectable neutralization of 501Y.V2 at Day 29. These data suggest that even low levels of neutralizing antibodies may contribute to protection from moderate/severe disease. In addition, Fc effector function and T cells may play an important role in protection by this vaccine against 501Y.V2.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.09.447722v1" target="_blank">Neutralizing antibodies elicited by the Ad26.COV2.S COVID-19 vaccine show reduced activity against 501Y.V2 (B.1.351), despite protection against severe disease by this variant.</a>
</div></li>
<li><strong>Oral subunit SARS-CoV-2 vaccine induces systemic neutralizing IgG, IgA and cellular immune responses and can boost neutralizing antibody responses primed by an injected vaccine</strong> -
<div>
The rapid spread of the COVID-19 pandemic, with its devastating medical and economic impacts, triggered an unprecedented race toward development of effective vaccines. The commercialized vaccines are parenterally administered, which poses logistic challenges, while adequate protection at the mucosal sites of virus entry is questionable. Furthermore, essentially all vaccine candidates target the viral spike (S) protein, a surface protein that undergoes significant antigenic drift. This work aimed to develop an oral multi-antigen SARS-CoV-2 vaccine comprised of the receptor binding domain (RBD) of the viral S protein, two domains of the viral nucleocapsid protein (N), and heat-labile enterotoxin B (LTB), a potent mucosal adjuvant. The humoral, mucosal and cell-mediated immune responses of both a three-dose vaccination schedule and a heterologous subcutaneous prime and oral booster regimen were assessed in mice and rats, respectively. Mice receiving the oral vaccine compared to control mice showed significantly enhanced post-dose-3 virus-neutralizing antibody, anti-S IgG and IgA production and N-protein-stimulated IFN-{gamma}and IL-2 secretion by T cells. When administered as a booster to rats following parenteral priming with the viral S1 protein, the oral vaccine elicited markedly higher neutralizing antibody titres than did oral placebo booster. A single oral booster following two subcutaneous priming doses elicited serum IgG and mucosal IgA levels similar to those raised by three subcutaneous doses. In conclusion, the oral LTB-adjuvanted multi-epitope SARS-CoV-2 vaccine triggered versatile humoral, cellular and mucosal immune responses, which are likely to provide protection, while also minimizing technical hurdles presently limiting global vaccination, whether by priming or booster programs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.09.447656v1" target="_blank">Oral subunit SARS-CoV-2 vaccine induces systemic neutralizing IgG, IgA and cellular immune responses and can boost neutralizing antibody responses primed by an injected vaccine</a>
</div></li>
<li><strong>DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging</strong> -
<div>
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is known to be more common in the elderly, who show also more severe symptoms and a higher risk of hospitalization and death. Here we show that the expression of the Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV2 cell receptor, increases during aging in mouse and human lungs, and following telomere shortening or dysfunction in mammalian cells and in mouse models. This increase is regulated at the transcription level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Indeed, ATM inhibition or the selective inhibition of telomeric DDR, through the use of antisense oligonucleotides, prevents Ace2 upregulation following telomere damage, in cultured cells and in mice. We propose that during aging telomeric shortening, by triggering DDR activation, causes the upregulation of ACE2, the SARS-CoV2 cell receptor, thus making the elderly likely more susceptible to the infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.09.447484v1" target="_blank">DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging</a>
</div></li>
<li><strong>Monitoring group activity of hamsters and mice as a novel tool to evaluate COVID-19 progression, convalescence and rVSV-ΔG-spike vaccination efficacy</strong> -
<div>
COVID-19 pandemic initiated a worldwide race toward the development of treatments and vaccines. Small animal models were the Syrian golden hamster and the K18-hACE2 mice infected with SARS-CoV-2 to display a disease state with some aspects of the human COVID-19. Group activity of animals in their home cage continuously monitored by the HCMS100 was used as a sensitive marker of disease, successfully detecting morbidity symptoms of SARS-CoV-2 infection in hamsters and in K18-hACE2 mice. COVID-19 convalescent hamsters re-challenged with SARS-CoV-2, exhibited minor reduction in group activity compared to naive hamsters. To evaluate rVSV-{Delta}G-spike vaccination efficacy against SARS-CoV-2, we used the HCMS100 to monitor group activity of hamsters in their home cage. Single-dose rVSV-{Delta}G-spike vaccination of immunized group showed a faster recovery compared to the non-immunized infected hamsters, substantiating the efficacy of rVSV-{Delta}G-spike vaccine. HCMS100 offers non-intrusive, hands-free monitoring of a number of home cages of hamsters or mice modeling COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.09.447687v1" target="_blank">Monitoring group activity of hamsters and mice as a novel tool to evaluate COVID-19 progression, convalescence and rVSV-ΔG-spike vaccination efficacy</a>
</div></li>
<li><strong>Multi-color super-resolution imaging to study human coronavirus RNA during cellular infection</strong> -
<div>
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus within 20 years that gave rise to a life-threatening disease and the first to reach pandemic spread. To make therapeutic headway against current and future coronaviruses, the biology of coronavirus RNA during infection must be precisely understood. Here, we present a robust and generalizable framework combining high-throughput confocal and super-resolution microscopy imaging to study coronavirus infection at the nanoscale. Employing the model human coronavirus HCoV-229E, we specifically labeled coronavirus genomic RNA (gRNA) and double-stranded RNA (dsRNA) via multicolor RNA-immunoFISH and visualized their localization patterns within the cell. The exquisite resolution of our approach uncovers a striking spatial organization of gRNA and dsRNA into three distinct structures and enables quantitative characterization of the status of the infection after antiviral drug treatment. Our approach provides a comprehensive framework that supports investigations of coronavirus fundamental biology and therapeutic effects.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.09.447760v1" target="_blank">Multi-color super-resolution imaging to study human coronavirus RNA during cellular infection</a>
</div></li>
<li><strong>The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour</strong> -
<div>
The SARS-CoV-2 spike protein is the first contact point between the SARS-CoV-2 virus and host cells and mediates membrane fusion. Recently, a fatty acid binding site was identified in the spike (Toelzer et al. Science 2020). The presence of linoleic acid at this site modulates binding of the spike to the human ACE2 receptor, stabilizing a locked conformation of the protein. Here, dynamical-nonequilibrium molecular dynamics simulations reveal that this fatty acid site is coupled to functionally relevant regions of the spike, some of them far from the fatty acid binding pocket. Removal of a ligand from the fatty acid binding site significantly affects the dynamics of distant, functionally important regions of the spike, including the receptor-binding motif, furin cleavage site and fusion-peptide-adjacent regions. The results also show significant differences in behaviour between clinical variants of the spike: e.g. the D614G mutation shows a significantly different conformational response for some structural motifs relevant for binding and fusion. The simulations identify structural networks through which changes at the fatty acid binding site are transmitted within the protein. These communication networks significantly involve positions that are prone to mutation, indicating that observed genetic variation in the spike may alter its response to linoleate binding and associated allosteric communication.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.07.447341v1" target="_blank">The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour</a>
</div></li>
<li><strong>Cellular Activities of SARS-CoV-2 Main Protease Inhibitors Reveal Their Unique Characteristics</strong> -
<div>
As an essential enzyme of SARS-CoV-2, the pathogen of COVID-19, main protease (MPro) triggers acute toxicity to its human cell host, an effect that can be alleviated by an MPro inhibitor with cellular potency. By coupling this toxicity alleviation with the expression of an MPro-eGFP fusion protein in a human cell host for straightforward characterization with fluorescent flow cytometry, we developed an effective method that allows bulk analysis of cellular potency of MPro inhibitors. In comparison to an antiviral assay in which MPro inhibitors may target host proteases or other processes in the SARS-CoV-2 life cycle to convene strong antiviral effects, this novel assay is more advantageous in providing precise cellular MPro inhibition information for assessment and optimization of MPro inhibitors. We used this assay to analyze 30 literature reported MPro inhibitors including MPI1-9 that were newly developed aldehyde-based reversible covalent inhibitors of MPro, GC376 and 11a that are two investigational drugs undergoing clinical trials for the treatment of COVID-19 patients in United States, boceprevir, calpain inhibitor II, calpain inhibitor XII, ebselen, bepridil that is an antianginal drug with potent anti-SARS-CoV-2 activity, and chloroquine and hydroxychloroquine that were previously shown to inhibit MPro. Our results showed that most inhibitors displayed cellular potency much weaker than their potency in direct inhibition of the enzyme. Many inhibitors exhibited weak or undetectable cellular potency up to 10 M. On contrary to their strong antiviral effects, 11a, calpain inhibitor II, calpain XII, ebselen, and bepridil showed relatively weak to undetectable cellular MPro inhibition potency implicating their roles in interfering with key steps other than just the MPro catalysis in the SARS-CoV-2 life cycle to convene potent antiviral effects. characterization of these molecules on their antiviral mechanisms will likely reveal novel drug targets for COVID-19. Chloroquine and hydroxychloroquine showed close to undetectable cellular potency to inhibit MPro. Kinetic recharacterization of these two compounds rules out their possibility as MPro inhibitors. Our results also revealed that MPI5, 6, 7, and 8 have high cellular and antiviral potency with both IC50 and EC50 values respectively below 1 M. As the one with the highest cellular and antiviral potency among all tested compounds, MPI8 has a remarkable cellular MPro inhibition IC50 value of 31 nM that matches closely to its strong antiviral effect with an EC50 value of 30 nM. Given its strong cellular and antiviral potency, we cautiously suggest that MPI8 is ready for preclinical and clinical investigations for the treatment of COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.08.447613v1" target="_blank">Cellular Activities of SARS-CoV-2 Main Protease Inhibitors Reveal Their Unique Characteristics</a>
</div></li>
<li><strong>A Pharmacophore Model for SARS-CoV-2 3CLpro Small Molecule Inhibitors and in Vitro Experimental Validation of Computationally Screened Inhibitors</strong> -
<div>
Among the biomedical efforts in response to the current coronavirus (COVID-19) pandemic, pharmacological strategies to reduce viral load in patients with severe forms of the disease are being studied intensively. One of the main drug target proteins proposed so far is the SARS-CoV-2 viral protease 3CLpro (also called Mpro), an essential component for viral replication. Ongoing ligand- and receptor-based computational screening efforts would be facilitated by an improved understanding of the electrostatic, hydrophobic and steric features that characterize small molecule inhibitors binding stably to 3CLpro, as well as by an extended collection of known binders. Here, we present combined virtual screening, molecular dynamics simulation, machine learning and in vitro experimental validation analyses which have led to the identification of small molecule inhibitors of 3CLpro with micromolar activity, and to a pharmacophore model that describes functional chemical groups associated with the molecular recognition of ligands by the 3CLpro binding pocket. Experimentally validated inhibitors using a ligand activity assay include natural compounds with available prior knowledge on safety and bioavailability properties, such as the natural compound rottlerin (IC50 = 37 mcM), and synthetic compounds previously not characterized (e.g. compound CID 46897844, IC50 = 31 mcM). In combination with the developed pharmacophore model, these and other confirmed 3CLpro inhibitors may provide a basis for further similarity-based screening in independent compound databases and structural design optimization efforts, to identify 3CLpro ligands with improved potency and selectivity. Overall, this study suggests that the integration of virtual screening, molecular dynamics simulations and machine learning can facilitate 3CLpro-targeted small molecule screening investigations. Different receptor-, ligand- and machine learning-based screening strategies provided complementary information, helping to increase the number and diversity of identified active compounds. Finally, the resulting pharmacophore model and experimentally validated small molecule inhibitors for 3CLpro provide resources to support follow-up computational screening efforts for this drug target.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.03.02.433618v2" target="_blank">A Pharmacophore Model for SARS-CoV-2 3CLpro Small Molecule Inhibitors and in Vitro Experimental Validation of Computationally Screened Inhibitors</a>
</div></li>
<li><strong>Emergency department admissions during COVID-19: explainable machine learning to characterise data drift and detect emergent health risks</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Supervised machine learning algorithms deployed in acute healthcare settings use data describing historical episodes to predict clinical outcomes. Clinical settings are dynamic environments and the underlying data distributions characterising episodes can change with time (a phenomenon known as data drift), and so can the relationship between episode characteristics and associated clinical outcomes (so-called, concept drift). We demonstrate how explainable machine learning can be used to monitor data drift in a predictive model deployed within a hospital emergency department. We use the COVID-19 pandemic as an exemplar cause of data drift, which has brought a severe change in operational circumstances. We present a machine learning classifier trained using (pre-COVID-19) data, to identify patients at high risk of admission to hospital during an emergency department attendance. We evaluate our model9s performance on attendances occurring pre-pandemic (AUROC 0.856 95%CI [0.852, 0.859]) and during the COVID-19 pandemic (AUROC 0.826 95%CI [0.814, 0.837]). We demonstrate two benefits of explainable machine learning (SHAP) for models deployed in healthcare settings: (1) By tracking the variation in a feature9s SHAP value relative to its global importance, a complimentary measure of data drift is found which highlights the need to retrain a predictive model. (2) By observing the relative changes in feature importance emergent health risks can be identified.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.05.27.21257713v2" target="_blank">Emergency department admissions during COVID-19: explainable machine learning to characterise data drift and detect emergent health risks</a>
</div></li>
<li><strong>Impact of vaccination on new SARS-CoV-2 infections in the United Kingdom</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The effectiveness of COVID-19 vaccination in preventing new SARS-CoV-2 infections in the general community is still unclear. Here, we used the Office for National Statistics (ONS) COVID-19 Infection Survey, a large community-based survey of individuals living in randomly selected private households across the UK, to assess the effectiveness of BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca; ChAdOx1) vaccines against any new SARS-CoV-2 PCR-positive tests, split according to self-reported symptoms, cycle threshold value (&lt;30 versus ≥30) as a surrogate for viral load, and gene positivity pattern (compatible with B.1.1.7 or not). Using 1,945,071 RT-PCR results from nose and throat swabs taken from 383,812 participants between 1 December 2020 and 8 May 2021, we found that vaccination with the ChAdOx1 or BNT162b2 vaccines already reduced SARS-CoV-2 infections ≥21 days after the first dose (61%, 95% CI 54 to 68% versus 66%, 95% CI 60 to 71%, respectively) with greater reductions observed after a second dose (79%, 95% CI 65 to 88% versus 80%, 95% CI 73 to 85%, respectively). Largest reductions were observed for symptomatic infections and/or infections with a higher viral burden. Overall, COVID-19 vaccination reduced the number of new SARS-CoV-2 infections, with the largest benefit received after two vaccinations and against symptomatic and high viral burden infections, and with no evidence of difference between the BNT162b2 and ChAdOx1 vaccines.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.22.21255913v2" target="_blank">Impact of vaccination on new SARS-CoV-2 infections in the United Kingdom</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>Collecting Respiratory Sound Samples From Corona Patients to Extend the Diagnostic Capability of VOQX Electronic Stethoscope to Diagnose COVID-19 Patients</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Diagnostic Test: Electronic stethoscope<br/><b>Sponsor</b>:   Sanolla<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Global Phase III Clinical Trial of Recombinant COVID- 19 Vaccine (Sf9 Cells)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Recombinant COVID-19 vaccine (Sf9 cells);   Other: Placebo control<br/><b>Sponsors</b>:   WestVac Biopharma Co., Ltd.;   West China 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>A Clinical Trial of Immunobridging and Lot-to-lot Consistency of COVID-19 Vaccine (Ad5-nCoV) in Different Age Groups.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.5ml;   Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.3ml<br/><b>Sponsors</b>:   CanSino Biologics Inc.;   Jiangsu Province Centers for Disease Control and Prevention<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety of an Inactivated SARS-CoV-2 Vaccine for Prevention of COVID-19 in Adults</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: Experimental Group<br/><b>Sponsor</b>:   Sinovac Research and Development Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mineralocorticoid Receptor Antagonist and Pulmonary Fibrosis in COVID-19.</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Interventions</b>:   Drug: Canrenoate Potassium;   Drug: Normal Saline<br/><b>Sponsor</b>:   Pomeranian Medical University Szczecin<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>Study of Allogeneic Adipose-Derived Mesenchymal Stem Cells for Treatment of COVID-19 Acute Respiratory Distress</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: COVI-MSC;   Drug: Placebo<br/><b>Sponsor</b>:   Sorrento Therapeutics, 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>Study to Evaluate a Single Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With COVID-19 (US)</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: COVI-DROPS;   Drug: Placebo<br/><b>Sponsor</b>:   Sorrento Therapeutics, 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>Immuno-bridging Study of Inactivated SARS-CoV-2 Vaccine in Healthy Population Aged 3-17 vs Aged 18 Years Old and Above</strong> - <b>Conditions</b>:   COVID-19 Pneumonia;   COVID-19<br/><b>Intervention</b>:   Biological: SARS-CoV-2 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>:   China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bifido- and Lactobacilli in Symptomatic Adult COVID-19 Outpatients</strong> - <b>Condition</b>:   COVID-19 Respiratory Infection<br/><b>Intervention</b>:   Other: Dietary Supplement<br/><b>Sponsor</b>:   Nordic Biotic Sp. z o.o.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To Evaluate the Safety and Efficacy of TQ Formula in Covid-19 Participants</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Drug: Black Seed Oil Cap/Tab<br/><b>Sponsor</b>:   Novatek Pharmaceuticals<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of Allogeneic Adipose-Derived Mesenchymal Stem Cells to Treat Post COVID-19 “Long Haul” Pulmonary Compromise</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Biological: COVI-MSC<br/><b>Sponsor</b>:   Sorrento Therapeutics, 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>Study of Monovalent and Bivalent Recombinant Protein Vaccines Against COVID-19 in Adults 18 Years of Age and Older</strong> - <b>Condition</b>:   COVID-19 (Healthy Volunteers)<br/><b>Interventions</b>:   Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent);   Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (bivalent);   Biological: Placebo<br/><b>Sponsors</b>:   Sanofi Pasteur, a Sanofi Company;   GlaxoSmithKline<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>Study on the Performance and Safety of Sentinox in COVID-19 Patients</strong> - <b>Condition</b>:   COVID-19 (SARS-CoV-2 Infection)<br/><b>Interventions</b>:   Device: Sentinox–Group A;   Device: Sentinox–Group B<br/><b>Sponsor</b>:   APR Applied Pharma Research s.a.<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>Intramuscular VIR-7831 (Sotrovimab) for Mild/Moderate COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Biological: VIR-7831<br/><b>Sponsors</b>:   Vir Biotechnology, Inc.;   GlaxoSmithKline<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Low-Dose Radiation Therapy to Lungs in Moderate COVID-19 Pneumonitis: A Case-Control Pilot Study</strong> - <b>Conditions</b>:   COVID-19;   Pneumonia<br/><b>Intervention</b>:   Radiation: Low dose radiotherapy<br/><b>Sponsor</b>:   Mahatma Gandhi Institute of Medical Sciences<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>Simple rapid in vitro screening method for SARS-CoV-2 anti-virals that identifies potential cytomorbidity-associated false positives</strong> - CONCLUSIONS: We describe the methodology for a simple in vitro drug screening assay that identifies potential anti-viral drugs via their ability to inhibit SARS-CoV-2-induced CPE. The additional growth assay illustrated how several drugs display anti-viral activity at concentrations that induce cytomorbidity. For instance, hydroxychloroquine showed anti-viral activity at concentrations that slow cell growth, arguing that its purported in vitro anti-viral activity arises from non-specific…</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>N-(4-Hydroxyphenyl) retinamide suppresses SARS-CoV-2 spike protein-mediated cell-cell fusion by a dihydroceramide delta4-desaturase 1-independent mechanism</strong> - The membrane fusion between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host cells is essential for the initial step of infection; therefore, the host cell membrane components, including sphingolipids, influence the viral infection. We assessed several inhibitors of the enzymes pertaining to sphingolipid metabolism, against SARS-CoV-2 spike protein (S)-mediated cell-cell fusion and viral infection. N-(4-hydroxyphenyl) retinamide (4-HPR), an inhibitor of dihydroceramide…</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>Investigating the active compounds and mechanism of HuaShi XuanFei formula for prevention and treatment of COVID-19 based on network pharmacology and molecular docking analysis</strong> - Traditional Chinese medicine (TCM) has exerted positive effects in controlling the COVID-19 pandemic. HuaShi XuanFei Formula (HSXFF) was developed to treat patients with mild and general COVID-19 in Zhejiang Province, China. The present study seeks to explore its potentially active compounds and pharmacological mechanisms against COVID-19 based on network pharmacology, molecular docking, and molecular dynamics (MD) simulation. All components of HSXFF were harvested from the pharmacology database…</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>Convalescent plasma therapy in patients with moderate-to-severe COVID-19: A study from Indonesia for clinical research in low- and middle-income countries</strong> - BACKGROUND: We explored the outcome of convalescent plasma (CP) treatment in patients with moderate and severe coronavirus disease 2019 (COVID-19) and investigated variables for the design of further trials in Indonesia.</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>Is there any role of intermittent fasting in the prevention and improving clinical outcomes of COVID-19?: intersection between inflammation, mTOR pathway, autophagy and calorie restriction</strong> - The coronavirus disease 2019 (COVID-19) pandemic is provoking a global public health crisis. Even though the academic world is intensively pursuing new therapies, there is still no “game changer” in the management of COVID 19. The Mammalian Target of Rapamycin (mTOR) is an ancient signaling system that has been proposed as a molecular tool used by coronaviruses and other RNA and DNA viruses in order to replicate and persist in the host cell. In recent years, Intermittent Fasting (IF), a practice…</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>Screening of world approved drugs against highly dynamical spike glycoprotein of SARS-CoV-2 using CaverDock and machine learning</strong> - The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes pathological pulmonary symptoms. Most efforts to develop vaccines and drugs against this virus target the spike glycoprotein, particularly its S1 subunit, which is recognised by angiotensin-converting enzyme 2. Here we use the in-house developed tool CaverDock to perform virtual screening against spike glycoprotein using a cryogenic electron microscopy structure (PDB-ID: 6VXX) and the representative structures of five…</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>Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms</strong> - Since its inception, the coronavirus disease 2019 (COVID-19) pandemic has infected millions of people around the world. Therefore, it is necessary to find effective treatments against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), as it is the viral source of COVID-19. Alkaloids are one of the most widespread plant-derived natural compounds with prominent antiviral effects. Accordingly, these phytochemicals have been promising candidates towards discovering effective treatments…</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>Comparative phytochemistry of flavaglines (= rocaglamides), a group of highly bioactive flavolignans from <em>Aglaia</em> species (Meliaceae)</strong> - Flavaglines are formed by cycloaddition of a flavonoid nucleus with a cinnamic acid moiety representing a typical chemical character of the genus Aglaia of the family Meliaceae. Based on biosynthetic considerations 148 derivatives are grouped together into three skeletal types representing 77 cyclopenta[b]benzofurans, 61 cyclopenta[bc]benzopyrans, and 10 benzo[b]oxepines. Apart from different hydroxy, methoxy, and methylenedioxy groups of the aromatic rings, important structural variation is…</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 infection activates a subset of intrinsic pathways to inhibit type I interferons in vitro and in vivo</strong> - SARS-CoV-2 infection poses a global challenge to human health. Upon viral infection, host cells initiate the innate antiviral response, which primarily involves type I interferons (I-IFNs), to enable rapid elimination of the invading virus. Previous studies revealed that SARS-CoV-2 infection limits the expression of I-IFNs in vitro and in vivo, but the underlying mechanism remains incompletely elucidated. In the present study, we performed data mining and longitudinal data analysis using…</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 tale of two diseases: Sarcoidosis, COVID-19 and new therapeutic options with dual RAS inhibition and tetanus-diphtheria vaccine</strong> - Sars Cov-2, the pathogen which belongs to the beta coronavirus family that is responsible for COVID-19, uses Angiotensin Converting Enzyme 2 (ACE2) as a receptor, which is responsible for controlling the actions of renin-angiotensin system (RAS). Sars Cov-2 - ACE2 binding leads to a RAS mediated immune response, which targets especially lungs to form ARDS, which in turn, is the most important cause of mortality in COVID-19. CD8^(+) T cell response dominates over CD4^(+) T cell response 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>Active components in Ephedra sinica Stapf disrupt the interaction between ACE2 and SARS-CoV-2 RBD: potent COVID-19 therapeutic agents</strong> - CONCLUSION: These findings suggested that quinoline-2-carboxylic acids in Ephedra sinica could be considered as potential therapeutic agents for COVID-19. Further, this study provided some justification for the ethnomedicinal use of Ephedra sinica 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>Changes in Language Style and Topics in an Online Eating Disorder Community at the Beginning of the Global COVID-19 Pandemic: Observational Study</strong> - CONCLUSIONS: While we observed a reduction in discussions about ED symptoms an increase of mental health and treatment-related topics was observed at the same time. This points to a change in the focus of the ED community from promoting potentially harmful weight loss methods to bringing attention to mental health and treatments for ED. These results together with heightened cognitive processing, increased social references, and reduced inhibition of negative emotions detected in discussions…</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 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation</strong> - SARS-CoV-2 infection causes broad-spectrum immunopathological disease, exacerbated by inflammatory co-morbidities. A better understanding of mechanisms underpinning virus-associated inflammation is required to develop effective therapeutics. Here we discover that SARS-CoV-2 replicates rapidly in lung epithelial cells despite triggering a robust innate immune response through activation of cytoplasmic RNA-sensors RIG-I and MDA5. The inflammatory mediators produced during epithelial cell infection…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunomodulatory role and potential utility of various nutrients and dietary components in SARS-CoV-2 infection</strong> - Recently, the outbreak of severe acute respiratory syndrome cornoavirus-2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become a great perturbation all around the globe and has many devastating effects on every aspect of life. Apart from the oxygen therapy and extracorporeal membrane oxygenation, Remdesivir and Dexamethasone have been proven to be efficacious against COVID-19, along with various vaccine candidates and monoclonal antibody cocktail therapy for Regeneron. All 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>Synergistic inhibition of two host factors that facilitate entry of Severe Acute Respiratory Syndrome Coronavirus 2</strong> - Repurposing FDA-approved inhibitors able to prevent infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could provide a rapid path to establish new therapeutic options to mitigate the effects of coronavirus disease 2019 (COVID-19). Proteolytic cleavages of the spike S protein of SARS-CoV-2, mediated by the host cell proteases cathepsin and TMPRSS2, alone or in combination, are key early activation steps required for efficient infection. The PIKfyve kinase inhibitor apilimod…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>폐마스크 밀봉 회수기</strong> - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR325788342">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COST EFFECTIVE PORTABLE OXYGEN CONCENTRATOR FOR COVID-19</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU324964715">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>METHOD OF IDENTIFYING SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2) RIBONUCLEIC ACID (RNA)</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU323956811">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IMPROVEMENTS RELATED TO PARTICLE, INCLUDING SARS-CoV-2, DETECTION AND METHODS THEREFOR</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU323295937">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DEEP LEARNING BASED SYSTEM FOR DETECTION OF COVID-19 DISEASE OF PATIENT AT INFECTION RISK</strong> - The present invention relates to Deep learning based system for detection of covid-19 disease of patient at infection risk. The objective of the present invention is to solve the problems in the prior art related to technologies of detection of covid-19 disease using CT scan image processing. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN324122821">link</a></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Wiederverwendbare Maske</strong> -
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Wiederverwendbare Maske, mit einem Maskenkörper (100), einem Fixierband (300) zum Befestigen des Maskenkörpers (100) an einem menschlichen Gesicht, einer auswechselbaren Schicht (200), die zwischen dem menschlichen Gesicht und dem Maskenkörper (100) angeordnet ist, und einem Fixierteil (400) zum Fixieren der auswechselbaren Schicht auf dem Maskenkörper (100).</p></li>
</ul>
<img alt="embedded image" id="EMI-D00000"/>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE325736702">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A COMPREHENSIVE DISINFECTION SYSTEM DURING PANDEMIC FOR PERSONAL ITEMS AND PROTECTIVE EQUIPMENT (PPE) TO SAFEGUARD PEOPLE</strong> - The current Covid-19 pandemic has led to an enormous demand for gadgets / objects for personal protection. To prevent the spread of virus, it is important to disinfect commonly touched objects. One of the ways suggested is to use a personal UV-C disinfecting box that is “efficient and effective in deactivating the COVID-19 virus. The present model has implemented the use of a UV transparent material (fused silica quartz glass tubes) as the medium of support for the objects to be disinfected to increase the effectiveness of disinfection without compromising the load bearing capacity. Aluminum foil, a UV reflecting material, was used as the inner lining of the box for effective utilization of the UVC light emitted by the UVC lamps. Care has been taken to prevent leakage of UVC radiation out of the system. COVID-19 virus can be inactivated in 5 minutes by UVC irradiation in this disinfection box - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN322882412">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UBIQUITOUS COMPUTING SYSTEM FOR MENTAL HEALTH MONITORING OF PERSON DURING THE PANDEMIC OF COVID-19</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU323295498">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种预判重症新冠肺炎（COVID-19）的标志物及其产品和用途</strong> - 本发明提供了一种预判重症疾病的标志物，所述的预判重症疾病的标志物为S100A12，序列为SEQ ID NO.1，所述的重症疾病为重症新冠肺炎、重症感染中的一种。S100A12基因作为标志物，在预判重症疾病时对全血中的S100A12基因的表达水平进行检测即可，无需对白细胞进行分离，简化检测流程。S100A12的表达水平可以指导感染类疾病包括新冠肺炎重症的预判，从而及早施治，降低病死率，具有很好的临床应用前景。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN325296031">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种新型冠状病毒COVID-19-S1蛋白的表达和纯化方法</strong> - 本发明属于生物技术领域，具体涉及一种新型冠状病毒COVID‑19‑S1蛋白的表达和纯化方法。本发明提供的方法，主要包括构建COVID‑19‑S1蛋白表达质粒、将COVID‑19‑S1蛋白表达质粒转化、培养表达COVID‑19‑S1蛋白、纯化COVID‑19‑S1蛋白等过程。本发明将能在293F细胞中高分泌表达蛋白的信号肽与Kozak区和编码人COVID‑19‑S1蛋白的基因进行重组，来提高目的蛋白的表达量和分泌量。采用本发明提供的方法，可以解决新型冠状病毒COVID‑19‑S1蛋白分泌量低、纯度低的问题，为免疫学快速诊断、制备单抗、开展解析蛋白结构研究等提供物质基础。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN325375143">link</a></p></li>
</ul>
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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>Netanyahu’s Likely Departure Is Not Easing the Fears of Palestinians</strong> - Attacks by settlers in the West Bank have been on the rise for years—and a new Israeli government is no guarantee of change. - <a href="https://www.newyorker.com/news/daily-comment/netanyahus-likely-departure-is-not-easing-the-fears-of-palestinians">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Is There Any Time Left for Maya Wiley?</strong> - The former City Hall lawyer, who has received the endorsement of Alexandria Ocasio-Cortez, considers herself the last progressive standing in New York’s mayoral race. - <a href="https://www.newyorker.com/news/our-local-correspondents/is-there-any-time-left-for-maya-wiley">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Importance of Teaching Dred Scott</strong> - By limiting discussion of the infamous Supreme Court decision, law-school professors risk minimizing the role of racism in American history. - <a href="https://www.newyorker.com/news/our-columnists/the-importance-of-teaching-dred-scott">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Fight for the Heart of the Southern Baptist Convention</strong> - How the Convention’s battle over race reveals an emerging evangelical schism. - <a href="https://www.newyorker.com/news/on-religion/the-fight-for-the-heart-of-the-southern-baptist-convention">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Fog of History Wars</strong> - A new battle is being waged over how we teach our country’s past. But old feuds remind us that history is continually revised, driven by new evidence and present-day imperatives. - <a href="https://www.newyorker.com/news/daily-comment/the-fog-of-history-wars">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The new Alzheimer’s drug that could break Medicare</strong> -
<figure>
<img alt="A person on a skateboard goes past a sign that reads “Biogen” outside the company’s headquarters." src="https://cdn.vox-cdn.com/thumbor/pqyvZzSNfTKm9q7xrGJ_7bptSko=/0x0:2667x2000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/69433045/GettyImages_1233323396_copy.0.jpg"/>
<figcaption>
Biogen Inc., headquartered in Cambridge, Massachusetts, has created a new drug to treat Alzheimer’s, called aducanumab. | Adam Glanzman/Bloomberg via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Patients are desperate for hope. But there are serious concerns about Biogen’s new $56,000 treatment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1IS5Ak">
Medicare, the federal health insurance program that covers Americans over 65, is facing an impossible dilemma: Should it cover <a href="https://www.vox.com/2018/7/25/17607376/dementia-alzheimers-drug-trial-biogen-eisai">a new and expensive medication for Alzheimer’s disease</a>, which afflicts 6 million Americans and for which there is no existing treatment, even though the drug might not actually work?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gqawou">
It is an enormous question. Alzheimer’s patients and other families with members who endure mild cognitive impairment that may progress to Alzheimer’s have been waiting decades for an effective treatment. For them, even a few more months of life with improved cognition, one more birthday party or a grandchild’s graduation, is the priority.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rC5P68">
But the evidence on whether Biogen’s treatment, called aducanumab, is effective is, at best, mixed; the FDA approved it this week over the <a href="https://www.biospace.com/article/fda-advisory-committee-rejects-biogen-s-alzheimer-s-treatment-/">objections of its own advisory committee</a>. And with a preliminary announced price of <a href="https://www.cnbc.com/2021/06/07/biogen-ceo-says-56000-annually-for-alzheimers-drug-is-fair-promises-not-to-hike-price-for-at-least-4-years.html">nearly $60,000 annually per patient</a>, covering the treatment could cost <a href="https://jamanetwork.com/journals/jama-health-forum/fullarticle/2771217">upward of $100 billion a year</a>, mostly to Medicare, which would almost <a href="https://www.kff.org/infographic/10-essential-facts-about-medicare-and-prescription-drug-spending/">double</a> the program’s drug spending. Patients themselves could be on the hook for thousands of dollars in out-of-pocket costs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ddEVCE">
What Medicare does about aducanumab will have major ramifications not only for the millions of patients who could potentially be eligible for the drug, but for the future of US health care writ large.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OJgAR0">
The dilemma results from a feature of the American health care system: Unlike in other countries, the federal government has little room to negotiate what Medicare will pay for treatments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5Wm1Ct">
Independent analysts think the drug is worth <a href="https://myemail.constantcontact.com/ICER-Issues-Statement-on-the-FDA-s-Approval-of-Aducanumab-for-Alzheimer-s-Disease.html?soid=1115682120931&amp;aid=2vOhd8l4Mrw">more like $8,000</a>, but Medicare has no authority to charge a lower price. Instead, the federal program is likely in effect obligated to cover the new drug now that it has FDA approval. The tools it has to make a determination about whether or not to cover aducanumab and for whom are fraught with legal and ethical risk.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0kbWkD">
The government now finds itself trying to figure out how to satisfy patients who desperately need help, even though scientists think this particular treatment lacks strong evidence for its effectiveness and policy experts warn it is setting up a budgetary nightmare for Medicare in the future.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pbCDn6">
“Every conversation we’re going to have for the next few years about health care access is going to be about this drug, whether implicitly or explicitly,” Rachel Sachs, a law professor at Washington University in St. Louis who studies drug pricing, told me this week.
</p>
<h3 id="bsBZtH">
The troubled path to aducanumab’s approval
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="09JXpE">
Alzheimer’s is a terrible disease that robs people of their agency during the final years of their lives and robs families of the loved ones they once knew. The emotional and financial costs are severe. And as the number of Americans over 65 <a href="https://www.census.gov/newsroom/press-releases/2020/65-older-population-grows.html">grows</a>, those costs are only expected to increase.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xtlaAv">
In recent history, the decades-long search for an effective treatment or cure has been driven by what’s known as <a href="https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/">the amyloid hypothesis</a>, which holds that plaque in the brain found in Alzheimer’s patients is at least in part responsible for the disease and removing that plaque could help relieve the symptoms.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jJ68Kp">
Aducanumab, accordingly, targets the amyloid plaque. Clinical trials of the drug started in 2015 but were <a href="https://investors.biogen.com/news-releases/news-release-details/biogen-and-eisai-discontinue-phase-3-engage-and-emerge-trials">halted</a> in March 2019 because it did not appear it would meet the threshold for clinical effectiveness established at the start of the trials. It appeared, in other words, as though the drug didn’t work.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DhtzPQ">
Normally, that would be the end of the story. But an unexpected twist came a few months later when Biogen revealed that, after additional data analysis with the FDA, some patients in one trial had actually seen “better but ultimately mixed results,” as the authors of <a href="https://www.healthaffairs.org/do/10.1377/hblog20210604.489197/full/">a Health Affairs post</a> on the controversy put it. Biogen announced it would push ahead with seeking FDA approval in October 2019, <a href="https://endpts.com/a-major-reshuffling-at-the-fda-opened-the-road-for-biogens-alzheimers-drug-can-it-cross-the-finish-line/">with the FDA’s apparent support</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="m6jJPt">
Then, in November 2020, Biogen and aducanumab faced what looked like the ultimate setback: The FDA’s advisory committee on neurological therapies <a href="https://www.biospace.com/article/fda-advisory-committee-rejects-biogen-s-alzheimer-s-treatment-/">voted</a> the data did not demonstrate the drug was clinically effective. The vote was all but unanimous, with zero in favor, 10 nays, and one uncertain. They raised concerns about potential side effects, such as brain swelling in patients who were given high doses.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G62HNe">
But, in defiance of its own advisory committee’s recommendation, the FDA granted aducanumab its approval on Monday. The news was welcomed by Alzheimer’s patient groups but roundly criticized by experts in drug development.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XdZEO0">
“The FDA … has failed in its responsibility to protect patients and families from unproven treatments with known harms,” the Institute for Clinical and Economic Review (ICER), an independent non-government group that gauges the value of new drugs, said in <a href="https://myemail.constantcontact.com/ICER-Issues-Statement-on-the-FDA-s-Approval-of-Aducanumab-for-Alzheimer-s-Disease.html?soid=1115682120931&amp;aid=2vOhd8l4Mrw">a blistering statement</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SZ92oH">
And the agency not only approved the drug over the advice of its scientific advisers, but it put effectively no restrictions on which patients with cognitive impairment should be given the drug, a decision that further stunned experts, <a href="https://www.statnews.com/2021/06/07/twist-fda-alzheimers-decision-no-limits-on-patients/">as STAT reported</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="za3CoA">
“For the FDA to approve it and with a very broad indication, I was shocked,” Stacie Dusetzina, who studies drug costs at Vanderbilt University, told me. “I really expected them to say no, based on the body of evidence.”
</p>
<h3 id="pR5dGQ">
Medicare almost always covers FDA-approved drugs
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Dodq7C">
Now that aducanumab is approved by the FDA, the issue of coverage falls largely to Medicare; because of the age of the patient population most affected by Alzheimer’s, the federal program is likely to bear the brunt of the drug’s costs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KnxQhB">
In practice, if the FDA approves a drug, Medicare will pay for it. Aducanumab would be covered through Medicare Part B, which covers outpatient care, because it is an infusion treatment administered directly by doctors. To be covered by Part B, medical care must be “reasonable and necessary” — a vague standard that has, for medications, historically been mostly synonymous with FDA approval.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4uqO0z">
Because the drug is covered by Part B, doctors will even have a financial incentive to prescribe it. For prescription drugs, the program pays physicians the average price plus 6 percent, a policy that both Presidents Obama and Trump <a href="https://www.healthaffairs.org/do/10.1377/hblog20181026.360332/full/">proposed</a> changing but nevertheless remains in place. Determining which patients would benefit from the drug requires expensive scans, and practices will be able to bill Medicare for those, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hxpG5s">
At the individual level, patients could face out-of-pocket costs anywhere from $0 for patients eligible for both Medicare and Medicaid, to $10,000 annually, since Medicare Part B can hold patients responsible for up to 20 percent of costs, advocates told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gm0DGC">
When I asked Russ Paulsen, chief operating officer of UsAgainstAlzheimer’s, about Biogen’s list price, he responded with an audible sigh, saying: “It’s a big number.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gtIEA8">
He continued: “We care a lot about making sure the people who are disproportionately affected by this disease, which includes poor people, have the ability to access this drug.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uvv3MK">
Medicare’s inability to determine the price it pays for aducanumab is a uniquely American problem compared to health systems in the rest of the developed world. Countries like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4194861/">Australia</a> and <a href="https://www.parliament.uk/globalassets/documents/post/postpn_364_Drug_Pricing.pdf">the United Kingdom</a> have independent boards that evaluate a new drug’s effectiveness and set a price based on that estimated value. The US pharma industry says the US system is important for encouraging innovation, and companies have made amazing breakthroughs, such as <a href="https://www.vox.com/science-and-health/2017/9/27/16350562/hepatitis-c-drug-prices-louisiana">the hepatitis-C drugs</a> that effectively cure that disease.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2dYjyR">
But, as the standards for approving have sometimes seemed to slip in recent years, the chances of the FDA approving very expensive drugs with only marginal benefits have risen.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xtKw6y">
“We don’t require prices to reflect the value of treatment, period,” Dusetzina said. “Companies can price their drugs as high as they want. Companies can also get drugs approved with little evidence.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uXdRAL">
So Biogen is planning to charge $56,000 annually for aducanumab. ICER, which evaluates the estimated value of new drugs, <a href="https://myemail.constantcontact.com/ICER-Issues-Statement-on-the-FDA-s-Approval-of-Aducanumab-for-Alzheimer-s-Disease.html?soid=1115682120931&amp;aid=2vOhd8l4Mrw">estimates</a>, based on the clinical evidence, that it’s worth more like $8,000; perhaps as little as $2,500 or as much as $23,100. Regardless, the price announced after Biogen secured FDA approval “far exceeds even this optimistic scenario,” ICER concluded.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TmK6Ju">
“If we were talking about a cure for Alzheimer’s disease, we would figure it out,” Dusetzina told me. “It would be so important to address that burden on our society, we would need to figure it out.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UKiL8Z">
But aducanumab is not that drug, according to the available data. So what is Medicare to do?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CUvPej">
Despite the tradition of honoring FDA approval, experts do not expect Medicare to simply announce it is going to cover the drug with no limitations. One option would be for the program to conduct “national coverage determination,” a lengthy review process to figure out whether to cover the drug and for which patients. (The price would not be on the table.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EaVHdL">
The decision that would lead to is unclear. Many experts are <a href="https://www.healthaffairs.org/do/10.1377/hblog20210604.489197/full/">urging</a> Medicare to pursue what is called “coverage with evidence development”: essentially setting up its own clinical trial by authorizing aducanumab for use by some patients and collecting real-world data on their outcomes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VkptwY">
“I think it’d be a really smart move,” Dusetzina, who recently joined Medicare’s payment advisory board, said. “This is the perfect time to reevaluate why we need to consider value when we consider what is a fair price for a treatment.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bBN8IO">
Along those lines, the private health insurer Cigna <a href="https://www.healthcarefinancenews.com/news/biogen-teaming-cigna-cvs-health-increase-access-its-alzheimers-drug">announced</a> it would pursue a value-based contract with Biogen to cover the drug, though it did not provide any more details.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EKnWIp">
But for Medicare, none of these options are ideal. A previous attempt to set up coverage with evidence development for a new cancer drug in 2017 ended up being scuttled after pushback from the drug industry and doctors. Patients with Alzheimer’s and their families are desperate for treatment and will likely object if Medicare tries to restrict access to the drug while undertaking that data collection.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NU8kXV">
Alzheimer’s advocates are mindful of aducanumab’s cost to the US health care system as well as individual patients, and its potential limitations. They are not necessarily opposed to more evaluation of its effectiveness.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fN07mg">
But their ultimate goal is to buy patients more time. As Paulsen told me: “This drug doesn’t do it perfectly, doesn’t do it amazingly well for every single person. But it’s the first one that does that.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZcqNxc">
They say they worry about restricting access to patients who are living with this disease right now, for whom time is running out. They point out that cancer drugs with marginal benefits have also been approved by the FDA, with exponentially higher costs per patient than aducanumab.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qWl7Y1">
“We do not want to see delays in the ability of patients and doctors to begin to discuss whether this treatment is right for them,” Robert Egge, chief public policy officer of the Alzheimer’s Association, said. “And if it is, if that’s their decision together, we want them to have access to it. What we do not want to see is a long protracted process that effectively delays the ability for people to begin this treatment now that approval has been given.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tRGSJc">
The stakes are enormous — for everyone. The cost of expensive drugs ultimately trickles down in the form of higher premiums or taxes. As the investment advisory firm Capital Alpha DC pointed out this week in a note that warned the drug “could break the Medicare program,” the Medicare trustees are expected to issue a report any time now with an updated estimate of when the program’s hospital benefit might start to become insolvent — which could be as soon as 2024.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qOp1jb">
As Sachs told me: “It’s very difficult to see how our health system moves through this without significant negative consequences.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Hx70nd">
Medicare’s inability to negotiate pharmaceutical prices has meant that a budget crisis is always just one drug approval away. With aducanumab, that crisis has arrived — even when evidence so far suggests there may be minimal benefit for patients in return.
</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The best $298 I ever spent: Oysters and a cocktail the night before I gave birth</strong> -
<figure>
<img alt="An illustration of a plate of oysters on the half shell and a bottle of Champagne." src="https://cdn.vox-cdn.com/thumbor/ouU2Gi-owcXYmyJDSBkd6myjb4g=/500x0:3500x2250/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/69432838/Oyster.0.jpg"/>
<figcaption>
Dana Rodriguez for Vox
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After nine months of “shoulds” still didn’t result in the outcome I’d envisioned, I decided to celebrate the chaos.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Lq6O8O">
I never really pictured my birth until halfway through my pregnancy, when I took a class on Zoom. Over the course of two weekends, a childbirth educator talked about avoiding unnecessary medical interventions and shared strategies for coping with the pain of labor without medication, like an epidural.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RUcnrA">
When I started the class, the closest thing I had to a birth plan was “anything but a C-section.” But as we practiced breathing techniques, visualizations, and long, sustained eye contact with our partners while pressing ice to our wrists, visions of my “ideal birth” came into focus. I knew I wanted the freedom to make my own choices about how my labor would go — to have agency, to follow my own intuition in the moment. Maybe I would labor in a tub, maybe I would refuse to push on my back in a hospital bed and squat down to the ground instead. Maybe I could even make it all the way without screaming for an epidural and earn that coveted trophy of childbirth: a “natural” birth.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NKTF4c">
At some point, that “could” slipped into “should,” and birth became something not just to experience, but also to achieve.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OYUucl">
During one of the classes, our instructor showed us videos of women in labor. As someone whose high school sex-ed curriculum had somehow not included “The Miracle of Life,” I’d never seen this before and had, in fact, never seen anything like it — women lowing and moaning, any semblance of self-consciousness stripped away by raw pain. I listened to their gasps and guttural groans and became overwhelmed with curiosity: In this moment, whose voice would come out of my mouth? Who would I become in this animal yielding? I couldn’t wait to find out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ReWlRd">
Late at night, as my future son’s in utero hiccups kept me awake, I dipped into birth Instagram and binged on the black-and-white images of women clutching their newborns to their chests in bloodied birthing tubs; women whose minds had turned fully inward in that moment, or maybe even transcended the walls of the room. As my third trimester dragged on, I daydreamed about my own labor: the warm bath I’d take before heading to the hospital, the music we’d play to get me through that last exhausting stretch of pushing. I pictured the idyllic photos I’d seen and superimposed myself on them, imagining my own body in that tub, my own face drawn into complete concentration. I made a labor playlist.
</p>
<div class="c-float-right">
<aside id="nWsyAB">
<q>Birth became something not just to experience, but also to achieve</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TDIMVs">
At 39 weeks, I waddled into the hospital for my appointment, just as I’d done once a week for the last month. I shared with the midwife on duty how suspenseful and frustrating, but also secretly thrilling, the mystery of spontaneous labor felt to me: Would it happen tomorrow, or two weeks from now, or tonight? I thought about it, frankly, all the time — what would happen, when it would happen, what we would do, what we would say — and knew it didn’t matter. I could think about it all I wanted, but ultimately my body would lead the way. After all, birth, we agreed, was about yielding control.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UZYiNL">
Then I heaved myself up onto the exam table. Five minutes later, all of the mystery fell away and any sense of control was indeed yielded. The baby, we found, was breech, a position that most providers (including my own) consider too high-risk for a vaginal delivery. He’d have to be born in a scheduled C-section instead.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xw1Rfe">
At this stage in my pregnancy, it was unlikely I’d have time to change things — though I could certainly try. According to the internet, there was no shortage of things I could attempt if I wanted it badly enough: chiropractor, Spinning Babies, acupuncture, moxibustion, inversions, floating in a swimming pool, and one extremely painful procedure in which a doctor tries to manually maneuver the baby into position from the outside.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uaAN2Y">
“You can drive yourself crazy trying to do all this stuff,” my doula said when I called her, sobbing, on my way home from the hospital, “and you need to know that it might not work.” Left to my own devices, I knew I’d easily fling myself down this rabbit hole and feel completely personally at fault if my efforts proved fruitless. I was also only three days away from my due date, with a baby wearing an umbilical cord around his neck.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Wrb1nG">
Instead, we scheduled the C-section. After weeks of reveling in the uncertainty of when, the mystery was suddenly distilled into something as clinical and banal as a Google calendar slot. He’d be born not in a room with twinkle lights, aromatherapy, and a birthing tub, but in a clean, cold operating room on the other side of an ugly blue curtain on the following Monday morning.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1H1PsQ">
At home that day, I cried on and off for approximately eight hours. I was shocked by the sheer force and relentlessness of my feelings: waves of sadness and disappointment as I processed the realization that I wouldn’t experience any of the moments I’d allowed myself to picture; I wouldn’t discover the depths of my own animal strength in the hardest parts of labor. The new reality was — after all that hoping and planning and grimacing with ice pressed to my wrist — I wouldn’t experience labor at all. I’m still not sure if I ever will.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mD6DHC">
I felt angry, too — at the situation, at my providers, but also at myself, for letting all those “maybes” take root and bloom into “shoulds.” For letting myself slip into the fantasy that I was in charge, that birth was something I could not only achieve but excel at. That the only thing separating me from my ideal birth was grit and effort and determination — wanting it badly enough, advocating for myself loudly enough. Intellectually, I was ashamed that I allowed myself to be fooled into even momentarily thinking that one kind of birth is more noble, more valid than another. Emotionally, I felt like I’d already failed the first test of motherhood before I’d even become one.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8sUAeG">
Somewhere in all this, I had a flickering moment of clarity and decided to make a Sunday night dinner reservation for me and my husband on the patio of one of my favorite special occasion restaurants. I like to tell people it was logistical, a type-A planner’s dream: If we can pinpoint the exact day and time we’ll become parents, why not squeeze in one hurrah of a nice meal, right under the wire? But if I’m being honest, I think it was a decision made a little bit out of spite. I’d spent the last nine months following the rules, preparing, abstaining, studying, visualizing, doing all the right things — after all that, if I still can’t get the birth I wanted, I can at least have a damn drink. (Besides, I thought, with only 12 more hours to go after nine months of pregnancy, one drink didn’t feel too irresponsible — he’s pretty much fully baked, right?)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o9FLZK">
So the night before our son would be born, and for the first time since the onset of the pandemic, I brushed my hair, put on a dress, swiped on some lipstick (and immediately wiped it off when I remembered masks), and went out to eat with my husband. We sat on the restaurant’s patio, and over the course of two hours, I feasted on one of the most expensive meals of my life while gleefully crossing off half the items on the “What Not to Eat When Pregnant” list: a platter of raw oysters, a little spoonful of white sturgeon caviar and a cured egg yolk on top of rice grits, and, yes, a drink — one perfect, effervescent French 75, made the old-fashioned way with Cognac.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A7nKME">
I worried that I would throw it all back up the next morning in the operating room as a side effect of the anesthesia, which I’d read about online. Beneath that worry were other, more gnawing fears: being wide awake for my own surgery; lying strapped to a table as a scrum of people rummaged around my abdominal cavity like the TSA inspecting a suitcase; witnessing the exact moment in which my life would irreversibly shift on its axis. You’d think all this would inhibit one’s appetite. I ate and drank anyway, and after a spring and summer of barely leaving the house, the two of us somehow racked up a $298 tab.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vBkmhn">
In the previous three days, I had experienced such an onslaught of emotion that I’d barely had time to reflect on the fact that I was days away from the most significant before-and-after moment of my life. And in the previous few months, I’d become so preoccupied with imagining those final hours leading up to birth that I’d nearly forgotten what awaited me on the other side. Sitting before an iced plate of oysters on the half shell and a sweating champagne flute, I could finally pause long enough to remember.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XMATVM">
The next morning, we arrived at the hospital before dawn, rolling a suitcase through the eerily empty hospital hallways. In the triage room, I changed into an ugly gown and laid in a bed while a half-dozen nurses did a lot of things to my body: swabbing, shaving, injecting, drawing. I curled into myself over the table as an anesthesiologist numbed my spine and a nurse held my hand. They laid me back and slipped my wrists through straps as the entire lower half of my body logged off from my nervous system. My husband, masked and scrubbed, came in and knelt beside me to tell me I was doing a good job. (I was not, in fact, doing anything, except nervously making jokes and weeping.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fHBZmB">
The physical sensations of birth I’d spent months imagining were replaced by the cold tingle of the table, the harsh glare of the fluorescent lights, the murmur of nurses and PAs making watercooler small talk over my abdominal cavity. I could not see or feel anything on the other side of the blue curtain suspended over my torso, but I could hear. And just as my silly little labor playlist cued up a song by Otis Redding, I heard the squawk of a whole new person entering the world, and the entire thing felt preordained, every last bit of it.
</p>
<div>
<aside id="vfbSCe">
<q>I heard the squawk of a whole new person entering the world, and the entire thing felt preordained, every last bit of it</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oGhqke">
There are two photos on my phone, separated by about 14 hours. In the first, I’m in a yellow lace maternity dress, holding a French 75, grinning under a pastel mask and posing next to an iced platter of raw oysters on the half shell. In the next, I’m masked, hair-netted, freshly Covid-19-swabbed, and giving an anxious, goofy thumbs-up from a gurney, waiting for someone to roll me into an operating room and deliver my son. There are no string lights or birthing tubs. But my birth wouldn’t have been mine without either of these moments. Both, I think, were a kind of labor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xR2Hu1">
One decadent night of oysters and champagne wouldn’t be enough to absolve me of disappointment — in fact, it took me months to even be able to use the word “birth” when talking about the day my son was born. (Until very recently, I called it “the day of my C-section” or the more Santa Claus-like “the day he came.”) It also wouldn’t soften the sting of envy I still catch myself feeling toward other mothers, or the ugly, insidious feeling that I didn’t earn the title of motherhood quite like they did.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ama0TP">
What that extravagant night on the patio did offer, though, was the chance to reclaim some agency, make a decision without subconsciously comparing notes to what I saw on birth Instagram. In retrospect, a fancy meal the night before my C-section wasn’t just a concession prize, but a rebuking of a culture that valorizes women’s pain and veils it as a virtue. In a strange way, it led me right back to what I wanted from the start: following my intuition, allowing myself to decide what I needed in the moment. I still experienced all of that, in a way. My intuition just happened to lead me to oysters and caviar, and, of course, my son.
</p>
<p class="c-end-para" data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wRWMSs">
Oh, and I didn’t throw up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pDdWPe">
<em>Gray Chapman is a freelance writer living in Atlanta, Georgia.</em>
</p></li>
<li><strong>How In the Heights’ creators turned the hit Broadway musical into a movie</strong> -
<figure>
<img alt="A man and a woman stand talking to one another on a film set." src="https://cdn.vox-cdn.com/thumbor/1kdAQ8e3Ix714bmA0NS1V9JLTn8=/410x0:2435x1519/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/69432747/rev_1_ITH_BROLL_0014_High_Res_JPEG.0.jpeg"/>
<figcaption>
Lin-Manuel Miranda and Quiara Alegría Hudes on the set of <em>In the Heights.</em> | Warner Bros.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Lin-Manuel Miranda, Quiara Alegría Hudes, and Jon M. Chu talk about the challenges and joys of adapting for the big screen.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LmX19P">
After years of development delays — and then a big pandemic delay — <a href="https://www.vox.com/22440448/in-the-heights-movie-review-miranda-ramos-chu-hudes"><em>In the Heights</em></a> is finally headed to the screen. Written by <em>Hamilton</em>’s Lin-Manuel Miranda and playwright Quiara Alegría Hudes, and directed by <em>Crazy Rich Asians</em>’ Jon M. Chu, it’s a joyous, electric movie musical that celebrates the mostly Latino community in Washington Heights, a neighborhood in upper Manhattan.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yeBSpg">
The movie taps into the big dreams of its characters, including bodega owner Usnavi (Anthony Ramos), aspiring designer Vanessa (Melissa Barrera), Stanford student Nina (Leslie Grace), car service dispatch operator Benny (Corey Hawkins), and many more of their friends and loved ones. Shot on location in the Heights, it feels like it’s hitting at the perfect moment, with theaters in the US reopening and people rediscovering their communities and the movies at the same time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AMTbAR">
Ahead of the film’s debut, I spoke with Miranda, Hudes, and Chu via Zoom, in separate conversations, about similar themes: how they saw their own youthful dreams reflected in the film, the genesis of the project, the challenges and thrills of adapting the stage play for the big screen, and shooting in a neighborhood like Washington Heights. Below, I’ve compiled our chats into one look at a vibrant movie musical that came along at just the right time.
</p>
<figure class="e-image">
<img alt="Two men stand near film cameras." src="https://cdn.vox-cdn.com/thumbor/XlMadhuQhMn_BCz6RFb07Z0i8Pw=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22648538/rev_1_ITH_04632_High_Res_JPEG.jpeg"/> <cite>Macall Polay/Warner Bros.</cite>
<figcaption>
Director Jon M. Chu and producer and composer Lin-Manuel Miranda on the set of <em>In the Heights.</em>
</figcaption>
</figure>
<h3 id="ELLX0T">
On the creators’ youthful dreams and love for musical theater
</h3>
<h4 id="84zDkm">
<strong>Lin-Manuel Miranda </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K8iFRG">
Theater saved my life. For me, it was like an invincibility cloak. So much of the trauma of high school is the life-or-death stakes inside your grade at any given time. But in theater, you make friends with kids in other grades. You’re doing something that none of you are getting paid for or getting credit for. You’re just trying to make something greater than the sum of your parts. And you suddenly have little pockets of allyship all over the school. I remember very distinctly when someone hated someone else, or someone wasn’t friends with me anymore, I’d be like, “Okay, I’m going to go visit my friends a grade younger and talk to them about it and maybe we’ll listen to <em>Rent</em> together.” The world gets so much bigger.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OxdUP2">
And you’re trying to make something together. I remember our “illegal” rehearsals, because school rehearsal wasn’t enough time. We would go to a church basement in Bay Ridge, Brooklyn. For me, that meant taking the A train to the D to the R, an hour and a half, to do rehearsals during spring break so that it could be the best thing it could be. We were giving our vacation to do that. The way you learn about sacrifice, and the way you learn that the world is bigger than the immediate drama of the present, is a lifesaver in high school.
</p>
<h4 id="h73xJ9">
<strong>Quiara Alegría Hudes </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4Pn98D">
As a teenager, I loved<strong> </strong>writing. I loved music, I loved books. I did love theater, too, though it wasn’t so accessible to me as a child. But the times I did get to go see plays and musicals, I was really rocked by them. I found it so fun to write. That was like my version of playing with Barbies. I would make a magazine. I would make a poem. I don’t know if I would even name it as my dream, because it was so much fun to do in the moment. It wasn’t about the end goal. It was about how great and wonderful it made me feel, just the creative act.
</p>
<h4 id="OvVlvG">
<strong>Jon M. Chu </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GqEfoc">
I grew up in the Bay Area, and my parents would take me to San Francisco every weekend, whether it was musical season, opera season, or ballet season. So I saw it all — whether I paid attention or not, that’s another thing. I’m the youngest of five kids, so you can imagine us getting restless in the seats!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UTJSPh">
But I loved it. It was always in me. I took tap dance for 12 years growing up, and piano, and drums, and saxophone, and violin, so music was always around.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZZfTkg">
I remember being in <em>Pacific Overtures</em> in fifth grade, a professional tour that was coming through. I played the boy in the tree. The incredible [original Broadway cast lead] <a href="https://www.masterworksbroadway.com/artist/mako/">Mako</a> was in it, and it was an all-Asian Broadway show. At that moment, that felt very normal to me. I know that that stayed with me through all these years.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0gezRe">
Even though I performed a lot growing up, as a kid, you don’t know if you’re a filmmaker or a storyteller, or <em>how</em> to do that, especially back then. So in a way, theater was the only way in. I realized I was a terrible actor and singer much later and realized that behind the scenes was much more my spot.
</p>
<h3 id="Tj4pDT">
How — and why — Miranda and Hudes wrote the original musical together
</h3>
<h4 id="WwDqjy">
<strong>Lin-Manuel Miranda </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cKlaBK">
A lot of things went into that incredibly fertile creative time for me. I wrote [the first draft of <em>In the Heights</em>] on a winter break [from college]. I didn’t sleep. My long-term girlfriend went abroad. So suddenly, I had all this time, and all this angst, which are two of the ingredients you need the most when you’re 19 years old.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2Himmi">
At that time I was living in the Latino program house [at Wesleyan University]. It was called La Casa de Albizu Campos, and it was on-campus housing. At Wesleyan, there’s a program house for every kind of cultural affinity. To get into La Casa, you needed to write an essay about how you plan to serve the Latino community at Wesleyan. My entrance was the arts. I was, I think, the only arts major in my house. I was there with engineering majors and math majors. But we were all first-generation or second-generation Latino kids. I didn’t have that experience in high school. And suddenly I had friends who were really just like me in that we were as fluent in some things — Marc Anthony, the TV we grew up with, <a href="https://www.newyorker.com/culture/culture-desk/the-improbable-charisma-of-walter-mercado">Walter Mercado</a> — as we were with mainstream American culture.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XuisSG">
I think that was a big part of me being able to access more of myself in my writing. Everything I’d written prior to then kind of sounded like [<em>Rent</em> composer] Jonathan Larson, kind of musical theater-ish, rock-ish stuff. But I didn’t bring any of my culture to it or any of my heritage to it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FYkuwT">
Living in that house, I realized, “Oh, there’s more out there like me. I just needed to write the truest version of what I know.”<em> </em>This was in 1999 or 2000, at the time of the first Latin pop boom. Ricky Martin, “Cup of Life.” Marc Anthony singing in English for the first time. Enrique Iglesias, “Bailamos.” I’m watching all these incredibly talented Latin guys.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qLuKWY">
But they’re all incredibly hot Latin guys, and I was like, “That’s not me<em>.” </em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7GG8cJ">
I had directed <em>West Side Story</em> at my high school years before and realized that there was nothing in the musical theater canon that played to any of my strengths. So it was like, “Let me write what is missing.” Then I had all of these other forces pushing on me that led to <em>In the Heights</em>. Can we talk about ourselves with love? Can we talk about our neighborhoods? And have a fully Latino cast?
</p>
<figure class="e-image">
<img alt="A dancer in a green dress is surrounded by other dancers in a dance club." src="https://cdn.vox-cdn.com/thumbor/69gj3fjWjklfYDXUU4J3NqkpOS0=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22648556/rev_1_ITH_02295r_High_Res_JPEG.jpeg"/> <cite>Macall Polay/Warner Bros.</cite>
<figcaption>
Melissa Barrera as Vanessa in <em>In the Heights.</em>
</figcaption>
</figure>
<h4 id="R8XH6M">
<strong>Quiara Alegría Hudes </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XL9urO">
I moved to New York in 2004, in August. I came to New York with a handful of plays I had written about the Latino community in Philadelphia, which is where I’m from. A producer heard one of those plays and was like, “I know this guy who’s writing a thing, and maybe you guys should really get together and have a conversation.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nyzE2m">
So Lin and I were put in a room together. We didn’t know each other but we were both kind of up to something similar, which is this urgent, joyous passion and habit of wanting to describe our life as young Latinos in this nation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YZMZTC">
When we met up — actually, at a cafe near where we ended up doing our off-Broadway run — we were like, “Are we long-lost cousins?” We both had these strong matriarchal figures who were basically community and family centerpieces, our abuelas. We also had parents who came to the United States. They didn’t have a completed community to just plug into; they had to literally build the community that they were inhabiting, through leadership, through advocating for services.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="icQVsJ">
So we had a lot in common and we wanted to join forces and tell the story.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SMwgKL">
When we were working on the stage version, we would get together sometimes once a week, sometimes two or three times a week. Often it would be in Lin’s apartment, up in Inwood [in upper Manhattan]. I would be writing, with my notepad or my laptop, curled on a corner of his green pleather sofa. I’d say, “I want to work on “<a href="https://www.youtube.com/watch?v=ieNK8PYoS4A">Sunrise</a>” for a moment.” But there’s not even a song yet called “Sunrise” — there’s just an idea of what it might be. So I’m like, “You go work on the second verse of Nina’s song ‘Breathe,’ because maybe it could have an idea<em>.”</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="97QQNW">
So he’s skateboarding up and down his very long hallway, which is how he comes up with ideas. I come up with ideas either by sitting statue-still or taking a walk. When one of us had an idea, we would write it out, then tell the other one what we had come up with. It’s a lot like a relay race, passing the baton back and forth. Then we would meet with Tommy Kail, the director, after a few of those sessions and share with him the work that we had come up with together. Tommy would ask questions, he would point out weaknesses, he would tell us, “Oh, this thing really resonates. Go further on that. Take that to the next step.”
</p>
<h4 id="HGfUbd">
<strong>Lin-Manuel Miranda </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KO3Vwj">
Part of the genesis of the show was Latino representation in musical theater, which has a miserable track record. I think the only place with a worse track record is Hollywood — maybe not worse, but super different. It’s very hard to find Latino stories without crime or drugs at the center of them when it comes to mainstream Hollywood representation. That’s just not what we were interested in, but it’s so prevalent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="d2Nmv1">
If you go read the reviews of the original Broadway show, they were like, “This is <em>Sesame Street</em>. There’s no drugs, there’s no crime.” We had to have the audacity to write about ourselves with love, and to write about struggling businesses and struggling with college and the stuff that everyone else has permission to write about but us, apparently. If we do it, we’re airbrushing.
</p>
<figure class="e-image">
<img alt="Five women in a beauty salon." src="https://cdn.vox-cdn.com/thumbor/ykeJeErRyJkPZ7kf-7L2NfnzZz8=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22648581/rev_1_ITH_11340r_High_Res_JPEG.jpeg"/> <cite>Macall Polay/Warner Bros.</cite>
<figcaption>
Melissa Barrera, Stephanie Beatriz, Leslie Grace, Daphne Rubin-Vega, and Dascha Polanco in <em>In the Heights. </em>
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V4dvk1">
It’s unfair to put any kind of undue burden of representation on <em>In the Heights</em>. Quiara and I are first-generation kids, and we write from our perspective. What we tried to do was grab the things we share. There are so many millions of stories — there’s a song in <em>Heights</em> called “Hundreds of Stories,” but there’s millions of stories — from the cultural specificities of the Puerto Rican American experience, the Dominican American experience, the Cuban American experience, and we couldn’t get our arms around all of that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WJt4OF">
What we can get our arms around is: If you come from somewhere else, what do you share? What do you pass on to your kids? How do you feel at home, or not at home? And have every character wrestle with variations on that question.
</p>
<h3 id="9cDErx">
Deciding what to change when migrating <em>In the Heights</em> from stage to screen
</h3>
<h4 id="0nJayo">
<strong>Jon M. Chu </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3iIHH0">
It’s crazy to think, but this is my first actual musical. I feel like I’ve been doing musicals my whole life, so it’s very strange to be like, “Oh, no, no, you actually haven’t incorporated lyrics and songs into your stuff.” That was a different experience, especially when you’re working with Lin-Manuel Miranda, who’s the greatest lyricist and musician of our time. He crammed so much into each song. I have to help the audience get clarity — not just hearing the words, but <em>understanding</em> the words.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EIYb9J">
That was a process for me. It wasn’t just expressing it through movement, although movement could help express those things. Movement was just one piece of many different types of language that we needed to use. The biggest challenge was finding a cast that spoke all these languages, that could ebb and flow between the languages without a blink of an eye, without you noticing when they jump to a new language. It had to be so natural to them, so that we felt that they were all coming from the same source of energy, not a new source of performance. The biggest thing we did was hire a cast that understood that instinctively, so I didn’t have to try to make that happen.
</p>
<h4 id="9Q79sc">
<strong>Quiara Alegría Hudes </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fKg0FN">
We had to make the decision: Are we going to keep <em>In the Heights</em> in 2008-2009, which was a different world than the one we were adapting it in? We decided to make it contemporary. So, what is the community talking about right now? One of those answers was immigration and our undocumented family, friends, neighbors. These have always been really important issues in the community. But the fever pitch, the way that immigration was being used as the sort of litmus test of Americanness, and even humanity — it felt like we had to address it. And I was really excited to address that more directly in the writing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PYvm68">
Another one was the national conversation that happened around microaggressions. That was new since <em>In the Heights</em> opened on the stage, at least at a national level. All of a sudden I had a new vocabulary for some of the experiences that Nina had been going through at college. It helped me articulate not just the financial stresses that her Stanford education put her family under, but also the cultural dislocation that she felt there, that was pretty profound, that made her wonder, “Is this worth it? Is this worth my parents sacrificing so much for when I’m not even sure I’m wanted there?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oCUkiN">
Those are some of the things that had happened in the intervening years. I was like, let me dig into this. Let me sink my teeth in.
</p>
<h4 id="cdJEZE">
<strong>Jon M. Chu</strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IqeidA">
One of the biggest choices we made at first was that this is not about gentrification. This is not about the big, bad mayor coming in and buying things out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tVlwpo">
In fact, there was no villain in this movie. This is a post-gentrification moment, a moment where it’s happening, so what are you going to do now? Everyone was going to deal with this in their own way, whether they’re going to fight it and protest it, or others are going to go with it and take advantage of it. Some want to leave, and some want to stay. Some people don’t know what to do and are figuring it out. That center really helped us find our path of what the story was.
</p>
<figure class="e-image">
<img alt="Three young men in a bodega." src="https://cdn.vox-cdn.com/thumbor/BCYjIQq5CB0zt7194sHMnUsDXz0=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22648584/rev_1_ITH_12215_High_Res_JPEG.jpeg"/> <cite>Macall Polay/Warner Bros.</cite>
<figcaption>
Corey Hawkins, Gregory Diaz IV, and Anthony Ramos in <em>In the Heights.</em>
</figcaption>
</figure>
<h4 id="cBGcnl">
<strong>Quiara Alegría Hudes </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KCGfYV">
Onstage, you have an intermission. You can cram more in, and people will have time to digest it and stuff. But it’s different on film. I knew we would have to cut some songs, maybe cut a character. I decided to cut the character of [Nina’s mother] Camila, for two reasons. I really love that character, so it wasn’t that I felt she didn’t work. It was that I could still focus on really important matriarchs in the community through [neighborhood matriarch] Abuela Claudia and through [local salon owner] Daniela, so I didn’t lose a conversation about what women’s values are in the community, and what the women bring to the table.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mnVvOm">
What I gained from it was that the relationship between Nina and her dad became more of a pressure cooker. She’s an only child. All of his hopes and dreams are on her. In some ways that is very inspiring for her and gives her a lot of direction. In other ways, that’s really unfair. She has to advocate for herself and her right to choose her own path.
</p>
<h3 id="CUxtZo">
Why Washington Heights wasn’t just a character, but a crew member and co-writer, too
</h3>
<h4 id="6WHDuO">
<strong>Jon M. Chu</strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Swf1wX">
Of course, <em>Do the Right Thing</em> is an inspiration to all movies in New York, I think, and to my own personal life. But the reality was, I didn’t know what it was going to be like until I got to Washington Heights, and I was shown this neighborhood by Lin and Quiara. They were the best tour guides you could ask for. Lin would say, “This is where I shot my home videos, in this tunnel at 191st Street — this is the spot.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rLtq2O">
I was like, “I’ve never seen this in a movie before. How can we get cameras down here?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AkSmbF">
They’re like, “That would take a lot of wires.” And I’m like, “Yeah, let’s do that. We have Warner Bros., they can do it.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="etJeUk">
Or I thought, “We could take these old subway cars and bring it down to this old subway station.” And we <em>could</em> do that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="usDxWK">
The pool — [we walked by and I saw it and said,] “What’s that?” Quiara said, “Oh, that’s the pool that we all swim at.” I’m like, “Okay, let’s go check it out.” We went in, and I thought, “This is incredible, I’ve never seen anything like that.” Quiara just says, “Yeah, this is our pool.” I said, “You guys swim in this? How funny would that be to do a Busby Berkeley/Esther Williams number in this thing, with people of all shapes and sizes and colors and tattoos and sneakers, and nobody matching? How beautiful could that be?” We walked away laughing. And then as we got in the van, I was like, “Oh, no, we have to do that. This is why we’re here.”
</p>
<figure class="e-image">
<img alt="A woman in a bikini on an inner tube in a pool, surrounded by other swimmers in inner tubes." src="https://cdn.vox-cdn.com/thumbor/FNgv2sJWtAzy8dNvHbiAn5-jqno=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22648590/rev_1_ITH_FP_0010_High_Res_JPEG.jpeg"/> <cite>Warner Bros.</cite>
<figcaption>
Melissa Barrera in <em>In the Heights.</em>
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SXqaSM">
I think the neighborhood spoke for itself. Washington Heights wasn’t just a cast member — it was a crew member, it was a co-writer, it was all those things. Even right now, it’s our biggest fan. The people who come from there, the way they are pumping up our movie — you can feel their spirit.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AVd0pS">
I couldn’t tell the difference between our background [actors] and the real neighborhood. Sometimes, there was no difference. There’d be that neighbor who was sitting at their stoop hanging out, playing dominoes, and I loved that we got to lean into that. My mom came to the set and I put her on the stoop. I said, “Stay here. We’re shooting this number. Don’t go anywhere.” My mom, you know, she can get into trouble.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hg3Da8">
So I go and shoot and I come back — she’s gone. I’m like, “Oh, no.” Then I hear yelling, I look up, and she’s on the second level of the building drinking beers with the neighbors outside the window. They’re like, “Oh, we saw her, and we just want to hang out.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="We84ni">
That’s Washington Heights for you. That’s the cultural exchange for you. I loved it so much that I had a son during the shooting of the movie, [and] I gave him the middle name Heights, because I just love that word. It made me feel the aspiration, the dreaming big, the dreaming beyond your windowsill. I wanted to say that word every day of my life. And I wanted him to hear that every day of his life.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qCH0vm">
The biggest compliment we get is this movie feels so New York. The reason it feels New York is because of that community. That’s New York. That’s not the Empire State Building New York. That’s Washington Heights.
</p>
<h4 id="tTRxm6">
<strong>Quiara Alegría Hudes </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ERAsYS">
The day we shot the “Carnaval” number, there was so much pressure that day, because we’re looking at all the flags. And we’re like, “Do we have every flag?” Because when you’re seeing it on the big screen, people want to see their flags. We can’t miss one or two. They will be shown. We had to work really hard and get all those flags in there.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DITFVv">
Afterwards, I hear people from screenings say, “I saw my flag, I saw my flag, I saw my flag!” That’s one of the great things about the big screen.
</p>
<h4 id="uSzLsL">
<strong>Jon M. Chu</strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cw6PIH">
Without my experience with <em>Crazy Rich Asians</em>, I’m not sure I would have understood how important a close-up of food is, or that you needed a food designer who understood the culture and all the little idiosyncrasies — what sauce was on the table! We needed to make room for that. I knew that was my job, to make the room where the cast, the crew, Lin, and Quiara could all speak up. They needed to make an environment for me where I could ask stupid questions and try to understand this thing, because I needed to then communicate that to the outside world who doesn’t know this community.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iLDj0C">
So I think that there was a beautiful grace amongst ourselves, a safe space that we could understand each other and that we could just connect on that. I couldn’t ask for a better community to do that.
</p>
<figure class="e-image">
<img alt="A group of swimmers in a community pool, with a camera rig in the foreground." src="https://cdn.vox-cdn.com/thumbor/KWkCjxEIQaEuGOIhBgVNjoo3hW4=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22648623/rev_1_ITH_03567_High_Res_JPEG.jpeg"/> <cite>Macall Polay/Warner Bros.</cite>
<figcaption>
Shooting one of the pool scenes in <em>In the Heights.</em>
</figcaption>
</figure>
<h3 id="eF893w">
A new meaning on the big screen
</h3>
<h4 id="51Q72k">
<strong>Jon M. Chu </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZisL8m">
While we were making this movie, I was going through a period of my life where I met the woman of my dreams, I got married, and I had just had my first little girl. So I was like, the story that I’m making right now is how I’ll tell my little girl what the world is like. And how do you do that?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LEnH8N">
I was also going through a period of time where I felt like my life with my family that I grew up with was changing and going away. It was sad to me. I kept thinking, “Our best days are in the past.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OYve8g">
But then I had my little girl, and realized, “Oh, I get to watch <em>Animaniacs</em> again and show her? I get to show her <a href="https://en.wikipedia.org/wiki/Out_of_This_World_(American_TV_series)"><em>Out of This World</em></a>? Oh, my best days are ahead.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CDI2tZ">
So I realized, this movie was about passing on your stories, about going through life your own way but knowing that your kids are going to have a totally different way, and you’re never going to understand it. That’s going to create conflict, but that’s okay, because that’s how we progress. That America is going to be not the place that we think it is — America’s always been a dream — but what we make it. We each move it along in our own way. That centered what the movie was about for me.
</p>
<h4 id="Ib65sW">
<strong>Quiara Alegría Hudes </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jjhHhs">
In the movie version, there’s so many strong matriarchs, and there’s the notion of what makes a strong Latina. [In the movie’s framing device,] Usnavi telling the story to these little kids, these little girls — in some ways, what he’s doing is sneakily saying, “Here’s four or five or six versions of what a strong Latina looks like. There’s no cookie-cutter mold. There’s different ways to do it, and to find your strength and to find your power.” And he’s telling this to these little girls to help them find <em>their</em> power.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1KQ2fs">
So one new addition [in the film] is the scene where he quizzes them on famous Latinas. That’s because I was reading the screenplay and thinking, “This is in there. How do I put my finger on it a bit more and still have it be fun and comic.”<em> </em>So we got that particular scene, which I love.
</p>
<figure class="e-image">
<img alt="A grandmother stands on a subway platform, lit from the ceiling, with dancers in the background." src="https://cdn.vox-cdn.com/thumbor/009dQ-tsRBdV0auCw3lBp2ytjig=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22648595/rev_1_ITH_FP_0019_High_Res_JPEG.jpeg"/> <cite>Warner Bros.</cite>
<figcaption>
Olga Merediz as Abuela Claudia in <em>In the Heights. </em>
</figcaption>
</figure>
<h3 id="Azqy1m">
Why they’re so glad they waited for a delayed release
</h3>
<h4 id="K0rbCn">
<strong>Quiara Alegría Hudes </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zt83tl">
I feel like this movie inadvertently became a really entertaining instruction manual for how we can be together again. Honestly, we’re rusty. We’re out of practice. But <em>In the Heights</em> is a bunch of people crammed into big spaces and crammed into small spaces, being community members together in the space.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QxX4ow">
There’s this tiny detail in the dinner scene where Daniela and Carla come in, and Carla hugs Abuela Claudia hello, and she just pinches her butt. I love it, because it’s so real. That’s totally my experience, too. We have to relearn, literally, how to hug the people that we are closest to. So it’s like the Ikea manual for getting back together with your friends and neighbors.
</p>
<h4 id="gw3Hll">
<strong>Jon M. Chu </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OnhMAX">
I love this movie so much. I was so excited to share this in the summer. This film has been a decade in the making. It was hard. But you know, we had other issues going on. We had to protect our families. We had to protect our neighborhoods. So [when the pandemic delay happened,] we could put it in a box and not think about it. I didn’t think about it. I think we were all really good at not thinking about it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8MuFRA">
Lin and I had a frank discussion last year: Should we just release it [on a streaming platform during the pandemic], to give it as a gift to people who needed it? My argument was that I’ve seen what movies can do with a whole community of people — of making movie stars that then start a whole new path. We had that in our hands. Why would we compromise that right now, and give it to people just for a short period of joy in their life, when they can have the joy later?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8vyG2G">
Plus Warner Bros. were going to spend tens of millions of dollars to make these stars <em>stars</em>. They are going to paint what the new face of the movie star is going to look like. And they’re going to make paths for other movies. It’s not just this movie.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vW06Zz">
That gave us focus. Who knew that we would hit just the right date, when things are opening up? And that it will premiere [at the Tribeca Film Festival] in Washington Heights, who knows how to deal with struggle, who knows how to get back up? In that number alone, “<a href="http://www.mtv.com/news/3177564/in-the-heights-mtv-movie-tv-awards/">Carnaval del Barrio</a>,” they’re going to show the world what it takes when you feel powerless to get back up and feel powerful.
</p>
<h4 id="Ig81xq">
<strong>Lin-Manuel Miranda </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EW2M5f">
This is a big-screen movie. I’m so glad we waited. Even though I was dragged kicking and screaming into waiting, I’m really glad we waited. Because I think a lot of people are gonna choose to see it together — and it’s a show about community.
</p>
<figure class="e-image">
<img alt="A busy street scene, with fire hydrants creating fountains for children to run through and the George Washington Bridge in the background." src="https://cdn.vox-cdn.com/thumbor/bkGImasS3Axev1Pu6dM7EC5fex0=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22648598/rev_1_ITH_TRLR_0004_High_Res_JPEG.jpeg"/> <cite>Warner Bros.</cite>
<figcaption>
Washington Heights, as seen in <em>In the Heights.</em>
</figcaption>
</figure>
<h3 id="rsFZ5Z">
What it was like to finally see the musical on a movie screen
</h3>
<h4 id="kmovme">
<strong>Lin-Manuel Miranda </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iihimd">
My first time seeing <em>In the Heights</em> on a movie screen was a few days ago [in mid-May], at a drive-in in Puerto Rico with my cousins — who, by the way, are named Kevin, Camila, and Daniella, all characters in the show. And believe me, Camila is like, “What do you owe me for cutting Camila out of the movie? The next movie is gonna be <em>named</em> after me.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UJyPCp">
To watch it in Puerto Rico on the big screen — as the kids say, it hits different. The applause after every number. I always say the best week of my artistic life was the week we brought the tour of <em>In the Heights </em>to Puerto Rico in 2011. I got to play with Usnavi and we got to pull those flags out. It healed something I didn’t know was busted to bring that show to Puerto Rico and have them be proud of it. And I got sort of an echo of that [when I saw the movie there].
</p>
<h4 id="G9tEz9">
<strong>Quiara Alegría Hudes </strong>
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n2T4SH">
By the time I got to see it on a big screen, honestly, I’d seen the screener so many times that the really new element for me was being amongst audience members. It was almost emotional after this year and a half of social distancing and isolation to just hear a story with other people. I was so tuned in to the family behind me and the family to the left of me. It was pretty clear to me they had never seen the stage version of <em>In the Heights</em>. So they were really taking in the story for the first time. They weren’t comparing it to something else.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uKonjD">
When they realized what was happening at the end, I could hear them gasp a little bit. I could hear them exclaim and be like, “Oh, my gosh, now that makes sense.”<em> </em>It was just such a joy experiencing it with other people.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FAPf2o">
What I’m excited about is what this movie will trigger in other writers and other creators. I’m focused less on, “Okay, what am I doing next?” What I want to do next is relax for a minute! I want to sit back and watch other writers tell their stories.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hFPhwJ">
I hope the movie opens doors. There’s a lot of Latino writers out there telling stories. But hopefully, if the movie is successful, producers view us less as a special interest or a one-time-only opportunity, and actually relax and say, “Okay, this can just become part of the commercial fabric or the producing fabric of what we’re making.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D9uBZ4">
So I’m hoping that it is successful. I want to see other people grab that baton and run.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7tOATr">
In the Heights <em>premiered — in Washington Heights — on June 9 as part of the Tribeca Film Festival. It opens in theaters and on HBO Max on June 11.</em><strong> </strong>
</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>All of our shooters are capable of winning in Tokyo Olympics: Pavel Smirnov</strong> - “Each and every one of them can finish on the podium, and I have seen a bit of Indian shooting over the years. On their day they can win medals at the highest level. Even gold,” Smirnov said.</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>Utterly ridiculous, witch hunt has to stop: Vaughan on investigation into alleged racist tweets</strong> - The probe into England cricketers’ old tweets is a “witch hunt” that must stop, says former skipper Michael Vaughan as the ECB investigates alleged r</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>Need to work hard and prove my worth for Tokyo selection: women’s hockey player Lilima Minz</strong> - Lilima, a key player for India in the midfield, made her Olympic debut in 2016 Rio Games when the women’s team qualified for the quadrennial event after 36 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>France eyes Euro 2020 glory as kick-off looms</strong> - France’s fearsome forward line makes them favourites to win a third European crown at the pan-continental event, while top-ranked Belgium and a youthful England side will be major threats.</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>Winning gold at Tokyo 2020 Paralympics will be special: Krishna Nagar</strong> - 21-year-old Krishna Nagar from Rajasthan clinched two gold medals at the Dubai 2021 Para Badminton International in April</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>Questions raised over drug advert by Kerala govt. firm</strong> - RSS quick to point out that drug is from cow products; health activists see bid to mislead public</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>CBI books former Arunachal Minister Tuki</strong> - Procedures not followed in awarding contracts as PWD minister.</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>Kapil Sibal slams fellow letter writer Jitin for switching to BJP, says it’s ‘politics of prasada’</strong> - The veteran Congress leader also said hypothetically if his party thinks of him as “dead wood” or of no utility, he may think of leaving</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>Tribal people carry pregnant woman in ‘doli’ for 10 km</strong> - They urge officials to construct a road in the area</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In Kerala, electricity and water bill arrears pile up during COVID-19 pandemic</strong> - Dues owed by electricity and water consumers to the Kerala State Electricity Board (KSEB) and the Kerala Water Authority (KWA) shoot up to over ₹2,000 crore each</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>Italian woman wakes up after 10 months in coma</strong> - Cristina Rosi, 37, was seven months pregnant when she suffered a heart attack in July last year.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pope rejects German cardinal’s offer to quit over abuse failures</strong> - Cardinal Reinhard Marx had offered to resign over the mishandling of the Catholic abuse crisis.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dutch find Czech crew remains at WW2 RAF bomber crash site</strong> - Five Czech airmen died when their RAF Wellington bomber was shot down over the Netherlands.</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>Biden to warn UK PM not to risk NI peace over Brexit</strong> - The US President and Boris Johnson will have their first face-to-face meeting on the eve of the G7.</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>Euro 2020: Ukraine told to remove ‘political slogan’ from shirt after Russia protests</strong> - Ukraine is told to remove a “political slogan” from its team’s Euro 2020 jersey by Uefa after Russia’s protests</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>Physicists find “definitive evidence” of mechanism behind brightest auroras</strong> - A resonant transfer of energy accelerates atmospheric electrons to sufficient energies. - <a href="https://arstechnica.com/?p=1771437">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>These macOS Monterey features won’t work on Intel Macs</strong> - Intel Macs’ lack of an equivalent to the M1’s Neural Engine may be to blame. - <a href="https://arstechnica.com/?p=1771941">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mystery malware steals 26M passwords from 3M PCs. Are you affected?</strong> - Massive trove can be used for ransomware, espionage, and more. - <a href="https://arstechnica.com/?p=1771883">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What would you pay for autonomous driving? Volkswagen hopes $8.50 per hour</strong> - Automaker also plans to offer video games that drivers can play while charging. - <a href="https://arstechnica.com/?p=1771839">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Don’t look now, but GameStop stock is approaching record highs again</strong> - Retail investors try to force another short squeeze as Cohen becomes chairman. - <a href="https://arstechnica.com/?p=1771837">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><strong>Midway through sex my girlfriend’s phone started ringing.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“That can wait,” I told her.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Hmm…It might be my boss,” she replied.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I tried to get her back into our sexual encounter. “<em>I’m</em> your boss, baby.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well, you don’t feel like him.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/incredibleinkpen"> /u/incredibleinkpen </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/nw9a4m/midway_through_sex_my_girlfriends_phone_started/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/nw9a4m/midway_through_sex_my_girlfriends_phone_started/">[comments]</a></span></p></li>
<li><strong>Fun fact: Australia’s biggest export is boomerangs.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It’s also their biggest import.
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/crazyfortaco"> /u/crazyfortaco </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/nwcbbd/fun_fact_australias_biggest_export_is_boomerangs/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/nwcbbd/fun_fact_australias_biggest_export_is_boomerangs/">[comments]</a></span></p></li>
<li><strong>Doctor, my bottom hurts right around the entrance.</strong> - <!-- SC_OFF -->
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Doctor: That’s the exit, as long as you call it the entrance it will hurt.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MDan25"> /u/MDan25 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/nwd64i/doctor_my_bottom_hurts_right_around_the_entrance/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/nwd64i/doctor_my_bottom_hurts_right_around_the_entrance/">[comments]</a></span></p></li>
<li><strong>Oral sex will make your day,</strong> - <!-- SC_OFF -->
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but anal sex will make your hole weak.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/totallycookingdrunk"> /u/totallycookingdrunk </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/nw51nw/oral_sex_will_make_your_day/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/nw51nw/oral_sex_will_make_your_day/">[comments]</a></span></p></li>
<li><strong>A man walks into a sperm bank</strong> - <!-- SC_OFF -->
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The doctor says “get a load of this guy”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Gothrenapp"> /u/Gothrenapp </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/nwc3sh/a_man_walks_into_a_sperm_bank/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/nwc3sh/a_man_walks_into_a_sperm_bank/">[comments]</a></span></p></li>
</ul>
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