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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>Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
We sought to characterize the role of the gastrointestinal immune system in the pathogenesis of the inflammatory response associated with COVID-19. We measured cytokines, inflammatory markers, viral RNA, microbiome composition and antibody responses in stool from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.09.03.20183947v2" target="_blank">Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19</a>
</div></li>
<li><strong>We distance most when our close circle does, not when we think we should</strong> -
<div>
Why do we adopt new rules, such as social distancing? Although human sciences research stresses the key role of social influence in behaviour change, most COVID-19 campaigns emphasise the diseases medical threat. In a global dataset (n= 6675), we investigated how social influences predict peoples adherence to distancing rules during the pandemic. Bayesian regression analyses controlling for stringency of local measures showed that people distanced most when they thought their close social circle did. Such social influence mattered more than people thinking distancing was the right thing to do. Peoples adherence also aligned with their fellow citizens, but only if they felt deeply bonded with their country. Self-vulnerability to the disease predicted distancing more for people with larger social circles. Collective efficacy and collectivism also significantly predicted distancing. To achieve behavioural change during crises, policymakers must emphasise shared values and harness the social influence of close friends and family.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/u74wc/" target="_blank">We distance most when our close circle does, not when we think we should</a>
</div></li>
<li><strong>The Efficacy of Plant-ionizers in Removing Aerosols for COVID-19 Mitigation</strong> -
<div>
Small size droplets/aerosols are believed to be potentially responsible for COVID-19 transmission in addition to large droplets and surface contamination (fomites). While large droplets and surface contamination can be relatively easier to deal with (i.e. using mask and proper hygiene measures), aerosols present a different challenge due to their ability to remain airborne for a long time. This calls for mitigation measures that can rapidly eliminate the airborne aerosols. Pre-COVID-19, an air ionizer has been touted as an effective tool to eliminate small particulates such as these. In this work, we sought to evaluate the efficacy of a novel plant-based air ionizers in eliminating aerosols. It was found that factors such as the ion concentration, humidity, and ventilation can drastically affect the aerosols removal efficacy. Furthermore, the aerosols removal rate was quantified in terms of ACH (air changes per hour)-equivalent unit, with ACH as high as 12 being achieved by using deploying a plant-based air ionizer in a small isolated office room. Lastly, this work provides an important and timely guidance on the effective deployment of plant ionizers in minimizing the risk of COVID-19 spread via airborne aerosols, especially in poorly-ventilated environment.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/2mh4c/" target="_blank">The Efficacy of Plant-ionizers in Removing Aerosols for COVID-19 Mitigation</a>
</div></li>
<li><strong>Positive correlation between long term emission of several air pollutants and COVID-19 deaths in Sweden</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Several recent studies have found troubling links between air pollution and both incidence and mortality of COVID-19, the pandemic disease caused by the virus SARS-CoV-2. Here, we investigate whether such a link can be found also in Sweden, a country with low population density and a relatively good air quality in general, with low background levels of important pollutants such as PM2.5 and NO2. The investigation is carried out by relating normalized emission levels of several air pollutants to normalized COVID-19 deaths at the municipality level, after applying a sieve function using an empirically determined threshold value to filter out noise. We find a fairly strong correlation for PM2.5, PM10 and SO2, and a moderate one for NOx. We find no correlation neither for CO, nor (as expected) for CO2. Our results are statistically significant and the calculations are simple and easily verifiable. Since the study considers only emission levels of air pollutants and not measurements of air quality, climatic and meteorological factors (such as average wind speeds) can trivially be ruled out as confounders. Finally, we also show that although there are small positive correlations between population density and COVID-19 deaths in the studied municipalities (which are for the most part rural and non densely populated) they are either weak or not statistically significant.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.05.20244418v1" target="_blank">Positive correlation between long term emission of several air pollutants and COVID-19 deaths in Sweden</a>
</div></li>
<li><strong>Short Research Report: Does Playing Apart Really Bring us Together? Investigating the Link Between Perceived Loneliness and the Use of Video Games During the COVID-19 Pandemic.</strong> -
<div>
During the COVID-19 pandemic, several countries implemented social distancing measures to contain virus transmission. However, these vital safety measures have the potential to impair mental health or well-being, for instance, from increased perceived loneliness. Playing social video games may offer a way to continue to socialize while adhering to social distancing measures. To examine this issue further, the present online survey investigated social gaming during the pandemic and its association to perceived loneliness within a German-speaking sample. Results indicated a small positive correlation between general gaming frequency and perceived loneliness. Detailed analysis revealed a negative association between perceived loneliness and increased social forms of video gaming. Specifically, gamers with more social motive for gaming perceived less loneliness, but gamers with a dominant escape motive demonstrated a positive link to perceived loneliness. The use of social gaming in times of social distancing seems to play a small but significant factor in perceived loneliness compared to other demographical data. The findings are discussed with respect to methodological limitations, effect sizes, and sample characteristics. The results enrich the current knowledge on video gaming and its link to social well-being and provide a more nuanced picture than simplistic investigations of screen time.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/zxhw3/" target="_blank">Short Research Report: Does Playing Apart Really Bring us Together? Investigating the Link Between Perceived Loneliness and the Use of Video Games During the COVID-19 Pandemic.</a>
</div></li>
<li><strong>Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement</strong> -
<div>
One third of COVID-19 patients develop significant neurological symptoms, yet SARS-CoV-2 is rarely detected in central nervous system (CNS) tissue, suggesting a potential role for parainfectious processes, including neuroimmune responses. We therefore examined immune parameters in cerebrospinal fluid (CSF) and blood samples from a cohort of patients with COVID-19 and significant neurological complications. We found divergent immunological responses in the CNS compartment, including increased levels of IL-12 and IL-12-associated innate and adaptive immune cell activation. Moreover, we found increased proportions of B cells in the CSF relative to the periphery and evidence of clonal expansion of CSF B cells, suggesting a divergent intrathecal humoral response to SARS-CoV-2. Indeed, all COVID-19 cases examined had anti-SARS-CoV-2 IgG antibodies in the CSF whose target epitopes diverged from serum antibodies. We directly examined whether CSF resident antibodies target self-antigens and found a significant burden of CNS autoimmunity, with the CSF from most patients recognizing neural self-antigens. Finally, we produced a panel of monoclonal antibodies from patients CSF and show that these target both anti-viral and anti-neural antigens, including one mAb specific for the spike protein that also recognizes neural tissue. This exploratory immune survey reveals evidence of a compartmentalized and self-reactive immune response in the CNS meriting a more systematic evaluation of neurologically impaired COVID-19 patients.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.09.11.293464v2" target="_blank">Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement</a>
</div></li>
<li><strong>CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2 and are differentially expressed in lung and kidney epithelial and endothelial cells</strong> -
<div>
As the COVID-19 pandemic continues to spread, investigating the processes underlying the interactions between SARS-CoV-2 and its hosts is of high importance. Here, we report the identification of CD209L/L-SIGN and the related protein CD209/DC-SIGN as receptors capable of mediating SARS-CoV-2 entry into human cells. Immunofluorescence staining of human tissues revealed prominent expression of CD209L in the lung and kidney epithelium and endothelium. Multiple biochemical assays using a purified recombinant SARS-CoV-2 spike receptor binding domain (S-RBD) and ectopically expressed CD209L and CD209 revealed that CD209L and CD209 interact with S-RBD. CD209L contains two N-glycosylation sequons, at sites N92 and N361, but only site N92 is occupied. Removal of the N-glycosylation at this site enhances the binding of S-RBD with CD209L. CD209L also interacts with ACE2, suggesting a role for heterodimerization of CD209L and ACE2 in SARS-CoV-2 entry and infection in cell types where both are present. Furthermore, we demonstrate that human endothelial cells are permissive to SARS-CoV-2 infection and interference with CD209L activity by knockdown strategy or with soluble CD209L inhibits virus entry. Our observations demonstrate that CD209L and CD209 serve as alternative receptors for SARS-CoV-2 in disease-relevant cell types, including the vascular system. This property is particularly important in tissues where ACE2 has low expression or is absent, and may have implications for antiviral drug development.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.06.22.165803v2" target="_blank">CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2 and are differentially expressed in lung and kidney epithelial and endothelial cells</a>
</div></li>
<li><strong>Who does or does not use the “Corona-Warn-App” and why?</strong> -
<div>
To slow the spread of SARS-CoV-2, the German government released the “Corona-Warn-App”, a smartphone application that warns users if they have come into contact with other users tested posi- tive for SARS-CoV-2. Since using the “Corona-Warn-App” is health-relevant behavior, it is essential to understand who is (and who is not) using it and why. In N = 1,972 German adults, we found that non-users were on average older, female, healthier, in training, and had low general trust in others. Most frequently named reasons by non-users were privacy concerns, doubts about the effectiveness of the app, and lack of technical equipment.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/e9fu3/" target="_blank">Who does or does not use the “Corona-Warn-App” and why?</a>
</div></li>
<li><strong>Big Five traits, approach-avoidance motivation, concerns and adherence with COVID-19 prevention guidelines during peak of pandemics in Croatia</strong> -
<div>
Without the vaccine, only way to prevent the spread of coronavirus is following COVID-19 preventive guidelines such as keeping social distance, wearing masks and gloves, reducing mobility, etc. Success depends on how many individuals strictly follow the suggestions from epidemiologists. In this study we examine who and why is adhering with the guidelines. A community sample of 500 participants fulfilled short Big Five Inventory, Questionnaire of Approach and Avoidance Motivation (QAAM) and two scales constructed according to the COVID-19 epidemiological guidelines in Croatia. The results of hierarchical regression analysis indicate that agreeable and conscientious individuals are complying more with preventive measures. In addition, approach, not avoidance, motivation appears to be more important in following the guidelines. Results are discussed in terms of framing messages to explain goals that might be reached by compliant behaviour rather than emphasizing negative consequences of pandemic as such messages seem to produce negative emotional states with no beneficial changes on the behavioural level.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/3edyb/" target="_blank">Big Five traits, approach-avoidance motivation, concerns and adherence with COVID-19 prevention guidelines during peak of pandemics in Croatia</a>
</div></li>
<li><strong>Role of favipiravir in the treatment of adult patients with moderate to severe COVID-19: a single-center, prospective, observational, sequential cohort study from Hungary</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Preliminary data suggests that favipiravir (FVP) might have a role in COVID-19 treatment. Methods: A single-center, prospective, observational, sequential cohort study was performed among consecutive adults hospitalized with PCR-confirmed COVID-19 between March-July,2020. Patients were screened for inclusion by a priori criteria, and were included in the favipiravir cohort if standard-of-care (SOC)+FVP, or the non-favipiravir group if SOC+other antiviral medications without FVP were administered for &gt;48 hours. Treatment allocation was done per national guidelines. For COVID-19 diagnosis and severity, ECDC and WHO definitions were utilized, and daily per protocol hospital follow-up was done. Primary composite end-point was disease progression (14-day all-cause death, need for mechanical ventilation, or immunomodulatory therapy). For statistical comparison, Fisher9s exact test and Mann-Whitney U-test were used. Results: In all, 75 patients were included per cohort. In the FVP cohort, chronic heart disease (36/75, 48.0% vs. 16/75, 21.3%, p&lt;0.01) and diabetes mellitus (23/75, 30.7% vs. 10/75, 13.3%, p&lt;0.01) were more prevalent, hospital LOS (18.5+/-15.5 days vs. 13.0+/-8.5 days, p&lt;0.01) was higher. Disease progression (17/75, 22.7% vs. 10/75, 13.3%, p=0.13), 14-day all-cause death (9/75, 12.0% vs. 10/75, 13.3%, p=0.8) and need for mechanical ventillation (8/75, 10.7% vs. 4/75, 5.3%, p=0.22) were similar between groups. Immunomodulatory therapies were administered frequently among patients receiving FVP (10/75, 13.3% vs. 1/75, 1.3%, p&lt;0.01). Conclusions: In this study, favipiravir did not seem to affect disease progression. Further data are needed to position this drug among the anti-SARS-CoV-2 armamentarium.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.26.20238014v1" target="_blank">Role of favipiravir in the treatment of adult patients with moderate to severe COVID-19: a single-center, prospective, observational, sequential cohort study from Hungary</a>
</div></li>
<li><strong>Ignoring the elephant in the room: factors contributing to inadequate access to condoms and sources of condoms during novel coronavirus diseases 2019 in South Africa.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Evidence has shown that the prescribed lockdown and physical distancing due to the novel coronavirus disease 2019 (COVID-19) have made accessing essential health care services much difficult in low-and middle-income countries (LMICs). Access to contraception is essential and should not be denied, even in a global crisis, because it is associated with several health benefits. It is paramount to maintain timely access to contraception without unnecessary barriers. Hence, this study examines the factors contributing to limited access to condoms and sources of condoms during the COVID-19 pandemic in South Africa (SA).The first secondary dataset on coronavirus from the National Income Dynamic Study (NIDS) conducted in SA during the coronavirus pandemic was employed in this study. This study involved 4,517 respondents. Data were analysed using frequency analysis, chi-square test and binary logistic regression analysis. Almost one-quarter of South Africans could not access condoms, and every 7 in 10 South Africans preferred public or government hospitals as a source of condoms. Female South Africans (aOR=0.86; 95% CI=0.69-1.08), those aged 35-45 (aOR=0.96; 95% CI=0.73-1.28) and those residing in KwaZulu-Natal province (aOR=0.30; 95% CI=0.17-0.52) were 14%, 4% and 70% respectively less likely to have access to condoms during the COVID-19 lockdown. Findings from the study suggest strategies and interventions that will be tailored towards non-obstruction of contraception access during the on-going COVID-19 or any future pandemic. Moreover, special consideration should be given to certain provinces, the uneducated and those in the 4th quintile of wealth-income in South Africa.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.09.11.20192849v2" target="_blank">Ignoring the elephant in the room: factors contributing to inadequate access to condoms and sources of condoms during novel coronavirus diseases 2019 in South Africa.</a>
</div></li>
<li><strong>Estimating the burden of COVID-19 on mortality, life expectancy and lifespan inequality in England and Wales: A population-level study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Deaths directly linked to COVID-19 infection may be misclassified, and the pandemic may have indirectly affected other causes of death. To overcome these measurement challenges, we estimate the impact of the COVID-19 pandemic on mortality, life expectancy and lifespan inequality from week 10, when the first COVID-19 death was registered, to week 47 ending November 20, 2020 in England and Wales through an analysis of excess mortality. Methods: We estimated age and sex-specific excess mortality risk and deaths above a baseline adjusted for seasonality with a systematic comparison of four different models using data from the Office for National Statistics. We additionally provide estimates of life expectancy at birth and lifespan inequality defined as the standard deviation in age at death. Results: There have been 57,419 (95% Prediction Interval: 54,197, 60,752) excess deaths in the first 47 weeks of 2020, 55% of which occurred in men. Excess deaths increased sharply with age and men experienced elevated risks of death in all age groups. Life expectancy at birth dropped 0.9 and 1.2 years for females and males relative to the 2019 levels, respectively. Lifespan inequality also fell over the same period by five months for both sexes. Conclusion: Quantifying excess deaths and their impact on life expectancy at birth provides a more comprehensive picture of the burden of COVID-19 on mortality. Whether mortality will return to -or even fall below- the baseline level remains to be seen as the pandemic continues to unfold and diverse interventions are put in place.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.07.16.20155077v2" target="_blank">Estimating the burden of COVID-19 on mortality, life expectancy and lifespan inequality in England and Wales: A population-level study</a>
</div></li>
<li><strong>Health Signatures During COVID-19: A Precision Fitness Case Study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
BACKGROUND Stay-at-home orders have proven a controversial, while effective, method of SARS-CoV-2 containment. However objective measures of how the pandemic and stay-at-home orders are affecting the daily health of uninfected individuals have been lacking. METHODS We investigated the effect of pandemic-related events on 61 individuals in San Antonio, Texas whose daily activity and sleep data were recorded via wearable activity trackers from April 2019 to August 2020. We assessed changes in six fitness metrics (steps walked, resting heart rate, sedentary minutes, wake duration after sleep onset, rapid eye movement (REM) duration, total sleep duration). Cluster analysis and time-course analysis identified trends in activity before, after and during stay-at-home orders. Quantitative measures of activities were compared to survey responses. RESULTS Four behavior patterns during stay-at-home orders were identified. Most individuals suffered declines in healthy habits compared to their daily activity in 2019 and early 2020 (e.g., up to 60% steps walked). Inflection points corresponded with key dates relevant to SARS-CoV-2 including the first reported case in the U.S. (Feb 29) and city-wide stay-at-home orders (Mar 23). Pre-existing conditions (diabetes, asthma) were associated with a steeper than average decline in sleep quality during stay-at-home orders. Unexpectedly, we also identified a group of predominately male individuals who improved their daily fitness during stay-at-home orders. CONCLUSIONS Objective measures of daily activity indicated most individuals9 fitness suffered at the onset of stay-at-home orders and slowly returned towards baseline. For a subset of individuals, fitness quantitatively improved - better sleep, more exercise, lower resting heartrate - during stay-at-home orders.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.07.20245001v1" target="_blank">Health Signatures During COVID-19: A Precision Fitness Case Study</a>
</div></li>
<li><strong>Stress-related emotional and behavioural impact following the first COVID-19 outbreak peak</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The coronavirus disease 2019 (COVID-19) pandemic poses multiple psychologically-stressful challenges and is associated with increased risk for mental illness. Previous studies have mostly focused on the psychopathological symptoms associated with the outbreak peak. Methods: We examined the behavioural and mental health impact of the pandemic in Israel using an online survey. We collected 12,125 responses from 4,933 adult respondents during six weeks encompassing the end of the first outbreak and the beginning of the second. We used clinically validated instruments (Brief Symptom Inventory 18 (BSI-18), Perceived stress scale (PSS), Brief COPE inventory) to assess anxiety- and depression-related emotional distress, symptoms, and coping strategies, as well as questions designed to specifically assess COVID-19-related concerns. Results: Respondents indicated worrying more about the situation in their country and their close ones contracting the virus, than about their own health and financial situation. The reported distress correlates with the number of new COVID-19 cases and higher emotional burden was associated with being female, younger, unemployed, living in low socioeconomic status localities, encountering more people, and experiencing physiological symptoms. Unexpectedly, older age and having a prior medical condition were associated with reduced emotional distress. Conclusions: Our findings show that inequalities in mental-health burden associated with the COVID-19 pandemic are relevant also following the initial outbreak, and highlight the environmental context and its importance in understanding individual ability to cope with the long-term stressful challenges of the pandemic.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.08.20245787v1" target="_blank">Stress-related emotional and behavioural impact following the first COVID-19 outbreak peak</a>
</div></li>
<li><strong>Characterising long-term covid-19: a rapid living systematic review</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Objective To understand the frequency, profile, and duration of persistent symptoms of covid-19 and to update this understanding as new evidence emerges. Design: A living systematic review produced in response to the rapidly evolving evidence base for long covid. Data sources Medline and CINAHL (EBSCO), Global Health (Ovid), WHO Global Research Database on covid-19, LitCOVID, and Google Scholar to 28th September 2020. Study selection Studies reporting long-term symptoms and complications among people with confirmed or suspected covid-19, both in those previously hospitalised and those never hospitalised. Only studies incorporating over 100 participants qualified for data extraction and were assessed for risk of bias. Results were analysed using descriptive statistics. Quality assessment Risk of bias was assessed using a quality assessment checklist for prevalence studies. Results Twenty-eight studies qualified for data extraction; 16 of these were cohort studies, ten cross-sectional, and two large case series. The analysis included 9,442 adults with covid-19 from 13 countries. The longest mean follow-up period was 111 (SD: 11) days post-hospital discharge. A wide range of systemic, cardiopulmonary, gastrointestinal, neurological, and psychosocial symptoms was reported, of which the most common were breathlessness, fatigue, smell and taste disturbance, and anxiety. Persistent symptoms were described across both previously hospitalised and non-hospitalised populations. The quality of evidence was low, with a high risk of bias and heterogeneity in prevalence. The incorporated studies demonstrated limited external validity, a lack of control subjects, and inconsistent data collection methods. Few studies were conducted in primary care, no studies focused solely on children, and no studies were set in low- and middle-income countries. Conclusion: Our findings suggest that long covid is a complex, heterogeneous condition; however, the limited evidence base currently precludes a precise definition of its symptoms and prevalence. There is a clear need for robust, controlled, prospective cohort studies, including different at-risk populations and settings, incorporating appropriate investigations, collected and recorded in a standardised way.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.08.20246025v1" target="_blank">Characterising long-term covid-19: a rapid living systematic review</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II / III Study of COVID-19 DNA Vaccine (AG0302-COVID19)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Group A (AG0302-COVID19);   Biological: Group A (Placebo);   Biological: Group B (AG0302-COVID19);   Biological: Group B (Placebo)<br/><b>Sponsors</b>:   AnGes, Inc.;   Japan Agency for Medical Research and Development<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>Ivermectin for Severe COVID-19 Management</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Ivermectin<br/><b>Sponsors</b>:   Afyonkarahisar Health Sciences University;   NeuTec Pharma<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids -</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Omegaven®;   Drug: Sodium chloride<br/><b>Sponsor</b>:   Karolinska University Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Efficacy, Safety and Immunogenicity Study of Inactivated SARS-CoV-2 Vaccine for Preventing Against COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell);   Biological: Placebo<br/><b>Sponsor</b>:   Chinese Academy of Medical Sciences<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>Convalescent Plasma Transfusion in Severe COVID-19 Patients in Jamaica</strong> - <b>Condition</b>:   COVID-19, Convalescent Plasma Treatment<br/><b>Intervention</b>:   Biological: Convalescent Plasma Infusion<br/><b>Sponsor</b>:   The University of The West Indies<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>The Protective Potential of Exercise Training on the Cardiopulmonary Morbidity After COVID-19</strong> - <b>Condition</b>:   COVID-19, SARS-CoV2<br/><b>Interventions</b>:   Behavioral: High intensity interval training;   Behavioral: Standard care<br/><b>Sponsor</b>:   Rigshospitalet, Denmark<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>Losartan and Spironolactone Treatment for ICU Patients With COVID-19 Suffering From ARDS</strong> - <b>Conditions</b>:   COVID-19;   ARDS<br/><b>Intervention</b>:   Drug: Losartan 50 mg and Spironolactone 25 mg pillules oral use<br/><b>Sponsor</b>:   Assistance Publique Hopitaux De Marseille<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>Convalescent Plasma for Treatment of COVID-19: An Open Randomised Controlled Trial</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: SARS-CoV-2 convalescent plasma;   Other: Standard of care<br/><b>Sponsors</b>:   Joakim Dillner;   Karolinska Institutet;   Danderyd Hospital;   Falu 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>Study to Assess Adverse Events and How Intravenous (IV) ABBV-47D11 Moves Through the Body of Adult Participants Hospitalized With Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>:   CoronaVirus Disease-2019 (COVID-19)<br/><b>Interventions</b>:   Drug: ABBV-47D11;   Drug: Placebo for ABBV-47D11<br/><b>Sponsor</b>:   AbbVie<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of TY027, a Treatment for COVID-19, in Humans</strong> - <b>Condition</b>:   Coronavirus Disease-2019 (COVID-19)<br/><b>Interventions</b>:   Biological: TY027;   Other: 0.9% saline<br/><b>Sponsor</b>:   Tychan Pte 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>Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers</strong> - <b>Condition</b>:   COVID 19 Vaccine<br/><b>Intervention</b>:   Biological: BCG vaccine<br/><b>Sponsors</b>:   Universidade Federal do Rio de Janeiro;   Ministry of Science and Technology, Brazil<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>At-Home Infusion Using Bamlanivimab in Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Drug: bamlanivimab<br/><b>Sponsors</b>:   Daniel Griffin, MD PhD;   Eli Lilly and Company;   Optum, 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>COVID-19 And Geko Evaluation: The CAGE Study</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Device: geko T3<br/><b>Sponsor</b>:   Lawson Health Research Institute<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 Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Biological: AT-100<br/><b>Sponsor</b>:   Airway 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>A Study of FOY-305 in Patients With SARS-Cov-2 Infection (COVID-19)</strong> - <b>Condition</b>:   SARS-CoV-2 Infection (COVID-19)<br/><b>Interventions</b>:   Drug: FOY-305;   Drug: Placebo<br/><b>Sponsor</b>:   Ono Pharmaceutical Co. Ltd<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>A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury</strong> - Drug repurposing has the advantage of identifying potential treatments on a shortened timescale. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high-content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce mucin-1 (MUC1) protein abundance. Elevated MUC1 levels predict the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and correlate with poor clinical outcomes. Our…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular docking, molecular dynamics, and in vitro studies reveal the potential of angiotensin II receptor blockers to inhibit the COVID-19 main protease</strong> - Drug repurposing is the most rapid and economic way nowadays to rapidly provide effective drugs for our pandemic coronavirus disease 2019 (COVID-19). It was a great debate about ARBs whether to be stopped or continued for patients using them especially at the beginning of the COVID-19 pandemic. In this study, we carried out a virtual screening for almost all members of ARBs (nine) against COVID-19 main protease. Molecular docking as one of the important computational techniques was performed in…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Are losartan and imatinib effective against SARS-CoV2 pathogenesis? A pathophysiologic-based in silico study</strong> - Proposing a theory about the pathophysiology of cytokine storm in COVID19, we were to find the potential drugs to treat this disease and to find any effect of these drugs on the virus infectivity through an in silico study. COVID-19-induced ARDS is linked to a cytokine storm phenomenon not explainable solely by the virus infectivity. Knowing that ACE2, the hydrolyzing enzyme of AngII and SARS-CoV2 receptor, downregulates when the virus enters the host cells, we hypothesize that hyperacute AngII…</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 cross-talk between epithelium and endothelium mediates human alveolar-capillary injury during SARS-CoV-2 infection</strong> - COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles…</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>Anti-inflammatory therapy for COVID-19 infection: the case for colchicine</strong> - The search for effective COVID-19 management strategies continues to evolve. Current understanding of SARS-CoV-2 mechanisms suggests a central role for exaggerated activation of the innate immune system as an important contributor to COVID-19 adverse outcomes. The actions of colchicine, one of the oldest anti-inflammatory therapeutics, target multiple mechanisms associated with COVID-19 excessive inflammation. While many COVID-19 trials have sought to manipulate SARS-CoV-2 or dampen the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploring active ingredients and function mechanisms of Ephedra-bitter almond for prevention and treatment of Corona virus disease 2019 (COVID-19) based on network pharmacology</strong> - CONCLUSION: Ephedra-bitter almonds were used to prevent and treat COVID-19 through directly inhibiting the virus, regulating immune responses, and promoting body repair. However, this work is a prospective study based on data mining, and the findings need to be interpreted with caution.</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>Metabolism and Interactions of Chloroquine and Hydroxychloroquine with Human Cytochrome P450 Enzymes and Drug Transporters</strong> - CONCLUSIONS: Chloroquine caused a statistically significant decrease of P450 2D6 activity in vitro and in vivo, inhibiting also its own metabolism by the enzyme. The inhibition indicates a potential for clinical drug-drug interactions when taken with other drugs that are predominant substrates of the P450 2D6. When chloroquine and hydroxychloroquine are used clinically with other drugs, substrates of P450 2D6 enzyme, attention should be given to substrate specific metabolism by P450 2D6 alleles…</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>Interrelated Mechanism by Which the Methide Quinone Celastrol, Obtained from the Roots of Tripterygium wilfordii, Inhibits Main Protease 3CL(pro) of COVID-19 and Acts as Superoxide Radical Scavenger</strong> - We describe the potential anti coronavirus disease 2019 (COVID-19) action of the methide quinone inhibitor, celastrol. The related methide quinone dexamethasone is, so far, among COVID-19 medications perhaps the most effective drug for patients with severe symptoms. We observe a parallel redox biology behavior between the antioxidant action of celastrol when scavenging the superoxide radical, and the adduct formation of celastrol with the main COVID-19 protease. The related molecular mechanism…</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 comparative analysis for anti-viral drugs: Their efficiency against SARS-CoV-2</strong> - Coronavirus, known as the coronavirus pandemic, is continuing its spread across the world, with over 42 million confirmed cases in 189 countries and more than 1.15 million deaths. Although, scientists focus on the finding novel drugs and vaccine for SARS-CoV-2, there is no certain treatment for it. Antiviral drugs such as; oseltamivir, favipiravir, umifenovir, lopinavir, remdesivir, hydroxychloroquine, chloroquine, azithromycin, ascorbic acid, corticosteroids, are mostly used for patients. They…</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>Dynamic Chest X-Ray Using a Flat-Panel Detector System: Technique and Applications</strong> - Dynamic X-ray (DXR) is a functional imaging technique that uses sequential images obtained by a flat-panel detector (FPD). This article aims to describe the mechanism of DXR and the analysis methods used as well as review the clinical evidence for its use. DXR analyzes dynamic changes on the basis of X-ray translucency and can be used for analysis of diaphragmatic kinetics, ventilation, and lung perfusion. It offers many advantages such as a high temporal resolution and flexibility in body…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing potential of FDA approved and investigational drugs for COVID-19 targeting SARS-CoV-2 spike and main protease and validation by machine learning algorithm</strong> - The present study aimed to assess the repurposing potential of existing antiviral drug candidates (FDA approved and investigational) against SARS-CoV-2 target proteins that facilitates viral entry and replication into the host body. To evaluate molecular affinities between antiviral drug candidates and SARS-CoV-2 associated target proteins such as spike protein (S) and main protease (M^(pro) ), a molecular interaction simulation was performed using MD software and subsequently the applicability…</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>Tracing the Path of Inhaled Nitric Oxide: Biological Consequences of Protein Nitrosylation</strong> - Nitric oxide (NO) is a comprehensive regulator of vascular and airway tone. Endogenous NO produced by nitric oxide synthases regulates multiple signaling cascades, including activation of soluble guanylate cyclase to generate cGMP, relaxing smooth muscle cells. Inhaled NO is an established therapy for pulmonary hypertension in neonates, and has been recently proposed for treatment of hypoxic respiratory failure and acute respiratory distress syndrome due to COVID-19. In this review, we summarize…</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>Enhancement of the IFN-beta-induced host signature informs repurposed drugs for COVID-19</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent for the outbreak of coronavirus disease 2019 (COVID-19). This global pandemic is now calling for efforts to develop more effective COVID-19 therapies. Here we use a host-directed approach, which focuses on cellular responses to diverse small-molecule treatments, to identify potentially effective drugs for COVID-19. This framework looks at the ability of compounds to elicit a similar transcriptional response to…</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>Geranii Herba as a Potential Inhibitor of SARS-CoV-2 Main 3CL(pro), Spike RBD, and Regulation of Unfolded Protein Response: An In Silico Approach</strong> - CONCLUSIONS: Hence, the compounds present in Geranii Herba could be used as possible drug candidates for the prevention/treatment of SARS-CoV-2 infection.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge</strong> - The RNA-dependent RNA polymerase (RdRp) is an essential enzyme for the viral replication process, catalyzing the viral RNA synthesis using a metal ion-dependent mechanism. In recent years, RdRp has emerged as an optimal target for the development of antiviral drugs, as demonstrated by recent approvals of sofosbuvir and remdesivir against Hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively. In this work, we overview the main sequence and…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</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>“AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2.”</strong> - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex.</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>Haptens, hapten conjugates, compositions thereof and method for their preparation and use</strong> - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels.</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>疫苗融合蛋白</strong> - 本申请涉及一种融合蛋白所述融合蛋白包括SARSCoV2抗原多肽和鞭毛蛋白或其片段。本申请还提供了所述融合蛋白的制备方法和用途。本申请所述的融合蛋白能够诱导机体产生针对SARSCoV类病毒的抗原的细胞免疫反应。</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AN EFFICIENT METHODOLOGY TO MANAGE THE ADMISSIONS IN HOSPITALS DURING THE PANDEMICS SUCH AS COVID 19</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种SARS-CoV-2假病毒小鼠体内包装系统及其制备方法</strong> - 本发明提供了一种假病毒小鼠体内包装系统的制备方法包括以下步骤S1基于慢病毒包装质粒系统和睡美人转座子系统构建SARSCoV2假病毒包装质粒系统S2将步骤S1中SARSCoV2假病毒包装质粒系统与睡美人转座酶表达质粒混合通过水动力注射的方式转染小鼠肝细胞然后睡美人转座子系统将SARSCoV2假病毒包装所需序列以剪切粘贴的方式整合到小鼠肝细胞的基因组。本发明可在小鼠体内持续制造分泌SARSCoV2假病毒可模拟靶器官被SARSCoV2病毒持续侵入攻击的过程从而可模拟出新冠肺炎COVID19的病理特征。基于SARSCoV2假病毒小鼠体内包装系统的动物模型安全性高不需要P3级实验室就能开展研究。利用水动力注射的方式引入SARSCoV2假病毒包装质粒系统操作简单成本低。</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>柴胡解毒药物组合物及其制备方法和应用</strong> - 本发明属于中药领域具体涉及一种柴胡解毒药物组合物及其制备方法和应用所述柴胡解毒药物组合物以质量份计由如下原料组分制成柴胡30<sub>60份黄芩15</sub>30份法半夏15<sub>30份生姜15</sub>30份大枣5<sub>10份枳实20</sub>40份大黄10<sub>20份桃仁10</sub>20份白芍15~30份。本发明的柴胡解毒药物组合物能够显著改善普通型COVID19引起的咳嗽能改善疫毒闭肺型重型COVID19引起的咳嗽显著改善疫毒闭肺型重型COVID19引起的胸闷、气短和乏力等主要症状。另外经大量临床观察本发明的柴胡解毒药物组合物能够显著改善疫毒闭肺型重型COVID19引起的发热面红咳嗽痰黄粘少或痰中带血喘憋气促疲乏倦怠口干苦粘大便不畅小便短赤等症状。</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>一种新型冠状病毒RBD核苷酸序列、优化方法与应用</strong> - 本发明公开了一种新型冠状病毒RBD核苷酸序列、优化方法与应用。属于基因工程技术领域。优化步骤1对野生型新型冠状病毒RBD核苷酸序列进行初步优化2将宿主细胞特异性高表达分泌蛋白信号肽序列进行优化3将人IgG1Fc核苷酸序列进行优化4将步骤2优化后的宿主细胞特异性高表达分泌蛋白信号肽核苷酸序列、步骤1得到的初步优化新型冠状病毒RBD核苷酸序列、连接子核苷酸序列和步骤3优化后的人IgG1Fc核苷酸序列依次连接即可。与现有技术相比本发明的有益效果产生的克隆表达效率比野生新型冠状病毒RBD序列提高了约12倍比中国仓鼠密码子偏性优化序列克隆表达效率提高了2倍。</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>ASSISTING COMPLEX FOR TAKING OF BIOMATERIAL FROM MOUTH IN PANDEMIC CONDITIONS</strong> - FIELD: medicine. SUBSTANCE: invention refers to medicine, namely to methods for contactless taking of biomaterial in tested person. Taking the biomaterial in the tested person is carried out in a room located in a dirty zone and separated by a partition from the clean zone, in which there is a laboratory assistant performing the procedure using a robotic complex. Complex includes digital controller, manipulator with tool unit, small manipulator, camera, monitor, control system of digital controller, manipulator, small manipulator, and complex control system. In the partition there are two holes: one for installation and passage of the swab, the other for the test tube installation. In the dirty zone there is a small manipulator having two actuators: one for movement of a test tube with a swab, and the second for positioning and placing a disposable mouthpiece. EFFECT: reduced risk of laboratory assistant and tested person infection by avoiding their direct contact. 17 cl, 1 dwg</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>Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19</strong> -</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></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>Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19</strong> -</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.</p>
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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>Trumps Attacks on Local Officials Are Spreading Hatred and Inciting Violence</strong> - The President is actively subverting the core elements of a peaceful democracy—and yet the response is strangely muted. - <a href="https://www.newyorker.com/news/our-columnists/trumps-attacks-on-local-officials-are-spreading-hatred-and-inciting-violence">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Life and COVID Death of a Revered Siberian Doctor</strong> - In a chaotic and overwhelmed hospital, a physician received the kind of indifferent medical care he spent his life trying to overcome. - <a href="https://www.newyorker.com/news/dispatch/the-life-and-covid-death-of-a-revered-siberian-doctor">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Deadly Cost of Americas Pandemic Politics</strong> - Vaccines are on the way, but until they arrive tens of thousands of lives depend on the battle for public opinion. - <a href="https://www.newyorker.com/science/medical-dispatch/the-deadly-cost-of-americas-pandemic-politics">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How Will We Tell the Story of the Coronavirus?</strong> - Curators at the National Museum of American History were planning an exhibit about pandemics when the virus struck. Now theyre collecting artifacts of the present. - <a href="https://www.newyorker.com/news/annals-of-communications/how-will-we-tell-the-story-of-the-coronavirus">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Britains Vaccine Program Brings Joy and Chauvinism</strong> - Brexit colors a rare bright day in the countrys management of the pandemic. - <a href="https://www.newyorker.com/news/letter-from-the-uk/britains-vaccine-program-brings-joy-and-chauvinism">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>How bad is your states Covid-19 outbreak?</strong> -
<figure>
<img alt="The profile of a person wearing a face mask, with an American flag in the background. " src="https://cdn.vox-cdn.com/thumbor/QsyJD7ZYX6tPU1azFGXpxYCVHOs=/0x0:4480x3360/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/67137721/1213314129.jpg.0.jpg"/>
<figcaption>
A volunteer greets local residents at a food distribution center in New York City on March 18, 2020. | John Moore/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
These maps show how your state is doing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CfP09B">
Americas national <a href="https://www.vox.com/coronavirus-covid19">Covid-19</a> epidemic continues, with the USs daily new cases still higher than most <a href="https://ourworldindata.org/coronavirus-data-explorer?zoomToSelection=true&amp;time=2019-12-31..latest&amp;country=AUS~AUT~BEL~CAN~CYP~CZE~DNK~EST~FIN~FRA~DEU~GRC~ISL~IRL~ISR~ITA~JPN~KOR~LVA~LTU~LUX~MLT~NLD~NZL~NOR~PRT~SMR~SGP~SVK~SVN~ESP~SWE~CHE~TWN~USA~GBR~EuropeanUnion&amp;region=World&amp;casesMetric=true&amp;interval=smoothed&amp;perCapita=true&amp;smoothing=7&amp;pickerMetric=location&amp;pickerSort=asc">developed nations</a> and the country recently surpassing <a href="https://coronavirus.jhu.edu/map.html">287,000 deaths</a> due to the disease.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gu9CQ6">
At the state level, things can look even worse than the national picture.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nSMVtm">
Public health experts look at a few markers to determine how bad things are in each state: the number of daily new cases; the infection rate, which can show how likely the virus is to spread; and the percentage of tests that come back positive, which should be low in a state with sufficient testing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LoLOzb">
A Vox analysis, updated weekly, indicates the vast majority of states report alarming trends across all three benchmarks for coronavirus outbreaks. Most states still report a high — sometimes very high — number of daily new Covid-19 cases. Most still have high infection rates. And most have test positive rates that are too high, indicating they dont have enough tests to track and contain the scope of their outbreaks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D9THKT">
Across these benchmarks, zero states fare well on all three metrics, suggesting no state has its outbreak under control right now. In fact, only one state — Vermont — meets even two of the three benchmarks.
</p>
<figure class="e-image">
<img alt="A map of each states Covid-19 epidemic, based on several metrics." src="https://cdn.vox-cdn.com/thumbor/-CLLyqbueBd8JLiElKWvG7vYwQ8=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22157783/Covid_epidemics_states_map.png"/>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KDuXOT">
One caveat: States are still catching up on backlogs as a result of Thanksgiving, which led to widespread underreporting of Covid-19 tests and cases. That could skew the numbers a bit this week — but likely not enough to alter the overall conclusions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MiZrHO">
Americas outbreaks, reaching from <a href="https://www.vox.com/future-perfect/2020/7/6/21308351/california-coronavirus-pandemic-covid-outbreak">California</a> to <a href="https://www.vox.com/future-perfect/2020/7/17/21324398/florida-coronavirus-covid-cases-deaths-outbreak">Florida</a>, are the result of the public and the countrys leaders never taking the virus seriously enough and, to the extent they did, letting their guard down prematurely. States, with the support of President Donald Trump, moved to reopen — often before they saw sizable drops in daily new Covid-19 cases, and at times so quickly they didnt have time to see if each phase of their reopening was leading to too many more cases.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y0kqr0">
The public embraced the reopenings, going out and often not adhering to recommended precautions like physical distancing and <a href="https://www.vox.com/future-perfect/21299527/masks-coronavirus-covid-19-studies-research-evidence">wearing a mask</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rCZmxX">
Even as cases began to fall later in the summer, Americas overall caseload remained very high. And yet many states moved to reopen once again, with much of the public embracing the looser restrictions and subsequently going out.
</p>
<aside id="LS5Zxw">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0e4Qxs">
Its this mix of government withdrawal and public complacency that experts have cited in explaining why states continue to struggle with getting the coronavirus under control.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oOGJ2h">
“Its a situation that didnt have to be,” Jaime Slaughter-Acey, an epidemiologist at the University of Minnesota, <a href="https://www.vox.com/2020/6/27/21302495/coronavirus-pandemic-second-wave-us-america">told me</a>. “For almost three months, you had opportunities to be proactive with respect to mitigating the Covid-19 pandemic and to help normalize culture to adopt practices that would stem the tide of transmissions as well as the development of Covid-19 complications. … It was not prioritized over the economy.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tXW7tc">
The effects are felt not just in terms of more infections, critical illnesses, new chronic conditions, and deaths, but in the long-term financial impact as the economy struggles, many people still refuse to go out, and businesses resist reopening during a pandemic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kSegNa">
“Dead people dont shop. They dont spend money. They dont invest in things,” Jade Pagkas-Bather, an infectious diseases expert and doctor at the University of Chicago, <a href="https://www.vox.com/future-perfect/2020/7/30/21331369/london-breed-coronavirus-covid-san-francisco-california-trump">told me</a>. “When you fail to invest in the health of your population, then there are longitudinal downstream effects.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AvfgV5">
The benchmarks tracked here by Vox dont cover every important facet of the pandemic. Hospital capacity was previously included among Voxs metrics, but its been removed due to <a href="https://www.sciencemag.org/news/2020/10/inside-story-how-trumps-covid-19-coordinator-undermined-cdc">inconsistent data reporting</a>. The data for <a href="https://www.vox.com/2020/7/29/21345590/covid-19-coronavirus-us-testing-contact-tracing-jobs">contact tracing</a>, when “disease detectives” track down people who may have been infected and push them to quarantine, is also poor. Some measures that are helpful for <a href="https://www.vox.com/2020/5/28/21270515/coronavirus-covid-reopen-economy-social-distancing-states-map-data">gauging whether a state can safely start to reopen</a>, like the total test count and whether cases have fallen in the previous two weeks, are excluded to focus more on the status of each states current Covid-19 outbreak.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4hXwY1">
But together, these three benchmarks help give an idea of how each state is doing in its fight against Covid-19. Nationwide, its pretty grim.
</p>
<h3 id="Dd7N4I">
<ol type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">All 50 states have too many daily new Covid-19 infections
</li></ol></h3>
<figure class="e-image">
<img alt="A map of Covid-19 case rates in each state." src="https://cdn.vox-cdn.com/thumbor/QutvTv9Bl9OFVr1f6dtWtx6_V-0=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22157787/Covid_cases_states_map.png"/>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FXHBBO">
<strong>Whats the goal?</strong> Fewer than four daily new coronavirus cases per 100,000 people per day, based on data from the <a href="https://github.com/nytimes/covid-19-data">New York Times</a> and the <a href="https://www.census.gov/data/tables/time-series/demo/popest/2010s-state-total.html">Census Bureau</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RtG3aH">
<strong>Which states meet the goal?</strong> None.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V2br1A">
<strong>Why is this important?</strong> The most straightforward way to measure whether any place is experiencing a big coronavirus outbreak is to look at the number of daily new Covid-19 cases.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S8VYoo">
Theres no widely accepted metric for how many cases, exactly, is too many. But experts told me that aiming for below four daily new cases per 100,000 is generally a good idea — a level low enough that a state can say its starting to get significant control over the virus.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rpQoMm">
A big caveat to this metric: Its only as good as a states testing. Cases can only get picked up if states are actually testing people for the virus. So if a state doesnt have enough tests, its probably going to miss a lot of cases, and the reported cases wont tell the full story. Thats why its important not to use this benchmark by itself, but to use it alongside metrics like the test positive rate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7qKhoC">
Along those lines, the number of daily new cases may give a delayed snapshot of a Covid-19 outbreak. If test results take a week to get reported to the state, then the count for daily new cases will really reflect the state of the outbreak for the previous week.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mh7TXT">
If testing is adequate in a state, though, the toll of daily new cases gives perhaps the best snapshot of how big a states Covid-19 outbreak is.
</p>
<h3 id="wQEiJj">
<ol start="2" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">The coronavirus is spreading too quickly in most states
</li></ol></h3>
<figure class="e-image">
<img alt="A map of the Rt in each state." src="https://cdn.vox-cdn.com/thumbor/BYRGkxlm7NsYPxznAI6aAYZKMmM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22157802/Covid_Rt_states_map.png"/>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zfocnp">
<strong>Whats the goal?</strong> An effective reproduction number, or Rt, below 1, based on data from <a href="https://rt.live/">Rt.live</a>, a site <a href="https://www.vox.com/recode/2020/4/21/21227855/coronavirus-spreading-by-state-instagram-effective-reproduction-rate">created by two Instagram founders</a> and a data analyst.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bFYgWY">
<strong>Which states meet the goal?</strong> Illinois, Iowa, Minnesota, Montana, New Mexico, North Dakota, South Dakota, Vermont, Washington, Wisconsin, and Wyoming — 11 states.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RBzGtC">
<strong>Why is this important?</strong> The Rt measures how many people are infected by each person with Covid-19. If the Rt is 1, then an infected person will, on average, spread the coronavirus to one other person. If its 2, then an infected person will spread it to two on average. And so on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bPA1oW">
Its an attempt, then, to gauge how quickly a virus is spreading. One way to think about it: Unlike the count for daily new cases, this gives you a snapshot not of a states Covid-19 outbreak today, but of where the outbreak is heading in the near future.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5o19f9">
The goal is to get the Rt below 1. If each infection doesnt lead to another, that would over time lead to zero new Covid-19 cases.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ofyz0C">
The estimated Rt can be very imprecise, with margins of error that make it hard to know for certain in any state if its really above or below 1. Different modelers can also come up with different estimates. Thats, unfortunately, just the reality of using limited data to come up with a rough estimate of a diseases overall spread.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vbh2DC">
The Rt also reflects an average. If 10 people are infected with Covid-19, nine spread it to no one else, and one spreads it to 10, that adds up to an Rt of 1. But it masks the fact that individuals, for whatever reason, can still cause superspreading events — which <a href="https://www.vox.com/21296067/coronavirus-covid-symptoms-superspreaders-superspreading-contagious-bars-restaurants">seem of particular concern with the coronavirus</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z79qcv">
And the Rt is only as good as the data that goes into calculating it. If a states data is poor quality or inconsistent, it might skew the picture. That can help explain why some states with bad and continuing outbreaks may fare better on this benchmark than others.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TIOrWD">
Still, the Rt is one of the better measures we have for tracking a pathogens spread across the whole population. When paired with the other metrics on this list, it can give us a sense of each states outbreak now and in the future.
</p>
<h3 id="yiycKy">
<ol start="3" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Most states positive rates for tests are too high
</li></ol></h3>
<figure class="e-image">
<img alt="A map of the coronavirus test positive rate in each state." src="https://cdn.vox-cdn.com/thumbor/NX4-N95ZfgRNoJXHIxCWqoGRE-A=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/22157811/Covid_positive_rates_map.png"/>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N2yZv8">
<strong>Whats the goal?</strong> Less than 5 percent of coronavirus tests coming back positive over the past week, based on data from the <a href="https://covidtracking.com/data/us-daily">Covid Tracking Project</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="80zaae">
<strong>Which states meet the goal?</strong> Hawaii, Maine, and Vermont — three states. Washington, DC, did as well.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="maem1O">
<strong>Why is this important?</strong> To properly track and contain coronavirus outbreaks, states need to have enough testing. There are all sorts of proposals for how much testing is needed in the US, up to the <a href="https://www.vox.com/2020/4/13/21215133/coronavirus-testing-covid-19-tests-screening">tens of millions</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DyBipc">
But one way to see if a state is testing enough to match its outbreak is the rate of tests that come back positive. An area with adequate testing should be testing lots and lots of people, many of whom dont have the disease or dont show severe symptoms. High positive rates indicate that only people with obvious symptoms are getting tested, so theres not quite enough testing to match the scope of an outbreak.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IHWwbs">
The goal for the positive rate is, in an ideal world, zero percent, since that would suggest that Covid-19 is vanquished entirely. More realistically, in a world going through a pandemic, the positive rate should be below 5 percent. But even if a state reaches 5 percent, experts argue it should continue trying to push that number further down — to match nations like <a href="https://ourworldindata.org/grapher/number-of-covid-19-tests-per-confirmed-case">Germany, New Zealand, and South Korea</a> that have gotten their positive rates below 3 percent and even 1 percent — in order to truly get ahold of their outbreaks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FHaY0P">
As long as a state is above 5 percent, chances are its still missing a significant number of Covid-19 cases. And the higher that number is, the more cases that are very likely getting missed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iJOYn9">
So even if your state is reporting a low number of daily new cases, a high positive rate should be a cause for alarm — a sign that theres an outbreak thats only hidden due to a lack of testing. And if your state is reporting a high number of daily new cases <em>and</em> a high positive rate, thats all the more reason for concern, suggesting the epidemic is even worse than the total case count indicates.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XL1e7U">
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RBRwjt">
</p></li>
<li><strong>How to make this winter not totally suck, according to psychologists</strong> -
<figure>
<img alt="Illustration of a girl at night." src="https://cdn.vox-cdn.com/thumbor/VGzYbjVk5ewV45hkjXMXMS6mym0=/25x0:5593x4176/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/67630049/girl_winter_GettyImages_95758653.0.jpg"/>
<figcaption>
Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
This one idea may help you conquer the dread of pandemic winter.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bhxcXc">
Im going to go out on a limb and say youre probably dreading this winter. Its becoming harder to socialize outdoors as the weather gets colder, and another Covid-19 surge has arrived. Many of us are feeling anxious about how were going to make it through the lonely, bleak months ahead.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3v1Cht">
I see a lot of people trying to <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-k/">cope with this anxiety</a> <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-u/">by drumming up one-off solutions</a>. Buy <a href="https://www.nytimes.com/2020/08/15/at-home/coronavirus-fall-patio-furniture.html">a fire pit</a>! Better yet, buy <a href="https://www.npr.org/2020/08/28/906725372/more-space-please-home-sales-booming-despite-pandemic-recession">a whole house</a>!<strong> </strong>Those may be perfectly fine ideas, as far as they go — but Id like to suggest a more effective way to think about reducing your suffering and increasing your happiness this winter.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="referO">
Instead of thinking about the myriad negative feelings you want to avoid and the myriad things you can buy or do in service of that, think about a single organizing principle that is highly effective at generating positive feelings across the board: Shift your focus outward.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vHZK1w">
“Studies show that anything we can do to direct our attention off of ourselves and onto other people or other things is usually productive and makes us happier,” said Sonja Lyubomirsky, a psychology professor at the University of California Riverside and author of <a href="https://www.amazon.com/How-Happiness-Scientific-Approach-Getting/dp/159420148X/ref=tmm_hrd_swatch_0?_encoding=UTF8&amp;qid=&amp;sr=" rel="sponsored nofollow noopener" target="_blank"><em>The How of Happiness: A Scientific Approach to Getting the Life You Want</em></a>. “A lot of lifes problems are caused by too much self-focus and self-absorption, and we often focus too much on the negatives about ourselves.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jIrft0">
Rather than fixating on our inner worlds and woes, we can strive to promote what some psychologists call “small self.” Virginia Sturm, who directs the Clinical Affective Neuroscience lab at the University of California San Francisco, <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-o/">defines</a> this as “a healthy sense of proportion between your own self and the bigger picture of the world around you.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PBSYE5">
This easy-to-remember principle is like an emotional Swiss Army knife: Open it up and youll find a bunch of different practices that research shows can<strong> </strong>cut through mental distress. Theyre useful anytime, and might be especially helpful during the difficult winter ahead (though theyre certainly no panacea for broader problems like mass unemployment or a failed national pandemic response).
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The practices involve cultivating different states — social connectedness, a clear purpose, inspiration — but all have one thing in common: They get you to focus on something outside yourself.
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A sense of social connectedness
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Some of the practices are about cultivating a sense of social connectedness. <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-b/">Decades of psychology research</a> have taught us that this is <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-n/">a key to happiness</a>.
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In fact, Lyubomirsky said, “I think it is <em>the</em> key to happiness.”
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Thats what <a href="https://www.adultdevelopmentstudy.org/">Harvards Study of Adult Development</a> discovered by following the lives of hundreds of people over 80 years, from the time they were teenagers all the way into their 90s. The massive longitudinal study revealed that the people who ended up happiest were the ones who really leaned into good relationships with family, friends, and community. Close relationships were better predictors of long and pleasant lives than money, IQ, or fame.
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Psychiatrist George Vaillant, who led the study from 1972 to 2004, summed it up like so: “The key to healthy aging is relationships, relationships, relationships.”
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Other studies have found evidence that social connections boost not only our mental health but also our physical health, helping to combat everything <a href="https://greatergood.berkeley.edu/topic/social_connection/definition#why-practice-social-connection">from memory loss to fatal heart attacks</a>.
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During our pandemic winter, you can socialize in person by, yes, gathering around a fire pit or maybe <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-p/">doubling your bubble</a>. But there are other ways to make you feel youre connected to others in a wider web. A great option is to perform an act of kindness — like donating to charity, or volunteering to read to a child or an older person online.
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“I do a lot of research on kindness, and it turns out people who help others end up feeling more connected and become happier,” Lyubomirsky told me.
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<a href="https://www.researchgate.net/publication/237624016_Boosting_Happiness_Buttressing_Resilience_Results_from_Cognitive_and_Behavioral_Interventions">Lyubomirskys research</a> shows that committing any type of kind act can make you happier, though you should choose something that fits your personality (for example, if you dont like<strong> </strong>kids, then reading to them might not be for you). You may also want to vary what you do, because once you get used to doing something, you start taking it for granted and dont get as much of a boost from it. By contrast, people who vary their kind acts show an increase in happiness immediately afterward and up to one month later. So you might call to check up on a lonely friend one day, deliver groceries to an older neighbor the next day, and make a donation the day after that.
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A sense of purpose
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Other practices are about cultivating a sense of purpose. Psychologists have found that having <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-x/">a clear purpose</a> is one of the most effective ways to cope with isolation.
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Steve Cole, a researcher at the University of California Los Angeles, studies interventions designed to help people cope with loneliness. Hes found that the ones that work tend to focus not on decreasing loneliness, but on increasing peoples sense of purpose. Recalling one <a href="https://www.changemakers.com/discussions/entries/la-intergenerational-generation-xchange-program">pilot program</a> that paired isolated older people with elementary school kids whom theyre asked to tutor and look out for, <a href="https://www.vox.com/science-and-health/2017/1/30/14219498/loneliness-hurts">Cole told Vox</a>, “Secretly, this is an intervention for the older people.”
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Philosophers have long noted the fortifying effects of a clear sense of purpose. “Nietzsche said if you find purpose in your suffering, you can tolerate all the pain that comes with it,” Jack Fong, a sociologist who researches solitude at California State Polytechnic University, Pomona, <a href="https://www.vox.com/future-perfect/2020/4/11/21212845/how-to-be-alone-coronavirus-quarantine-isolation-solitude">told me</a>. “Its when people dont see a purpose in their suffering that they freak out.”
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Experienced solitaries confirm this. Billy Barr, whos been living alone in an abandoned mining shack high up in the Rocky Mountains for almost 50 years, <a href="https://wamu.org/story/20/04/01/tips-from-someone-with-50-years-of-social-distancing-experience/">says</a> we should all keep track of something. In his case, its the environment. How high is the snow today? What animals appeared this month? For decades, hes been tracking the answers to these questions, and his records have actually <a href="https://www.theatlantic.com/science/archive/2017/01/billy-barr-climate-change/512198/">influenced climate change science</a>.
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Now, he suggests that people get through the pandemic by participating in a citizen science project such as <a href="https://www.cocorahs.org/">CoCoRaHS</a>, which tracks rainfall.
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“I would definitely recommend people doing that,” he <a href="https://wamu.org/story/20/04/01/tips-from-someone-with-50-years-of-social-distancing-experience/">told</a> WAMU. “You get a little rain gauge, put it outside, and youre part of a network where theres thousands of other people doing the same thing as you, the same time of the day as youre doing it.” (Notice, again, that this is really about sensing youre part of the larger world around you.)
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Other citizen science projects are looking for laypeople to <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-q/">classify wild animals caught on camera</a> or <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-a/">predict the spread of Covid-19</a>.
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If citizen science isnt your jam, find something else that gives you a sense of purpose, whether its writing that novel youve been kicking around for years, signing up to volunteer with a <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-f/">mutual aid group</a>, or whatever else.
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A sense of inspiration
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Finally, some practices are about cultivating a sense of inspiration — which can take the form of gratitude, curiosity, or awe.
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Regularly feeling gratitude helps protect us from <a href="https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.330.5738&amp;rep=rep1&amp;type=pdf">stress and depression</a>.
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“When you feel grateful, your mind turns its attention to what is perhaps the greatest source of resilience for most humans: other humans,” David DeSteno, a psychology professor at Northeastern University and the author of <a href="https://www.amazon.com/Emotional-Success-Power-Gratitude-Compassion/dp/0544703103/?tag=onpointbooks-20" rel="sponsored nofollow noopener" target="_blank"><em>Emotional Success</em></a>, told me. “By reminding you that youre not alone — that others have contributed to your well-being — it reduces stress.”
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So one thing you can do this winter is try gratitude journaling. This simple practice — jotting down things youre grateful for once or twice a week — has gained popularity over the past few years. But studies show there are <a href="https://greatergood.berkeley.edu/article/item/tips_for_keeping_a_gratitude_journal">more and less effective ways to do it</a>. Researchers say its better to write in detail about one particular thing, really savoring it, than to dash off a superficial list of things. They recommend that you try to focus on people youre grateful to, because thats more impactful than focusing on things, and that you focus on events that surprised you, because they generally elicit stronger feelings of thankfulness.
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Another practice is to write a letter of gratitude to someone. Research shows it significantly increases your levels of gratitude, even if you never actually send the letter. And the effects on the brain can last for months. In one <a href="https://www.ncbi.nlm.nih.gov/pubmed/26746580">study</a>, subjects who participated in gratitude letter writing expressed more thankfulness and showed more activity in their pregenual anterior cingulate cortex — an area involved in predicting the outcomes of our actions — three months later.
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Feeling a sense of curiosity or awe about the world around you is likewise shown to boost emotional well-being.
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“Awe makes us feel like our problems are very trivial in the big scheme of things,” Lyubomirsky said. “The idea that you are this tiny speck in the universe gives you this bigger-picture perspective, which is really helpful when youre too self-focused over your problems.”
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For example, a <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-e/">study recently published in the journal <em>Emotion</em></a> investigated the effects of “awe walks.” Over a period of eight weeks, 60 participants took weekly 15-minute walks outdoors. Those who were encouraged to seek out moments of awe during their walks ended up showing more of the “small self” mindset, greater increases in daily positive emotions, and greater decreases in daily distress over time, compared to a control group who walked without being primed to seek out awe.
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“What we show here is that a very simple intervention — essentially a reminder to occasionally shift our energy and attention outward instead of inward — can lead to significant improvements in emotional wellbeing,” <a href="https://voxcom.cmail19.com/t/d-l-cjkjuc-jytjceij-s/">said</a> Sturm, the lead author.
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So, bottom line: When the world between your two ears is as bleak as the howling winter outside, shifting your attention outward can be powerfully beneficial for your mental health. And hey, even in the dead of winter, a 15-minute awe walk outdoors is probably something you can do.
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<em>If you or anyone you know is anxious, depressed, upset, or needs to talk, there are people who want to help. Text CRISIS to 741741 for free, confidential crisis counseling.</em>
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<a href="https://www.vox.com/future-perfect-newsletter"><em>Sign up for the Future Perfect newsletter</em></a>. <em>Twice a week, youll get a roundup of ideas and solutions for tackling our biggest challenges: improving public health, decreasing human and animal suffering, easing catastrophic risks, and — to put it simply — getting better at doing good.</em>
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<li><strong>Susan Choi talks process, teenagers, and the infamously tricky ending of Trust Exercise</strong> -
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<img alt="" src="https://cdn.vox-cdn.com/thumbor/fCEruHVl1Kf8z3oExs6LMO0rk-4=/200x0:3400x2400/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/68485648/headshots_1605285625916.0.jpg"/>
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Susan Choi, left, and Constance Grady. | Left, Heather Weston. Right, Kainaz Amaria/Vox.
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The author isnt sure how much she believes her own unreliable narrator.
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<em>The Vox Book Club is linking to </em><a href="https://go.redirectingat.com/?id=66960X1516588&amp;xs=1&amp;url=https://bookshop.org/shop/voxbookclub&amp;referrer=vox.com&amp;sref=https://www.vox.com/culture/2020/9/2/21406088/brit-bennett-interview-watch-live-vanishing-half-vox-book-club&amp;xcust=___vx__e_21315900__r_vox.com/vox-book-club__t_w__d" rel="sponsored nofollow noopener" target="_blank"><em><strong>Bookshop.org</strong></em></a><em> to support local and independent booksellers.</em>
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The Vox Book Club spent this very nerve-wracking November leaning into a spirit of uncertainty with Susan Chois twisty, vexing, knife-sharp novel, <a href="https://go.redirectingat.com?id=66960X1516588&amp;xs=1&amp;url=https%3A%2F%2Fbookshop.org%2Fbooks%2Ftrust-exercise%2F9781250231260&amp;referrer=vox.com&amp;sref=https%3A%2F%2Fwww.vox.com%2Fculture%2F22163906%2Fsusan-choi-trust-exercise-interview-vox-book-club" rel="sponsored nofollow noopener" target="_blank"><em>Trust Exercise</em></a>. And at the end of the month, as is tradition, we met up with her on Zoom to get the scoop. Over the course of our conversation, Choi walked us through her writing process, whats so confusing about teenagers as a category, and even a little about how to approach <a href="https://www.vox.com/culture/21579367/trust-exercise-ending-explained-susan-choi"><em>Trust Exercise</em>s infamously tricky ending</a>.
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Check out the video above to watch our full conversation. Ive also collected a few highlights, lightly edited for length and clarity, below.
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If you are still in the mood for reading after all this, the Vox Book Club will be spending December on Tamsyn Muirs <a href="https://go.redirectingat.com?id=66960X1516588&amp;xs=1&amp;url=https%3A%2F%2Fbookshop.org%2Fbooks%2Fgideon-the-ninth%2F9781250313188&amp;referrer=vox.com&amp;sref=https%3A%2F%2Fwww.vox.com%2Fculture%2F22163906%2Fsusan-choi-trust-exercise-interview-vox-book-club" rel="sponsored nofollow noopener" target="_blank"><em>Gideon the Ninth</em></a>. <a href="https://confirmsubscription.com/h/d/533DCA62F59CA120"><strong>Sign up for our newsletter</strong></a> to make sure you dont miss anything in the meantime.
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Now lets talk about trust.
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<strong>Youve said you started working on </strong><em><strong>Trust Exercise</strong></em><strong> as a break from other projects. So when you began doing that work, did you know the way the structure would develop? Or were you more straightforwardly telling this high school romance story?</strong>
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I didnt have any idea how the structure would develop. I didnt even really think of it as a structure that would need to develop because I just was trying to do some writing of any kind to get through the day. The project that I was working on just wasnt going well. And so I think I initially thought, “Maybe this will be a short story.”
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I started putting stuff into a file that I called <em>Trust Exercise</em> from the very beginning. But I didnt think of it as a book or anything, just a space where I could write some stuff. That wasnt the stuff that I wasnt succeeding with, at the time.
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<strong>And so when did that transform into this very structured, very intense project?</strong>
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There were two kind of critical moments where [the project] started changing. One was in the fall of 2016, when I was, again, actively working on something else. These pages had been lying untouched for the better part of the year, maybe a whole year, actually. And a train of angry thoughts that Ive described elsewhere, having to do with the election, ended with me thinking, “I wonder if theres anybody in that story of mine whos as angry as I am right now.” It was this idle thought. But I think that there must have been something else going on at a deeper level.
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A lot of the time with me, writing is happening when Im not aware of it. Im sure its true of all writers. Theres that active time that youre sitting at your keyboard or your desk or whatever and actually trying to put words together. And then theres all this passive time that youre walking around, seemingly doing other things, as far as you can tell. But I think that our minds are at work.
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So that day, I think I must have had this material on my mind without realizing it. Because as soon as I had that thought, my immediate answer was, “I know who it is in the world, that story, whos angry.” I just knew.
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She was this very minor character, who I paid almost no attention to. And the fact that I paid almost no attention to her was part of why I understood that she was angry. I suddenly thought, “Thats exactly why shes angry.” Because youve paid almost no attention to her, and how do you know shes not worthy of being at the center of this book, instead of being a footnote on the edge?
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That was the big moment where the book took that turn that you see it taking now as you read it.
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<strong>I know youve gone back a few times to the academy in your fiction and to the idea of exploring the power disparities between student and teacher. What draws you to exploring that relationship in your fiction?</strong>
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Part of it is that learning and teaching are at the center of my life and always have been. Im the daughter of a professor, and I have spent a lot of time in school. Im a teacher now, and Im really incredibly attached to my role as a teacher. I dont think that Id be a very happy writer if I didnt also teach writing because its very solitary, writing, and it really helps me a lot to be connected with students. So in the same way that Im attached to that educational setting, Im alert all the time to the ways in which it goes wrong.
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Stories like that are always catching my attention: stories of teachers who have been accused of abuse, ways in which students are exploited or just let down. All of us are probably interested in the stories because weve all been a student at some point, if were lucky, but I just paid particular attention to them. And theres so many stories that have been accumulating, even before <a href="https://www.vox.com/metoo">Me Too</a> really shed a harsh light on this. There were so many stories that were coming up constantly about alleged cases of abuse on the part of teachers of their students. And so all of that was going into this file in the back of my brain.
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<strong>One of the things that I think the book captures so well is this experience, as you said, of how weve all been a student. The structure allows you to experience both feeling yourself to be really adult and mature when youre 15, when youre like, “Yes, I know what Im doing.” And then you slip into Karens point of view, and its like, “Oh, no, those are children.” So how do you think about capturing that disparity and the dual sense of having been a kid and feeling like you know everything and, in retrospect, just not knowing anything at all?</strong>
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We have these very layered selves, right? We evolve. Ive just been reading <a href="https://www.vox.com/culture/2019/5/10/18563409/exhalation-ted-chiang-review">Ted Chiang</a>, and in one of his great stories, the narrator speaks of not being the same man as he was in the past, but of being continuous with him. I love that phrase, “continuous with him.” Like, yeah, Im not the same girl I was when I was 15. But Im continuous with her. Were still in close communication.
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What was interesting to me was these situations in which a former student came forward, years or even decades later, to speak out about something that had happened to them when they were young. And often, it was not until they were in middle age, like me, that they were able to articulate what they felt had happened. I was really fascinated by that because I thought, “There are all these different selves that are at work at the same time.” Theres that youthful self that might have felt that it was choosing that situation, or might have felt that it was in control. And then theres this older self that is horrified by what happened. And then theres that youthful self that was actually really injured and that the other youthful self didnt maybe want to acknowledge.
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It was really interesting to me to think about all of the different ways in which we might feel ourselves affected by those situations. And I wasnt consciously thinking, like, “Is there a way that I can capture this in the structure of the story?” But I did want to capture that change that I felt even just generationally, between the ways in which we thought about these things when I was younger and the ways in which we think about them now.
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I have teenage children now. And the things that I assume about whats happening to them in school are very different from the things that I thought were okay when I was a student their same age.
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<strong>Theres such a nice contrast with the kids in this book. Because on the one hand, theyre so much more isolated than the teens of today are. They dont have the internet, they hardly ever leave their town. But on the other hand, they just are assumed to be independent and basically adults in so many ways. Its a very interesting look at how quickly that little slice of life has changed.</strong>
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And also they very much want to be treated like that. I think thats part of the conundrum that Im still always so compelled by. Not in terms of this book, which is for me part of the past, but in terms of the issues of, what are people at this age? Theyre not children. Theyre not adults. They have this enormous intelligence, and often powers of discernment that outstrip those of the adults around them, and at the same time, vastly less life experience. They want to be treated with respect, and we have to treat them with respect. And at the same time, theres a certain amount of sheltering that is required.
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It is really freaking confusing, I have to say, as a parent and just as a human being. And I often wonder if were striking the balance correctly now.
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I had so much independence when I was a teenager, and I think teenagers today have vastly less. I dont know if thats better. And at the same time, I think that I was open to certain situations that I really wasnt ready for. And happily, unlike so many, Ive been really lucky to have emerged unscathed from my teenage years.
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Its a give and take. We need to protect more, and at the same time, not smother and hover and let them become adults.
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<strong>Theres such a jolt when Karen takes over the book and electrifies everything. One of the things that I was surprised worked as well as it did was the way she slips back and forth from first to third person, in the same sentence. That sort of unstable identity and sense of what she wants to tell us. How did you think about that slippage in her voice while you were writing?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qaGexb">
The most honest answer would be that I didnt think about it a lot. Initially, it was part of the voice that came to me. And its weird, but narrative voices, for me, always have to be tuned into. Its really hard for me to make one. Its more like I think about a character for a while, and then I sort of start to hear how they sound. I heard Karen sounding like that pretty early on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="prfdwr">
In fact, the very first line that occurred to me was the very first line in that section. Its something like, “Karen stood outside Skylight Books waiting for her old friend, the author.” And when I heard that, because I did hear it before I wrote it down, I knew that it was Karen narrating herself, in that kind of tongue in cheek, but also kind of bitter, badass way that you might narrate your own day, if you were being sarcastic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n1OBHc">
I knew that Karen was narrating herself, and that she was doing it both to be kind of funny and because she was really angry. And it wasnt until Id written much of that section that I had the sense that Karen objects to the way her story has been told to this point, so now shes telling her story. Which includes narrating her story as if she were an omniscient narrator, observing herself, but also then breaking in and being like, “Its me, Karen. Dont forget, its me, Karen talking about Karen.” So that sense of what it meant that she would switch back and forth between those registers came later. And it was really the sound of it that I heard first.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BMaUpL">
<strong>Since this book came out, </strong><a href="https://www.vox.com/2020/2/5/21079162/karen-name-insult-meme-manager"><strong>the name Karen has picked up a lot of different associations</strong></a><strong>. Do you think that will change how a reader will approach that part of the book now?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wkg9nQ">
I think it really depends on how deeply that reader is already imprinted by the kind of cultural “Karen” idea. You know, Karen who calls the police if youre barbecuing in the park and you happen to be a Black person. Or Karen who goes straight for the manager if she doesnt get the refund that she wants. If you have a lot of those Karens knocking around in your mind already, then its going to be hard not to see this Karen in that light.
</p>
<aside id="WibXR4">
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bu8t5U">
Which, interestingly, almost fits with this Karens character. Because her name isnt Karen. She bears it like a cross. She basically says, “My name never was Karen, but fine. I know that you named me Karen because you wanted to denigrate me.” Thats part of her complaint.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DyJg2C">
Its so funny, because I have nothing against the name Karen. In fact, I know lovely wonderful Karens who are understandably aggrieved by this way in which their name has come to mean now. But I did think it was the kind of name that someone might resent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0rg2so">
<strong>I want to talk a little bit about David, too. In the Sarah section, hes a point-of-view character, and hes very sympathetic and easy to understand. And then by the time we get to Karen, hes kind of calcified into this much darker and less likable character, and you dont get inside his head in the same way. Karen has what seems like a pretty good idea of what hes thinking, but were not in there the way we were with Sarah. So how did you think about that character arc as it developed? </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jPYOnP">
Im not sure Im willing to say that Karen has a pretty good idea of<strong> </strong>what Davids thinking. If I had to choose favorites in the book, which Im glad I dont have to do, I really love Karen. I really love that character. And I find her to be the most believable character emotionally. But I also think that shes very suspect in many of her observations, if not maybe all of them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zh8ccy">
Karen is an interesting problem for me as a reader. Like, I made Karen, and then I was like, “Wow, what a conundrum. I dont know whether to believe a word you say, Karen.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="d6L3w1">
I find her to be emotionally incredibly honest. But that doesnt mean that the way in which she reports on the world is all to be trusted because her emotions are so strong. And one of the things that she hates and resents is the David-Sarah love affair, by which she feels incredibly — not just excluded, but just kind of shown up for the rest of her life. Karen cant get over the fact that when they were young, young people, David and Sarah had this romance that is kind of beyond any romantic experience Karen has ever had. She still resents that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6LGkcu">
Theres this moment when David and Sarah are reunited, and Karen kind of doesnt want to see it. You end up seeing it through the corner of Karens eye. Shes almost not really wanting to acknowledge that something emotionally consequential is happening. So I do think that Karen delivers a highly exaggerated David and Sarah.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9L20Bn">
And then thats one of the things that I wanted the book to sort of trouble the reader with: Are the David and Sarah that we meet through Karen at all fair depictions of David and Sarah? Or are they distorted in the same way that Karen feels Sarah the author distorted Karen the minor character in part one?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZObRsw">
I think its interesting that David is both incredibly, I hope, for readers, compelling, and for me, the author, almost the only redeemable male character in the entire book. David is the character who loves and doesnt prey on anyone. And in a way, if he does become calcified, its because love didnt work out for him. Its not for a darker reason.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zl4oou">
But the other thing that I like is that Karen and David actually do have this bond. Karen doesnt really want to admit it, but David gives her a chance. And that was something that was really important to me too, is that David is the person who gives Karen, knowingly, the chance to be a star on the stage finally, and unknowingly gives her this opportunity to carry out this act of revenge.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vlRoyx">
<strong>So much of what gives this book its power is how elliptically it talks around the trauma at the center, so you have trouble seeing what it is. Do you think that writing around the traumatic experience creates something more emotionally truthful than just sort of straightforwardly being like, “Well, this happened and it was terrible”?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="phB4ox">
I think that theres definitely a lot to be said for the “this happened and it was terrible” school of writing. And I dont know if theres necessarily any way to decide which is more effective. I dont think either is more effective.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zOT3Xh">
In the case of what was going on in this book, I did want to explore going back again to what I keep sort of returning to, which is these real life stories that I was intrigued by, and the delay, always this extremely long delay between the moment at which something happened and the moment at which whoever it was felt able to speak. And I was really interested in that delay. I kept kind of trying to get in there and think like, “Well, whats in that delay?” In large part, this book was about that problem, the problem with what happens when you cant say, “Well, this happened and it was terrible.” And often it is possible to immediately say, “This happened and it was terrible.” But what if you cant?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="I7C3Iw">
<strong>So now were going to open it up to audience Q&amp;A. We have a couple questions about the setting of this book. Jenna asks, “Its in the south and it seems suburban. Is the location intentionally not disclosed?” And then Anonymous says, “As a Houstonian, it seems obvious Houston is the setting.” But theyre curious as to why you hinted so much without wanting to go so far as to name the city.</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WZrB0a">
Houstons my city, and I love Houston. But Im really, really particular about the role of the place in a story. Im really preoccupied by places, and I like writing about places. And I also like writing about settings.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RF40or">
When I say “place,” I mean, like, Chicago. Versus a setting, and by “setting” I mean a kind of place that has a certain kind of influence on its inhabitants. And I want <em>Trust Exercise</em> to happen in a setting, not a place, if that makes sense.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ENy8Wo">
It is very much like Houston, but I didnt want it to be a Houston story, in part because I wanted to broaden that context and explore the things that made me want to write about Houston. Which werent just Houston, but other aspects of Houston that it shares with similar places. Primarily for me, the dichotomy between, say, a Houston and in New York, where I live now — growing up in Houston, there was no mass transit, and the car was the currency. And if you didnt have a car, you didnt have a life until you had a car. I wanted those realities to feel really urgent to the reader, and for Houston not to distract from the fact that thats the way life is in so many places for young people, if theres no mass transit.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ogfFIZ">
I love Houston dearly, but I wanted the things that I was exploring about Houston to also connect the reader to other places. This story could be happening in so many places where theres no mass transit, and where its not a cultural capital, yet. Its not LA, its not New York. And so those young people think, “I have to get out of here to be who I want to be.” And the answer to that feeling is a feeling thats shared by people in a lot of different places.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9713l6">
<strong>We have a few different questions, of course, about </strong><a href="https://www.vox.com/culture/21579367/trust-exercise-ending-explained-susan-choi"><strong>the ending</strong></a><strong>. John says, “Im guessing you dont want to explain every detail, but Id like to hear as much as youre willing to divulge/discuss about the final section. What do you feel we should pay closer attention to about this book? What do you feel most readers miss and might benefit from rereading?”</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wOa9Jz">
I dont know if I can say theres something most readers miss. Ive been awed by the way most readers read this book. Ive felt in the end that I missed things.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0Htpwu">
I have very specific ideas about what happens in the end. I didnt write this book to go, “Who knows! Anything could have happened!” For me, something very specific happened. And there were specific motivations on the parts of various characters to alter or change details to conceal certain aspects of their experiences.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WynF9o">
Readers have argued in favor of other things having happened in this book than what I intended, and their arguments are so convincing and so well grounded that Ive ended up feeling like I missed certain ways in which this book can operate.
</p>
<aside id="BJmhRc">
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</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ERhFVZ">
But I will say, about the ending: Part two unleashes uncertainty about part one. Karen says, “That was all this book that my friend Sarah — who isnt even named that — wrote about us, and she lied.” So then youre like, “Whats true?” But then you spend time with Karen, and Karen challenges her own credibility. As I said, I believe every word that Karen says, but I also believe that Karen is really unreliable. Which is a conundrum.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hzVDsg">
With part three, Ive thought a lot about how to signal to the reader that part three is solid. Part three is on the bedrock of fictional realism as we understand it from novel-reading. When we read novels, we know that theyre made up because theyre novels. But they operate under these conventions that weve all internalized. And one of them is the conventions of realism, in which we conclude that what were reading in the novel is true to the world of that story. I wanted part three to be that in this book, to be the true, conventional realism of the book. Where the reader would arrive there and go, “Oh, for the world of this story and these characters, this is the truth. Its not all of it, but what were seeing is the truth.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Nn44MH">
Claire doesnt know that shes a character in a story. Claires the first person you encounter who is not identified by Karen as being just a bunch of characters in Sarahs book, in part one. Nor are they someone knowingly narrating and trying to set the record straight. Thats Karen in part two. But Claire doesnt know that shes in a story. Just like any movie that you see, where youre like, “Oh, these characters, were supposed to think that this is their life.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TtXtWq">
Thats what I wanted the reader to conclude from part three. I dont know if I succeeded, but that would be my pact about the book. That was what I meant: for the reader to feel in part three that they are peeking through that fourth wall and into a real fictional world.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Sa2PLo">
<a href="https://www.vox.com/culture/2020/12/2/21816296/gideon-ninth-harrow-tamsyn-muir-locked-tomb-trilogy-vox-book-club"><em>Join us in December to discuss </em>Gideon the Ninth</a><em>, and </em><a href="https://confirmsubscription.com/h/d/533DCA62F59CA120"><em>subscribe to the Vox Book Club newsletter</em></a><em> to be sure not to miss anything.</em>
</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>Rahul reveals success secret</strong> - The ODIs and T20Is were a learning curve for us</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>SC relief for associations, clubs</strong> - Says restraint to entertain cases need not continue</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hernan, Le Fondre star for Mumbai City</strong> - The win against Chennaiyin helps the side consolidate its position at the top</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>Champions League | PSG, Basaksehir stage walk-out</strong> - UEFA to open disciplinary case over alleged racial slur</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>Leipzig sends United to Europa League</strong> - Juventus bests Barcelona for Group G honours; Racism rears its ugly head; Lazio makes the grade</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>Defer property tax hike by a year, VCCI urges CM</strong> - Property owners worried about ten-fold rise in outgo</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>Leprosy eradication project yet to gather steam</strong> - Health dept. dragging its feet on programme to detect hidden, untreated cases</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>Haryana Police arrest 16 dreaded criminals</strong> - 3 of them carried bounty on their heads</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>KCR to inaugurate party office, Rythu Vedika in Siddipet today</strong> - 2,400 double bedroom houses to be formally handed over to the poor</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>401 recoveries, 181 COVID-19 cases in Thiruvananthapuram</strong> - Three more deaths take districts total toll to 579</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>Brexit: Boris Johnson in crunch EU trade deal talks in Brussels</strong> - Boris Johnson and the European Commission president try to break deadlock at Brussels dinner.</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>Hundreds of thousands of Russian Covid patients named online by mistake</strong> - An official blames human error for hundreds of Excel spreadsheets being uploaded to the internet.</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>Jacques Jordaens: Baroque masterpiece found in Brussels town hall</strong> - The oldest known version of the Holy Family, hung in a town planning office, was thought a copy.</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 to start research into enhanced soldiers</strong> - A report calls for work on developing implants and other technological improvements.</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>Pfizer/BioNTech vaccine docs hacked from European Medicines Agency</strong> - The EMA, which is assessing two Covid-19 vaccines, launches a “full investigation” after the attack.</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>COVID data manager investigated, raided for using publicly available password</strong> - Not only does the whole state share one password, but its posted publicly. - <a href="https://arstechnica.com/?p=1728641">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pornhub blocks uploads and downloads in crackdown on child-sexual-abuse videos</strong> - Pornhub will only allow uploads by verified users, bans downloads of most videos. - <a href="https://arstechnica.com/?p=1728673">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Physicists solve 150-year-old mystery of equation governing sandcastle physics</strong> - “This came as a big surprise. I expected a complete breakdown of conventional physics.” - <a href="https://arstechnica.com/?p=1728509">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Starship will again attempt a high-altitude flight on Wednesday</strong> - The weather in South Texas is again rather nice. - <a href="https://arstechnica.com/?p=1728634">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two allergic reactions to Pfizer vaccine lead to warning in UK</strong> - People with “significant” history of allergies told to avoid jab. - <a href="https://arstechnica.com/?p=1728676">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Guys, dont install adblock</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I did, and now the hot singles in my area dont want to meet me any more.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Gil-Gandel"> /u/Gil-Gandel </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/k9pcxu/guys_dont_install_adblock/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/k9pcxu/guys_dont_install_adblock/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I asked my partner if I was the only one, shes been with.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She said, “Yes, the others were at least sevens or eights”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/jhutto2"> /u/jhutto2 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/k9o9g5/i_asked_my_partner_if_i_was_the_only_one_shes/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/k9o9g5/i_asked_my_partner_if_i_was_the_only_one_shes/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>For cake day, I wanted to share my grandpas favorite joke when I was growing up: “Wanna hear a dirty joke?”</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
-A man fell in a mud puddle.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wanna hear a clean joke? -The man took a bath with bubbles.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wanna hear a dirtier joke? -Bubbles was the woman next door.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Edit: thank you for my first silver and gold
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Edit 2: I really only expected maybe 1 comment, lol. This really kinda took off. Thanks to you all for the awards and internet points. Thats wild, you guys/gals are awesome.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Viperman22xx"> /u/Viperman22xx </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/k9d3ib/for_cake_day_i_wanted_to_share_my_grandpas/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/k9d3ib/for_cake_day_i_wanted_to_share_my_grandpas/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two Texans are sitting in a small town bar, where one bragged to the other: “You know, I had me every woman in this town, except my mother and my sister.”</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well,” his buddy replied, “between you and me we got em all.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/k9hff4/two_texans_are_sitting_in_a_small_town_bar_where/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/k9hff4/two_texans_are_sitting_in_a_small_town_bar_where/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Three men were flying in a small plane when the engine failed</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
To their disappointment, there were only two parachutes on board. After a couple of minutes of silence, one of the men said:
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Look, guys, I need to take one of the parachutes. Im a single father with three children to feed.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The other two agreed and gave him one of the backpacks. The father put it on and jumped off the falling plane.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“So, its me or you now, eh?”, said one of the two men still on the plane
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Oh, just take a parachute and jump off,” said the other one
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“But then youll die”
</p>
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“Nah, dude, Ill just take the second parachute”
</p>
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“What do you mean? You just gave it to that guy that jumped off”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I gave him the backpack where we kept the food. After all, he said hes got kids to feed.”
</p>
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Edit: for all the critics down in the comments - I havent heard any versions of this joke other than this one, so theres no way Id know that its better with Donald Trump or with a boy scout. Its just an English translation of a random joke I saw in my grandfathers newspaper (yes, English is not my first language).
</p>
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Also, heres the mandatory thank you for all the awards.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/thisistoolong"> /u/thisistoolong </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/k9necp/three_men_were_flying_in_a_small_plane_when_the/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/k9necp/three_men_were_flying_in_a_small_plane_when_the/">[comments]</a></span></p></li>
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