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<title>12 September, 2023</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Nuclearization of maternal support networks in the UK and the US during the COVID-19 pandemic: impact on women’s financial and emotional wellbeing</strong> -
<div>
The social isolation resulting from governments’ responses to the COVID-19 pandemic likely limited support available to mothers. Evidence suggests tasks like childcare and domestic work fell disproportionately on mothers during the pandemic, with consequences for their wellbeing. We explore how the pandemic affected emotional and practical support available to mothers between March and August 2020 and whether changes in support are associated with changes in their paid work and mental health. Data were collected in August 2020 from 1528 UK and US mothers with at least one child under 5-years using a cross-sectional survey and are analysed using regression models. Women’s in-person contact with support networks decreased, while virtual interactions increased. Most mothers experienced a ‘nuclearization’ of in-person support: childcare from fathers and siblings increased or remained constant but decreased from the grandparental generation. Women receiving less support during the pandemic had higher odds of reducing participation in paid work. Associations between support and mental health are limited. We also identify women who concurrently experienced reduced support and increased need for help, representing a particularly vulnerable group. The nuclearization of maternal social networks likely increased physical and emotional pressures on the immediate family, risking parental burnout and affecting reductions in female participation in paid labour. There is a need for reliable and affordable childcare options that help reduce women’s burden of unpaid care labour, allowing them to re-enter (or remain in) paid labour.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/ne2kv/" target="_blank">Nuclearization of maternal support networks in the UK and the US during the COVID-19 pandemic: impact on women’s financial and emotional wellbeing</a>
</div></li>
<li><strong>The high infectivity of the SARS-CoV-2 Omicron variant is associated with an exclusive S477N spike receptor-binding domain mutation</strong> -
<div>
The spike glycoprotein receptor-binding domain (RBD) of SARS-CoV-2 facilitates viral binding to the ACE2 receptor and mediates viral infectivity. The Delta and Omicron variants of concern are the most infectious strains, presenting mutated amino acid residues in their spike RBD. The Omicron variant quickly dominated the COVID-19 pandemic, indicating its greater spreadability. Omicron spreading might be associated with mutational substitutions at spike RBD residues. We employed in silico molecular dynamics (MD) simulation of the spike RBD-ACE2 interaction to compare the impact of specific mutations of the Delta and Omicron variants. The MD of the spike-ACE2 interaction showed the following: i) the amino acid profile involved in the spike-ACE2 interaction differs between Delta and Omicron; ii) the Omicron variant establishes several additional interactions, highlighting the spike RBD (S477), which is a flexible mutational residue. Since the S477N mutation is exclusive to Omicron, which may initiate binding with ACE2, the increased infectivity of Omicron might be associated not only with a mutated RBD but also with unmutated (e.g., G476 and L492) residues, initiating binding due to the influence of the N477 mutation. Compared to previous variants, Omicron N477 residue represents a novelty within the spike-ACE2 interaction dynamics interface.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.11.557161v1" target="_blank">The high infectivity of the SARS-CoV-2 Omicron variant is associated with an exclusive S477N spike receptor-binding domain mutation</a>
</div></li>
<li><strong>Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires</strong> -
<div>
Antibodies and helper T cells play important roles in SARS-CoV-2 infection and vaccination. We sequenced B- and T-cell receptor repertoires (BCR/TCR) from the blood of 251 infectees, vaccinees, and controls to investigate whether features of these repertoires could predict subjects' SARS-CoV-2 neutralizing antibody titer (NAbs), as measured by enzyme-linked immunosorbent assay (ELISA). We sequenced recombined immunoglobulin heavy-chain (IGH), TCRbeta (TRB), and TCRdelta (TRD) genes in parallel from all subjects, including select B- and T-cell subsets in most cases, with a focus on their hypervariable CDR3 regions, and correlated this AIRRseq data with demographics and clinical findings from subjects' electronic health records. We found that age affected NAb levels in vaccinees but not infectees. Intriguingly, we found that vaccination, but not infection, has a substantial effect on non-productively recombined IGHs, suggesting a vaccine effect that precedes clonal selection. We found that repertoires' binding capacity to known SARS-CoV-2-specific CD4+ TRBs performs as well as the best hand-tuned fuzzy matching at predicting a protective level of NAbs, while also being more robust to repertoire sample size and not requiring hand-tuning. The overall conclusion from this large, unbiased, clinically well annotated dataset is that B- and T-cell adaptive responses to SARS-CoV-2 infection and vaccination are surprising, subtle, and diffuse. We discuss methodological and statistical challenges faced in attempting to define and quantify such strong-but-diffuse repertoire signatures and present tools and strategies for addressing these challenges.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.08.556703v1" target="_blank">Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires</a>
</div></li>
<li><strong>Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1</strong> -
<div>
The highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential to evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live SARS-CoV-2 neutralization assay to compare the neutralization evasion ability of BA.2.86 with other emerged SARS-CoV-2 subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, and XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 and FL.1.5.1. Our results show that BA.2.86 is less neutralization evasive than XBB sublineages. Among all the tested variants, CH.1.1 exhibits the greatest neutralization evasion. In comparison to XBB.1.5, the more recent XBB descendants, particularly EG.5.1 and FL.1.5.1, display increased resistance to neutralization induced by parental COVID-19 mRNA vaccine and a BA.5-Bivalent-booster. In contrast, XBC.1.6 shows a slight reduction but remains comparable sensitivity to neutralization when compared to BA.5. Furthermore, a recent XBB.1.5-breakthrough infection significantly enhances the breadth and potency of cross-neutralization. These findings reinforce the expectation that the upcoming XBB.1.5 mRNA vaccine would likely boost the neutralization of currently circulating variants, while also underscoring the critical importance of ongoing surveillance to monitor the evolution and immune evasion potential of SARS-CoV-2 variants.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.10.557047v1" target="_blank">Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1</a>
</div></li>
<li><strong>Protocol for primary human lung organoid-derived air-liquid interface in vitro model to study response to SARS-CoV-2</strong> -
<div>
This article presents a comprehensive protocol for establishing primary human lung organoid-derived air-liquid interface (ALI) cultures from cryopreserved human lung tissue. These cultures serve as a physiologically relevant model to study human airway epithelium in vitro. The protocol encompasses lung tissue cryostorage, tissue dissociation, lung epithelial organoid generation, and ALI culture differentiation. It also demonstrates SARS-CoV-2 infection in these cultures as an example of their utility. Quality control steps, ALI characterization, and technical readouts for monitoring virus response are included in the study. For additional details on the use and execution of this protocol, please refer to Diana Cadena Castaneda et al. (https://doi.org/10.1016/j.isci.2023.107374).
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.10.557067v1" target="_blank">Protocol for primary human lung organoid-derived air-liquid interface in vitro model to study response to SARS-CoV-2</a>
</div></li>
<li><strong>Enhanced Omicron subvariant cross-neutralization efficacy of a monovalent SARS-CoV-2 BA.4/5 mRNA vaccine encoding a noncleaved, nonfusogenic spike antigen</strong> -
<div>
The rapid emergence of diverse SARS-CoV-2 variants, notably the Omicron variant, poses challenges to vaccine development. Here, we present a noncleaved, nonfusogenic spike (S) protein eliciting robust B- and T-cell immune responses against Omicron BA.5. The antigen incorporates the R685S and R815A mutations, effectively preventing the shedding of the S1 subunit and eliminating fusogenic activity of the resulting S antigen, termed S(SA). Through reverse genetic analysis, we found that the noncleaved form S protein with the R685S mutation enhances ACE2-dependent viral entry in vitro compared to the wild-type S protein, without increasing the virulence of the mutant virus in mice. The mRNA vaccine encoding the Omicron BA.4/5 S(SA) antigen conferred protective immunity in mice following two doses of 1 ug psi-UTP- or UTP-incorporated mRNA vaccines. Despite a roughly 6-fold reduction in neutralizing potency, both mRNA vaccines exhibited broad neutralizing efficacy against Omicron subvariants, including the XBB lineage variants XBB.1.5 and XBB.1.16.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.10.557088v1" target="_blank">Enhanced Omicron subvariant cross-neutralization efficacy of a monovalent SARS-CoV-2 BA.4/5 mRNA vaccine encoding a noncleaved, nonfusogenic spike antigen</a>
</div></li>
<li><strong>Bayesian phylogenetics on globally emerging SARS-CoV-2 variant BA.2.86 suggest global distribution and rapid evolution</strong> -
<div>
Using bioinformatic pipelines and Bayseian phylogenetic analyses, we characterized a SARS-CoV-2 variant designated by the World Health Organization as a variant under monitoring in August 2023. Here we analyze the genomes of this SARS-CoV-2 variant, BA.2.86, deposited into GISAID within the two weeks of its emergence (2023-08-14 first submission to 2023-08-31), including the first BA.2.86 genome reported from a traveler originating from Japan. We present bioinformatics methods using publicly available tools to help analysts identify the lineage-defining 12 nucleotide insertion (S:Ins16MPLF), which is often masked by most bioinformatics pipelines. We also applied maximum-likelihood and Bayesian phylogenetics to demonstrate the high mutational rate of the tree branch leading to the emergence of BA.2.86, hinting at possible origins, and predict that BA.2.86 emerged around May 2023 and spread globally rapidly. Taken together, these results provide a framework for more rigorous bioinformatics approaches for teams performing genomic surveillance on viral respiratory pathogens.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.08.556912v1" target="_blank">Bayesian phylogenetics on globally emerging SARS-CoV-2 variant BA.2.86 suggest global distribution and rapid evolution</a>
</div></li>
<li><strong>Characterization of SARS-CoV-2 Convalescent Patients’ Serological Repertoire Reveals High Prevalence of Iso-RBD Antibodies</strong> -
<div>
While our understanding of SARS-CoV-2 pathogenesis and antibody responses following infection and vaccination has improved tremendously since the outbreak in 2019, the sequence identities and relative abundances of the individual constituent antibody molecules in circulation remain understudied. Using Ig-Seq, we proteomically profiled the serological repertoire specific to the whole ectodomain of SARS-CoV-2 prefusion-stabilized spike (S) as well as to the receptor binding domain (RBD) over a 6-month period in four subjects following SARS-CoV-2 infection before SARS-CoV-2 vaccines were available. In each individual, we identified between 59 and 167 unique IgG clonotypes in serum. To our surprise, we discovered that ~50% of serum IgG specific for RBD did not recognize prefusion-stabilized S (referred to as iso-RBD antibodies), suggesting that a significant fraction of serum IgG targets epitopes on RBD inaccessible on the prefusion-stabilized conformation of S. On the other hand, the abundance of iso-RBD antibodies in nine individuals who received mRNA-based COVID-19 vaccines encoding prefusion-stabilized S was significantly lower (~8%). We expressed a panel of 12 monoclonal antibodies (mAbs) that were abundantly present in serum from two SARS-CoV-2 infected individuals, and their binding specificities to prefusion-stabilized S and RBD were all in agreement with the binding specificities assigned based on the proteomics data, including 1 iso-RBD mAb which bound to RBD but not to prefusion-stabilized S. 2 of 12 mAbs demonstrated neutralizing activity, while other mAbs were non-neutralizing. 11 of 12 mAbs also bound to S (B.1.351), but only 1 maintained binding to S (B.1.1.529). This particular mAb binding to S (B.1.1.529) 1) represented an antibody lineage that comprised 43% of the individual's total S-reactive serum IgG binding titer 6 months post-infection, 2) bound to the S from a related human coronavirus, HKU1, and 3) had a high somatic hypermutation level (10.9%), suggesting that this antibody lineage likely had been elicited previously by pre-pandemic coronavirus and was re-activated following the SARS-CoV-2 infection. All 12 mAbs demonstrated their ability to engage in Fc-mediated effector function activities. Collectively, our study provides a quantitative overview of the serological repertoire following SARS-CoV-2 infection and the significant contribution of iso-RBD antibodies, demonstrating how vaccination strategies involving prefusion-stabilized S may have reduced the elicitation of iso-RBD serum antibodies which are unlikely to contribute to protection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.08.556349v1" target="_blank">Characterization of SARS-CoV-2 Convalescent Patients’ Serological Repertoire Reveals High Prevalence of Iso-RBD Antibodies</a>
</div></li>
<li><strong>The role of ion dissolution in metal and metal oxide surface inactivation of SARS-CoV-2</strong> -
<div>
Antiviral surface coatings are under development to prevent viral fomite transmission from high-traffic touch surfaces in public spaces. Copper's antiviral properties have been widely documented; but the antiviral mechanism of copper surfaces is not fully understood. We screened a series of metal and metal oxide surfaces for antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19). Copper and copper oxide surfaces exhibited superior anti-SARS-CoV-2 activity; however, level of antiviral activity was dependent upon the composition of the carrier solution used to deliver virus inoculum. We demonstrate that copper ions released into solution from test surfaces can mediate virus inactivation, indicating a copper ion dissolution-dependent antiviral mechanism. Level of antiviral activity is, however, not dependent on the amount of copper ions released into solution per se. Instead, our findings suggest that degree of virus inactivation is dependent upon copper ion complexation with other biomolecules (e.g., proteins/metabolites) in the virus carrier solution that compete with viral components. Although using tissue culture-derived virus inoculum is experimentally convenient to evaluate the antiviral activity of copper-derived test surfaces, we propose that the high organic content of tissue culture medium reduces the availability of "uncomplexed" copper ions to interact with the virus, negatively affecting virus inactivation and hence surface antiviral performance. We propose that laboratory antiviral surface testing should include virus delivered in a physiologically relevant carrier solution (saliva or nasal secretions when testing respiratory viruses) to accurately predict real-life surface antiviral performance when deployed in public spaces.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.08.556901v1" target="_blank">The role of ion dissolution in metal and metal oxide surface inactivation of SARS-CoV-2</a>
</div></li>
<li><strong>Brain infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern is a severe outcome in K18-hACE2 transgenic mice</strong> -
<div>
Background: SARS-CoV-2 is a respiratory virus with neurological complications including loss of smell and taste, headache, and confusion that can persist for months or longer. Severe neuronal cell damage has also been reported in some cases. The objective of this study was to compare the infectivity of Wild-type, Delta, and Omicron variants in transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) receptor under the control of the keratin 18 promoter (K18) and characterize the progression of infection and inflammatory response in the lung and brain of these animals. Methods: K18-hACE2 female mice were intranasally infected with Wild-type, Delta, or Omicron variants and euthanized either at 3 days post-infection (dpi) or at the humane endpoint. None of the animals infected with the Omicron variant reached the humane endpoint and were euthanized at day 8 dpi. Virological and immunological analyses were performed in the lungs, olfactory bulbs, medulla oblongata, and brains. Results: We established that Wild-type, Delta, and Omicron infect the lung and brain of K18-hACE2 mice. At 3 dpi, mice infected with the Omicron variant show lower levels of viral RNA than those infected with Wild-type or Delta in the lung and brain. However, they still demonstrate upregulation of cytokines and chemokines, indicating that the Omicron variant can induce pulmonary and neuronal inflammation despite reduced viral proliferation after infection. At the humane endpoint/8dpi, there is a significant increase in viral RNA in mice infected with the Wild-type or Delta variant brains. However, viral RNA levels in Omicron-infected mice did not increase significantly as compared to 3dpi, and the expression of cytokines and chemokines in the brain, olfactory bulb, and medulla oblongata was downregulated, suggesting that infection by the Omicron variant results in attenuated neuroinflammation as compared with Wild-type and Delta.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.08.556906v1" target="_blank">Brain infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern is a severe outcome in K18-hACE2 transgenic mice</a>
</div></li>
<li><strong>A Bayesian approach to identifying the role of hospital structure and staff interactions in nosocomial transmission of SARS-CoV-2</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Nosocomial infections threaten patient safety, and were widely reported during the COVID-19 pandemic. Effective hospital infection control requires a detailed understanding of the role of different transmission pathways, yet these are poorly quantified. Using patient and staff data from a large UK hospital we demonstrate a method to infer unobserved epidemiological event times efficiently and disentangle the infectious pressure dynamics by ward. A stochastic individual-level, continuous-time state-transition model was constructed to model transmission of SARS-CoV-2, incorporating a dynamic staff-patient contact network as time-varying parameters. A Metropolis-Hastings MCMC algorithm was used to estimate transmission rate parameters associated with each possible source of infection, and the unobserved infection and recovery times. We found that the total infectious pressure exerted on an individual in a ward varied over time, as did the primary source of transmission. There was marked heterogeneity between wards; each ward experienced unique infectious pressure over time. Hospital infection control should consider the role of between-ward movement of staff as a key infectious source of nosocomial infection for SARS-CoV-2. With further development, this method could be implemented routinely for real-time monitoring of nosocomial transmission and to evaluate interventions.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.11.23295353v1" target="_blank">A Bayesian approach to identifying the role of hospital structure and staff interactions in nosocomial transmission of SARS-CoV-2</a>
</div></li>
<li><strong>Comparison of COVID-19 and Influenza-Related Outcomes in the United States during Fall-Winter 2022-2023</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Three years into the pandemic, SARS-COV-2 remains a significant burden in comparison to other respiratory illnesses; however, many of the monitoring tools available during the early phase of the COVID-19 pandemic have been phased out, making it more difficult to track the current burden of outpatient medical encounters and hospitalizations, especially for at-risk groups. The objective of this analysis was to characterize the frequency and severity of medically-attended COVID-19 and influenza during peak influenza activity in the pediatric (0-17), adult (18-64), and older adult (65+) populations and characterize the prevalence of underlying medical conditions among patients hospitalized with COVID-19. Methods: This was a cross-sectional analysis of individuals in the Veradigm Health Insights EHR Database linked to Komodo claims data with a medical encounter of claim between October 1, 2022, and March 31, 2023. We captured age, sex, and underlying medical conditions associated with higher risk for severe COVID-19 during a 12-month baseline period. We identified patients with medical encounters with a diagnosis of COVID-19 or influenza between October 1, 2022, and March 31, 2023, and stratified them into 5 mutually exclusive categories based on the highest level of care received with that diagnosis during the season (intensive care unit [ICU] &gt; hospitalization without ICU &gt; emergency department &gt; urgent care &gt; other outpatient). Results: Among the 23,526,196 individuals in the dataset, 5.0% had a COVID-19-related medical encounter, and 3.0% had an influenza-related medical encounter during the 6 month observation period. The incidence of hospitalizations with a COVID-19 diagnosis was 4.6 times higher than the incidence of hospitalizations with an influenza diagnosis. Hospitalizations with COVID-19 were higher in all age groups. Nearly all adults hospitalized with COVID-19 had at least one underlying medical condition, but 25.8% of 0-5-year-olds and 18.3% of 6-17-year-olds had no underlying medical conditions. Conclusions: COVID-19 continues to place a heavy burden on the United States healthcare system and was associated with more medical encounters in all age groups, including hospitalizations, than influenza during a 6-month period that included the 2022-2023 peak influenza activity.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.08.23295262v1" target="_blank">Comparison of COVID-19 and Influenza-Related Outcomes in the United States during Fall-Winter 2022-2023</a>
</div></li>
<li><strong>A Network Analysis of Molecular Interactions to Study the Development of New-onset Diabetes and Hypertension after COVID-19 Infection Using Bioinformatics Tools.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Introduction: The association between COVID-19 infection and the development of new-onset diabetes and hypertension is an emerging area of research. However, a comprehensive understanding of the underlying molecular mechanisms is still lacking. Network analysis using bioinformatics tools can provide valuable insights into the complex molecular interactions involved in these conditions after COVID-19 infection. Objective: This study aims to use bioinformatics tools to analyze the network of molecular interactions related to new-onset diabetes and hypertension following COVID-19 infection. Methods: Data from publicly available databases were utilized, including gene expression profiles and protein-protein interaction information. Differential expression analysis was performed to identify genes that were differentially expressed in individuals with new-onset diabetes and hypertension after COVID-19 infection compared to healthy controls. A protein interaction network was constructed using bioinformatics tools to explore the functional relationships among the identified differentially expressed genes. Results: The network analysis revealed several key proteins and pathways related to the pathogenesis of new-onset diabetes and hypertension after COVID-19 infection. Notably, proteins involved in insulin signaling, glucose metabolism, inflammation, and blood pressure regulation were found to be prominently associated. The signaling pathway and the renin-angiotensin system were identified as key pathways in this context. Conclusion: This study provides insights by showing a network-based perspective on the molecular interactions involved in the development of new-onset diabetes and hypertension after COVID-19 infection. Keywords: COVID-19 infection, diabetes, hypertension, network analysis, bioinformatics.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.10.23295323v1" target="_blank">A Network Analysis of Molecular Interactions to Study the Development of New-onset Diabetes and Hypertension after COVID-19 Infection Using Bioinformatics Tools.</a>
</div></li>
<li><strong>MEGA: Machine Learning-Enhanced Graph Analytics for Infodemic Risk Management</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The COVID-19 pandemic brought not only global devastation but also an unprecedented infodemic of false or misleading information that spread rapidly through online social networks. Network analysis plays a crucial role in the science of fact-checking by modeling and learning the risk of infodemics through statistical processes and computation on mega-sized graphs. This paper proposes MEGA, <i>M</i>achine Learning-<i>E</i>nhanced <i>G</i>raph <i>A</i>nalytics, a framework that combines feature engineering and graph neural networks to enhance the efficiency of learning performance involving massive graphs. Infodemic risk analysis is a unique application of the MEGA framework, which involves detecting spambots by counting triangle motifs and identifying influential spreaders by computing the distance centrality. The MEGA framework is evaluated using the COVID-19 pandemic Twitter dataset, demonstrating superior computational efficiency and classification accuracy.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.10.24.20215061v6" target="_blank">MEGA: Machine Learning-Enhanced Graph Analytics for Infodemic Risk Management</a>
</div></li>
<li><strong>Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform</strong> -
<div>
Reverse genetic systems enable the engineering of RNA virus genomes and are instrumental in studying RNA virus biology. With the recent outbreak of the COVID-19 pandemic, already established methods were challenged by the large genome of SARS-CoV-2. Herein we present an elaborated strategy for the rapid and straightforward rescue of recombinant plus-stranded RNA viruses with high sequence fidelity, using the example of SARS-CoV-2. The strategy called CLEVER (CLoning-free and Exchangeable system for Virus Engineering and Rescue) is based on the intracellular recombination of transfected overlapping DNA fragments allowing the direct mutagenesis within the initial PCR-amplification step. Furthermore, by introducing a linker fragment (harboring all heterologous sequences) viral RNA can directly serve as a template for manipulating and rescuing recombinant mutant virus, without any cloning step. Overall, this strategy will facilitate recombinant SARS-CoV-2 rescue and accelerate its manipulation. Using our protocol, newly emerging variants can quickly be engineered to further elucidate their biology. To demonstrate its potential as a reverse genetics platform for plus-stranded RNA viruses, the protocol has been successfully applied for the cloning-free rescue of recombinant Chikungunya and Dengue virus.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.11.540343v4" target="_blank">Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform</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>A 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: hAd5-S-Fusion+N-ETSD;   Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>:   ImmunityBio, Inc.<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>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</strong> - <b>Conditions</b>:   Immunosuppression;   COVID-19<br/><b>Intervention</b>:   Biological: NVX-CoV2372<br/><b>Sponsors</b>:   University of Wisconsin, Madison;   Novavax<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome</strong> - <b>Conditions</b>:   Post-COVID-19 Syndrome;   Long-COVID-19 Syndrome<br/><b>Intervention</b>:   Behavioral: Aerobic Exercise Training<br/><b>Sponsors</b>:   University of Witten/Herdecke;   Institut für Rehabilitationsforschung Norderney<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>Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations</strong> - <b>Conditions</b>:   Influenza;   COVID-19;   Influenza Immunogencity;   COVID-19 Immunogenicity<br/><b>Interventions</b>:   Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster);   Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster);   Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)<br/><b>Sponsors</b>:   Duke University;   Centers for Disease Control and Prevention;   Arizona State University;   University Hospitals Cleveland Medical Center;   University of Pittsburgh;   Washington University School of Medicine;   Valleywise Health;   VA Northeast Ohio Health Care;   Senders Pediatrics<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>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>:   Bronchoalveolar Lavage<br/><b>Intervention</b>:   Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>:   Mohamed Abd Elmoniem Mohamed;   Marwa Salah Abdelrazek Ghanem;   Mohammad Khairy El-Badrawy;   Tamer Ali Elhadidy;   Dalia Abdellateif Abdelghany<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1 Study to Assess the Safety, Reactogenicity, and Immunogenicity of a SARS-CoV-2 Booster Vaccine (LEM-mR203) in Healthy Adults</strong> - <b>Conditions</b>:   COVID-19 Infection;   COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>:   Biological: LEM-mR203;   Biological: Placebo<br/><b>Sponsor</b>:   Lemonex<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>Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Intervention</b>:   Biological: B/HPIV3/S-6P<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   Johns Hopkins Bloomberg School of Public Health;   National Institutes of Health (NIH)<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Determine the Tolerability of Intranasal LMN-301</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: LMN-301<br/><b>Sponsor</b>:   Lumen Bioscience, 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>The Effectiveness of Natural Resources for Reducing Stress</strong> - <b>Conditions</b>:   Distress, Emotional;   COVID-19<br/><b>Interventions</b>:   Combination Product: Balneotherapy plus complex;   Combination Product: Combined nature resources treatment;   Other: Nature therapy procedure<br/><b>Sponsors</b>:   Klaipėda University;   Research Council of Lithuania<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID Immune Profiling</strong> - <b>Conditions</b>:   Long COVID;   POTS - Postural Orthostatic Tachycardia Syndrome;   Autonomic Dysfunction<br/><b>Interventions</b>:   Diagnostic Test: IL-6;   Diagnostic Test: cytokines (IL-17, and IFN-ɣ);   Behavioral: Compass 31<br/><b>Sponsors</b>:   Vanderbilt University Medical Center;   American Heart Association<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 Healthy Microbiome, Healthy Mind</strong> - <b>Conditions</b>:   Critical Illness;   COVID-19;   PICS;   Cognitive Impairment;   Mental Health Impairment;   Weakness, Muscle;   Dysbiosis<br/><b>Intervention</b>:   Behavioral: Fermented Food Diet<br/><b>Sponsor</b>:   Mayo Clinic<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Farnesoid X receptor enhances epithelial ACE2 expression and inhibits viral-induced IL-6 secretion: implications for intestinal symptoms of SARS-CoV-2</strong> - CONCLUSION: By virtue of its ability to modulate epithelial ACE2 expression and inhibit virus-mediated pro-inflammatory cytokine release, FXR represents a promising target for development of new approaches to prevent intestinal manifestations of SARS-CoV-2.</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 spike glycans to inhibit SARS-CoV2 viral entry</strong> - SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety…</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>PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell- and tissue-specific manner</strong> - ADP-ribosyltransferases (ARTs) mediate the transfer of ADP-ribose from NAD^(+) to protein or nucleic acid substrates. This modification can be removed by several different types of proteins, including macrodomains. Several ARTs, also known as PARPs, are stimulated by interferon indicating ADP-ribosylation is an important aspect of the innate immune response. All coronaviruses (CoVs) encode for a highly conserved macrodomain (Mac1) that is critical for CoVs to replicate and cause disease,…</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 evaluation of Azvudine in the prospective treatment of COVID-19 based on four phase III clinical trials</strong> - Azvudine (FNC) is a synthetic nucleoside analog used to treat adult patients living with human immunodeficiency virus-1 (HIV-1) infection with high viral load. After phosphorylation, Azvudine inhibits RNA-dependent RNA polymerase, leading to the discontinuation of RNA chain synthesis in viruses. In addition, Azvudine is the first dual-target nucleoside oral drug worldwide to simultaneously target reverse transcriptase and viral infectivity factors in the treatment of HIV infection. On 9 August…</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>Altered DNA methylation underlies monocyte dysregulation and innate exhaustion memory in sepsis</strong> - Innate immune memory is the process by which pathogen exposure elicits cell-intrinsic states to alter the strength of future immune challenges. Such altered memory states drive monocyte dysregulation during sepsis, promoting pathogenic behavior characterized by pro-inflammatory, immunosuppressive gene expression in concert with emergency hematopoiesis. Epigenetic changes, notably in the form of histone modifications, have been shown to underlie innate immune memory, but the contribution of DNA…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In Vivo Antiviral Efficacy of LCTG-002, a Pooled, Purified Human Milk Secretory IgA product, Against SARS-CoV-2 in a Murine Model of COVID-19</strong> - Immunoglobulin A (IgA) is the most abundant antibody (Ab) in human mucosal compartments including the respiratory tract, with the secretory form of IgA (sIgA) being dominant and uniquely stable in these environments. sIgA is naturally found in human milk, which could be considered a global resource for this biologic, justifying the development of human milk sIgA as a dedicated airway therapeutic for respiratory infections such as SARS-CoV-2. In the present study, methods were therefore developed…</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>Cationic Chitosan Derivatives for the Inactivation of HIV-1 and SARS-CoV-2 Enveloped Viruses</strong> - Cationic chitosan derivatives have been widely studied as potential antimicrobial agents. However, very little is known about their antiviral activity and mode of action against enveloped viruses. We investigated the ability of hydroxypropanoic acid-grafted chitosan (HPA-CS) and N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) to inactivate enveloped viruses like the human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 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>Preventive treatment of coronavirus disease-2019 virus using coronavirus disease-2019-receptor-binding domain 1C aptamer by suppress the expression of angiotensin-converting enzyme 2 receptor</strong> - The cause of the worldwide coronavirus disease-2019 (COVID-19) pandemic is the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is known to employ the same entry portal as SARS-CoV, which is the type 1 transmembrane angiotensin-converting enzyme 2 (ACE2) receptor. The receptor-binding domain (RBD) is located on the spike S-protein’s S1 subunit of the spike glycoprotein. The most important and effective therapy method is inhibiting the interaction between the ACE2 receptor and 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>Natural PAK1 inhibitors: potent anti-inflammatory effectors for prevention of pulmonary fibrosis in COVID-19 therapy</strong> - One of the main efforts of scientists to study drug development is the discovery of novel antiviral agents that could be beneficial in the struggle against viruses that cause diseases in humans. Natural products are complex metabolites that are designed and synthesised by different sources in an attempt to optimise nature. Recently, natural products are still a source of biologically active molecules, facilitating drug discovery. A p21-activating kinase PAK1 is a key regulator of cytoskeletal…</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>Nirmatrelvir/ritonavir-induced elevation of blood tacrolimus levels in a patient in the maintenance phase post liver transplantation</strong> - Nirmatrelvir is an orally administered anti-SARS-CoV-2 drug used in combination with ritonavir, the drug-metabolizing cytochrome P450 (CYP) 3A inhibitor, to evade metabolism and extend bioavailability. Meanwhile, the immunosuppressant tacrolimus is a CYP3A4/5 substrate, and CYP3A inhibition results in drug-drug interactions. Herein, we report the case of a coronavirus disease 19 (COVID-19) patient in the maintenance phase post liver transplantation, receiving tacrolimus treatment, with a marked…</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>Comparison of Zinc Oxide Nanoparticle Integration into Non-Woven Fabrics Using Different Functionalisation Methods for Prospective Application as Active Facemasks</strong> - The development of advanced facemasks stands out as a paramount priority in enhancing healthcare preparedness. In this work, different polypropylene non-woven fabrics (NWF) were characterised regarding their structural, physicochemical and comfort-related properties. The selected NWF for the intermediate layer was functionalised with zinc oxide nanoparticles (ZnO NPs) 0.3 and 1.2wt% using three different methods: electrospinning, dip-pad-dry and exhaustion. After the confirmation of ZnO NP…</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>Membrane-Targeting Perylenylethynylphenols Inactivate Medically Important Coronaviruses via the Singlet Oxygen Photogeneration Mechanism</strong> - Perylenylethynyl derivatives have been recognized as broad-spectrum antivirals that target the lipid envelope of enveloped viruses. In this study, we present novel perylenylethynylphenols that exhibit nanomolar or submicromolar antiviral activity against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and feline infectious peritonitis virus (FIPV) in vitro. Perylenylethynylphenols incorporate into viral and cellular membranes and block the entry of the virus into the host cell….</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>Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?</strong> - Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE-AAT) in which the two proteins are covalently bound. The lack of this complex, together with 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>Small Molecules Targeting Viral RNA</strong> - The majority of antivirals available target viral proteins; however, RNA is emerging as a new and promising antiviral target due to the presence of highly structured RNA in viral genomes fundamental for their replication cycle. Here, we discuss methods for the identification of RNA-targeting compounds, starting from the determination of RNA structures either from purified RNA or in living cells, followed by in silico screening on RNA and phenotypic assays to evaluate viral inhibition. Moreover,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Screening, Synthesis and Biochemical Characterization of SARS-CoV-2 Protease Inhibitors</strong> - The severe acute respiratory syndrome-causing coronavirus 2 (SARS-CoV-2) papain-like protease (PL^(pro)) and main protease (M^(pro)) play an important role in viral replication events and are important targets for anti-coronavirus drug discovery. In search of these protease inhibitors, we screened a library of 1300 compounds using a fluorescence thermal shift assay (FTSA) and identified 53 hits that thermally stabilized or destabilized PL^(pro). The hit compounds structurally belonged to two…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Wisconsin G.O.P.’s Looming Judicial Attack</strong> - A state Supreme Court justice—recently elected in a landslide—may be impeached before she ever hears a case. - <a href="https://www.newyorker.com/news/daily-comment/the-wisconsin-gops-looming-judicial-attack">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Narendra Modi’s New New Delhi</strong> - A multibillion-dollar revamp of India’s capital complex reflects the Prime Minister’s vision for the country’s future—and what he wants to erase from its past. - <a href="https://www.newyorker.com/news/dispatch/narendra-modis-new-new-delhi">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can Teachers and Parents Get Better at Talking to One Another?</strong> - Families are more anxious than ever to find out what happens in school. But there may be value in a measure of not-knowing and not-telling. - <a href="https://www.newyorker.com/news/annals-of-education/can-teachers-and-parents-get-better-at-talking-to-one-another">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The U.A.W. Strike Threat Poses a Tricky Political Challenge for Biden</strong> - As the negotiating deadline approaches, the issues at stake go beyond wages and benefits to whether the union’s members will benefit or suffer from the transition to electric vehicles. - <a href="https://www.newyorker.com/news/our-columnists/the-uaw-strike-threat-poses-a-tricky-political-challenge-for-biden">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Real Stakes of the Google Antitrust Trial</strong> - The case, centering on Google’s dominance in the search-engine industry, will have implications that ripple throughout the tech world, and beyond. - <a href="https://www.newyorker.com/news/daily-comment/the-real-stakes-of-the-google-antitrust-trial">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Why Biden isn’t getting a credible primary challenger</strong> -
<figure>
<img alt="Joe Biden walking down airplane steps at night." src="https://cdn.vox-cdn.com/thumbor/JKotKN9ExPEssEfdWAcwwbHVTXo=/688x0:6192x4128/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72638206/GettyImages_1653660608.0.jpg"/>
<figcaption>
US President Joe Biden disembarks from the Air Force One upon his arrival at the airport on the eve of the two-day G20 summit in New Delhi on September 8, 2023. | Saul Loeb/AFP via Getty
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Many Democrats fear a challenge would pave the way to Trump’s victory. Are they right?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pfspfq">
In <a href="https://www.pbs.org/newshour/nation/most-democrats-dont-want-biden-to-seek-a-2nd-term-poll-says">poll</a> after <a href="https://www.axios.com/2023/09/07/poll-biden-2024-second-term-democrat-voters-cnn">poll</a> this year, many and sometimes even <a href="https://www.wsj.com/articles/lack-of-voter-enthusiasm-poses-hurdle-for-joe-bidens-re-election-ee3cfa57">most</a> Democratic voters have said they don’t want <a href="https://www.vox.com/joe-biden">President Joe Biden</a> to be the party’s nominee again in 2024, mainly because of his age. And yet Biden, who isn’t facing a credible primary challenger, seems to have that renomination locked up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Kj8Jfb">
<a href="https://nymag.com/intelligencer/2023/09/why-isnt-a-mainstream-democrat-challenging-biden-2024.html">Jonathan Chait of New York magazine is wondering</a> why that is. “The demand for a different option is robust,” Chait writes. “What is mystifyingly absent is the supply.” In his telling, many politically skilled Democrats, such as Michigan Gov. Gretchen Whitmer and Georgia Sen. Raphael Warnock, could run and have a reasonable shot at defeating Biden and winning the presidency — but they aren’t.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rMHsJK">
On the website formerly known as <a href="https://www.vox.com/twitter">Twitter</a>, many Democrats <a href="https://twitter.com/jonathanchait/status/1700499587394334780/retweets/with_comments">pilloried Chait for his article</a>, but the specific reasons for the pillorying differed in an interesting way. Some <a href="https://twitter.com/moojv77/status/1700560391414120455">argued</a> <a href="https://twitter.com/scarylawyerguy/status/1700518481286881468">that</a> Biden is a strong candidate, basically saying that reports of his political weakness are greatly exaggerated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jlcVAU">
But others simply <a href="https://twitter.com/Will_Bunch/status/1700566568831246565">claimed</a> the process of challenging Biden in a primary would inevitably prove so divisive and damaging that it would help Trump win in 2024. This logic implies that, even if Democrats fear Biden has serious weaknesses, it’s better to stick with him.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dvc0GE">
I think the second argument, while being convenient for Biden’s interests, is likely correct. But rather than take it for granted, it’s worth examining its underlying assumptions in more detail. Why isn’t any credible candidate giving a primary challenge a shot? And what would happen if someone did?
</p>
<h3 id="xRszGZ">
Challenging the incumbent president is a messy process
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pPs0LM">
Primaries are democracy in action: the people (or at least the rather <a href="https://www.vox.com/policy-and-politics/23412858/nevada-question-3-final-five-voting-katherine-gehl">limited, unrepresentative subset</a> of the people willing to turn out for a partisan primary) vote to choose a nominee. Primaries are also often, in practice, messy, expensive, and divisive.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CEmol4">
All incumbents naturally would rather avoid serious primary challenges, for their own interests — that’s one less election to worry about. Parties also frequently try to deter such challenges, in part due to the belief that a cleared field is better for the party’s general election chances, and in part for reasons of control. As a result, credible primaries to incumbents at any level are pretty rare. Potential contenders demur both because these contests are difficult to win and because even trying them means running afoul of the party establishment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GhPAVS">
Incumbent presidents in particular really prefer to avoid primaries, due partly to the messy history of how such contests unfolded in the second half of the 20th century:
</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jNYUEs">
In 1968, LBJ faced challenges from Gene McCarthy and Robert F. Kennedy over the Vietnam War. He soon abandoned his reelection bid, and his vice president, Hubert Humphrey, got the nomination at the convention instead. Humphrey lost in the general election to Richard Nixon.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gsxSJM">
In 1976, Gerald Ford was challenged from the right by Ronald Reagan, who did quite well but ultimately fell short of victory. Ford lost in the general election to Jimmy Carter.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="e8V4Sq">
In 1980, Carter was challenged from the left by Ted Kennedy, who won several states and took his fight to the convention before falling short. Carter lost the general election to Reagan.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fyqEFq">
In 1992, George H. W. Bush was challenged by commentator Pat Buchanan, who didn’t manage to win any states. Bush lost in the general election to Bill Clinton. No president since has faced a credible primary challenge.
</li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xgX5dM">
Except for LBJ, all of these primaried presidents won the primary but lost the general election. That suggests that defeating an incumbent president in the primary is difficult. The conventional wisdom is that it also makes them the party more likely to lose the general election, though that is difficult to prove, since all of these incumbents were primaried because they were already unpopular.
</p>
<h3 id="ECQOsZ">
The Biden- and Trump-specific factors
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uW3q8w">
Of the candidates mentioned above, the one a primary challenge worked out best for is Reagan. He fell short of beating Ford in 1976, but then Ford lost, and Reagan had effectively established himself as the frontrunner for 1980. So in a vacuum, you might think an ambitious Democrat would try to do something similar.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HImh4y">
The difference is that Biden’s general election defeat would not mean installing a Georgia peanut farmer in the presidency, but rather <a href="https://www.vox.com/donald-trump">Donald Trump</a>, whose potential return to power terrifies Democrats.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bcE5D3">
And the risk of being blamed for Trump’s return to power may well be giving many challengers pause. A primary challenge against Biden seems unlikely to succeed but could well result in him limping into the general election wounded. It also basically amounts to an attempted hostile takeover of the Democratic Party, which would likely earn the eternal enmity of that party’s establishment — and perhaps many of the party’s voters, should the challenger get the blame for enabling a Trump victory.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="v5gfa8">
“While rank-and-file voters fret about Biden’s age, experienced pols know a primary would wreck the Democratic Party and ensure a Trump dictatorship in 2025,” <a href="https://twitter.com/Will_Bunch/status/1700566568831246565">Philadelphia Inquirer columnist Will Bunch argues</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MWRTc6">
Chait suggests that a primary against Biden need not be all that divisive — that it could be positively friendly by not being based on issues at all. “The entire campaign message could be that he has performed a valuable service to the country but is getting on in years,” he writes — a sort of <a href="https://knowyourmeme.com/memes/sure-grandma-lets-get-you-to-bed">Sure Grandpa, let’s get you to bed</a> campaign.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BRKeK2">
Yet even if that was the challenger’s approach, it would entail a Democrat validating one of Trump’s biggest critiques of Biden, placing it at the center of <a href="https://www.vox.com/media">the media</a> agenda for months. If the challenger is serious about trying to win, things are unlikely to stay so friendly throughout the contest.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8cyuzy">
If Biden does end up losing to Trump with some sort of age incident playing a major role, there will certainly be much second-guessing about how Democrats drifted into a foreseeable disaster. But the logic seems sound enough. An ambitious Democrat likely thinks waiting for 2028 is preferable to sticking their neck out to challenge Biden, since this year they’d likely lose and may even become a party pariah.
</p></li>
<li><strong>What Vladimir Putin and Kim Jong Un’s meeting might bring</strong> -
<figure>
<img alt="Vladimir Putin and Kim Jong Un, in profile," src="https://cdn.vox-cdn.com/thumbor/E0oIiOWe4MfDaSKRE8pADSkaqEg=/0x0:2915x2186/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72638070/1139381562.0.jpg"/>
<figcaption>
Russian President Vladimir Putin welcomes North Korean leader Kim Jong Un prior to their talks at the Far Eastern Federal University campus on Russky island in the far-eastern Russian port of Vladivostok on April 25, 2019.  | Alexander Zemlianchenko/AFP via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Kim Jong Un left for a Russian economic summit this week, but weapons could be on the table.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fNTQNe">
It’s happening: North Korean dictator Kim Jong Un will meet Russian President Vladimir Putin as part of an <a href="https://www.reuters.com/world/kremlin-says-laos-will-be-top-guest-economic-forum-no-word-nkoreas-kim-2023-09-09/">economic summit in Vladivostok, Russia, this week</a>, a rare public show of diplomacy that could have consequences for both nations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9okc8N">
On <a href="https://www.reuters.com/world/north-koreas-kim-appears-have-departed-russia-summit-with-putin-ytn-2023-09-11/">Monday morning US time</a>, South Korean officials reported that the heavily armored train that Kim uses to travel internationally was s<a href="https://www.reuters.com/world/north-koreas-kim-appears-have-departed-russia-summit-with-putin-ytn-2023-09-11/">potted en route to Russia’s Far East</a>. And Monday, the Kremlin confirmed the meeting, saying in a short statement that Kim would visit “in the coming days.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L3FduR">
As Russia continues its <a href="https://www.vox.com/russia-invasion-ukraine">war in Ukraine</a> and <a href="https://www.vox.com/north-korea">North Korea</a> develops it nuclear arsenal, the possibility of the two autocrats meeting — and what that could mean for their respective military projects — has raised consternation and concern among Western observers. Though it’s a possibility that in exchange for the ammunition and artillery Russia needs it might agree to share nuclear weapons technology with Kim, that’s really a worst-case scenario and not necessarily the likeliest one. Experts say that economic and trade deals, as well as low-level military cooperation agreements, are more likely to accompany any potential ammo purchases.<strong> </strong>Regardless, the meeting could signal the beginning of a<strong> </strong>renewed,<strong> </strong>closer relationship between the two.
</p>
<h3 id="O2jOnT">
What will this meeting look like?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dSx3Ru">
The Soviet Union and, later, Russia have had a relationship with North Korea since its founding. In recent decades, however, the relationship has been much more about public niceties than substance<strong> — </strong>especially after the collapse of the Soviet Union in 1991.<strong> </strong>Kim traveled to Vladivostok in 2019 for a meeting with Putin, but this year’s affair is likelier to yield more public cooperation, and especially military cooperation, between the two pariah nations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="76pe4w">
Officially, this is an economic summit;<strong> </strong>Russia is hosting a multilateral gathering to strengthen economic ties among nations in its orbit, including Laos. Thus far, other details about the Kim-Putin direct meeting have been scarce.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U3h0dP">
So<strong> </strong>one key factor in understanding what comes out of the meeting will be looking at who goes in, said Michael Madden, a non-resident fellow at the Stimson Center. Kim travels with a fairly small entourage when he does leave the country, and there are a few key members of his inner circle in attendance, including his sister <a href="https://www.economist.com/the-economist-explains/2023/08/09/who-is-kim-yo-jong-north-koreas-propagandist-in-chief">Kim Yo Jong</a> who is the de facto head of North Korea’s propaganda department and a key strategic mind in the regime. Kim’s retinue, according to Madden, includes elites like Central Military Commission Vice Chairman Ri Pyong Chol, who essentially oversees North Korea’s defense industry; and Economic Affairs Department Director O Su Yong, who oversees economic affairs including foreign trade and labor contracts.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eQJTd4">
“[Kim’s] travel party to Russia is very heavy with personnel from the military and defense industry,” Madden said. “The most notable person going to Russia is [Korean People’s Army] Navy Commander Adm. Kim Myong Sik,” who last week attended the launch of a submarine which Kim intends to make nuclear-capable. “If we wanted to assume an ‘instant analysis’ perspective then we can say Admiral Kim’s presence means that North Korea will attempt to acquire deeper knowledge on submarines and submarine launched ballistic missiles,” but it could simply mean a reintroduction of port visits that Russian and North Korean military personnel previously conducted.
</p>
<h3 id="CqKmyr">
Should the US be worried about a Putin-Kim confab?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BeCYlr">
It’s of course worth paying attention when leaders of two<strong> </strong>nuclear-armed countries get together in the same room, but this meeting seems to be more of a public acknowledgment of back-channel talks that have been ongoing for some time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mm3AeI">
In the past, Russia has treated North Korea as an obviously junior partner — something that was evident at the last meeting between Kim and Putin in 2019, when the Russian government housed the North Korean delegation in a college dorm rather than a luxury hotel, Bruce Bennett, an adjunct international and defense researcher at the Rand Corporation, told Vox in an interview.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zZnYcQ">
But Russia is in a different position now, with extreme international sanctions impacting its economy and its artillery hitting the battlefield faster than domestic production can keep up. To that end, Sergei Shoigu, the Russian defense minister, <a href="https://www.bbc.com/news/world-asia-66321742">visited Pyongyang in July</a> to attend a military parade and tour a weapons exhibition. Shoigu’s trip was “the first defense ministerial visit in over 10 years that we know of,” Madden said, and its likeliest outcome will be increased visible cooperation between the two militaries.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7ZM41b">
Though specific statistics about North Korea’s military stocks are unknown, it’s one of the most heavily militarized nations on Earth. It reportedly has about six months of artillery and anti-tank weapons built up in case of conflict with South Korea, as Bennett told Vox. But the quality of those weapons is questionable at best. That doesn’t mean Moscow doesn’t want to acquire them — just that it’s not clear how effective they would be on the battlefield if does.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="udZOuq">
Whatever Russia buys, if anything, that information might not become publicly available. Rather, what we might see coming out of the meeting is trade agreements involving dual-use technologies: tech ostensibly created for civilian use that could have military capabilities.<strong> </strong>“It gives [North Korea] a certain degree of plausible deniability,” Madden said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="InEyil">
For North Korea, on the other hand, there are two competing priorities: what Kim wants, and what the nation desperately needs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uu6hdA">
Kim prioritizes the nuclear program as a deterrent and as leverage to get sanctions lifted or at least relaxed, but recent tests have shown that the nuclear program lacks the miniaturization technology to properly weaponize the nuclear technology — unlike US and Russian weapons systems. Though Russia could assist with such technology, Madden said, it’s a bad bet for both sides to share too much information, as nuclear technology is closely guarded even between allies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yICSlY">
Instead, Kim may settle for support that could help address some domestic issues:<strong> </strong>What North Korean people <a href="https://www.38north.org/2023/01/food-insecurity-in-north-korea-is-at-its-worst-since-the-1990s-famine/">need </a>is food and energy, not weapons technology. A UN estimate cited in <a href="https://www.economist.com/asia/2023/03/21/north-koreans-are-at-growing-risk-of-starvation">the Economist </a>indicates that 42 percent of the population was malnourished between 2019 and 2021. Poor <a href="https://www.38north.org/2023/01/food-insecurity-in-north-korea-is-at-its-worst-since-the-1990s-famine/">domestic food production</a> for the past several years is bad enough, but because the regime can’t really export due to sanctions, it doesn’t have the foreign currency to import food and energy stores, either, not to mention the fact that the regime closed the country’s borders during the Covid-19 pandemic, meaning no food could get in.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GPnqAo">
North Korean elites seem to be fed up with Kim’s obsessive spending on nuclear weapons to the detriment of actual basic necessities (and even their luxuries), Bennett said, which is a real threat to the regime. Russia sharing food, oil or direct financial assistance could be<strong> </strong>a place Putin could help. The two countries will likely discuss labor contracts for North Korean workers, which may include military contractors as well.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SPLCRo">
It’s worth <a href="https://twitter.com/johncarlbaker/status/1699119046078173657">America thinking about what these two countries growing closer means</a>. But there are also limits: Though <a href="https://www.vox.com/china">China</a>, Russia, and North Korea cooperate because they’re progressively being shut out of the global economic system, they’re also in competition — Russia and China for global influence and North Korea and China for influence in the region, Bennett said. “You’ve got overlapping imperialist objectives,” Bennett said. “It sounds like their three-sided partnership is a cool thing, but [the] underlying condition is, that might not go so well.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CXZsfU">
A meeting between two men with world-destructive ambitions is hardly a good thing, but it may not be as catastrophic as it initially seems. There is likely to be little trustworthy information about the summit that is made publicly available, so the outcome of these meetings will take time to become visible — but the worst-case scenario is far from the only possibility here.
</p></li>
<li><strong>Wildfire risk is everywhere and growing</strong> -
<figure>
<img alt="Palm trees silhouetted against an orange sky caused by wildfire." src="https://cdn.vox-cdn.com/thumbor/yW6KcRm2lVkgh6aNHWg_rE_FH5g=/397x0:3600x2402/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72638027/1615229307.0.jpg"/>
<figcaption>
This year, wildfires in Maui killed hundreds, marking the deadliest fire in the US in more than a century. Wildfires were once rare in Hawaii, but human activity in recent decades has made them more common and extreme. | Gonzalo Marroquin/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The ingredients for catastrophic wildfires are found in all corners of the country. Here are areas facing increased risk.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WgZsbB">
All a wildfire needs is oxygen, an ignition to spark it, and fuel to burn. Its crackling embers and flickering flames don’t know the difference between the California foothills, where residents are used to fire, and more unexpected locales, like the New Jersey coastline, the Florida peninsula, or the slopes of the Blue Ridge Mountains. As the immense destruction of the fire in Lāhainā, Maui, continues to unfold, experts who study wildfires say the blaze fits a disturbing pattern of fires in the <a href="https://www.usfa.fema.gov/wui/what-is-the-wui.html">wildland-urban interface</a>, where people and homes mingle with burnable vegetation. “Every single state in the US where we have vegetation, and particularly where we have vegetation intermixing with communities, we have the potential for extreme fire disasters,” said Crystal Kolden, a pyrogeographer who studies fire across time and space at the University of California Merced.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HEipzG">
According to researchers and numerous tools mapping wildfire risk, hundreds of cities, towns and communities outside the flammable, arid West that’s known for its wildfires face similarly high risk. The models tell the tale of surprising fire risk for homes near forests, shrublands, prairies, and coastal marshes: They include populated areas in <a href="https://wildfirerisk.org/explore/risk-to-homes/34/">New Jersey’s</a> Manchester and Bass River townships, as well as dollops of development throughout the Eastern coastline that are downwind from over a million acres of pine forests— ripe fuel for fast-moving fires. “That scenario is catastrophic,” said Greg McLaughlin, New Jersey Forest Fire Service chief. “That’s what we plan for.” The state has already seen 13 major wildfires this year, about triple the average.
</p>
<figure class="e-image">
<img alt="A map of areas facing heightened wildfire risk in New Jersey." src="https://cdn.vox-cdn.com/thumbor/sWT_kH2OmNz5QhLXX7HJoRiISes=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24913286/download.png"/> <cite>U.S. Department of Agriculture, U.S. Forest Service, Wildfirerisk.org</cite>
<figcaption>
Populated areas in New Jersey have, on average, greater risk than 55 percent of states in the US.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QXSmrq">
Homes, towns, and reservations in <a href="https://wildfirerisk.org/explore/risk-to-homes/27/">northern Minnesota</a> are also at moderate to very high risk. In the western corner, prairie grasses are often quick to burn; in the east, flammable spruce and conifer forests surround the gateway communities to the Boundary Waters Canoe Area Wilderness like <a href="https://wildfirerisk.org/explore/overview/27/27137/2700019142/">Ely</a>. Risk extends throughout the state to communities just north of the Minneapolis-St. Paul metro area.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="F0UcES">
Other pockets of high and very high fire risk include the Gulf of Mexico near the Texas-Louisiana border, home to flammable coastal vegetation and large swaths of Florida peninsula, where grasses, cattails, and the dense everglades can easily combust. Communities on the eastern, downwind side of the Blue Ridge Mountains in North Carolina and the towns tucked near the heavily forested Appalachian Mountains in southern Kentucky are also surrounded by thick forests and prone to wildfire. Here, there’s precedent: Blazes that started in Great Smoky Mountains National Park swept downwind in 2016 and killed 14 people in Gatlinburg, Tennessee.
</p>
<figure class="e-image">
<img alt="Appalachian wildfire risk. " src="https://cdn.vox-cdn.com/thumbor/MAt07343osdRQd3b8oHuoemx53Q=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24913404/London__Kentucky.png"/> <cite>U.S. Department of Agriculture, U.S. Forest Service. Wildfirerisk.org</cite>
<figcaption>
Southern Kentucky towns are surrounded by dense vegetation and face heightened fire risk.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="t7xXwQ">
Wildfire risk is modeled by combining the likelihood and the intensity of a blaze with an area’s exposure and susceptibility. Widely used models include the US Forest Service’s <a href="https://wildfirerisk.org/">Wildfire Risk to Communities</a>, the Federal Emergency Management Agency’s (FEMA) <a href="https://hazards.fema.gov/nri/wildfire">National Risk Index</a>, and <a href="https://riskfactor.com/">Risk Factor</a>, a model created by the nonprofit First Street Foundation that looks at fire and other climate risks down to the neighborhood and address level. Some models use the same data but parse risk differently, looking at just housing units or also factors like building values and population to determine a final risk. Some models are searchable by address or neighborhood, while others summarize risk at a county or state level.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z79Kmr">
While risk modeling maps aren’t predictive, they can be eerie in hindsight. “Scientifically, physically, we know where these risk regions are,” said Daniel Swain, a climate scientist at the University of California Los Angeles. “And they’re everywhere.” One model says Merryville, Louisiana, where wildfire recently forced a <a href="https://www.kulr8.com/news/national/entire-louisiana-town-evacuated-amid-unprecedented-wildfires/video_4f559429-87a6-5076-a242-7739f6bac987.html#:~:text=Background,-Semi%2DTransparent&amp;text=State%20authorities%20evacuated%20the%20entire,home%20were%20forced%20to%20leave">town-wide evacuation</a>, has a higher wildfire risk than 72 percent of communities in the country; another says the town has a moderate risk of wildfire over the next 30 years. And <a href="https://wildfirerisk.org/explore/overview/15/15009/1500042950/">Lāhainā</a>, for example, had a very high risk of wildfire, more than 92 percent of communities in the country. Now, upward of 115 people are dead and hundreds are still missing. “There are lots of places that are flammable, and there are places that are becoming more flammable, and then there’s places that are becoming more flammable that weren’t on our radar,” said Jennifer Balch, a fire ecologist at the University of Colorado Boulder.
</p>
<h3 id="00Vw8q">
A devastating pattern, worsened by climate change
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="x0zdSA">
While each fire has its own context, a pattern keeps repeating: fast-moving fires that sweep through communities and catch their inhabitants off guard. Strong winds are a common thread between blazes like the <a href="https://www.marshallfiremap.com/">Marshall Fire</a>, a grass fire that destroyed 1,000 homes in Colorado in 2021, the Almeda Fire, which burned 600 homes in southern Oregon in 2020, and the recent fire on Maui. But wind needs to line up with another wildfire risk factor — dry vegetation — to be dangerous. “That really might not happen often at all, barely ever in some places,” Swain said. “But when it does, watch out.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="i7lX7O">
Places with high wildfire risk include coastal areas with vegetation like Phragmites, an invasive wetland grass that’s found throughout the Eastern seaboard and elsewhere, or cogon and sawgrasses, found in the Florida marshes. Invasive species are often adapted to take over landscapes quickly after fire, pushing out native grasses and providing a carpet of especially flammable fuel for the next blaze.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HLu8Ia">
Many ecosystems evolved with fire as a natural element of the landscape, said Allissa Reynolds, the wildfire prevention supervisor for the Minnesota Department of Natural Resources Division of Forestry. But <a href="https://headwaterseconomics.org/natural-hazards/federal-wildfire-policy/">fire suppression</a> <a href="https://www.vox.com/policy">policies</a> and the stifling of Indigenous burning practices limited natural and human-introduced fire in the last century, causing a <a href="https://catalog.extension.oregonstate.edu/em9230/html">buildup</a> of excess fuel.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iPGsYx">
Today, <a href="https://www.nature.com/articles/s41586-023-06444-3">climate change</a> further stacks the deck toward a higher risk of wildfire, even in places that have been traditionally too wet to burn with much frequency or severity. Wet conditions can allow fuels to grow, but heat waves can quickly dry them out. “It’s getting easier and easier for vegetation to dry out to critical levels,” Swain said. Wildfire risk then concentrates in the “driest dry spells and the hottest hot spells,” he said. And risk factors don’t have to line up often to be dangerous if and when they do.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sAanKX">
That’s happening right now in Minnesota, where most of the state is experiencing some level of drought. The state has already seen almost its yearly average of fires, despite fall, a historically active time, still to come. It’s occurring in New Jersey, where an increasing number of fires are happening outside the usual mid-March to mid-May fire season. And it’s underway in the Gulf Coast during hurricane season, where unusual drought and heat at a time that should be wet are fueling over 600 fires burning in <a href="https://www.vox.com/climate/2023/8/30/23852363/louisiana-wildfires">Louisiana</a>, including the largest fire in recorded state history. “While we’re pretty good and practiced at emergency response, not so much on the wildfires,” Louisiana Gov. John Bel Edwards told <a href="https://www.cbsnews.com/news/louisiana-tiger-island-fire-largest-wildfire-states-history-doubles-in-size/">CBS News</a>.
</p>
<h3 id="OzqmZx">
When flames meet homes<strong> </strong>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BqZBoS">
Between 1992 and 2015, 1 million homes were within the perimeter of a wildfire and almost 59 million more were within roughly half a mile, according to one <a href="https://www.mdpi.com/2571-6255/3/3/50#:~:text=During%20the%20study%20period%20(1992,see%20methods%20for%20accuracy%20assessment).">study</a>. While there’s been <a href="https://www.pnas.org/doi/10.1073/pnas.1718850115">increasing development</a> in the wildland urban interface in recent years — to the tune of more than 32 million residential homes — new homes aren’t the whole story. “That’s a broad generalization that I don’t think adequately captures the scale of risks that we’re seeing,” said Kimiko Barrett, a research and policy analyst at Headwaters Economics, a research organization in Montana.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YON7BV">
Economics play a role here, too: Rising housing costs mean more populations priced out of urban areas find more affordable housing in the nearby shrubs and woodlands that pose more wildfire risk. “Suggesting that people just shouldn’t keep building out there is a really privileged viewpoint that ignores why people move to the fringes of these areas,” Kolden said. Plus, many Indigenous settlements would be considered to be in the wildland urban interface today, by modern definitions. “People have been living at moderate densities in fire-prone places for a long time,” said Chris Roos, an environmental archaeologist. Tribes used and continue to use fire to steward and manage the land, often lighting many small fires to improve hunting and gathering opportunities as well as lower their wildfire risk.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YvGoXC">
But wildfires that continue to torch communities prompt questions of not just where we live but how we prepare. “It’s tragic that we don’t currently have this larger education about what to do in a no-notice evacuation event, what to do if you get caught by a wildfire,” Kolden said. Fire-prone areas are already working to mitigate their risk and develop evacuation plans for the worst-case scenario. Members of the Forest Service, land management agencies, local fire departments, and county emergency managers are sitting down throughout Minnesota and the rest of the country to create community wildfire protection <a href="https://www.usfa.fema.gov/downloads/pdf/publications/creating_a_cwpp.pdf">plans</a>; the process opens the door to federal funding that can pay for things like creating fuel breaks and turning yard waste into wood chips. Prescribed burning that targets areas with an accumulation of vegetation is a priority in New Jersey, and an almost 1,400 acre thinning <a href="https://www.nj.gov/dep/parksandforests/forest/allenroad/">project</a> in the Bass River State Forest is slated to start in September, with the goal of removing excess fuel.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xmUNFe">
It will also take investment in urban environments — like retrofitting old homes with fire-resistant building materials and creating building codes for new development — to curb the wildfire crisis and lessen risk, Barrett said. “The inertia of the political system and us as a society continue to believe we can get through this wildfire crisis if we just focus on the forest and the wild lands,” she said. Wildfire isn’t just a Western problem or a forest problem or a rural problem. Given the right combination of factors, wildfire can occur where you least expect it — in suburbia or in the former capital of the Hawaiian Kingdom.
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>All about ‘800’: Muthiah Muralidharan and actor Madhurr Mittal on the cricketing biopic</strong> - As he awaits the release of his biopic ‘800,’ Sri Lankan cricketing legend Muthiah Muralidharan goes down memory lane, discussing growing up in Kandy where he developed his unique bowling technique</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>Daily quiz | On September 12, 2023</strong> - A quiz on the singles Grand Slam career of Novak Djokovic who won the US Open on Sunday to equal Margaret Court’s record of 24 Major titles</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>Rohit Sharma completes 10,000 ODI runs, second fastest after Kohli</strong> - Virat Kohli who scored fastest 13,000 runs in ODIs was the fastest to cross the milestone.</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>Women’s Asian Champions Trophy: India to begin campaign against Thailand on Oct 27</strong> - The Asian Champions Trophy will see Korea, Malaysia, Thailand, Japan, China, and India go into battle to lift the coveted trophy.</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>Asia Cup 2023 | Sri Lanka vs India | India opts to bat against Sri Lanka in Super 4 match</strong> - While Sri Lanka are playing unchanged XI, India brought in Axar Patel in place of Shardul Thakur.</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>Union Health Minister Mansukh Mandaviya confirms two Nipah virus deaths in Kerala</strong> - Mr. Mandaviya said a central team of experts has been sent to Kerala to take stock of the situation and assist the State government in the management of the Nipah virus 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>Watching porn in one’s privacy not an offence under Section 292 of IPC: HC</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>SGOU approves the curriculum framework for four-year UG programmes</strong> - A student who successfully completes three years will get a graduation certificate. Forty four more credits are required for the fourth year and on successful completion, an honours degree or an honours with research degree will be awarded</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>Sanatana Dharma row | Will pull out tongue and gouge out eyes: Union Minister Shekhawat on Udhayanidhi’s comments</strong> - On September 2, Udhayanidhi Stalin, son of Tamil Nadu Chief Minister M.K. Stalin, alleged that the Sanatana Dharma is against equality and social justice, and that it should be eradicated</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>Most Indians who consume news online like to watch, not read | Data</strong> - In India, the role of mobile news aggregators as primary news sources is on the rise</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>Putin and Kim: Friends in need (of ammunition)</strong> - Russia needs weapons. N Korea has weapons. It’s a match made in the geo-political realities of 2023.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why mobile saunas are being sent to Ukraine’s front line</strong> - The Ukraine war has put Russia’s nervous neighbours on high alert, reports Europe editor Katya Adler.</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>Venice to back €5 fee for day-trip tourists</strong> - The charge - which will apply to all visitors aged over 14 - is designed to tackle soaring tourism.</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>Stolen Van Gogh handed to Dutch art sleuth in Ikea bag</strong> - Arthur Brand met an unnamed man under a tree during a mysterious, years-long quest to find the work.</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>Soviet invasions of Hungary and Czechoslovakia were wrong, Putin says</strong> - Russian President Vladimir Putin also said that the West has ‘no friends, only interests’.</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>FDA approves and authorizes updated COVID boosters for everyone 6 months and up</strong> - The fall boosters target XBB.1.5 and have shown effective against current variants. - <a href="https://arstechnica.com/?p=1967187">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Top-end Roomba can now refill itself with water via furniture-sized dock</strong> - The do-it-all dock has a faux wood top, making it look like a small table. - <a href="https://arstechnica.com/?p=1967124">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Unearthed touchscreen iMac G3 prototype evokes a very different era of Apple</strong> - 25 years ago, Apple was cool with firms hacking up kiosk-friendly touch iMacs. - <a href="https://arstechnica.com/?p=1967015">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Genesis Electrified GV70 is a truly luxurious electric SUV</strong> - It’s quick, comfortable, and almost silent. And it fast-charges in 18 minutes. - <a href="https://arstechnica.com/?p=1967090">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Scientists figured out how to write in water</strong> - German physicists used an ion-exchange microbead as a very tiny “pen.” - <a href="https://arstechnica.com/?p=1966985">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>The parish priest needs his house painted so he offers the job to one of his altar boys. The first day the kid paints the entire inside of the house, he’s sweating like hell but eventually gets it finished. The priest commends him on the work and with a flourish hands him a £5.00 note.</strong> - <!-- SC_OFF --></p>
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The boy looks at the money and says to the priest, “Thanks very much Father,…you’re a virgin.” The priest is a bit startled but makes no remark.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The next day the boy has to paint the outside of the house; it’s a really hot day and he just manages to finish the job without collapsing. The priest looks at the job and this time gives the lad another £5.00 note. Once again the lad looks at the money and says, “Thanks very much Father, you really are a virgin.” At this stage the priest decides to take action. “Tommy,” he says, “that’s twice you’ve called me a virgin. Do you have any idea what the word means?” “Yes,” says the kid, “a tight cunt.”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16g7v5t/the_parish_priest_needs_his_house_painted_so_he/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16g7v5t/the_parish_priest_needs_his_house_painted_so_he/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An old man decides he wants to meet his grandson before he dies</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He lives in the wilderness like a hermit so he hardly ever meets anyone. So he invites his young grandson over to mark one item off his bucket list. His grandson arrives and notices his grandfather is scarred all over and missing some of his limbs, most noticeably one of his hands.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“How did you lose your hand?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“A lion bit it off during one of my hunting trips. Speaking of that, I was an avid hunter and have an impressive trophy room, let me show you”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The grandfather leads his grandson to his trophy room. It is filled with large animal heads mounted on the walls. The boy is in awe of all the different animals.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“There are lots of stories to tell with some of these , several even attacked me before I managed to kill them. This leopard here? Its name is Eerie. I named it that because it bit off my ear. I generally like to name them after something they took from me so I remember our encounter better”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
As the boy looks around from animal to animal, he starts to ask about the stories behind them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What about that great big Crocodile? Does that one have a story?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Yes, it took several of my toes, so I named it Toto”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What about this Tiger?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“It took my eye, so it is named Iris”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Then the boy’s eyes are caught by an enormous lion, the most majestic trophy of them all.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“That must be the Lion that took your hand! Did you name it Hans?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Good guess, but no, I named it Hancock”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/RainierxWolfcastle"> /u/RainierxWolfcastle </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16gha80/an_old_man_decides_he_wants_to_meet_his_grandson/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16gha80/an_old_man_decides_he_wants_to_meet_his_grandson/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kinky sisters……..</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A bus full of Nuns falls of a cliff and they all die.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They arrive at the gates of heaven and meet St. Peter. St. Peter says to them "Sisters, welcome to Heaven.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In a moment I will let you all though the pearly gates, but before I may do that, I must ask each of you a single question. Please form a single-file line." And they do so.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
St. Peter turns to the first Nun in the line and asks her “Sister, have you ever touched a penis?” The Sister Responds “Well… there was this one time… that I kinda sorta… touched one with the tip of my pinky finger…”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
St. Peter says “Alright Sister, now dip the tip of your pinky finger in the Holy Water, and you may be admitted.” and she did so.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
St. Peter now turns to the second nun and says “Sister, have you ever touched a penis?” “Well…. There was this one time… that I held one for a moment…”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Alright Sister, now just wash your hands in the Holy Water, and you may be admitted” and she does so.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Now at this, there is a noise, a jostling in the line. It seems that one nun is trying to cut in front of another!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
St. Peter sees this and asks the Nun “Sister Susan, what is this? There is no rush!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Sister Susan responds “Well if I’m going to have to gargle this stuff, I’d rather do it before Sister Mary sticks her ass in it!”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MercyReign"> /u/MercyReign </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16gcfv7/kinky_sisters/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16gcfv7/kinky_sisters/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My wife likes it when I blow air on her when she’s hot…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
but honestly… I’m not a fan.
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/TheQuietKid22"> /u/TheQuietKid22 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16giret/my_wife_likes_it_when_i_blow_air_on_her_when_shes/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16giret/my_wife_likes_it_when_i_blow_air_on_her_when_shes/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What do you call an impatient man from Bangkok who moved to the capital city of the Republic of China for a writing job, got kidnapped, covered in multicolored paint and restrained with rope?</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A tied-up, tye-dyed, Type-A, Taipei-Thai typist.
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/RiRikkulous"> /u/RiRikkulous </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16gmk99/what_do_you_call_an_impatient_man_from_bangkok/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16gmk99/what_do_you_call_an_impatient_man_from_bangkok/">[comments]</a></span></p></li>
</ul>
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