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<title>13 February, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Efficacy of Host Cell Serine Protease Inhibitor MM3122 against SARS-CoV-2 for Treatment and Prevention of COVID-19</strong> -
<div>
We have developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases including TMPRSS2, matriptase and hepsin. TMPRSS2 is a membrane associated protease which is highly expressed in the upper and lower respiratory tract and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell receptor binding, entry, replication, and dissemination of new virion particles. We have previously shown that compound MM3122 exhibited subnanomolar potency against all three proteases and displayed potent antiviral effects against SARS-CoV-2 in a cell-viability assay. Herein, we demonstrate that MM3122 potently inhibits viral replication in human lung epithelial cells and is effective against the XBB.1.5 and EG.5.1 variant of SARS-CoV-2. Further, we have evaluated MM3122 in a mouse model of COVID-19 and have demonstrated that MM3122 administered intraperitoneally (IP) before (prophylactic) or after (therapeutic) SARS-CoV-2 infection had significant protective effects against weight loss and lung congestion, and reduced pathology. Amelioration of COVID-19 disease was associated with a reduction in pro-inflammatory cytokines and chemokines production after SARS-CoV-2 infection. Prophylactic, but not therapeutic, administration of MM3122 also reduced virus titers in the lungs of SARS-CoV-2 infected mice. Therefore, MM3122 is a promising lead candidate small molecule drug for the treatment and prevention of infections caused by SARS-CoV-2 and other coronaviruses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.09.579701v1" target="_blank">Efficacy of Host Cell Serine Protease Inhibitor MM3122 against SARS-CoV-2 for Treatment and Prevention of COVID-19</a>
</div></li>
<li><strong>FABP4 as a Therapeutic Host Target Controlling SARS-CoV2 Infection</strong> -
<div>
Host metabolic fitness is a critical determinant of infectious disease outcomes. In COVID-19, obesity and aging are major high-risk disease modifiers, although the underlying mechanism remains unknown. Here, we demonstrate that fatty acid binding protein 4 (FABP4), a critical regulator of metabolic dysfunction in these conditions, regulates SARS-CoV2 pathogenesis. Our study revealed that elevated FABP4 levels in COVID-19 patients strongly correlate with disease severity. In adipocytes and airway epithelial cells we found that loss of FABP4 function by genetic or pharmacological means impaired SARS-CoV2 replication and disrupted the formation of viral replication organelles. Furthermore, treatment of infected hamsters with FABP4 inhibitors alleviated lung damage and fibrosis and reduced lung viral titers. These results highlight a novel host factor critical for SARS-CoV2 infection and the therapeutic potential of FABP4-targeting agents in treating COVID-19 patients.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.10.579717v1" target="_blank">FABP4 as a Therapeutic Host Target Controlling SARS-CoV2 Infection</a>
</div></li>
<li><strong>Pathways in the brain, heart, and lung influenced by SARS-CoV-2 NSP6 and SARS-CoV-2 regulated miRNAs: an in silico study hinting cancer incidence</strong> -
<div>
The influence of SARS-CoV-2 non-structural protein in the host's tissue-specific complexities remains a mystery and needs more in-depth attention because of COVID-19 recurrence and long COVID. Here we investigated the influence of SARS-CoV-2 transmembrane protein NSP6 (Non-structural protein 6) in three major organs - the brain, heart, and lung in silico. To elucidate the interplay between NSP6 and host proteins, we analyzed the protein-protein interaction network of proteins interacting with NSP6 interacting proteins. Reported host interacting partners of NSP6 were ATP5MG, ATP6AP1, ATP13A3, and SIGMAR1. Pathway enrichment analyses provided global insights into biological pathways governed by differentially regulated genes in the three tissues after COVID-19 infection. Hub genes of tissue-specific protein interactome were analysed for drug targets and many were found. miRNA-gene network for the tissue-specific regulated proteins was sought. Comparing this list with the gene list targetted by SARS-CoV-2 regulated miRNAs, we found three and two common genes in the brain and lung respectively. Among the five common proteins revealed as potential therapeutic targets across the three tissues, four non-approved drugs and one approved drug could target Galectin 3 (LGALS3) and AIFM1 respectively. Increased expression of LGALS3 (that was upregulated in the heart after COVID-19 infection) is observed in multiple cancers and acts as a modulator for tumor progression. COVID-19 infection also causes myocardial inflammation and heart failure (HF). HF is observed to be increasing cancer incidence. The present scenario of long COVID-19 and recurrent COVID-19 infections warrants in-depth studies to probe the effect of COVID-19 infection on increased cancer incidence.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.11.578752v1" target="_blank">Pathways in the brain, heart, and lung influenced by SARS-CoV-2 NSP6 and SARS-CoV-2 regulated miRNAs: an in silico study hinting cancer incidence</a>
</div></li>
<li><strong>Generative artificial intelligence performs rudimentary structural biology modelling</strong> -
<div>
Natural language-based generative artificial intelligence (AI) is increasingly used by researchers in numerous fields, including the biological sciences. To date, the most commonly used tool grounded in this technology is Chat Generative Pre-trained Transformer (ChatGPT). While ChatGPT is typically used for natural language text generation, other intriguing application modes have recently been identified. We have recently reported the ability of ChatGPT to interpret the central dogma of molecular biology and the genetic code. Here we explored how ChatGPT-4 might be able to perform rudimentary structural biology modelling and drug binding analysis. We prompted ChatGPT-4 to model 3D structures for the 20 standard amino acids as well as an -helical polypeptide chain, with the latter involving incorporation of the Wolfram plugin for advanced mathematical computation. We also used ChatGPT-4 for structural analysis of drug-protein binding interaction between nirmatrelvir and its target, the SARS-CoV-2 main protease. For amino acid modelling, distances and angles between atoms of the generated structures in most cases approximated to experimentally determined value. For -helix modelling, the generated structures were comparable to that of an experimentally determined -helical structure. However, both amino acid and -helix modelling were sporadically error-prone and molecular complexity was not well tolerated. The binding interaction analysis revealed the ability of ChatGPT-4 to identify amino acid residues of the SARS-CoV-2 main protease involved in binding nirmatrelvir along with corresponding bond distances. Despite current limitations, we show the capacity of generative AI to perform basic structural biology modelling with atomic-scale accuracy. These results provide precedent for the potential use of generative AI in structural biology as this technology continues to advance.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.10.575113v4" target="_blank">Generative artificial intelligence performs rudimentary structural biology modelling</a>
</div></li>
<li><strong>Mathematical Modelling Indicates Th-cell Targeted Antibody-Dependent Cellular Cytotoxic Is a Crucial Obstacle Hurdling HIV Vaccine Development</strong> -
<div>
HIV poses a significant threat to human health. Although some progress has been made in the development of an HIV vaccine, there is currently no reported success in achieving an effective and fully functional vaccine for HIV. This highlights the challenges involved in HIV vaccine development. Through mathematical modeling, we have conducted a systematic study on the impact of antibody-dependent cellular cytotoxicity (ADCC) on HIV-specific immune responses. Unlike other viral infections, the ADCC effect following HIV infection may cause significant damage to the follicular center Th cells, leading to apoptosis of follicular center cells and rapid death of effector Th cells. This impedes the generation of neutralizing antibodies and creates barriers to viral clearance, thereby contributing to long-term infection. Another challenge posed by this effect is the substantial reduction in vaccine effectiveness, as effective antigenic substances such as gp120 bind to Th cell surfaces, resulting in the apoptosis of follicular center Th cells due to ADCC, hindering antibody regeneration. To address this issue, we propose the concept of using bispecific antibodies. By genetically editing B cells to insert the bispecific antibody gene, which consists of two parts targeting the CD4 binding site of HIV, such as the broadly neutralizing antibody 3BNC117, and the other targeting antibodies against other viruses, such as the spike protein of SARS-CoV-2. We can simultaneously enhance the levels of two pathogen-specific antibodies through stimulation with non-HIV-antigens corresponding to the other part of the chimeric antibody, such as the spike protein. This study contributes to the elucidation of the pathophysiology of HIV, while also providing a theoretical framework for the successful development of an HIV vaccine.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.07.579394v1" target="_blank">Mathematical Modelling Indicates Th-cell Targeted Antibody-Dependent Cellular Cytotoxic Is a Crucial Obstacle Hurdling HIV Vaccine Development</a>
</div></li>
<li><strong>Identifying causal role of COVID-19 in immunopsychiatry models</strong> -
<div>
This preprint is a 1000-word Viewpoint that explores methodological considerations of the COVID-19 pandemic for immunopsychiatry. It has been accepted for publication in Brain, Behavior, and Immunity for a special issue on Immunopsychiatry and COVID-19. Specifically, we discuss the treatment of COVID-19 as a confounding versus mediating variable in immunopsychiatric research. We leverage simulated data varied in sample and effect size to illustrate key considerations. Further, we highlight the statistical implications of each of these scenarios. Recommendations and key considerations for the field are briefly discussed.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/w4d5u/" target="_blank">Identifying causal role of COVID-19 in immunopsychiatry models</a>
</div></li>
<li><strong>Data-driven recombination detection in viral genomes</strong> -
<div>
Recombination is a key molecular mechanism for the evolution and adaptation of viruses. The first recombinant SARS-CoV-2 genomes were recognized in 2021; as of today, more than ninety SARS-CoV-2 lineages are designated as recombinant. In the wake of the COVID-19 pandemic, several methods for detecting recombination in SARS-CoV-2 have been proposed; however, none could faithfully confirm manual analyses by experts in the field. We hereby present RecombinHunt, a novel, automated method for the identification of recombinant/mosaic genomes purely based on a data-driven approach. RecombinHunt compares favorably with other state-of-the-art methods and recognizes recombinant SARS-CoV-2 genomes (or lineages) with one or two breakpoints with high accuracy, within reduced turn-around times and small discrepancies with respect to the expert manually-curated standard nomenclature. Strikingly, applied to the complete collection of viral sequences from the recent monkeypox epidemic, RecombinHunt identifies recombinant viral genomes in high concordance with manually curated analyses by experts, suggesting that our approach is robust and can be applied to any epidemic/pandemic virus. In conclusion, RecombinHunt represents a breakthrough in the detection of recombinant viral lineages in pandemic/epidemic scenarios and could substantially improve/advance community-based approaches for the detection of recombinant viral genomes based on phylogenetic analyses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.05.543733v2" target="_blank">Data-driven recombination detection in viral genomes</a>
</div></li>
<li><strong>Social Comparison for Concern and Action on Climate Change, Racial Injustice, and COVID-19</strong> -
<div>
Preventing the negative impacts of major, intersectional social issues hinges on personal concern and willingness to take action. This research examines social comparison in the context of climate change, racial injustice, and COVID-19 during Fall 2020. Participants in a U.S. university sample (n = 288), reported personal levels of concern and action and estimated peers’ concern and action regarding these three issues. Participants estimated that they were more concerned than peers for all three issues, and took more action than peers regarding COVID-19 and climate change. Participants who reported higher levels of personal concern also estimated that they took greater action than peers (relative to participants who reported lower levels of concern). Exploratory analyses found that perceived personal control over social issues increased participants’ concern and action for racial injustice and climate change, but yielded no change for COVID-19. This indicates that issue-specific features, including perceived controllability, may drive people to differently assess their experiences of distinct social issues.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/6j2zq/" target="_blank">Social Comparison for Concern and Action on Climate Change, Racial Injustice, and COVID-19</a>
</div></li>
<li><strong>Genome-wide association study reveals different T cell distributions in peripheral blood of healthy individuals at high genetic risk of type 1 diabetes and long COVID</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The immune system plays a crucial role in many human diseases. In this context, genome-wide association studies (GWAS) offer valuable insights to elucidate the role of immunity in health and disease. The present multi-omics study aimed to identify genetic determinants of immune cell type distributions in the blood of healthy individuals and to assess whether the distributions of these cells may play a role for autoimmune and COVID-19 disease risk. To this end, the frequencies of different immune cells in 483 healthy individuals from the Berlin Aging Study II were quantified using flow cytometry, and GWAS was performed for 92 immune cell phenotypes. Additionally, we performed linear regression analyses of immune cell distributions using polygenic risk scores (PRS) based on prior GWAS for five autoimmune diseases as well as for COVID-19 infection and post-COVID syndrome (“long COVID”). We validated seven previously described immune loci and identified 13 novel loci showing genome-wide significant (α=5.00E-8) association with different immune cell phenotypes. The most significant novel signal was conferred by the SLC52A3 locus, encoding for a riboflavin transporter protein, which was associated with na&amp;iumlve CD57+ CD8+ T cells (p=4.13E-17) and colocalized with SLC52A3 expression. Several novel loci contained immunologically plausible candidate genes, e.g., variants near TBATA and B3GAT1 representing genes associated with T cell phenotypes. The PRS of type 1 diabetes were significantly associated with CD8+ T cells at different differentiation states (p≤7.02E-4), and PRS of long COVID were associated with early-differentiated CD4+ T cells (p≤1.54E-4). In conclusion, our extensive immune cell GWAS analyses highlight several novel genetic loci of likely relevance for immune system function. Furthermore, our PRS analyses point to a shared genetic basis between immune cell distributions in healthy adults and T1D (CD8+ T cells) as well as long COVID (CD4+ T cells).
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.08.24302520v1" target="_blank">Genome-wide association study reveals different T cell distributions in peripheral blood of healthy individuals at high genetic risk of type 1 diabetes and long COVID</a>
</div></li>
<li><strong>Implementation of Smart Triage combined with a quality improvement program for children presenting to facilities in Kenya and Uganda: An interrupted time series analysis.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
PLOS DH (298/300 word limit) Sepsis occurs predominantly in low-middle-income countries. Sub-optimal triage contributes to poor early case recognition and outcomes from sepsis. We evaluated the impact of Smart Triage using improved time to intravenous antimicrobial administration in a multisite interventional study. Smart Triage was implemented (with control sites) in Kenya (February 2021-December 2022) and Uganda (April 2020-April 2022). Children presenting to the outpatient departments with an acute illness were enrolled. A controlled interrupted time series was used to assess the effect on time from arrival at the facility to intravenous antimicrobial administration. Secondary analyses included antimicrobial use, admission rates and mortality (NCT04304235). During the baseline period, the time to antimicrobials decreased significantly in Kenya (132 and 58 minutes) at control and intervention sites, but less in Uganda (3 minutes) at the intervention site. Then, during the implementation period in Kenya, the time to IVA at the intervention site decreased by 98 min (57%, 95% CI 81-114) but increased by 49 min (21%, 95% CI: 23-76) at the control site. In Uganda, the time to IVA initially decreased but was not sustained, and there was no significant difference between intervention and control sites. At the intervention sites, there was a significant reduction in IVA utilization of 47% (Kenya) and 33% (Uganda), a reduction in admission rates of 47% (Kenya) and 33% (Uganda) and a 25% (Kenya) and 75% (Uganda) reduction in mortality rates compared to the baseline period. We showed significant improvements in time to intravenous antibiotics in Kenya but not Uganda, likely due to COVID-19, a short study period and resource constraints. The reduced antimicrobial use and admission and mortality rates are remarkable and welcome benefits but should be interpreted cautiously as these were secondary outcomes. This study underlines the difficulty of implementing technologies and sustaining quality improvement in resource-poor health systems.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.09.24302601v1" target="_blank">Implementation of Smart Triage combined with a quality improvement program for children presenting to facilities in Kenya and Uganda: An interrupted time series analysis.</a>
</div></li>
<li><strong>Physicians experiences with telemedicine during the COVID-19 pandemic in India</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Purpose: Digital health is an important factor in Indias healthcare system. Inclusive policy measures, a fertile technological landscape, and relevant infrastructural development with unprecedented levels of telemedicine adoption catalysed by the recent COVID-19 pandemic have thrown open new possibilities and opportunities for clinicians, end-users, and other stakeholders. Nevertheless, there are still several challenges to properly integrating and scaling telemedicine use in India. This studys objective was to understand the views of practising physicians in India on the use of telemedicine and the challenges experienced during the accelerated rollout during the first wave of the COVID-19 pandemic. Methods: We acquired data through an anonymous, cross-sectional, internet-based survey of physicians (n=444) across India on the COVID-19 frontline. These responses were subjected to qualitative data analysis (via inductive coding and thematic analyses) and descriptive statistics, as appropriate. Results: Most responses (n=51) were categorised under a code indicating that telemedicine-led healthcare delivery compromised treatment quality. The second largest proportion of responses (n=22) suggested that Accessibility, quality and maturity of software and hardware infrastructure was a considerable challenge. Conclusions: Despite the considerable uptake, perceived benefits, and the foreseen positive role of telemedicine in India, several challenges of telemedicine use (viz., technical, user experience-based integration, and non-user-based integration challenges) have been identified. These must be addressed through suggested relevant opportunities to realise telemedicines potential and help inform the future design of effective telemedicine policy and practice in India.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.10.24302616v1" target="_blank">Physicians experiences with telemedicine during the COVID-19 pandemic in India</a>
</div></li>
<li><strong>Factors associated with knowledge, attitudes, and behaviors regarding antiviral medications for COVID-19 among US adults</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Little is known about public perceptions of antivirals for the treatment of mild-to-moderate COVID-19 in the United States (US). Our objective was to explore adult perceptions toward COVID-19 antivirals with the goal of improving outreach communications about antivirals for COVID-19. Methods: During July 2022, potential respondents 18 years and older were randomly sampled from a national opt-in, non-representative, cross-sectional internet panel, with oversampling of African Americans, Hispanics, and adults 65 years and older. Respondents were asked about sociodemographic factors, and knowledge, attitudes, and perceptions regarding COVID-19 antivirals. Results were weighted to represent the non-institutionalized US adult population. Results: Among 1,155 respondents, 51% were female, 60% were 18-49 years, 21% were 50-64 years, and 19% were 65 years or older. Compared to those aged 18-49 years and 50-64 years, a greater proportion of adults 65 years and older were knowledgeable about COVID-19 antivirals and would take them if they tested positive or their doctor recommended them. Adults 65 years and over and those reporting immunosuppression or disability had the highest rates of willingness to take antivirals. For all groups, the proportion of people willing to take antivirals increased by &gt;20% if recommended by their doctor. Respondents in the 50-64 and 65+ groups who were sure they would take COVID-19 antivirals were more likely to be fully vaccinated and less likely to be living in isolation. Conclusion: Groups that are less likely to have been vaccinated, those living in isolation, and those not sure about whether they would take an antiviral or not may be at risk for not receiving treatment to prevent severe COVID-19 outcomes. However, trust in doctor recommendations may be enough to overcome individual patient concerns about COVID-19 antivirals. Targeted initiatives to educate those at risk for severe COVID-19 outcomes about the effectiveness of antivirals, including those who are unvaccinated given their increased risk of severe disease, may be needed to further lower this population9s risk of severe COVID-19.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.11.23299148v2" target="_blank">Factors associated with knowledge, attitudes, and behaviors regarding antiviral medications for COVID-19 among US adults</a>
</div></li>
<li><strong>SARS-COV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice</strong> -
<div>
The coronavirus disease of 2019 (COVID-19) pandemic that has led to more than 700 million confirmed cases and near 7 million deaths. Although Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus mainly infects the respiratory system, neurological complications are widely reported in both acute infection and long-COVID cases. Despite the success of vaccines and antiviral treatments, neuroinvasiveness of SARS-CoV-2 remains as an important question, which is also centered on the mystery whether the virus is capable of breaching the barriers into the central nervous system. By studying the K18-hACE2 infection model, we observed clear evidence of microvascular damage and breakdown of the blood-brain barrier (BBB). Mechanistically, SARS-CoV-2 infection caused pericyte damage, tight junction loss, endothelial activation and vascular inflammation, which together drive microvascular injury and BBB impairment. In addition, the blood-cerebrospinal fluid barrier at the choroid plexus was also impaired after infection. Therefore, cerebrovascular and choroid plexus dysfunctions are important aspects of COVID-19 and may contribute to the neurological complications both acutely and in long COVID.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.09.579589v1" target="_blank">SARS-COV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice</a>
</div></li>
<li><strong>Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity</strong> -
<div>
Protein S (PS), the critical plasma cofactor for the anticoagulants tissue factor (TF) pathway inhibitor (TFPI) and activated protein C (APC), circulates in two functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP) (anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we identified a shear-dependent interaction between PS and von Willebrand Factor (VWF) by mass spectrometry. Consistently, plasma PS and VWF comigrated in both native and agarose gel electrophoresis. The PS/VWF interaction was blocked by TFPI but not APC, suggesting an interaction with the C-terminal sex hormone binding globulin (SHBG) region of PS. Microfluidic systems, mimicking arterial laminar flow or disrupted turbulent flow, demonstrated that PS stably binds VWF as VWF unfolds under turbulent flow. PS/VWF complexes also localized to platelet thrombi under laminar arterial flow. In thrombin generation-based assays, shearing plasma decreased PS activity, an effect not seen in the absence of VWF. Finally, free PS deficiency in COVID-19 patients, measured using an antibody that binds near the C4BP binding site in SHBG, correlated with changes in VWF, but not C4BP, and with thrombin generation. Our data suggest that PS binds to a shear-exposed site on VWF, thus sequestering free PS and decreasing its anticoagulant activity, which would account for the increased thrombin generation potential. As many viral infections present with free PS deficiency, elevated circulating VWF, and increased vascular shear, we propose that the PS/VWF interaction reported here is a likely contributor to virus-associated thrombotic risk.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.08.579463v1" target="_blank">Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity</a>
</div></li>
<li><strong>Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion</strong> -
<div>
The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolated and characterized XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing &gt;80% of circulating variants in January 2024. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor &gt;30 additional changes. These variants replicated in IGROV-1 but no longer in Vero E6 and were not markedly fusogenic. They potently infected nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remained active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals were markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhanced NAb responses against both XBB and BA.2.86 variants. JN.1 displayed lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary trajectory of these variants combines increased fitness and antibody evasion.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.20.567873v3" target="_blank">Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion</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>SGB for COVID-induced Parosmia</strong> - <b>Conditions</b>: COVID-19-Induced Parosmia <br/><b>Interventions</b>: Drug: Stellate Ganglion Block; Drug: Placebo Sham Injection <br/><b>Sponsors</b>: Washington University School of Medicine <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>Investigating the Effectiveness of Vimida</strong> - <b>Conditions</b>: Long COVID; Post COVID-19 Condition <br/><b>Interventions</b>: Behavioral: vimida <br/><b>Sponsors</b>: Gaia AG; Medical School Hamburg; Institut Long-Covid Rostock <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>Effects of Physiotherapy Via Video Calls on Cardiopulmonary Functions, Physical Function, Cognitive Function, Activity Daily Livings, and Quality of Life in Patients With COVID-19</strong> - <b>Conditions</b>: COVID-19; Long COVID-19; Cardiopulmonary Function; Physical Function <br/><b>Interventions</b>: Behavioral: Exercise training <br/><b>Sponsors</b>: Chulabhorn Hospital <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>Acute Cardiovascular Responses to a Single Exercise Session in Patients With Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise session; Behavioral: Control session <br/><b>Sponsors</b>: University of Nove de Julho <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>Reducing Respiratory Virus Transmission in Bangladeshi Classrooms</strong> - <b>Conditions</b>: SARS-CoV2 Infection; Influenza Viral Infections; Respiratory Viral Infection <br/><b>Interventions</b>: Device: Box Fan; Device: UV Germicidal Irradiation Lamp Unit; Device: Combined: Box Fan and UV Germicidal Irradiation Lamp Units <br/><b>Sponsors</b>: Stanford University; Centers for Disease Control and Prevention; International Centre for Diarrhoeal Disease Research, Bangladesh <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>SMILE: Clinical Trial to Evaluate Mindfulness as Intervention for Racial and Ethnic Populations During COVID-19</strong> - <b>Conditions</b>: Anxiety; COVID-19 Pandemic <br/><b>Interventions</b>: Behavioral: Mindfulness <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; National Institute on Minority Health and Health Disparities (NIMHD); RTI International <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 to Learn About a Combined COVID-19 and Influenza Shot in Healthy Adults</strong> - <b>Conditions</b>: Influenza, Human; SARS-CoV-2 Infection; COVID-19 <br/><b>Interventions</b>: Biological: BNT162b2 (Omi XBB.1.5)/RIV; Biological: BNT162b2 (Omi XBB.1.5); Biological: RIV; Other: Normal saline placebo <br/><b>Sponsors</b>: Pfizer <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Impact of the Covid-19 Pandemic on Orthopedic Trauma Management</strong> - <b>Conditions</b>: Trauma; COVID-19 Pandemic <br/><b>Interventions</b>: Other: epidemyolojical <br/><b>Sponsors</b>: Bakirkoy Dr. Sadi Konuk Research and Training Hospital <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>The Effects of Nutritional Intervention on Health Parameters in Participants With Type 2 Diabetes Mellitus</strong> - <b>Conditions</b>: Diabetes Mellitus Type 2; Diabetes Mellitus Type 2 in Obese; Diabetes; Diabetes Mellitus Non-insulin-dependent; Hypertension; Type 2 Diabetes Mellitus <br/><b>Interventions</b>: Behavioral: Nutritional Intervention <br/><b>Sponsors</b>: Sao Jose do Rio Preto Medical School; Fundação de Amparo à Pesquisa do Estado de São Paulo <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>Open-label, Multi-centre, Non-Inferiority Study of Safety and Immunogenicity of BIMERVAX for the Prevention of COVID-19 in Adolescents From 12 Years to Less Than 18 Years of Age.</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: BIMERVAX <br/><b>Sponsors</b>: Hipra Scientific, S.L.U; Veristat, Inc.; VHIR; Asphalion <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 of Amantadine for Cognitive Dysfunction in Patients With Long-Covid</strong> - <b>Conditions</b>: Long COVID; Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Drug: Amantadine; Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management <br/><b>Sponsors</b>: University of Texas Southwestern Medical Center <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>Balance Acceptance and Commitment Therapy for Long COVID</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Long COVID <br/><b>Interventions</b>: Behavioral: Balance Acceptance and Commitment Therapy <br/><b>Sponsors</b>: King’s College London <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on the Effect of Incentive Spirometer-based Respiratory Training on the Long COVID-19</strong> - <b>Conditions</b>: COVID-19 Pandemic; Diabetes; Hypertension; Cardiac Disease; Long COVID <br/><b>Interventions</b>: Behavioral: Incentive Spirometer respiratory training <br/><b>Sponsors</b>: National Taipei University of Nursing and Health Sciences; Tri-Service General Hospital <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>Combination of Polygonatum Rhizoma and Scutellaria baicalensis triggers apoptosis through downregulation of PON<sub>3</sub> -induced mitochondrial damage and endoplasmic reticulum stress in A549 cells</strong> - CONCLUSION: SP inhibits proliferation of lung cancer A549 cells by downregulating PON(3) -induced apoptosis in the mitochondrial and ER pathways.</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>Omicron BA.4/5 neutralization and cell-mediated immune responses in relation to baseline immune status and breakthrough infection among PLWH: A follow-up cohort study</strong> - There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell-mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 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>Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV</strong> - CONCLUSION: Our results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous.</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>Nebulized pH-Responsive Nanospray Combined with Pentoxifylline and Edaravone to Lungs for Efficient Treatments of Acute Respiratory Distress Syndrome</strong> - The COVID-19 pandemic has become an unprecedented global medical emergency, resulting in more than 5 million deaths. Acute respiratory distress syndrome (ARDS) caused by COVID-19, characterized by the release of a large number of pro-inflammatory cytokines and the production of excessive toxic ROS, is the most common serious complication leading to death. To develop new strategies for treating ARDS caused by COVID-19, a mouse model of ARDS was established by using lipopolysaccharide (LPS)….</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>Influenza vaccination during the 2021/22 season: A data-linkage test-negative case-control study of effectiveness against influenza requiring emergency care in England and serological analysis of primary care patients</strong> - We present England 2021/22 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related emergency care use in children aged 1-17 and in adults aged 50+, and serological findings in vaccinated vs unvaccinated adults by hemagglutination inhibition assay. Influenza vaccination has been routinely offered to all children aged 2-10 years and adults aged 65 years + in England. In 2021/22, the offer was extended to children to age 15 years, and adults aged 50-64…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of molecular mechanisms of riboflavin anti-COVID-19 action reveals anti-inflammatory efficacy rather than antiviral activity</strong> - CONCLUSIONS: It is concluded that riboflavin reveals anti-inflammatory rather than antiviral activity for SARS-CoV-2 infection.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An enhanced broad-spectrum peptide inhibits Omicron variants in vivo</strong> - The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) poses a major challenge to vaccines and antiviral therapeutics due to their extensive evasion of immunity. Aiming to develop potent and broad-spectrum anticoronavirus inhibitors, we generated A1-(GGGGS)7-HR2m (A1L35HR2m) by introducing an angiotensin-converting enzyme 2 (ACE2)-derived peptide A1 to the N terminus of the viral HR2-derived peptide HR2m through a long flexible linker,…</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>Mesenchymal stromal cells (MSCs) as a therapeutic agent of inflammatory disease and infectious COVID-19 virus: live or dead mesenchymal?</strong> - The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various…</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>Genetic justification of COVID-19 patient outcomes using DERGA, a novel data ensemble refinement greedy algorithm</strong> - Complement inhibition has shown promise in various disorders, including COVID-19. A prediction tool including complement genetic variants is vital. This study aims to identify crucial complement-related variants and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID-19 patients hospitalized between April 2020 and April 2021 at three referral centres were analysed using an artificial intelligence-based algorithm to predict disease outcome (ICU vs….</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>Milk Antiviral Proteins and Derived Peptides against Zoonoses</strong> - Milk is renowned for its nutritional richness but also serves as a remarkable reservoir of bioactive compounds, particularly milk proteins and their derived peptides. Recent studies have showcased several robust antiviral activities of these proteins, evidencing promising potential within zoonotic viral diseases. While several publications focus on milk’s bioactivities, antiviral peptides remain largely neglected in reviews. This knowledge is critical for identifying novel research directions…</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 Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions</strong> - Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: (i) the ability to fight infections; (ii) the activation of blood coagulation or blood clot lysis systems; (iii) the activation of digestive enzymes; and (iv)…</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 Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury</strong> - Nowadays, acute respiratory distress syndrome (ARDS) still has a high mortality rate, and the alleviation and treatment of ARDS remains a major research focus. There are various causes of ARDS, among which pneumonia and non-pulmonary sepsis are the most common. Trauma and blood transfusion can also cause ARDS. In ARDS, the aggregation and infiltration of neutrophils in the lungs have a great influence on the development of the disease. Neutrophils regulate inflammatory responses through various…</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>Unveiling the Antiviral Properties of Panduratin A through SARS-CoV-2 Infection Modeling in Cardiomyocytes</strong> - Establishing a drug-screening platform is critical for the discovery of potential antiviral agents against SARS-CoV-2. In this study, we developed a platform based on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to investigate SARS-CoV-2 infectivity, with the aim of evaluating potential antiviral agents for anti-SARS-CoV-2 activity and cardiotoxicity. Cultured myocytes of iPSC-CMs and immortalized human cardiomyocyte cell line (AC-16) were primarily characterized for 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>Ligand-Based Design of Selective Peptidomimetic uPA and TMPRSS2 Inhibitors with Arg Bioisosteres</strong> - Trypsin-like serine proteases are involved in many important physiological processes like blood coagulation and remodeling of the extracellular matrix. On the other hand, they are also associated with pathological conditions. The urokinase-pwlasminogen activator (uPA), which is involved in tissue remodeling, can increase the metastatic behavior of various cancer types when overexpressed and dysregulated. Another member of this protease class that received attention during the SARS-CoV 2 pandemic…</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>Phytochemical Elucidation and Effect of <em>Maesa indica</em> (Roxb.) Sweet on Alleviation of Potassium Dichromate-Induced Pulmonary Damage in Rats</strong> - Maesa indica (Roxb.) Sweet is one of the well-known traditionally-used Indian plants. This plant is rich in secondary metabolites like phenolic acids, flavonoids, alkaloids, glycosides, saponins, and carbohydrates. It contains numerous therapeutically active compounds like palmitic acid, chrysophanol, glyceryl palmitate, stigmasterol, β-sitosterol, dodecane, maesaquinone, quercetin 3-rhaminoside, rutin, chlorogenic acid, catechin, quercetin, nitrendipine, 2,3-dihydroxypropyl…</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>What Do We Owe a Prison Informant?</strong> - A man in Georgia says he risked his life for years and was abandoned. But there are very few rules protecting those who provide law enforcement with information. - <a href="https://www.newyorker.com/news/letter-from-the-south/what-do-we-owe-a-prison-informant">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Is the Media Prepared for an Extinction-Level Event?</strong> - Ads are scarce, search and social traffic is dying, and readers are burned out. The future will require fundamentally rethinking the press’s relationship to its audience. - <a href="https://www.newyorker.com/news/the-weekend-essay/is-the-media-prepared-for-an-extinction-level-event">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Friendship Challenge</strong> - How envy destroyed the perfect connection between two teen-age girls. - <a href="https://www.newyorker.com/magazine/2024/02/12/the-friendship-challenge">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Art World Before and After Thelma Golden, by Calvin Tomkins</strong> - When Golden was a young curator in the nineties, her shows, centering Black artists, were unprecedented. Today, those artists are the stars of the art market. - <a href="https://www.newyorker.com/magazine/2024/02/12/the-art-world-before-and-after-thelma-golden">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Teen’s Fatal Plunge Into the London Underworld</strong> - After Zac Brettler mysteriously plummeted into the Thames, his grieving parents were shocked to learn that he’d been posing as an oligarch’s son. Would the police help them solve the puzzle of his death? - <a href="https://www.newyorker.com/magazine/2024/02/12/a-teens-fatal-plunge-into-the-london-underworld">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>A prescription for housing?</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/qBFjMi_qyAmPjQeKFtytlJlUQoM=/334x0:5667x4000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73135430/AP22173647270711.0.jpg"/>
<figcaption>
A sign indicating the availability of a home to rent stands outside a building in Philadelphia on June 22, 2022. | Matt Rourke/AP
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
States prepare to use Medicaid for rental assistance for the first time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K8lzwh">
For more than a decade, researchers and advocates have argued that housing is a fundamental part of health care.<strong> </strong>Beginning this fall, for the first time, federal Medicaid dollars will start going toward paying some people’s rent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uuxObi">
It’s a<strong> </strong>significant policy development. Congressional regulations have long barred Medicaid funds from being used to pay for rent for people staying outside of nursing homes or medical facilities like hospitals. And while some states have used philanthropy or<strong> </strong>state-based Medicaid<strong> </strong>funding<strong> </strong>to pay for housing, those pots of money were extremely limited.<strong> </strong>Now, with rates of unsheltered homelessness reaching <a href="https://www.npr.org/homelessness-affordable-housing-crisis-rent-assistance">record highs in 2023</a>, and rents growing <a href="https://www.npr.org/2024/01/25/1225957874/housing-unaffordable-for-record-half-all-u-s-renters-study-finds">to their most unaffordable levels ever</a>, some states are preparing to use federal Medicaid dollars in the hopes that health will improve as housing stabilizes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A2BkBP">
The Biden administration has made this possible through<strong> </strong><a href="https://healthlaw.org/wp-content/uploads/2018/09/Fact-Sheet-Medicaid-1115-Waivers-July-2018-with-ToC.pdf">a longstanding Medicaid waiver program</a><strong> </strong>that allows states to test out new Medicaid ideas.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eZ29mn">
For nearly a decade, the federal agency that runs Medicare and Medicaid has been warming to the idea that housing could be health care. Since 2015, the Centers for Medicare and Medicaid Services<strong> </strong><a href="https://na.eventscloud.com/file_uploads/818900a38ece771159876b13997c5a4d_CMS.pdf">has affirmed</a> that Medicaid funds could go toward services that help people move into new housing, like moving costs or security deposits. In 2018, an influential federal commission<strong> </strong><a href="https://www.macpac.gov/wp-content/uploads/2018/10/Medicaid%E2%80%99s-Role-in-Housing.pdf">told Congress that</a>, while it’s long been known that poor housing conditions can worsen health outcomes, more recent data suggests that providing supportive housing to chronically homeless people<strong> </strong>also reduces ER visits in ways that case management or other outpatient services does not.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3rl4PA">
The “<a href="https://www.vox.com/policy-and-politics/22567034/us-health-care-trends-social-determinants-of-health">housing is health care</a>” mantra got another major boost during the pandemic, when calls to stay at home to avoid catching and spreading disease grew louder and more urgent. Communities that halted <a href="https://www.vox.com/23140987/evictions-housing-rent-assistance-erap-tenant">evictions</a> saw lower rates of <a href="https://www.vox.com/coronavirus-covid19">Covid-19</a>, a stark example of how access to housing is linked to health.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zSUTj2">
And in 2022, the Biden administration <a href="https://www.medicaid.gov/sites/default/files/2023-01/addrss-hlth-soc-needs-1115-demo-all-st-call-12062022.pdf">encouraged</a> states to consider using Medicaid dollars for “health-related social needs” like housing, nutrition, and transportation — part of <a href="https://www.whitehouse.gov/wp-content/uploads/2023/11/SDOH-Playbook-3.pdf">a broader White House effort</a> to address social determinants of health.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YzxYcj">
“We think it’s incredibly exciting,” Dan Tsai, the deputy administrator and director of the Center for Medicaid and CHIP Services, told me. “This is a firm, clear stance, and we spent about a year of this administration working through how to define and create with guardrails the role of Medicaid in housing and nutrition.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VgWIzX">
Tsai said their conclusion was based on both common sense and evidence-based practices, that for some groups of people, throwing “the same old against the wall” just would not drive better health.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VF4Gj4">
Jeff Olivet, the executive director of the US Interagency Council on Homelessness, similarly told me he sees the ability to use Medicaid dollars for purposes like rent as “a real potentially game-changing set of supports” to help people exit homelessness and then stay stably housed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hwQnPj">
Not everyone thinks this possibility is a good move for Medicaid, an already strained federal program <a href="https://www.acr.org/Practice-Management-Quality-Informatics/ACR-Bulletin/Articles/June-2023/Medicaid-Reimbursement-Is-Not-Keeping-Pace-With-Medicare">with notoriously low reimbursement rates</a> for doctors that disincentive treating patients. Just <a href="https://shelterforce.org/2023/06/05/how-states-can-use-medicaid-to-address-housing-costs/#:~:text=Up%20to%203%20percent%20of,substantial%20investments%20in%20housing%20services.">3 percent</a> of a state’s Medicaid spending can go toward “health-related social needs” like housing, but that could still easily amount to billions of dollars annually. Others doubt the claims that paying for housing will drive down overall government spending.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PBnLAX">
Sherry Glied, a dean and professor of public service at New York University, <a href="https://jamanetwork.com/journals/jama-health-forum/fullarticle/2808719">warned recently of “mission creep” in health systems</a>, arguing that having hospitals and other medical institutions focus on the provision of social services could be a “dangerous distraction” from their core mission of serving patients, and one that policymakers should discourage.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gMIpMZ">
The failure of Congress to dedicate more money to agencies like the Department of Housing and Urban Development is how we got to this point, said senior policy director for National Health Care for the Homeless Council Barbara DiPietro.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cPWC4t">
“More and more states are desperate to find any help, and that’s why they’re turning to Medicaid because they’re not getting real assistance from HUD,” she told Vox. “And Medicaid is an entitlement program while housing is not.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VDPMMl">
The new pilot program authorizes Medicaid dollars for up to six months of rent and<strong> </strong>could herald much bigger shifts down the line if state results show improvements in health outcomes or cost-savings. It could also augur much larger shifts across state and federal governments to bring about more comprehensive visions of health care.
</p>
<h3 id="38WClN">
Arizona and Oregon will go first
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IlozvX">
The federal government has approved a handful of states to use waivers to finance rental assistance for up to six months. The first states to put this into practice are Arizona starting this October, and Oregon this November. The two are planning to target different subpopulations of Medicaid beneficiaries, and both are scrambling to figure out how to make this all possible given shortages of affordable housing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D2iAzA">
Oregon’s Medicaid program currently provides coverage to roughly <a href="https://www.thenewsguard.com/news/getting-ready-oregon-health-and-housing-leaders-prepare-for-medicaid-expansion/article_8a97ccbe-7e7f-11ee-b290-af3d8d283982.html">1.5 million Oregonians</a>, and the state estimates 125,000 of those people will soon be eligible to qualify for rental assistance under this new waiver. Oregon is opting to target beneficiaries at risk of becoming homeless, in effect using the funds as a preventive tool to help stave off the devastating <a href="https://academic.oup.com/socpro/article-abstract/63/1/46/1844105?login=false">economic</a>, <a href="https://www.healthaffairs.org/do/10.1377/hpb20210315.747908/">physical</a>, and <a href="https://jech.bmj.com/content/70/4/409">mental harms</a> that come with losing one’s home. Individuals will literally get a “prescription” for housing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bMk0tM">
To refer eligible people, the state will look to partner with community-based organizations. Housing nonprofits that get involved in this work will need to train their caseworkers as certified community health workers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GJIn5E">
“It’s a little scary for them, because they don’t want to become medical providers in the same way a doctor doesn’t want to become a housing provider,” Dave Baden, the deputy director of Oregon’s Health Authority, told me. “We can’t medicalize the housing world.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="khbpGm">
Over time, Baden hopes the state will be able to use this kind of funding to pay rent for people living on the streets, but he thinks Oregon needs to increase its housing supply first.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VdQmEQ">
“This Medicaid waiver is not magically going to make housing exist, and I feel like we would have gummed our work to focus on those who were houseless to start with,” he said. “I don’t want to create a false benefit where we say, ‘Hey, Amy, here’s six months of rent, oh, I’m sorry I don’t have any housing for you.’”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sTTL92">
Arizona, by contrast, is planning to target people designated as having a <a href="https://www.azahcccs.gov/AHCCCS/Downloads/SMIDeterminationProcess.pdf">serious mental illness</a>, building off a similar but much smaller <a href="https://www.azahcccs.gov/AHCCCS/Initiatives/AHP/">state program</a> that subsidizes rent for about 3,000 Medicaid beneficiaries each year.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gyI1d4">
That program, which is not time-limited, has been considered an extraordinary success: <a href="https://www.azahcccs.gov/Resources/Downloads/HousingWaiverRequest/AHCCCSHousingHealthOpportunitiesH2OWaiverAmendment.pdf">State data</a> showed financing rent led to a 31 percent reduction in ER visits, a 44 percent reduction in inpatient hospital stays, and savings overall to Arizona’s Medicaid program of more than $5,500 per member per month.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fyaAr3">
“That’s one of the big reasons we felt so strongly about pursuing [the 1115 waiver] and being able to federalize some of that work,” said Alex Demyan, an assistant director with Arizona’s Health Care Cost Containment System. “We’re in a unique and advantageous position because we have a runway.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C05pPz">
With <a href="https://nlihc.org/housing-needs-by-state/arizona">a significant affordable housing shortage</a>, Arizona is looking to authorize a new kind of housing provider to help with supply issues, known as an “<a href="https://stateofreform.com/featured/2023/10/ahcccs-continues-working-with-cms-to-strengthen-housing-services-for-medicaid-members/">enhanced shelter.</a>” These will be new organizations that contract with Medicaid to provide mostly congregate housing, and get reimbursed on a per-diem basis.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1TVmMr">
Demyan sees the opportunity to use Medicaid for rent as potentially transformative. “It’s a huge deal; this kind of cutting-edge work is really what makes working in Medicaid so rewarding in a lot of ways,” Demyan told me. “We get to play around in the sandbox of health policy and do things differently. I don’t think it’s any secret that there are better ways that we can do things.”
</p>
<h3 id="9Qfxgn">
The fine print
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ae7EYu">
As Oregon and Arizona — as well as other states that have applied to use federal Medicaid dollars for rent like New York, California, Hawaii, and Washington — prepare for the opportunity, they are hoping to build collaboration between government agencies, private companies, and community nonprofits that historically have rarely worked together.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="StasS3">
“There has to be some system-level linkage between the housing and homelessness systems and the medical services; otherwise, we are very concerned about what will happen to people at the end of their six months,” said Marcella Maguire, the director of Health Systems Integration for the Corporation for Supportive Housing. “This funding will put more people into an already underresourced system. Long-term, I think it will reduce strain, but short-term it will increase strain.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Cqx0mv">
DiPietro, of the National Health Care for the Homeless Council, said she has some worries about how states might use this new Medicaid opportunity to jump people ahead of those waiting in the established line for subsidized housing, or even how receiving Medicaid funding could threaten their eligibility for other homeless services programs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KWLcQf">
Olivet, of the US Interagency Council on Homelessness, said the eligibility issue is “certainly on our radar screen” and that his agency wants to serve as “connective tissue” to ensure federal policies are implemented in a strategic way. But state Medicaid departments have a “tremendous role” to play in shaping the specifics of each waiver, Olivet added, and coordination between health and housing providers “is where the real work will happen.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oKBD6f">
Richard Cho, a senior housing and services adviser at HUD, told me there’s legal precedent for these kinds of eligibility concerns and that his agency is working closely <a href="https://acl.gov/HousingAndServices/Accelerator">to provide technical assistance to states</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZHcCBG">
When asked if he thinks Medicaid could one day fund rent for longer than six months, Tsai, of CMS, emphasized the importance of getting data first from these pilots. “It’s a huge first step,” he said. “No one believes Medicaid is here to supplant or replace the role of housing and nutritional agencies, but at the same time, clearly there’s a better way.”
</p>
<h3 id="EjMoA9">
The cost-effectiveness gamble
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DIiGM7">
One undoubtedly appealing aspect of the policy proposal is that by paying for housing, Medicaid spending could ultimately go down over time, similar to how it worked with Arizona’s smaller program. It’s well-documented that people experiencing homelessness use significantly more health care resources on average than people with stable housing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1i2OPb">
Proponents point to some encouraging research to back the idea, like a California permanent supportive housing program that <a href="https://www.rand.org/pubs/research_reports/RR1694.html">reduced the use of expensive medical care</a> and resulted in a roughly 20 percent net savings of total public cost. Another <a href="https://shelterforce.org/2023/06/05/how-states-can-use-medicaid-to-address-housing-costs/">program</a> in New York reduced inpatient hospital days by 40 percent, inpatient psychiatric admissions by 27 percent, and ER visits by 26 percent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eCpfnv">
But other research evidence is less persuasive. One <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631101/">literature review published in 2022</a> found “mixed and mostly low-certainty evidence” that interventions to drive housing affordability and stability led to improved adult health outcomes. Another study published <a href="https://www.healthaffairs.org/doi/10.1377/hlthaff.2023.01046">this month</a> found participants had no difference in ER visits, inpatient use, or chronic disease control, but did report real mental health improvements, particularly from housing providers who showed them compassion.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cD5iLB">
“The success of health care–based housing interventions must not be judged solely by short-term chronic disease control and changes in health care use,” the study authors argued. “Given the complexity of US health care systems, innovations <a href="https://pubmed.ncbi.nlm.nih.gov/34057398/">often struggle</a> to demonstrate return on investment … [and] had our evaluation measured only health care use and chronic disease control, we would have overlooked the strong relational connection between patients and their advocates and missed the housing program’s possible effects on the social burden of disease in the <a href="https://www.hhs.gov/sites/default/files/surgeon-general-social-connection-advisory.pdf">current epidemic</a> of social isolation in the US.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A7BCiA">
Paula Lantz, a professor of health policy at the University of Michigan, told me she’s very supportive of Medicaid programs getting into housing interventions but has doubts about whether it will ultimately reduce costs, and notes there are moral challenges of really studying that question over time. “If you have a bunch of people in a control group who you know need services and help and you’re using them for research, the longer [they’re denied help], the larger the ethical issues there are,” she said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0tUyI6">
Lantz says she worries that if the waivers don’t save Medicaid money, critics might seize on that to attack health care spending more broadly. Demyan, the assistant director with Arizona’s state Medicaid program, told me he would not be surprised if there’s “an initial bump in increase in cost of care” as states transition to this new model.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8OYsYl">
And what if it’s not, ultimately, cost-effective?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OaY66H">
Tsai, the federal Medicaid official, said he’s confident there are “inefficiencies” in the system, and that governments can use funding in “wiser” ways to target certain groups of people. He also stressed the need to think about public savings over time, to remember some that many of the country’s biggest health disparities didn’t happen overnight.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LziAEF">
Still, Tsai acknowledges, there is currently a lot of “unmet need” in health care, and saving money isn’t the only thing that matters. “That is why we want to evaluate very objectively,” he said, “and why we want to look at both health outcomes and cost.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cpZDoJ">
</p></li>
<li><strong>The moral and strategic case for arming Ukraine</strong> -
<figure>
<img alt="Ukrainian border guards training in snow gear." src="https://cdn.vox-cdn.com/thumbor/PQ7mgB616TXiDuSPU6UPzj3wL7M=/810x0:7622x5109/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73135409/1996774240.0.jpg"/>
<figcaption>
Ukrainian border guards conduct training on patrolling the borderline in February. | Viacheslav Ratynskyi/Anadolu via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Congress should have approved Ukraine aid yesterday.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lq8hRo">
As the Senate considered approving $61 billion to Ukraine this weekend, <a href="https://www.vox.com/donald-trump">Donald Trump</a> published an all-caps rant making his opposition clear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fKSEZ0">
“FROM THIS POINT FORWARD, ARE YOU LISTENING U.S. SENATE(?), NO MONEY IN THE FORM OF FOREIGN AID SHOULD BE GIVEN TO ANY COUNTRY UNLESS IT IS DONE AS A LOAN,” he wrote <a href="https://truthsocial.com/@realDonaldTrump/posts/111908663705756439">on his Truth Social</a> platform on Friday.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RPfUXR">
The Senate rejected Trump’s order, <a href="https://www.nytimes.com/2024/02/12/us/politics/senate-ukraine-aid.html">passing the bill Tuesday morning 70-29</a>. But the bill still needs to <a href="https://www.nytimes.com/2024/02/11/us/republican-senators-ukraine-israel-bill.html">clear the Republican-controlled House</a>, where the former president’s influence has proven powerful in the past. Indeed, House Speaker Mike Johnson (R-LA) has <a href="https://twitter.com/SpeakerJohnson/status/1757210505570087039">already stated opposition to the Senate aid bill</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hquusX">
Which makes now a good time to remind ourselves that the objections to Ukraine aid are absurd.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Qq1Vxm">
Supporting Ukraine’s defense is one of the single easiest foreign policy calls of my lifetime, a policy that has both protected Ukrainians from Russian slaughter and advanced America’s geopolitical interests in Europe. It has done so at a relatively low cost in dollars and zero cost in American lives. There is nothing to gain by abandoning it, and everything to lose.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SI2MQT">
Let’s start with the most basic point: <a href="https://www.vox.com/russia">Russia</a>’s invasion of Ukraine was an act of evil. Since the war’s beginning, the Russian government and its propaganda outlets have openly announced that their war aim is to seize Ukrainian territory and subjugate its government to the Kremlin.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YbwkYl">
This was evident not just in words, like <a href="https://www.washingtonpost.com/world/2024/02/08/tucker-carlson-putin-interview-released/">President Vladimir Putin’s recent interview with Tucker Carlson</a>, but also in deeds. The war began with a <a href="https://www.vox.com/2022/3/18/22977801/russia-ukraine-war-losing-map-kyiv-kharkiv-odessa-week-three">failed</a> lightning thrust targeting the Ukrainian capital in Kyiv, during which Russian forces engaged in horrific atrocities: <a href="https://www.vox.com/23020696/ukraine-russia-genocide-allegations">executing entire families</a> and <a href="https://www.cbc.ca/news/world/civilian-attacks-russia-ukraine-1.6958649">indiscriminately bombing populated areas</a>.
</p>
<aside id="gaoVEA">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r0adfD">
There are many problems with the Ukrainian government it is <a href="https://www.wsj.com/articles/politics-and-elections-on-pause-in-ukraine-for-war-298f0eb8">an imperfect democracy</a> whose <a href="https://www.nytimes.com/2024/02/08/world/europe/zelensky-general-valery-zaluzhny-ukraine-military.html?smtyp=cur&amp;smid=tw-nytimesworld">battlefield performance has worsened</a> as the war degenerated into a kind of stalemate. Its maximalist stated objective of winning all its territory back through force may very well be impossible.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QiMJAZ">
But the justice of its basic cause is unimpeachable. Ukraine is fighting a classic war of self-defense, a country protecting its people and its sovereignty from a large neighboring dictatorship that wishes to crush it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FuhGM2">
And the success of Ukraine’s war hinges crucially on American support.
</p>
<h3 id="6zpfZP">
Why American aid is so important
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3VpMFw">
The United States, labeled “the arsenal of democracy” during World War II, is playing that role again today. America is providing Ukraine with advanced weapons systems, like <a href="https://www.vox.com/2022/6/4/23150697/how-ukraines-new-weapons-different-battlefield-russia-himars-nato">HIMARS mobile artillery</a>, and ammunition that neither the Ukrainians nor European allies can get to the field on their own in sufficient numbers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TWaSER">
Currently, American funding has been effectively suspended due to the holdup in <a href="https://www.vox.com/congress">Congress</a>. We can already see the consequences: Ukrainian fighters, <a href="https://www.ft.com/content/6594e548-8b2e-4c95-a589-7d9e358062d2">working with a third of the ammunition they need to fight</a>, being forced to retreat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nQKhTH">
What happens if the aid dries up indefinitely? Vox’s Josh Keating <a href="https://www.vox.com/world-politics/24002840/ukraine-russia-war-united-states-aid-volodymyr-zelensky-vladimir-putin-europe-congress-border">reported on this extensively</a>, and his sources painted a grim picture:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="heaMRh">
“A failure to supply military aid to Ukraine isn’t going to cause an immediate Russian victory, but it is going to change the character of the war,” said Franz-Stefan Gady, a defense analyst with the Center for a New American Security who has made multiple research trips to the front lines in Ukraine. Gady said that while Ukraine’s military has traditionally been an “artillery dominant military force,” without shells for those guns, “they would likely start pursuing more asymmetric strategies. That is, withdrawing from certain sectors of the front lines into urban settlements, trying to draw Russian forces into urban combat.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jCdvRu">
This scenario is … a grim prospect for Ukraine’s civilians. Urban combat always has an extremely high civilian death toll and given the heavy-handed tactics employed by the Russian military, the list of Ukrainian cities and towns entirely decimated by war — Mariupol, Bakhmut — would likely grow.
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hr88Uq">
Even if you see <a href="https://newrepublic.com/article/173752/what-happened-biden-human-rights-agenda-modi">the US government as human rights hypocrites</a> or don’t believe protecting Ukrainian lives is America’s concern, the outcome of this war directly affects US interests.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="y6Y6R2">
Currently, the fighting is mostly in Ukraine’s more rural eastern half. If it moves west, into the heart of Ukraine’s largest cities, it moves closer to nearby NATO treaty allies. The odds of a scary spillover incident — of a miscalculation that could trigger a wider war between Russia and the American-led alliance — would rise accordingly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZguzZI">
At present, the best way to limit the risk of war between nuclear-armed powers is to help Ukraine keep Russia physically further away from NATO borders. Continuing aid, by contrast, is unlikely to trigger a direct escalation between Russia and the United States — <a href="https://www.rand.org/pubs/research_briefs/RBA2807-1.html">as the past two years of fighting have shown</a>.
</p>
<h3 id="2UazGS">
Global security is worth a lot more than $61 billion
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aBJhXX">
Again, it is unlikely that Ukraine will simply defeat Russia and win back all of its territories. The most likely scenario for the war’s end is — like most wars — negotiation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GdfuVk">
But as in any negotiation, leverage matters. Political scientists often describe war as itself a process of bargaining, one in which it’s <a href="https://www.amazon.com/War-Punishment-Causes-Termination-First/dp/0691049440">rational for states to continue fighting</a> until the balance of power between the two sides is clear. To bring about a settlement in which Russia’s aggression is punished rather than rewarded, Ukraine needs to be strong on the battlefield.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L8y2KR">
And if Russia is rewarded, it has an incentive to engage in more provocations on NATO’s frontier. A world where Ukraine is forced to the table by American abandonment is <a href="https://www.theatlantic.com/newsletters/archive/2024/02/if-russia-wins/677398/">a vastly more dangerous one</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qijoNw">
Sixty-one billion dollars sure sounds like a lot of money. But the amount it purchases — sovereignty for an embattled democracy, civilian safety from Russian massacres, and decreasing the odds of a terrifying wider war — is easily worth the price. For Congress to do anything but rush it through would be an appalling betrayal not just of Ukraine, but of America.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VCmOJL">
<em>This story appeared originally in </em><a href="https://www.vox.com/today-explained-podcast"><em>Today, Explained</em></a><em>, Vox’s flagship daily newsletter. </em><a href="https://www.vox.com/pages/today-explained-newsletter-signup"><em><strong>Sign up here for future editions</strong></em></a><em>.</em>
</p></li>
<li><strong>The race to replace George Santos, explained</strong> -
<figure>
<img alt="George Santos looks down while inside a car with the windows rolled up." src="https://cdn.vox-cdn.com/thumbor/iIBWsuNpv-b6BUSgb4tfr1zDwtQ=/445x0:4000x2666/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73135326/1843218464.0.jpg"/>
<figcaption>
George Santos is gone, and the race to replace him is a squeaker. | Victor J. Blue/Bloomberg via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Is the situation really so dire for Democrats? Tuesday’s special election will give us a clue.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JefLWU">
Even the race to replace <a href="https://www.vox.com/policy-and-politics/2023/1/24/23569138/george-santos-scandal-lies">George Santos</a> in <a href="https://www.vox.com/congress">Congress</a> is packed with drama.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FBa6Yq">
The <a href="https://nymag.com/intelligencer/2023/11/george-santos-is-leaving-congress-the-most-george-santos-way.html">historic expulsion</a> of Santos in December has prompted a rare special election in a swing congressional district that could prove a bellwether for November. A Democratic win in New York’s Third Congressional District, which <a href="https://www.vox.com/joe-biden">Joe Biden</a> won by 8 in 2020, would further shrink the already tenuous Republican majority and make it that much easier for Democrats to win back the House. A Republican hold, though, would be a huge boost for the GOP in the Long Island district located on the edge of New York City. After all, if they can survive <a href="https://www.vox.com/policy-and-politics/23520848/george-santos-fake-resume">George Santos</a>’s scandals in the suburbs, perhaps<strong> </strong>they can survive <a href="https://www.vox.com/donald-trump">Donald Trump</a>’s too.
</p>
<h3 id="VrGG4u">
Who are the candidates?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B3TqQ6">
Democrats are running perhaps their strongest possible candidate in the district: former Rep. Tom Suozzi. Suozzi represented the seat for three terms before giving it up in 2022 for a long-shot primary challenge to incumbent Gov. Kathy Hochul. Suozzi is a longtime local politician who is well-liked and has cultivated a moderate image. In contrast, the Republican candidate, Mazi Pilip, is a relative newcomer to politics, albeit one with a sterling biography. A first-term member of the county legislature and a mother of seven, Pilip is an Ethiopian Jew who served in the Israel Defense Forces before immigrating to the United States with her husband. She has run a cautious, sheltered campaign, dodging reporters and holding relatively few public events.
</p>
<h3 id="kumm9M">
What are the polls saying?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rOtpnE">
The limited public polling available shows that the race will be very close. A recent <a href="https://scri.siena.edu/wp-content/uploads/2024/02/NY030224-CrosstabsFinal.pdf">Newsday/Siena College poll</a> shows Suozzi with a narrow 48 percent to 44 percent lead, and one from <a href="https://emersoncollegepolling.com/new-yorks-3rd-congressional-district-poll-suozzi-holds-slight-edge-over-pilip/">Emerson College</a> gives the Democrat an almost identical 50 percent to 47 percent margin. Both polls show Biden being deeply unpopular in the district with an approval rating under 40 percent, and the Siena poll shows Donald Trump winning a head-to-head matchup against Biden by a 47 percent to 42 percent margin in the district.
</p>
<h3 id="rAzuHk">
Why is this close?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qpPkdb">
First of all, it’s close because no one particularly cares about George Santos anymore. The disgraced former Congress member hasn’t been a major issue in the election, and local Republicans have done a good job of <a href="https://nymag.com/intelligencer/2023/11/the-blood-feud-between-george-santos-new-york-republicans.html">distancing themselves</a> from him. Most called for Santos to be ousted from Congress over a year ago, and now Santos is simply viewed by voters as an aberration.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tb1qpw">
But there are also dynamics on the ground in the district that make it different from other suburban areas where Democrats have surged in the Trump era. Instead, it was a place where Republicans had made significant gains in local elections in recent years. Steve Israel, who represented a similar district in Congress for eight terms before retiring in 2016, told Vox that “it had strongly over-performed for Republicans and underperformed for Democrats, even while Democrats have been winning handily in suburbs across the rest of the country.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UgYh7s">
In particular, Israel pointed to anxiety about crime and migrants in a district that borders New York City. “When progressives talked about defunding the police and cashless bail, that pushes a lot of moderate suburban voters to Republicans,” said the former Democratic representative. “A lot of suburban voters are either cops or know cops.” Further, he pointed out that “a lot of suburban voters [in the district] commute to New York City. So you’ve had this perfect storm of headlines on crime. And then add to that more recent headlines about migrants being bused into Manhattan. And that has triggered anxieties in a population that is generally moderate, that is generally progressive on social issues.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IRCsdF">
These trends were clear in 2022 when Republicans overwhelmingly carried the district. Lee Zeldin, the GOP nominee for governor, won it by double digits as Republicans picked up a number of House seats in New York while having a disappointing night elsewhere.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aVwiX1">
The other key factor keeping things close is the strength of the Nassau County Republican Party. It’s one of the <a href="https://www.nytimes.com/2024/02/12/nyregion/republicans-nassau-pilip-santos.html">last political machines</a> in the country and has a strong get-out-the-vote operation that has been credited with helping Republicans win an array of local races in recent years and creating a strong bench in the district. There’s the belief among Republicans that, if the race is close, it will carry Pilip to victory, despite the fact that Suozzi and his allies have outspent her on TV and radio ads.
</p>
<h3 id="656vkx">
What does this mean nationally?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xxdJ1X">
At the most basic level, a Democratic win on Tuesday reduces the Republican majority on Capitol Hill to just three votes. With House Speaker <a href="https://nymag.com/intelligencer/2023/10/house-speaker-mike-johnson-the-nice-guy-who-finished-first.html">Mike Johnson</a> struggling to keep his conference united, this will make his task that much harder as Congress faces yet another government funding deadline in March — let alone as he deals with contentious issues like aid to Ukraine and <a href="https://www.vox.com/immigration">immigration reform</a>. A Republican win would give him just a little extra breathing room and provide a morale boost.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nHwdVS">
Further, Democrats see their path to taking back the House as winning the 18 GOP congressional districts that Joe Biden won in 2020. This is one of them, and if they can’t pick up this one, it bodes ill for their prospects in the other 17 districts — particularly the six other districts in New York and New Jersey.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LjI67y">
At a broader level, it becomes a referendum on how much the migrant crisis will be an issue in 2024. As <a href="https://www.migrationpolicy.org/news/border-numbers-fy2023#:~:text=The%202.5%20million%20encounters%20of,of%20year%2Dend%20government%20statistics">unprecedented</a> numbers of undocumented immigrants enter the United States, straining social services in cities across the country, the issue has become increasingly front of mind for voters. Republicans have harped on it throughout the campaign, forcing Suozzi to go on the defensive about it. With the special election being the only one held in a competitive seat before November’s presidential election, the result will be a key data point moving forward on the topic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IFcsJp">
It will also be a measuring stick for how much <a href="https://www.vox.com/abortion">abortion</a> will continue to be a live political issue now that more than a year has passed since the <a href="https://www.vox.com/scotus">Supreme Court</a> <a href="https://www.vox.com/2022/5/3/23055125/roe-v-wade-abortion-rights-supreme-court-dobbs-v-jackson">overturned <em>Roe v. Wade</em></a>. Suozzi has run as a stalwart pro-abortion-rights candidate, while Pilip has broadly labeled herself as “pro-life” while dodging more detailed questions about how she would vote on Capitol Hill.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="f4CR0H">
And as Democrats respectively stay focused on abortion and Republicans on immigration, the result on Tuesday will be a clear indicator which of the two issues voters are more focused on ahead of November.
</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>Young sailors Banny and Akshay await their big break</strong> - HYDERABAD</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>Coimbatore showjumper wins laurels at the Junior National Equestrian Championship</strong> - Aradhana Anand fought it out at the Junior National Equestrian Championship to win two golds and a bronze medal</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>India’s oldest living Test cricketer Dattajirao Gaekwad dies at 95</strong> - He played for India between 1952 and 1961, captaining the national team in 1959 when it toured England.</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>Pakistan Super League hit by pullouts of overseas cricketers</strong> - The PSL begins in Lahore on February 17 and all the six franchises have been hit hard with several players opting to play in other tournaments</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>Premier League | Chelsea snatch last-gasp win at struggling Palace</strong> - The 3-1 win was Chelsea’s 13th straight league win over Crystal Palace — a club record.</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>Karnataka CM felicitates Australian Open doubles title winner Rohan Bopanna, announces cash prize of ₹50 lakh</strong> - Bopanna was accompanied by his family during the meeting with the CM on February 13</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>Only one death sentence confirmed by High Court in 2023, lowest since 2000: Data</strong> - With 120 death sentences imposed by trial courts and 561 prisoners under the sentence of death, 2023 marked the highest number of prisoners on death row in nearly two decades</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>Reality tech firm unveils digital twin of Mohammed Quli Qutb Shah’s tomb</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>Former I-T officer inducted into Kerala CM’s personal staff as reward for his clean chit in SNC-Lavalin case, alleges Shaun George</strong> - Shaun George alleges that R. Mohan gave clean chit to Pinarayi Vijayan in his capacity as Additional Director of Income Tax, Director General of Income Tax, Kochi, in a report dated July 24, 2008</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 Indian islands</strong> - Prime Minister Narendra Modi recently encouraged travel to Lakshadweep. In the Interim Budget, the Finance Minister announced that the island would get funds to improve its infrastructure. How well do you know India’s major islands?</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>Greece on the brink of legalising same-sex marriage</strong> - A bill would allow gay couples to marry and adopt, but it faces opposition from the Orthodox Church.</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 US economy is powering ahead of Europe’s</strong> - A fast-growing economy, low jobless numbers and falling inflation - how the US outpaced competitors.</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>Watch: Huge fire engulfs new Swedish water park</strong> - Video shows huge flames and thick smoke rising from large water slides in Gothenburg.</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>Europe ‘needs a decade to build up arms stocks’</strong> - The head of Rheinmetall, Germany’s biggest defence firm, says Europe’s ammunition stocks are currently empty.</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>Polish state TV host decries past anti-LGBT output</strong> - Wojciech Szelag apologised to LGBT people for the TVP Info channel’s “hateful words” targeted at them.</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>A new generation of storm chasers takes on Mother Nature in Twisters trailer</strong> - “You don’t face your fears, you ride ’em.” - <a href="https://arstechnica.com/?p=2002700">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ongoing campaign compromises senior execs’ Azure accounts, locks them using MFA</strong> - The wide range of employee roles targeted indicates attacker’s multifaceted approach. - <a href="https://arstechnica.com/?p=2002911">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>F-Zero courses from a dead Nintendo satellite service restored using VHS and AI</strong> - There’s still a $5,000 prize for the original Japanese Satellaview broadcasts. - <a href="https://arstechnica.com/?p=2002898">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>“Very sick” pet cat gave Oregon resident case of bubonic plague</strong> - The person’s cat was reportedly extremely ill and had a draining abscess. - <a href="https://arstechnica.com/?p=2002891">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prime Video cuts Dolby Vision, Atmos support from ad tier—and didn’t tell subs</strong> - To get them back, you must pay an extra $2.99/month for the ad-free tier. - <a href="https://arstechnica.com/?p=2002778">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>Roman soldier says, “We lost a man and now number only 99”. His centurion replies, “I see”. The soldier responds…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
No, XCIX
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/NYY15TM"> /u/NYY15TM </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1aphfeg/roman_soldier_says_we_lost_a_man_and_now_number/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1aphfeg/roman_soldier_says_we_lost_a_man_and_now_number/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mary is invited to her boyfriend Johnny’s home for dinner and to meet his parents</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She’s very nervous about meeting them, and is on her best manners so as to ensure she gives her best impression.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The parents are warm and seem pleased to make her acquaintance after all they’ve heard from Johnny. The family dog Fido is also very friendly and soon takes a liking to her.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They sit to sumptuous dinner which the parents have prepared and begin eating and making conversation. Fido wants to stay close to his new best friend and seats himself uunder Mary’s chair.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Soon into the meal, Mary begins to regret the extra large burger she had for lunch. The gas is building uncomfortably inside her and she realises she has no choice but to let it out. Not wanting to make a bad impression she carefully squeezes the fart out as quietly as she can. Only the slightest noise can be heard and nobody seems to notice. But nobody could ignore the smell. The mother looks over in Mary’s direction, spots Fido and sternly exclaims “Fido!”. Mary is relieved to be rid of her fart and relieved that Fido has taken the blame.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The evening continues amicably but soon the pressure begins to build again. Mary lets another, bigger fart free, a little more boldly this time. Everyone could hear and nobody would be able to mistake the direction the fart came from. Fortunately, to Mary’s satisfaction, the mother again looks toward Mary then at Fido and once more exclaims “Fido!”. The poor dog looks up guiltily. Mary feels a little bad for the dog but is glad to have a way to relieve herself without embarassing herself.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Mary is relaxed now, getting along very well with the parents and confident that she is making a good impression on her boyfriend’s parents. The pressure of another large fart again builds in her gut but now she knows the dog will take the blame she doesn’t bother holding back. She let’s free a roaring, explosive and eye-watering fart that makes everyone stop their dinner. The mother puts her utensils down, rubs her eyes and angrily shouts at the dog “Fido! This is the last time! Get out from under there before she shits on you!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/robreim"> /u/robreim </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1apf6xq/mary_is_invited_to_her_boyfriend_johnnys_home_for/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1apf6xq/mary_is_invited_to_her_boyfriend_johnnys_home_for/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Union Brothel</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A grumpy old man walks into a brothel and asks the madam “Is this a union brothel?” “No, sir,” she replies “I’ve owned and operated this bordello for 50 years without a union!” “Well, I’m a union man, so I only visit union brothels!” the man replies as he slams the door on his way out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Three more cathouses, the same thing. Until he visits the very last bang shack in town; where the madam says “Why yes, we’re the only union pleasure house this side of the Mississippi!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“That’s great!” he shouted excitedly “I want an hour with your prettiest, most voluptuous girl!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I’m sure you do.” she replied “But Agnes has seniority!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/daschande"> /u/daschande </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1apcxqy/a_union_brothel/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1apcxqy/a_union_brothel/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What do you call a man with no arms and no legs fighting with his cat?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Claude
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/kickypie"> /u/kickypie </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1apmka6/what_do_you_call_a_man_with_no_arms_and_no_legs/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1apmka6/what_do_you_call_a_man_with_no_arms_and_no_legs/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>John asks his high school crush Mary to the senior prom</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The day arrives, and he picks her up in his dad’s car, sporting a fresh new suit, and he’s just buzzing with excitement to be going out with the most beautiful girl in the world.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Once they arrive Mary insists they take their picture together - it’s a long line of other couples but eventually they get to the front and get their picture
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Afterward they make their way to the auditorium and Mary turns to John and says, “ooohh they have cookies! Will you get me one?” John quickly obliges, only to find that there’s another long line at the concession table. He eventually secures a chocolate chip cookie and brings it over to Mary.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“This is amazing but listen, I didn’t have diner yet, will you get me a slice of pizza?” John agrees, eager to make his date happy and once again waits in the long line for pizza.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He returns with the food and watches her eat, very eager to get to dance with her. She looks up at him and bats her eyelashes “John, this has all made me rather thirsty, will you bring me a glass of punch?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
John obliges again, eager to impress his date. He makes his way over to the drink table and finds that there’s no punch line.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/rebekoning"> /u/rebekoning </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1apbq5r/john_asks_his_high_school_crush_mary_to_the/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1apbq5r/john_asks_his_high_school_crush_mary_to_the/">[comments]</a></span></p></li>
</ul>
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