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<title>24 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>Who has the flu? Early winter 2023-24 spread of flu and COVID-19</strong> -
<div>
Winter 2023-24 has seen an unusual confluence of a variety of respiratory illnesses, ranging from flu to RSV (Respiratory Syncytial Virus) and COVID-19. Between December 21, 2023 and January 29, 2024, we surveyed 30,460 individuals aged 18 and older across all 50 states plus the District of Columbia. We asked them if they had experienced an Influenza-like Illness (ILI) defined as experiencing a fever and cough, or a fever and sore throat, and/or if they had been diagnosed with COVID-19, over the previous month. Amongst those who responded yes to such questions, we asked them whether or not they had sought medical attention. In this report, we summarize our findings across a variety of demographic subgroups, including age, race, education, income, gender, and geography.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/wfx3g/" target="_blank">Who has the flu? Early winter 2023-24 spread of flu and COVID-19</a>
</div></li>
<li><strong>Thymidine Phosphorylase Mediates SARS-CoV-2 Spike Protein Enhanced Thrombosis in K18-hACE2TG Mice</strong> -
<div>
COVID-19, caused by SARS-CoV-2, is associated with arterial and venous thrombosis, thereby increasing mortality. SARS-CoV-2 spike protein (SP), a viral envelope structural protein, is implicated in COVID-19-associated thrombosis. However, the underlying mechanisms remain unknown. Thymidine phosphorylase (TYMP), a newly identified prothrombotic protein, is upregulated in the plasma, platelets, and lungs of patients with COVID-19 but its role in COVID-19-associated thrombosis is not defined. In this study, we found that wild-type SARS-CoV-2 SP significantly promoted arterial thrombosis in K18-hACE2TG mice. SP-accelerated thrombosis was attenuated by inhibition or genetic ablation of TYMP. SP increased the expression of TYMP, resulting in the activation of signal transducer and activator of transcription 3 (STAT3) in BEAS-2B cells, a human bronchial epithelial cell line. A siRNA-mediated knockdown of TYMP inhibited SP-enhanced activation of STAT3. Platelets derived from SP-treated K18-hACE2TG mice also showed increased STAT3 activation, which was reduced by TYMP deficiency. Activated STAT3 is known to potentiate glycoprotein VI signaling in platelets. While SP did not influence ADP- or collagen-induced platelet aggregation, it significantly shortened activated partial thromboplastin time and this change was reversed by TYMP knockout. Additionally, platelet factor 4 (PF4) interacts with SP, which also complexes with TYMP. TYMP enhanced the formation of the SP/PF4 complex, which may potentially augment the prothrombotic and procoagulant effects of PF4. We conclude that SP upregulates TYMP expression, and TYMP inhibition or knockout mitigates SP-enhanced thrombosis. These findings indicate that inhibition of TYMP may be a novel therapeutic strategy for COVID-19-associated thrombosis.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.23.581661v1" target="_blank">Thymidine Phosphorylase Mediates SARS-CoV-2 Spike Protein Enhanced Thrombosis in K18-hACE2TG Mice</a>
</div></li>
<li><strong>A specific phosphorylation-dependent conformational switch of SARS-CoV-2 nucleoprotein inhibits RNA binding</strong> -
<div>
The nucleoprotein (N) of SARS-CoV-2 encapsidates the viral genome and is essential for viral function. The central disordered domain comprises a serine-arginine-rich domain (SR) that is hyperphosphorylated in infected cells. This modification is thought to regulate function of N, although mechanistic details remain unknown. We use time-resolved NMR to follow local and long-range structural changes occurring during hyperphosphorylation by the kinases SRPK1/GSK-3/CK1, thereby identifying a conformational switch that abolishes interaction with RNA. When 8 approximately uniformly-distributed sites are phosphorylated, the SR domain competitively binds the same interface as single-stranded RNA, resulting in RNA binding inhibition. Phosphorylation by PKA does not prevent RNA binding, indicating that the pattern resulting from the physiologically-relevant kinases is specific for inhibition. Long-range contacts between the RNA-binding, linker and dimerization domains are also abrogated, phenomena possibly related to genome packaging and unpackaging. This study provides insight into recruitment of specific host kinases to regulate viral function.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.22.579423v1" target="_blank">A specific phosphorylation-dependent conformational switch of SARS-CoV-2 nucleoprotein inhibits RNA binding</a>
</div></li>
<li><strong>A pan-tissue, pan-disease compendium of human orphan genes</strong> -
<div>
Species-specific genes are ubiquitous in evolution, with functions ranging from prey paralysis to survival in subzero temperatures. Because they are typically expressed under limited conditions and lack canonical features, such genes may be vastly under-identified, even in humans. Here, we leverage terabytes of human RNA-Seq data to identify thousands of highly-expressed transcripts that do not correspond to any Gencode-annotated gene. Many may be novel ncRNAs although 80% of them contain ORFs that have the potential of encoding proteins unique to Homo sapiens (orphan genes). We validate our findings with independent strand-specific and single-cell RNA-seq datasets. Hundreds of these novel transcripts overlap with deleterious genomic variants; thousands show significant association with disease-specific patient survival. Most are dynamically regulated and accumulate selectively in particular tissues, cell-types, developmental stages, tumors, COVID-19, sex, and ancestries. As such, these transcripts hold potential as diagnostic biomarkers or therapeutic targets. To empower future discovery, we provide a compendium of these huge RNA-Seq expression data, and RiboSeq data, with associated metadata. Further, we supply the gene models for the novel genes as UCSC Genome Browser tracks.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.21.581488v1" target="_blank">A pan-tissue, pan-disease compendium of human orphan genes</a>
</div></li>
<li><strong>Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike</strong> -
<div>
The trimeric spike protein plays an essential role in the SARS-CoV-2 virus lifecycle, facilitating virus entry through binding to the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediating viral and host membrane fusion. The SARS-CoV-2 spike contains an allosteric fatty acid (FA) binding site at the interface between two neighbouring receptor-binding domains. This site, also found in some other coronaviruses, binds free fatty acids such as linoleic and oleic acid, and other small molecules. Understanding allostery and how this site modulates the behaviour of different regions in this protein could potentiate the development of promising alternative strategies for new coronavirus therapies. Here, we apply dynamical nonequilibrium molecular dynamics (D-NEMD) simulations to investigate allosteric effects and identify the communication pathways in the fully glycosylated spike in the original SARS-CoV-2 ancestral variant. The results reveal the allosteric networks that connect the FA site to important functional regions of the protein, including some more than 40 Angstroms away. These regions include the receptor binding motif, an antigenic supersite in the N-terminal domain, the furin cleavage site, the regions surrounding the fusion peptide and a second allosteric site known to bind heme and biliverdin. The networks identified here highlight the complexity of the allosteric modulation in this protein and reveal a striking and unexpected connection between different allosteric sites. Notably, 65% of amino acid substitutions, deletions and insertions in the Alpha, Beta, Delta, Gamma and Omicron variants map onto or close to the identified allosteric pathways.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.06.565757v2" target="_blank">Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike</a>
</div></li>
<li><strong>The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: a promising therapeutic compound against the cytokine storm</strong> -
<div>
The challenges of the COVID-19 pandemic have highlighted an increasing clinical demand for safe and effective treatment options against an overzealous immune defence response, also known as the "cytokine storm". Andrographolide is a naturally derived bioactive compound with promising anti-inflammatory activity in many clinical studies. However, its cytokine-inhibiting activity, in direct comparison to commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), has not been extensively investigated in existing literature. The anti-inflammatory activities of andrographolide and common NSAIDs, such as diclofenac, aspirin, paracetamol and ibuprofen were measured on lipopolysaccharide (LPS) and interferon-{gamma} induced RAW264.7 cells. The levels of PGE2, nitric oxide (NO), TNF- &amp; LPS-induced release of pro-inflammatory cytokines on differentiated human macrophage THP-1 cells were measured against increasing concentrations of andrographolide and aforementioned NSAIDs. The associated mechanistic pathway was examined on NF{kappa}B using flow cytometry on the human endothelial-leukocyte adhesion molecule (ELAM9) (E-selectin) transfected RAW264.7 cells with green fluorescent protein (GFP). Andrographolide exhibited broad and potent anti-inflammatory and cytokine-inhibiting activity in both cell lines by inhibiting the release of IL-6, TNF- and IFN-{gamma}, which are known to play a key role in the etiology of cytokine storm and the pathogenesis of inflammation. In comparison, the tested NSAIDs demonstrated weak or no activity against proinflammatory mediators except for PGE2, where the activity of andrographolide (IC50 = 8.8 M, 95% CI= 7.4 to 10.4 M) was comparable to that of paracetamol (IC50 = 7.73 M, 95% CI = 6.14 to 9.73 M). The anti-inflammatory action of andrographolide was associated with its potent downregulation of NF{kappa}B. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.21.581396v1" target="_blank">The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: a promising therapeutic compound against the cytokine storm</a>
</div></li>
<li><strong>Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies</strong> -
<div>
SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) {beta} sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as “sustainers”), but not in “decliners”. Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic bacteria. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly-responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.06.543529v3" target="_blank">Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies</a>
</div></li>
<li><strong>Integrating population-level and cell-based signatures for drug repositioning</strong> -
<div>
Genetics-informed drug repositioning presents a streamlined and cost-efficient way to broaden therapeutic options. However, leveraging the full spectrum of molecular signatures remains underexplored. We introduce TReD (Transcriptome-informed Reversal Distance), integrating population-level disease signatures robust to reverse causality and cell-based drug-induced response profiles. TReD embeds the disease signature and drug profile in a high-dimensional normed space, quantifying the reversal potential of candidate drugs in a disease-related cell screen assay. For illustration, we apply TReD to COVID-19 and type 2 diabetes (T2D). We identify 37 potential drugs against COVID-19, over 70% (27/37) with prior associations, and eight supported by clinical trials. For T2D, we observe reversal signals for 86 compounds on multiple disease signatures, with more than 40% supported by published literature. In summary, we propose a comprehensive genetics-anchored framework integrating population-level signatures and cell-based screens that can accelerate the search for new therapeutic strategies.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.25.564079v2" target="_blank">Integrating population-level and cell-based signatures for drug repositioning</a>
</div></li>
<li><strong>Changes in risk perception during the COVID-19 pandemic in Southeast Alaska: Self-identified determinants of risk and protective behaviors</strong> -
<div>
Social and cultural context shapes how communities perceive health, well-being, and risk. Risk perception can change over time as a product of new information and improved understanding. We investigate risk perception and protective behaviors in Southeast Alaska during the first year of the COVID-19 pandemic. Surveys were circulated at two time points: (1) April-June 2020, before COVID-19 reached epidemic levels in the region, and (2) November 2020-February 2021. Ordinary least squares (OLS) regression models were used to analyze how demographic characteristics of the respondent population influenced risk perception. OLS models were again used to predict how individuals engaged in protective behaviors while controlling for risk perceptions. Controlling for demographic characteristics, risk perception increased as age increased for perceived risk of getting sick and dying from COVID-19, males perceived lower risk in general for all tested variables, and Alaska Native respondents perceived higher risk than non-Alaska Native respondents. Controlling for risk perception, results for protective behaviors were mixed; however, the strongest association identified was that knowing someone with a positive COVID-19 diagnosis increased protective behaviors. Between the two time points, risk perceptions increased significantly for variables related to oneself, others, and community members becoming infected with COVID-19. Protective behaviors like traveling less than normal, buying more cleaning products, and engaging in more subsistence gathering significantly increased. Identifying patterns of risk perception and protective behaviors, and especially how they change over time, are critical to developing place-specific public health recommendations, action, and preparedness plans against future infectious threats.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/4avp7/" target="_blank">Changes in risk perception during the COVID-19 pandemic in Southeast Alaska: Self-identified determinants of risk and protective behaviors</a>
</div></li>
<li><strong>Physical distancing and the perception of interpersonal distance in the COVID-19 crisis</strong> -
<div>
In the wake of the COVID-19 pandemic, it has been mandated to keep enlarged distances from others. We interviewed 136 German subjects over five weeks from the end of March to the end of April 2020 during the first wave of infections about their preferred interpersonal distance (IPD) before, during, and after the COVID-19 pandemic. In response to the pandemic, subjects adapted to distance requirements and preferred a larger IPD. This enlarged IPD was judged to persist after the crisis partially. People anticipated keeping more IPD to others even if there was no longer any risk of a SARS-CoV-2 infection. We also sampled two follow-up measurements, one in August, after the first wave had been flattened, and one in October 2020, at the beginning of the second wave. We discuss our findings in light of proxemic theory and an indicator for socio-cultural adaptation beyond the course of the pandemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/95n3p/" target="_blank">Physical distancing and the perception of interpersonal distance in the COVID-19 crisis</a>
</div></li>
<li><strong>Maturing neutrophils of lower density associate with thrombocytopenia in Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome</strong> -
<div>
Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by strong neutrophil activation. Neutrophils are the most abundant immune cell type in the circulation and are specially equipped to rapidly respond to infections. They are more heterogenous than previously appreciated, with specific neutrophil subsets recently implicated in inflammation and immunosuppression. Furthermore, neutrophils can be divided based on their density to either low-density granulocytes (LDGs) or "normal density" polymorphonuclear cell (PMN) fractions. In the current study we aimed to identify and characterize the different neutrophil subsets in the circulation of PUUV-HFRS patients. PMNs exhibited an activation of antiviral pathways, while circulating LDGs were increased in frequency following acute PUUV-HFRS. Furthermore, cell surface marker expression analysis revealed that PUUV-associated LDGs are primarily immature and most likely reflect an increased neutrophil production from the bone marrow. Interestingly, both the frequency of LDGs and the presence of a "left shift" in blood associated with the extent of thrombocytopenia, one of the hallmarks of severe HFRS, suggesting that immature neutrophils could play a role in disease pathogenesis. These results imply that elevated circulating LDGs might be a general finding in acute viral infections. However, in contrast to the COVID-19 associated LDGs described previously, the secretome of PUUV LDGs did not show significant immunosuppressive ability, which suggests inherent biological differences in the LDG responses that can be dependent on the causative virus or differing infection kinetics.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.19.580937v1" target="_blank">Maturing neutrophils of lower density associate with thrombocytopenia in Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome</a>
</div></li>
<li><strong>Confirmation of Covid Infection Status and Reporting of Long Covid Symptoms in a Population-Based Birth Cohort: No Evidence of a Nocebo Effect</strong> -
<div>
Some patients with COVID-19 develop symptoms after the acute infection, known as ‘Long COVID’. We examined whether or not confirmation of COVID-19 infection status could act as a nocebo, using data from questionnaires distributed to the Avon Longitudinal Study of Parents and Children cohort. We examined associations between confirmation of COVID-19 infection status (confirmed by a positive test versus unconfirmed) and reporting of Long COVID symptoms. We explored the roles of sex and anxiety as potential moderators. There was no clear evidence of a strong association between confirmation of COVID-19 infection status and the Long COVID composite score, physical or psychological symptoms, or duration of symptoms. There was no clear evidence of moderation by sex or anxiety. We therefore found no evidence of a nocebo effect. Our data suggest that this psychological mechanism does not play a role in the medical symptomatology experienced by patients with Long COVID.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/pwq9b/" target="_blank">Confirmation of Covid Infection Status and Reporting of Long Covid Symptoms in a Population-Based Birth Cohort: No Evidence of a Nocebo Effect</a>
</div></li>
<li><strong>Affordable private rental supply and demand: short-term disruption (2016–2021) and longer-term structural change (1996–2021)</strong> -
<div>
This research analyses the ABS Census to reveal changes in the supply of private rental housing affordable and available to lower-income households (Q1 and Q2 households) over both the short term (2016–21) and the longer term (1996–2021). It also provides analysis of how COVID-19 policy and population responses temporarily altered the long-run structural trajectory of the private rental sector (PRS) in Australia. In 2021, the Australian PRS housed more than 2.363 million households, a 17 per cent increase of nearly 340,000 households since the 2016 Census. This growth has been greater than total household growth in each intercensal period since 1996. Between 2016 and 2021 PRS growth was concentrated at mid-market levels; in dwellings renting from around $300–$530 per week ($2021). This continues a major change trend first established in 2011, reinforcing the structural shift to a market concentration of dwellings renting at mid-to-higher levels. The long-term shift in the national distribution of PRS household incomes reveals the growth of households with incomes at mid to high levels ($1,246 a week and above). In 1996, these ‘wealthier’ households comprised 40 per cent of all PRS households (or 489,000 households); in 2021, they comprised 64 per cent (or 1,519,000 households), a 211 per cent increase. In comparison, the total number of PRS households increased by 91 per cent between 1996 and 2021 (from 1,234,000 households to 2,362,000). Over the same time frame, there has been a relatively constant total number of lower income renters in the PRS; 508,000 households in1996 and 488,000 in 2024. Nevertheless, there was a shortage of 348,000 affordable and available private rental homes for very-low income (Q1) households in 2021 and that, as a result, 82 per cent of Q1 PRS households paid unaffordable rents.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/h3tfk/" target="_blank">Affordable private rental supply and demand: short-term disruption (2016–2021) and longer-term structural change (1996–2021)</a>
</div></li>
<li><strong>COVID-19 and Changes in Young Adults’ Weight Concerns</strong> -
<div>
The COVID-19 pandemic introduced fundamental challenges to nearly all aspects of college students’ lives, yet changes in key domains of their health, including weight concerns, remain untested. The current study utilized a longitudinal project comprised of 355 young-adult college students (Mage=19.5, 66.8% female, 33.2% male) oversampled for recent substance use behavior. Participants completed multiple assessments (mode=5) from September 2017 to September 2021. Piecewise growth-curve models tested whether COVID-19 onset was associated with changes in the trajectories of young adults’ weight concerns. Analyses also examined participants’ sex as a moderator of these trajectories. On average, participants reported a significant increase in weight concern levels around the start of COVID-19, although weight concern slopes were not significantly different before and after COVID-19. Additionally, moderation analyses showed that females (but not males) had a significant increase in weight concern levels after COVID-19 onset.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/wuhvb/" target="_blank">COVID-19 and Changes in Young Adults’ Weight Concerns</a>
</div></li>
<li><strong>Mathematical Modeling of Impacts of Patient Differences on Renin-Angiotensin System and Applications to COVID-19 Lung Fibrosis Outcomes</strong> -
<div>
Patient-specific premorbidity, age, and sex are significant heterogeneous factors that influence the severe manifestation of lung diseases, including COVID-19 fibrosis. The renin-angiotensin system (RAS) plays a prominent role in regulating the effects of these factors. Recent evidence suggests patient-specific alteration of RAS homeostasis with premorbidity and the expression level of angiotensin converting enzyme 2 (ACE2) during COVID-19. However, conflicting evidence suggests decreases, increases, or no changes in RAS after SARS-CoV-2 infection. In addition, detailed mechanisms connecting the patient-specific conditions before infection to infection-induced RAS alteration are still unknown. Here, a mathematical model is developed to quantify the systemic contribution of heterogeneous factors of RAS during COVID-19. Three submodels are connected–an ABM COVID-19 in-host lung tissue model, a RAS model, and a fibrosis model to investigate the effects of patient-group-specific factors in the systemic alteration of RAS and collagen deposition in the lung. The model results indicate cell death due to inflammatory response as a major contributor to the reduction of ACE and ACE2. In contrast, there are no significant changes in ACE2 dynamics due to viral-bound internalization of ACE2. Reduction of ACE and ACE2 reduces the homeostasis of RAS, including angiotensin II (ANGII), in the lung tissue. At the same time, the decrease in ACE2 increases systemic ANGII and results in severe lung injury and fibrosis. The model explains possible mechanisms for conflicting evidence of RAS alterations in previously published studies, and simulated results are consistent with reported RAS peptide values for SARS-CoV-2-negative and SARS-CoV-2-positive patients. We observed decreased RAS peptides for all patient groups with aging in both sexes. In contrast, large variations in the magnitude of reduction were observed between male and female patients in the older and middle-aged groups. We also predicted that feedback of ANGII{middle dot}AT1R to renin could restore ANGI homeostasis but fails to restore homeostasis values of RAS peptides downstream of ANGI. In addition, the results show that ACE2 variations with age and sex significantly alter RAS peptides and lead to collagen deposition with slight variations depending on age and sex. This model may find further applications in patient-specific calibrations of tissue models for acute and chronic lung diseases to develop personalized treatments.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.06.515367v2" target="_blank">Mathematical Modeling of Impacts of Patient Differences on Renin-Angiotensin System and Applications to COVID-19 Lung Fibrosis Outcomes</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>GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: GS-441524; Drug: Placebo <br/><b>Sponsors</b>: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <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>The Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19 <br/><b>Interventions</b>: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) <br/><b>Sponsors</b>: Selda Sarıkaya; Zonguldak Bulent Ecevit University <br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt</strong> - <b>Conditions</b>: Mucormycosis; Rhinocerebral (Etiology); COVID-19 <br/><b>Interventions</b>: Procedure: debridment <br/><b>Sponsors</b>: Nasser Institute For Research and Treatment <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>Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 <br/><b>Interventions</b>: Drug: Hyperbaric oxygen <br/><b>Sponsors</b>: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk <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>Mindfulness-based Mobile Applications Program</strong> - <b>Conditions</b>: COVID-19; Cell Phone Use; Nurse; Mental Health <br/><b>Interventions</b>: Device: mindfulness-based mobile applications program <br/><b>Sponsors</b>: Yu-Chien Huang <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>Attention Training for COVID-19 Related Distress</strong> - <b>Conditions</b>: Anxiety <br/><b>Interventions</b>: Behavioral: Attention Bias Modification; Behavioral: Attention Control Training; Behavioral: Neutral training <br/><b>Sponsors</b>: Palo Alto University <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Correlation of Antibody Response to COVID-19 Vaccination in Pregnant Woman and Transplacental Passage Into Cord Blood.</strong> - <b>Conditions</b>: Covid-19 <br/><b>Interventions</b>: Diagnostic Test: COVID-19 Spike Protein IgG Quantitative Antibody (CMIA) <br/><b>Sponsors</b>: Vachira Phuket Hospital <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine as Homologue Booster (Immunobridging Study)</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines; COVID-19 Virus Disease <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia; Indonesia-MoH <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: CD40.RBDv vaccin (SARS-Cov2 Vaccin) <br/><b>Sponsors</b>: ANRS, Emerging Infectious Diseases; LinKinVax; Vaccine Research Institute (VRI), France <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>High-definition Transcranial Direct Current Ctimulation and Chlorella Pyrenoidosa to Reduce Cardiovascular Risk</strong> - <b>Conditions</b>: Cardiovascular Diseases; Long Covid19 <br/><b>Interventions</b>: Other: High Definition-transcranial Direct Current Stimulation; Dietary Supplement: Chlorella Pyrenoidosa <br/><b>Sponsors</b>: Federal University of Paraíba; City University of New York <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>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>
</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>Antiviral Protein-Protein Interaction Inhibitors</strong> - Continually repeating outbreaks of pathogenic viruses necessitate the construction of effective antiviral strategies. Therefore, the development of new specific antiviral drugs in a well-established and efficient manner is crucial. Taking into account the strong ability of viruses to change, therapies with diversified molecular targets must be sought. In addition to the widely explored viral enzyme inhibitor approach, inhibition of protein-protein interactions is a very valuable strategy. In…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structural insights into IL-6 signaling inhibition by therapeutic antibodies</strong> - Antibody inhibitors of the interleukin-6 (IL-6) signaling pathway, such as tocilizumab and sarilumab, have been used to treat rheumatoid arthritis, chimeric antigen receptor T cell-induced cytokine storm, and severe COVID-19 pneumonia. Here, we solve the cryogenic electron microscopy structures of sarilumab and tocilizumab in complex with IL-6R to resolutions of 3.2 and 3.3 Å, respectively. These structures reveal that both tocilizumab and sarilumab bind to the D3 domain of IL-6R. The binding…</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>Time Course of the Interaction Between Oral Short-Term Ritonavir Therapy with Three Factor Xa Inhibitors and the Activity of CYP2D6, CYP2C19, and CYP3A4 in Healthy Volunteers</strong> - CONCLUSION: This trial with three microdosed FXaI suggests that at most the rivaroxaban dose should be reduced during short-term ritonavir, and only in patients receiving high maintenance doses. Thorough time series analyses demonstrated differential effects on three different drug-metabolising enzymes over time with immediate profound inhibition of CYP3A4 and only slow recovery after discontinuation.</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>Naphthoquinone derivatives as potential immunomodulators: prospective for COVID-19 treatment</strong> - Inflammation plays a crucial role in COVID-19, and when it becomes dysregulated, it can lead to severe outcomes, including death. Naphthoquinones, a class of cyclic organic compounds widely distributed in nature, have attracted significant interest due to their potential biological benefits. One such naphthoquinone is 3,5,8-trihydroxy-6-methoxy-2-(5-oxohexa-1,3-dienyl)-naphthanthene-1,4-dione (3,5,8-TMON), a compound produced by fungi. Despite its structural similarity to shikonin, limited…</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>Cholesterol and COVID-19-therapeutic opportunities at the host/virus interface during cell entry</strong> - The rapid development of vaccines to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been critical to reduce the severity of COVID-19. However, the continuous emergence of new SARS-CoV-2 subtypes highlights the need to develop additional approaches that oppose viral infections. Targeting host factors that support virus entry, replication, and propagation provide opportunities to lower SARS-CoV-2 infection rates and improve COVID-19 outcome. This includes…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of an ellipticine derivative as TLR3 inhibitor against influenza A virus and SARS-CoV-2</strong> - Influenza and COVID-19 continue to pose global threats to public health. Classic antiviral drugs have certain limitations, coupled with frequent viral mutations leading to many drugs being ineffective, the development of new antiviral drugs is urgent. Meanwhile, the invasion of influenza virus can cause an immune response, and an excessive immune response can generate a large number of inflammatory storms, leading to tissue damage. Toll-like receptor 3 (TLR3) recognizes virus dsRNA to ignite 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>Investigating the Antibody Imprinting Hypothesis among Canadian Paramedics after SARS-CoV-2 Omicron Variant Circulation</strong> - Recent research has highlighted the Omicron variant’s capacity to evade immune protection conferred by wild-type (WT) mRNA vaccines. Despite this observation, the potential involvement of antigenic sin phenomena remains unclear. Our hypothesis posited that a greater number of prior WT vaccine doses might lead to reduced anti-Omicron neutralization Abs following Omicron infection. To investigate this, we analyzed blood samples from human participants in the COVID-19 Occupational Risk,…</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 art of hijacking: how Nsp1 impacts host gene expression during coronaviral infections</strong> - Non-structural protein 1 (Nsp1) is one of the first proteins produced during coronaviral infections. It plays a pivotal role in hijacking and rendering the host gene expression under the service of the virus. With a focus on SARS-CoV-2, this review presents how Nsp1 selectively inhibits host protein synthesis and induces mRNA degradation of host but not viral mRNAs and blocks nuclear mRNA export. The clinical implications of this protein are highlighted by showcasing the pathogenic role of Nsp1…</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 case report of QTc prolongation: Drug induced or myocarditis in Severe Acute Respiratory Syndrome Coronavirus 2</strong> - Remdesivir is a nucleotide prodrug of an adenosine analog. It binds to the viral Ribonucleic Acid (RNA)-dependent RNA polymerase and inhibits viral replication by terminating RNA transcription prematurely. Remdesivir has demonstrated in vitro and in vivo activity against Severe Acute Respiratory Syndrome Coronavirus 2; it also acts in vitro neutralization activity against the Omicron variant and its subvariants. We reported a 54-years-old woman admitted with Coronavirus disease 2019. Considering…</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>Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer’s, and diabetes</strong> - The COVID-19 pandemic caused by the SARS-CoV-2 virus has greatly affected global health. Emerging evidence suggests a complex interplay between Alzheimer’s disease (AD), diabetes (DM), and COVID-19. Given COVID-19’s involvement in the increased risk of other diseases, there is an urgent need to identify novel targets and drugs to combat these interconnected health challenges. Lysophosphatidic acid receptors (LPARs), belonging to the G protein-coupled receptor family, have been implicated in…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synergistic inhibition effects of andrographolide and baicalin on coronavirus mechanisms by downregulation of ACE2 protein level</strong> - The SARS-CoV-2 virus, belonging to the Coronavirus genus, which poses a threat to human health worldwide. Current therapies focus on inhibiting viral replication or using anti-inflammatory/immunomodulatory compounds to enhance host immunity. This makes the active ingredients of traditional Chinese medicine compounds ideal therapies due to their proven safety and minimal toxicity. Previous research suggests that andrographolide and baicalin inhibit coronaviruses; however, their synergistic…</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>Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage</strong> - Viruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue tissue damage through proteolytic degradation of the extracellular matrix. Here, we assess the potential of protease inhibitors (PI) derived from potatoes in inhibiting viral infection and reducing tissue damage. The original full spectrum of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Individual ingredients of NP-101 (Thymoquinone formula) inhibit SARS-CoV-2 pseudovirus infection</strong> - Thymoquinone TQ, an active ingredient of Nigella Sativa, has been shown to inhibit COVID-19 symptoms in clinical trials. Thymoquinone Formulation (TQF or NP-101) is developed as a novel enteric-coated medication derivative from Nigella Sativa. TQF consists of TQ with a favorable concentration and fatty acids, including palmitic, oleic, and linoleic acids. In this study, we aimed to investigate the roles of individual ingredients of TQF on infection of SARS-CoV-2 variants in-vitro, by utilizing…</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>Design, synthesis and biological evaluation of novel 1,2,4a,5-tetrahydro-4H-benzo[b][1,4]oxazino[4,3-d][1,4]oxazine-based AAK1 inhibitors with anti-viral property against SARS-CoV-2</strong> - Coronavirus entry into host cells hinges on the interaction between the spike glycoprotein of the virus and the cell-surface receptor angiotensin-converting enzyme 2 (ACE2), initiating the subsequent clathrin-mediated endocytosis (CME) pathway. AP-2-associated protein kinase 1 (AAK1) holds a pivotal role in this pathway, regulating CME by modulating the phosphorylation of the μ subunit of adaptor protein 2 (AP2M1). Herein, we report a series of novel AAK1 inhibitors based on previously reported…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Role of epinephrine in attenuating cytokine storm, decreasing ferritin, and inhibiting ferroptosis in SARS-CoV-2</strong> - CONCLUSION: Epinephrine may attenuate CS and inhibit ferroptosis which is an iron-dependent, non-apoptotic mode of cell death. Epi interacts with ferric and/or ferrous iron and built a stable complex that impedes activation of beta-adrenergic receptors. Epi may cause marked decrease of ferritin and other inflammatory markers. Epi may be used to decrease iron overload which is associated with many medical diseases like type 2 diabetes mellitus and cardiometabolic diseases such as coronary heart…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Humanitarian Catastrophe in Gaza Can Only Get Worse</strong> - Trying to project the death toll from Israel’s military campaign over the next six months. - <a href="https://www.newyorker.com/news/q-and-a/the-humanitarian-catastrophe-in-gaza-can-only-get-worse">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Legal Weed in New York Was Going to Be a Revolution. What Happened?</strong> - Lawsuits. Unlicensed dispensaries. Corporations pushing to get in. The messy rollout of a law that has tried to deliver social justice with marijuana. - <a href="https://www.newyorker.com/magazine/2024/02/26/legal-weed-in-new-york-was-going-to-be-just-and-fair-what-happened">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Snake with the Emoji-Patterned Skin</strong> - In the wild, ball pythons are usually brown and tan. In America, breeding them to produce eye-catching offspring has become a lucrative, frenetic, and—for some—troubling enterprise. - <a href="https://www.newyorker.com/magazine/2024/02/26/inside-the-world-of-designer-ball-pythons">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Matt Gaetz’s Chaos Agenda</strong> - The Florida Republican is among the most brazen and controversial figures in Donald Trump’s G.O.P. He’s also among the most influential. - <a href="https://www.newyorker.com/magazine/2024/02/26/matt-gaetz-profile">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Trials of Alejandro Mayorkas</strong> - The Secretary of Homeland Security has been forced to respond to an unprecedented flow of migrants to the U.S.-Mexico border. Why are Republicans in Congress impeaching him for it? - <a href="https://www.newyorker.com/magazine/2024/02/26/the-trials-of-alejandro-mayorkas">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The South Carolina primary is a joke. It tells us something deadly serious.</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/8V_9EBh9GJ_NGfTV_CM-3EH342k=/227x0:3160x2200/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73161261/2011424610.0.jpg"/>
<figcaption>
Trump speaks at a campaign rally. | Nic Antaya/Bloomberg via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Trump’s seemingly inevitable romp to victory in Nikki Haley’s home state reveals how strong his hold on the GOP is — and how dangerous he remains to democracy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="766p1G">
Tonight, South Carolina will hold its <a href="https://www.vox.com/politics/2023/2/23/23611828/2024-republican-presidential-candidates-trump-hurd">Republican presidential primary</a>, in which <a href="https://www.vox.com/donald-trump">Donald Trump</a> <a href="https://projects.fivethirtyeight.com/polls/president-primary-r/2024/south-carolina/">is all but certain</a> to crush rival <a href="https://www.vox.com/policy-and-politics/2023/2/14/23599194/nikki-haley-donald-trump-2024-presidential-campaign">Nikki Haley</a> in her home state. Ordinarily, this might feel like big news, as the Palmetto State tends to host one of the most important early contests. <a href="https://www.vox.com/joe-biden">Joe Biden</a>’s 2020 victory in the state, after dismal finishes in Iowa and New Hampshire, is one of the biggest<em> </em>reasons he’s president today.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wLLvTo">
But the coming vote feels irrelevant: The 2024 Republican primary <a href="https://projects.fivethirtyeight.com/polls/president-primary-r/2024/south-carolina/">isn’t and never has been a competitive primary</a>. Trump simply wasn’t going to lose a contest for the hearts and minds of the Republican base. <a href="https://www.politico.com/news/magazine/2023/05/18/donald-trump-paradox-gop-00097458">Ideologically</a>, <a href="https://www.theatlantic.com/politics/archive/2024/02/trump-dominance-business-republicans-congress/677391/">psychologically</a>, even <a href="https://www.nytimes.com/2023/12/02/books/review/the-kingdom-the-power-and-the-glory-tim-alberta.html">spiritually</a> — it’s the Trump party through and through.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LZmc8I">
I <a href="https://damonlinker.substack.com/p/the-unfolding-of-the-inevitable1?utm_source=post-email-title&amp;publication_id=865987&amp;post_id=140927756&amp;utm_campaign=email-post-title&amp;isFreemail=true&amp;r=7ttw&amp;open=false">and</a> others <a href="https://plus.thebulwark.com/p/the-ballad-of-ron-and-nikki?utm_source=post-email-title&amp;publication_id=87281&amp;post_id=140925445&amp;utm_campaign=email-post-title&amp;isFreemail=false&amp;r=7jgsk&amp;utm_medium=email">have</a> been <a href="https://www.vox.com/2024-elections/2023/9/27/23890683/second-republican-debate-gop-fake-rnc-trump">arguing</a> <a href="https://www.vox.com/23979441/nikki-haley-afp-koch-republican-billionaire-trump">this</a> for <a href="https://www.vox.com/23287527/trump-gop-control-august-gop-primary-2022">years</a> <a href="https://www.vox.com/policy-and-politics/22274429/republicans-anti-democracy-13-charts">now</a>. Yet during those same years, many prominent people in politics and the media deluded themselves into thinking he might be dethroned. They have been wrong every time and continued to be wrong long after the strength of Trump’s grip on the GOP could not be denied.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rDSLic">
There’s a lesson to be learned from this track record of failure, one deeper than just “Republicans really like Donald Trump.” Trump’s persistence tells us something critical about the <em>nature</em> of the current Republican party — and why it’s become <a href="https://www.vox.com/policy-and-politics/22274429/republicans-anti-democracy-13-charts">such a danger to American democracy</a>.
</p>
<h3 id="k30Wck">
How Trump keeps wiggling his way out of jams
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zdx19M">
Ever since the early stages of the 2016 GOP primary, the same pattern has repeated itself over and over again: Some new development that looked politically dangerous for Trump ends up not mattering at all. This happened so many times in the <a href="https://www.vox.com/presidential-election">2016 election</a> cycle <em>alone</em> that it became a running joke during the campaign.
</p>
<figure class="e-image">
<img alt="Tweet that says “Well, I’d like to see ol Donny Trump wriggle his way out of THIS jam! Trump wriggles his way out of the jam easily. Ah! Well. Nevertheless.”" src="https://cdn.vox-cdn.com/thumbor/rsb7vL6f7GqW4XF_BzqIPKkAFWE=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25300718/2bc.jpg"/> <cite><span class="citation" data-cites="BronzeHammer">@BronzeHammer</span></cite>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iDYeFg">
The pattern continued through Trump’s presidency, and <a href="https://www.vox.com/2022/6/8/23156442/january-6-committee-trump-polarization-fatigue">most strikingly after January 6</a> — when Trump managed to maintain majority support in the Republican party after inciting an honest-to-god insurrection. At that point, you’d think it would be obvious that Trump was going to cruise to renomination in 2024. Yet somehow, the delusions of a Trump collapse persisted.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Rzyx5c">
During the January 6 Committee meetings in summer 2022, there was widespread speculation that <a href="https://www.npr.org/2022/07/30/1114578872/trump-desantis-pence-president-2024?utm_term=nprnews&amp;utm_source=twitter.com&amp;utm_campaign=politics&amp;utm_medium=social">the dramatic public hearings had weakened Trump’s hold on the GOP</a>. Republican primary voters proceeded to <a href="https://www.vox.com/23287527/trump-gop-control-august-gop-primary-2022">disprove this theory</a> by booting the House members who voted for his impeachment and nominating full-MAGA election deniers, like Arizona’s Kari Lake, to contest key swing races around the country.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BEDWNm">
These candidates performed poorly in the <a href="https://www.vox.com/policy-and-politics/23357154/2022-midterm-elections-guide">2022 midterms</a>, while <a href="https://www.vox.com/ron-desantis">Florida Gov. Ron DeSantis</a> cruised to reelection. This led many observers to see DeSantis as a possible Trump killer, with some going so far as to <a href="https://nymag.com/intelligencer/2023/01/why-desantis-is-on-track-to-beat-trump.html">anoint DeSantis the frontrunner in early 2023</a>. Soon after that, <a href="https://www.vox.com/politics/24034491/iowa-caucus-results-polls-desantis-trump-haley-ramaswamy-republican-party">DeSantis’s poll numbers collapsed</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eCab0S">
After the DeSantis train crashed, Trump skeptics crowned Haley <a href="https://www.axios.com/2023/12/06/debate-tests-nikki-haley-momentum-2024-gop-president">the next anti-Trump Republican hope</a>. She secured <a href="https://afpaction.com/wp-content/uploads/2023/11/AFPA-Endorsement-Memo-.pdf">critical funding from Americans for Prosperity Action</a>, the political arm of the Koch empire, in November — raising the Haley hype to surprising heights going into 2024. In mid-January, prominent pundit Jonathan Rauch gave Haley <a href="https://www.theunpopulist.net/p/nikki-haley-has-a-shot-at-beating?utm_source=post-email-title&amp;publication_id=461280&amp;post_id=140530753&amp;utm_campaign=email-post-title&amp;isFreemail=true&amp;r=7ttw">roughly a 40 percent chance</a> to win the primary, adding that “the odds might shift in her favor quickly.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iCL85j">
Then she lost by double-digits in her supposed stronghold of New Hampshire, and the writing was on the wall in great big bold letters.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2XUVso">
None of this speculation tracked Trump’s poll numbers. The former president <a href="https://www.realclearpolling.com/polls/president/republican-primary/2024/national">consistently led in the polling averages</a>, generally by wide margins. So why did so many get this so wrong?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0IbAOU">
Sometimes, the explanation is mundane wishcasting: centrist or anti-Trump Republicans desperately wishing to avoid a choice between a threat to democracy and a Democrat. But in some cases, there’s a more interesting explanation — that even some of the GOP’s critics didn’t fully appreciate what it had become.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2P9ZOM">
New York magazine’s Jonathan Chait, one of the more perceptive of these critics, was an early booster of DeSantis’s chances. In August of last year, he admitted that he had gotten it wrong — and wrote <a href="https://nymag.com/intelligencer/2023/08/what-i-got-wrong-about-ron-desantis-vs-donald-trump.html">an interesting column</a> trying to explain why he erred. Chait’s basic argument is that Trump’s cult of personality was far more powerful than he had appreciated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rvW1Va">
“Defeating Trump in a contest determining who can most effectively advance ideological or party goals is difficult but attainable. It is obviously impossible to defeat Trump in a contest of who is most loyal to Trump,” Chait concluded.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OzkqVZ">
This is surely a key part of the story. But it also raises a more fundamental question that Chait doesn’t attempt to answer: <em>Why</em> does the Republican base have such unwavering faith in the man?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E5TCRW">
Trump’s celebrity charisma alone isn’t enough of an explanation. Otherwise, former California Gov. Arnold Schwarzenegger would bestride the GOP like a colossus. Nor is Trump’s fawning coverage in the conservative media. Fox News has repeatedly tried to turn the Republican base away from Trump and toward figures like DeSantis, only to have to kiss the ring when the voters didn’t follow their lead.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pgeXpj">
The answer, at least as far as I can tell, is that Trump’s cult is the product of his unique ability to channel the cultural grievances at the heart of the current Republican party.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N2ZAPa">
<a href="https://www.vox.com/2023/8/4/23818817/trump-support-david-brooks-economic-anxiety">Again and again</a>, social scientists found that the best predictor of Trump support among Republican voters is the degree to which they feel discomfort with the changing nature of American demographics and social norms. Trump has sold himself as the only person capable of fighting back against the alleged elite conspiracy behind these changes, saying things like “I alone can fix it” and “<a href="https://www.theguardian.com/us-news/2023/mar/05/i-am-your-retribution-trump-rules-supreme-at-cpac-as-he-relaunches-bid-for-white-house">I am your retribution</a>.” From these building blocks, he has created a <a href="https://www.politico.com/news/magazine/2023/05/18/donald-trump-paradox-gop-00097458">full-scale political movement</a> dedicated to reconquering America.
</p>
<figure class="e-image">
<img alt="A crowd of people in Trump merch, many of whom are holding up smartphones to film." src="https://cdn.vox-cdn.com/thumbor/ft-QlL72tOtf_uSMDJHAQOE4qyo=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25300722/2018990694.jpg"/> <cite>Scott Olson/Getty Images</cite>
<figcaption>
The crowd as former President Donald Trump arrives at a rally on February 17, 2024, in Waterford, Michigan.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="59AZx3">
Trump’s appeal isn’t premised on delivering concrete policy goals, nor even “owning the libs” with high-profile stunts. It is about assuaging the sense of <a href="https://www.sciencedirect.com/science/article/abs/pii/S0962629822000725">fear and resentment</a> at their America being replaced: about achieving victories that assuage the sense of psychological assault created by things like mass immigration, a Black president, shifting gender roles, and <a href="https://www.vox.com/money/2023/4/12/23680135/bud-light-boycott-dylan-mulvaney-travis-tritt-trans">a beloved beer brand</a> cutting an ad with a <a href="https://www.vox.com/lgbtq">trans</a> <a href="https://www.vox.com/influencers">influencer</a>. Donald Trump, as a figure, represents the America they know and love. His victories are their victories, his defeats their defeats.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2I9kYc">
This frame helps us understand why Trump can’t be beaten inside Republican politics. It also clarifies why Trump has been able to steer the Republican party so harshly against democracy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Vk8cX5">
By making his very person into a stand-in for the existential struggle for America’s soul, he has created a world where any loss represents an intolerable blow against everything good about the country. Such a setback can only come from a place of deep corruption — from the Swamp and “Democrat-controlled cities.” And if American democracy has truly been subverted this thoroughly, the logical conclusion is clear: We have to “<a href="https://www.npr.org/2021/02/10/966396848/read-trumps-jan-6-speech-a-key-part-of-impeachment-trial">fight like hell</a>” to save it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="w8IKa2">
The South Carolina primary’s irrelevance points to this deeper and darker story. It is one we must wrestle with in order to truly appreciate the stakes in the coming general election.
</p></li>
<li><strong>How US conservatives fell for two of Latin America’s most controversial leaders</strong> -
<figure>
<img alt="Bukele gestures with CPAC branding behind him." src="https://cdn.vox-cdn.com/thumbor/CbPsfhH5HRWP-Vc9Qvbfos1GVwU=/334x0:5667x4000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73161209/2023789911.0.jpg"/>
<figcaption>
Nayib Bukele speaks at CPAC on February 22, 2024. | Photo by Brendan Smialowski/AFP via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Javier Milei, Nayib Bukele, and Donald Trump are all working out of the same populist playbook.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="T7egQO">
Meet two of the hot speakers at this year’s Conservative Political Action Conference (CPAC): Presidents Nayib Bukele of El Salvador and Javier Milei of Argentina, two of Latin America’s most flamboyant right-wing populists.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rjQzpO">
CPAC started in 1974 as an annual gathering of conservatives; over the years it has turned into a days-long, livestreamed far-right spectacle. Policy is discussed and refined while movement luminaries like former President Donald Trump and House GOP Chair Elise Stefanik are given the opportunity to share their ideas with a receptive audience.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O3Pngq">
It might be a little <a href="https://twitter.com/benjamingoggin/status/1760717639175852426?s=46">sleepier than usual</a> this year, but the conference still reveals where American conservatism is headed. And the two Latin American leaders’ presence underscores the right’s continued affinity for populist and even illiberal leadership — particularly when combined with <a href="https://www.journalofdemocracy.org/articles/latin-america-erupts-millennial-authoritarianism-in-el-salvador/">modern personal brands built online</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4qZtVZ">
They aren’t the first extremist leaders to speak at CPAC: Viktor Orbán of Hungary and Jair Bolsonaro of Brazil have featured in past years. Like Orbán and Bolsonaro, Bukele and Milei are staunch populists who have proposed radical solutions to serious problems in their countries.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bS2QMT">
The American right <a href="https://thehill.com/homenews/house/4334231-roy-leads-republicans-congratulating-milei-election-win-argentina/">finds those radical proposals attractive</a>, even if the policies likely couldn’t — or shouldn’t — be instituted in the US. Bukele has, seemingly, mitigated El Salvador’s serious gang violence problem through mass arrests and incarceration, while Milei’s economic policies are supposed to right Argentina’s inflation-plagued economy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IwlbfY">
Trump, the presumptive Republican nominee for president, has praised both men; though he has yet to meet Milei, the former president enjoyed a friendly relationship with Bukele. Other conservative figures, including Rep. Chip Roy (R-TX) of the Freedom Caucus, have <a href="https://roy.house.gov/media/press-releases/icymi-milei-shows-us-spending-cuts-can-be-done">praised</a> Milei’s push for <a href="https://roy.house.gov/media/press-releases/rep-chip-roy-leads-colleagues-congratulating-argentina-president-elect-milei">“limited” government</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bDPViz">
The two leaders are important voices at CPAC as conservatives work to draw in Latin American voters before the election in November; Bukele in particular is <a href="https://www.latimes.com/espanol/california/articulo/2022-07-12/entre-el-populismo-y-la-constitucion-bukele-busca-la-reeleccion-apelando-al-apoyo-de-la-diaspora-salvadorena">popular</a> among Salvadorans living in the US. But their presence at the conference is about more than trying to win votes, Erica Frantz, a professor of political science at Michigan State University, told Vox — it’s about creating a particular type of international far-right ideology.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="daCm0o">
“Linking Milei and Bukele with the Trump movement is advantageous for all parties involved,” she said. “For Milei and Bukele, it gives them the opportunity to strengthen an alliance with the potential presidential candidate most likely to be sympathetic to their authoritarian ambitions.” For Trump and his supporters, “it is a chance to send a message to supporters that its style of politics is gaining steam outside US borders.”
</p>
<h3 id="oVIYmg">
Bukele and Milei were elected to tackle big issues
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CAwaee">
Bukele has had a long relationship with the pro-Trump right since his first presidential election in 2019. That relationship started online, among cryptocurrency enthusiasts. The ideology underlying cryptocurrency is decidedly libertarian, with many adherents calling for the abolition of treasuries and central banks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8xZouZ">
Bukele’s profile rose when El Salvador began accepting bitcoin as legal tender, and he’s remained popular despite the damage it’s done to the country’s economy following the cryptocurrency crash of 2022. But the leader’s crypto fixation — which is affecting the country’s <a href="https://crsreports.congress.gov/product/pdf/R/R47083">ability to secure international financing</a> — is almost quaint in the face of his authoritarian turn, ostensibly to address the country’s serious crime problem.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8hjDWh">
Gangs controlled most aspects of life in the country, which was once known for having the <a href="https://www.wsj.com/articles/the-country-with-the-highest-murder-rate-now-has-the-highest-incarceration-rate-b5401da7">highest murder rate in the world</a>. With a campaign of mass arrests, Bukele has indeed tackled El Salvador’s crime problem. But that has come at a steep cost, <a href="https://www.vox.com/world-politics/2023/3/5/23621004/el-salvador-prison-bukele-ms13-barrio-18">as I explained last year</a>:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8h4602">
Successive presidential administrations have taken different approaches — many have adopted the <em>mano dura</em>, or “iron hand” tack, instituting harsh crackdowns to mitigate the violence. But Bukele is on an entirely different level; his administration has imprisoned tens of thousands, <a href="https://www.hrw.org/report/2022/12/07/we-can-arrest-anyone-we-want/widespread-human-rights-violations-under-el">many arbitrarily</a>, repeatedly extended a <a href="https://www.hrw.org/news/2022/05/02/el-salvador-evidence-serious-abuse-state-emergency">state of emergency</a> severely curtailing the rights of ordinary citizens, and attacked and even detained his critics in the press.
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="x0xrpe">
The country now instead boasts the highest incarceration rate in the world.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="k4nypq">
Despite the human rights violations, Bukele’s policies have been popular in El Salvador. Given the astounding level of violence that ordinary people have suffered under the gangs’ power — and the rapidity with which the violence decreased — it’s not ultimately that surprising that Bukele won a second term in office, despite the fact that he has dismantled parts of El Salvador’s democracy, manipulating institutions from the country’s <a href="https://www.wola.org/2021/05/el-salvador-attorney-general-constitutional-court/">Constitutional Court </a>to its <a href="https://apnews.com/article/el-salvador-nayib-bukele-election-8637667ca3b9f35c9ffd2baf805a9ade">legislature</a>, to do so.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KOmFAi">
Though the policy appears to be working in the immediate term, critics argue it isn’t sustainable for two major reasons. The first is that Bukele has made no effort to build a long-term social or economic infrastructure as an alternative to gang violence. The second is that the sense of security people currently feel requires sacrificing other forms of security, such as the rule of law. “[Bukele’s] popularity is built on illegality and undemocratic actions,” Noah Bullock, the executive director of the human rights organization Cristosal, told Vox. “There is no historic precedent where the use of state violence has produced lasting peace.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E80UxX">
That didn’t stop Bukele from suggesting the US ought to learn from his policies during his CPAC speech on Thursday. “We can clearly see the signs of a declining society because our own hit rock bottom decades ago,” he told the cheering audience. He urged Americans to look at “big cities in decline like Baltimore, Portland, New York, just to name a few places where crime and drugs have become the daily norm.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wf5A8O">
Milei has only been in office for a couple of months, so he’s had less time to implement his libertarian economic policies. And he might not be able to do that much; already in his brief tenure, the congress voted down his party’s <a href="https://www.cels.org.ar/web/en/2024/01/on-mileis-omnibus-bill/">omnibus bill</a>, which included fiscal measures aimed at managing inflation as well as an attempt to secure <a href="https://english.elpais.com/international/2024-02-03/javier-milei-overcomes-first-obstacle-in-congress-to-his-mega-reform-bill.html">emergency legislative powers</a> for, potentially, his entire four-year term. Along with deregulation and privatization efforts, the omnibus bill hinted at Milei’s social agenda: It would have reduced prenatal parental leave for women and <a href="https://theconversation.com/how-argentinas-protesters-are-responding-to-a-new-president-who-wants-to-end-environmental-protections-and-sell-off-natural-resources-222200">slashed environmental protections</a> in favor of business interests.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qL302O">
Milei will speak at the conference Saturday, most likely about his efforts to privatize state enterprises and cut down on regulations — both topics with great appeal to CPAC’s audience.
</p>
<h3 id="g6efnV">
US conservatives benefit from Bukele and Milei’s illiberal policies
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="v6oanc">
Bukele and Milei were each granted a mandate by presenting extreme solutions to serious problems in their countries that have long frustrated citizens. But they have clear ideologies and proclivities toward illiberalism that emerge within those contexts, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xXduUe">
“They are able to articulate a real problem in society and propose solutions,” Daniel Rothschild, executive director of the Mercatus Center at George Mason University, told Vox. When people are truly struggling, they respond to those policies, “even if they are illiberal.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TY2THy">
In his speech on Thursday evening, Bukele warned that the US was headed for the same kind of violent, gang-plagued system that defined El Salvador. But he, like Trump and other conservatives, exaggerates the problem the US faces. Trump and his allies have argued that cities (especially those in Democratic-controlled states) are full of violence, and they have also made a bogeyman out of the gang Mara Salvatrucha, or MS13, which has terrorized El Salvador along with Barrio 18.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cK9puq">
It is true that MS13 actually started in the US and has had a presence here. It is also true that violent crime, including homicide, <a href="https://www.themarshallproject.org/2023/11/03/violent-crime-property-data-nibrs-ucr-fbi-2022">increased</a> during the social upheaval of the pandemic, and that certain kinds of property crimes have increased. But violent crime is now at pre-pandemic levels and has trended downward overall since the 1990s. In other words, there’s simply no parallel to the violence and terror wrought by gang violence in El Salvador.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0ucxOO">
It’s not hard to see why Trump and others at CPAC would want to champion someone like Bukele. He exemplifies “tough on crime” rhetoric and, to their minds, proves that the only way to avoid the “American carnage” Trump warned of in his 2017 inauguration speech is to restrict human and civil rights and undo democratic norms and institutions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OHhOEU">
Milei, despite having struggled to pass his policies, similarly embodies conservative ideals. His <a href="https://www.vox.com/world-politics/2023/12/17/24003970/argentina-president-javier-milei">efforts</a> to curb government spending and significantly reduce the size of the government echo the Republican party’s rhetoric of limited government and tighter belts — but the US isn’t dealing with <a href="https://www.reuters.com/business/retail-consumer/cant-buy-new-jeans-argentinas-100-inflation-draws-crowds-used-clothes-markets-2023-11-13/">140 percent inflation</a> or a<a href="https://apnews.com/article/argentina-poverty-levels-uca-study-milei-devaluation-d5cb0a20b1e768efdeafbad5bf05eded"> 57 percent poverty rate</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="imp7DO">
It’s still early in Milei’s tenure, but it is important to note that he and Bukele — like Trump — exemplifies what Frantz and others call a “personalist” leader. “The party that supports them is intricately linked to their persona rather than a clear policy platform,” Frantz explained.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iASMcf">
Social media is an important tool in the personalist leader’s playbook that Milei, Bukele, and Trump have all used to their advantage — they don’t have to go through establishment channels that might soften their policies or their rhetoric.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CXlCC0">
That social media following has created a wave of “millennial authoritarianism,” as researcher Manuel Meléndez-Sánchez <a href="https://www.journalofdemocracy.org/articles/latin-america-erupts-millennial-authoritarianism-in-el-salvador/">termed the phenomenon</a>, which brands these leaders as iconoclasts who reject the “establishment.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UjB7qt">
“With personalist parties,” Frantz said, “leaders pretty much have a free rein to behave as they please, and — particularly when their party gains majority legislative representation — the door is wide open for democracy to deteriorate.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kV5IAb">
Even if Milei is struggling to pass his policies in Argentina, he’s still able to paint himself as a warrior in the fight against socialism, as he <a href="https://voz.us/javier-milei-confirms-his-presence-at-cpac-his-speech-will-focus-on-fighting-socialism-and-corruption/?lang=en">apparently will do</a> in his CPAC speech. That will solidify his ideological link to US conservatives and show “a very clear picture” of how far-right politicians “learn from each other, how they are connected with each other, and they are sharing an agenda that, far from being local, is a global network,” Paula Avila-Guillen, a human rights lawyer and executive director of the Women’s Equality Center, told Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="76P9Bp">
Ultimately, US conservatives like Bukele and Milei because they are hardliners who are using extreme tactics to deal with society’s problems — and are willing to thumb their noses at institutions to get there. As Frantz told Vox, their presence at CPAC is “an effort to cue the conservative base to see authoritarian rhetoric as ‘normal’ and strongman rule as the only solution to society’s problems.” In other words, the message is that not only is there nothing to fear from Trump’s more <a href="https://www.vox.com/2023/12/15/23990986/trump-2024-democracy-consolidated-culture-campaign">anti-democratic tendencies</a>, but there’s much to gain from them.
</p></li>
<li><strong>America’s first moon landing in 50 years, explained</strong> -
<figure>
<img alt="A hangar-sized room with an American flag on one wall and a crowd of cheering people." src="https://cdn.vox-cdn.com/thumbor/W3xFnW5KbWoK7Z_eam-LpfltzBE=/544x0:4900x3267/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73160580/2031473324.0.jpg"/>
<figcaption>
Intuitive Machines employees cheer during a watch party moments after they became the first commercial company to softly land on the moon on February 22, 2024, in Houston. | Raquel Natalicchio/Houston Chronicle/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The groundbreaking development speaks to the growing role of private companies in space.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j0OlSI">
Houston, the US is officially back on the moon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FLE35L">
On Thursday, an unmanned lunar spacecraft called Odysseus made the first US moon landing in 50 years. The spacecraft, which was produced by Texas-based engineering firm Intuitive Machines, marks major progress in the country’s ongoing investments in space exploration and provides helpful new data that can be applied to upcoming lunar missions, and even trips to Mars.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="v5KzzA">
Odysseus is also the first private spacecraft to ever land on the moon, underscoring how American businesses are taking a more prominent role in US space endeavors.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ItGF87">
Their interest and involvement in space has meant the ability to test more technology more quickly, something that has been evident in <a href="https://www.vox.com/2023/4/21/23692946/spacex-starship-rocket-explosion-launch">SpaceX’s rocket launches</a>, including repeated failed missions. Bolstered by government funding and a faster-moving experimental mentality, these companies are able to refine their offerings at a swifter pace than a government agency, which might often have to deal with more regulations and red tape.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cSAXb0">
“We’re seeing quite a large growth in the number of companies and private interests in the space business,” said Johns Hopkins University physics and astronomy professor Charles Bennett.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7CtSpq">
While private companies have long been key partners for <a href="https://www.vox.com/space">NASA</a>, Bennett said they’ve taken charge of more aspects of space exploration in recent years. <a href="https://www.vox.com/spacex">SpaceX</a>, for example, has become a key developer of rockets and intends to launch its own commercial missions. Additionally, the industry as a whole has seen a surge in growth and funding as more <a href="https://fortune.com/2023/07/24/space-industry-revenue-growth-five-years/">governments and consumers</a> across the globe have become increasingly interested in space.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xpZyz2">
Odysseus’s successful journey will ultimately be useful to scientists as they prepare for NASA’s manned Artemis missions, set to travel <a href="https://www.nasa.gov/news-release/nasa-shares-progress-toward-early-artemis-moon-missions-with-crew/#:~:text=NASA%20will%20now%20target%20September,remains%20on%20track%20for%202028.">around the moon in 2025 and land there in 2026</a>. Those missions are dedicated to establishing a long-term US presence on the moon, with the goal of using that experience to inform later journeys to Mars.
</p>
<h3 id="eRBSxz">
The moon landing, explained
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lv3wjU">
Odysseus, a robotic spacecraft, touched down in the region of the moon’s south pole on Thursday evening following <a href="https://www.washingtonpost.com/technology/2024/02/23/intuitive-machines-odysseus-moon-landing-drama/">a somewhat rocky descent</a>. Intuitive Machines announced then on X that it was working to <a href="https://twitter.com/int_machines/status/1760838333851148442?s=46&amp;t=Lu0kB_ydmg_jFB62_csFaw">“downlink the first images from the lunar surface.”</a> Notably, Odysseus is an autonomous spacecraft, which means it was able to land itself on the moon, a <a href="https://www.politico.com/news/2023/08/21/russia-moon-crash-india-landing-00112101">challenge</a> that <a href="https://www.space.com/moon-crash-march-2022-china-rocket-body">has foiled</a> numerous <a href="https://www.scientificamerican.com/article/chandrayaan-3-makes-historic-touchdown-on-the-moon/">past missions</a>.
</p>
<div id="nML4Wz">
<blockquote class="twitter-tweet">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" dir="ltr" lang="en">
After troubleshooting communications, flight controllers have confirmed Odysseus is upright and starting to send data. <br/>Right now, we are working to downlink the first images from the lunar surface.
</p>
— Intuitive Machines (<span class="citation" data-cites="Int_Machines">@Int_Machines</span>) <a href="https://twitter.com/Int_Machines/status/1760838333851148442?ref_src=twsrc%5Etfw">February 23, 2024</a>
</blockquote></div></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gh4xHo">
Odysseus will stay on the moon for about one week before it’s expected to run out of power. As part of the trip, it brought six scientific experiments for NASA, including one designed to test navigation capabilities, and six commercial items, including a <a href="https://www.cnn.com/2024/02/22/style/jeff-koons-moon-phases-odysseus-landing/index.html">sculpture by artist Jeff Koons</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xiL3fG">
The vehicle is the first from the US to make this landing since Apollo 17 in 1972. More recently, <a href="https://www.vox.com/china">China</a> and Japan have also landed rovers on the moon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0s9vbi">
This mission was made possible by <a href="https://www.forbes.com/sites/brianbushard/2024/02/22/spacecraft-makes-first-us-moon-landing-in-over-50-years/?sh=1d111c2716bb">NASA’s Commercial Lunar Payload Services program</a> and is set to aid the agency’s broader Artemis initiative, which is focused on using research on the moon to inform future missions to Mars. For this project, Intuitive Machines received <a href="https://www.nbcrightnow.com/national/nasa-paid-intuitive-machines-118-million-to-ship-science-hardware-to-better-understand-and-mitigate/image_86cbbdf7-6ee4-5f5f-abe7-a176dad0bca3.html">$118 million</a> in funding from NASA to build the lunar lander and transport experiments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9Qla06">
A renewed focus on the moon is driven by both commercial and scientific interests, Bennett noted. For companies that are interested in space, there could be goals of mining minerals and other resources on the moon, he says. <a href="https://www.abc.net.au/news/science/2024-02-24/odysseus-lander-why-is-america-returning-to-the-moon/103504018">For scientists</a>, it could be an opportunity to study the presence of water on the moon and how it could help fuel trips to Mars. (<a href="https://www.abc.net.au/news/science/2024-02-24/odysseus-lander-why-is-america-returning-to-the-moon/103504018">As ABC News Australia reported</a>, frozen water at the moon’s south pole could be used to make fuel, a potentially helpful prospect for astronauts in the future.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ykr3KN">
“It’s really exciting,” Geza Gyuk, the director of astronomy at the Adler Planetarium &amp; Astronomy Museum, <a href="https://www.cbsnews.com/chicago/news/moon-landing-adler-expert/">told CBS News</a>. “It’s part of the Artemis Project, so this is sort of testing out the technologies necessary to deliver payloads to the moon.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gLx09q">
Additionally, these missions are taking place against an ongoing <a href="https://www.abc.net.au/news/science/2024-02-24/odysseus-lander-why-is-america-returning-to-the-moon/103504018">backdrop of geopolitical competition</a> with entities including the Chinese government, which has seen three spacecraft land on the moon in the span of a decade. “It is a fact: we’re in a space race,” <a href="https://www.politico.com/news/2023/01/01/we-better-watch-out-nasa-boss-sounds-alarm-on-chinese-moon-ambitions-00075803">NASA Administrator Bill Nelson</a> previously told Politico about the urgency behind the US establishing a presence on the moon.
</p>
<h3 id="ViPJlh">
What this means for space exploration
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O1zvZk">
In addition to Intuitive Machines, several other companies, including <a href="https://www.vox.com/elon-musk">Elon Musk</a>’s SpaceX, <a href="https://www.vox.com/jeff-bezos">Jeff Bezos</a>’s Blue Origin, and Richard Branson’s Virgin Galactic, are working on tech and vehicles for taking the next steps in space.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CA28aM">
Between 2013 and 2022, private equity firms poured $272 billion into more than 1,700 private space companies, <a href="https://www2.deloitte.com/us/en/insights/industry/aerospace-defense/future-of-space-economy.html">according to a Deloitte report</a>. And the industry is only <a href="https://kpmg.com/au/en/home/insights/2020/05/30-voices-on-2030-future-of-space/space-business-models.html">expected to grow</a> in the next decade.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jqn9rM">
For now, Bennett notes that the interests of private companies and the public sector have intersected, with companies helping NASA conduct scientific experiments. He said, however, that one day those could potentially conflict.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EApZ8J">
At this time, the moon landing has been touted by officials as a milestone for the current private endeavors as well as public ones. “Today, for the first time in the history of humanity, a commercial company, an American company, launched and led the voyage up there,” <a href="https://twitter.com/SenBillNelson/status/1760832835630285138">NASA Administrator Bill Nelson said in a video<strong> </strong>statement</a>. “This feat is a giant leap forward for all of humanity.”
</p>
<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>Czar, Westlake, Helios, True Punch and Ricordo shine</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>One month before IPL, Sawai Man Singh Stadium and RCA office sealed by Rajasthan Sports Council</strong> - Sohan Ram Choudhary, however, gave the assurance that the venue will host the IPL matches and all other games that are slated to be organised.</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>Indian compound archers bag two gold medals</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>Rajnath approves cash rewards for military personnel who won medals in Asian Games, Asian Para Games</strong> - For both Asian Games as well as Asian Para Games, gold medal winners will receive a cash reward of ₹25 lakh each, silver medal winners ₹15 lakh each and bronze medal winners ₹10 lakh each</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>Leverkusen breaks Bayern’s German record to go 33 games unbeaten, extends lead in Bundesliga to 11 points</strong> - The buildup to the match against Mainz was dominated by speculation over the future of Leverkusen coach Xabi Alonso, with his former clubs Bayern and Liverpool looking for new coaches for next season.</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>Assam Hindu group starts poster campaign against missionary schools</strong> - This followed the expiry of a deadline set by another group to remove the idols of Jesus Christ and Mother Mary from the school premises</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>Priest injured as school students race in Kottayam church grounds</strong> - Six out of the eight cars used by the accused were impounded by the police.</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>Orthodox church synod endorses Catholicos’ directive proscribing clergy from party politics</strong> - The move comes in view of a series of distressing events that unfolded after one of its priests, Fr. Shaiju Kurien took membership of the Bharatiya Janata Party</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>DDMA issues public advisory as mercury soars</strong> - This posed threats like sunburn, sunstroke and dehydration. Fire breakouts owing to piled up garbage dumps and dry grass-filled plots was another potential danger.</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>NIA attaches houses of 4 accused in narco-terror case in Jammu and Kashmir’s Kupwara</strong> - A total of 12 accused have been arrested and 15 have been charge-sheeted so far in the case</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>Two years into Russia’s invasion, exhausted Ukrainians refuse to give up</strong> - Ukrainians may be fatigued by the war, but they still see it as a fight for survival.</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>Spanish police search gutted flats after nine killed</strong> - Cladding as well as high winds are being blamed for the flame in the 14-floor complex in Valencia.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine says it has downed second Russian spy plane</strong> - An A-50 radar detection aircraft is reportedly shot down over Russia, more than 200km from the front line.</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>Eight in hospital after smell at Sweden security HQ</strong> - Hundreds of security service workers are evacuated after reports of an unusual smell in the building.</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>Germany legalises cannabis, but makes it hard to buy</strong> - Under the law backed by MPs, possession will be legal, but strict rules mean it will be complicated.</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>Yelp: It’s gotten worse since Google made changes to comply with EU rules</strong> - Users are even more likely to stick with Google due to one change, says Yelp. - <a href="https://arstechnica.com/?p=2005729">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RTO doesn’t improve company value, but does make employees miserable: Study</strong> - Data is consistent with bosses using RTO to reassert control and scapegoat workers. - <a href="https://arstechnica.com/?p=2005794">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Vending machine error reveals secret face image database of college students</strong> - Facial-recognition data is typically used to prompt more vending machine sales. - <a href="https://arstechnica.com/?p=2005753">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plucky crew of Star Trek: Discovery seeks a strange artifact in S5 trailer</strong> - “It has been a hell of a journey. But everything ends someday.” - <a href="https://arstechnica.com/?p=2005705">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Avast ordered to stop selling browsing data from its browsing privacy apps</strong> - Identifiable data included job searches, map directions, “cosplay erotica.” - <a href="https://arstechnica.com/?p=2005605">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>I got arrested in Alabama on a million counts of murder.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I jerked off.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/JoeFas"> /u/JoeFas </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1aygmqn/i_got_arrested_in_alabama_on_a_million_counts_of/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1aygmqn/i_got_arrested_in_alabama_on_a_million_counts_of/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A friend was bragging to me that he was having sex with a girl and also her twin.I asked….How can you tell them apart?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He replied…her brother has a moustache!
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/berkleysquare"> /u/berkleysquare </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1ayoso1/a_friend_was_bragging_to_me_that_he_was_having/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1ayoso1/a_friend_was_bragging_to_me_that_he_was_having/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I boarded a crowded flight the other day and I saw an empty seat next to this guy……</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I sat down, took off my shoes, and cracked open a beer. I was just starting to relax when the guy gets really angry and starts swearing at me. The next thing I know the police are throwing me off the plane! Fucking pilots. No chill.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/icecreamivan"> /u/icecreamivan </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1ayinhg/i_boarded_a_crowded_flight_the_other_day_and_i/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1ayinhg/i_boarded_a_crowded_flight_the_other_day_and_i/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A rabbi, a priest, and a minister are playing poker when the cops raid the game.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The lead officer questions the priest, “Father Murphy, were you gambling?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Father Murphy silently asks God to forgive him for what he is about to say. “No, Officer. I was not gambling.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The cop turns to the minister, “Pastor Johnson, were you gambling?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Pastor Johnson also appeals to Heaven. “No, Officer. I was not gambling.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The cop finally turns to the rabbi. “Rabbi Goldstein, were you gambling?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Gambling?” he asks, glancing at the priest and the minister. “With who?”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/peacheatery"> /u/peacheatery </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1ay5sx2/a_rabbi_a_priest_and_a_minister_are_playing_poker/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1ay5sx2/a_rabbi_a_priest_and_a_minister_are_playing_poker/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A minister, a priest, and a rabbi are debating whose religion is the one true religion.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
To settle this once for all, the priest suggests they all go out into the woods and convert a bear to their religion. Whoever converts a bear would be the deemed the winner. The three agree to the terms, and head out into the woods…
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A week later, the priest and the minister meet back up. The minister asks “So how’s your bear doing?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The priest says, “My bear has already started the Bible. He should be done with it soon.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The minister says, “Oh, that’s nothing. My bear’s already finished the Bible. I’m baptizing him next Sunday.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The rabbi walks up covered in bruises and cuts, and one of his arms is in a sling.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Oh my God, what happed to you?” said the minister.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The rabbi says, “You know, thinking back, I probably shouldn’t have started with the circumcision.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Plutopiter"> /u/Plutopiter </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1ayk3l6/a_minister_a_priest_and_a_rabbi_are_debating/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1ayk3l6/a_minister_a_priest_and_a_rabbi_are_debating/">[comments]</a></span></p></li>
</ul>
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