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<title>15 January, 2024</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Eliminating the missing cone challenge through innovative approaches</strong> -
<div>
Microcrystal electron diffraction (MicroED) has emerged as a powerful technique for unraveling molecular structures from microcrystals too small for X-ray diffraction. However, a significant hurdle arises with plate-like crystals that consistently orient themselves flat on the electron microscopy grid. If, as is typically the case, the normal of the plate correlates with the axes of the crystal lattice, the crystal orientations accessible for measurement are restricted because the grid cannot be arbitrarily rotated. This limits the information that can be acquired, resulting in a missing cone of information. We recently introduced a novel crystallization strategy called suspended drop crystallization and proposed that this method could effectively address the challenge of preferred crystal orientation. Here we demonstrate the success of the suspended drop crystallization approach in eliminating the missing cone in two samples that crystallize as thin plates: bovine liver catalase and the COVID-19 main protease (Mpro). This innovative solution proves indispensable for crystals exhibiting preferred orientations, unlocking new possibilities for structure determination by MicroED.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.11.575283v1" target="_blank">Eliminating the missing cone challenge through innovative approaches</a>
</div></li>
<li><strong>Human mobility patterns to inform sampling sites for early pathogen detection and routes of spread: a network modeling and validation study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Detecting and foreseeing pathogen dispersion is crucial in preventing widespread disease transmission. Human mobility is a critical issue in human transmission of infectious agents. Through a mobility data-driven approach, we determined municipalities in Brazil that could make up an advanced sentinel network, allowing for early detection of circulating pathogens and their associated transmission routes. Methods: We compiled a comprehensive dataset on intercity mobility spanning air, road, and waterway transport, and constructed a graph-based representation of Brazil9s mobility network. The Ford-Fulkerson algorithm, coupled with centrality measures, were employed to rank cities according to their suitability as sentinel hubs. Findings: Our results disentangle the complex transportation network of Brazil, with flights alone transporting 79.9 million (CI 58.3 to 10.1 million) passengers annually during 2017-22, seasonal peaks occurring in late spring and summer, and roadways with a maximum capacity of 78.3 million passengers weekly. We ranked the 5,570 Brazilian cities to offer flexibility in prioritizing locations for early pathogen detection through clinical sample collection. Our findings are validated by epidemiological and genetic data independently collected during the SARS-CoV-2 pandemic period. The mobility-based spread model defined here was able to recapitulate the actual dissemination patterns observed during the pandemic. By providing essential clues for effective pathogen surveillance, our results have the potential to inform public health policy and improve future pandemic response efforts. Interpretation: Our results unlock the potential of designing country-wide clinical sample collection networks using data-informed approaches, an innovative practice that can improve current surveillance systems.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.12.24301207v1" target="_blank">Human mobility patterns to inform sampling sites for early pathogen detection and routes of spread: a network modeling and validation study</a>
</div></li>
<li><strong>Critically-ill COVID-19 susceptibility gene CCR3 shows natural selection in sub-Saharan Africans</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The prevalence of COVID-19 critical illness varies across ethnicities, with recent studies suggesting that genetic factors may contribute to this variation. The aim of this study was to investigate natural selection signals of genes associated with critically-ill COVID-19 in sub-Saharan Africans. Severe COVID-19 SNPs were obtained from the HGI website. Selection signals were assessed in 661 sub-Sahara Africans from 1000 Genomes Project using integrated haplotype score (iHS), cross-population extended haplotype homozygosity (xpEHH), and fixation index (Fst). Allele frequency trajectory analysis of ancient DNA samples were used to validate the existing of selection in sub-Sahara Africans. We also used Mendelian randomization to decipher the correlation between natural selection and critically-ill COVID-19. We identified that CCR3 exhibited significant natural selection signals in sub-Sahara Africans. Within the CCR3 gene, rs17217831-A showed both high iHS (Standardized iHS = 2) and high XP-EHH (Standardized XP-EHH = 2.5) in sub-Sahara Africans. Allele frequency trajectory of CCR3 rs17217831-A revealed natural selection occurring in the recent 1,500 years. Natural selection resulted in increased CCR3 expression in sub-Sahara Africans. Mendelian Randomization provided evidence that increased blood CCR3 expression and eosinophil counts lowered the risk of critically ill COVID-19. Our findings suggest that sub-Saharan Africans are less vulnerable to critically ill COVID-19 due to natural selection and identify CCR3 as a potential novel therapeutic target.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.12.24301202v1" target="_blank">Critically-ill COVID-19 susceptibility gene CCR3 shows natural selection in sub-Saharan Africans</a>
</div></li>
<li><strong>Risk factors for experiencing Long-COVID symptoms: Insights from two nationally representative surveys</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Long COVID (LC) is a complex and multisystemic condition marked by a diverse range of symptoms, yet its associated risk factors remain poorly defined. Methods: Leveraging data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS) and National Health Interview Survey (NHIS), both representative of the United States population, this study aimed to identify demographic characteristics associated with LC. The sample was restricted to individuals aged 18 years and older who reported a positive COVID-19 test or doctor9s diagnosis. We performed a descriptive analysis comparing characteristics between participants with and without LC. Furthermore, we developed multivariate logistic regression models on demographic covariates that would have been valid at the time of the COVID-19 infection. Results: Among the 124,313 individuals in BRFSS and 10,131 in the NHIS reporting either a positive test or doctor9s diagnosis for COVID-19 (Table), 26,783 (21.5%) in BRFSS and 1,797 (17.1%) in NHIS reported LC. In the multivariate logistic regression model, we found middle age, female gender, Hispanic ethnicity, lack of a college degree, and residence in non-metropolitan areas associated with higher risk of LC. Notably, the initial severity of acute COVID-19 was strongly associated with LC risk. In contrast, significantly lower ORs were reported for Non-Hispanic Asian and Black Americans compared to Non-Hispanic White. Conclusions: In the United States, there is marked variation in the risk of LC by demographic factors and initial infection severity. Further research is needed to understand the underlying cause of these observations.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.12.24301170v1" target="_blank">Risk factors for experiencing Long-COVID symptoms: Insights from two nationally representative surveys</a>
</div></li>
<li><strong>Estimated number of lives directly saved by COVID-19 vaccination programs in the WHO European Region, December 2020 to March 2023</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: By March 2023, 54 countries, areas and territories (thereafter “CAT”) reported over 2.2 million coronavirus disease 2019 (COVID-19) deaths to the World Health Organization (WHO) Regional Office for Europe (1). Here, we estimate how many lives were directly saved by vaccinating adults in the Region, from December 2020 through March 2023. Methods: We estimated the number of lives directly saved by age-group, vaccine dose and circulating Variant of Concern (VOC) period, both regionally and nationally, using weekly data on COVID-19 mortality and COVID-19 vaccine uptake reported by 34 CAT, and vaccine effectiveness (VE) data from the literature. We calculated the percentage reduction in the number of expected and reported deaths. Findings: We found that vaccines reduced deaths by 57% overall (CAT range: 15% to 75%), representing ~1.4 million lives saved in those aged ≥25 years (range: 0.7 million to 2.6 million): 96% of lives saved were aged ≥60 years and 52% were aged ≥80 years; first boosters saved 51%, and 67% were saved during the Omicron period. Interpretation: Over nearly 2.5 years, most lives saved by COVID-19 vaccination were in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among these most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.12.24301206v1" target="_blank">Estimated number of lives directly saved by COVID-19 vaccination programs in the WHO European Region, December 2020 to March 2023</a>
</div></li>
<li><strong>The relationship between gut and nasopharyngeal microbiome composition can predict the severity of COVID-19</strong> -
<div>
Background: Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that displays great variability in clinical phenotype. Many factors have been described to be correlated with its severity but no specific determinants of infection outcome have been identified yet, maybe due the complex pathogenic mechanisms. The microbiota could play a key role in the infection and in the progression and outcome of the disease. Hence, SARS-CoV-2 infection has been associated with nasopharyngeal and gut dysbiosis and higher abundance of opportunistic pathogens. Methods: To identify new prognostic markers for the disease, a multicenter prospective observational cohort study was carried out in COVID-19 patients that were divided in three cohorts according to their symptomatology: mild (n=24), moderate (n=51) and severe/critical (n=31). Faecal and nasopharyngeal samples were taken and the microbiota was analysed. Results: Microbiota composition could be associated with the severity of the symptoms and the linear discriminant analysis identified the genera Mycoplasma and Prevotella as severity biomarkers in nasopharyngeal samples, and Allistipes, Enterococcus and Escherichia in faecal samples. Moreover, M. salivarium was defined as a unique microorganism in COVID-19 patients' nasopharyngeal microbiota while P. bivia and P. timonensis were defined in faecal microbiota. A connection between faecal and nasopharyngeal microbiota in COVID-19 patients was also identified as a strong positive correlation between P. timonensis (faeces) towards P. dentalis and M. salivarium(nasopharyngeal) was found in critically ill patients. Conclusions: This ratio could be used as a novel prognostic biomarker for severe COVID-19 patients.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.11.575201v1" target="_blank">The relationship between gut and nasopharyngeal microbiome composition can predict the severity of COVID-19</a>
</div></li>
<li><strong>Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors</strong> -
<div>
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant global morbidity and mortality. A crucial viral protein, the non-structural protein 14 (nsp14), catalyzes the methylation of viral RNA and plays a critical role in viral genome replication and transcription. Due to the low mutation rate in the nsp region among various SARS-CoV-2 variants, nsp14 has emerged as a promising therapeutic target. However, discovering potential inhibitors remains a challenge. In this work, we introduce a computational pipeline for the rapid and efficient identification of potential nsp14 inhibitors by leveraging virtual screening and the NCI open compound collection, which contains 250,000 freely available molecules for researchers worldwide. The introduced pipeline provides a cost-effective and efficient approach for early-stage drug discovery by allowing researchers to evaluate promising molecules without incurring synthesis expenses. Our pipeline successfully identified seven promising candidates after experimentally validating only 40 compounds. Notably, we discovered NSC620333, a compound that exhibits a strong binding affinity to nsp14 with a dissociation constant of 427 {+/-} 84 nM. In addition, we gained new insights into the structure and function of this protein through molecular dynamics simulations. We identified new conformational states of the protein and determined that residues Phe367, Tyr368, and Gln354 within the binding pocket serve as stabilizing residues for novel ligand interactions. We also found that metal coordination complexes are crucial for the overall function of the binding pocket. Lastly, we present the solved crystal structure of the nsp14-MTase complexed with SS148 (PDB:8BWU), a potent inhibitor of methyltransferase activity at the nanomolar level (IC50 value of 70 {+/-} 6 nM). Our computational pipeline accurately predicted the binding pose of SS148, demonstrating its effectiveness and potential in accelerating drug discovery efforts against SARS-CoV-2 and other emerging viruses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.03.560722v3" target="_blank">Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors</a>
</div></li>
<li><strong>Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection</strong> -
<div>
Susceptibility to respiratory virus infections (RVIs) varies widely across individuals. Because the gut microbiome impacts immune function, we investigated the influence of intestinal microbiota composition on RVI and determined that segmented filamentous bacteria (SFB), naturally acquired or exogenously administered, protected mice against influenza virus (IAV) infection. Such protection, which also applied to respiratory syncytial virus and SARS-CoV-2, was independent of interferon and adaptive immunity but required basally resident alveolar macrophages (AM). In SFB-negative mice, AM were quickly depleted as RVI progressed. In contrast, AM from SFB-colonized mice were intrinsically altered to resist IAV-induced depletion and inflammatory signaling. Yet, AM from SFB-colonized mice were not quiescent. Rather, they directly disabled IAV via enhanced complement production and phagocytosis. Accordingly, transfer of SFB-transformed AM into SFB-free hosts recapitulated SFB-mediated protection against IAV. These findings uncover complex interactions that mechanistically link the intestinal microbiota with AM functionality and RVI severity.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.21.558814v2" target="_blank">Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection</a>
</div></li>
<li><strong>Neural Network-Assisted Humanization of COVID-19 Hamster scRNAseq Data Reveals Matching Severity States in Human Disease</strong> -
<div>
Translating findings from animal models to human disease is essential for dissecting disease mechanisms, developing and testing precise therapeutic strategies. The coronavirus disease 2019 (COVID-19) pandemic has highlighted this need, particularly for models showing disease severity-dependent immune responses. Single-cell transcriptomics (scRNAseq) is well poised to reveal similarities and differences between species at the molecular and cellular level with unprecedented resolution. However, computational methods enabling detailed matching are still scarce. Here, we provide a structured scRNAseq-based approach that we applied to scRNAseq from blood leukocytes originating from humans and hamsters affected with moderate or severe COVID-19. Integration of COVID-19 patient data with two hamster models that develop moderate (Syrian hamster, Mesocricetus auratus) or severe (Roborovski hamster, Phodopus roborovskii) disease revealed that most cellular states are shared across species. A neural network-based analysis using variational autoencoders quantified the overall transcriptomic similarity across species and severity levels, showing highest similarity between neutrophils of Roborovski hamsters and severe COVID-19 patients, while Syrian hamsters better matched patients with moderate disease, particularly in classical monocytes. We further used transcriptome-wide differential expression analysis to identify which disease stages and cell types display strongest transcriptional changes. Consistently, hamster's response to COVID-19 was most similar to humans in monocytes and neutrophils. Disease-linked pathways found in all species specifically related to interferon response or inhibition of viral replication. Analysis of candidate genes and signatures supported the results. Our structured neural network-supported workflow could be applied to other diseases, allowing better identification of suitable animal models with similar pathomechanisms across species.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.11.574849v1" target="_blank">Neural Network-Assisted Humanization of COVID-19 Hamster scRNAseq Data Reveals Matching Severity States in Human Disease</a>
</div></li>
<li><strong>Investigating willingness to share autonomous shuttles with strangers: The mediating effects of trust and optimism</strong> -
<div>
If autonomous vehicles are to have beneficial impacts on society, people must be willing to use them in their everyday lives. Many studies have engaged in questions regarding the technology of automation and how drivers will interact with it. However, little research has focused on the social situation arising from small shared autonomous shuttles (SASs) used in public transportation. This study aims to investigate a conceptual framework suggested by previous research and the MAVA-model. We tested a conceptual model where the background variables’ impact is mediated through trust in SASs and technology optimism. Our two dependent variables were the intention to use SASs with strangers without a steward onboard and the importance of social distance. The current article uses data collected using two identical online surveys conducted in 2020 (n=922) and 2021 (n=608). The data were collected before and after a pilot using SAS was employed in a suburban area outside Oslo. Examining the same population before and after the pilot gives us crucial insight into the development of attitudes toward automated vehicles when exposed to them in regular traffic. We find that trust in SASs and technological optimism positively predict willingness to use SAS. However, the passage of time had a negative effect on trust and tech-optimism, which in turn lowered the intentions to use. The background variables have little effect on the mediators. Contrary to previous research, we find that familiarity with the pilots predicted lower technological optimism and thus lower intentions to use. Older participants and women reported less trust in SASs and less tech-optimism compared to others. In the next step, these mediators lowered the intention to use SASs. These two groups also feel that it is more important to be able to keep social distance while riding SASs. The participants who use active transport modes think it is less important with social distance. The ongoing COVID-19 pandemic may also impact the results. The proposed model was less suited for predicting desire for social distance than for intentions to use. Our results suggest that future pilots should take care not to leave a negative impression by employing immature technology in neighborhoods, as this may be detrimental to the perception of SASs. Furthermore, transportation providers should take care to meet the social needs of exposed groups in the novel social context created by SASs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/x4v3h/" target="_blank">Investigating willingness to share autonomous shuttles with strangers: The mediating effects of trust and optimism</a>
</div></li>
<li><strong>Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease</strong> -
<div>
Nonstructural protein 5 (Nsp5) is the main protease of SARS-CoV-2 that cleaves viral polyproteins into individual polypeptides necessary for viral replication. Here, we show that Nsp5 binds and cleaves human tRNA methyltransferase 1 (TRMT1), a host enzyme required for a prevalent post-transcriptional modification in tRNAs. Human cells infected with SARS-CoV-2 exhibit a decrease in TRMT1 protein levels and TRMT1-catalyzed tRNA modifications, consistent with TRMT1 cleavage and inactivation by Nsp5. Nsp5 cleaves TRMT1 at a specific position that matches the consensus sequence of SARS-CoV-2 polyprotein cleavage sites, and a single mutation within the sequence inhibits Nsp5-dependent proteolysis of TRMT1. The TRMT1 cleavage fragments exhibit altered RNA binding activity and are unable to rescue tRNA modification in TRMT1-deficient human cells. Compared to wildtype human cells, TRMT1- deficient human cells infected with SARS-CoV-2 exhibit reduced levels of intracellular viral RNA. These findings provide evidence that Nsp5-dependent cleavage of TRMT1 and perturbation of tRNA modification patterns contribute to the cellular pathogenesis of SARS-CoV-2 infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.527147v3" target="_blank">Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease</a>
</div></li>
<li><strong>Science knowledge and trust in medicine affect individuals’ behavior in pandemic crises</strong> -
<div>
In pandemic crises such as the COVID-19 pandemic, individuals’ behavior has a strong impact on epidemiological processes. Compliance with prevention guidelines, such as social distancing, is critical to avoid further spreading an infectious disease or to slow down its spread. However, some individuals also or instead engage in panic behavior, such as hoarding. We investigate how education prepares individuals to respond adequately by modelling the path from seeking information about COVID-19 to eventual behavior. Based on a sample of N = 1,182 adult Americans, gathered at the pandemic’s onset (March 2020), we conclude that science knowledge helps individuals convert information into coronavirus knowledge. This knowledge then helps individuals avoid panic behavior. Individuals lacking coronavirus knowledge and science knowledge still comply with prevention guidelines when they have a general trust in medicine. Individuals lacking knowledge still follow prevention guidelines when they trust in medicine. Facilitating science knowledge and trust in science through education and targeted public health messaging are likely to be of fundamental importance for bringing crises such as the 2020 COVID-19 pandemic under control.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/tmu8f/" target="_blank">Science knowledge and trust in medicine affect individuals’ behavior in pandemic crises</a>
</div></li>
<li><strong>Individual Psychological Responses to the SARS-CoV-2 Pandemic: Different Clusters and Their Relation to Risk-Reducing Behavior</strong> -
<div>
Understanding individual difference in psychological responses toward the Coronavirus (SARS-CoV-2) crisis is essential to the adequate handling of the current pandemic. Based on a sample of 1,182 American adult residents (stratified for age and gender; data collection March 13 to 15, 2020), we found three distinct clusters of psychological responses (i.e., informed, panic, and ignorant). Clusters differed regarding their knowledge about the virus, SARS-CoV-2-related anxiety (i.e., worry and emotionality), and evaluation of the SARS-CoV-2 crisis’s severity. Cluster membership was strongly associated with both SARS-CoV-2 risk-reducing, reasonable behavior and unreasonable behavior. Finally, clusters could be linked to systematic differences in broader personality dimensions (i.e., Dark Triad and Big Five). Our study provides and validates a set of clusters of individual psychological responses to the SARS-CoV-2 pandemic and the resulting behavior. It functions as a pivotal starting point for longitudinal observations on the effectiveness of public health communications in this global challenge.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/k8unc/" target="_blank">Individual Psychological Responses to the SARS-CoV-2 Pandemic: Different Clusters and Their Relation to Risk-Reducing Behavior</a>
</div></li>
<li><strong>The pandemic, COVID-19 disease and perinatal health</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Adverse effects of COVID-19 on perinatal health have been documented, however there is a lack of research that separates individual disease from other changing risks during the pandemic period. We linked California statewide birth and hospital discharge data for 2019-2020, and compared health indicators among 3 groups of pregnancies: [a] 2020 delivery with COVID-19, [b] 2020 delivery with no documented COVID-19, and [c] 2019 pre-pandemic delivery. We aimed to quantify the links between COVID-19 and perinatal health, separating individual COVID-19 disease (a vs b) from the pandemic period (b vs c). We examined the following health indicators: preterm birth, hypertensive disorders of pregnancy, gestational diabetes mellitus and severe maternal morbidity. We applied model based standardization to estimate “average effect of treatment on the treated” risk differences (RD), and adjusted for individual and community-level confounders. Among pregnancies in 2020, those with COVID-19 disease had higher burdens of preterm birth (RD[95% confidence interval (CI)]=2.8%[2.1,3.5]), hypertension (RD[95% CI]=3.3%[2.4,4.1]), and severe maternal morbidity (RD[95% CI]=2.3%[1.9,2.7]) compared with pregnancies without COVID-19 (a vs b) adjusted for confounders. Pregnancies in 2020 without COVID-19 had a lower burden of preterm birth (RD[95% CI]=-0.4%[-0.6,-0.3]), particularly spontaneous preterm, and a higher burden of hypertension (RD[95% CI]=1.0%[0.9,1.2]) and diabetes RD[95%CI]=0.9%[0.8,1.1] compared with pregnancies in 2019 (b vs c) adjusted for confounders. Protective associations of the pandemic period for spontaneous preterm birth may be explained by socioenvironmental and behavioral modifications, while increased maternal conditions may be due to stress and other behavioral changes. To our knowledge, our study is the first to distinguish between individual COVID-19 disease and the pandemic period in connection with perinatal outcomes.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.11.24301106v1" target="_blank">The pandemic, COVID-19 disease and perinatal health</a>
</div></li>
<li><strong>Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naÏve individuals with Long COVID</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology. Methods: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. Results: Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-β and CNTF, among soluble analytes. Conclusions: Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.11.24300929v1" target="_blank">Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naÏve individuals with Long COVID</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>Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction</strong> - <b>Conditions</b>: Long Haul COVID-19; Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders <br/><b>Interventions</b>: Drug: Sodium Citrate; Drug: Normal Saline; Other: Olfactory Training Kit - “The Olfactory Kit, by AdvancedRx” <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill <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>Phase II, Double Blind, Randomized Trial of CX-4945 in Viral Community Acquired Pneumonia</strong> - <b>Conditions</b>: Community-acquired Pneumonia; SARS-CoV-2 -Associated Pneumonia; Influenza With Pneumonia <br/><b>Interventions</b>: Drug: CX-4945 (SARS-CoV-2 domain); Drug: Placebo (SARS-CoV-2 domain); Drug: CX-4945 (Influenza virus domain); Drug: Placebo (Influenza virus domain) <br/><b>Sponsors</b>: Senhwa Biosciences, 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>Edge AI-deployed DIGItal Twins for PREDICTing Disease Progression and Need for Early Intervention in Infectious and Cardiovascular Diseases Beyond COVID-19 - Investigation of Biomarkers in Dermal Interstitial Fluid</strong> - <b>Conditions</b>: Heart Failure <br/><b>Interventions</b>: Device: Use of the PELSA System for dISF extraction <br/><b>Sponsors</b>: Charite University, Berlin, Germany <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase III Clinical Study Evaluating the Efficacy and Safety of WPV01 in Patients With Mild/Moderate COVID-19</strong> - <b>Conditions</b>: Mild to Moderate COVID-19 <br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo <br/><b>Sponsors</b>: Westlake Pharmaceuticals (Hangzhou) Co., Ltd. <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>Integrated Mindfulness-based Health Qigong Intervention for COVID-19 Survivors and Caregivers</strong> - <b>Conditions</b>: COVID-19 Infection <br/><b>Interventions</b>: Other: Mindfulness-based Health Qigong Intervention <br/><b>Sponsors</b>: The Hong Kong Polytechnic University <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>Effect of Aerobic Exercises Versus Incentive Spirometer Device on Post-covid Pulmonary Fibrosis Patients</strong> - <b>Conditions</b>: Lung Fibrosis Interstitial; Post-COVID-19 Syndrome <br/><b>Interventions</b>: Other: Aerobic Exercises; Device: Incentive Spirometer Device; Other: Traditional Chest Physiotherapy <br/><b>Sponsors</b>: McCarious Nahad Aziz Abdelshaheed Stephens; Cairo University <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>SARS-CoV-2 and Influenza A/B in Point-of-Care and Non-Laboratory Settings</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Aptitude Medical Systems Metrix COVID/Flu Test <br/><b>Sponsors</b>: Aptitude Medical Systems; Biomedical Advanced Research and Development Authority <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>Can Doctors Reduce COVID-19 Misinformation and Increase Vaccine Uptake in Ghana? A Cluster-randomised Controlled Trial</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Motivational Interviewing, AIMS; Behavioral: Facility engagement <br/><b>Sponsors</b>: London School of Economics and Political Science; Innovations for Poverty Action; Ghana Health Services <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>Long COVID Ultrasound Trial</strong> - <b>Conditions</b>: Long Covid <br/><b>Interventions</b>: Device: Splenic Ultrasound <br/><b>Sponsors</b>: SecondWave Systems Inc.; University of Minnesota; MCDC (United States Department of Defense) <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>Immunogenicity After COVID-19 Vaccines in Adapted Schedules</strong> - <b>Conditions</b>: Coronavirus Disease 2019; COVID-19 <br/><b>Interventions</b>: Drug: BNT162b2 30µg; Drug: BNT162b2 20µg; Drug: BNT162b2 6µg; Drug: mRNA-1273 100µg; Drug: mRNA-1273 50µg; Drug: ChAdOx1-S [Recombinant] <br/><b>Sponsors</b>: Universiteit Antwerpen <br/><b>Completed</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>Alarming Rise in Global Rabies Cases Calls for Urgent Attention: Current Vaccination Status and Suggested Key Countermeasures</strong> - In the wake of rising rabies cases worldwide, especially after the COVID-19 pandemic, it is time to understand the scenario better and suggest technically sound and plausible countermeasures. This article is an attempt at this perspective. Although a critical zoonotic viral disease, rabies is preventable. Medico-legally, the ailment is classified as furious rabies and paralytic rabies. The four world bodies, namely, the World Health Organisation (WHO), the Food and Agriculture Organisation…</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>Identification and evaluation of antiviral activity of novel compounds targeting SARS-CoV-2 virus by enzymatic and antiviral assays, and computational analysis</strong> - The viral genome of the SARS-CoV-2 coronavirus, the aetiologic agent of COVID-19, encodes structural, non-structural, and accessory proteins. Most of these components undergo rapid genetic variations, though to a lesser extent the essential viral proteases. Consequently, the protease and/or deubiquitinase activities of the cysteine proteases M^(pro) and PL^(pro) became attractive targets for the design of antiviral agents. Here, we develop and evaluate new bis(benzylidene)cyclohexanones (BBC)…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In silico network pharmacology study on Glycyrrhiza glabra: Analyzing the immune-boosting phytochemical properties of Siddha medicinal plant against COVID-19</strong> - Immunosenescence is a pertinent factor in the mortality rate caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The changes in the immune system are strongly associated with age and provoke the deterioration of the individual’s health. Traditional medical practices in ancient India effectively deal with COVID-19 by boosting natural immunity through medicinal plants. The anti-inflammatory and antiviral properties of Glycyrrhiza glabra are potent in fighting against COVID-19…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of furopyridine-based compounds as novel inhibitors of Janus kinase 2: In silico and in vitro studies</strong> - Janus kinase 2 (JAK2), one of the JAK isoforms participating in a JAK/STAT signaling cascade, has been considered a potential clinical target owing to its critical role in physiological processes involved in cell growth, survival, development, and differentiation of various cell types, especially immune and hematopoietic cells. Substantial studies have proven that the inhibition of this target could disrupt the JAK/STAT pathway and provide therapeutic outcomes for cancer, immune disorders,…</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>Massively parallel profiling of RNA-targeting CRISPR-Cas13d</strong> - CRISPR-Cas13d cleaves RNA and is used in vivo and for diagnostics. However, a systematic understanding of its RNA binding and cleavage specificity is lacking. Here, we describe an RNA Chip-Hybridized Association-Mapping Platform (RNA-CHAMP) for measuring the binding affinity for &gt; 10,000 RNAs containing structural perturbations and other alterations relative to the CRISPR RNA (crRNA). Deep profiling of Cas13d reveals that it does not require a protospacer flanking sequence but is exquisitely…</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>Human conjunctiva organoids to study ocular surface homeostasis and disease</strong> - The conjunctival epithelium covering the eye contains two main cell types: mucus-producing goblet cells and water-secreting keratinocytes, which present mucins on their apical surface. Here, we describe long-term expanding organoids and air-liquid interface representing mouse and human conjunctiva. A single-cell RNA expression atlas of primary and cultured human conjunctiva reveals that keratinocytes express multiple antimicrobial peptides and identifies conjunctival tuft cells. IL-4/-13…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inactivation mechanism of cold plasma combined with 222 nm ultraviolet for spike protein and its application in disinfecting of SARS-CoV-2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that has precipitated a worldwide pandemic of coronavirus disease since 2019. Developing an effective disinfection strategy is crucial to prevent the risk of surface cross-contamination by SARS-CoV-2. This study employed pseudovirus and the receptor-binding domain (RBD) protein of SARS-CoV-2 as models to investigate the spike protein inactivation process and its underlying mechanisms using a novel…</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 TNF<em>-α</em> in the Pathogenesis of Migraine</strong> - CONCLUSION: To this end, TNF-α plays a critical role in chronification, and inhibiting its signaling would likely be a crucial strategy for migraine therapy.</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>TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflammatory consequences</strong> - After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural flavonoid pectolinarin computationally targeted as a promising drug candidate against SARS-CoV-2</strong> - Coronavirus disease-2019 (COVID-19) has become a global pandemic, necessitating the development of new medicines. In this investigation, we identified potential natural flavonoids and compared their inhibitory activity against spike glycoprotein, which is a target of SARS-CoV-2 and SARS-CoV. The target site for the interaction of new inhibitors for the treatment of SARS-CoV-2 has 82% sequence identity and the remaining 18% dissimilarities in RBD S1-subunit, S2-subunit, and 2.5% others. Molecular…</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>Structure-based Virtual Screening from Natural Products as Inhibitors of SARS-CoV-2 Spike Protein and ACE2-h Receptor Binding and their Biological Evaluation In vitro</strong> - CONCLUSION: Compound B-8 can be used as a scaffold to develop new and more efficient antiviral drugs.</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>Lipid Metabolism Modulation during SARS-CoV-2 Infection: A Spotlight on Extracellular Vesicles and Therapeutic Prospects</strong> - Extracellular vesicles (EVs) have a significant impact on the pathophysiological processes associated with various diseases such as tumors, inflammation, and infection. They exhibit molecular, biochemical, and entry control characteristics similar to viral infections. Viruses, on the other hand, depend on host metabolic machineries to fulfill their biosynthetic requirements. Due to potential advantages such as biocompatibility, biodegradation, and efficient immune activation, EVs have emerged as…</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><em>FHL2</em> Inhibits SARS-CoV-2 Replication by Enhancing <em>IFN-β</em> Expression through Regulating <em>IRF-3</em></strong> - SARS-CoV-2 triggered the global COVID-19 pandemic, posing a severe threat to public health worldwide. The innate immune response in cells infected by SARS-CoV-2 is primarily orchestrated by type I interferon (IFN), with IFN-β exhibiting a notable inhibitory impact on SARS-CoV-2 replication. FHL2, acting as a docking site, facilitates the assembly of multiprotein complexes and regulates the transcription of diverse genes. However, the association between SARS-CoV-2 and FHL2 remains unclear. 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>Comparative Analysis of Cyclization Techniques in Stapled Peptides: Structural Insights into Protein-Protein Interactions in a SARS-CoV-2 Spike RBD/hACE2 Model System</strong> - Medicinal chemistry is constantly searching for new approaches to develop more effective and targeted therapeutic molecules. The design of peptidomimetics is a promising emerging strategy that is aimed at developing peptides that mimic or modulate the biological activity of proteins. Among these, stapled peptides stand out for their unique ability to stabilize highly frequent helical motifs, but they have failed to be systematically reported. Here, we exploit chemically diverse helix-inducing i,…</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>Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs</strong> - Human society is facing the threat of various viruses. Proteases are promising targets for the treatment of viral infections. In this study, we collected and profiled 170 protease sequences from 125 viruses that infect humans. Approximately 73 of them are viral 3-chymotrypsin-like proteases (3CL^(pro)), and 11 are pepsin-like aspartic proteases (PAPs). Their sequences, structures, and substrate characteristics were carefully analyzed to identify their conserved nature for proposing a…</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 Elusive Promise of a Real 2024 Republican Race Against Donald Trump</strong> - On the Nikki Haley scenario and the eternal optimism of a New Year. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/the-elusive-promise-of-a-real-2024-republican-race-against-donald-trump">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How the Biden Administration Defends Its Israel Policy</strong> - Isaac Chotiner interviews John Kirby, the strategic-communications coördinator for the National Security Council, about the Biden Administration’s policy on Israel. - <a href="https://www.newyorker.com/news/q-and-a/how-the-biden-administration-defends-its-israel-policy">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Did Nikki Haley Lose Her Nerve?</strong> - The former U.N. Ambassador has been gaining ground on Donald Trump. But, at the fifth Republican debate, she remained stuck in a race for second place. - <a href="https://www.newyorker.com/news/our-columnists/did-nikki-haley-lose-her-nerve">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Trump Receives a Warm Embrace in Frigid Iowa</strong> - Before the caucuses, snow had kept the former President away from his enthusiastic crowds. On Saturday, he finally arrived in Des Moines. - <a href="https://www.newyorker.com/news/dispatch/trump-receives-a-warm-embrace-in-frigid-iowa">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Iowa Caucuses: When Ron DeSantis Forgot His Coat</strong> - On the eve of the Iowa caucuses, the Florida governor faces blizzards, skeptical voters, and the chill of his own campaign. - <a href="https://www.newyorker.com/news/dispatch/when-ron-desantis-forgot-his-coat-iowa-caucuses">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>How Trump went from disgraced insurrectionist to GOP frontrunner</strong> -
<figure>
<img alt="Donald Trump, surrounded by a crowd, raises a fist in the air and wears a serious expression." src="https://cdn.vox-cdn.com/thumbor/WKuSP8EBzSKDuao42_ys3VW4RcQ=/262x0:4333x3053/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73055716/1905676250.0.jpg"/>
<figcaption>
Former US President and Republican presidential candidate Donald Trump departs after speaking at a rally in Clinton, Iowa, on January 6, 2024. | Tannen Maury/AFP via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The deep roots of Trump’s staying power.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FWpEyh">
For a brief moment in January 2021, it was possible to imagine that <a href="https://www.vox.com/donald-trump">Donald Trump</a>’s days at the apex of American politics were over.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qVTmIn">
After all, the marriage between Trump and the Republican Party had always been one of convenience. And by the winter of 2021, the latter no longer had much use for the former. Trump had just cost the GOP a winnable election, as his historic unpopularity overwhelmed the advantages of incumbency. He’d then proceeded to put the American republic — and, more relevantly, Republican elites — in mortal danger. By <a href="https://www.vox.com/policy-and-politics/2021/1/6/22217657/us-capitol-breach-trump-rally-presidential-election">January 6</a>, the GOP had already secured its side of Trump’s Faustian bargain: its promised tax cuts and <a href="https://www.vox.com/scotus">Supreme Court</a> seats. Now the party could comfortably kick its authoritarian interloper to the curb.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4BmH9k">
Shortly after the Capitol riot, Mitch McConnell attempted to do just that, declaring Trump personally responsible for an assault on <a href="https://www.cnbc.com/2021/01/19/trump-provoked-capitol-riot-mitch-mcconnell-says.html#:~:text=%E2%80%9CThey%20tried%20to%20use%20fear,not%20even%20for%20one%20night.">“the rule of law”</a> in the United States, <a href="https://www.vox.com/2021/1/19/22239007/mcconnell-blames-trump-capitol-riot">saying from the Senate floor</a>, “The mob was fed lies. They were provoked by the president and other powerful people.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TQVPOd">
Since then, Trump <a href="https://www.nbcnews.com/meet-the-press/meetthepressblog/numbers-trump-backed-candidates-fared-midterms-rcna61524">helped cost</a> Republicans multiple Senate races, got himself <a href="https://www.vox.com/politics/2023/9/7/23862786/trump-e-jean-carroll-defamation">held civilly liable</a> for sexual assault and <a href="https://www.vox.com/trump-investigations/23832341/trump-charges-prison-time-sentence-indictments">indicted four times, facing 91 criminal charges</a> — and became the GOP’s most likely 2024 presidential nominee. As of this writing, Trump leads his closest primary rival by <a href="https://projects.fivethirtyeight.com/polls/president-primary-r/2024/national/">nearly 50 points </a>in national polls and <a href="https://projects.fivethirtyeight.com/polls/president-primary-r/2024/iowa/">by 34 points</a> in Iowa.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ubwvbI">
That an aspiring authoritarian is also the standard-bearer of a major political party is obviously an unfortunate turn of events for democracy. But it’s also a strategic setback for the GOP: Despite her low name recognition, former South Carolina Gov. <a href="https://www.vox.com/policy-and-politics/2023/2/14/23599194/nikki-haley-donald-trump-2024-presidential-campaign">Nikki Haley</a> <a href="https://www.realclearpolling.com/polls/president/general/2024/haley-vs-biden">polls better</a> against <a href="https://www.vox.com/joe-biden">Joe Biden</a> than <a href="https://www.realclearpolitics.com/epolls/2024/president/us/general_election_trump_vs_biden_vs_kennedy-8272.html">Trump does</a>. Given the Democratic president’s dismal approval rating and advanced age, a minimally normal-seeming Republican nominee might well win November’s election in a landslide. Trump’s singular toxicity is Biden’s lifeline. Or so the president’s <a href="https://www.cnn.com/2023/12/21/politics/biden-campaign-strategy/index.html">campaign seems to believe</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="l1eLK2">
Nevertheless, judging by the polls, Trump is in a stronger position to win the presidency in November than he was at this time in 2016. And a Trump presidency has never been a more alarming prospect than it is today. In the immediate aftermath of the Capitol riot, Trump <a href="https://www.cnbc.com/2021/01/13/trump-condemns-capitol-violence-a-week-after-riot-as-he-faces-second-impeachment-trial.html">disavowed the mob</a> that had violently interrupted Congress’s tally of Electoral College votes. Now, he lionizes the January 6 insurrectionists as <a href="https://www.washingtonpost.com/national-security/2024/01/06/trump-jan-6-rewrite-presidential-election/">“political prisoners.”</a>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jpLYn2">
Trump entered office in 2017 as a political neophyte with scant understanding of the executive branch. Today, he boasts a <a href="https://www.nytimes.com/2023/07/17/us/politics/trump-plans-2025.html#:~:text=July%2018%2C%202023-,Donald%20J.,authority%20directly%20in%20his%20hands.">comprehensive plan</a> for bending the administrative state to his will. In recent years, right-wing think tanks have recruited a cadre of MAGA loyalists ready to staff a Trumpified civil service and developed blueprints for consolidating his power over federal law enforcement. In court, meanwhile, Trump’s lawyers <a href="https://www.nytimes.com/2024/01/10/us/politics/trump-immunity-prosecution-assassination.html">recently argued</a> that the US president has absolute immunity from criminal prosecution unless impeached and convicted by Congress. When asked by a judge whether this meant that a president could order the assassination of a political rival and face no criminal repercussions — so long as he persuaded his allies in Congress to block an impeachment — Trump’s attorneys affirmed that this is indeed their understanding of the law.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HROgY1">
The GOP’s failure to break free from Trump constitutes a dereliction of its core duties as a political party. Parties exist, among other things, to organize political conflict in a manner conducive to both their own electoral interests and the maintenance of democratic rule. By most accounts, the Republican old guard has no great fondness for the man who executed a hostile takeover of their party, saddled them with daily political headaches during his time in office, and then instigated an insurrection that nearly got some GOP leaders pummeled, if not killed. Yet McConnell and his allies have proven incapable of steering their party in another direction.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GnXnuN">
You could attribute this failure to various contingent factors. Perhaps things would have been different if the GOP’s anti-Trump wing hadn’t invested so many resources into <a href="https://www.vox.com/2024-elections/2023/8/25/23845763/ron-desantis-republican-debate-elizabeth-warren-comparison">Florida’s exceptionally uncharismatic governor</a>, or if Biden’s weak poll numbers hadn’t undermined critiques of Trump’s “electability,” or if Nikki Haley hadn’t <a href="https://www.npr.org/2024/01/08/1223567778/nikki-haley-went-from-confederate-flag-removal-to-omitting-slavery-as-civil-war-">stumbled into doing apologetics</a> for the confederacy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iC4w9l">
But such contingencies are inadequate to explain the scale of Trump’s polling advantage or, by extension, the depths of the <a href="https://www.vox.com/politics/2023/2/23/23611828/2024-republican-presidential-candidates-trump-hurd">GOP primary</a> electorate’s tolerance for the former president’s authoritarian criminality.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MflHhd">
Rather, the Republicans’ inability to oust Trump is a symptom of deep, structural pathologies in American political life — specifically, the decades-long decay of our nation’s political parties and the radicalization of the GOP base.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hxzqbb">
Over the past half-century, changes in American society have shifted power away from formal party structures and toward donors, political action committees (PACs), issue advocacy groups, and <a href="https://www.vox.com/media">the media</a>. And as the parties have grown institutionally disempowered, they’ve also lost much of their social standing. Today, highly partisan voters are motivated less by affection for their party than by fear and loathing for the other. All this has made it more difficult for party leaders to choose optimal candidates, dictate legislative priorities, and set boundaries on members’ conduct.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="X6vwmp">
Such erosion in party authority helps explain why Republican leaders have struggled to oust a billionaire interloper whom they largely revile. It does not tell us, however, why Republican primary voters are at once so attracted to Trump and so unconcerned by his authoritarian tendencies or legal woes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Wg5iA5">
To understand the resilience of Trump’s appeal, one must look to the conservative movement’s decades-long cultivation of paranoid outrage, social distrust, and contempt for the give-and-take of democratic politics.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rS1Frb">
Together, the weakening of America’s political parties and the maniacal recklessness of the conservative movement have brought Trump to the brink of renomination and the United States to the verge of a democratic crisis.
</p>
<h3 id="gauHnz">
How America’s parties grew hollow
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hI6BCh">
In their new book, <a href="https://press.princeton.edu/books/hardcover/9780691248554/the-hollow-parties"><em>The Hollow Parties</em></a><em>, </em>political scientists Daniel Schlozman and Sam Rosenfeld chart the decline of America’s major parties and the rise of the modern conservative movement. Schlozman and Rosenfeld persuasively argue that these two trends are deeply intertwined, and that the GOP’s lurch toward authoritarianism is inextricable from both.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mkgQ5I">
For much of the 19th and 20th centuries, US political parties were relatively strong institutions. The Democrats and Republicans were less ideologically coherent and disciplined than their peers in Western Europe, but the two parties exercised considerable autonomy over their internal affairs and boasted strong bonds of affection and loyalty from many of their constituencies. Democratic and Republican leaders could compel a degree of party discipline through their power to dispense patronage and campaign funds, while party officials largely controlled the candidate selection process. Meanwhile, through their urban machines, local chapters, and allied trade <a href="https://www.vox.com/unions">unions</a> and civic organizations, the parties were a positive presence in many constituents’ daily lives.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HTvQwZ">
Under these conditions, no one could become a party’s presidential candidate without winning over much of its officialdom, which boasted both formal power and popular influence.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JKgLZ3">
But beginning in the 1970s, the parties’ autonomy and social standing steadily eroded. The upheavals of the ’60s increased tensions between activists and leaders in both parties, as progressives mobilized against Lyndon B. Johnson’s war in Vietnam and conservatives raged at the GOP’s (relatively) liberal northeastern wing. In the face of such internal schisms, both parties struggled to defend the prerogatives of party officials in internal governance and eventually gave rank-and-file voters more sovereignty over candidate selection through state primaries.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zez4i7">
In practice, this development weakened state and local party organizations, which no longer had direct authority over nominating contests. It also greatly enhanced the mass media’s influence over politics, since news coverage decisions and advertisements hold more sway in primary elections than they do in <a href="https://time.com/4324031/smoke-filled-room-history/">smoke-filled rooms</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xkAFRt">
Around the same time, popular participation in local political parties and other civic groups collapsed. Such institutions had helped tether parties to ordinary constituents. But mass-membership organizations were <a href="https://www.oupress.com/9780806136271/diminished-democracy/">increasingly displaced</a> by issue-oriented advocacy groups run by <a href="https://nymag.com/intelligencer/2022/10/education-polarization-diploma-divide-democratic-party-working-class.html">educated professionals</a> and accountable only to a narrow donor base.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PIThhl">
As <a href="https://www.vox.com/tv">television</a> advertisements and polling operations became increasingly central to electoral politics, the cost of campaigns skyrocketed. Congress successfully imposed limits on the amount of money individuals could contribute to political parties, but the Supreme Court barred restrictions on independent political spending. Taken together, these developments transferred funding (and therefore power) away from parties and toward PACs and outside groups that did not answer to party officials.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2BtHzo">
In Schlozman and Rosenfeld’s view, these developments, among others, have turned the Democrats and Republicans into “hollow parties”: “hard shells … unrooted in communities and unfelt in ordinary people’s day-to-day lives.” In the hollow era of American politics, networks of “unattached paraparty groups, devoid of popular accountability, overshadow formal party organizations at all levels,” while activists and ordinary voters alike harbor less pride or affection for their party than contempt for its rival.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TTCuoU">
Trump’s initial conquest of the GOP in 2016 and his resilient grip on red America’s loyalties in 2024 are inextricable from the formal parties’ decline. The Republican Party did not choose to give Trump a prominent place in conservative politics. No GOP operative looked at the serially bankrupt, libertine reality star and said, “We should make this guy into a leading spokesperson for the Republican point of view.” Rather, Fox News made that decision because <a href="https://www.nytimes.com/2016/09/17/us/politics/donald-trump-birther-obama.html">Trump’s “birther” conspiracy</a> theorizing was good for ratings. And once conservative media anointed Trump a tribune of enraged Republicans, the GOP had little capacity to veto his bid for its presidential nomination. The Republican old guard’s attempts to break with Trump after January 6 were halfhearted. But even if McConnell and company had made a more robust effort to oust him, they likely still would have lacked the formal powers and popular legitimacy to break with their voters’ favorite insurrectionist.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GJgWch">
And yet, as a glance across the aisle makes clear, the hollowing out of American parties is not sufficient to explain the Trump phenomenon or the GOP’s broader pathologies. In the Democratic Party, hollowness has manifested in <a href="https://www.washingtonpost.com/us-policy/2022/06/05/biden-manchin-white-house/">frustrated legislative ambitions,</a> <a href="https://nymag.com/intelligencer/2022/10/education-polarization-diploma-divide-democratic-party-working-class.html">declining working-class support</a>, poor message discipline, <a href="https://www.slowboring.com/p/the-parties-cant-decide">difficulty setting policy priorities,</a> and an inability to replace Biden with a younger, more popular 2024 standard-bearer. (Democratic elites generally recognize that Biden’s advanced age and poll numbers render him a suboptimal nominee. But since the president can only be replaced through a divisive primary, rather than through a quick negotiation between party officials, Democrats have decided that staying the course is their best bad option.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RuVGTi">
Yet the Democratic establishment has nevertheless retained some legitimacy in the eyes of its rank-and-file voters, as its success in marshaling support <a href="https://www.vox.com/2020/3/4/21164091/sanders-biden-super-tuesday-endorsements-primary-2020">behind Biden in the 2020 primary demonstrated</a>. More critically, the party has had little difficulty preventing random authoritarians from commandeering its ballot line, or performing Congress’s most basic duties, such as keeping the government funded (a task that seems to <a href="https://www.cnn.com/2024/01/11/politics/partial-government-shutdown-what-happens/index.html">perennially confound today’s GOP</a>).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M94Qhr">
Thus, the GOP’s hollowness explains why its leaders lack the tools to block the nomination of a would-be tyrant who commands more respect in red America than the party itself does. But the weakening of American parties doesn’t tell us <em>why</em> Republican voters have more respect for an authoritarian conman than for their party’s traditional leadership. Broad changes in civic organization, <a href="https://www.vox.com/campaign-finance">campaign finance</a> rules, and media technology did not force the GOP to embrace a toxic brand of right-wing populism. The conservative movement did.
</p>
<h3 id="puzJHC">
The conservative movement was born Trumpy
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sLtV4M">
There are many ways to narrate the conservative movement’s decades-long drift toward authoritarianism. A comprehensive account of that phenomenon would require a lengthy book (if not a library aisle) and touch on the backlash to the civil rights movement, the sexual revolution, the traumas of deindustrialization, and the post-1970s explosion in income inequality, among myriad other economic and social developments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PKkt8b">
And yet, as Schlozman and Rosenfeld emphasize, the qualities that made the conservative movement amenable to Trumpism were present from its inception.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tHjRdY">
The modern right was born in opposition to the moderate Republicanism of the postwar years. Disenfranchised by a GOP leadership that had made peace with the existence of Social Security, labor unions, and the near-term existence of a communist bloc, the conservative movement’s founding generation harbored contempt for the Republican establishment and a cynical attitude toward political parties as such. After all, in their view, America’s parties had delivered the nation into the tyranny of New Deal liberalism, and much of Eurasia into that of Soviet totalitarianism. (Such conservatives tended to attribute their ideology’s every setback to establishment treachery, rather than to the inevitable give-and-take of democratic politics or limits of American power.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rqJmsj">
The conservative movement’s reliance on the cultivation of outrage and apocalyptic paranoia also dates back to its infancy. Many in the movement genuinely believed that the State Department was brimming with communists and that Eisenhower was dragging America down the road to serfdom. But even (relatively) level-headed conservatives recognized the political utility of promoting hysteria. In the 1960s, the advent of direct-mail fundraising expanded the resources available to conservative organizations and issue campaigns. And the right quickly discovered that their prospective donors were far more likely to put a check in the mail once worked up into a frenzy of terror and indignation. As the conservative movement’s “<a href="https://www.nybooks.com/articles/2020/04/23/republican-fundraising-pulpit/">funding father</a>” Richard Viguerie told NPR’s Terry Gross, when it comes to political giving, “people are motivated by anger and fear much more so than positive emotions.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eg3557">
The right’s contempt for mainstream politics and penchant for catastrophism informed its ruthless approach to political combat. For the movement’s leading functionaries, the headlong pursuit of power took precedence over honesty or social responsibility. Conservative operatives therefore cheered the displacement of formal party committees by unaccountable, dark money PACs that facilitated smear campaigns. As Terry Dolan, co-founder of the National Conservative Political Action Committee, <a href="https://www.washingtonpost.com/archive/lifestyle/1980/08/10/the-new-right-brigade/24c8ed98-3af7-4385-9c0e-f973bea20612/">said in 1980</a>, “A group like ours could lie through its teeth and the candidate it helps stays clean.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SUMEfb">
Combine these three tendencies — to perennially blame every ideological defeat on a traitorous GOP establishment, to stoke apocalyptic rage about the direction of the country, and to pursue power by any means necessary — and you aren’t far away from a recipe for Trumpism.
</p>
<h3 id="INZLNz">
The politics of right-wing hysteria don’t age like fine wine
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FN9zHf">
If the conservative movement undermined healthy partisan politics from its outset, the right’s most destructive tendencies grew more destabilizing over time. It was one thing for the right to rage against a genuinely moderate Republican establishment. It was another to slander and delegitimize an <em>already</em> extremely right-wing one. Yet the conservative movement did not forfeit its iconoclastic outlook after it conquered the GOP in the 1980s. Rather, the right carried on attributing every subsequent compromise with political reality and social change as a betrayal by its leaders and grounds for replacing them with more reactionary ones. Now, the leader of the House Republicans is a member of the far-right Freedom Caucus — and, according to some of his colleagues, still <a href="https://www.reuters.com/world/us/us-house-republican-hardliners-challenge-johnson-over-spending-deal-2024-01-10/">a treacherous sellout to the powers that be</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JOJreo">
In its early years, conservatives’ cultivation of paranoid rage was at least directed at galvanizing support for concrete policy goals. Viguerie’s direct-mail campaign to <a href="https://onlinelibrary.wiley.com/doi/10.1111/j.1741-5705.2010.03792.x">preserve US control of the Panama Canal </a>might have histrionically overstated the importance of that objective, but it was genuinely aimed at preserving US sovereignty over the waterway. By contrast, in recent decades, the conservative movement’s most powerful institutions — Fox News and right-wing talk radio — have been principally motivated by the pursuit of high ratings, not policy change. Their promotion of fear and alienation has therefore been untempered by any practical political considerations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="blzYZc">
Meanwhile, in the late 20th century, the right’s tactical ruthlessness manifested as a willingness to stoke racial grievances, spread lies, and interfere in Democratic primaries in pursuit of an electoral victory. Today, the right is not merely taking an unscrupulous approach to building majorities, but seeking to wield power in defiance of them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="srbdxM">
From the era of Richard Nixon to that of George W. Bush, many white Christian conservatives understood themselves to be a silent (moral) majority whose will was frustrated by an overweening liberal elite. But demographic and cultural change gradually impeded on this self-conception. The election of an African American president, the increasingly <a href="https://nymag.com/intelligencer/2022/12/gop-house-republicans-esg-woke-wall-street.html">unabashed social liberalism of corporate America</a>, and the nation’s <a href="https://nymag.com/intelligencer/2021/04/gallup-poll-church-gop-christian-right-2024-democracy.html">steadily declining religiosity</a> have all deepened the conservative base’s sense of dispossession. In some parts of red America, economic decline compounded cultural alienation, as jobs and capital fled small industrial towns for major urban centers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gnrjoz">
For the Republican Party, the declining demographic weight of white conservatives was happily mitigated by their coalition’s geographic efficiency. America’s state legislatures, House of Representatives, Electoral College battlegrounds, and <a href="https://www.vox.com/policy-and-politics/2019/12/17/21011079/senate-bias-2020-data-for-progress">Senate</a> all tended to overrepresent white rural areas. And this overrepresentation could be enhanced through gerrymandering and (at least, <a href="https://www.vox.com/policy-and-politics/2019/2/21/18230009/voter-id-laws-fraud-turnout-study-research">theoretically</a>) voter restrictions, such as voter ID laws and felon disenfranchisement. Add to this a conservative Supreme Court majority, and Republicans proved capable of exercising significant influence over public policy even as <a href="https://www.washingtonpost.com/politics/2021/01/04/remarkable-gop-admission-undermining-electoral-college-threatens-our-best-path-white-house/">they lost the popular vote in seven of the last eight presidential elections</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dJr6Sb">
The need to publicly justify this anti-majoritarian power, however, increasingly led conservatives to explicitly critique democratic government — or, more commonly, to suggest that some voters were more equal than others. After a Democrat won the Wisconsin governorship in 2018, Republicans in the state’s heavily gerrymandered legislature voted to transfer various official powers away from the incoming governor and toward itself. The Republican State House speaker Robin Vos <a href="https://www.nytimes.com/2018/12/06/upshot/wisconsin-republicans-rural-urban-voters.html">justified</a> this power grab by saying, “If you took Madison and Milwaukee out of the state election formula, we would have a clear majority. We would have all five constitutional officers and we would probably have many more seats in the Legislature.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fQdlKd">
The insinuation that <em>real</em> Americans should not have to share power with Democratic constituencies gained a more coherent ideological expression in the “great replacement” narrative, a conspiracy theory that<strong> </strong>holds that Democrats deliberately flooded the US with obedient foreigners so as to permanently disempower white Americans. As future Trump White House adviser Michael Anton put the point in his infamous 2016 essay “<a href="https://claremontreviewofbooks.com/digital/the-flight-93-election/">The Flight 93 Election</a>,” the “ceaseless importation of Third World foreigners with no tradition of, taste for, or experience in liberty means that the electorate grows more left, more Democratic, less Republican, less republican, and less traditionally American with every cycle.” <a href="https://www.vox.com/2023/4/25/23697600/tucker-carlson-tonight-fox-news-dominion-lawsuit">Tucker Carlson</a> mainstreamed these sentiments, <a href="https://www.mediamatters.org/tucker-carlson/tucker-carlson-worst-attack-our-democracy-160-years-how-about-immigration-act-1965">declaring</a> on Fox News that the “worst attack on our democracy in 160 years” had been “the Immigration Act of 1965,” which had “completely changed the composition of America’s voter rolls, purely to benefit the Democratic Party.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IT2BVT">
Put all of this together and you’re left with a conservative base that despises the Republican congressional leadership, believes that their most fundamental values and interests are under existential threat, trusts right-wing infotainers more than party officials, and views their nation’s majority party as illegitimate.
</p>
<h3 id="9IMzfM">
Conservatives have too little trust in liberal democracy to recoil from Trump’s attacks on it
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rnhxtX">
In this context, McConnell and his allies had little prospect of persuading the Republican faithful that Trump had disqualified himself from high office by fomenting an insurrection on January 6. In fact, as the Washington Post’s Isaac Arnsdorf and Josh Dawsey <a href="https://www.washingtonpost.com/national-security/2024/01/06/trump-jan-6-rewrite-presidential-election/">report,</a> pressure to whitewash the events of that day emerged organically from the party’s grassroots and was then amplified by conservative media.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TKTXaK">
In the first months after the insurrection, even Trump felt compelled to decry the siege of the Capitol as “terrible.” But friends and families of the rioters took a different view and promulgated it over their social networks. Carlson, still in his post at Fox News, rallied to their cause. Soon, GOP members of Congress found themselves confronted with constituent demands to defend the January 6 rioters. As Arnsdorf and Dawsey report:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UI49HH">
“It came from the grass roots,” said a former senior House Republican leadership aide. The aide, who like several others spoke on the condition of anonymity to describe private interactions, said most Republicans who had been at the Capitol “knew exactly what happened, knew how wrong it was, and knew that Donald Trump was responsible” but shifted after hearing from constituents.
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RuPdpK">
If the conservative base was too contemptuous of the political system to take an attempted insurrection seriously, there was little prospect of it abandoning Trump in the face of his legal woes. Indeed, to a voter who deems their nation’s institutions catastrophically corrupt, felony indictments can look like endorsements — the Justice Department’s way of vouching for Trump’s bonafides as a threat to the system.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Wz2Dlp">
Trump’s staying power is, therefore, a byproduct of both the weakness of America’s political parties and extremism of the modern right. Various social forces hollowed out the GOP, and the conservative movement filled its remaining shell with a toxic form of reactionary populism.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uvK0C9">
Trump’s conquest of this broken party has thrown American democracy into an acute crisis. Yet even if Biden prevails in November, the fundamental challenge to democratic politics in the US will remain. So long as America’s parties remain hollow — and our right radicalized — something menacing will always be threatening to fill the void.
</p></li>
<li><strong>How to decode the Iowa caucuses result</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/CsOye1PpFpWQHXhOa7tzo9rB1dA=/221x0:5146x3694/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73055696/GettyImages_1923501933__1_.0.jpg"/>
<figcaption>
Campaign signs for Republican presidential candidates, former U.N. Ambassador Nikki Haley and Florida Gov. Ron Desantis line the road in front of Drake University, where CNN hosted a presidential debate on January 10, 2024 in Des Moines, Iowa. | Chip Somodevilla/Getty
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Who wins” isn’t as simple as who comes in first. Here’s what Trump, DeSantis, and Haley each need.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="q9nT8Q">
The question of who will win the Iowa caucuses isn’t as simple as who comes in first place.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LvprFN">
“Winning” Iowa doesn’t get you much except bragging rights and an insignificant number of delegates. The true importance of the contest is in how it can shape the perceptions of the political world — <a href="https://www.vox.com/media">the media</a>, donors, activists, politicians, and voters — of who can win.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Kjfvrw">
So the candidates’ true goal is to exceed the expectations the political world has for their Iowa performance. Which means the results will need a bit of decoding.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DoBiv7">
For instance, if <a href="https://www.vox.com/donald-trump">Donald Trump</a> wins but his vote share or margin of victory is unexpectedly small, this will be covered as a shocking development that throws his seeming inevitability into question.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="F0LdaA">
And a bad result in Iowa might not impact <a href="https://www.vox.com/policy-and-politics/2023/2/14/23599194/nikki-haley-donald-trump-2024-presidential-campaign">Nikki Haley</a>’s campaign much, but such a result for <a href="https://www.vox.com/ron-desantis">Ron DeSantis</a> would all but doom his hopes of defeating Trump. Here’s what each candidate needs.
</p>
<h3 id="Wu1LvD">
Expectations for Trump are for a huge win
</h3>
<figure class="e-image">
<img alt="Donald Trump speaking into a microphone in front of a banner declaring “Trump country: Make America great again.”" src="https://cdn.vox-cdn.com/thumbor/SPN2DR3KdLOyDwOxtpAPwXu49D0=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25222425/GettyImages_1912793546.jpg"/> <cite>Anna Moneymaker/Getty Images</cite>
<figcaption>
Current Republican presidential candidate and former US President Donald Trump speaks at a campaign event on January 6, 2024, in Newton, Iowa.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dGhEKO">
Most political indicators currently suggest Trump will win the GOP nomination easily, and that the first step toward this will be a big win in Iowa.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CtWMwE">
Polls of Iowa Republicans<a href="https://www.realclearpolling.com/polls/president/republican-primary/2024/iowa-caucus"> show Trump getting</a> about 50 percent support, more than 30 points ahead of any other competitor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vGGPmI">
That’s where his expectations are set. If Trump ends up doing about that well, or even better, it will confirm the political world’s belief that he’s the overwhelming favorite.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="w1O22O">
The flipside is that if Trump underperforms polls — getting around 40 percent or lower, or having another contender come surprisingly close to him — he will be deemed a “loser” of Iowa even though he won because the results showed his support looking less rock-solid than expected. Much chatter would then ensue about whether he is more vulnerable than commonly believed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IpClsv">
An actual Trump <em>loss</em> in Iowa currently seems so unlikely that, if it happens, it would make the political cognoscenti question everything they think they know about this race.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hLqcrx">
Still, even a shocking Iowa defeat wouldn’t doom Trump’s campaign. He currently leads in every other state too. Iowa is understood to be kind of a quirky contest; weird things can happen there. And back during the 2016 nomination contest, Trump actually lost Iowa but went on to win anyway.
</p>
<h3 id="YHEsM4">
Expectations for Nikki Haley in Iowa are low
</h3>
<figure class="e-image">
<img alt="Nikki Haley holds a microphone while standing in front of a backdrop that reads “Pick Nikki January 15.”" src="https://cdn.vox-cdn.com/thumbor/TGOpjB610UiYKYHRzT-stJa1ZQQ=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25222432/GettyImages_1925437353.jpg"/> <cite>Win McNamee/Getty Images</cite>
<figcaption>
Republican presidential candidate former UN Ambassador Nikki Haley speaks during a campaign event on January 11, 2024 in Ankeny, Iowa
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9K9xeV">
Haley, by contrast, has some upside in Iowa, but the consequences for a bad performance there may not be so awful to her.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y0Wc7e">
That’s in part because Haley has been generally viewed as on the rise (even though her <a href="https://www.realclearpolitics.com/epolls/2024/president/2024gop.html">national poll performance</a> remains quite weak). But it’s mainly because Haley has prioritized the next contest — New Hampshire’s primary on January 23 — over Iowa. She has <a href="https://abcnews.go.com/Politics/haley-downplays-iowa-new-hampshire-voters-correct-caucuses/story?id=106100774">been explicit</a> about this, telling a New Hampshire town hall that their crowd would “correct” Iowa’s result.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p7ACRf">
Iowa’s conservative base and the heavy influence evangelical activists have there aren’t a great fit for Haley, who is running as more of a traditional establishment Republican. All last year, Haley <a href="https://www.realclearpolling.com/polls/president/republican-primary/2024/iowa-caucus">was polling</a> third in Iowa behind DeSantis, and most recent polls show her about tied with him (though one <a href="https://www.suffolk.edu/-/media/suffolk/documents/academics/research-at-suffolk/suprc/polls/other-states/2024/1_10_2024_iowa_marginals.pdf?la=en&amp;amp;hash=11C2F3A4AF682D1BF2DDB23F961240BA74D6742A">shows her jumping ahead</a> to second).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Qa8bmI">
In Iowa, Haley trails Trump by 35 points in polls. But in New Hampshire, she’s 14 points behind Trump,<a href="https://www.realclearpolitics.com/epolls/2024/president/2024gop.html"> on average</a>. The Granite State is clearly a more promising opportunity for her. And its voters are famous for thumbing their noses at Iowa’s picks, meaning they might not hold a bad Iowa performance against Haley.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xsvk6z">
The low expectations for Haley in Iowa even make it possible that, if she comes in a strong second place (ahead of DeSantis and closer than expected to Trump), she could be deemed the “real” winner by many in the political world. But either way, it’s New Hampshire that will determine whether Haley’s campaign is for real.
</p>
<h3 id="VJMSNK">
Ron DeSantis needs to do really well to show his campaign has a pulse
</h3>
<figure class="e-image">
<img alt="A sign reading “DeSantis 2024” is seen in a snowy field beside a road and three makeshift wooden crosses." src="https://cdn.vox-cdn.com/thumbor/qtDTQNl_VS7FdZZqleOUHCyLUJU=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25222435/GettyImages_1926077022.jpg"/> <cite>Kevin Dietsch/Getty Images</cite>
<figcaption>
A sign supporting Republican presidential candidate Florida Gov. Ron DeSantis is seen on January 11, 2024 in Ogden, Iowa.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yQUcM9">
Because DeSantis’s campaign is so widely viewed as doomed, he needs a dramatic success in Iowa to alter those perceptions and justify staying in the race.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7jYky6">
After spending much of the past year<a href="https://www.realclearpolling.com/polls/president/republican-primary/2024/national"> declining in the polls</a> and<a href="https://www.politico.com/news/2023/09/06/desantis-donors-florida-election-00114080"> losing donors</a>, DeSantis has bet everything on Iowa as his best shot for a comeback. He has the endorsement of the state’s governor and has spent years cultivating right-wing activists.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uVhDJ4">
But he’s spent most of the past year a distant second to Trump in<a href="https://www.realclearpolling.com/polls/president/republican-primary/2024/iowa-caucus"> Iowa polls</a>, and the most recent polls show him and Haley — who, again, hasn’t prioritized the state — neck-and-neck. And, unlike Haley, he doesn’t have a more promising opportunity coming up: DeSantis is polling at an awful 6.5 percent in<a href="https://www.realclearpolling.com/polls/president/republican-primary/2024/new-hampshire"> New Hampshire</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VJ12cx">
To revitalize his chances in the race, DeSantis really needs to over-perform in Iowa. A distant second place edging out Haley likely wouldn’t be good enough. Perhaps a strong second, much closer than expected to Trump, would do the trick. Anything short of that would likely mean curtains for him, since he’d lose his last remaining support from GOP donors.
</p>
<h3 id="LowpIX">
Vivek Ramaswamy needs to prove he’s a real candidate
</h3>
<figure class="e-image">
<img alt="Vivek Ramaswamy holding a microphone in front of a backdrop of an American flag, a Don’t Tread On Me flag, and an Iowa flag." src="https://cdn.vox-cdn.com/thumbor/ZbC7gGic2wp6MOTROsSiMvJhAQU=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25222438/GettyImages_1915751718.jpg"/> <cite>Alex Wroblewski/Bloomberg via Getty Images</cite>
<figcaption>
Vivek Ramaswamy, chairman and co-founder of Strive Asset Management and 2024 Republican presidential candidate, during a campaign event at the Iowa State Capitol in Des Moines, Iowa, on January 10, 2024.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JS5uiF">
As for<a href="https://www.vox.com/2024-elections/23720391/vivek-ramaswamy-affirmative-action-woke-capitalism-ideas"> Vivek Ramaswamy</a>, he’s more of a wild card. After a brief burst of attention several months ago, media and GOP voter attention have largely moved on from the former biotech CEO, who’s been stuck at single digits in polls nationally and in all the early states.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3gJPua">
Polls do show Ramaswamy doing slightly better in Iowa (where he averages 6.5 percent) than in other early states (where he averages 3 to 5 percent). And he has been<a href="https://www.nbcnews.com/politics/2024-election/vivek-ramaswamy-completes-double-tour-every-iowa-county-rcna131847"> campaigning very intensely in Iowa</a>, visiting each of the state’s 99 counties twice. If he has a hardcore base of intense supporters who are disproportionately likely to turn out, the low-turnout caucuses could be an opportunity to punch above his weight.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WC7TjQ">
Conversely, an unimpressive performance in Iowa would likely suggest Ramaswamy won’t do too well anywhere else, either. Single digits are not enough anymore. Ramaswamy has tried to set an achievable expectation by saying he hopes to finish at least third in Iowa, but that would likely not be enough to make him a serious contender, given his lack of prospects in other early states.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6QCHSk">
Ramaswamy is largely self-funding his campaign and could theoretically stay in as long as he wants since donors won’t be able to force his hand by stopping payment of his staffers’ salaries. But anything other than an extraordinary overperformance in Iowa would result in him being written off by the political world.
</p></li>
<li><strong>What China wants out of Myanmar’s civil war</strong> -
<figure>
<img alt="MYANMAR-CONFLICT" src="https://cdn.vox-cdn.com/thumbor/L4ch3aKXykQSih3BuLFcv7KTTPM=/254x0:4275x3016/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73054599/1851374184.7.jpg"/>
<figcaption>
Photo by STR/AFP via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Despite China’s attempts to negotiate a regional ceasefire, Myanmar’s civil war won’t end soon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="x4YjEG">
In Myanmar, a brief ceasefire between a powerful alliance of ethnic armed groups and the ruling military junta appears to have been broken just hours after it was negotiated at <a href="https://www.vox.com/china">China</a>’s urging.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YCUV66">
The Three Brotherhood Alliance, one of the factions fighting in a coordinated armed struggle against the Tatmadaw (Myanmar’s military junta), agreed to the ceasefire Friday in the Chinese provincial capital of Kunming, about 250 miles from Myanmar’s northeast border with China. <a href="https://www.rfa.org/english/news/myanmar/brotherhood-junta-ceasefire-01122024055623.html">The ceasefire provision was seemingly limited to Shan state</a>, which borders China, and aimed at protecting Chinese interests and civilians in the region.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5bKDBU">
But by Friday, <a href="https://www.irrawaddy.com/news/burma/myanmar-junta-breaks-chinese-brokered-ceasefire-tnla.html">the military had broken the agreement</a>, according to a statement from the <a href="https://www.crisisgroup.org/asia/south-east-asia/myanmar/b177-treading-rocky-path-taang-army-expands-myanmars-shan-state">Ta’ang National Liberation Army</a> (TNLA), one of the ethnic armed groups, along with the Arakan Army and the Myanmar National Democratic Alliance Army, in the Three Brotherhood Alliance. The junta <a href="https://www.irrawaddy.com/news/burma/myanmar-junta-breaks-chinese-brokered-ceasefire-tnla.html">attacked multiple positions in northern Shan State Friday and Saturday</a>, the Irrawaddy and <a href="https://www.facebook.com/khitthitnews">local Burmese</a> <a href="https://www.facebook.com/MeKongNewsMM">outlets reported</a>. Vox is unable to independently verify the claims.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wYG5Et">
The ceasefire came after <a href="https://twitter.com/YeMyoHein5/status/1745515862478471173">multiple rounds of talks</a><a href="https://twitter.com/YeMyoHein5/status/1739299942299242604"> between the Tatmadaw and the Three Brotherhood Alliance</a>. Both sides <a href="https://www.france24.com/en/asia-pacific/20231216-myanmar-s-three-brotherhood-alliance-seizes-town-from-military-despite-china-backed-ceasefire">reportedly</a> <a href="https://apnews.com/article/china-three-brotherhood-alliance-shan-state-6a9db01e4cd65876998ae0c04032c902">broke a previous ceasefire agreement negotiated last month</a>, and some observers did not expect the current agreement to hold.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jZtRwh">
“The three parties, the three ethnic armed organizations up on the border actually had no intention in participating in these talks and did so really only because of very strong Chinese pressure,” Jason Tower, country director for the Burma program at the US Institute of Peace, told Vox. “And I think that the ceasefire was really doomed to fail from the outset, given that there was just no intention on the part of the different parties to seriously engage in any form of deeper dialogue about the situation.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fvSnuk">
But the ceasefire, though it involves a critically important armed group, did not apply to other parts of Myanmar, where ethnic armed groups and People’s Defense Forces — or PDFs, armed groups that developed after the 2021 coup that returned the junta to power — are continuing Operation 1027, the offensive against the Tatmadaw that the Three Brotherhood Alliance began on October 27 of last year.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xQI1fZ">
“I don’t really see this as the other groups seeing this as a sense of betrayal, but it’s triggering more frustration toward China, because they see China’s increasingly becoming an obstacle to them being able to advance their objectives of eradicating the military dictatorship and pushing the military out of the political space,” Tower said.
</p>
<h3 id="UU3A3j">
There’s no going back to the status quo
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JE3VHI">
With few interruptions, Myanmar has been in a state of protracted civil war and military rule for most of its history as an independent nation. The country began instituting democratic reforms in the 2020s and held elections in 2015 and 2020, which the opposition National League for Democracy (NLD) won. The military, which is also called the Sit-Tat or the State Administration Council (SAC), detained President Win Myint and democracy activist Aung San Suu Kyi, as well as other members of the NLD, on the day the new Parliament was to meet for the first time following the election, in February 2021. Former military officer Myint Swe became acting president, declared a state of emergency, and handed over control of the country to the military.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HVlIuB">
<a href="https://www.cfr.org/backgrounder/myanmar-history-coup-military-rule-ethnic-conflict-rohingya#chapter-title-0-5">Armed ethnic groups are nothing new in Myanmar</a> — it’s a highly ethnically diverse nation, but the majority Bamar group has always enjoyed a privileged position in society, including in the military and the government. Meanwhile, smaller ethnic groups, such as the Shan, Karen, and Rakhine groups, have historically faced serious discrimination, both under British colonial rule and under military dictatorships. These Ethnic Armed Organizations (EAOs) have, in many cases, been fighting the government for years in order to gain more autonomy for their regions or ethnic groups.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="coeP9m">
Myanmar has been mired in a deadly civil war since the 2021 coup. The<a href="https://www.wilsoncenter.org/sites/default/files/media/uploads/documents/ASIA_220519_1YearOn-BRIEF_V1r2.pdf"> conflict started with peaceful protests against the military dictatorship</a>, but the junta’s violent crackdown on protesters eventually led to the creation of the PDFs and armed rebellion. In return, the military used its significant firepower, including <a href="https://www.usip.org/publications/2023/03/atrocities-myanmar-documenting-juntas-attacks-civilians#:~:text=Hundreds%20of%20civilians%20have%20been,infrastructure%20like%20health%20care%20clinics.">mortars, landmines, and missiles</a>, against the armed groups and <a href="https://www.amnesty.org/en/latest/news/2023/10/myanmar-28-civilians-killed-in-military-air-strike-new-investigation-and-witness-testimony/">civilians</a>. Over 6,000 civilians were killed in the fighting between February 2021 and September 2022, according to <a href="https://cdn.cloud.prio.org/files/c675c059-ec75-4abf-8fbb-ab13067bfeaf/Counting-Myanmars-Dead-PRIO-Paper-2023.pdf?inline=true">Peace Research Institute Oslo</a>. Nearly 2 million people were internally displaced as of October 2, <a href="https://data.unhcr.org/en/documents/details/104833">according to the UN</a>; these numbers have only increased since the 1027 offensive.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FIIkTn">
Operation 1027 likely took months of planning and has shown impressive coordination between the alliance, other ethnic armed organizations, and PDFs. That’s a new dimension in the ongoing fight against military leadership, experts told Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oHCTcu">
“This level of cooperation is not exactly unprecedented, but I think the scale of the operation and what they’ve managed to pull off … I’ve never really seen anything to this extent,” David Mathieson, an independent analyst based in Thailand, <a href="https://www.vox.com/world-politics/2023/11/25/23975516/myanmar-military-junta-tatmadaw-three-brotherhood-alliance-china">told Vox in November. </a>“I think it shows a combination of long-term cooperation between the three main groups,” or the Three Brotherhood Alliance, which have been collaborating in some fashion since 2009, and more recent collaboration with other ethnic armed organizations such as the Bamar People’s Liberation Army, Mathieson said.
</p>
<h3 id="IUFwSE">
What’s China’s role in Myanmar’s civil war?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ce3cRo">
China has become increasingly concerned with the prevalence of so-called “<a href="https://www.nytimes.com/interactive/2023/12/17/world/asia/myanmar-cyber-scam.html">pig butchering</a>” schemes in its border areas, including northern Shan state. That illicit <a href="https://www.vox.com/economy">economy</a> is run by Chinese criminal organizations and targets Chinese workers, who are lured to Southeast Asia with promises of jobs — only to be kidnapped and taken to remote areas in Myanmar, Cambodia, or Laos to be used as slaves. There, they are forced to lure people across the world into relationships, with the eventual goal of stealing money through <a href="https://www.vox.com/crypto">cryptocurrency</a> fraud. In recent months, <a href="https://www.wsj.com/world/asia/china-rounds-up-31-000-suspects-in-sweeping-pig-butchering-crackdown-00af42f0">China has pushed both EAOs and the junta to go after perpetrators</a> and extradite them to China.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ezgD45">
But Shan state is critical for the resistance movement to control because it relies on the border with China to access weapons, medical care, and currency, Tower said. Furthermore, as Thiha Wint Aung, an independent analyst from Myanmar, told Vox, “gaining control over the northern Shan State signifies an expansion of territories where they can operate unimpeded.” Lashio and Muse, key strategic points for trade with China, are still controlled by the military, Aung said, but are surrounded by resistance forces.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E1Budi">
But Shan state — and Myanmar — are also strategically important for China, Tower said, and China has been working with the military for the past two decades to secure its interests there. “[China] has partnered closely with the Myanmar military to build out all of this infrastructure to build out a multibillion dollar pipeline, which is the only source of pipe natural gas to China’s southwestern provinces,” Tower told Vox. “And the Myanmar military has, until recently, been the key party providing security to that.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0q4YgK">
China also relies on Myanmar for access to the<a href="https://carnegieendowment.org/2023/04/18/surrounding-ocean-prc-influence-in-indian-ocean-pub-89608"> Malacca Strait,</a> a critical transit route for trade which connects China and other Asian countries to Africa, Europe, and the Middle East through the Indian Ocean. That’s particularly important when it comes to China’s energy supply, as <a href="https://carnegieendowment.org/2023/04/18/surrounding-ocean-prc-influence-in-indian-ocean-pub-89608">Darshana Baruah</a>, director of the Indian Ocean Program at the Carnegie Endowment for International Peace, explained in an April testimony before the House Foreign Affairs subcommittee on the Indo-Pacific. “Nine of China’s top ten crude oil suppliers transit the Indian Ocean,” Baruah said in the testimony.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a2SMmk">
Though China has worked with both EAOs and the military, it is likely placing its hope in the Tatmadaw to protect its interests, despite its tenuous grip on power, economic incompetence, and engagement in criminal activities, Tower said. “I think [China’s] preference is ultimately for a weak military that is highly dependent on China, that will give China deals that it wouldn’t otherwise be able to secure, and which China can work with, along with several other [EAOs] that it [trusts] up in its border area, to secure its interests, and ultimately, to further advance its interests in the Indian Ocean area,” he told Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iqzC8y">
Even if China negotiates future ceasefire agreements, they’re not likely to hold for long, and violence will continue in Myanmar for the foreseeable future, Aung said. “The Ethnic Armed Organizations (EAOs) are acutely aware that their gained territories will never be peaceful as long as the military regime remains in power in Naypyitaw,” Myanmar’s capital.
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>India’s gold rush continues in Jakarta as Yogesh wins double</strong> - Yogesh claimed the individual gold medal after shooting 573, finishing ahead of silver winner Muad Al Balushi of Oman (570) and Indonesia’s Anang Yulianto (567)</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Daily Quiz | On Ranji Trophy</strong> - The Ranji Trophy is one of the most prominent domestic cricket championships in India. A quiz on the premier competition</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>Sachin Tendulkar calls out fake video, expresses concern about misuse of technology</strong> - The fake video shows Sachin talking about the merits of a gaming application</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Premier League | Richarlison, Bentancur score as Tottenham salvage 2-2 draw with Man United</strong> - Rasmus Hojlund’s early opener was cancelled out by Richarlison and Rodrigo Bentancur levelled again for Spurs after Marcus Rashford had put United back in front.</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>Morning Digest | President Murmu on 3-day visit to Meghalaya, Assam from today; Modi to release first instalment of PM-JANMAN scheme for pucca homes to one lakh beneficiaries, and more</strong> - Here is a select list of stories to start the day</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>In Pics | Jallikattu season begins in Tamil Nadu</strong> - Jallikattu is an age-old event celebrated mostly in Tamil Nadu as part of Pongal celebrations</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>Situation in J&amp;K under control, increase in terror activities in Rajouri-Poonch: Army chief</strong> - He, however, asserted that due to the efforts of the security personnel, there has been a significant drop in violence in the interior areas of Jammu and Kashmir</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>Karnataka BJP appoints district unit presidents ahead of 2024 Lok Sabha polls</strong> - State unit president B.Y. Vijayendra appointed heads to 39 district units</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>Want to make Manipur peaceful, harmonious again: Rahul on 2nd day of Nyay Yatra</strong> - Several people, a number of them women and children, had lined up along the yatra route and cheered on Mr. Gandhi as his bus made its way along several busy areas in Senapati</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>No question of sparing anyone in Hanagal gangrape case: CM Siddaramaiah</strong> - The chief minister promises stringent action against perpetrators, denies allegations of cover-up by the BJP</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>Germany’s far right seek revolution in farmers’ protests</strong> - As farmers blockade roads over subsidy cuts, neo-Nazi or monarchist groups are turning up at rallies.</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 shot down Russian A-50 spy plane</strong> - Army chief Gen Valerii Zaluzhnyi said the air force had “destroyed” an A-50 radar detection aircraft.</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>King Frederik: Tens of thousands turn out for succession</strong> - King Frederik becomes the new monarch of Denmark, following Queen Margarethe’s abdication.</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>Iceland lava slowing down after day of destruction</strong> - Defences built after an eruption in December have partially contained the lava, but some have been breached.</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>Russian poet and Putin critic Lev Rubinstein dies after car crash</strong> - The 76-year-old was a key figure in the Soviet underground literary scene and a staunch Kremlin critic.</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>The 5 most interesting PC monitors from CES 2024</strong> - Lines keep blurring between work and play screens, and OLED overwhelms. - <a href="https://arstechnica.com/?p=1995280">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Would Luddites find the gig economy familiar?</strong> - Luddites were hardly the anti-tech dullards historians have painted them to be. - <a href="https://arstechnica.com/?p=1995716">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CDC reports dips in flu, COVID-19, and RSV—though levels still very high</strong> - The dips may be due to holiday lulls and CDC is monitoring for post-holiday increase. - <a href="https://arstechnica.com/?p=1995823">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reddit must share IP addresses of piracy-discussing users, film studios say</strong> - Reddit says First Amendment rights protect it from having to disclose users’ info. - <a href="https://arstechnica.com/?p=1995738">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Space Force is changing the way it thinks about spaceports</strong> - There’s not much available real estate to grow Cape Canaveral’s launch capacity. - <a href="https://arstechnica.com/?p=1995665">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Shogun’s fiancée has disappeared, and one of his samurais gives him a letter found in her room.</strong> - <!-- SC_OFF --></p>
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“Forget your bride and marry me. Send me a sign tomorrow. Or i’ll turn her into a frog. - Sorceress of the mountain.”, says the letter.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The shogun knowing that, according to the legends, this sorceress was absolutely beautiful and extremely powerful, and that it would even be good to have a wife with such attributes, thinks for a few moments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
But he decides to recover his bride, especially because his honor is in check, this kidnapping would create a scandal in the empire, and after all his bride is attractive enough to him, and so he walks around the palace looking for someone who can discreetly help with this situation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He finds a ninja from a clan he trusts most, dressed all in black and masked, standing near the palace. And then he asks him to quickly go to the forest, find his bride, and bring his beloved back in complete secrecy. Tells him she’s an attractive woman who may be somewhere close to the sorceress. And with a map, he marks a place for them to meet later.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Yes sir! I’m going to get her! Without waking anyone, at night!”, says the ninja, who immediately runs towards the forest.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The shogun hides on the outskirts of the city by the place he marked, a small storage shelter. And waits for nightfall.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A few minutes later the ninja returns, carrying a tatami wrapped around someone. He carefully places it on the floor and unwraps, revealing a beautiful female oni, a legendary forest dwelling being, with immense breasts, highly attractive and sexy despite her red skin and horns on her head, sleeping inside.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Ninja, this is not my fiancée… she must be an ally of the sorceress. My fiancée is human,” whispers the shogun.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Forgive my mistake, sir! I’ll go get her”, whispers the ninja, who then carefully wraps the tatami again, puts it over his shoulder. And runs, again, towards the forest.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Some time later, the ninja returns, again with that tatami wrapped around another person, which he carefully places on the floor and unwraps. Revealing another woman sleeping inside, she is wearing ceremonial robes and has strange blue symbols tattooed on her skin. And she is very beautiful, despite her unusual appearance.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Ninja, this is not my fiancée… She must be one of the sorceress’ apprentices. My fiancée is a member of the nobility. Pay attention to her clothes. I am counting on you,” whispers the shogun.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Forgive my mistake, sir! I’ll go get her”, whispers the ninja, who then wraps the tatami again, puts it over his shoulder, and runs towards the forest once more.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
And after a while, the ninja returns with his tatami wrapped around someone else. Which he carefully places on the floor and unwraps. Once again revealing a woman sleeping inside. She is wearing noble clothes and is quite attractive, but much older than the shogun.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Ninja, that’s not my fiancée… She’s my fiancée’s mother!!!!!,” screams the shogun in absolute surprise. He then notices he has screwed up, becomes very nervous thinking about the consequences, feels sick, passes out and falls to the floor making a loud noise.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The woman on the tatami then opens her eyes, stares at the shogun, and asks, “Daughter, don’t you think you’ve gone too far?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Ah mom… I just wanted to be absolutely sure that he wouldn’t accept any other woman in my place,” replies the ninja.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Ms_Kratos"> /u/Ms_Kratos </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/19714pq/the_shoguns_fiancée_has_disappeared_and_one_of/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/19714pq/the_shoguns_fiancée_has_disappeared_and_one_of/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man is flying in a hot-air balloon and realizes he is lost.</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He reduces height and spots a man below. He lowers the balloon farther and shouts, “Excuse me! Can you tell me where I am?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man below says: “Yes, you’re in a hot-air balloon, hovering 30 feet above this field.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“You must be an engineer,” says the balloonist.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I am,” replies the man. “How did you know?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well,” says the balloonist, “everything you have told me is technically correct, but it’s no use to anyone.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man below says, “You must be in management.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I am,” replies the balloonist, “but how did you know?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well,” says the man, “you don’t know where you are or where you’re going, but you expect me to be able to help. You’re in the same position you were before we met, but now it’s my fault.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/boingggoesmyschlong"> /u/boingggoesmyschlong </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1974cbb/a_man_is_flying_in_a_hotair_balloon_and_realizes/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1974cbb/a_man_is_flying_in_a_hotair_balloon_and_realizes/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A physicist, a biologist, and a mathematician are having lunch</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
at a local bistro. They’re sitting by the window and while they’re waiting for their food, they notice a person walk into the house across the street. A few minutes later, two people walk out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Huh,” says the physicist, “what’s up with that? There must have been an error in our observation when the single person walked in!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The physicist then looks at the biologist who says, “Nah, it’s obvious the person that walked in reproduced asexually - that’s why two people walked out.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They both look at the mathematician, who says, “Oh, I have no idea what happened there. All I know is that if one more person walks into that house, it’ll be empty.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/XennialBoomBoom"> /u/XennialBoomBoom </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/196t0ll/a_physicist_a_biologist_and_a_mathematician_are/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/196t0ll/a_physicist_a_biologist_and_a_mathematician_are/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Putin is held hostage by a terrorist.</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A Russian truckdriver stops at the back of a long queue on the motorway. He sees a policeman walking down the line of stopped cars to briefly talk to the drivers. As the policeman approaches the truck, the truckdriver rolls down his window and asks, What’s going on?" Policeman: “A terrorist is holding Putin hostage in a car. He’s demanding 10 million rubles, or he’ll douse Putin in petrol and set him on fire. So we’re asking drivers for donations.” Driver: “Oh, ok. How much do people donate on average.” Policeman: “About a gallon.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/boingggoesmyschlong"> /u/boingggoesmyschlong </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/19748sn/putin_is_held_hostage_by_a_terrorist/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/19748sn/putin_is_held_hostage_by_a_terrorist/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Three women are sitting in a cafe, talking about their husbands.</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“My husband is a miner,” says Heather. “I like being in bed with him because he has an incredible shaft.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Mine is a dentist,” says Linda. “I like being in bed with him because no one can drill like he can.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“You’re both lucky,” says Martha. “My husband’s a mailman.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What’s wrong with that?” asks Heather.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well,” says Martha, “he always delivers late, and half the time it’s in the wrong slot.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/wimpykidfan37"> /u/wimpykidfan37 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/196ofz4/three_women_are_sitting_in_a_cafe_talking_about/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/196ofz4/three_women_are_sitting_in_a_cafe_talking_about/">[comments]</a></span></p></li>
</ul>
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