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<title>15 December, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>How Generative AI Portrays Science. Interviewing ChatGPT from the Perspective of Different Audience Segments</strong> -
<div>
Generative AI in general and ChatGPT in particular have risen in importance. ChatGPT is widely known and used increasingly as an information source for different topics, including science. It is therefore relevant how ChatGPT portrays science and science-related topics. Research on this question is lacking, however. Hence, we “interview” ChatGPT and reconstruct how it presents science, scientists, scientific misbehavior and controversial scientific fields. Combining qualitative and quantitative content analysis, we find that, generally, ChatGPT portrays science largely as the STEM disciplines, in a positivist-empiricist way and a positive light. We compare ChatGPT’s responses to different simulated user profiles and two versions of GPT and find similarities in that the scientific consensus on questions like climate change, COVID-19 vaccinations or astrology is consistently conveyed across them. Beyond these similarities in substance, however, pronounced differences are found in the personalization of responses to different user profiles and between GPT-3.5 and GPT-4.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/erf36/" target="_blank">How Generative AI Portrays Science. Interviewing ChatGPT from the Perspective of Different Audience Segments</a>
</div></li>
<li><strong>A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia</strong> -
<div>
Pathogen clearance and resolution of inflammation in patients with pneumonia require an effective local T cell response. Nevertheless, local T cell activation may drive lung injury, particularly during prolonged episodes of respiratory failure characteristic of severe SARS-CoV-2 pneumonia. While T cell responses in the peripheral blood are well described, the evolution of T cell phenotypes and molecular signatures in the distal lung of patients with severe pneumonia caused by SARS-CoV-2 or other pathogens is understudied. Accordingly, we serially obtained 432 bronchoalveolar lavage fluid samples from 273 patients with severe pneumonia and respiratory failure, including 74 unvaccinated patients with COVID-19, and performed flow cytometry, transcriptional, and T cell receptor profiling on sorted CD8+ and CD4+ T cell subsets. In patients with COVID-19 but not pneumonia secondary to other pathogens, we found that early and persistent enrichment in CD8+ and CD4+ T cell subsets correlated with survival to hospital discharge. Activation of interferon signaling pathways early after intubation for COVID-19 was associated with favorable outcomes, while activation of NF-{kappa}B-driven programs late in disease was associated with poor outcomes. Patients with SARS-CoV-2 pneumonia whose alveolar T cells preferentially targeted the Spike and Nucleocapsid proteins tended to experience more favorable outcomes than patients whose T cells predominantly targeted the ORF1ab polyprotein complex. These results suggest that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterize patients who recover, yet these responses progress to NF-{kappa}B activation against non-structural proteins in patients who go on to experience poor clinical outcomes.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.13.571479v1" target="_blank">A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia</a>
</div></li>
<li><strong>Scm6A: A fast and low-cost method for quantifying m6A modifications at the single-cell level</strong> -
<div>
It is widely accepted that m6A exhibits significant intercellular specificity, which poses challenges for its detection using existing m6A quantitative methods. In this study, we introduce Scm6A, a machine learning-based approach for single-cell m6A quantification. Scm6A leverages input features derived from the expression levels of m6A trans regulators and cis sequence features, and found that Scm6A offers remarkable prediction efficiency and reliability. To further validate the robustness and precision of Scm6A, we applied a winscore-based m6A calculation method to conduct m6A-seq analysis on CD4+ and CD8+ T-cells isolated through magnetic-activated cell sorting (MACS). Subsequently, we employed Scm6A for analysis on the same samples. Notably, the m6A levels calculated by Scm6A exhibited a significant positive correlation with m6A quantified through m6A-seq in different cells isolated by MACS, providing compelling evidence for Scm6A's reliability. Additionally, we performed single-cell level m6A analysis on lung cancer tissues as well as blood samples from COVID-19 patients, and demonstrated the landscape and regulatory mechanisms of m6A in different T-cell subtypes from these diseases. In summary, our work has yielded a novel, dependable, and accurate method for single-cell m6A detection. We are confident that Scm6A have broad applications in the realm of m6A-related research.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.14.571511v1" target="_blank">Scm6A: A fast and low-cost method for quantifying m6A modifications at the single-cell level</a>
</div></li>
<li><strong>Inactivation of the Niemann Pick C1 cholesterol transporter 1 (NPC1) restricts SARS-CoV-2 infection</strong> -
<div>
The Niemann Pick C1 (NPC1) protein is an intracellular cholesterol transporter located in the late endosome/lysosome (LE/Ly) and is involved in cholesterol mobilization. Loss-of-function mutations of the NPC1 gene lead to accumulation of cholesterol and sphingolipids in LE/Ly, resulting in severe fatal NPC1 disease. Cellular alterations associated with NPC1 inactivation affect both the integrity of lipid rafts and the endocytic pathway. Because the angiotensin-converting enzyme 2 (ACE2) and type 2 serine transmembrane protease (TMPRSS2) of the SARS-CoV-2 Spike (S) protein also localize to lipid rafts, we sought to investigate the hypothesis that NPC1 inactivation would generate an intrinsically unfavorable barrier to SARS-CoV-2 entry. In this study, we demonstrate that NPC1 pharmacological inactivation or CRISP/R-Cas mediated ablation of NPC1 dramatically reduced SARS-CoV-2 infectivity. More specifically, our findings demonstrate that pharmacological inactivation of NPC1 results in massive accumulation of ACE2 in the autophagosomal/lysosomal compartment. A &gt;40-fold decrease in virus titer indicates that this effectively prevents VSV-Spike-GFP infection by impeding virus binding and entry. A similarly marked decrease in viral infectivity is observed in cells that had NPC1 expression genetically abrogated. These observations were further confirmed in a de novo SARS-CoV-2 infection paradigm, where cells were infected with the naturally pathogenic SARS-CoV-2. Overall, this work offers strong evidence that NPC1 function is essential for successful SARS-CoV-2 infection, thus implicating NPC1 as a potential therapeutic target in COVID-19 management.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.13.571570v1" target="_blank">Inactivation of the Niemann Pick C1 cholesterol transporter 1 (NPC1) restricts SARS-CoV-2 infection</a>
</div></li>
<li><strong>Differential outcomes of infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern in K18-hACE2 transgenic mice</strong> -
<div>
Background: SARS-CoV-2 is a respiratory virus with neurological complications including loss of smell and taste, headache, and confusion that can persist for months or longer. Severe neuronal cell damage has also been reported in some cases. The objective of this study was to compare the infectivity of Wild-type virus, Delta and Omicron variants in transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) receptor under the control of the keratin 18 promoter (K18) and characterize the progression of infection and inflammatory response in the lung, brain medulla oblongata and olfactory bulbs of these animals. We hypothesized that Wild-type, Delta and Omicron differentially infect K18-hACE2 mice, thereby inducing distinct cellular responses. Methods: K18-hACE2 female mice were intranasally infected with Wild-type, Delta, or Omicron variants and euthanized either at 3 days post-infection (dpi) or at the humane endpoint. None of the animals infected with the Omicron variant reached the humane endpoint and were euthanized at day 8 dpi. Virological and immunological analyses were performed in the lungs, olfactory bulbs, medulla oblongata, and brains. Results: Mice infected with Wild-type and Delta display higher levels of viral RNA in the lungs than mice infected with Omicron at 3dpi. Viral RNA levels in the brains of mice infected with the Wild-type virus were however significantly lower than those observed in mice infected with either Delta or Omicron at 3dpi. Viral RNA was also detected in the medulla oblongata of mice infected by all these virus strains at 3dpi. At this time point, mice infected with the Delta virus display a marked upregulation of inflammatory makers both in the lungs and brains. Upregulation of inflammatory markers was also observed in the brains of mice infected with Omicron but not in mice infected with the Wild-type virus, suggesting that during the initial phase of the infection only the Delta and Omicron variants induce strong inflammatory response in the brain. At the humane endpoint/8dpi, mice infected by any of these strains display elevated levels of viral RNA and upregulation of a subset of inflammatory markers in the lungs. There was also a significant increase in viral RNA in the brains of mice infected with Wild-type and Delta, as compared to 3dpi. This was accompanied by an increase in the expression of most cytokines and chemokines. In contrast, mice infected with the Omicron variant showed low levels of viral RNA and downregulation of cytokines and chemokines expression at 8dpi, suggesting that brain inflammation by this variant is attenuated. Reduced RNA levels and downregulation of inflammatory markers was also observed in the medulla oblongata and olfactory bulbs of mice infected with Omicron, while infection by Wild-type and Delta resulted in high levels of viral RNA and increased expression of inflammatory makers in these organs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.08.556906v2" target="_blank">Differential outcomes of infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern in K18-hACE2 transgenic mice</a>
</div></li>
<li><strong>Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease</strong> -
<div>
Codon optimization describes the process used to increase protein production by use of alternative but synonymous codon changes. In SARS-CoV-2 mRNA vaccines codon optimizations can result in differential secondary conformations that inevitably affect a protein’s function with significant consequences to the cell. Importantly, when codon optimization increases the GC content of synthetic mRNAs, there can be an inevitable enrichment of G-quartets which potentially form G-quadruplex structures. The emerging G-quadruplexes are favorable binding sites of RNA binding proteins like helicases that inevitably affect epigenetic reprogramming of the cell by altering transcription, translation and replication. In this study, we performed a RNAfold analysis to investigate alterations in secondary structures of mRNAs in SARS-CoV-2 vaccines due to codon optimization. We show a significant increase in the GC content of mRNAs in vaccines as compared to native SARS-CoV-2 RNA sequences encoding the spike protein. As the GC enrichment leads to more G-quadruplex structure formations, these may contribute to potential pathological processes initiated by SARS-CoV-2 molecular vaccination.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/bcsa6/" target="_blank">Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease</a>
</div></li>
<li><strong>Examining perceptions of stress, wellbeing and fear among Hungarian adolescents and their parents under lockdown during the COVID-19 pandemic</strong> -
<div>
Intensified anxiety responses and even symptoms of post-traumatic stress are commonly observed under quarantine conditions. In this study, the effects on fear, anxiety and wellbeing of the recent pandemic caused by SARS-CoV-2 were investigated in a sample of otherwise healthy Hungarians. Taking the family as a microsystem, differences in gender, age, family relationships and time spent in isolation were the main focus of this investigation. 346 parent-child dyads were examined; the children were 11-17 years of age. Standard psychological questionnaires (Perceived Stress Scale, WHO Wellbeing Index), and an open question test (the Metamorphosis test) were used, and the results analysed with the aid of basic statistical methods. Stress levels and wellbeing displayed a significant negative correlation with each other in both parents and children. Parental stress and levels of wellbeing had a weak but significant impact on the wellbeing of their children. Among the demographic variables examined, none of them was found to explain the wellbeing or stress level of parents. Natural catastrophes, such as pandemics, create a stressful social environment for parents, and therefore directly impact the psychological wellbeing of all family members.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/feth3/" target="_blank">Examining perceptions of stress, wellbeing and fear among Hungarian adolescents and their parents under lockdown during the COVID-19 pandemic</a>
</div></li>
<li><strong>Acceptability and feasibility of a theatre-based wellness programme to support people living with Long COVID: a single arm feasibility study.</strong> -
<div>
Objectives: To determine acceptability and feasibility of a theatre-based wellness programme to support the health and wellbeing of people with long COVID. Design: Single group, repeated measures feasibility study. Setting: Community centre and online. Participants: Adults with a diagnosis of long COVID experiencing breathlessness, mild to moderate pain, and/or loneliness. Intervention: A six-week participatory creative intervention delivered to two groups of participants, one online and one in-person. The groups were facilitated by movement, voice and drama consultants and designed to improve wellbeing, fatigue, pain, strength and balance through a series of breathing exercises, visualisation, group singing and sound imagery, storytelling, movement exercises and poetry. Primary outcome measures: Acceptability of the intervention and feasibility of recruitment procedures and data collection. Secondary outcome measures: Changes in mental health, wellbeing, quality of life, loneliness, social support, fatigue, breathlessness, and post-COVID-19 functional status. Results: 20 participants took part in the intervention, 19 completed baseline assessments and 16 completed study follow-up. Most participants found the programme acceptable and feasible and improvements were identified in all outcomes at 8-week follow-up, including decreases in generalised anxiety and depressive symptoms, loneliness, shortness of breath, respiratory dysfunction, chronic fatigue and increased mental wellbeing, social support, and self-rated health. Key programme features and mechanisms of action that led to improvements in health and wellbeing were identified in qualitative interviews. Barriers to engagement included: activities being outside of the participant’s comfort zone, ongoing and fluctuating long COVID symptoms, emotional consequences of sharing experiences with the group and connectivity and connecting with others online. Conclusions: A six-week theatre-based programme was perceived as acceptable to most participants and resulted in positive psychosocial impacts. The findings provide a rationale for supporting the ongoing development of this and related programmes and for scaling up research into arts programmes to support people living with long COVID.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/k25qj/" target="_blank">Acceptability and feasibility of a theatre-based wellness programme to support people living with Long COVID: a single arm feasibility study.</a>
</div></li>
<li><strong>Artificial Intelligence and Robotics for Reducing Waste in the Food Supply Chain: Systematic Literature Review, Theoretical Framework, and Research Agenda</strong> -
<div>
The COVID-19 pandemic has unraveled the inefficiencies in the global food supply chain. One glaring distortion is the wastage of close to a third of global food production, in the face of widespread food insecurity. With population explosion and climate change as additional pressure points, reducing food waste has emerged as an urgent imperative for achieving food security for all. In this paper, we develop a research framework and agenda for the use of Artificial Intelligence and robotics in reducing food loss and waste. The Cognitive Automation for Food (COGAF) has been developed as a theoretical framework for guiding future research. This framework delineates the research landscape into five distinct research streams: sensory enhancement, cognitive automation, physical automation, sensory-motor fusion, and collaborative automation. In order to develop a systematic research agenda, propositions have been developed in each of these research streams. In conjunction with the COGAF framework, this research agenda attempts to provide a road map for future research and knowledge creation pertaining to the use of AI and robotics to reduce food loss and waste.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/h3jgb/" target="_blank">Artificial Intelligence and Robotics for Reducing Waste in the Food Supply Chain: Systematic Literature Review, Theoretical Framework, and Research Agenda</a>
</div></li>
<li><strong>Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Biological evidence suggests ursodeoxycholic acid (UDCA) - a common treatment of cholestatic liver disease - may prevent severe COVID-19 outcomes. With the approval of NHS England, we conducted a population-based cohort study using primary care records, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. We estimated the hazard of COVID-19 hospitalisation or death between 1 March 2020 and 31 December 2022, comparing UDCA treatment to no UDCA treatment in a population with indication. Of 11,320 eligible individuals, 642 were hospitalised or died with COVID-19 during follow-up, 402 (63%) events among UDCA users. After confounder adjustment, UDCA was associated with a 21% (95% CI 7%-33%) relative reduction in the hazard of COVID-19 hospitalisation or death, consistent with an absolute risk reduction of 1.3% (95% CI 1.0%-1.6%). Our findings support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.11.23299191v1" target="_blank">Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform</a>
</div></li>
<li><strong>A software tool for at-home measurement of sensorimotor adaptation</strong> -
<div>
Sensorimotor adaptation is traditionally studied in well-controlled laboratory settings with specialized equipment. However, recent public health concerns such as the COVID-19 pandemic, as well as a desire to recruit a more diverse study population, have led the motor control community to consider at-home study designs. At-home motor control experiments are still rare because of the requirement to write software that can be easily used by anyone on any platform. To this end, we developed software that runs locally on a personal computer. The software provides audiovisual instructions and measures the ability of the subject to control the cursor in the context of visuomotor perturbations. We tested the software on a group of at-home participants and asked whether the adaptation principles inferred from in-lab measurements were reproducible in the at-home setting. For example, we manipulated the perturbations to test whether there were changes in adaptation rates (savings and interference), whether adaptation was associated with multiple timescales of memory (spontaneous recovery), and whether we could selectively suppress subconscious learning (delayed feedback, perturbation variability) or explicit strategies (limited reaction time). We found remarkable similarity between in-lab and at-home behaviors across these experimental conditions. Thus, we developed a software tool that can be used by research teams with little or no programming experience to study mechanisms of adaptation in an at-home setting.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.12.571359v1" target="_blank">A software tool for at-home measurement of sensorimotor adaptation</a>
</div></li>
<li><strong>Identification of an allele-specific transcription factor binding interaction that regulates PLA2G2A gene expression</strong> -
<div>
The secreted phospholipase A2 (sPLA2) isoform, sPLA2-IIA, has been implicated in a variety of diseases and conditions, including bacteremia, cardiovascular disease, COVID-19, sepsis, adult respiratory distress syndrome, and certain cancers. Given its significant role in these conditions, understanding the regulatory mechanisms impacting its levels is crucial. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs), including rs11573156, that are associated with circulating levels of sPLA2-IIA. Through Genotype-Tissue Expression (GTEx), 234 expression quantitative trait loci (eQTLs) were identified for the gene that encodes for sPLA2-IIA, PLA2G2A. SNP2TFBS (https://ccg.epfl.ch/snp2tfbs/) was utilized to ascertain the binding affinities between transcription factors (TFs) to both the reference and alternative alleles of identified SNPs. Subsequently, ChIP-seq peaks highlighted the TF combinations that specifically bind to the SNP, rs11573156. SP1 emerged as a significant TF/SNP pair in liver cells, with rs11573156/SP1 interaction being most prominent in liver, prostate, ovary, and adipose tissues. Further analysis revealed that the upregulation of PLA2G2A transcript levels through the rs11573156 variant was affected by tissue SP1 protein levels. By leveraging an ordinary differential equation, structured upon Michaelis-Menten enzyme kinetics assumptions, we modeled the PLA2G2A transcription's dependence on SP1 protein levels, incorporating the SNP's influence. Collectively, these data strongly suggest that the binding affinity differences of SP1 for the different rs11573156 alleles can influence PLA2G2A expression. This, in turn, can modulate sPLA2-IIA levels, impacting a wide range of human diseases.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.12.571290v1" target="_blank">Identification of an allele-specific transcription factor binding interaction that regulates PLA2G2A gene expression</a>
</div></li>
<li><strong>Leveraging Tuberculosis Programs for Future Pandemic Preparedness: A Retrospective Look on COVID-19</strong> -
<div>
Worldwide, COVID-19 has decimated healthcare systems and highlighted the pressing need to ensure resilience for future pandemics. Given the almost 30% likelihood of another respiratory disease similar to COVID-19 manifesting in the next 10 years, it is imperative to prioritize pandemic preparedness in the immediate future. To this end, tuberculosis (TB) and its management share many similarities to respiratory disease protection, offering an opportunity to dually strengthen TB programs and protect against future pandemics. Looking at data from the World Health Organization (WHO), Global Fund, Our World in Data, and domestic health ministries. It was hypothesized that countries that had better TB program strength going into the pandemic fared better with COVID-19 than those with poorer TB treatment. It was found that countries that recovered their TB program strength (as measured by TB treatment coverage percentages) to or above pre-pandemic levels fared better in terms of COVID-19 pandemic incidence and death. Case studies helped identify common factors across resilient TB platforms in dually successful COVID-19 and TB countries, including community trust, co-epidemic responses that were able to maintain continuity of care, sustained innovation, comprehensive communication across public and private sectors, and maintenance of donor support for TB programs through the pandemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/t23ed/" target="_blank">Leveraging Tuberculosis Programs for Future Pandemic Preparedness: A Retrospective Look on COVID-19</a>
</div></li>
<li><strong>EduMap: Navigating a Learning Adventure</strong> -
<div>
Directed study maps are often used in order to create an overlay of knowledge relations. However, these connections often have to manually be created by subject matter and IT experts, which, although are a ground truth, limit these user to the topics of the maps at hand. To address this, we propose EduMap, which takes advantage of GPT 3.5 in a few-shot setting to create a study map for any user-provided topic. We conducted two user studies to address various aspects of the map: (1) A quantitative study to test out the effectiveness of this map medium in the context of navigating information concerning COVID-19 in a expert-curated graph, and (2) A quantitative study to test out the accuracy and usefulness of GPT-generated graphs. Our results show that the map medium is effective, and, though the graphs produced make sense, there is work to be done before it can be considered ground truth, with issues of vague topics and improper connections between topics arising. Altogether, our results establish a baseline for AI-generated study maps to be improved upon in the future with ground truth to create a more trustworthy software.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/edarxiv/ez2bk/" target="_blank">EduMap: Navigating a Learning Adventure</a>
</div></li>
<li><strong>Self-inhibiting percolation and viral spreading in epithelial tissue</strong> -
<div>
SARS-CoV-2 induces delayed type-I/III interferon production, allowing it to escape the early innate immune response. The delay has been attributed to a deficiency in the ability of cells to sense viral replication upon infection, which in turn hampers activation of the antiviral state in bystander cells. Here, we introduce a cellular automaton model to investigate the spatiotemporal spreading of viral infection as a function of virus and host-dependent parameters. The model suggests that the considerable person-to-person heterogeneity in SARS-CoV-2 infections is a consequence of high sensitivity to slight variations in biological parameters near a critical threshold. It further suggests that within-host viral proliferation can be curtailed by the presence of remarkably few cells that are primed for IFN production. Thus, the observed heterogeneity in defense readiness of cells reflects a remarkably cost-efficient strategy for protection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.12.571279v1" target="_blank">Self-inhibiting percolation and viral spreading in epithelial tissue</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Pilot Study of Liraglutide (A Weight Loss Drug) in High Risk Obese Participants With Cognitive and Memory Issues</strong> - <b>Conditions</b>: Multiple Sclerosis; Long COVID; Long Covid19; Obese; Obesity; Obesity, Morbid; Acute Leukemia in Remission <br/><b>Interventions</b>: Drug: Liraglutide Pen Injector [Saxenda]; Other: Medication Diary <br/><b>Sponsors</b>: University of Chicago <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>EXERCISE TRAINING USING AN APP ON PHYSICAL CARDIOVASCULAR FUNCTION INDIVIDUALS WITH POST-COVID-19 SYNDROME</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise; Behavioral: Control <br/><b>Sponsors</b>: University of Nove de Julho <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1 Trial of Recombinant COVID-19 Trivalent Protein Vaccine （CHO Cell）LYB002V14 in Booster Vaccination</strong> - <b>Conditions</b>: SARS-CoV-2; COVID-19 Vaccine <br/><b>Interventions</b>: Biological: 30μg dose of LYB002V14; Biological: 60μg dose of LYB002V14; Biological: placebo <br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Vaccine Effectiveness Against Recurrent Infection Among Lung Cancer Patients and Biomarker Research</strong> - <b>Conditions</b>: COVID-19 Recurrent; Lung Cancer; Vaccination; Antibody; Chemotherapy; Immune Checkpoint Inhibitor <br/><b>Interventions</b>: Biological: Any Chinese government-recommended COVID-19 booster vaccine <br/><b>Sponsors</b>: Peking Union Medical College Hospital <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IMMUNERECOV CONTRIBUTES TO IMPROVEMENT OF RESPIRATORY AND IMMUNOLOGICAL RESPONSE IN POST-COVID-19 PATIENTS.</strong> - <b>Conditions</b>: Long Covid19; Dietary Supplements; Respiratory Tract Infections; Inflammation <br/><b>Interventions</b>: Dietary Supplement: Nutritional blend (ImmuneRecov). <br/><b>Sponsors</b>: Federal University of São Paulo <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>Physical Activity Coaching in Patients With Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Self-monitoring; Behavioral: Goal setting and review; Behavioral: Education; Behavioral: Feedback; Behavioral: Contact; Behavioral: Exercise; Behavioral: Report; Behavioral: Social support; Behavioral: Group activities; Behavioral: World Health Organization recommendations for being physically active <br/><b>Sponsors</b>: University of Alcala; Professional College of Physiotherapists of the Community of Madrid <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on Post-Acute COVID-19 Syndrome in Improvement of COVID-19 Rehabilitated Patients by Respiratory Training</strong> - <b>Conditions</b>: COVID-19, Post-Acute COVID-19 Syndrome, Dyspnea, Incentive Spirometer <br/><b>Interventions</b>: Device: breathing training <br/><b>Sponsors</b>: Tri-Service General Hospital <br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID</strong> - <b>Conditions</b>: Long COVID; Post Acute Sequelae of COVID-19; Post-Acute COVID-19 <br/><b>Interventions</b>: Drug: Ensitrelvir; Other: Placebo <br/><b>Sponsors</b>: Timothy Henrich; Shionogi 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>Low-intensity Aerobic Training Associated With Global Muscle Strengthening in Post-COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Procedure: muscle strengthening <br/><b>Sponsors</b>: Centro Universitário Augusto Motta <br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Intravenous Immunoglobulin Replacement Therapy for Persistent COVID-19 in Patients With B-cell Impairment</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: Immunoglobulins <br/><b>Sponsors</b>: Jaehoon Ko <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>Effect of Inhaled Hydroxy Gas on Long COVID Symptoms</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Device: Hydroxy gas <br/><b>Sponsors</b>: Oxford Brookes 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>Community Care Intervention to Decrease COVID-19 Vaccination Inequities</strong> - <b>Conditions</b>: COVID-19 Vaccination <br/><b>Interventions</b>: Behavioral: Community Health Worker Intervention to Enhance Vaccination Behavior (CHW-VB) <br/><b>Sponsors</b>: RAND; Clinical Directors Network; National Institute on Minority Health and Health Disparities (NIMHD) <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>PROmotion of COVID-19 BOOSTer VA(X)Ccination in the Emergency Department - PROBOOSTVAXED</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Vaccine Messaging; Behavioral: Vaccine Acceptance Question <br/><b>Sponsors</b>: University of California, San Francisco; National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Duke University; Baylor College of Medicine; Thomas Jefferson University <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating a Comprehensive Multimodal Outpatient Rehabilitation Program for PASC Program to Improve Functioning of Persons Suffering From Post-COVID-19 Syndrome: A Randomized Controlled Trial</strong> - <b>Conditions</b>: Post-Acute COVID-19; Post-Acute COVID-19 Syndrome; Post-Acute COVID-19 Infection; Long COVID; Long Covid19; Dyspnea; Orthostasis; Cognitive Impairment <br/><b>Interventions</b>: Other: Comprehensive Rehabilitation; Other: Augmented Usual Care <br/><b>Sponsors</b>: University of Pennsylvania; Medical College of Wisconsin; National Institutes of Health (NIH) <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>Multilevel Intervention of COVID-19 Vaccine Uptake Among Latinos</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Multilevel Intervention <br/><b>Sponsors</b>: San Diego State University <br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An overview of the role of Niemann-pick C1 (NPC1) in viral infections and inhibition of viral infections through NPC1 inhibitor</strong> - Viruses communicate with their hosts through interactions with proteins, lipids, and carbohydrate moieties on the plasma membrane (PM), often resulting in viral absorption via receptor-mediated endocytosis. Many viruses cannot multiply unless the host’s cholesterol level remains steady. The large endo/lysosomal membrane protein (MP) Niemann-Pick C1 (NPC1), which is involved in cellular cholesterol transport, is a crucial intracellular receptor for viral infection. NPC1 is a ubiquitous…</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>Acarbose reduces Pseudomonas aeruginosa respiratory tract infection in type 2 diabetic mice</strong> - CONCLUSIONS: This study confirmed the attenuating effect of acarbose on P. aeruginosa RTIs in T2DM and nondiabetic mice and investigated its mechanism, providing novel support for its clinical application in related diseases.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An exonuclease-resistant chain-terminating nucleotide analogue targeting the SARS-CoV-2 replicase complex</strong> - Nucleotide analogues (NA) are currently employed for treatment of several viral diseases, including COVID-19. NA prodrugs are intracellularly activated to the 5’-triphosphate form. They are incorporated into the viral RNA by the viral polymerase (SARS-CoV-2 nsp12), terminating or corrupting RNA synthesis. For Coronaviruses, natural resistance to NAs is provided by a viral 3’-to-5’ exonuclease heterodimer nsp14/nsp10, which can remove terminal analogues. Here, we show that the replacement of the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical phenotype and outcome of persistent SARS-CoV-2 replication in immunocompromised hosts: a retrospective observational study in the Omicron era</strong> - CONCLUSION: Ongoing SARS-CoV-2 replication in the lower respiratory tract is a relevant differential diagnosis in patients with severe immunosuppression and continuous cough, fever or dyspnoea even if nasopharyngeal swabs test negative for SARS-CoV-2. Especially in B cell-depleted patients, this may lead to inflammatory or fibrotic-like pulmonary changes, which are partially reversible after inhibition of viral replication. Antiviral therapy seems to be most effective in combination and over a…</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>Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research</strong> - As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID-19) today, arbidol often involves drug-drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 μL incubation system was used to study the inhibitory…</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>Tumor Treating Fields (TTFields) demonstrate antiviral functions <em>in vitro</em>, and safety for application to COVID-19 patients in a pilot clinical study</strong> - Coronaviruses are the causative agents of several recent outbreaks, including the COVID-19 pandemic. One therapeutic approach is blocking viral binding to the host receptor. As binding largely depends on electrostatic interactions, we hypothesized possible inhibition of viral infection through application of electric fields, and tested the effectiveness of Tumor Treating Fields (TTFields), a clinically approved cancer treatment based on delivery of electric fields. In preclinical models,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing of Rutan showed effective treatment for COVID-19 disease</strong> - Previously, from the tannic sumac plant (Rhus coriaria), we developed the Rutan 25 mg oral drug tablets with antiviral activity against influenza A and B viruses, adenoviruses, paramyxoviruses, herpes virus, and cytomegalovirus. Here, our re-purposing study demonstrated that Rutan at 25, 50, and 100 mg/kg provided a very effective and safe treatment for COVID-19 infection, simultaneously inhibiting two vital enzyme systems of the SARS-CoV-2 virus: 3C-like proteinase (3CLpro) and RNA-dependent…</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>Inhibition of the K<sub>Ca</sub>2 potassium channel in atrial fibrillation: a randomized phase 2 trial</strong> - Existing antiarrhythmic drugs to treat atrial fibrillation (AF) have incomplete efficacy, contraindications and adverse effects, including proarrhythmia. AP30663, an inhibitor of the K(Ca)2 channel, has demonstrated AF efficacy in animals; however, its efficacy in humans with AF is unknown. Here we conducted a phase 2 trial in which patients with a current episode of AF lasting for 7 days or less were randomized to receive an intravenous infusion of 3 or 5 mg kg^(-1) AP30663 or placebo. The…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Angiotensin Converting Enzyme 2 Does Not Facilitate Porcine Epidemic Diarrhea Virus Entry into Porcine Intestinal Epithelial Cells and Inhibits It-induced Inflammatory Injury by Promoting STAT1 Phosphorylation</strong> - ACE2 has been confirmed to be a functional receptor for SARS-CoV and SARS-CoV-2, but research on animal coronaviruses, especially PEDV, are still unknown. The present study investigated whether ACE2 plays a role in receptor recognition and subsequent infection during PEDV invasion of host cells. IPEC-J2 cells stably expressing porcine ACE2 did not increase the production of PEDV-N but inhibited its expression. Porcine ACE2 knockout cells was generated by CRISPR/Cas9 genome editing in IPEC-J2…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The environmental impact of mask-derived microplastics on soil ecosystems</strong> - During the COVID-19 pandemic, a significant increased number of masks were used and improperly disposed of. For example, the global monthly consumption of approximately 129 billion masks. Masks, composed of fibrous materials, can readily release microplastics, which may threaten various soil ecosystem components such as plants, animals, microbes, and soil properties. However, the specific effects of mask-derived microplastics on these components remain largely unexplored. Here, we investigated…</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>Hospital healthcare workers’ use of facial protective equipment before the COVID-19 pandemic, implications for future policy</strong> - CONCLUSION: This study identified key determinants of FPE behavior. A review of context specific FPE guidance for ED by infection prevention and control professionals would help to promote practicable, sustainable compliance.</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>Hybrid immunity from SARS-CoV-2 infection and mRNA BNT162b2 vaccine among Thai school-aged children</strong> - CONCLUSIONS: Immune response that arises from BNT162b2 vaccine after natural infection and infection after 2 doses of BNT162b2 was higher than infection after partially-vaccinated children.</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>Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and M<sup>PRO</sup> enzymes of SARS-CoV-2</strong> - CONCLUSION: The IC(50) for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of the clinical efficacy of racecadotril in the treatment of neonatal calves with infectious diarrhea</strong> - Racecadotril, used as an antidiarrheal drug in humans and some animals such as the dog, inhibits peripheral enkephalinase, which degrades enkephalins and enkephalinase inhibition induces a selective increase in chloride absorption from the intestines. The study material consisted of 46 calves with infectious diarrhea and 14 healthy calves in the age 2-20 days. The calves were divided into eight groups; healthy calves (HG), healthy calves administered racecadotril (HRG), calves with…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An ncRNA transcriptomics-based approach to design siRNA molecules against SARS-CoV-2 double membrane vesicle formation and accessory genes</strong> - CONCLUSION: Our novel in silico pipeline integrates effective methods from previous studies to predict and validate siRNA molecules, having the potential to inhibit viral replication pathway in vitro. In total, this study identified 17 highly specific siRNA molecules targeting NSP3, 4, and 6 and accessory genes ORF3a, 7a, 8, and 10 of SARS-CoV-2, which might be used as an additional antiviral treatment option especially in the cases of life-threatening urgencies.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What Did COP28 Really Accomplish?</strong> - At the end of the day—or record-hot year—what matters is not what language countries agree to but what they actually do. - <a href="https://www.newyorker.com/news/daily-comment/what-did-cop28-really-accomplish">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Year of Ozempic</strong> - We may look back on new weight-loss drugs as some of the greatest advances in the annals of chronic disease. - <a href="https://www.newyorker.com/culture/2023-in-review/the-year-of-ozempic">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Colorado Reconsiders Letting Trump on the Ballot</strong> - A Colorado Supreme Court case is one of several considering whether Trump should be disqualified under the Fourteenth Amendment, but it has proceeded the furthest. - <a href="https://www.newyorker.com/news/daily-comment/colorado-reconsiders-letting-trump-on-the-ballot">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The U.N. Human-Rights Chief and the Fugitive Princess of Dubai</strong> - Michelle Bachelet’s private meeting with Sheikha Latifa bint Mohammed Al Maktoum was viewed as proof that a long-imprisoned royal was finally free. In her first interview about the encounter, Bachelet reveals her doubts. - <a href="https://www.newyorker.com/news/news-desk/the-un-human-rights-chief-and-the-fugitive-princess-of-dubai">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How a Student Group Is Politicizing a Generation on Palestine</strong> - Activists with Students for Justice in Palestine have mobilized major campus demonstrations in support of Gaza—and provided an intellectual framework for protesters watching what’s happening in the Middle East. - <a href="https://www.newyorker.com/news/annals-of-education/how-a-generation-is-being-politicized-on-palestine">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>A new approach to measuring what’s going on in our minds</strong> -
<figure>
<img alt="Santiago Ramón y Cajal working at his desk with a microscope and medicinal bottles, writing on paper." src="https://cdn.vox-cdn.com/thumbor/TNK1daUQuXbAdowaleGb0vQaPFY=/22x0:5295x3955/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72965618/GettyImages_152195326.0.jpg"/>
<figcaption>
Santiago Ramón y Cajal, neuroscientist and artist who shared the 1906 Nobel Prize in medicine with Camillo Golgi. | Universal Images Group via Getty
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Quantifying the “complexity” of consciousness can tell us how rich our experiences are.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TQOdgi">
Sometimes when I’m looking out across the northern meadow of Brooklyn’s Prospect Park, or even the concrete parking lot outside my office window, I wonder if someone like Shakespeare or Emily Dickinson could have taken in the same view and seen <em>more. </em>I don’t mean making out blurry details or more objects in the scene. But through the lens of their minds, could they encounter the exact same world as me and yet have a richer experience?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ojicVK">
One way to answer that question, at least as a thought experiment, could be to compare the electrical activity inside our brains while gazing out upon the same scene, and running some statistical analysis designed to actually tell us whose brain activity indicates more richness. But that’s just a loopy thought experiment, right?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UnHFsf">
Not exactly. One of the newest frontiers in the science of the mind is the <a href="https://www.biorxiv.org/content/10.1101/2023.12.05.570101v1">attempt to measure</a> consciousness’s “complexity,” or how diverse and integrated electrical activity is across the brain. Philosophers and neuroscientists alike <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10325487/">hypothesize</a> that more complex brain activity signifies “richer” experiences.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wUwIJX">
The idea of measuring complexity stems from <a href="https://www.quantamagazine.org/how-claude-shannons-information-theory-invented-the-future-20201222/">information theory</a> — a mathematical approach to understanding how information is stored, communicated, and processed —which doesn’t provide wonderfully intuitive examples of what more richness actually means. Unless you’re a computer person. “If you tried to upload the content onto a hard drive, it’s how much memory you’d need to be able to store the experience you’re having,” <a href="https://profiles.sussex.ac.uk/p156234-adam-barrett">Adam Barrett</a>, a professor of machine learning and data science at the University of Sussex, told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NIQiHA">
Another approach to understanding richness is to look at how it changes in different mental states. Recent studies have found that <a href="https://www.nature.com/articles/s42003-023-04474-1">measures of complexity</a> are lowest in patients under general anesthesia, higher in ordinary wakefulness, and higher still in psychedelic trips, which can notoriously turn even the most mundane experiences — say, my view of the parking lot outside my office window — into <a href="https://www.vox.com/future-perfect/23972716/psychedelics-meaning-science-psychedelic-mushrooms-ketamine-psilocybin-mysticism">profound and meaningful encounters</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3K34js">
Increasing richness isn’t just like cranking up the color saturation of a picture or getting a bigger hard drive. It seems to imply an increase in the depth of how we experience the world. Complexity is what you see in the equations, richness is what that feels like in the mind.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="00gM5e">
Although measuring brain complexity is still in relative infancy, the nascent ability to gauge something like richness is a pretty incredible development — not only for <a href="https://www.vox.com/neuroscience">neuroscience</a> but for how we think about well-being more broadly. With innovations like these, we can go beyond the <a href="https://www.vox.com/the-highlight/23862090/subjective-wellbeing-wealth-philanthropy-gdp-happiness-givewell">blurry question of happiness</a>, which doesn’t have an accepted neurological measure that can translate across social and cultural differences, and ask more targeted questions, like whether our experiences are richer. As these approaches mature, scientists might develop a deeper understanding of all the different, tractable ways that consciousness can change for the better.
</p>
<h3 id="2bavvt">
From staining neurons black to measuring the brain’s complexity
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="spZBZp">
In the 1800s, scientists studying the mind didn’t yet know what a neuron looked like, let alone how they worked. That breakthrough came in <a href="https://embryo.asu.edu/pages/neuron-doctrine-1860-1895">1873</a>, when physician Camillo Golgi discovered that by immersing brain tissue in a potassium dichromate solution and then dunking it in a bath of silver nitrate, the neuron would turn black, making it visible under a microscope.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N5rHCD">
The Spanish neuroscientist Santiago Ramón y Cajal, when observing newly stained neural tissue in 1887, discovered that contrary to the reigning reticular theory (which held that the nervous system was a continuous network of cells smushed together with no gaps), neurons were indeed separated from each other. Sprouting from the neuron’s edges were spindly little axons and dendrites, but they didn’t seem to create permanent bridges between the neurons, leading him to conclude that communication between neurons likely wasn’t all that important in explaining their main functions. Instead, individual neurons were taken as the nervous system’s fundamental units, or building blocks, an idea that solidified into “the <a href="https://embryo.asu.edu/pages/neuron-doctrine-1860-1895">neuron doctrine</a>.”
</p>
<figure class="e-image">
<img alt="An ink illustration of a root- or vein-like structure of connected tendrils. spreading upward." src="https://cdn.vox-cdn.com/thumbor/grgMXPbGUE9GaAt3GLxonLSRuyQ=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25162910/GettyImages_1404548943.jpg"/> <cite>VW Pics/Universal Images Group</cite>
<figcaption>
Neuroscientist and artist Santiago Ramón y Cajal’s drawings of neuroanatomy were collected into a book, <em>The Beautiful Brain: The Drawings of Santiago Ram</em>ó<em>n y Cajal.</em>
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MpuP7i">
Through the 20th century, developments in electrophysiology led to a sharper understanding of the connections between neurons, and the importance of the little electrical impulses that travel across synapses. But the basic perspective of focusing on neurons themselves, rather than the holistic electrical processes that they’re conduits for, remained dominant. This approach has gotten quite good at breaking the brain into distinct parts and explaining how they contribute to specific functions, like vision or controlling your fingers. The downside is that many theories of consciousness struggle with what’s called the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538094/">binding problem</a> — the question of how all the separate parts fit back together to generate a unified conscious experience.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2lnBUs">
Recent improvements to electroencephalography (EEG, those skull caps with a bunch of electrodes that measure the brain’s electrical activity) made it possible to look deeper inside the workings of the brain, opening the way for neuroscientist Giulio Tononi and biologist Gerald Edelman’s 1998 paper: <a href="https://www.science.org/doi/10.1126/science.282.5395.1846">Consciousness and Complexity</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2vizX9">
Their publication was the first to propose a direct measure of the complexity of brain activity, an idea that matured into <a href="https://www.nature.com/articles/nrn.2016.44">Integrated Information Theory</a>, or IIT. According to IIT, consciousness arises where the underlying neural activity is both “integrated” and “differentiated.” Integration refers, roughly, to how synchronized electrical activity is across the brain. Differentiation is the diversity of that activity. You can think of them in terms of weaving a tapestry. Integration is how many different threads are woven in, while differentiation is the variety of colors used. Together, these two determine the complexity of a given state of consciousness. That, in turn, approximates its richness.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1qOHaw">
In theory, anyway. At the time, the idea ran ahead of technology. “It became apparent over the years that it’s quite hard to measure those two things simultaneously,” Barrett told me, “and it turned out that the differentiation aspect alone, without thinking about integration, did quite well at being able to distinguish between different states of consciousness.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iMsZ7k">
That said, our measures are improving quickly. Barrett co-authored <a href="https://www.biorxiv.org/content/10.1101/2023.12.05.570101v1">a study</a> released as a pre-print last week that compared a new measure of complexity — what they call “statistical complexity” — to Lempel-Ziv complexity, which was first <a href="https://ieeexplore.ieee.org/document/1055501">proposed</a> in 1976 and is still the field’s leading measure. While Lempel-Ziv captures only the differentiation aspect, their findings suggest that the new measure successfully brings integration back into the mix, affording greater precision.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Qtp7Nr">
As progress continues, IIT may creep closer to its grand ambition: constructing an equation that can measure and describe the richness of conscious experience in any physical system, whether human, animal, or machine. “That fails at the moment,” said Barrett, “but I’m very interested in seeing if we could come up with a plausible equation. That’s sort of the holy grail for me.”
</p>
<h3 id="VbRIOy">
So what do we make of richness?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="niyx1w">
If a plausible equation isn’t the kind of thing that occupies your dreams, a concrete measure for something like richness could bring some sorely needed innovation to our ideas around <a href="https://www.vox.com/mental-health">mental health</a>. The Diagnostic and Statistical Manual of Mental Disorders (the DSM-5) contains <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810039/#B27-behavsci-06-00005">298</a> diagnoses to help clinicians classify just about every shade of mental disorder they might encounter. When it comes to the positive dimensions of mental health, however, our language is comparatively sparse.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="m5w5kP">
“Happiness” is a very nebulous idea, especially when you <a href="https://www.vox.com/the-highlight/23862090/subjective-wellbeing-wealth-philanthropy-gdp-happiness-givewell">try to measure it</a>. We in the West, unlike the Buddhists, have not developed rigorous taxonomies for all the rungs on the mental ladder — from our default modes to the ecstasies, grades of zest, or senses of “<a href="https://sashachapin.substack.com/p/how-i-attained-persistent-self-love#footnote-1-47192004">deep okayness</a>” that lurk in the <a href="https://www.vox.com/future-perfect/23836358/meditation-mindfulness-enlightenment-science-contemplative-buddhism-spirituality">upper realms of well-being</a> (reportedly, anyway). If we can quantify the richness of our minds, maybe it could jumpstart the process of finding other tractable dimensions we can add to our conceptions of well-being.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pSuR36">
Of course, quantifying something important always <a href="https://philpapers.org/go.pl?aid=NGUVCH">carries risks</a> (à la <a href="https://www.oxfordreference.com/display/10.1093/oi/authority.20110803095859655">Goodhart’s law</a>: when a measure becomes a target, it ceases to be a good measure), and being wise about how to make sense of these new ideas will be bumpy. It’s tempting, for example, to simply think that when it comes to richness, more is always better. But researchers, like <a href="https://www.vox.com/future-perfect">Future Perfect</a> 50 honoree <a href="https://www.vox.com/23896208/robin-carhart-harris-professor-neurology-psychedelics-ucsf-future-perfect-50-2023">Robin Carhart-Harris</a>, believe that the brain evolved to hold levels of complexity below a threshold called “criticality,” rather than just maximize it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="k5jnAv">
In information theory, criticality marks the optimal balance of complexity for processing information, a perch between order and chaos. Or in terms of the mind, between the rigidity and flexibility of mental habits. Too much complex activity pushes the brain over the edge. That might offer a temporarily exciting state of mind (as psychedelic trips can), but in terms of efficiently processing information to be successful creatures in the world, a never-ending acid trip is probably not the ideal state. “A brain at criticality may be a ‘happier’ brain,” Carhart-Harris <a href="https://www.frontiersin.org/articles/10.3389/fnhum.2014.00020/full#h12">writes</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jvP96B">
If criticality means greater well-being calls for a particular balance of complexity, not just as much as we can muster, that doesn’t mean that we’re all, by default, naturally tuned to that balance. As our measures and technologies improve, maybe we’ll get better at identifying when someone’s ordinary brain activity is below criticality, and a burst of complexity could serve as a boon to well-being. Maybe we’ll develop new ways of growing richer, not just in our bank accounts (though that may help), but in the ways that we experience the world.
</p></li>
<li><strong>What Trump has already taken from us</strong> -
<figure>
<img alt="Trump wears a navy blue suit jacket and a red tie, and raises his right hand in a fist. Behind him, a screen displays the words: Florida Is Trump Country" src="https://cdn.vox-cdn.com/thumbor/c-LpKp_nCBrxf3U9ZhY11ToNVJc=/203x0:4195x2994/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72965555/1771549284.0.jpg"/>
<figcaption>
Trump holds a rally at Ted Hendricks Stadium in Hialeah, Florida, on November 8, 2023. | Alon Skuy/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Democracy is a culture — and Trump is destroying it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vbadCU">
In the long arc of human history, the modern democratic era is a mere blip.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4filC3">
Humans first began residing in city-like agricultural settlements <a href="https://www.science.org/content/article/when-did-humans-settle-down-house-mouse-may-have-answer">about 10,000 years ago</a>. The American and French revolutions, widely seen as the dawn of the democratic age, took place less than 250 years ago. For most of subsequent history, so-called “democracies” didn’t meet minimal modern standards — most notably by restricting the franchise to white, property-owning men.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JvYJ6Y">
Democracy as we know it — a system formally premised on equal citizenship for everyone — is <a href="https://ourworldindata.org/grapher/countries-with-universal-right-to-vote-lexical">really a 20th-century invention</a>. The degree to which it has become the consensus gold standard for human governance, both in the United States and around the world, is nothing short of miraculous.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9cgvTm">
This development is not just a function of democracy’s military victories or constitutional innovations. It has depended fundamentally on the global rise of <em>a democratic culture —</em> a set of ideas, beliefs, and expectations centering on the notion that democracy is the only just and feasible way to run a society.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZpUo4W">
Democracy has grown and matured by turning into a self-fulfilling prophecy: It persists because everyone in a society believes it should and will exist. If democratic culture dims, democracy’s prospects dim with it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fJJJwy">
The United States, the first country to claim the mantle of democracy in the modern era, has long had an exceptionally strong democratic culture. Belief in democratic ideals, liberal rights, and the basics of constitutional government are so fundamental to American identity that they’ve been collectively described as the country’s “<a href="https://www.npr.org/2021/04/12/985036148/can-americas-civil-religion-still-unite-the-country">civil religion.</a>”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wwUhBN">
Yet today, America’s vaunted democratic culture is withering before our eyes. American democracy, once seemingly secure, is now in so much trouble that <a href="https://www.npr.org/2023/10/25/1208373493/political-violence-democracy-2024-presidential-election-extremism">75 percent of Americans</a> believe that “the future of American democracy is at risk in the 2024 presidential election,” according to a study by the Public Religion Research Institute and the Brookings Institution.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JVm0rv">
This withering took off during <a href="https://www.vox.com/donald-trump">Donald Trump</a>’s rise to power and has continued apace in his post-presidency. The more he <a href="https://www.vox.com/2023/11/14/23958866/trump-vermin-authoritarian-democracy">attacks the foundations of the democratic system</a>, the less everyone — both his supporters and his opponents — believe American democracy is both healthy and likely to endure.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QFFCTi">
Moreover, he has birthed an anti-democratic movement inside the Republican Party dedicated to advancing his vision (or something like it). These Republicans vocally and loudly argue American democracy is a sham — and that dire measures are justified in response. This faction is already influential, and will likely become more so given its especial prominence among the ranks of young conservatives.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BwyWSN">
As worrying as the prospect of a second Trump term is, the damage he and his allied movement have already done to American democratic culture is not hypothetical: It’s already here, it’s getting worse, and it will likely persist — even if Trump loses in 2024.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RnB2Vx">
Put differently, Trump has already robbed us of our sense of security and faith in our democracy. The consequences of that theft are not abstract, but rather ones we’ll all have to deal with for years to come.
</p>
<h3 id="VSi9XH">
How democratic culture protects democracy
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6d5b6b">
To understand how democratic culture works — and how Trump’s behavior damages it — it’s important to start with a political science concept called “democratic consolidation.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tgGyFg">
The idea, which grew out of the study of new and fragile democracies, is that merely creating a formal democratic system isn’t enough to ensure its survival. Rather, democracies only become stable when no major political actors even think of breaking its most fundamental rules. Once such a culture has been constructed, democracy becomes the only game in town: the only conceivable means for attaining and wielding political power.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jRpSjc">
There are many different ways to think about the process of consolidation. Some center around the idea of <a href="https://www.vox.com/23055620/supreme-court-legitimacy-crisis-abortion-roe">political legitimacy</a> — whether public and political elites come to believe that their democratic government has the moral right to rule. Larry Diamond, a political scientist at Stanford, defined democratic consolidation <a href="https://muse.jhu.edu/article/225379/pdf">in a 1994 article</a> as “the process by which democracy becomes so broadly and profoundly legitimate among its citizens that it is very unlikely to break down.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W30JHP">
Others focus less on legitimacy than on political calculation. In<a href="https://irihs.ihs.ac.at/id/eprint/1026/1/pw_50.pdf"> a 1997 paper</a>, Central European University’s Andreas Schedler argued that a democracy is most at risk when both elites and the mass public believe that it won’t last. If members of competing factions are afraid that the other side might seize power undemocratically, they become more willing to try to do it themselves. But when everyone believes that democracy will likely survive and that power can’t or won’t be seized in some extralegal fashion, they become more likely to play by the rules.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iQMhMF">
“Democracy is consolidated,” Schedler writes, “when actors think it actually will last well into the future.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5yfUcJ">
These two factors, legitimacy and expectations, are deeply intertwined. The more widespread a government’s legitimacy among the citizenry, the more reason people have to be confident it will persist. The more stable a democracy seems, the more likely people are to see it as a legitimate source of authority.
</p>
<figure class="e-image">
<img alt="A young man wearing eyeglasses and a T-shirt with an American flag design holds a small American flag in his hand. Beside him, a woman in a white headscarf and sunglasses also holds a small American flag. " src="https://cdn.vox-cdn.com/thumbor/zX1hN3d_MBr3qxatIoow01vo4lk=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25163509/809266352.jpg"/> <cite>Keith Bedford/The Boston Globe/Getty Images</cite>
<figcaption>
A crowd listen to a reading of the Declaration of Independence at the Old State House in Boston, Massachusetts, on July 4, 2017.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vqj7UQ">
So once a country has managed to establish a democratic culture, it tends to build on itself over time. Statistically, one of the strongest predictors of a democracy’s future survival is how long it has already been in place. Older democracies tend to have such robust democratic cultures that their fraying seems unimaginable.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DP1mMW">
The United States is often described as the oldest democracy in the world — and not without justification. While it fell far short of <a href="https://www.theatlantic.com/magazine/archive/2021/03/voting-rights-act-democracy/617792/">many basic democratic standards until fairly recently</a>, America has been holding electoral contests that produced peaceful transfers of power for its entire history. The consensus on democracy’s most basic idea, that the people should get to determine who rules them, has been remarkably strong in American public culture (even when the definition of “the people” was unacceptably shrunken).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TFomuB">
For this reason, post-civil rights America was long seen as the most consolidated of consolidated democracies. Yet today, there are serious fears that American democracy may not be long for this world. The gold standard consolidated democracy may no longer be consolidated at all.
</p>
<h3 id="Ahh4Su">
The great unsettling of American democracy
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="86h3D6">
In the United States, democracy’s positive feedback loop turned negative. Republican attacks on the legitimacy of America’s democratic institutions caused Democrats to doubt their very survival — leading Democrats to take actions that Republicans (incorrectly) perceive as further undermining the system’s legitimacy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VexmdP">
The process was visible during Trump’s rise in 2016, when his partisans began casting the contest with Hillary Clinton in apocalyptic terms — “charge the cockpit or you die,” as <a href="https://nymag.com/intelligencer/article/michael-antons-flight-93-election-trump-coup.html">one famous pro-Trump metaphor went</a>. But it really accelerated after the <a href="https://www.vox.com/2020-presidential-election">2020 election</a>, when Trump argued that the election was stolen from him and attempted <a href="https://www.vox.com/policy-and-politics/2022/6/10/23162442/january-6-committee-hearing-june-10-trump-fascist">a kind of coup</a> rather than accepting defeat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5fB2zD">
Polling has consistently shown that large majorities of Republicans believe that Biden stole the election from Trump — that is, that America’s last presidential election <em>was not decided democratically</em>. Political scientists have confirmed that <a href="https://www.washingtonpost.com/politics/2022/01/07/republicans-big-lie-trump/">they’re not just saying this</a>: Republicans sincerely believe that American democracy is not functioning in a legitimate fashion, that it’s rigged against them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xerzFs">
Trump’s attempt to overturn the election made it plain to his opponents that he posed a clear and present threat to American democracy. Democrats began talking, and acting, like the country was in the midst of an existential crisis — making<a href="https://www.vox.com/policy-and-politics/2022/12/19/23453073/2022-year-democracy-russia-ukraine-china-iran-america-brazil"> the preservation of democracy a central issue in the 2022 midterms</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E9pQba">
Today, it’s common among pro-Trump Republican partisans to jeer at the invocation of democratic values (“muh democracy” is a common sarcastic phrase on right-leaning social media). They see liberals and Democrats warnings about Trump as an insincere ploy to defend a corrupt system and scorn them accordingly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9Xvk9p">
Anti-democratic rhetoric is not the sole province of Trump and a handful of his most online supporters.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ghGn3c">
Current Speaker of the House Mike Johnson (R-LA) was the architect of the House Republican caucus’s <a href="https://www.nbcnews.com/politics/congress/mike-johnson-january-6-house-speaker-nominee-rcna122081">legal argument for overturning the 2020 election</a>. Amazingly, Johnson was not perceived as the most radical candidate during the contentious fight to choose a speaker: He was a consensus alternative to Rep. Jim Jordan (R-OH), <a href="https://www.newyorker.com/news/our-columnists/the-symbiotic-democracy-eroding-relationship-between-donald-trump-and-jim-jordan">a dogmatic Trump ally</a> who (<a href="https://www.theatlantic.com/politics/archive/2023/10/us-house-democracy-threat-republican-speaker-race/675679/">per some reports</a>) was the House Republican most deeply involved in Trump’s election overthrow effort.
</p>
<figure class="e-image">
<img alt="Rep. Johnson sits with a somber expression on his face. Rep. Jordan stands beside him and points a finger in the air, wearing a serious and displeased expression." src="https://cdn.vox-cdn.com/thumbor/Mj6CLcsseuZysf7JL-AdwxB20Qk=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25163530/1240746132.jpg"/> <cite>Tom Williams/CQ-Roll Call/Getty Images</cite>
<figcaption>
Republican Reps. Mike Johnson (left) and Jim Jordan (right) attend a House Judiciary meeting on May 18, 2022.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JlPvLb">
In <a href="https://www.theunpopulist.net/p/markers-to-identify-a-rightwing-authoritarian">a recent piece in the Unpopulist</a>, the libertarian writer Radley Balko compiled a long list of other influential Republicans who have made their disdain for democracy plain. Some examples included:
</p>
<ul>
<li id="Uqbjpf">
Kash Patel, a high-level <a href="https://www.vox.com/trump-administration">Trump administration</a> official rumored to be a top pick for CIA director, vowed to “go after” his enemies in government and <a href="https://www.vox.com/media">the media</a> “<a href="https://abcnews.go.com/US/kash-patel-tells-members-media-government-after-trumps/story?id=105432592">criminally or civilly</a>” if returned to power.
</li>
<li id="SQB4HU">
Mike Davis, a Republican lawyer on Trump’s attorney general shortlist, says he would use that power to engage in a “<a href="https://www.mediamatters.org/donald-trump/mike-davis-promises-reign-terror-if-trump-appoints-him-acting-attorney-general">reign of terror</a>” in which they “<a href="https://news.yahoo.com/gonna-put-kids-cages-meet-200752325.html?guccounter=1&amp;guce_referrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmNvbS8&amp;guce_referrer_sig=AQAAALQAKfJGxzM5zb81S3hXEOC7xJXf2o88AUk2kkQICbnT33Rm9d6f3FF8BQm41MMaPS-RJV7F66V1ybx52keNvLeNFCpYyilV_FfZr89l9JPBg_Bg2loJMTRYKDoGyPGqc_0YVXVT1KzTFdAYLjOcMcYcjLyNETlF-wT32lwtJLYF">put kids in cages</a>” and “detain a lot of people in the DC gulag.”
</li>
<li id="cRD5vJ">
Sen. J.D. Vance (R-OH) <a href="https://nymag.com/intelligencer/2022/05/j-d-vance-republican-senate-hillbilly-elegy-dangerous-authoritarian.html">advised Trump</a> to fire “every civil servant in the administrative state” and “replace them with our people.”
</li>
<li id="CSvmBM">
Presidential candidate <a href="https://www.nbcnews.com/politics/2024-election/vivek-ramaswamy-january-6-inside-job-conspiracy-theory-rcna128463">Vivek Ramaswamy went</a> on a conspiratorial rant during the December primary debate — calling the January 6, 2021, Capitol riot an “inside job,” defending the white nationalist “Great Replacement” theory, accusing “<a href="https://www.vox.com/big-tech">Big Tech</a>” of stealing the 2020 election, and indulging in 9/11 trutherism.
</li>
<li id="lIf73K">
Texas Attorney General Ken Paxton has opened <a href="https://www.texasattorneygeneral.gov/news/releases/attorney-general-ken-paxton-opens-investigation-media-matters-potential-fraudulent-activity">a criminal investigation into Media Matters</a>, a liberal media watchdog, in retaliation for its criticism of Elon Musk’s content moderation on <a href="https://www.vox.com/twitter">Twitter</a> (also known as X).
</li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UEejOT">
The official veer into authoritarianism Balko documents is underpinned by an intellectual climate on the right that’s <a href="https://www.nytimes.com/2022/12/14/us/politics/extremism-republicans.html">socializing the next generation of Republicans into extremism</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9PLcrA">
Take the pseudonymous writer Bronze Age Pervert, for example. Identified as a <a href="https://www.theatlantic.com/magazine/archive/2023/09/bronze-age-pervert-costin-alamariu/674762/">Yale-trained political theorist named Costin Alamariu</a>, BAP is a pop-Nietzchean extremist who refers to his political enemies as subhuman “bugmen” and describes his own politics as “fascism or ‘something worse.’” Despite (or perhaps because) of this bizarre presentation, he is <a href="https://www.motherjones.com/politics/2023/10/bronze-age-pervert-costin-alamariu/">widely read by young Republican staffers</a>. Nate Hochman, a former <a href="https://www.vox.com/ron-desantis">Ron DeSantis</a> speechwriter, <a href="https://www.nytimes.com/2022/08/03/magazine/claremont-institute-conservative.html">told the New York Times</a> that “every junior staffer in the Trump administration read [BAP’s manifesto] ‘Bronze Age Mindset.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fra7Ti">
Among liberals and the left, the response to this has been increasing talk about playing constitutional hardball to stop the right — and even murmurs of outright alternatives to existing political arrangements.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IMjbss">
In a recent <a href="https://www.washingtonpost.com/opinions/2023/11/30/trump-dictator-2024-election-robert-kagan/">Washington Post</a> essay announcing that “a Trump dictatorship is increasingly inevitable,” the writer Robert Kagan counsels Democratic governors to resist Trump rule through “a form of nullification” — the doctrine of states’ rights underpinning pre-Civil War Southern resistance to the Union. In <a href="https://www.amazon.com/Democracy-Lasts-Forever-Constitution-Threatens-ebook/dp/B0CJGYQNY2">a forthcoming book</a> titled <em>No Democracy Last Forever</em>, eminent legal scholar Erwin Chemerinsky argues that Americans need to think about “forms of secession” from the Union.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WFNq8m">
This is what it looks like when a democracy de-consolidates. The shared expectation that the American system deserves its citizens’ respect has collapsed; so too has the shared sense that there’s no alternative to democratic rules and elections for the foreseeable future.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="foj2UX">
This is not just a Trump phenomenon: The loss of faith in American democracy runs deep.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HS74cT">
The social forces unleashed by the MAGA movement are<a href="https://www.vox.com/2016/9/19/12933072/far-right-white-riot-trump-brexit"> bigger and more primal than one man</a>. The political rise of figures like Johnson, Vance, and Ramaswamy — all younger vehicles for Trump-style anti-democratic politics — points toward a post-Trump right that continues to attack democracy’s foundations. So too does <a href="https://www.amazon.com/Reactionary-Spirit-Insidious-Political-Tradition-ebook/dp/B0CMQB8S94">the anti-democratic right’s ascent to political power in advanced democracies around the world</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ePA5nt">
There’s <a href="https://www.vox.com/policy-and-politics/2022/12/19/23453073/2022-year-democracy-russia-ukraine-china-iran-america-brazil">plenty of cause for hope</a> that American democratic culture can be repaired. But it’s important to start from a place of realism about the problem — that we are in the midst of an unprecedented kind of democratic collapse: the de-consolidation of the world’s oldest and most deeply rooted democracy, fueled primarily by <a href="https://www.vox.com/policy-and-politics/22274429/republicans-anti-democracy-13-charts">the Republican party’s institutional turn against democratic ideals</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TihXDc">
Trump may not win next year. But he has already succeeded in taking something vital from us — our faith in a bright democratic future.
</p></li>
<li><strong>What your credit score actually means</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/Ny5EOQZLgEjPeRdLJwbBDIduSps=/240x0:1680x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72963954/VDC_XEP_061_credit_scores_Thumb_SYN.0.jpg"/>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It’s not just you. Credit scores are confusing as hell.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hO61Tz">
When credit scores were invented just a few decades ago, they were hailed as a way to democratize lending. Today, they’ve become so essential that not having one can lock you out of daily life. Having a low score can make life challenging, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cQRy71">
These scores have a long history — and a lot of problems. In this video, we’ll show you where they came from, how they’ve changed over the years, and explain what that three-digit number means for you.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HlqInf">
This video is presented by Secret. Secret doesn’t have a say in our editorial decisions, but they make videos like this possible.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5WUsJ7">
You can find the video above and the entire library of <a href="https://www.youtube.com/channel/UCLXo7UDZvByw2ixzpQCufnA"><strong>Vox’s videos on YouTube</strong></a>.
</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>Double Scotch, Mystical Air, Honest Desire and Philosophy shine</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Booster Shot shines</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To honour Dhoni’s contribution to Indian cricket, No. 7 jersey retired, says Rajeev Shukla</strong> - The iconic India captain last played for the country in the 2019 World Cup semifinal against New Zealand.</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>AUS vs PAK first Test | Pakistan digs in as Lyon edges closer to 500 Test wickets</strong> - But it was a slow grind with Pakistan runs coming off 53 overs after Aamer Jamal took 6-111 on debut to help dismiss the hosts for 487.</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>Dhoni’s contempt plea | Madras High Court sentences IPS officer to 15 days imprisonment</strong> - Justices S.S. Sundar and Sunder Mohan, however, suspend the sentence imposed on G Sampath Kumar for 30 days in order to enable him to file an appeal before Supreme Court</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>Farmers to get interest waiver on medium-, long-term cooperative loans if they pay up principal amount</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CPI(M) in Kerala perceives cracks in Opposition UDF over Centre’s ‘financial embargo’ on State</strong> - CPI(M) State secretary M.V. Govindan says IUML leader P.K. Kunhalikutty has evinced interest to cooperate with ruling LDF to wrest what the Centre financially owed Kerala and fight against Union Government’s ‘economically stifling trespasses’ on fiscal federalism</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>CM Siddaramaiah announces series of projects for development of North Karnataka</strong> - This includes preparing a comprehensive action plan for promoting prominent tourist destinations and developing an industrial estate on 2,000 acres of land near Belagavi.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SC stays proceedings against Randeep Surjewala in 23-year-old case</strong> - A Bench headed by Chief Justice of India D.Y. Chandrachud issued notice to Uttar Pradesh.</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>Activists stage protest condemning Israel’s attack on Palestine</strong> -</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>Hungary blocks €50bn of EU funding for Ukraine</strong> - Hungary blocks new funding just hours after a deal is struck on starting talks to admit Ukraine to the EU.</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 gas giant Gazprom makes £39m profit in North Sea</strong> - The state-owned Russian energy firm earned £39m from its Dutch-UK gas field in 2022, accounts show.</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>Alex Batty: ‘I love you, I want to come home’</strong> - Alex Batty, 17, went missing in 2017 and British officials are preparing to bring him back to the UK later.</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>Alex Batty: How delivery driver found lost teen on unlit mountain road</strong> - It was the middle of the night when Fabien Accidini stumbled across a young man on an unlit road.</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>Channel migrants: One dead, another injured, says French coastguard</strong> - A boat with 66 people on board got into trouble near the French coast, the coastguard says.</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>Rocket Report: Signs of life from Blue Origin; SpaceX preps next Starship</strong> - Baguette One isn’t a joke, but it sure sounds like one. - <a href="https://arstechnica.com/?p=1991267">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>If AI is making the Turing test obsolete, what might be better?</strong> - The Turing test focuses on the ability to chat—can we test the ability to think? - <a href="https://arstechnica.com/?p=1991004">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Suspects can refuse to provide phone passcodes to police, court rules</strong> - Phone-unlocking case law is “total mess,” may be ripe for Supreme Court review. - <a href="https://arstechnica.com/?p=1991289">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MDMA—aka ecstasy—submitted to FDA as part of PTSD therapy</strong> - If FDA approved, it would require the DEA to reclassify MDMA. - <a href="https://arstechnica.com/?p=1991296">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Space Force chief: Timing of Chinese spaceplane launch “no coincidence”</strong> - US and Chinese spaceplanes are “two of the most watched objects” in orbit. - <a href="https://arstechnica.com/?p=1991189">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
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