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<title>19 September, 2023</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Evidence associating neutrophilia, lung damage, hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality in critically ill COVID-19 patients</strong> -
<div>
Background: COVID-19 severity and high in-hospital mortality are often associated with severe hypoxemia, hyperlactatemia, and acidosis. Since neutrophil numbers in severe COVID-19 can exceed 80% of the total circulating leukocytes and that they are massively recruited to infected lungs, we investigated whether metabolic acidosis mediated by the glycolytic neutrophils is associated with lung damage and impaired oxygen delivery in critically ill patients. Methods: Based on prospective mortality outcome, 102 critically ill-hospitalized COVID-19 patients were divided into two groups: ICU-Survivors (ICU-S, n=36) and ICU-Non-survivors (ICU-NS, n=66). Blood samples were collected from patients and control subjects to explore correlations between neutrophil counts, lung damage, glycolysis, blood lactate, blood pH, hemoglobin oxygen saturation, and mortality outcome. We also interrogated isolated neutrophils for glycolytic activities and for apoptosis using high-throughput fluorescence imaging complemented with transcriptomic analyses. Stratified survival analyses were conducted to estimate mortality risk associated with higher lactate among predefined subgroups. Results: Neutrophil counts were consistently higher in critically ill patients while exhibiting remarkably lower apoptosis. Transcriptomic analysis revealed miRNAs associated with downregulation of genes involved in neutrophils apoptosis. Both CT lung damage scores and neutrophil counts predicted mortality. Severinghaus fitting of hemoglobin oxygen saturation curve revealed a right-shift indicating lower oxygen capacity in non-survivors, which is consistent with lower blood-pH observed in the same group. Levels of blood lactate were increased in patients but significantly more in the ICU-NS relative to the control group. ROC analysis followed by Kaplan-Meyer survival analysis stratified to the obtained cut-off values showed that CT damage scores, neutrophil counts, and lactate levels are predictors of mortality within 15 days following blood collection. Conclusion: The current results implicate neutrophilia as a potential player in metabolic acidosis and deranged oxygen delivery associating SARS-CoV-2 infection thus contributing to mortality outcome.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.17.558185v1" target="_blank">Evidence associating neutrophilia, lung damage, hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality in critically ill COVID-19 patients</a>
</div></li>
<li><strong>Third dose COVID-19 mRNA vaccine enhances IgG4 isotype switching and recognition of Omicron subvariants by memory B cells after with mRNA but not adenovirus priming</strong> -
<div>
Background: Booster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary vaccinations involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially affect the immune response to booster doses. We here examined the effects of homologous (mRNA/mRNA) and heterologous (adenoviral vector/mRNA) vaccination on antibody and memory B cell (Bmem) responses against ancestral and Omicron subvariants. Methods: Healthy adults who received primary BNT162b2 (mRNA) (n=18) or ChAdOx1 (vector) (n=25) vaccination were sampled 1-month and 6-months after their 2nd and 3rd dose (homologous or heterologous) vaccination. Recombinant spike receptor-binding domain (RBD) proteins from ancestral, Omicron BA.2 and BA.5 variants were produced for ELISA-based serology, and tetramerized for immunophenotyping of RBD-specific Bmem. Results: Dose 3 boosters significantly increased ancestral RBD-specific plasma IgG and Bmem in both cohorts. Up to 80% of ancestral RBD-specific Bmem expressed IgG1+. IgG4+ Bmem were detectable after primary mRNA vaccination, and expanded significantly to 5-20% after dose 3, whereas heterologous boosting did not elicit IgG4+ Bmem. Recognition of Omicron BA.2 and BA.5 by ancestral RBD-specific plasma IgG increased from 20% to 60% after the 3rd dose in both cohorts. Reactivity of ancestral RBD-specific Bmem to Omicron BA.2 and BA.5 increased following a homologous booster from 40% to 60%, but not after a heterologous booster. Conclusion: A 3rd mRNA dose generates similarly robust serological and Bmem responses in homologous and heterologous vaccination groups. The expansion of IgG4+ Bmem after mRNA priming might result from the unique vaccine formulation or dosing schedule affecting the Bmem response duration and antibody maturation.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.15.557929v1" target="_blank">Third dose COVID-19 mRNA vaccine enhances IgG4 isotype switching and recognition of Omicron subvariants by memory B cells after with mRNA but not adenovirus priming</a>
</div></li>
<li><strong>Moving Beyond the Gradient: Social Classes as Group Contexts Defined by Multiple Forms of Capital</strong> -
<div>
Social class is a complex multidimensional phenomenon. Yet social psychologists have typically used indicators of SES or “social rank” to proxy class. Informed by sociology and cultural psychology, we treat social classes as group contexts characterized by the interplay of material, social, and cultural capital. Subjecting three datasets to latent profile analysis (LPA; N = 30,332), we uncover qualitatively distinct class groupings within the U.S. population—each characterized by a unique pattern of capital (Studies 1–3). Consistent with theory in cultural psychology, class formation is guided by a reciprocal relationship between material capital (income and assets) and social capital (interpersonal ties). Across studies, we predict and observe one profile (the “middle/upper class”) that exhibits high material capital but low levels of social capital, and another profile (the “vulnerable workers”) that displays modest material capital but very high social capital. Studies 2 and 3 illuminate the adaptive value of vulnerable workers’ high social capital, with this group reporting similar mental and physical health outcomes to the middle/upper class (Studies 2 and 3) and leveraging their social networks to protect against health impacts of the Covid-19 pandemic (Study 3). Our work reveals that tradeoffs between material and social capital occur most reliably at the group (not individual) level; that class effects are not monotonic, but reflect higher-order interactions between forms of capital; and that LPA can be a fruitful analytic approach when combined with careful theorization, validation of profiles against appropriate covariates, and preregistration.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/ph3ze/" target="_blank">Moving Beyond the Gradient: Social Classes as Group Contexts Defined by Multiple Forms of Capital</a>
</div></li>
<li><strong>Public Engagement with COVID-19 Preprints: Bridging the Gap Between Scientists and Society</strong> -
<div>
The surge in preprint server use, especially during the Covid-19 pandemic, necessitates a reex-amination of their significance in the realm of science communication. This study rigorously investigates discussions surrounding preprints, framing them within the contexts of systems theory and boundary objects in scholarly communication. An analysis of a curated selection of COVID-19-related preprints from bioRxiv and medRxiv was conducted, emphasizing those that transitioned to journal publications, alongside the associated commentary and Twitter activity. The dataset was bifurcated into comments by biomedical experts versus those by non-experts, encompassing both academic and general public perspectives. Findings revealed that while peers dominated nearly half the preprint discussions, their presence in Twitter dia-logues was markedly diminished. Yet, intriguingly, the themes explored by these two groups diverged considerably. Preprints emerged as potent boundary objects, reinforcing, rather than obscuring, the delineation between scientific and non-scientific discourse. They serve as cru-cial conduits for knowledge dissemination and foster inter-disciplinary engagements. None-theless, the interplay between scientists and the wider public remains nuanced, necessitating strategies to incorporate these diverse discussions into the peer review continuum without compromising academic integrity and to cultivate sustained engagement from both experts and the broader community.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/75gs6/" target="_blank">Public Engagement with COVID-19 Preprints: Bridging the Gap Between Scientists and Society</a>
</div></li>
<li><strong>Sex-specific differences in physiological parameters related to SARS-CoV-2 infections among a national cohort (COVI-GAPP study)</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Considering sex as a biological variable in modern digital health solutions, we investigated sex-specific differences in the trajectory of four physiological parameters across a COVID-19 infection. A wearable medical device measured breathing rate, heart rate, heart rate variability, and wrist skin temperature in 1163 participants (mean age = 44.1 years, standard deviation [SD]=5.6; 667 [57%] females). Participants reported daily symptoms and confounders in a complementary app. A machine learning algorithm retrospectively ingested daily biophysical parameters to detect COVID-19 infections. COVID-19 serology samples were collected from all participants at baseline and follow-up. We analysed potential sex-specific differences in physiology and antibody titres using multilevel modelling and t-tests. Over 1.5 million hours of physiological data were recorded. During the symptomatic period of infection, men demonstrated larger increases in skin temperature, breathing rate and heart rate as well as larger decreases in heart rate variability than women. The COVID-19 infection detection algorithm performed similarly well for men and women. Our study belongs to the first research to provide evidence for differential physiological responses to COVID-19 between females and males, highlighting the potential of wearable technology to inform future precision medicine approaches. This work has received support from the Princely House of the Principality of Liechtenstein, the government of the Principality of Liechtenstein, the Hanela Foundation in Switzerland, and the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement No 101005177. This Joint Undertaking receives support from the European Union9s Horizon 2020 research and innovation programme and EFPIA.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.17.23295693v1" target="_blank">Sex-specific differences in physiological parameters related to SARS-CoV-2 infections among a national cohort (COVI-GAPP study)</a>
</div></li>
<li><strong>Increased neurovirulence of omicron BA.5 and XBB variants over BA.1 in K18-hACE2 mice and human brain organoids</strong> -
<div>
The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation is retained for later variants like BA.5 and XBB remains controversial. We show that BA.5 and XBB isolates were significantly more pathogenic in K18-hACE2 mice than a BA.1 isolate, showing increased neuroinvasiveness, resulting in fulminant brain infection and mortality, similar to that seen for original ancestral isolates. BA.5 also infected human cortical brain organoids to a greater extent than the BA.1 and original ancestral isolates. In the brains of mice, neurons were the main target of infection, and in human organoids neuronal progenitor cells and immature neurons were infected. Although fulminant brain infection is not a feature of COVID-19, evidence for brain infection and brain damage in some COVID-19 patients with severe disease is becoming compelling, with the results herein suggesting that evolving omicron variants may have increasing intrinsic neuropathogenic potential.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.22.521696v2" target="_blank">Increased neurovirulence of omicron BA.5 and XBB variants over BA.1 in K18-hACE2 mice and human brain organoids</a>
</div></li>
<li><strong>Adherence Behaviors to Prevent COVID: The Role of Anxiety and Prosocial Behaviors</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In situations of acute stress, individuals may engage in prosocial behaviors or alternatively, individuals may engage in risk taking self-oriented behaviors. The COVID-19 pandemic created large stress-promoting conditions that impacted individuals9decisions to adhere to COVID-19 preventative behaviors. The aim of this study is to examine the relationship between anxiety during the pandemic and adherence behaviors to prevent the spread of COVID-19, and the moderating influence prosocial behaviors. Method: 54 undergraduate students completed online questionnaires during the second wave of the pandemic: prosocial behaviors, anxiety, and COVID-19 preventive behaviors. Moderation analyses were conducted using Process in SPSS. Results: Results demonstrated a statistically significant interaction of public prosocial behavior with state anxiety([beta]= -.17, p=.01) predicting engagement in COVID-19 preventative behaviors. At low levels of anxiety, low levels of prosocial public behaviors were associated with higher engagement in COVID-19 preventative behaviors. In contrast, high levels of public prosocial behavior were associated with lower engagement in COVID-19 preventative behaviors at low levels of anxiety. Conclusion: Results provide information that can aid at in the creation of anxiety reducing interventions that could increase adherence to COVID-19 preventative behaviors.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.18.23295630v1" target="_blank">Adherence Behaviors to Prevent COVID: The Role of Anxiety and Prosocial Behaviors</a>
</div></li>
<li><strong>Deep learning-based prediction of one-year mortality in the entire Finnish population is an accurate but unfair digital marker of aging</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Accurately predicting short-term mortality is important for optimizing healthcare resource allocation, developing risk-reducing interventions, and improving end-of-life care. Moreover, short-term mortality risk reflects individual frailty and can serve as digital aging marker. Previous studies have focused on specific, high-risk populations. Predicting all-cause mortality in an unselected population incorporating both health and socioeconomic factors has direct public health relevance but requires careful fairness considerations. Methods: We developed a deep learning model to predict 1-year mortality using nationwide longitudinal data from the Finnish population (N = 5.4 million), including &gt;8,000 features and spanning back up to 50 years. We used the area under the receiver operating characteristic curve (AUC) as a primary metric to assess model performance and fairness. Findings: The model achieved an AUC of 0.944 with strong calibration, outperforming a baseline model that only included age and sex (AUC = 0.897). The model generalized well to different causes of death (AUC &gt; 0.800 for 45 out of 50 causes), including COVID-19 which was not present in the training data. The model performed best among young females and worst in older males (AUC = 0.910 vs. AUC = 0.718). Extensive fairness analyses revealed that individuals belonging to multiple disadvantaged groups had the worst model performance, not explained by age and sex differences, reduced healthcare contact, or smaller training set sizes within these groups. Conclusion: A deep learning model based on nationwide longitudinal multi-modal data accurately identified short-term mortality risk holding the potential for developing a population-wide in-silico aging marker. Unfairness in model predictions represents a major challenge to the equitable integration of these approaches in public health interventions.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.18.23295726v1" target="_blank">Deep learning-based prediction of one-year mortality in the entire Finnish population is an accurate but unfair digital marker of aging</a>
</div></li>
<li><strong>Сan we start to ignore the SARS-CoV-2 disease?</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Current WHO reports claim a decline in COVID-19 testing. Many countries are reporting no new infections. In particular, USA, China and Japan have registered no cases and COVID-19 related deaths since May 15, 2023. To discuss consequences of ignoring SARS-CoV-2 infection, we compare endemic characteristics of the disease in 2023 with ones estimated before using 2022 datasets. The accumulated numbers of cases and deaths reported to WHO by 10 most infected countries and global figures were used to calculate the average daily numbers of cases and deaths per capita (DCC and DDC) and case fatality rates (CFR) for two periods in 2023. The average values of daily deaths per million still vary between 0.12 and 0.41. It means that annual global number of COVID-19 related deaths is still approximately twice higher than the seasonal influenza mortality. Increase of CFR values in 2023 show that SARS-CoV-2 infection is still dangerous despite of increasing the vaccination level. Very low CFR figures in South Korea and very high ones in the UK 4 need further investigations.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.18.23295709v1" target="_blank">Сan we start to ignore the SARS-CoV-2 disease?</a>
</div></li>
<li><strong>Detecting episodic evolution through Bayesian inference of molecular clock models</strong> -
<div>
Molecular evolutionary rate variation is a key aspect of the evolution of many organisms that can be modelled using molecular clock models. For example, fixed local clocks revealed the role of episodic evolution in the emergence of SARS-CoV-2 variants of concern. Like all statistical models, however, the reliability of such inferences is contingent on an assessment of statistical evidence. We present a novel Bayesian phylogenetic approach for detecting episodic evolution. It consists of computing Bayes factors, as the ratio of posterior and prior odds of evolutionary rate increases, effectively quantifying support for the effect size. We conducted an extensive simulation study to illustrate the power of this method and benchmarked it to formal model comparison of a range of molecular clock models using (log) marginal likelihood estimation, and to inference under a random local clock model. Quantifying support for the effect size has higher sensitivity than formal model testing and is straight-forward to compute, because it only needs samples from the posterior and prior distribution. However, formal model testing has the advantage of accommodating a wide range molecular clock models. We also assessed the ability of an automated approach, known as the random local clock, where branches under episodic evolution may be detected without their a priori definition. In an empirical analysis of a data set of SARS-CoV-2 genomes, we find `very strong’ evidence for episodic evolution. Our results provide guidelines and practical methods for Bayesian detection of episodic evolution, as well as avenues for further research into this phenomenon.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.17.545443v2" target="_blank">Detecting episodic evolution through Bayesian inference of molecular clock models</a>
</div></li>
<li><strong>A highly divergent SARS-CoV-2 lineage B.1.1 sample in a patient with long-term COVID-19</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
We report the genomic analysis of a highly divergent SARS-CoV-2 sample obtained in October 2022 from an HIV+ patient with presumably long-term COVID-19 infection. Phylogenetic analysis indicates that the sample is characterized by a gain of 89 mutations since divergence from its nearest sequenced neighbor, which had been collected in September 2020 and belongs to the B.1.1 lineage, largely extinct in 2022. 33 of these mutations were coding and occurred in the Spike protein. Of these, 17 are lineage-defining in some of the variants of concern (VOCs) or are in sites where another mutation is lineage-defining in a variant of concern, and/or shown to be involved in antibody evasion, and/or detected in other cases of persistent COVID-19; these include some “usual suspects,” such as Spike:L452R, E484Q, K417T, Y453F, and N460K. Molecular clock analysis indicates that mutations in this lineage accumulated at an increased rate compared to the ancestral B.1.1 strain. This increase is driven by the accumulation of nonsynonymous mutations, for an average dN/dS value of 2.2, indicating strong positive selection during within-patient evolution. Additionally, there is reason to believe that the virus had persisted for at least some time in the gastrointestinal tract, as evidenced by the presence of mutations that are rare in the general population samples but common in samples from wastewater. Our analysis adds to the growing body of research on evolution of SARS-CoV-2 in chronically infected patients and its relationship to the emergence of variants of concern.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.14.23295379v1" target="_blank">A highly divergent SARS-CoV-2 lineage B.1.1 sample in a patient with long-term COVID-19</a>
</div></li>
<li><strong>Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA</strong> -
<div>
Self-amplifying RNA (saRNA) will revolutionize vaccines and in situ therapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with modified nucleotides (modNTPs), such as N1-methylpseudouridine (N1m{Psi}), reduce the interferon response and enhance expression levels. Multiple attempts to use modNTPs in saRNA have been unsuccessful, leading to the conclusion that modNTPs are incompatible with saRNA, thus hindering further development. Here, contrary to the common dogma in the field, we identify multiple modNTPs that when incorporated into saRNA at 100% substitution confer immune evasion and enhance expression potency. Transfection efficiency enhances by roughly an order of magnitude in difficult to transfect cell types compared to unmodified saRNA, and interferon production reduces by &gt;8 fold compared to unmodified saRNA in human peripheral blood mononuclear cells (PBMCs). Furthermore, we demonstrate expression of viral antigens in vitro and observe significant protection against lethal challenge with a mouse-adapted SARS-CoV-2 strain in vivo. A modified saRNA vaccine, at 100-fold lower dose than a modified mRNA vaccine, results in a statistically improved performance to unmodified saRNA and statistically equivalent performance to modified mRNA. This discovery considerably broadens the potential scope of self-amplifying RNA, enabling entry into previously impossible cell types, as well as the potential to apply saRNA technology to non-vaccine modalities such as cell therapy and protein replacement.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.15.557994v1" target="_blank">Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA</a>
</div></li>
<li><strong>Modeling the emergence of viral resistance for SARS-CoV-2 during treatment with an anti-spike monoclonal antibody</strong> -
<div>
The COVID-19 pandemic has led to over 760 million cases and 6.9 million deaths worldwide. To mitigate the loss of lives, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with susceptible variants. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3-4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response anti-viral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.14.557679v1" target="_blank">Modeling the emergence of viral resistance for SARS-CoV-2 during treatment with an anti-spike monoclonal antibody</a>
</div></li>
<li><strong>Temporal profiling of human lymphoid tissues reveals coordinated defence to viral challenge</strong> -
<div>
Adaptive immunity is generated in lymphoid organs, but how these structures defend themselves during infection in humans is unknown. The nasal epithelium is a major site of viral entry, with adenoid nasal-associated lymphoid tissue (NALT) generating early adaptive responses. Here, using a nasopharyngeal biopsy, we examined longitudinal immune responses in NALT following viral challenge, using SARS-CoV-2 infection as a natural experimental model. In acute infection, infiltrating monocytes formed a subepithelial and peri-follicular shield, recruiting NET-forming neutrophils, whilst tissue macrophages expressed pro-repair molecules during convalescence to promote the restoration of tissue integrity. Germinal centre B cells expressed anti-viral transcripts that inversely correlated with fate-defining transcription factors. Among T cells, tissue-resident memory CD8 T cells alone showed clonal expansion and maintained cytotoxic transcriptional programmes into convalescence. Together our study provides a unique insight into how human nasal adaptive immune responses are generated and sustained in the face of viral challenge.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.15.558006v1" target="_blank">Temporal profiling of human lymphoid tissues reveals coordinated defence to viral challenge</a>
</div></li>
<li><strong>VirEvol platform:accurate prediction and visualization of SARS-CoV-2 evolutionary trajectory based on protein language model, structural information and immunological recognition mechanism</strong> -
<div>
Predicting the mutation direction of SARS-CoV-2 using exploratory computational methods presents a challenging, yet prospective, research avenue. However, existing research methods often ignore the effects of protein structure and multi-source viral information on mutation prediction, making it difficult to accurately predict the evolutionary trend of the SARS-CoV-2 S protein receptor-binding domain (RBD). To overcome this limitation, we proposed an interpretable language model combining structural, sequence and immune information. The dual utility of this model lies in its ability to predict SARS-CoV-2's affinity for the ACE2 receptor, and to assess its potential for immune evasion. Additionally, it explores the mutation trend of SARS-CoV-2 via a genetic algorithm-directed evolution. The model exhibits high accuracy in both regards and has displayed promising early warning capabilities, effectively identifying 13 out of 14 high-risk strains, marking a success rate of 93%.". This study provides a novel method for discerning the molecular evolutionary pattern, as well as predicting the evolutionary trend of SARS-CoV-2 which is of great significance for vaccine design and drug development of new coronaviruses. We further developed VirEvol, a unique platform designed to visualize the evolutionary trajectories of novel SARS-CoV- 2 strains, thereby facilitating real-time predictive analysis for researchers. The methodologies adopted in this work may inspire new strategies and offer technical support for addressing challenges posed by other highly mutable viruses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.15.557978v1" target="_blank">VirEvol platform:accurate prediction and visualization of SARS-CoV-2 evolutionary trajectory based on protein language model, structural information and immunological recognition mechanism</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 Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: HH-120;   Drug: placebo<br/><b>Sponsor</b>:   Huahui Health<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2</strong> - <b>Conditions</b>:   COVID-19;   SARS-CoV-2<br/><b>Interventions</b>:   Drug: VYD222;   Drug: Normal saline<br/><b>Sponsor</b>:   Invivyd, Inc.<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>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</strong> - <b>Conditions</b>:   Immunosuppression;   COVID-19<br/><b>Intervention</b>:   Biological: NVX-CoV2372<br/><b>Sponsors</b>:   University of Wisconsin, Madison;   Novavax<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents</strong> - <b>Conditions</b>:   Vaccine-Preventable Diseases;   COVID-19 Pandemic;   Health-Related Behavior;   Health Knowledge, Attitudes, Practice;   Narration<br/><b>Interventions</b>:   Behavioral: Baseline surveys;   Behavioral: Digital Storytelling Intervention;   Behavioral: Information Control Intervention<br/><b>Sponsors</b>:   Arizona State University;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)<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>Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203)</strong> - <b>Conditions</b>:   COVID-19 Infection;   COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>:   Biological: LEM-mR203;   Biological: Placebo<br/><b>Sponsor</b>:   Lemonex<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Intervention</b>:   Biological: B/HPIV3/S-6P<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   Johns Hopkins Bloomberg School of Public Health;   National Institutes of Health (NIH)<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Determine the Tolerability of Intranasal LMN-301</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: LMN-301<br/><b>Sponsor</b>:   Lumen Bioscience, Inc.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children</strong> - <b>Conditions</b>:   Fever After Vaccination;   Fever;   Seizures Fever<br/><b>Interventions</b>:   Biological: Pfizer-BioNTech COVID-19 Vaccine;   Biological: Routine Childhood Vaccinations<br/><b>Sponsors</b>:   Duke University;   Kaiser Permanente;   Columbia University;   Children’s Hospital Medical Center, Cincinnati;   Centers for Disease Control and Prevention<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect of Cognitive Behavioral Therapy on Post-Traumatic Stress Symptoms in Nursing Students</strong> - <b>Condition</b>:   Trauma and Stressor Related Disorders<br/><b>Intervention</b>:   Other: Cognitive Behavioral Therapy Group<br/><b>Sponsor</b>:   Necmettin Erbakan University<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID Immune Profiling</strong> - <b>Conditions</b>:   Long COVID;   POTS - Postural Orthostatic Tachycardia Syndrome;   Autonomic Dysfunction<br/><b>Interventions</b>:   Diagnostic Test: IL-6;   Diagnostic Test: cytokines (IL-17, and IFN-ɣ);   Behavioral: Compass 31<br/><b>Sponsors</b>:   Vanderbilt University Medical Center;   American Heart Association<br/><b>Not yet recruiting</b></p></li>
</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>How does the Immunological System Change during the SARS-COV-2 Attack? A Clue for the New Immunotherapy Discovery</strong> - The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) is one of the biggest unsolved global problems of the 21st century for which there has been no definitive cure yet. Like other respiratory viruses, SARS-COV-2 triggers the host immunity dramatically, causing dysfunction in the immune system, both innate and adaptive, which is a common feature of COVID-19 patients. Evidence shows that in the early stages of COVID-19, the immune system is suppressed…</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>Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection</strong> - TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to…</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>Host heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation</strong> - SARS-CoV-2 infection causes spike-dependent fusion of infected cells with ACE2 positive neighboring cells, generating multi-nuclear syncytia that are often associated with severe COVID. To better elucidate the mechanism of spike-induced syncytium formation, we combine chemical genetics with 4D confocal imaging to establish the cell surface heparan sulfate (HS) as a critical stimulator for spike-induced cell-cell fusion. We show that HS binds spike and promotes spike-induced ACE2 clustering,…</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>Prostaglandin E<sub>2</sub> and myocarditis; friend or foe?</strong> - This review article summarizes the role of prostaglandin E(2) (PGE(2)) and its receptors (EP1-EP4) as it relates to the inflammatory cardiomyopathy, myocarditis. During the COVID-19 pandemic, the onset of myocarditis in a subset of patients prompted a debate on the use of nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, which act to inhibit the actions of prostaglandins. This review aims to further understanding of the role of PGE(2) in the pathogenesis or protection 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>SADS-CoV nsp1 inhibits the IFN-β production by preventing TBK1 phosphorylation and inducing CBP degradation</strong> - Swine acute diarrhea syndrome (SADS) is first reported in January 2017 in Southern China. It subsequently causes widespread outbreaks in multiple pig farms, leading to economic losses. Therefore, it is an urgent to understand the molecular mechanisms underlying the pathogenesis and immune evasion of Swine acute diarrhea syndrome coronavirus (SADS-CoV). Our research discovered that SADS-CoV inhibited the production of interferon-β (IFN-β) during viral infection. The nonstructural protein 1 (nsp1)…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bioprospecting the potential of metabolites from a Saharan saline soil strain Nocardiopsis dassonvillei GSBS4</strong> - Saharan soil samples collected in El-Oued province have been investigated for actinobacteria as a valuable source for the production of bioactive metabolites. A total of 273 isolates were obtained and subjected to antagonistic activity tests against human pathogenic germs. A strain with a broad-spectrum antimicrobial activity was selected and identified as Nocardiopsis dassonvillei GSBS4, with high sequence similarities to N. dassonvillei subsp. dassonvillei^(T) X97886.1 (99%) based on…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cholesterol and Ceramide Facilitate Membrane Fusion Mediated by the Fusion Peptide of the SARS-CoV-2 Spike Protein</strong> - SARS-CoV-2 entry into host cells is mediated by the Spike (S) protein of the viral envelope. The S protein is composed of two subunits: S1 that induces binding to the host cell via its interaction with the ACE2 receptor of the cell surface and S2 that triggers fusion between viral and cellular membranes. Fusion by S2 depends on its heptad repeat domains that bring membranes close together and its fusion peptide (FP) that interacts with and perturbs the membrane structure to trigger fusion….</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>Live imaging of the airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread</strong> - SARS-CoV-2 initiates infection in the conducting airways, which rely on mucocilliary clearance (MCC) to minimize pathogen penetration. However, it is unclear how MCC impacts SARS-CoV-2 spread after infection is established. To understand viral spread at this site, we performed live imaging of SARS-CoV-2 infected differentiated primary human bronchial epithelium cultures for up to 9 days. Fluorescent markers for cilia and mucus allowed longitudinal monitoring of MCC, ciliary motion, and…</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>Exploring the medicinal potential of Dark Chemical Matters (DCM) to design promising inhibitors for PLpro of SARS-CoV-2 using molecular screening and simulation approaches</strong> - The growing concerns and cases of COVID-19 with the appearance of novel variants i.e., BA.2.75. BA.5 and XBB have prompted demand for more effective treatment options that could overcome the risk of immune evasion. For this purpose, discovering novel small molecules to inhibit druggable proteins such as PLpro required for viral pathogenesis, replication, survival, and spread is the best choice. Compounds from the Dark chemical matter (DCM) database is consistently active in various screening…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structure adaptation in Omicron SARS-CoV-2/hACE2: Biophysical origins of evolutionary driving forces</strong> - Since its emergence, the COVID-19 threat has been sustained by a series of transmission waves initiated by new variants of the SARS-CoV-2 virus. Some of these arise with higher transmissivity and/or increased disease severity. Here we use molecular dynamics simulations to examine the modulation of the fundamental interactions between the receptor binding domain (RBD) of the spike glycoprotein and the host cell receptor (human angiotensin-converting enzyme 2: hACE2) arising from Omicron variant…</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>Occurrence, formation, and proteins perturbation of disinfection byproducts in indoor air resulting from chlorine disinfection</strong> - Increased amounts of chlorine disinfectant have been sprayed to inactivate viruses in the environment since the COVID-19 pandemic, and the health risk from chemicals, especially disinfection byproducts (DBPs), has unintentionally increased. In this study, we characterized the occurrence of haloacetic acids (HAAs) and trihalomethanes (THMs) in indoor air and evaluated their formation potential from typical indoor ingredients. Subsequently, the adverse effect of chloroacetic acid on A549 cells was…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In silico evidences of Mpro inhibition by a series of organochalcogen-AZT derivatives and their safety in Caenorhabditis elegans</strong> - CONCLUSIONS: We have found that compounds S116l (a Tellurium AZT-derivative) and S116h (a Selenium-AZT derivative) presented more promising effects both in silico and in vivo, being strong candidates for further in vivo studies.</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>Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation</strong> - SARS-CoV-2 causes the severe respiratory disease COVID-19. Remdesivir (RDV) was the first fast-tracked FDA approved treatment drug for COVID-19. RDV acts as an antiviral ribonucleoside (adenosine) analogue that becomes active once it accumulates intracellularly. It then diffuses into the host cell and terminates viral RNA transcription. Previous studies have shown that certain nucleoside analogues unintentionally inhibit mitochondrial RNA or DNA polymerases or cause mutational changes to…</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>Outcomes of a social media campaign to promote COVID-19 vaccination in Nigeria</strong> - The COVID-19 pandemic has been an historic challenge to public health and behavior change programs. In low -and middle-income countries (LMICs) such as Nigeria, there have been challenges in promoting vaccination. Vaccine hesitancy and social norms related to vaccination may be important factors in promoting or inhibiting not only COVID vaccination, but other routine vaccinations as well. The aim of this study was to conduct a national-level quasi-experimental evaluation of a social media based…</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>Phytoconstituents as potential therapeutic agents against COVID-19: a computational study on inhibition of SARS-CoV-2 main protease</strong> - The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has become a global health crisis, and the urgent need for effective treatments is evident. One potential target for COVID-19 therapeutics is the main protease (Mpro) of SARS‑CoV‑2, an essential enzyme for viral replication. Natural compounds have been explored as a source of potential inhibitors for Mpro due to their safety and availability. In this study, we employed a…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Freedom for Five Americans Doesn’t End Flash Points with Iran</strong> - The prisoner exchange will almost certainly not stop an Iranian tactic that has spanned more than four decades. - <a href="https://www.newyorker.com/news/daily-comment/freedom-for-five-americans-doesnt-end-flash-points-with-iran">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Ken Paxton Verdict Is Not the Vindication Republicans Want</strong> - The Texas attorney general was acquitted of corruption charges, but the trial further damaged the Republican brand. - <a href="https://www.newyorker.com/news/letter-from-the-southwest/the-ken-paxton-verdict-is-not-the-vindication-republicans-want">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Fight Against Climate Change Returns to the Streets</strong> - But this movement clearly needs to expand again. - <a href="https://www.newyorker.com/news/daily-comment/the-fight-against-climate-change-returns-to-the-streets">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Pope’s Coming Vatican Showdown with American Conservatives</strong> - Francis’s recent journeys ahead of the October synod may be signals about the future direction of the Church. - <a href="https://www.newyorker.com/news/daily-comment/the-popes-coming-vatican-showdown-with-american-conservatives">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Futility of the Never Trump Billionaires</strong> - Benjamin Wallace-Wells writes about the difficulties facing Republican Party factions that hope to put forth a nominee who can stand as a strong alternative to Donald Trump. - <a href="https://www.newyorker.com/news/daily-comment/the-futility-of-the-never-trump-billionaires">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The US hired a leading economist to fix how it allocates foreign aid. Here’s his plan.</strong> -
<figure>
<img alt="New USAID chief economist Dean Karlan." src="https://cdn.vox-cdn.com/thumbor/HhH437jR3rx7-AeUuwdlpJPPPdY=/0x0:3343x2507/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72663906/Dean1_Credit_Michael_Marsland_Yale_University.0.jpg"/>
<figcaption>
New USAID chief economist Dean Karlan. | Yale/ Michael Marsland
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Dean Karlan explains his plan to get USAID to take evidence more seriously.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YtvVSC">
The US spends more, in absolute dollars, on foreign aid than <a href="https://www.oecd.org/dac/financing-sustainable-development/ODA-2022-summary.pdf#page=2">any other rich nation</a>. But <a href="https://www.vox.com/future-perfect/23274306/usaid-foreign-aid-effectiveness-evidence-grants">a lot of development experts question</a> whether the primary American aid institution, the US Agency for International Development (USAID), is spending its budget in a way that helps the most people, most effectively.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IDTzxY">
USAID relies heavily on a <a href="https://foreignpolicy.com/2021/05/18/usaid-biden-power-contracts-money-procurement/">small number of well-connected contractors</a> to deliver most aid, while other groups are often deterred from even applying by the process’s complexity. Use of rigorous evaluation methods like randomized controlled trials — where development programs are tested on a random subset of the target population to see if they work — <a href="https://www.wilsoncenter.org/article/passing-baton-data-and-evidence">are the exception, not the norm</a>. If the goal is for the vast majority of USAID’s <a href="https://crsreports.congress.gov/product/pdf/IF/IF10261">$41 billion-odd annual budget</a> to go to proven, evidence-based programs implemented in a cost-effective way, a goal that its administrators have shared for decades, there’s still a long way to go.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ApyfMV">
One of the agency’s current leaders tasked with changing this status quo is its chief economist, Dean Karlan. At the time of his appointment last year, Karlan was already a giant in the field of development economics. He founded <a href="https://poverty-action.org/about">Innovations for Poverty Action</a>, one of the most influential research groups conducting rigorous evaluations of anti-poverty interventions in the developing world, and has taught at Princeton, Yale, and most recently Northwestern. His papers have touched on everything from efforts to <a href="https://ageconsearch.umn.edu/nanna/record/28411/files/dp050917.pdf?withWatermark=0&amp;withMetadata=0&amp;version=1&amp;registerDownload=1">increase household savings in the Philippines</a> to <a href="https://www.nber.org/system/files/working_papers/w18463/w18463.pdf">agricultural insurance in Ghana</a> to <a href="https://www.econstor.eu/bitstream/10419/39347/1/52491091X.pdf">entrepreneurship classes in Peru</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ur3u2P">
His appointment was perceived as a <a href="https://www.vox.com/future-perfect/23854173/foreign-aid-cash-benchmarking-evidence-usaid">major victory</a> for people in and around USAID who want its programs to rely more on rigorous evidence, and Karlan reached out to <a href="https://www.vox.com/future-perfect">Future Perfect</a> for his first public interview on his approach to the job. A transcript of our conversation, edited for length and clarity, follows.
</p>
<hr class="p-entry-hr" id="baNLeh"/>
<h4 id="31rwyc">
Dylan Matthews
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GZZ1cO">
I’m curious about how one goes about integrating evidence into the USAID spending process.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DKMZic">
What’s your model of how that works? How does the agency budget go from unallocated to allocated to specific projects? And where are the points where you can inject evidence into that?
</p>
<h4 id="g2FoCv">
Dean Karlan
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9b7TQN">
There’s one punchline philosophy, which is to apply a bit of behavioral economics to the process. The mantra of applied behavioral economics is to make it easy. Make it easy for people to do the thing that they would say they want to do in a moment of deep reflection and full information.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WnfkRb">
That doesn’t actually tell you much, but it does tell you that we’re trying to understand the processes that are in place, and how to get information in the right way to the right people at that right point in time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="byX7fU">
I was really overwhelmed with welcome emails, welcome notes, welcome sentiments. There’s a lot of like-minded people in USAID. I’m not saying it’s been perfect, but there’s been a lot of welcoming people who say, “I want to make these changes, here’s where the challenges have been.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="y5aqCE">
We have not produced in academia the kinds of “how-to” guides dialed into the kinds of things USAID does. It’s not the nature of what academics do. Some of what we need to do is more meta-analysis, more and more synthesizing of the existing research to the specific kinds of programs that USAID does.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8iaQ2k">
It’s not just a collection of interesting papers, but more prescriptive. That’s part of what I mean by “make it easy.” Say you’re a really enterprising person in a [USAID country] mission, and said, “I’m going to go read Dean’s paper on financial inclusion.” My paper was not really dialed in to them in a way that would lend itself to saying, “What exactly do I stick in this request for proposals as an activity design?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mSuwYW">
That’s one set of work. Some of it is about is about culture change and some of it is about education. It’s taking people who are super eager, but just not as exposed to what constitutes strong evidence and what’s weak evidence. One of the most important shifts is recognizing that when we talk about using evidence, we’re not talking about using <em>USAID</em> evidence. We’re talking about using the global evidentiary base.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JaUwtE">
There’s a kind of a cultural instinct, when you ask, “What’s the evidence we have on X,” to look inside USAID and what USAID has produced. In fact, evidence is evidence. Who cares who paid for it? The cash studies are a perfect example of this. Sure, USAID has some landmark projects, which are super exciting. But the fact is, that’s something like 5 or 10 percent of the evidentiary base of the impact of cash transfer programs. So if you want to know what to expect from giving out cash to people, you don’t just look at the things that USAID paid for.
</p>
<h4 id="HBNoW2">
Dylan Matthews
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="i30lAL">
Sometimes what people mean by “effectiveness” versus “cost-effectiveness” versus “evaluation” versus “impact evaluations” can get a little muddled. There are subtle but very important distinctions between these things.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZZ04KT">
What’s the bar you’re setting? What kinds of evidence and information do you want and what are some examples of of evidence or information that would fall short of that standard?
</p>
<h4 id="tueo6F">
Dean Karlan
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XczOZB">
So let’s take programs at the household or the community delivery level, where there’s some service — could be in-kind, could be cash, could be a training, could be a community meeting — but there’s some delivery of a service.
</p>
<h4 id="pv6kbY">
Dylan Matthews
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jQGrPN">
Can you give an example of that kind of evaluation? Examples of “does it work” evaluations are easier to think of, at least for me. You imagine a <a href="https://www.vox.com/future-perfect/23152657/poverty-cash-graduation-ultra-poor-brac">graduation program</a>, say, where recipients get cash or other assets and some training in hopes they “graduate” out of extreme poverty. We’ve had randomized trials testing if that works. What’s a trial that estimates how best to set up a given program?
</p>
<h4 id="CYYEqb">
Dean Karlan
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Pfs7we">
One example you just named: graduation programs. Inside the evaluation, there was a test of group versus individual high-frequency meetings with households, to help with the income-generating activities that the program was trying to promote.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W3vrYn">
Say I have three goats. I want to someday have seven goats and then 10 goats. I’m building a plan to get there and having regular check-ins to help deal with issues that might be arising and help these households think about how to stay on track.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Qvez6a">
There were two competing ways of doing that. One is to hold individual meetings. The other is as a community. One thinking on individual meetings is that the households might get more customized, tailored information. They might also have things that are private that they don’t want to share publicly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="q2WTcJ">
On the other hand, the group meeting might help build social capital. It might help people learn from each other’s issues. On the cost side, group meetings are cheaper because one field agent goes and has one meeting with many people at once.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5aY4hd">
So there’s a clear trade-off, and we didn’t know the answer. We’ve now seen this tested in two different instances on the same program. In both instances, it made absolutely no difference, which means “do groups” because those are cheaper to do.
</p>
<h4 id="9zLxhQ">
Dylan Matthews
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K7oH3e">
What are some of the biggest barriers to integrating evidence that USAID staff have brought up to you? What makes it <em>not</em> easy?
</p>
<h4 id="5i0KcJ">
Dean Karlan
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j4zam9">
One answer is a lack of good synthesis. One of the biggest bottleneck issues is that there isn’t a step in the process for [evidence]. In the process of issuing an award, there’s no step that says, “And now check and see, of the proposed activities, what’s the cost-effectiveness estimate that we have?” That’s not an explicit step.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Te9LSj">
There’s are also bandwidth issues; there’s a lot of competing demands. Some of these demands relate to important issues on gender, environment, fairness in the procurement process. These add steps to the process that need to be adhered to. What you end up with is a lot of overworked people, and then you’re saying, “Here’s one more thing to do.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cyiOPh">
It’s really important that we make that step, ideally, a negative cost step.
</p>
<h4 id="6MUgIT">
Dylan Matthews
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hBG2Ra">
A <a href="https://pdf.usaid.gov/pdf_docs/PA00X78R.pdf">recent internal review</a> suggested not just that the share of USAID projects getting a formal impact evaluation is low, but the share of impact evaluations rated high quality is very low — about 3 percent. What’s your diagnosis there? Is it a lack of training? Is it unclear expectations about what makes an evaluation high quality?
</p>
<h4 id="wT5Rbz">
Dean Karlan
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="npA1Ec">
I think there’s some misinformation about what makes something high quality. But I also don’t think that’s the core problem we face. I do expect and want to see more impact evaluations done at USAID. Don’t get me wrong. That is a goal.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8szgdn">
I don’t care what proportion of our awards get impact evaluations. That’s not a metric that’s important to me. What’s important to me is, are there evidence gaps where we, USAID, could help fill them?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GpYnIT">
If we are in a good position to learn more, then that is a great opportunity for us to have an even bigger impact than our award, by helping to produce knowledge in that area. That’s not measured by what proportion of our awards are we doing impact evaluations on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LcfbJR">
Let’s take <a href="https://teachingattherightlevel.org/">teaching at the right level</a> in education as an example, or cash transfers would be another one. Cash transfers had 50, 100 or so randomized trials done on them. Teaching at the right level, not as many, but maybe a dozen. There are cases where we might be doing those, and there’s not a good argument for why we should do an impact evaluation. We should do a process check to make sure that we’re delivering what was delivered. But asking the big picture question about what the impact is, is just adding a drop in an already fairly full bucket of information about the impact of those activities.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9hYbzP">
So that’s a good example of where, you know, 3 percent is too high. I’m not saying three percent is high globally for USAID. I do think the number should be higher. But the point is, it should be guided by where we can be learning something that helps the world, not by just counting our awards and saying what proportion of them have impact evaluations.
</p></li>
<li><strong>Google’s Bard isn’t just for search anymore</strong> -
<figure>
<img alt="An eyeball with the Google logo reflected in it." src="https://cdn.vox-cdn.com/thumbor/PELyYl3HjBrCO8Gn5xiWS4VrT7g=/517x0:4654x3103/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72663808/GettyImages_828896290.0.jpg"/>
<figcaption>
Google’s new Bard extensions might get more eyes on its generative AI offerings. | Leon Neal/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Microsoft was first to AI search, but Google can now pull stuff in from Gmail, Docs, Maps, and more — for free.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JP4ztq">
The buzz around consumer <a href="https://www.vox.com/2023/4/28/23702644/artificial-intelligence-machine-learning-technology">generative AI</a> has <a href="https://www.vox.com/technology/2023/8/19/23837705/openai-chatgpt-microsoft-bing-google-generating-less-interest">died down</a> since its early 2023 peak, but <a href="https://www.vox.com/google">Google</a> and <a href="https://www.vox.com/microsoft">Microsoft</a>’s battle for AI supremacy may be heating up again.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JW5Qob">
Both companies are releasing updates to their AI products this week. Google’s additions to Bard, its generative AI tool, are <a href="https://bard.google.com/">live now</a> (but just for English speakers for the time being). They include the ability to integrate Bard into Google apps and use it across any or all of them. Microsoft is set to announce AI innovations on Thursday, though it hasn’t said much more than that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TTKB99">
The updates may give us a better idea of how we’re most likely to use generative AI in our daily lives. Instead of assisting us with searching the internet and generating blocks of text based on the results, they’ll be embedded in apps we use all the time, combing through our lives to assist us with our various tasks. That is, they’ll be less of a party trick and more of a party planner.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dTymdM">
“What we’ve learned over the first six months led us to this moment,” Jack Krawczyk, product lead for Bard, told Vox. “A pretty profound and pivotal moment in the very, very short history of consumer language models.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CxssrW">
One of the biggest new Bard features is Bard Extensions, which lets users add Bard to Google tools and apps, including Gmail, Drive, <a href="https://www.vox.com/youtube">YouTube</a>, Maps, Flights, and Hotels.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NNvvBF">
“We’re allowing people, as they’re collaborating with Bard, to bring in content from their Gmail, from Docs, from Google Drive,” Krawczyk said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M3Wv2Y">
Google’s <a href="https://blog.google/products/bard/google-bard-new-features-update-sept-2023/">examples</a> of how this might work include planning a trip across Gmail, Flights, Hotel, and YouTube (travel planning seems to be <a href="https://www.cntraveler.com/story/ai-chatbots-future-of-travel">everyone’s favorite use case</a>, though results may vary), as well as pulling information from a résumé stored on Google Drive and summarizing it to help write a cover letter in Docs or Gmail. Google’s enterprise product, Workspace, had <a href="https://workspace.google.com/blog/product-announcements/duet-ai-in-workspace-now-available">some generative AI integrations</a> already with its Duet AI, but not across all of these apps and not available to the general public, as Bard’s now are.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xnFnqW">
What’s coming from Microsoft is less clear, but the company <a href="https://www.theverge.com/2023/3/16/23642833/microsoft-365-ai-copilot-word-outlook-teams">has already</a> integrated generative AI into various Microsoft products. Those tools are for its enterprise customers, though, and they come at a cost: Generative AI-enhanced <a href="https://www.vox.com/linkedin">LinkedIn</a> is available for <a href="https://techcrunch.com/2023/03/15/linkedin-expands-its-generative-ai-assistant-to-recruitment-ads-and-writing-profiles/">premium subscribers</a>; users have to <a href="https://blogs.microsoft.com/blog/2023/07/18/furthering-our-ai-ambitions-announcing-bing-chat-enterprise-and-microsoft-365-copilot-pricing/">pay to add</a> Copilot to Microsoft 365 (which is itself a paid service), and there’s even an “<a href="https://www.microsoft.com/en-us/bing/chat/enterprise/?form=MA13FV">enterprise</a>” version of Bing Chat. If the goal is widespread adoption by consumers, free is going to reel in a lot more of them than something that costs money. This also assumes that Microsoft, which is very much an enterprise software company, is even going for the general consumer beyond its Bing ambitions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="l1fUvv">
Taken in tandem and depending on what Microsoft has to say on Thursday, these can also be seen as the second wave of major AI announcements from those companies since the big unveiling of internet search integration <a href="https://www.vox.com/recode/2023/1/26/23571710/microsoft-open-ai-chatgpt-google">early this year</a> that kicked off the <a href="https://www.vox.com/recode/2023/3/4/23624033/openai-bing-bard-microsoft-generative-ai-explained">AI Search Race</a>. Google, and especially Microsoft, hailed AI search as the future of internet search, but it <a href="https://www.vox.com/technology/2023/8/19/23837705/openai-chatgpt-microsoft-bing-google-generating-less-interest">doesn’t seem</a> to have set the world on fire. Microsoft’s Bing <a href="https://www.wsj.com/tech/ai/microsoft-bing-search-artificial-intelligence-google-competition-6e51ec04">saw only a tiny traffic bump</a>. Google’s Bard isn’t as integrated into Google search as Bing’s chatbot is into Bing, and it’s still labeled “experimental.” It feels more like something Google is offering to people who already know it’s there and just want to give it a try, while Bing is pushing Bing Chat as a feature of its search that it wants as many people as possible to use.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gbm2jq">
It’s understandable why Microsoft pushed the new Bing so hard: It had a partnership with the hottest company in the field, OpenAI, and, with Google dominating so much of the search market, Microsoft had very little to lose if Bing Chat flopped and a lot to gain if it caught on. But Google’s <a href="https://www.vox.com/technology/2023/3/22/23651093/google-bard-ai-chatbot-microsoft-chat-gpt-generative">more reserved approach</a> might’ve been the right one in the end. Generative AI continues to struggle with <a href="https://www.cnn.com/2023/08/29/tech/ai-chatbot-hallucinations/index.html">hallucinations</a> that make it an unreliable source of information. It’s also not clear how many people really want their internet search engines to come up with text responses that attempt to summarize the whole of the internet rather than links pointing to the outside authorities from which chatbots scrape their data.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cJ8R4N">
Another new Bard feature seems to take the last several months of chatbot foibles into account: The “Google it” button under Bard responses can now be used to help double-check its accuracy. Statements it can verify are highlighted in green if Bard finds links that back them up and orange if it finds links that say something different.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B3gIiW">
“People are much more willing to interact and collaborate when they know someone is willing to admit ‘I’m not confident about this’ or ‘I made a mistake,’” Krawczyk said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sjSZjU">
It is, if nothing else, a nod to the significant accuracy issues that chatbots have demonstrated, which makes them difficult to trust as the collective knowledge summarizers they were touted as, especially when it came to searching the internet. Perhaps when the source data is users’ own emails and docs, and the requests are for writing based on summaries of those things, users will be more willing to integrate them into their daily lives and tasks. Then again, we’ve seen AI personal assistants before — including <a href="https://www.wired.com/story/the-curious-case-of-the-missing-google-assistant/">from Google</a> — and they <a href="https://www.theverge.com/2021/12/23/22851451/amazon-alexa-by-the-way-use-case-functionality-plateaued">never really</a> caught on the way their developers hoped they would. Generative AI assistants might go the same way. Or they might fulfill the promise that old-school AI assistants never did.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YX82kO">
“A language model is going to be able to integrate in with your personal life,” Krawczyk said. “We’re used to technology doing things <em>for</em> us … Bard is doing things <em>with</em> us.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iHEiCi">
Now we’ll see who wants that integration and what they use it for.
</p></li>
<li><strong>Sound of Freedom wants to raise awareness about child trafficking. Here’s what it’s really doing.</strong> -
<figure>
<img alt="A black-and-white image shows two men standing together, one holding a child, with a light shining brightly from behind them." src="https://cdn.vox-cdn.com/thumbor/ItFlW7xUFe383E_1JqTFPzgwHrc=/336x0:1776x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72452872/SOF_Background_Key_Art_2_1920x1080_20230510_BP_V3_lowres.0.jpg"/>
<figcaption>
A promotional image for Sound of Freedom. The movie has been an unexpected box office hit thanks to word of mouth from conservatives. | Angel Studios
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Is a movie still just a movie if it becomes a culture war battleground?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="y3UZ4h">
Usually when the culture war comes to the <a href="https://www.vox.com/movies">movies</a>, it’s in the form of conservative backlash to films they perceive as too liberal. Increasingly, however, conservative filmmakers, often working outside of Hollywood’s studio system, are grabbing the spotlight with <a href="https://www.vox.com/culture/2018/3/19/17136066/i-can-only-imagine-mercyme-movie-box-office-faith-based-gods-not-dead-paul-apostle">unexpected hits</a>, some packed with ideology and <a href="https://www.vox.com/culture/2018/4/3/17180138/gods-not-dead-light-darkness-evangelical-christian-persecution-race">tinged</a> with hallmarks of the modern right-wing worldview: moral panic, hints of vast leftist conspiracies, and a sense of persecution.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Lw08R4">
The latest surprise right-wing hit to tick these bingo squares is <em>Sound of Freedom</em>. The film stars Jim Caviezel in the very (very) loosely true story of Tim Ballard, who founded the <a href="https://www.vice.com/en/article/k7a3qw/a-famed-anti-sex-trafficking-group-has-a-problem-with-the-truth">controversial</a> anti-trafficking organization Operation Underground Railroad, or OUR. Coasting on word of mouth and a mountain of free publicity from influential supporters like <a href="https://www.vox.com/elon-musk">Elon Musk</a> and Mel Gibson, <em>Sound of Freedom</em> went head to head against <em>Indiana Jones and the Dial of Destiny</em> in its July 4 opening weekend and wound up <a href="https://www.hollywoodreporter.com/movies/movie-news/sound-of-freedom-box-office-movie-theaters-1235532352/">reportedly out-earning</a> the Harrison Ford-led sequel by several million on opening day (if its maker Angel Studios’ on-site accounting is to be believed). It’s since gone on to earn nearly $<a href="https://www.boxofficemojo.com/title/tt7599146/">50 million</a>. Not bad for an indie outsider.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3wycON">
But <em>Sound of Freedom</em> has also generated a considerable amount of scathing left-wing backlash, aimed at both the movie itself, with its <a href="https://www.vox.com/2020/10/9/21504910/qanon-conspiracy-theory-facebook-ban-trump">QAnon</a>-adjacent rhetoric, and the film’s target audience. Multiple left-wing critics have spent parts of their reviews of the film itself denigrating the way its fans are watching it, with one critic seemingly <a href="https://slate.com/culture/2023/07/sound-of-freedom-movie-jim-caviezel-trafficking-qanon.html">appalled</a> that audiences “acted like they were at <em>Top Gun</em>.” For their part, those audiences have flocked to the theater with the zeal of parishioners. Some fans have <a href="https://www.youtube.com/watch?v=TtjVrwzcr2Q">described</a> attending the movie as a “duty,” while others have spun <a href="https://twitter.com/ninoboxer/status/1678138506453893121">conspiracy theories</a> that movie theaters are <a href="https://www.newsweek.com/sound-freedom-fury-multiple-people-claim-ac-not-working-during-film-1812374">trying to prevent them</a> from seeing the film — which, of course, just generates more determination to watch the film to spite the libs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jMct2t">
Yet the patriotic zeal behind <em>Sound of Freedom</em> might mask more than murky political agendas: According to <a href="https://www.newsweek.com/sound-freedom-funder-fabian-marta-arrest-child-kidnapping-1817498">a report</a> by Newsweek and the <a href="https://www.courts.mo.gov/cnet/cases/newHeader.do?inputVO.caseNumber=2322-CR01608&amp;inputVO.courtId=CT22#charges">police report</a>, one of the film’s financial backers was recently charged with accessory to<strong> </strong>felony kidnapping. And even more disturbing, well into the film’s theatrical run, <a href="https://www.vice.com/en/article/k7z74x/tim-ballard-sound-of-freedom-operation-underground-railroad-stepped-away">Vice reported</a> that Ballard had suddenly “stepped away” from his position as head of OUR for unknown reasons, despite still continuing to promote and do press for <em>Sound of Freedom</em>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n2ppat">
In September, Vice ultimately <a href="https://www.vice.com/en/article/pkaqvn/tim-ballards-departure-from-operation-underground-railroad-followed-sexual-misconduct-investigation">confirmed</a> with OUR representatives that Ballard had resigned from OUR on June 22, 2023, and was no longer affiliated with OUR in any way. The details come from an <a href="https://www.vice.com/en/article/m7b3ex/tim-ballard-left-operation-underground-railroad-after-investigation-into-claims-made-by-employees">anonymous letter</a>, first reported on by Vice and then made public by independent Utah journalist <a href="https://americancrimejournal.com/acj-investigates/operation-underground-railroad-o-u-r/">Lynn Packer</a> on <a href="https://youtu.be/nT-ESKtdWQg?t=236">Packer’s YouTube channel</a> on September 17. According to the letter, Ballard’s departure was prompted by an investigation into a sexual harassment complaint involving seven women filed against him by an OUR employee. The letter contains horrific allegations against Ballard, including that he used the aims of OUR — saving sex trafficking victims — to “deceitfully and extensively groom” female employees into role-playing as his “wife” during rescue trips. He would then use the ruse of being husband and wife to allegedly coerce them into performing sexual acts with him, including showering together, sharing a bed, and “doing ‘whatever it takes’ to save a child.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hz84Jn">
Clearly, there’s a lot happening around this film — and while <em>Sound of Freedom</em> ostensibly wants to create awareness about child trafficking, that theme has mostly gotten lost in all the noise.
</p>
<h3 id="k52QrB">
<em>Sound of Freedom</em> is its own, highly effective, hype machine
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wg97U6">
<em>Sound of Freedom</em> was filmed in 2018 by director Alejandro Gómez Monteverde, but its release was delayed after <a href="https://www.vox.com/culture/2019/3/20/18273477/disney-fox-merger-deal-details-marvel-x-men">Disney acquired</a> its original distributor, Fox — a fact that has led to <a href="https://www.nytimes.com/2023/07/11/business/sound-of-freedom-trafficking.html">false rumors</a> that Hollywood tried to shut the film down. When the film languished in Disney limbo, Angel Studios, a small independent film company based in Utah, <a href="https://www.usatoday.com/story/entertainment/movies/2023/07/12/sound-of-freedom-movie-controversy/70405543007/">stepped in</a>. Angel has had a string of recent Christian hits like the 2019 streaming series <em>The Chosen</em>, which landed on <a href="https://www.vox.com/netflix">Netflix</a>, and <em>His Only Son</em>, 2023’s other Christian box office success. Angel <a href="https://www.nytimes.com/2023/07/11/business/sound-of-freedom-trafficking.html">partly crowdfunded</a> the film’s $5 million distribution budget from “angel investors”, i.e., studio superfans like <a href="https://www.instagram.com/p/CuiUlIPPAAF/">Tony Robbins</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PMwy4z">
With all that indie outsider energy combined with the long delay in release, <em>Sound of Freedom</em> was primed to feed a meta-narrative about the right’s sense of oppression at the hands of the left. Still, while most mainstream media reviewers have either <a href="https://www.rottentomatoes.com/m/sound_of_freedom">been dismissive</a> of the film or ignored it altogether, <em>Sound of Freedom</em> has its unexpected champions. <a href="https://variety.com/2023/film/reviews/sound-of-freedom-review-jim-caviezel-1235660035/"><em>Variety </em>called it</a> a “solid,” “disquieting” thriller and praised Caviezel’s performance as his finest since <em>The</em> <em>Passion of the Christ</em>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2iT3Y0">
At the root of the film’s power seems to be its “urgency” toward its subject matter; fans apparently leave the theater galvanized to proselytize on its behalf, spreading the word about the dangers and rampant devastation of child trafficking — and, most of all, about OUR and its all-important rescue missions.
</p>
<div class="c-float-right">
<aside id="Xci3gX">
<q>It’s a hype machine that’s not just a hype machine, but a patriotic, perhaps even divinely mandated, responsibility</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WbPyxd">
That evangelism plays right into film studio Angel’s marketing strategy, which <a href="https://www.indiewire.com/news/business/sound-of-freedom-box-office-analysis-crowdfunding-pay-it-forward-1234881363/">encourages moviegoers</a> to buy tickets for other would-be converts — in fact, after the film’s end credits, Caviezel himself <a href="https://jezebel.com/sound-of-freedom-review-1850596160">urges fans</a> to buy more tickets at the studio’s website in order to “make <em>Sound of Freedom</em> the <em>Uncle Tom’s Cabin</em> of 21st century slavery.” In the lead-up to its release, Angel <a href="https://www.reddit.com/r/movies/comments/14u11pm/is_the_sound_of_freedom_a_legit_good_movie_or/jrf3h4j/">anecdotally</a> piggy-backed on a <a href="https://www.newyorker.com/magazine/2006/05/22/hollywood-heresy">long</a> <a href="https://www.backstage.com/magazine/article/hollywood-marketing-films-churches-38793/">tradition</a> of Christian film marketing by targeting churches and encouraging block ticket sales in order to engage entire communities and spread word of mouth. (Some of the film’s detractors have <a href="https://www.reddit.com/r/WhitePeopleTwitter/comments/14z8rgn/to_absolutely_no_ones_surprise_that_qanon_movie/jrwu6a3/">disputed</a> the movie’s box office success, noting that some theaters <a href="https://twitter.com/CocoaFox023/status/1679696985199378432">appear to be sold out</a> when they aren’t, that user reviews on websites like IMDb read like bot spam, and that the online ticketing system Angel encourages fans to use may be vulnerable to manipulation.) In June, for the film’s July 4 release, Elon Musk <a href="https://twitter.com/elonmusk/status/1668822025098387458">offered</a> the production free publicity; on July 1, Mel Gibson went viral for <a href="https://www.instagram.com/p/CuLIf7nOnPO/">promoting</a> the film. “The first step in eradicating this crime is awareness,” he intoned solemnly. “Go see <em>Sound of Freedom</em>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jj7Lxn">
It’s easy to see how emotionally charged all of this is — it’s a hype machine that’s not just a hype machine, but a patriotic, perhaps even divinely mandated, responsibility. Adjacent to this urgent, awareness-raising narrative, however, sits <a href="https://www.vox.com/2020/10/9/21504910/qanon-conspiracy-theory-facebook-ban-trump">QAnon</a> — the baseless extremist conspiracy theory that high-powered liberals and elites are trafficking children and harvesting their adrenalin in order to attain eternal life. <em>Sound of Freedom</em> doesn’t explicitly reference QAnon or any of its most common narratives, and Ballard has <a href="https://www.newsweek.com/sound-freedom-movie-creator-tim-ballard-responds-qanon-allegations-sick-1812204">brushed off</a> the connection — but in the same breath he speaks of liberals “running interference” for traffickers by creating such rumors. Arguably more damning: Caviezel’s open embrace of QAnon. The actor has repeatedly referenced QAnon rhetoric; he recently promoted <em>Sound of Freedom </em>on former Trump-admin and extremist <a href="https://www.vox.com/2022/7/17/23217452/steve-bannon-january-6-trump-propaganda-election">Steve Bannon</a>’s podcast by <a href="https://www.vanityfair.com/hollywood/2021/04/jim-caviezel-decries-the-adrenochroming-of-children-as-if-thats-a-thing">referencing</a> the aforementioned (false) adrenalin harvesting, a.k.a. “adrenochroming.” He also recently <a href="https://twitter.com/travis_view/status/1678881092802330624">defended QAnon</a> by comparing its detractors to Nazi and Klan apologists.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Za2ptX">
None of this directly links the film to QAnon. But it doesn’t help that reviewers who’ve been less than charitable about the film have been deluged with harassment from people calling them pedophiles and groomers. Rolling Stone’s Miles Klee, who, in his <a href="https://www.rollingstone.com/tv-movies/tv-movie-reviews/sound-of-freedom-jim-caviezel-child-trafficking-qanon-movie-1234783837/">review</a>, highlighted numerous examples of <em>Sound of Freedom</em> fans linking themselves to QAnon, <a href="https://thehandbasket.substack.com/p/how-rolling-stones-miles-klee-became">told journalist Marisa Kabas</a> that “the intensity of the death threats and pedophile smears outstripped any previous hate campaign I’ve experienced in my career.” (Disclaimer: Both Klee and Kabas are former colleagues and friends.) Still, Klee also noted that to the film’s fans he was just “a convenient embodiment” of evil for “a demographic that thinks child abusers and groomers make up the entire government, entertainment industry, and media, and all run cover for each other.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jV2OPy">
These two competing meta-narratives about the film have overshadowed the film itself. But if the primary objection to <em>Sound of Freedom</em> is that it’s a giant dog whistle for QAnon recruitment, then, the <a href="https://www.nytimes.com/2023/07/11/business/sound-of-freedom-trafficking.html">counterargument</a> from its supporters usually goes that the film’s subject matter ought to transcend politics, despite how politically charged it is. After all, everyone should want to protect children, right?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fsILse">
Well, not everyone. One of the film’s apparent financial backers, Fabian Marta, was arrested on July 23 on felony charges of accessory to child kidnapping in Missouri. If convicted, Marta could face a lengthy sentence, with a minimum of 10 years in prison.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Sig41F">
So the question then becomes: Is protecting children what <em>Sound of Freedom</em> is really valorizing?
</p>
<h3 id="lErUaB">
The real organization behind <em>Sound of Freedom</em> is also its own hype machine
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5GNxTM">
<em>Sound of Freedom</em> heavily fictionalizes the real-life figure of Ballard, a Mormon with a self-reported history of work with the CIA (unconfirmed per a <a href="https://www.vice.com/en/article/k7a3qw/a-famed-anti-sex-trafficking-group-has-a-problem-with-the-truth">Vice investigation</a>) and Homeland Security, who founded OUR in 2013 out of a desire to do more to fight human trafficking. The group quickly made a splash via dramatic self-promotion, including producing a <a href="https://ourrescue.org/films">movie</a>, <em>The Abolitionist</em> (2016), and a podcast, <em>In the Trenches</em>. In 2017, MAGA whisperer <a href="https://www.vox.com/culture/2018/8/8/17376824/trump-fan-art-maga-dinesh-dsouza-jon-mcnaughton">Jon McNaughton</a> produced an <a href="https://www.facebook.com/OURrescue/photos/a.1582633588641067/2036459536591801/">infamous painting</a> which depicts Ballard and a bevy of white people as modern-day Harriet Tubmans, carrying trafficked victims to freedom while Abraham Lincoln and a crowd of American patriots look on approvingly. OUR <a href="https://www.cbsnews.com/news/one-mans-mission-to-rescue-child-sex-trafficking-victims/">filmed at least one</a> of its early sting operations, a faux house party which <a href="https://foreignpolicy.com/2015/07/22/the-new-abolitionists-mexico-dominican-republic-human-trafficking-mormon-our/">reporters actually attended</a> and which Ballard has used to bolster his claims to expertise. This is one of the glitzier heroic moments that <em>Sound of Freedom</em> depicts onscreen.
</p>
<div class="c-float-right">
<aside id="PBS0HM">
<q>Calls to protect children are really about attacking left-wing ideology</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ypjx9C">
In reality, however, OUR has come under repeated scrutiny for making false claims about its exploits, <a href="https://www.vice.com/en/article/k7a3qw/a-famed-anti-sex-trafficking-group-has-a-problem-with-the-truth">including</a> taking credit for missions and rescues it had no part in, failing to give adequate support to rescued survivors, falsely claiming partnerships with other rescue organizations, and being vague and obfuscatory about what its missions are and where its sizeable donor funds are going. (The organization claims this is to protect the safety of victims.) One Utah prosecutor <a href="https://www.deseret.com/utah/2023/5/12/23717081/davis-county-attorneys-office-closes-investigation-into-operation-underground-railroad">spent years</a> pursuing criminal charges against the group, though without ultimately bringing a case. In 2014, Ballard, then the CEO of OUR, allegedly used a <a href="https://www.vice.com/en/article/bvxev5/inside-a-massive-anti-trafficking-charitys-blundering-overseas-missions">psychic medium</a> as his “source” for trying to locate a missing child. “He’s not making decisions tactically,” an anonymous source <a href="https://www.vice.com/en/article/bvxev5/inside-a-massive-anti-trafficking-charitys-blundering-overseas-missions">told Vice in 2021</a> about their experiences with Ballard. “He’s making decisions like a reality TV producer.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Rf8z2k">
With the news emerging that Ballard has spent years using OUR as a grooming ground for women, it’s possible the project served as less of a public service and more like his personal vanity RPG; indeed, part of his alleged grooming strategy was to literally role-play husband-and-wife with various women while on rescue missions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ncM7rw">
That doesn’t mean, however, that Ballard’s crusade hasn’t been influential. In fact, it’s perfect for capitalizing on a cultural moment in which public concern about trafficked children is arguably at an all-time high. The <a href="https://www.vox.com/policy-and-politics/22252171/qanon-donald-trump-conspiracy-theories">ongoing spread</a> of QAnon as well as the recent reappearance of classic anti-LGBTQ <a href="https://www.vox.com/culture/23025505/leftist-groomers-homophobia-satanic-panic-explained">“groomer” rhetoric</a> have given conservatives the ultimate perfect excuse to demonize liberalism. Just as Ballard’s real goal seems to be less about protecting children and more about promoting Tim Ballard, calls to protect children are really about attacking left-wing ideology, no matter how bizarrely unfounded such attacks are.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AMzObr">
Ballard himself has leaned all the way into these murky elisions; in 2020, he <a href="https://www.nytimes.com/2020/08/12/technology/qanon-save-the-children-trafficking.html">described</a> QAnon to the New York Times as a positive development, helping people to “open their eyes” to the reality of human trafficking. That same year, he <a href="https://twitter.com/TimBallard/status/1282535670104219648">seemed to affirm</a> a false conspiracy theory, created in QAnon communities, that <a href="https://www.bbc.com/news/world-53416247">the furniture retailer Wayfair</a> was facilitating child trafficking.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gwWZ85">
More recently, while promoting <em>Sound of Freedom</em> on <em>Fox &amp; Friends</em>, Ballard <a href="https://www.mediamatters.org/fox-friends/tim-ballards-misleading-anti-trafficking-rhetoric-slips-seamlessly-transphobia-and">claimed</a> that allowing <a href="https://www.vox.com/lgbtq">trans teens</a> to transition would somehow lead to lowered ages of consent and implied that American immigration <a href="https://www.vox.com/policy">policies</a> were leading to increased child trafficking. It is true that reports of illegal labor exploitation of migrant children have <a href="https://www.nytimes.com/2023/04/17/us/politics/migrant-child-labor-biden.html">increased dramatically</a> since the pandemic; however, reports of a widespread child sex trafficking phenomenon <a href="https://www.mediamatters.org/fox-friends/tim-ballards-misleading-anti-trafficking-rhetoric-slips-seamlessly-transphobia-and">are false</a>, a straightforward, old-school “think of the children” moral panic. Like all moral panics, this one gets used to justify hatred against perceived outsiders, in this case immigrants and queer and trans people.
</p>
<h3 id="86cepL">
Can any of this just be about going to the movies? (Alas, probably not.)
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CA7uPU">
None of this should erase the horrifying reality of human trafficking or its impact on victims and survivors. Director Monteverde’s father and brother were both <a href="https://www.dailymail.co.uk/news/article-3246253/Father-brother-Hollywood-film-director-Alejandro-Gomez-Monteverde-murdered-kidnapped-Mexican-home.html">murdered by drug traffickers</a> in 2015, so if anyone has a personal interest in making a film about the dangers of trafficking and the elite corruption that enables it, it’s him.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TvkbbF">
Yet all of this debate erases another quirk surrounding <em>Sound of Freedom</em> — that without the film’s meta-narratives, it’s just a passably entertaining action thriller, a la <em>Taken</em>. If you don’t think too hard about it (why does Caviezel’s Ballard, as Klee observes, spend the whole movie talking about protecting children while fully ignoring his own?), it’s just a good time at the movies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cluwIn">
But is that <em>allowed</em>? Are conservatives allowed to simply have fun at the movies, even if they’re having fun watching a film that reifies the extremist rhetoric in which they are steeped? Are liberals allowed to have fun at the movies if the dumb action flick they’re watching is also doubling as a conspiracy theory recruitment tool? Can the answer to both of these questions just be “yes,” simply because it’s summer and we’re all very tired, without some vital existential fight being lost?
</p>
<div class="c-float-right">
<aside id="keyasB">
<q>Can faith-based cultural products exist without also fomenting extremism — and would their target audiences even want them? </q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VjVWeU">
Uncertainty over these concerns might be why some reviewers have been so harsh on audiences at <em>Sound of Freedom</em> for merely watching the film. <a href="https://slate.com/culture/2023/07/sound-of-freedom-movie-jim-caviezel-trafficking-qanon.html">Slate</a> lowkey fat-shamed the audience (“The audience toted jumbo buckets of popcorn and trash can–sized sodas”) while <a href="https://www.rollingstone.com/tv-movies/tv-movie-reviews/sound-of-freedom-jim-caviezel-child-trafficking-qanon-movie-1234783837/">Rolling Stone</a> high-key age-shamed them. (“Nonetheless, the mostly white-haired audience around me could be relied on to gasp, moan in pity, mutter condemnations, applaud, and bellow ‘Amen!’ at moments of righteous fury … not even the occasional nasty coughing fit — and we had no shortage of those — could break the spell.”) Meanwhile, the audience can’t decide if they’re being oppressed because the theater is <a href="https://twitter.com/CitizenFreePres/status/1677684847689752577">too hot</a> or because the theater is <a href="https://twitter.com/AleksDjuricic/status/1677701863834112001">too cold</a> — but many of them seem <a href="https://twitter.com/cpamba33/status/1677706539975557120">convinced</a> they’re being oppressed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vu4DlX">
And if, as one analyst <a href="https://variety.com/2023/film/box-office/sound-of-freedom-box-office-success-1235664837/">told Variety</a>, “The strong response to faith-based films reflects a demand by an underserved audience who are hungry for entertainment that reflects their values and beliefs,” then the question becomes one that many people of faith <a href="https://www.vox.com/culture/2019/11/18/20961543/david-bazan-interview-strange-negotiations-pedro-lion">have grappled with</a>: Can such faith-based cultural products even exist at this point, let alone serve their specific malnourished target audience, without also fomenting extremist rhetoric, bigotry, and attacks on progressive ideals? If such works can somehow manifest, would their target audiences even want them?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Cf5Fhp">
It’s arguable that for many evangelicals and other conservatives, the answer would be no. The controversy and the sense of persecution that accompany these films only increases the dopamine high many get from rebelling against the evil mainstream media by … watching this fairly mainstream movie. These are conservatives, after all, whose worldview frames patriarchal norms as <a href="https://www.vox.com/policy-and-politics/2020/7/9/21291493/donald-trump-evangelical-christians-kristin-kobes-du-mez">synonymous with strength and leadership</a>, which is again synonymous with patriotism. The rugged individualism and masculine rogue operatives on display in <em>Sound of Freedom</em> are precisely tailored to cater to their views of idealized America; it must be profoundly validating to see such a fully formed conservative image of masculinity draped in the trappings of a typical glossy blockbuster.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EWYxkb">
Still, that masculine heroism is by no means unique to <em>Sound of Freedom</em>; it’s not as though Hollywood has ever missed the opportunity to cater to conservative audiences with a strong male archetype. And it’s hard to feel too much pity for an “underserved” faith-based populace, given that conservative ideology, from <a href="https://www.vox.com/culture/23667960/yellowstone-cast-drama-paleyfest-2023-costner-returning-season-five-release-date-show-ending"><em>Yellowstone</em></a> to <a href="https://www.vox.com/2018/11/16/18069756/green-book-review-racism-schomburg-segregation-golden-globes"><em>Green Book</em></a>, still permeates mainstream Hollywood narratives. If audiences acted like they were at <em>Top Gun</em>, that’s arguably because they basically were.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Bdiw8Q">
Just as films like <a href="https://www.vox.com/23141487/top-gun-maverick-us-military-hollywood-oscar-winner-best-sound"><em>Top Gun</em></a> serve to keep us from criticizing America’s military-industrial complex, <em>Sound of Freedom</em> aims to keep us from scrutinizing hyperbolic, alarmist cries about child trafficking too closely. That, ironically, helps shut down useful conversation about the best way to effectively help curb trafficking. The point of such myths, after all, isn’t really to save children, but to create shrill narratives with which to demonize the left and other perceived outsiders. Just as OUR itself is something of a smokescreen, <em>Sound of Freedom</em> is ultimately a form of extremist propaganda — and that extremism is at least as dark and dangerous as the very thing <em>Sound of Freedom</em> wants to combat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HS7Z91">
<em><strong>Clarification, August 29, 12:30 pm ET:</strong></em><em> This story was originally published on July 14 and has been updated to clarify that investor Fabian Marta faces accessory to kidnapping charges.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2syRGi">
<em><strong>Update, September 18, 5:40 pm ET:</strong></em><em> This story has been updated to include allegations of sexual misconduct against Tim Ballard.</em>
</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>Lot of talent in Indian football, but get big coaches, focus on youth programmes, says Chukwu</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>Asian Games 2023: Indian men’s hockey team leaves for Hangzhou</strong> - India will begin their campaign against Uzbekistan on September 24</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>Malaala pulls off a stunning win in Rani Rudrama Devi Cup</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>King’s Ransom excels</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>Indian rifle shooter Nischal bags silver in Rio World Cup</strong> - Nischal on September 18 gave India its second medal on the concluding day of the tournament.</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>Wildlife photography workshop at IIIT-Basar</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>New marine tardigrade species named after former President A.P.J. Abdul Kalam</strong> - The new species, discovered from Mandapam in south-east Tamil Nadu, belongs to genus Batillipes and has been named Batillipes kalami</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>Here are the big stories from Karnataka today</strong> - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated by Nalme Nachiyar.</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>CUET-UG to be conducted from May 15-31; CUET-PG from March 11-28</strong> - UGC Chairman M. Jagadesh Kumar said results will be announced within three weeks of last test</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>Bodies of 3 women recovered after land subsidence in Dhanbad’s coal mine area</strong> - The women got trapped in the deep crater after the soil caved in at Gondudih colliery in the command area of Bharat Coking Coal Limited (BCCL) on Sunday, officials said</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>Azerbaijan launches operation against Nagorno-Karabakh</strong> - The defence ministry begins “anti-terrorist” operations in its breakaway region under Armenian control.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Germany bans neo-Nazi group Hammerskins</strong> - German authorities crack down on the skinhead group known for organising far-right concerts.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Former Belarus ‘hit squad’ member to stand trial in Switzerland</strong> - Yury Garavsky is charged with the forced disappearance of three Belarusian opposition figures.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine sues EU neighbours over food imports ban</strong> - Kyiv says Slovakia, Poland and Hungary act illegally - but they say they need to protect their farmers.</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>Jenni Hermoso: Spain forward says ‘nothing has changed’ as boycotting players are called up</strong> - Jenni Hermoso says the decision to call up players who are boycotting the national team is proof “nothing has changed” at the Spanish FA.</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>Chinese hackers have unleashed a never-before-seen Linux backdoor</strong> - SprySOCKS borrows from open source Windows malware and adds new tricks. - <a href="https://arstechnica.com/?p=1969201">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>More than half of Americans plan to get updated COVID shot</strong> - There’s a sharp partisan divide, but interest blows away uptake of the last booster. - <a href="https://arstechnica.com/?p=1969186">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Keeping Google’s search secrets protects its monopoly, DOJ argues in court</strong> - The DOJ objected when the court removed the public from the Google trial on Monday. - <a href="https://arstechnica.com/?p=1969165">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A water carrier just won the hardest cycling race on the planet</strong> - The cycling drama came to a head on top of the most demanding mountain in Europe. - <a href="https://arstechnica.com/?p=1968852">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Autoworker strike could give GM breathing room to fix battery production</strong> - A production pause could let GM solve a battery cell manufacturing headache. - <a href="https://arstechnica.com/?p=1969136">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A backpacker walks into a pub in Ireland</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It’s a small pub, clearly quite old. There’s only two people in the pub, the bartender and another customer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The intrepid backpacker, weary from his travels, takes a seat, orders himself a pint, and introduces himself to his fellow patron of the pub.
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He asks the man’s name and the man stares at him for a few seconds and then says
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“Do you see that pier down there?”
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The backpacker says “aye”
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“I built it with my bare hands, but do they call me Seamus the pier builder? Noooooo……”
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He’s silent for a few minutes then he says
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“Do you see that shed out back?”
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“Aye”
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“I built it with my bare hands, but do they call me Seamus the shed builder? Noooooo…….”
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He’s silent a few more minutes then he says
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“Do you see that stone wall over there?”
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“Aye”
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“I built it with my bare hands, but do they call me Seamus the wall builder? Noooooo……”
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And then he says
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“But you fuck ONE goat!!!!”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/actinium226"> /u/actinium226 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16mito3/a_backpacker_walks_into_a_pub_in_ireland/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16mito3/a_backpacker_walks_into_a_pub_in_ireland/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Shocking to hear about Russell Brand, isn’t it?</strong> - <!-- SC_OFF --></p>
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I had no idea he was a comedian.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MarketingCoding"> /u/MarketingCoding </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16m6w6x/shocking_to_hear_about_russell_brand_isnt_it/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16m6w6x/shocking_to_hear_about_russell_brand_isnt_it/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I used to steal comedians’ jokes and not credit them.</strong> - <!-- SC_OFF --></p>
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I still do, but I used to, too.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/housevil"> /u/housevil </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16mkgpe/i_used_to_steal_comedians_jokes_and_not_credit/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16mkgpe/i_used_to_steal_comedians_jokes_and_not_credit/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Husband and wife are shopping…</strong> - <!-- SC_OFF --></p>
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A Husband and Wife went shopping together just before Christmas. The wife quickly noticed that her husband was missing and because they had a lot to do she called him on his cell phone.<br/> After the husband picked up the phone his wife said " Where are you, you know we have lots to do!“<br/> He said”You remember the jewelers we went into about 10 years ago, and you fell in love with that diamond necklace? I could not afford it at the time and I said that one day I would get it for you?“<br/> Little tears started to flow down her cheeks and she got all choked up and said”Yes, I do remember that shop!!!" she replied.<br/> "Well I am in the yoyo shop next door to that.
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/dirtybird971"> /u/dirtybird971 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16lvv87/husband_and_wife_are_shopping/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16lvv87/husband_and_wife_are_shopping/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I just got wrongfully fired from my job for “being in a state of constant sexual arousal”</strong> - <!-- SC_OFF --></p>
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Which is absolutely ridiculous. Everyone around me knows that I’m a dedicated employee who is always hard at work.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/ItIsMyBurnerAccount"> /u/ItIsMyBurnerAccount </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16mb96v/i_just_got_wrongfully_fired_from_my_job_for_being/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16mb96v/i_just_got_wrongfully_fired_from_my_job_for_being/">[comments]</a></span></p></li>
</ul>
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