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<title>25 July, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>The use and acceptability of preprints in health and social care settings: a scoping review</strong> -
<div>
Background: Preprints are open and accessible scientific manuscript or report that is shared publicly, through a preprint server, before being submitted to a journal. The value and importance of preprints has grown since its contribution during the public health emergency of the COVID-19 pandemic. Funders and publishers are establishing their position on the use of preprints, in grant applications and publishing models. However, the evidence supporting the use and acceptability of preprints varies across funders, publishers, and researchers. The scoping review explored the current evidence on the use and acceptability of preprints in health and social care settings by publishers, funders, and the research community throughout the research lifecycle. Methods: A scoping review was undertaken with no study or language limits. The search strategy was limited to the last five years (2017-2022) to capture changes influenced by COVID-19 (e.g., accelerated use and role of preprints in research). The review included international literature, including grey literature, and two databases were searched: Scopus and Web of Science (24 August 2022). Results: 379 titles and abstracts and 193 full text articles were assessed for eligibility. Ninety-eight articles met eligibility criteria and were included for full extraction. For barriers and challenges, 26 statements were grouped under four main themes (e.g., volume/growth of publications, quality assurance/trustworthiness, risks associated to credibility, and validation). For benefits and value, 34 statements were grouped under six themes (e.g., openness/transparency, increased visibility/credibility, open review process, open research, democratic process/systems, increased productivity/opportunities). Conclusions: Preprints provide opportunities for rapid dissemination but there is a need for clear policies and guidance from journals, publishers, and funders. Cautionary measures are needed to maintain the quality and value of preprints, paying particular attention to how findings are translated to the public. More research is needed to address some of the uncertainties addressed in this review.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/nug4p/" target="_blank">The use and acceptability of preprints in health and social care settings: a scoping review</a>
</div></li>
<li><strong>Revealing and evaluation of antivirals targeting multiple druggable sites of RdRp complex in SARS-CoV-2</strong> -
<div>
SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) complex consisting of nsp12, nsp7, and nsp8 as the key enzyme for viral genome replication and is a proven antiviral drug target. In this study, molecular interactions of nsp7 and nsp8 with nsp12 and the active site of nsp12 were coterminously targeted using in-silico screening of small molecule libraries to identify potential antivirals. Surface plasmon resonance (SPR) based assay using purified nsp7 and nsp8 proteins was developed, and the binding of identified molecules to targets was validated. The antiviral efficacy of identified small molecules was evaluated using cell-based assays, and potent antiviral effect with EC50 values of 0.56 uM, 0.73 uM, and 2.8 uM was demonstrated by fangchinoline, cepharanthine, and sennoside B, respectively. Further in vivo, investigation using hACE2 mice is being conducted. This is the first study that targets multiple sites in the RdRp complex of SARS-CoV-2 using a structure-based molecular repurposing approach and suggests potential therapeutic options for emerging variants of SARS-CoV-2.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.24.550324v1" target="_blank">Revealing and evaluation of antivirals targeting multiple druggable sites of RdRp complex in SARS-CoV-2</a>
</div></li>
<li><strong>Endothelial SARS-CoV-2 infection is not the underlying cause of COVID19-associated vascular pathology in mice</strong> -
<div>
Endothelial damage and vascular pathology have been recognized as major features of COVID-19 since the beginning of the pandemic. Two main theories regarding how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) damages endothelial cells and causes vascular pathology have been proposed: direct viral infection of endothelial cells or indirect damage mediated by circulating inflammatory molecules and immune mechanisms. However, these proposed mechanisms remain largely untested in vivo. Here, we utilized a set of new mouse genetic tools1 developed in our lab to test both the necessity and sufficiency of endothelial human angiotensin-converting enzyme 2 (hACE2) in COVID19 pathogenesis. Our results demonstrate that endothelial ACE2 and direct infection of vascular endothelial cells does not contribute significantly to the diverse vascular pathology associated with COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.24.550352v1" target="_blank">Endothelial SARS-CoV-2 infection is not the underlying cause of COVID19-associated vascular pathology in mice</a>
</div></li>
<li><strong>Biophysical principles predict fitness of SARS-CoV-2 variants</strong> -
<div>
SARS-CoV-2 is under constant selective pressure from antibodies while requiring efficient binding to host cells for successful infection. Here we focus specifically on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, a key determinant of viral entry into host cells. Through a comprehensive approach, comprising large-scale sequence analysis of SARS-CoV-2 variants and the formulation of a fitness function based on protein folding and binding thermodynamics, we unravel the relationship between the epidemiological fitness contribution of the RBD and its biophysical properties. We developed a biophysical model mapping the phenotype space, characterized by binding constants to cell receptors and antibodies, onto the fitness landscape for variants ranging from the ancestral Wuhan Hu-1 to the Omicron BA.1 . Using equilibrium statistical mechanics, we show how fitness can be expressed as a function of binding constants to cell receptors and antibodies and validate our findings through experimentally measured binding affinities and population data on frequencies of variants. This forms the basis for a comprehensive epistatic map, relating the genotype space to fitness. Our study thus delivers a tool for predicting the fitness of variants harboring previously unseen mutations, and sheds light on the impact of specific mutations on viral fitness. These insights offer not only greater understanding of viral evolution but also potentially aid in guiding public health decisions in the battle against COVID-19 and future pandemics.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.23.549087v1" target="_blank">Biophysical principles predict fitness of SARS-CoV-2 variants</a>
</div></li>
<li><strong>AmpliDiff: An Optimized Amplicon Sequencing Approach to Estimating Lineage Abundances in Viral Metagenomes</strong> -
<div>
Metagenomic profiling algorithms commonly rely on genomic differences between lineages, strains or species to infer the relative abundances of sequences present in a sample. This observation plays an important role in the analysis of diverse microbial communities, where targeted sequencing of 16S and 18S rRNA, both well-known hypervariable genomic regions, have led to insights in microbial diversity and the discovery of novel organisms. However, the variable nature of discriminatory regions can also act as a double-edged sword, as the sought after variability can make it difficult to design primers for their amplification through PCR. Moreover, the most variable regions are not necessarily the most informative regions for the purpose of differentiation; one should focus on regions which maximize the number of lineages that can be distinguished. Here we present AmpliDiff, a computational tool that simultaneously finds such highly discriminatory genomic regions, as well as primers allowing for the amplification of these regions. We show that regions and primers found by AmpliDiff can be used to accurately estimate relative abundances of SARS-CoV-2 lineages, for example in wastewater sequencing data. We obtain mean absolute prediction errors that are comparable with using whole genome information to estimate relative abundances. Furthermore, our results show that AmpliDiff is robust against incomplete input data, and that primers designed by AmpliDiff continue to bind to genomes originating from months after the primers were selected. With AmpliDiff we provide an effective and efficient alternative to whole genome sequencing for estimating lineage abundances in viral metagenomes.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.22.550164v1" target="_blank">AmpliDiff: An Optimized Amplicon Sequencing Approach to Estimating Lineage Abundances in Viral Metagenomes</a>
</div></li>
<li><strong>Genomic epidemiology of European Aspergillus fumigatus causing COVID-19-associated pulmonary aspergillosis in Europe</strong> -
<div>
The opportunistic fungus Aspergillus fumigatus has been found to cause coinfections in patients with severe SARS-CoV-2 virus infection, leading to COVID-19-associated pulmonary aspergillosis (CAPA). The CAPA all-cause mortality rate is approximately 50% and may be complicated by azole-resistance. Genomic epidemiology can help shed light on the genetics of A. fumigatus causing CAPA including the prevalence of alleles that are associated with azole-resistance. Here, a population genomic analysis of 21 CAPA isolates from four European countries is presented. The CAPA isolates were compared with A. fumigatus from a wider population of 167 non-CAPA clinical isolates and 73 environmental isolates. Bioinformatic analysis and antifungal susceptibility testing were performed to quantify resistance and identify possible genetically-encoded azole-resistant mechanisms. Phylogenetic analysis of the 21 CAPA isolates showed a lack of genetic distinction from the wider A. fumigatus population, with isolates distributed within two distinct clades (A and B), with the majority of the CAPA isolates in clade B (71.4%). The prevalence of phenotypic azole-resistance in CAPA was 14.3% (n=3/21); all three CAPA isolates contained a known resistance-associated cyp51A polymorphism. CAPA isolates are drawn from the wider A. fumigatus population rather than forming a unique genetic background showing that COVID-19 patients are susceptible to the entire A. fumigatus population. However, the relatively high prevalence of azole-resistance alleles that we document poses a threat to treatment success rates, warranting enhanced detection and surveillance of A. fumigatus genotypes in these patients. Furthermore, potential changes to antifungal first-line treatment guidelines may be needed to improve patient outcomes.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.21.550109v1" target="_blank">Genomic epidemiology of European Aspergillus fumigatus causing COVID-19-associated pulmonary aspergillosis in Europe</a>
</div></li>
<li><strong>Phylogeny and evolution of the SARS-CoV-2 spike gene from December 2022 to February 2023</strong> -
<div>
Background: By the end of 2022, new variants of SARS-CoV-2, such as BQ.1.1.10, BA.4.6.3, XBB, and CH.1.1, emerged with higher fitness than BA.5. Methods: The file (spikeprot0304), which contains spike protein sequences, isolates collected before March, 4, 2023, was downloaded from Global Initiative on Sharing All Influenza Data (GISAID). A total of 188 different spike protein sequences were chosen, of which their isolates were collected from December 2022 to February 2023. These sequences did not contain undetermined amino acid X, and each spike protein sequence had at least 100 identical isolate sequences in GISAID. Phylogenetic trees were reconstructed using IQ-TREE and MrBayes softwares. A median-join network was reconstructed using PopART software. Selection analyses were conducted using site model of PAML software. Results: The phylogenetic tree of the spike DNA sequences revealed that the majority of variants belonged to three major lineages: BA.2 (BA.1.1.529.2), BA.5 (BA.1.1.529.5), and XBB. The median network showed that these lineages had at least six major diversifying centers. The spike DNA sequences of these diversifying centers had the representative accession IDs (EPI_ISL_) of 16040256 (BN.1.2), 15970311 (BA.5), 16028739 (BA.5.11), 16028774 (BQ.1), 16027638 (BQ.1.1.23), and 16044705 (XBB.1.5). Selection analyses revealed 26 amino-acid sites under positive selection. These sites included L5, V83, W152, G181, N185, V213, H245, Y248, D253, S255, S256, G257, R346, R408, K444, V445, G446, N450, L452, N460, F486, Q613, Q675, T883, P1162, and V1264. Conclusion: The spike proteins of SARS-CoV-2 from December 2022 to February 2023 were characterized by a swarm of variants that were evolved from three major lineages: BA.2 (BA.1.1.529.2), BA.5 (BA.1.1.529.5), and XBB. These lineages had at least six diversifying centers. Selection analysis identified 26 amino acid sites were under positive selection. Continued surveillance and research are necessary to monitor the evolution and potential impact of these variants on public health.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.23.549423v1" target="_blank">Phylogeny and evolution of the SARS-CoV-2 spike gene from December 2022 to February 2023</a>
</div></li>
<li><strong>Factors influencing COVID-19 vaccination decision-making among African American and Hispanic pregnant and postpartum women in Deep South</strong> -
<div>
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Background COVID-19 vaccination is vital for ending the pandemic but concerns about its safety among pregnant and postpartum women, especially among African American (AA) and Hispanic women, persist. This study aims to explore factors that influence vaccination decision-making among AA and Hispanic pregnant and postpartum women through women’s experiences and maternal care providers’ (MCPs) observations. Methods From January and August 2022, we conducted semi-structured interviews with AA and Hispanic women and MCPs. Participants were recruited from obstetric and pediatric clinics in South Carolina, and all births took place after March 2020. Thematic analysis was employed for data analysis. Results The study involved 19 AA and 20 Hispanic women, along with 9 MCPs, and revealed both barriers and facilitators to COVID-19 vaccination. The factors that influence pregnant and postpartum women’s decision about COVID-19 vaccine uptake included: 1) awareness of health threats associated with COVID-19 vaccines, 2) vaccine availability and accessibility, 3) vaccine-related knowledge and exposure to misinformation, 4) concerns regarding pre-existing health conditions and potential side effects of COVID-19 vaccines, 5) emotional factors associated with vaccination decision-making processes, 6) concerns about the well-being of infants, 7) cultural perspectives, and 8) encouragement by trusted supporters. Conclusion Findings suggest that reliable information, social support, and trusted doctors’ advice can motivate COVID-19 vaccination. However, barriers such as misinformation, mistrust in the health care system, and fears related to potential side effects impede vaccination uptake among AA and Hispanic pregnant and postpartum women. Future interventions should target these barriers, along with health disparities, involve trusted doctors in outreach, and initiate vaccine conversations to promote vaccination among this population.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.20.23292951v1" target="_blank">Factors influencing COVID-19 vaccination decision-making among African American and Hispanic pregnant and postpartum women in Deep South</a>
</div></li>
<li><strong>Mechanistic and thermodynamic characterization of antivirals targeting druggable pocket of SARS-CoV-2 nucleocapsid</strong> -
<div>
The N-terminal (NTD) and the C-terminal (CTD) domains comprises the structure of the SARS-CoV-2 Nucleocapsid (N) protein. Crystal structure of the SARS-CoV-2 N protein determined by Kang et al, 2020, reveals the N-terminal RNA binding domain as a unique drug binding site. The present study targets this unique pocket with identified antivirals using structure-based drug repurposing approach. The high-affinity binding of potential molecules was characterised thermodynamically using Isothermal titration calorimetry. The selected molecules showed an inhibitory RNA binding potential between 8.8 micromolar and 15.7 micromolar IC50 when evaluated with a fluorescent-based assay. Furthermore, in an in vitro cell-based antiviral assay, these ten antiviral molecules demonstrated high effectiveness in halting SARS-CoV-2 replication. Telmisartan and BMS-189453, the two highly potent antivirals, have ~0.98 micromolar and 1.02 micromolar EC50 values with the selective index of &gt;102, and &gt;98, respectively. For the first time, this study presents drug molecules specifically targeting the NTD of SARS-CoV-2, offering essential insights for the development of therapeutic interventions against this virus, which is still a potential global threat to public health.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.03.12.484092v4" target="_blank">Mechanistic and thermodynamic characterization of antivirals targeting druggable pocket of SARS-CoV-2 nucleocapsid</a>
</div></li>
<li><strong>Impact of Emerging COVID-19 variants on psychosocial health: A Systematic Review</strong> -
<div>
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Background: The COVID-19 pandemic has had significant psychological effects on individuals and communities around the world. Studies have found that the prevalence of anxiety and depression symptoms increased significantly during the pandemic. The goal of the study is to understand how the emerging new virus variants keep the world in a state of fear and the ways in which mental health measures can be implemented and adopted to alleviate anxiety. Methods: A broad search for observational studies were carried out in Pubmed, Google Scholar, Clinical Key, and World Medical Library. Studies that reported and/or related the existence of anxiety generated by suffering or not from diseases caused by the new emerging Covid-19 viruses and that for which the full text of the article was accessible were included in the study while systematic review and meta-analysis and studies in groups were excluded. Results: 22 studies were included in the review. The deleterious psychosocial effects were the restructuring of life, establishment of unhealthy habits, emergence of “corona phobia”, fear and stigma of being afflicted with the disease and spreading it to loved ones, and lack of contact with others. Increased rates of depression and anxiety were also seen. The circulating variants responsible for these main psychosocial repercussions were: Epsilon, Zeta, Eta, Iota, Kappa, Alpha, Beta, Gamma, and Delta. Social support was found to be protective. Conclusion: Hence interventions targeted at promoting mental health should be considered a public health priority.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.23.23293040v1" target="_blank">Impact of Emerging COVID-19 variants on psychosocial health: A Systematic Review</a>
</div></li>
<li><strong>Genomic Analysis and Surveillance of Respiratory Syncytial Virus (RSV) Using Wastewater-Based Epidemiology (WBE)</strong> -
<div>
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Respiratory syncytial virus (RSV) causes severe infections in infants, immunocompromised or elderly individuals resulting in annual epidemics of respiratory disease. Currently, limited clinical RSV surveillance and the lack of predictable RSV seasonal dynamics and limits the public health response. Wastewater-based epidemiology (WBE) has the capacity to determine levels of health-associated biomarkers and has recently been used globally as a key metric in determining prevalence of SARS-CoV-2 in the community. However, the application of genomic WBE for the surveillance of other respiratory viruses is limited. In this study, we present an integrated genomic WBE approach, using RT-qPCR and partial sequencing of the G gene to monitor RSV levels and variants in the community across 2 years encompassing two periods of high RSV clinical positivity in Northern Ireland. We report increasing detection of RSV in wastewater concomitant with increasing numbers of RSV positive clinical cases. Furthermore, analysis of wastewater-derived RSV sequences permitted subtyping, genotyping, and identification of distinct circulating lineages within and between seasons. Altogether, our genomic WBE platform has the potential to complement ongoing global surveillance efforts and aid the management of RSV by informing the timely deployment of pharmaceutical and non-pharmaceutical interventions.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.21.23293016v1" target="_blank">Genomic Analysis and Surveillance of Respiratory Syncytial Virus (RSV) Using Wastewater-Based Epidemiology (WBE)</a>
</div></li>
<li><strong>Incubation-period estimates of Omicron (BA.1) variant from Taiwan, December 2021-January 2022, and its comparison to other SARS-CoV-2 variants: a statistical modeling, systematic search and meta-analysis</strong> -
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Background: The ongoing COVID-19 pandemic has seen several variants of concern, including the Omicron (BA.1) variant which emerged in October 2021. Accurately estimating the incubation period of these variants is crucial for predicting disease spread and formulating effective public health strategies. However, existing estimates often conflict because of biases arising from the dynamic nature of epidemic growth and selective inclusion of cases. This study aims to accurately estimate of the Omicron (BA.1) variant incubation period based on data from Taiwan, where disease incidence remained low and contact tracing was comprehensive during the first months of the Omicron outbreak. Methods: We reviewed 100 contact-tracing records for cases of the Omicron BA.1 variant reported between December 2021 and January 2022, and found enough information to analyze 70 of these. The incubation period distribution was estimated by fitting data on exposure and symptom onset within a Bayesian mixture model using gamma, Weibull, and lognormal distributions as candidates. Additionally, a systematic literature search was conducted to accumulate data for estimates of the incubation period for Omicron (BA.1/2, BA.4/5) subvariants, which was then used for meta-analysis and comparison. Results: The mean incubation period was estimated at 3.5 days (95% credible interval: 3.1-4.0 days), with no clear differences when stratified by vaccination status or age. This estimate aligns closely with the pooled mean of 3.4 days (3.0-3.8 days) obtained from a meta-analysis of other published studies on Omicron subvariants. Conclusions: The relatively shorter incubation period of the Omicron variant, as compared to previous SARS-CoV2 variants, implies its potential for rapid spread but also opens the possibility for individuals to voluntarily adopt shorter, more resource-efficient quarantine periods. Continual updates to incubation period estimates, utilizing data from comprehensive contact tracing, are crucial for effectively guiding these voluntary actions and adjusting high socio-economic cost interventions.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.20.23292983v1" target="_blank">Incubation-period estimates of Omicron (BA.1) variant from Taiwan, December 2021-January 2022, and its comparison to other SARS-CoV-2 variants: a statistical modeling, systematic search and meta-analysis</a>
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<li><strong>Artificial Intelligence in Biomedicine: Systematic Review</strong> -
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Abstract Artificial Intelligence (AI) is a rapidly progressing technology with its applications expanding exponentially over the past decade. While initial breakthroughs predominantly focused on deep learning and computer vision, recent advancements have facilitated a shift towards natural language processing and beyond. This includes generative models, like ChatGPT, capable of understanding the 9grammar9 of software code, analog signals, and molecular structures. This research undertakes a comprehensive examination of AI trends within the biomedical domain, including the impact of ChatGPT. We explore scientific literature, clinical trials, and FDA-approval data, utilizing a thematic synthesis approach and bibliometric mapping of keywords to examine numerous subsets from over a hundred thousand unique records found in prominent public repositories up to mid- July 2023. Our analysis reveals a higher prevalence of general health-related publications compared to more specialized papers using or evaluating ChatGPT. However, the growth in specialized papers suggests a convergence with the trend observed for other AI tools. Our findings also imply a greater prevalence of publications using ChatGPT across multiple medical specialties compared to other AI tools, indicating its rising influence in complex fields requiring interdisciplinary collaboration. Leading topics in AI literature include radiology, ethics, drug discovery, COVID-19, robotics, brain research, stroke, and laparoscopy, indicating a shift from laboratory to emergency medicine and deep-learning-based image processing. Publications involving ChatGPT predominantly address current themes such as COVID-19, practical applications, interdisciplinary collaboration, and risk mitigation. Radiology retains dominance across all stages of biomedical R&amp;D, spanning preprints, peer-reviewed papers, clinical trials, patents, and FDA approvals. Meanwhile, surgery-focused papers appear more frequently within ChatGPT preprints and case reports. Traditionally less represented areas, such as Pediatrics, Otolaryngology, and Internal Medicine, are starting to realize the benefits of ChatGPT, hinting at its potential to spark innovation within new medical sectors. AI application in geriatrics is notably underrepresented in publications. However, ongoing clinical trials are already exploring the use of ChatGPT for managing age-related conditions. The higher frequency of general health-related publications compared to specialized papers employing or evaluating ChatGPT showcases its broad applicability across multiple fields. AI, particularly ChatGPT, possesses significant potential to reshape the future of medicine. With millions of papers published annually across various disciplines, efficiently navigating the information deluge to pinpoint valuable studies has become increasingly challenging. Consequently, AI methods, gaining in popularity, are poised to redefine the future of scientific publishing and its educational reach. Despite challenges like quality of training data and ethical concerns, prevalent in preceding AI tools, the wider applicability of ChatGPT across diverse fields is manifest. This review employed the PRISMA tool and numerous overlapping data sources to minimize bias risks.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.23.23292672v1" target="_blank">Artificial Intelligence in Biomedicine: Systematic Review</a>
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<li><strong>Comparison of the analytical and clinical sensitivity of thirty-four rapid antigen tests with the most prevalent SARS-CoV-2 variants of concern during the COVID-19 pandemic in the UK</strong> -
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Background The continued emergence of SARS-CoV-2 variants of concern (VOC) requires timely analytical and clinical evaluation of antigen-based rapid diagnostic tests (Ag-RDTs) especially those that are recommended for at home use. Methods The limit of detection (LOD) of 34 Ag-RDTs was evaluated using the most encountered SARS-CoV-2 VOC viral isolates (Alpha, Delta, Gamma, Omicron BA.1, Omicron BA.5) and the wild type (WT). Clinical sensitivity was further evaluated for five Ag-RDT utilising retrospective samples (Alpha, Delta, Omicron BA.1) and one Ag-RDT utilising prospective clinical samples (Delta and Omicron BA.1). Findings For the WT, Alpha, Delta, Gamma and Omicron (BA.1) variants 22, 32, 29, 31 and 32 of the 34 Ag-RDTs evaluated met the World Health Organisations (WHO) target product profile (TPP), respectively. Of the 31 Ag-RDTs included for Omicron BA.5 evaluation 29 met the WHO TPP. Additionally, the LODs for samples spiked with Omicron BA.5 were significantly lower than all other VOCs included (p&lt;0.001). In the retrospective clinical evaluation when comparing RNA copies/mL, the Ag-RDTs detected Alpha and Omicron (BA.1) more sensitively than the Delta VOC. Samples with high RT-qPCR Cts (Ct&gt;25) resulted in reduced test sensitivities across all variants. We used linear regression to model the 50% and 95% LOD of clinical samples and observed statistically similar results for all tests. In the prospective clinical samples, the sensitivity was statistically similar for the Delta VOC 71.9% (CI 95% 53.3-86.6%) and Omicron VOC 84.4% (CI95% 75.3-91.2%). Interpretation Test performance differs between SARS-CoV-2 VOCs, and high sensitivity was achieved when testing the Omicron BA.5 VOC compared to the WHO Ag-RDT requirements. Continuous evaluations must be performed to monitor test performance.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.24.23293072v1" target="_blank">Comparison of the analytical and clinical sensitivity of thirty-four rapid antigen tests with the most prevalent SARS-CoV-2 variants of concern during the COVID-19 pandemic in the UK</a>
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<li><strong>Reactivation of herpesvirus type-6 and IgA/IgM-mediated responses to activin-A underpin Long COVID, including affective symptoms and chronic fatigue syndrome.</strong> -
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Background: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in Long COVID. Objectives: To investigate whether Long COVID and depressive, anxiety and chronic fatigue syndrome (CFS) symptoms, are associated with IgA/IgM/IgG to SARS-CoV-2, human Herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. Methods: We examined 90 Long COVID patients and 90 healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5′-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR). Results: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6 and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the Long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve=0.876); the topmost predictors were: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top-5 predictors of affective symptoms due to Long COVID were: IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r=0.636). The top-5 predictors of CFS due to Long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r=0.709). Conclusion: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of Long COVID as well as the severity of affective symptoms and CFS due to Long COVID.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.23.23293046v1" target="_blank">Reactivation of herpesvirus type-6 and IgA/IgM-mediated responses to activin-A underpin Long COVID, including affective symptoms and chronic fatigue syndrome.</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>Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: theophylline;   Drug: Placebo<br/><b>Sponsor</b>:   Washington University School of Medicine<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine.</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Procedure: Lymph node aspiration / Blood sampling<br/><b>Sponsor</b>:   Assistance Publique - Hôpitaux de Paris<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>COVID-19 Trial of the Candidate Vaccine MVA-SARS-2-S in Adults</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: MVA-SARS-2-S;   Other: Placebo<br/><b>Sponsors</b>:   Universitätsklinikum Hamburg-Eppendorf;   German Center for Infection Research;   Philipps University Marburg Medical Center;   Ludwig-Maximilians - University of Munich;   University Hospital Tuebingen;   CTC-NORTH<br/><b>Withdrawn</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>Immunoadsorption vs. Sham Treatment in Post COVID-19 Patients With Chronic Fatigue Syndrome</strong> - <b>Conditions</b>:   Fatigue;   Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>:   Procedure: Immunoadsorption vs. sham immunoadsorption<br/><b>Sponsor</b>:   Hannover Medical School<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>Non-ventilated Prone Positioning in the COVID-19 Population</strong> - <b>Conditions</b>:   COVID-19;   Proning;   Oxygenation;   Length of Stay<br/><b>Interventions</b>:   Other: Proning group;   Other: Control group<br/><b>Sponsor</b>:   Baylor St. Luke’s Medical Center<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Treatment of Long COVID (TLC) Feasibility Trial</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Low-dose Naltrexone (LDN);   Drug: Cetirizine;   Drug: Famotidine;   Drug: LDN Placebo;   Drug: Cetirizine Placebo;   Drug: Famotidine Placebo<br/><b>Sponsors</b>:   Emory University;   CURE Drug Repurposing Collaboratory (CDRC)<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, Efficacy, and Dosing of VIX001 in Patients With Neurological Symptoms of Post Acute COVID-19 Syndrome (PACS).</strong> - <b>Conditions</b>:   Post-Acute COVID-19 Syndrome;   Cognitive Impairment;   Neurological Complication<br/><b>Intervention</b>:   Drug: VIX001<br/><b>Sponsor</b>:   Neobiosis, LLC<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>PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19</strong> - <b>Condition</b>:   SARS-CoV-2<br/><b>Interventions</b>:   Drug: Upamostat;   Drug: Placebo (PO)<br/><b>Sponsors</b>:   Henry M. Jackson Foundation for the Advancement of Military Medicine;   Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies;   FHI Clinical, Inc.;   RedHill Biopharma Limited<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>:   Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)<br/><b>Interventions</b>:   Drug: MBS-COV;   Drug: Placebo<br/><b>Sponsor</b>:   Oneness Biotech Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression</strong> - <b>Conditions</b>:   COVID 19 Disease;   Mild to Moderate COVID 19 Disease;   SARS-CoV-2;   Infectious Disease;   Severe Acute Respiratory Syndrome Coronavirus 2<br/><b>Interventions</b>:   Drug: Tafenoquine Oral Tablet;   Drug: Placebo<br/><b>Sponsor</b>:   60P Australia Pty Ltd<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19</strong> - <b>Conditions</b>:   Asthenia;   COVID-19;   Functional MRI;   Cognitive Impairment<br/><b>Interventions</b>:   Other: Structural and functional MRI;   Drug: Ethyl methyl hydroxypyridine succinate + Meldonium;   Drug: Placebo<br/><b>Sponsor</b>:   Promomed, LLC<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>NDV-HXP-S Vaccine Clinical Trial (COVIVAC)</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: COVIVAC vaccine<br/><b>Sponsors</b>:   Institute of Vaccines and Medical Biologicals, Vietnam;   National Institute of Hygiene and Epidemiology (NIHE), Vietnam;   Center for Disease Control of Thai Binh Province, Vietnam<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>MR-spectroscopy in Post-covid Condition Prior to and Following a Yoga Breathing Intervention</strong> - <b>Conditions</b>:   Post COVID-19 Condition;   Somatic Symptom Disorder<br/><b>Interventions</b>:   Behavioral: yoga;   Behavioral: social contact<br/><b>Sponsor</b>:   Medical University Innsbruck<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>Clinical Evaluation of SARS-COV-2 (COVID-19), Influenza and RSV 8-Well MT-PCR Panel for In Vitro Diagnostics</strong> - <b>Condition</b>:   Respiratory Viral Infection<br/><b>Interventions</b>:   Diagnostic Test: SARS-COV-2, Influenza and RSV 8-Well MT-PCR Panel;   Diagnostic Test: BioFire Respiratory Panel 2.1<br/><b>Sponsor</b>:   AusDiagnostics Pty Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Expressive Interviewing Agents to Support Health-Related Behavior Change</strong> - <b>Condition</b>:   Mental Stress<br/><b>Intervention</b>:   Other: Expressive Interviewing<br/><b>Sponsors</b>:   University of Michigan;   University of Texas at Austin<br/><b>Completed</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Korean Red Ginseng Relieves Inflammation and Modulates Immune Response Induced by Pseudo-Type SARS-CoV-2</strong> - Few studies have reported the therapeutic effects of Korean red ginseng (KRG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the positive effects of KRG on other viruses have been reported and the effects of KRG on pulmonary inflammatory diseases have also been studied. Therefore, this study investigated the therapeutic effects of KRG-water extract (KRG-WE) in a pseudo-type SARS-CoV-2 (PSV)-induced lung injury model. Constructing the pseudovirus, human…</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>Vector-delivered artificial miRNA effectively inhibits Porcine epidemic diarrhea virus replication</strong> - CONCLUSIONS: In summary, these results suggest that an RNAi based on amiRNA targeting the conserved region of the virus is an effective method to improve PEDV nucleic acid inhibitors and provide a novel treatment strategy for PEDV infection.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Deciphering the role of fucoidan from brown macroalgae in inhibiting SARS-CoV-2 by targeting its main protease and receptor binding domain: Invitro and insilico approach</strong> - The current study investigated the role of fucoidan from Padina tetrastromatica and Turbinaria conoides against 3-chymotrypsin like protease (3CL^(pro)) and receptor binding domain (RBD) spike protein of SARS-CoV-2 using an invitro and computational approach. The 3CL^(pro) and RBD genes were successfully cloned in pET28a vector, expressed in BL-21DE3 E. coli rosetta cells and purified by ion exchange affinity and size exclusion chromatography. Fucoidan extracted from both biomass using green…</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>Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases</strong> - Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies….</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 kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy</strong> - SARS-CoV-2 (COVID-19) exerts profound changes in the kynurenine (Kyn) pathway (KP) of tryptophan (Trp) metabolism that may underpin its pathophysiology. The KP is the main source of the vital cellular effector NAD+ and intermediate metabolites that modulate immune and neuronal functions. Trp metabolism is the top pathway influenced by COVID-19. Sixteen studies established virus-induced activation of the KP mediated mainly by induction of indoleamine 2,3-dioxygenase (IDO1) in most affected…</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>Regulation of autophagy by SARS-CoV-2: The multifunctional contributions of ORF3a</strong> - Severe acute respiratory syndrome-coronavirus-1 (SARS-CoV-2) regulates autophagic flux by blocking the fusion of autophagosomes with lysosomes, causing the accumulation of membranous vesicles for replication. Multiple SARS-CoV-2 proteins regulate autophagy with significant roles attributed to ORF3a. Mechanistically, open reading frame 3a (ORF3a) forms a complex with UV radiation resistance associated, regulating the functions of the PIK3C3-1 and PIK3C3-2 lipid kinase complexes, thereby…</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>Fangchinoline inhibits the PEDV replication in intestinal epithelial cells via autophagic flux suppression</strong> - Animal and human health are severely threatened by coronaviruses. The enteropathogenic coronavirus, porcine epidemic diarrhea virus (PEDV), is highly contagious, leading to porcine epidemic diarrhea (PED), which causes large economic losses in the world’s swine industry. Piglets are not protected from emerging PEDV variants; therefore, new antiviral measures for PED control are urgently required. Herein, the anti-PEDV effects and potential mechanisms of fangchinoline (Fan) were investigated. Fan…</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>Silver N-heterocyclic carbene complexes are potent uncompetitive inhibitors of the papain-like protease with antiviral activity against SARS-CoV-2</strong> - The ongoing SARS-CoV-2 pandemic has caused a high demand for novel innovative antiviral drug candidates. Despite promising results, metal complexes have been relatively unexplored as antiviral agents in general and in particular against SARS-CoV-2. Here we report on silver NHC complexes with chloride or iodide counter ligands that are potent inhibitors of the SARS-CoV-2 papain-like protease (PL^(pro)) but inactive against 3C-like protease (3CL^(pro)) as another SARS-CoV-2 protease. Mechanistic…</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>Nanoparticle approaches for the renin-angiotensin system</strong> - The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural fucoidans inhibit coronaviruses by targeting viral spike protein and host cell furin</strong> - Fucoidans are a class of long chain sulfated polysaccharides and have multiple biological functions. Herein, four natural fucoidans extracted from Fucus vesiculosus, F. serratus, Laminaria japonica and Undaria pinnatifida, were tested for their HCoV-OC43 inhibition and found to demonstrate EC(50) values ranging from 0.15 to 0.61 µg/mL. That from U. pinnatifida exhibited the most potent anti-HCoV-OC43 activity with an EC(50) value of 0.15 ± 0.02 µg/mL, a potency largely independent of its sulfate…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>One master and two servants: One Zr(Ⅳ) with two ligands of TCPP and NH<sub>2</sub>-BDC form the MOF as the electrochemiluminescence emitter for the biosensing application</strong> - Here we put forward an innovative “one master and two servants” strategy for enhancing the ECL performance. A novel ECL luminophore named Zr-TCPP/NH(2)-BDC (TCPP@UiO-66-NH(2)) was synthesized by self-assembly of meso-tetra(4-carboxyphenyl)porphine (TCPP) and 4-aminobenzoic acid (NH(2)-BDC) with Zr clusters. TCPP@UiO-66-NH(2) has a porous structure and a highly ordered structure, which allows the molecular motion of TCPP to be effectively confined, thereby inhibiting nonradiative energy transfer….</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>Understanding structure activity relationships of Good HEPES lipids for lipid nanoparticle mRNA vaccine applications</strong> - Lipid nanoparticles (LNPs) have shown great promise as delivery vehicles to transport messenger ribonucleic acid (mRNA) into cells and act as vaccines for infectious diseases including COVID-19 and influenza. The ionizable lipid incorporated within the LNP is known to be one of the main driving factors for potency and tolerability. Herein, we describe a novel family of ionizable lipids synthesized with a piperazine core derived from the HEPES Good buffer. These ionizable lipids have unique…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification and validation of fusidic acid and flufenamic acid as inhibitors of SARS-CoV-2 replication using DrugSolver CavitomiX</strong> - In this work, we present DrugSolver CavitomiX, a novel computational pipeline for drug repurposing and identifying ligands and inhibitors of target enzymes. The pipeline is based on cavity point clouds representing physico-chemical properties of the cavity induced solely by the protein. To test the pipeline’s ability to identify inhibitors, we chose enzymes essential for SARS-CoV-2 replication as a test system. The active-site cavities of the viral enzymes main protease (M^(pro)) and papain-like…</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>Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants</strong> - Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge to worldwide public health. The SARS-CoV-2 receptor-binding domain (RBD) is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated the impact of RBD mutations, including 5 variants of concern (VOC) or interest-including Omicron (BA.2)-and 33 common point mutations, both on IgG recognition and ACE2-binding inhibition, as well as…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A quantum chemical study on the anti-SARS-CoV-2 activity of TMPRSS2 inhibitors</strong> - Nafamostat and camostat are known to inhibit the spike protein-mediated fusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by forming a covalent bond with the human transmembrane serine protease 2 (TMPRSS2) enzyme. Previous experiments revealed that the TMPRSS2 inhibitory activity of nafamostat surpasses that of camostat, despite their structural similarities; however, the molecular mechanism of TMPRSS2 inhibition remains elusive. Herein, we report the energy profiles of the…</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>A New Lawsuit Alleges That Leonard Leo Called for the Arrest of a Pro-Choice Protester</strong> - The court filing claims that the Federalist Society leader, a champion of free speech, urged police to violate the First Amendment rights of a demonstrator near his Maine home. - <a href="https://www.newyorker.com/news/news-desk/a-new-lawsuit-alleges-that-leonard-leo-called-for-the-arrest-of-a-pro-choice-protester">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Puzzling, Increasingly Rightward Turn of Mario Vargas Llosa</strong> - The writer has shocked many by endorsing Latin America and Spain’s rising authoritarian movements. - <a href="https://www.newyorker.com/news/daily-comment/the-puzzling-increasingly-rightward-turn-of-mario-vargas-llosa">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Day in the Life of Congress’s “Traffic Cop”</strong> - The House Committee on Rules decides which bills go forward. Jim McGovern, the ranking Democrat, has watched a decades-long erosion of the process. - <a href="https://www.newyorker.com/news/the-political-scene/a-day-in-the-life-of-jim-mcgovern-us-congress">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pope Francis’s Peace Envoy Comes to Washington</strong> - Can a progressive cardinal—who’s seen as a possible future Pope—help bring an end to the war in Ukraine? - <a href="https://www.newyorker.com/news/daily-comment/pope-franciss-peace-envoy-comes-to-washington">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Will Biden’s Meetings with A.I. Companies Make Any Difference?</strong> - Voluntary commitments from the likes of OpenAI, Microsoft, and Google could be a small step toward meaningful A.I. regulations—or a way for Big Tech to write its own rules. - <a href="https://www.newyorker.com/news/daily-comment/will-bidens-meetings-with-ai-companies-make-any-difference">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Psychedelics might revolutionize therapy. What happens if you remove the trip?</strong> -
<figure>
<img alt="A colorful pill against a blue background." src="https://cdn.vox-cdn.com/thumbor/j6OpS4wTg_R9wfS2q-eSyMM2XvY=/0x949:3630x3672/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72481201/GettyImages_145958929.0.jpg"/>
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Getty Images
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Tripless” drugs might open more opportunities for psychiatry. Just don’t call them psychedelics.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TDXfea">
Today’s <a href="https://www.vox.com/future-perfect/23721486/ketamine-dmt-lsd-psychedelics-magic-mushrooms-legalization-recreation-psilocybin">psychedelic renaissance</a> is thriving thanks to a list of drugs that you could count on just one hand. MDMA, psilocybin, LSD, and DMT are driving a <a href="https://www.nytimes.com/2021/05/09/health/psychedelics-mdma-psilocybin-molly-mental-health.html">revolution in psychiatry</a> while opening <a href="https://newrepublic.com/article/169525/psychonauts-training-psychedelics-dmt-extended-state">new frontiers in the exploration of consciousness</a>. If you expand to your other hand with drugs like ketamine and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/ibogaine">ibogaine</a>, there’s enough mystery in that small gang of substances to keep researchers busy for decades.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TyfL5W">
But what if there were hundreds, or thousands, more? Drugs are like tiny Legos that can be rearranged in a staggering variety of ways. Chemists have hardly begun to discover all the endless molecular forms contained within the psychedelic arena. In the 1960s, the biochemist Alexander Shulgin, who introduced MDMA to the world, <a href="https://www.nytimes.com/2005/01/30/magazine/dr-ecstasy.html">invented nearly 200 psychedelics</a> (largely in his backyard laboratory, where he used sheet metal to keep the squirrels out). When President Richard Nixon <a href="https://psychedelics.berkeley.edu/law/">outlawed psychedelics in 1970</a>, drug discovery went dark.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UoMV1H">
Nearly two decades into <a href="https://www.vox.com/future-perfect/23721486/ketamine-dmt-lsd-psychedelics-magic-mushrooms-legalization-recreation-psilocybin">a revival of psychedelic research</a>, the doors of drug discovery have swung wide open once again, and the latest development is roiling psychedelia, revealing fault lines that split the field into two.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wbDOyt">
The question: Can we tinker just enough with the molecular structure of psychedelic compounds so as to retain their therapeutic benefits, but ditch the trip? And should we? For many, the trip is the point. Cutting it out would be, to use 1960s terminology, a major bummer. Beyond a stream of unusual and profound experiences, many researchers believe that the insights people have on their trips <a href="https://pubs.acs.org/doi/10.1021/acsptsci.0c00194">are necessary</a> for securing the long-term benefits, which can range from <a href="https://pubmed.ncbi.nlm.nih.gov/16826400/">personally meaningful experiences</a> to treating conditions such as <a href="https://pubmed.ncbi.nlm.nih.gov/27909165/">depression</a> or <a href="https://pubmed.ncbi.nlm.nih.gov/25213996/">addiction</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="utQjX5">
For others, the trip is a barrier to treatment. Not everyone wants to have their entire consciousness rearranged in unfamiliar and sometimes <a href="https://bulletin.hds.harvard.edu/a-theological-reckoning-with-bad-trips/">unsettling</a> ways for a little while. And integrating trips into existing models of therapy is both time-consuming and expensive. In Australia, the <a href="https://www.nature.com/articles/d41586-023-02093-8">first country to legalize</a> medically prescribed psychedelic therapy (which spans multiple days), one <a href="https://www.abc.net.au/news/2023-03-18/psychedelic-charity-accused-lobbying-tga-mdma-psilocybin/102103782">psychiatrist’s estimate</a> put the combined cost of medication and the therapists’ time around $10,000 at the estimate’s lower end. In the US, Oregon is the first state to offer licensed access for adults over 21, where a single session <a href="https://psychedelicspotlight.com/oregons-first-licensed-psilocybin-center-charges-2800-for-one-session-are-the-costs-justifiable/">costs $2,800</a>. “Take your pick: Comorbidities, cost, convenience, or other challenges will get in the way for some people who may not be able to access those [psychedelic] treatments,” Mark Rus, the CEO of Delix Therapeutics, a company working on developing variations on tripless psychedelics, told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PCU39N">
In 2020, a group of researchers led by Delix co-founder and chemist David Olson <a href="https://www.nature.com/articles/s41586-020-3008-z">published work suggesting</a> tripless psychedelics are possible. In this case, a reengineered form of ibogaine — a psychoactive substance with dissociative properties found in a West African shrub, traditionally <a href="https://www.herbalgram.org/resources/herbalgram/issues/93/table-of-contents/bkrvw_iboga/">used by the Bwiti religion</a> in Gabon and being studied today for its <a href="https://time.com/5951772/ibogaine-drug-treatment-addiction/">anti-addictive potential</a> — still displayed therapeutic effects while leaving out the distortions of consciousness, at least in mice. In the years since, <a href="https://www.science.org/doi/10.1126/science.abl8615">more papers have come</a> out demonstrating that reengineered psychedelics like LSD can retain therapeutic effects while losing the trip — but again, all in mice.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W3kvYG">
Now, these psychedelic-inspired, tripless drugs are heading into human trials for the first time. In June, Delix Therapeutics announced a successful first round of dosing as part of their <a href="https://www.delixtherapeutics.com/news/delix-therapeutics-announces-completion-of-1st-cohort-dosing-dose-escalation-approval-in-phase-i-trial-for-novel-compound-dlx-001/">Phase I clinical trials</a> of DLX-001, a ”non-hallucinogenic” version of MDMA. If the results replicate in humans, the implications could be significant. Rid of the trip, these drugs could prove safe and therapeutically effective to take at home, bypassing the need (and expense) for multiple in-person sessions and staffing. But even if such drugs prove effective in mitigating conditions like depression, anxiety, or addiction, according to others in the field, you’d be missing out on the very thing that makes psychedelics so <a href="https://link.springer.com/article/10.1007/s00213-006-0457-5">reliably</a> <a href="https://www.vice.com/en/article/5dg9a5/the-life-changing-realisations-that-people-had-on-psychedelics">life-changing</a>.
</p>
<h3 id="y5pYWp">
Why would you want a psychedelic without the trip?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UWBU3l">
With all the talk of a <a href="https://www.theguardian.com/society/2021/sep/26/psychedelics-renaissance-new-wave-of-research-puts-hallucinogenics-forward-to-treat-mental-health">psychedelic renaissance</a>, it’s easy to get the wrong idea. Sixty-eight percent of Americans have never tried psychedelics, according to <a href="https://docs.cdn.yougov.com/w0tzky5izb/crosstabs_Psychedelics.pdf">a recent YouGov poll</a>. A <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205319/">survey of mental health service users</a> found that 20 percent still viewed psychedelics as unsafe, even under medical supervision, citing concerns about adverse effects (among other concerns like lack of knowledge and illegality). Leading researchers are already preparing for the “<a href="https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2795948">bursting of the psychedelic hype bubble</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yJbr8e">
Yet the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905125/">vast majority of clinical psychedelic trips lean positive</a>. Users consistently report them as among <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033615/">the most meaningful experiences of their lives</a>, on par with the birth of one’s first-born child. And the <a href="https://www.nytimes.com/2022/01/05/well/psychedelic-drugs-mental-health-therapy.html">list of promising therapeutic applications</a> is growing. While uncommon, bad trips and negative side effects <a href="https://themicrodose.substack.com/p/what-is-a-bad-trip-5-questions-for">still happen</a>, and the effects can persist for <a href="https://akjournals.com/configurable/content/journals%24002f2054%24002f6%24002f3%24002farticle-p211.xml">weeks</a> or even <a href="https://bulletin.hds.harvard.edu/a-theological-reckoning-with-bad-trips/">years</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BVRYUL">
After a shot of mescaline (an LSD-like psychedelic found in several species of cacti), the French existential philosopher Jean-Paul Sartre saw a hallucinatory assortment of crustaceans that followed him around for weeks. “After I took mescaline, I started seeing crabs around me all the time. I mean they followed me into the street, into class,” <a href="https://www.theparisreview.org/blog/2019/08/21/sartres-bad-trip/">he recalled</a>. Today, we would call this episode hallucinogenic persisting perception disorder, <a href="https://www.frontiersin.org/articles/10.3389/fneur.2022.878609/full">an extremely rare side effect</a>, and part of the reason clinical studies <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592297/#b31-1871054">screen for participants</a> with a predisposition for psychotic disorders.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tkZPyp">
No matter what sort of new mental health paradigm psychedelics may catalyze, between those with conditions that raise the risks of a trip, and those who may simply prefer to avoid experiencing one, there will be plenty of people who can benefit from different treatment options. If scientists can cut the trip out of psychedelics while leaving some of the therapeutic benefits intact, patients could take these drugs at home for a fraction of both the expense and time commitment of psychedelic therapy, widening the umbrella of treatment options to serve the over <a href="https://mhanational.org/issues/state-mental-health-america">50 million Americans</a> who reported some kind of mental illness in 2020.
</p>
<h3 id="w7Wc5i">
Just don’t call them psychedelics
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ezHPRy">
One wrinkle in the development of these new drugs is semantic: If you successfully carve out the trip, what you are left with is not a psychedelic. And frankly, finding a name for these new compounds offers no simple options, and lots of room for confusion.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kZIw7s">
Olson coined the term “<a href="https://journals.sagepub.com/doi/10.1177/1179069518800508">psychoplastogen</a>,” drawing a boundary around the class of drugs that can rapidly boost <a href="https://www.psychologytoday.com/us/basics/neuroplasticity">neuroplasticity</a> after a single dose. That distinguishes them from SSRI depression treatments like Prozac, which only boost neuroplasticity when <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025168/#:~:text=Antidepressant%20drugs%20are%20associated%20with,arborization%20and%20new%20synapse%20formation.">taken over time</a>. But both classical psychedelics and their new tripless relatives fit within the definition of psychoplastogens. To specify the tripless variety, you’ll find the offputting term “non-hallucinogenic psychoplastogen,” which poses no threat of catching on outside of academia. Instead, some have turned to calling them <a href="https://markets.businessinsider.com/news/stocks/five-companies-developing-second-generation-psychedelics-for-mental-health-1031305973">second-generation psychedelics</a>, or “<a href="https://www.theguardian.com/science/2021/apr/28/non-hallucinogenic-psychedelics-scientists-close-in-on-compound">non-hallucinogenic psychedelics</a>,” which grate against the very meaning of the word psychedelic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W8BPA6">
Etymologically, <em>psychedelic</em> draws on the Ancient Greek for “mind manifesting,” referring directly to what scientists today call the “<a href="https://www.frontiersin.org/articles/10.3389/fphar.2017.00974/full">acute subjective experiences</a>.” The psychiatrist Humphry Osmond <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC381240/#:~:text=Huxley%20suggested%20%E2%80%9Cphanerothyme%2C%E2%80%9D%20from,To%20fathom%20Hell%20or%20soar">came up with the name</a> in conversation with the philosopher and novelist Aldous Huxley in the 1950s, writing: “To fathom Hell or soar angelic / Just take a pinch of psychedelic.” A non-hallucinogenic psychedelic that subjectively manifests nothing out of the ordinary is an oxymoron.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DxBQN0">
To Rus and Olson, that’s fine. They’re in the business of psychoplastogens, not psychedelics. What matters is the untapped healing potential in rapid spikes of neuroplasticity, not how their new drugs compare and contrast to traditional psychedelics.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RGvm3e">
As far as naming goes, “neuroplastogen” is <a href="https://journals.lww.com/neurosurgery/Fulltext/2023/04000/Psychedelic_Assisted_Therapy_and_Psychedelic.5.aspx">beginning</a> to stick as a term describing the tripless category of psychoplastogens. We could still do with a Huxley-and-Osmand-like literary intervention to come up with something smoother, but until then, it’s an improvement.
</p>
<h3 id="n2OY26">
How scientists carved the trip out of psychedelics (in mice)
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Fff8Gz">
While plenty of mystery still blankets the tripping brain, the classical psychedelics — psilocybin mushrooms, DMT, LSD, and mescaline — are at least known to all <a href="https://www.science.org/doi/10.1126/science.adf0435">bind to the same serotonin 2A receptor</a>, which is believed to be one of the main mechanisms underlying <a href="https://academic.oup.com/ijnp/article/26/3/155/6770039">changes in activity across key brain circuits</a> related to conscious experience.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cAsDww">
One approach to untangling the trip from the therapy, <a href="https://www.science.org/doi/10.1126/science.abl8615">published by a group of biochemists</a> from the Shanghai Institute of Biochemistry and Cell Biology last year, involved zooming in a layer deeper. Instead of stopping at the observation of which receptor the drugs bind to, they looked at how the molecules actually fit into the curvature of the receptor. The fit is not perfectly snug, so using a method known as X-ray crystallography, they were able to see where the contact points are.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="H2UyQE">
By shooting X-rays through a crystallized replica of a compound, and based on how the rays twist and turn through the crystal, you can determine how all the atoms therein are arranged, creating a sort of atomic map. A co-author on the publication, Sheng Wang, first used the method <a href="https://www.cell.com/cell/fulltext/S0092-8674(16)31749-4">in a 2017 study</a> to see how LSD fits into the related serotonin 2B receptor, and found that it slots into a cavity known as the orthosteric binding pocket (OBP).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C56KIm">
In the <a href="https://www.science.org/content/article/no-hallucinations-lsd-relatives-appear-treat-depression-mice-without-obvious-side">2022 publication, Wang and colleagues</a> produced six new crystalline drug replicas, this time bound to the 2A receptor. They found that in addition to the OBP, some, but not all, compounds also nestle into a nearby second cavity, the extended binding pocket (EBP).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hXa1PP">
Next, they dosed mice with each of the drugs. In mice, head twitching is taken as the sign of a trip, while increasing the amount of time they struggle to stay afloat in a cylinder of water before simply allowing themselves to drown is the sign of antidepressant effects (this is known as the forced swimming test, and we <a href="https://www.the-scientist.com/news-opinion/forced-swim-test-criticized-as-uninformative--cruel-66184">should stop doing it</a>). Wang and colleagues learned that drugs slotting into the EBP show hallucinatory effects, while drugs that only fit into the OBP — like serotonin — display only antidepressant effects.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pHXefL">
Armed with that insight, they created new variations of LSD designed to lean away from the EBP, focusing on the OBP. The result, at least in mice, was two relatives of LSD that achieved the hoped-for result: no head twitching, but more time spent keeping afloat in the depression tank; in other words, like Delix’s MDMA variant, a new potential neuroplastogen.
</p>
<h3 id="N4wtzy">
How much of the therapy will humans lose without the trip?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XzCwJa">
Despite recent advances, jumping from head-twitching and water-treading in mice to carving out psychedelic experiences while still treating depression in humans is a serious leap. “I just find it very implausible that you’ll see full and enduring benefits from psychedelics without the acute subjective effects [or: the trip],” David Yaden, an assistant professor at Johns Hopkins who works in the Center for Psychedelic and Consciousness Research, told me <a href="https://www.vox.com/future-perfect/23721486/ketamine-dmt-lsd-psychedelics-magic-mushrooms-legalization-recreation-psilocybin">earlier this year</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KVnhLG">
In <a href="https://pubs.acs.org/doi/10.1021/acsptsci.0c00194">a 2021 paper</a>, Yaden and his colleague <a href="https://www.nytimes.com/interactive/2023/04/03/magazine/roland-griffiths-interview.html">Roland Griffiths</a> contend that to get the <em>full</em> beneficial effects of psychedelics, the trip is necessary. That’s not exactly controversial: Even Olson, the Delix co-founder, who <a href="https://pubs.acs.org/doi/10.1021/acsptsci.0c00192">published a counterpoint</a> on the same day, agrees. The trip may be “critical for achieving <em>maximal</em> efficacy,” he writes. However, Olson argues that whatever benefits are left over after cutting out the trip can still have value, especially since they may be able to reach wider patient populations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Z7Vh1Q">
How much benefit remains depends on an unsettled question in the world of psychedelic therapy: Is rapidly boosting neuroplasticity, on its own, good treatment? Olson believes so, and there’s some preclinical research in drugs like <a href="https://pubs.acs.org/doi/10.1021/acsptsci.0c00192">ketamine, MDMA</a>, and <a href="https://www.nature.com/articles/s41586-020-3008-z">ibogaine</a> to back it up. More recently, however, a preprint study reported <a href="https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v1">ketamine was given to subjects under anesthesia</a> (eliminating any associated trip), and found <a href="https://www.science.org/content/article/ketamine-no-better-placebo-alleviating-depression-unusual-trial-finds">no difference from placebo</a>, suggesting that something about having the experience makes a difference.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NRZlPL">
At the University of Wisconsin-Madison, anesthesiology professor Matthew Banks is tinkering with something in between leaving the trip alone and anesthesia: What if you let people have their full-on psychedelic experience, but then erase their memory of the trip altogether? Do you need to remember a trip for the benefits to stick?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xeVwAV">
As part of an eight-person <a href="https://www.wired.com/story/psychedelics-study-design-research-rcts/">pilot study</a> at the university’s <a href="https://research.pharmacy.wisc.edu/tcrps/">Transdisciplinary Center for Research in Psychoactive Substances</a>, participants received both psilocybin and midazolam, an amnesia-inducing drug used to leave conscious experience intact, but wipe away memories (it’s often used to help patients forget about <a href="https://www.giejournal.org/article/S0016-5107(08)02621-7/fulltext#:~:text=A%20combination%20of%20midazolam%20and,studies%20have%20compared%20their%20efficacy.">colonoscopies</a>). “It’s like you’re one of those philosophical zombies. You’re conscious and having conversations, but you have no recollection the next day,” Banks said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="48s1OK">
He explained that getting the dosing right is tricky because psilocybin seems to lay down durable memories, which Banks speculates is due to the elevated neuroplasticity. Once researchers boosted the dose enough to wipe most of the trip from memory, the benefits seemed to have departed, too. “There appears to be something happening where we’re wiping out some of those long-term behavioral effects of the drug,” Banks said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TdHUcG">
In part, this was likely because participants were healthy volunteers, not patients suffering from conditions like treatment-resistant depression. Since neuroplastogens are imagined as therapies, the amnesia study doesn’t tell us much about their fate in treating mental illness. While Banks admitted that successful preclinical studies in mice “open the possibility that all the hallucinogenic stuff is largely irrelevant” for therapeutic outcomes, he believes that “it really does matter what you actually do with all that plasticity.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dXDtYq">
If neuroplastogens become take-at-home pills, then they do away with both parts of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226617/">psychedelic therapy</a>: the psychedelic experience, and the therapy itself. Robin Carhart-Harris, a professor of neurology at the University of California, San Francisco, pointed out <a href="https://www.nytimes.com/2022/07/15/opinion/hallucinations-psychedelics-depression.html">to the New York Times</a> last year that plasticity is just a greater capacity to be reshaped. Whether for better or worse may depend on what happens after you take the drug. Pairing trips with therapy helps guide the plasticity towards beneficial outcomes. Without the trip, Carhart-Harris said in the Times, the result could be underwhelming: a drug that creates “a little bit of plasticity but it’s not really transformative.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LvqfIJ">
However, just because neuroplastogens are entirely unlike psychedelic therapy doesn’t mean they can’t still offer their own benefits. Instead of using plasticity to reprogram a particular habit, let alone <a href="https://www.nature.com/articles/s41598-021-01209-2">altering one’s metaphysical view</a> of the universe, Rus described how they may help repair the neuronal wear and tear associated with everything from chronic stress to neurodegenerative diseases such as Alzheimer’s. Sustained stress can grind away at neurons and affect brain connectivity, especially in key regions such as <a href="https://journals.sagepub.com/doi/10.1177/24705470211029254">the prefrontal cortex</a>. Simply spiking neuroplasticity may help repair the worn neurons, and bring those dampened networks of connectivity back online.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FRnDU3">
“What these new psychoplastogens are really good at doing is rapidly regrowing those spines [which connect neurons] and restoring circuit-level connectivity. The degree to which that repaired connectivity results in the behavioral changes or feelings that one seeks, time and data will ultimately tell,” Rus said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1mtL9g">
No one believes current-generation antidepressants — SSRIs such as Prozac and Lexapro — are the pinnacle of depression treatments. In the space between Prozac and psychedelic therapy, there’s plenty of room for middling treatments that improve upon what we have now, but fall short of the transformative trips one might have on psychedelics.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BvACpB">
Human trials will tell whether neuroplastogens may find a place in the cultural medicine cabinet. But these are just one category among hundreds of thousands of potential new psychedelic-inspired drugs that await discovery now that research is back online. Our single-digit list of psychoactive compounds is already transforming minds and industries alike. As that inventory expands, we may discover that the psychedelics we’re familiar with were only the modest beginnings of what will come next.
</p></li>
<li><strong>Why you feel grouchy on super hot days</strong> -
<figure>
<img alt="A cartoon drawing of three people walking through an urban park on a sunny day. A woman carrying a small backpack sweats with her hand on her head. A man looks disgruntled and sweats while holding a grocery bag. A woman in sunglasses fans herself under a tree." src="https://cdn.vox-cdn.com/thumbor/UpbFpePi413ON5RTPrQBIiWdWjE=/899x0:5843x3708/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72481141/GettyImages_1456882589.0.jpg"/>
<figcaption>
Getty Images/iStockphoto
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
What we know — and what we don’t — about how heat affects mental health.
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Extreme heat impacts everything it touches — <a href="https://www.vox.com/climate/2023/7/21/23799004/invisible-consequences-extreme-heat-physical-mental-health">the body</a>, <a href="https://www.washingtonpost.com/climate-environment/2022/07/20/heat-wave-road-railway-buckling/">infrastructure</a>, <a href="https://cropwatch.unl.edu/2016/impacts-extreme-heat-stress-and-increased-soil-temperature-plant-growth-and-development">plant life</a> — and even things it doesn’t. It’s hard to ignore the physical sensations of discomfort and sweat on a hot day, but high temperatures can have a negative effect on <a href="https://www.vox.com/mental-health">mental health</a>, too. Given the <a href="https://www.nytimes.com/2023/07/15/us/heat-wave-weather-numbers-records.html">record-breaking heat</a> bearing down on the US, <a href="https://abcnews.go.com/International/european-heat-wave-breaking-records-relief-sight/story?id=101493619">Europe</a>, <a href="https://www.reuters.com/world/china/chinese-tourists-brave-scorching-heat-see-flaming-mountains-2023-07-19/">China</a>, and <a href="https://nymag.com/intelligencer/article/worldwide-heat-wave-numbers.html">Iran</a>, millions of people may be feeling a change in their mood.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ncTXEc">
While <a href="https://www.sciencedirect.com/science/article/abs/pii/S0013935119303433">studying heat waves and mortality in India</a> as a Fulbright fellow, <a href="https://www.bu.edu/sph/profile/amruta-nori-sarma/">Amruta Nori-Sarma</a>, now an assistant professor in the department of environmental health at the Boston University School of Public Health, realized how much science didn’t understand about the health impacts of extreme heat. Although she was specifically looking to identify heat-related deaths, Nori-Sarma was interested in the health issues that might lead to mortality during extreme heat events. “We know a lot about the physical health impacts of extreme heat,” she says, “but what about the mental health impacts?”
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In 2022, Nori-Sarma and her colleagues published <a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2789481">a study</a> examining the association between heat and mental health-related emergency room visits among US adults. During the hottest days of the summer, more people went to the emergency room for mental health conditions like substance use disorders, mood and anxiety disorders, stress disorders, other behavioral disorders, and more.
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How can people care for their mental health on an ever-warming planet? There are few answers, but Nori-Sarma hopes further research will help illuminate who is most vulnerable to heat-related mental distress and how mental health clinicians can best care for patients when it’s hot.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Dc933G">
This interview has been edited and condensed for clarity.<em> </em>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V8vceZ">
<strong>Could you explain the results of your emergency room visit study?</strong>
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We used a database of commercial health insurance claims across the US to look at adults who were visiting the emergency department between 2010 and 2019 during the summers. The effort was to try and get at this question: What are the different types of mental health outcomes that people experienced because of extreme heat exposure? So in that study, we were comparing the four or five hottest days of each summer to the coolest days of the summer. We saw elevated rates of emergency department visits very broadly across all mental health outcomes. But specifically, we did see elevated rates of emergency department visits for a variety of specific outcomes, including things like substance use disorders, mood [and] anxiety disorders, stress disorders, schizophrenia, self-harm, as well as childhood-onset personality and behavioral disorders.
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We saw increased rates of emergency department visits pretty uniformly between men and women, and also pretty uniformly across age groups, which was really interesting. So even younger adults that we might think would be more healthy in the face of these extreme weather events experience greater need for emergency care for mental health issues during heat. One of the other things that I thought was really interesting in this study is that we actually saw higher rates of emergency department visits during summertime heat periods in the northern parts of the US compared to the southern parts of the US, which is kind of counterintuitive, because it’s hotter in the southern US. What that speaks to is maybe there are adaptive measures that are already put in place for communities in the southern US that experience hotter summers — things like air conditioning in homes, for example.
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<strong>What is going on to cause these mental health issues?</strong>
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In this current study, we weren’t able to assess at an individual level because all we have is the insurance claims data. We are not able to dig more deeply into the biological mechanisms. But we have a couple of theories.
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One that I think is probably the most prevalent is the way that extreme heat disrupts sleep. When it’s hot outside, it’s more difficult to sleep, you’re more uncomfortable. If you’re living in a place where you don’t have access to air conditioning, that might further disrupt your sleep. The reason why I think this is plausible is because all of these different health outcomes that I mentioned earlier are so different from each other. There’s not a strong biological pathway that leads to all of these different outcomes. Substance use disorder is very different from mood anxiety disorders is very different from schizophrenia. The fact that we see similar increases in the rates of emergency department visits for all of these different health endpoints indicates to me that heat is an external stressor that’s somehow exacerbating people’s existing symptoms.
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<strong>Does heat impact our everyday mood, or does it seem to have the greatest effect on people who already have some of these conditions, like anxiety or schizophrenia?</strong>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KMhGcO">
That’s a good question and another one that’s really difficult to answer with the data that we have, because these are emergency department visits, these are some of the most extreme presentations that people will have in terms of their outcomes. But I think it’s entirely likely that heat is impacting your day-to-day mood. If you have extreme heat, it makes it more difficult to cope with other stressors. If we can catch people when they’re just irritated or anxious, then we might be able to prevent, down the line, an extreme <a href="https://www.vox.com/health-care">health care</a> need.
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<strong>What should individuals keep in mind as they care for their mental health in this time of unprecedented heat?</strong>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Th25Gq">
One of the things that’s really important is <a href="https://www.vox.com/even-better/23800261/tips-extreme-heat-heatwave">feeling like you’re prepared</a> in case an extreme heat period happens — so knowing what resources are available to you. Cities, like Boston, have cooling centers, in case you’re caught in a location where there’s not good cooling during an extreme heat period. Not spending a lot of time outdoors in the sun or, if we have to, making sure we’re hydrated.
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The other thing that I think is really important is relying on our social networks. It’s about checking in with ourselves, but also checking in on your friends and family, checking in on your neighbors, making sure that the people around you know what resources are available and are being taken care of during periods of extreme heat.
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<strong>You mentioned that gender and age didn’t impact the rate of emergency room visits in your study. But are there any other factors that might make somebody more vulnerable for heat-related mental distress?</strong>
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Yes. The study that we conducted with this dataset has led to a lot of additional questions that we can answer, but we only have access to commercial insurance beneficiaries. What about people who are on public insurance? Or what about people who don’t have health insurance? How are those folks coping with extreme heat? This is really important. This is a next step for our research. This is one of the most vulnerable populations: people who are of low socio-economic means who may be leveraging emergency departments as a front line for their health care needs, because that’s the best access to care that they have.
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Other than that, diving more deeply into people who are receiving different forms of treatment for their ongoing mental health conditions and how that might be impacting both their experience of extreme heat and also their mental health conditions. That’s another really important, vulnerable population that we need to focus on. There’s medications that affect our body’s ability to thermoregulate. Anti-schizophrenia medications are ones that come to mind. People who have schizophrenia and who are taking medication for it might have a reduced ability for their own body to thermoregulate. That’s why sometimes you see people in extreme heat who are wearing layers and layers of jackets and clothing. It’s because their body has lost the ability to thermoregulate due to the medication usage.
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<strong>How does summer seasonal affective disorder (SAD) differ from winter SAD?</strong>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fON50a">
I’m not as familiar with wintertime seasonal affective disorder. My understanding of SAD during the winter is that it’s very much correlated with the number of daylight hours that we have and the body’s ability to hormonally regulate and cope with reduced periods of daylight. I think that seasonal affective disorder in the summer is more correlated with the overwhelming nature of the heat exposure. Even if people are able to be out in the daylight for longer periods during the summer, the fact that it seems more difficult to do that if it’s extremely hot outside and you’re limited to an air-conditioned space, I think that’s the mechanism for summertime disorders.
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<strong>Is there anything you find surprising or misunderstood about heat and how it affects our mental health?</strong>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DLtjqj">
A thing that people don’t tend to think about as much is that a lot of people right now, and especially a lot of young people, are already facing additional levels of <a href="https://www.vox.com/even-better/23778284/tips-cope-climate-anxiety">anxiety and stress around climate change</a>. Having that baseline level of anxiety already elevated because you’re anticipating future events is also a problem. It might limit our ability to cope as these events are occurring. It might reduce our resilience in the face of future summertime extremes. One of the things that I’m really interested in is what are the ways in which this anticipation of ongoing climate change is also impacting people’s need for emergency care or other types of health care.
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<strong>What other questions do you want to answer in your research?</strong>
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We’re working on the question of who are the most vulnerable in society and trying to see what resources we have to understand the impact of extreme heat exposures on people who experience homelessness or housing insecurity, people who don’t have access to health insurance, people who are repeat visitors for psychiatric emergency services. We’re doing that on a smaller scale in the greater Boston area.
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The other thing that I think is a really important factor is what role do clinicians play in keeping their patients safe. Are clinicians aware of the elevated need for emergency care during extreme heat waves? What can we do to support clinicians so that they’re understanding the impact that climate and extreme heat are having on their patients? We’re starting by talking with the clinicians. The translation of our results would be seeing more patients in the emergency department when it’s hot. Do physicians experience that? And if they do, what are the things that they are noticing about their patients when they’re coming in for emergency department visits? We can get their perspective on what are the manifestations of these different mental health outcomes during extreme heat. When do we see them? And how can we provide better services for people in advance?
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<li><strong>Carlee Russell: A missing Black woman and a social media frenzy, explained</strong> -
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<img alt="Carlee Russell, seated cross-legged on a woven deck chair, wears a formal light pink dress and a pearl necklace." src="https://cdn.vox-cdn.com/thumbor/f7rDPqOYoRnl6HYBJqAwTDxer-k=/0x0:2048x1536/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72474644/carleerussell.0.jpeg"/>
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Carlee Russell. | Hoover Police Department
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What the viral story of a missing Alabama woman says about all of us.
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From the beginning, the <a href="https://www.nytimes.com/2023/07/15/us/alabama-missing-woman.html">details of Carlee Russell’s disappearance seemed destined to cause an internet frenzy</a>: Russell, a Black 25-year-old nursing student, went missing from the side of a highway in Hoover, Alabama, on the night of July 13, shortly after calling 911 to report a child wandering alone on the side of the highway.
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Russell’s brother’s girlfriend, on the phone with her following her 911 call, <a href="https://www.nytimes.com/2023/07/15/us/alabama-missing-woman.html">reported hearing</a> Carlee scream and what sounded like the phone being dropped. When the police reached Carlee’s car just a few minutes after her 911 call, they found her phone and wig nearby, along with her purse and the food she’d just picked up for dinner inside of her car. Neither Russell nor a toddler was anywhere to be found.
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Less than two weeks later, after her return and a story police said they couldn’t confirm, an attorney speaking for Russell admitted there was no kidnapping: “My client apologizes for her actions to this community,” Russell’s attorney said in a press conference on Monday. “We ask for your prayers for Carlee as she addresses her issues and attempts to move forward, understanding she made a mistake in this matter.” The attorney confirmed that they are in touch with the local district attorney’s office about possible charges against Russell in the case.
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In the days after her disappearance, Russell<strong> </strong><a href="https://www.google.com/search?q=carlee+russell++tiktok&amp;rlz=1C1GGRV_enUS748US748&amp;ei=pMq6ZOnTO5Wo5NoPvsWnYA&amp;ved=0ahUKEwjpte-0s6CAAxUVFFkFHb7iCQwQ4dUDCBA&amp;uact=5&amp;oq=carlee+russell++tiktok&amp;gs_lp=Egxnd3Mtd2l6LXNlcnAiFmNhcmxlZSBydXNzZWxsICB0aWt0b2syCxAAGIAEGLEDGIMBMggQABiKBRiGA0jwG1COGliOGnAEeACQAQCYAU6gAU6qAQExuAEDyAEA-AEBwgIIEAAYogQYsAPiAwQYASBBiAYBkAYC&amp;sclient=gws-wiz-serp">went viral on TikTok</a> and <a href="https://twitter.com/search?q=carlee%20russell&amp;src=typeahead_click">other social media platforms</a>, and received <a href="https://www.cnn.com/2023/07/14/us/carlee-russell-missing-alabama/index.html">national media attention</a> as law enforcement agencies searched for her. The chilling details surrounding her disappearance — and the prospect that a child was used to lure her into danger — likely contributed to it going viral: Fears about human trafficking and abduction have <a href="https://www.vox.com/culture/23794355/sound-of-freedom-controversy-true-story-qanon">become a bigger part of the national conversation</a> in recent years.
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But then, 49 hours after she went missing, Russell showed up at the doorstep of her family home. Everyone who’d been following the case had a lot of questions. So, apparently, did the police.
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In a <a href="https://www.facebook.com/HooverPD/videos/848612810031212/">news conference on July 19</a>, Hoover Police Chief Nick Derzis revealed that detectives had been unable to verify many of the things that Russell had told investigators in the brief interview she gave them following her return.
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According to Derzis, Russell said that after calling 911, a man emerged from the trees near the highway to say he was checking on the child. She then said the man forced her into a car, and “the next thing she remembers is being in the trailer of an 18-wheeler,” <a href="https://www.cnn.com/2023/07/19/us/what-we-know-carlee-russell-alabama/index.html">said</a> Derzis. Russell said that the man who kidnapped her had orange hair with a bald spot, and that she heard the voice of a woman who was with him but never saw her face.
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At one point, she said, she managed to escape from the trailer, but was recaptured and taken to a house where she was forced to undress and be photographed. After being put in another vehicle, Russell said she escaped again, and was able to make it to her home by running through the woods.
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Derzis <a href="https://www.cbsnews.com/news/carlee-russell-timeline-alabama-woman-missing-found/">shared some other details</a> that seemed to cast doubt on Russell’s story. Video footage showed Russell <a href="https://www.npr.org/2023/07/19/1188663432/police-still-have-no-proof-of-a-missing-toddler-after-carlee-russell-returns-hom">leaving the spa</a> she worked at the day of her disappearance reportedly concealing a bathrobe, toilet paper, and other items. Those items, as well as the snacks she purchased from Target shortly before her disappearance, were missing, despite her purse and other belongings being left with the vehicle.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4f4xE1">
Derzis also noted that Russell drove 600 yards while on the phone with 911 saying she was watching the child, and police said they received no other reports of a toddler walking alone. (Video footage on the highway <a href="https://www.youtube.com/watch?v=nBphRpVRN5o">appears to show</a> only one figure, Russell, on the side of the road.) “To think that a toddler, barefoot, that could be 3 or 4 years old, could travel six football fields without getting in the roadway, without crying, it’s very hard for me to understand,” Derzis <a href="https://www.cbsnews.com/news/carlee-russell-disappearance-police-havent-found-evidence-of-toddler-on-alabama-highway/">said</a>.
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Then there were the <a href="https://www.nbcnews.com/news/us-news/cops-havent-verified-carlee-russell-story-says-nude-photos-taken-missi-rcna95065">internet searches</a> on Russell’s mobile phone: In the days before her arrest, Derzis said, Russell was searching for information about one-way bus tickets and how to take money from a cash register without getting caught. She also looked into whether someone had to pay for an <a href="https://amberalert.ojp.gov/">Amber Alert</a> — a government program that helps alert communities when children are missing. On the day she went missing, Russell apparently searched for the movie <em>Taken</em>, <a href="https://www.imdb.com/title/tt0936501/">a 2008 thriller</a> in which Liam Neeson plays a dad who hunts down human traffickers who kidnapped his teenage daughter and her best friend.
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“I do think it’s highly unusual … on the day someone gets kidnapped … that they’re searching the internet, Googling the movie <em>Taken</em>, about an abduction. I find that very strange,” Derzis said.
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<h3 id="6wFVHq">
Why the Carlee Russell story took off and what the social media response about it says
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He didn’t come right out and say it, but the subtext seemed clear: Police had serious<strong> </strong>doubts about Russell’s story.
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And just as quickly as social media users rushed to share concern for Russell and the details about her disappearance, so too did they rush to offer their opinions on the latest developments.
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Some <a href="https://www.tiktok.com/@_bernardtaylor/video/7257642677503069486">criticized Russell for perpetrating what appeared to be a hoax</a> and argued that her story would make it harder for people to believe families when other Black women go missing.
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Others condemned the rush to judgment, noting that Russell <a href="https://twitter.com/blackgirlinmain/status/1681764605171847170">could have mental health issues</a> that the public isn’t aware of and pointing out that <a href="https://twitter.com/marclamonthill/status/1681829381361086464">missing Black women rarely receive the same amount of media attention</a> white women do. A few said they were just <a href="https://twitter.com/search?q=carlee%2C%20happy%20she%27s%20home&amp;src=typed_query&amp;f=live">happy Russell was home</a>, regardless of what happened.
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There’s still much about Russell’s story we don’t know, and certain things we may never understand, including the state of Russell’s mental health. But if<strong> </strong>past prosecutions of <a href="https://www.nytimes.com/2022/09/19/us/sherri-papini-kidnapping-hoax-sentence.html">women</a> <a href="https://abc7chicago.com/chloe-stein-missing-person-fake-kidnapping/13215813/">who staged their own</a> <a href="https://www.jacksonville.com/story/news/2019/09/16/quinn-gray-saga-story-behind-ponte-vedra-housewife-who-faked-her-own-kidnapping/984758007/">disappearances</a> are any indication, police will likely be unsympathetic if they think they have strong evidence that she fabricated her disappearance.<strong> </strong>
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When a story about a possible crime sparks national attention to the extent this one did, it doesn’t happen in a vacuum. The reactions are informed not only by the facts of the case, but filtered through broader contexts that exist outside the particulars of the incident. And those responses can tell us a lot about the culture in which we live.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="csoj12">
The public concern about Russell’s case was driven in part by the understanding that <a href="https://www.nytimes.com/2021/09/22/business/media/gabby-petito-missing-white-woman-syndrome.html">Black women rarely receive the same amount of attention that white women</a> get when they go missing. It was also driven by the frightening details around her disappearance, including the reports of a lost child. America has been consumed by a<a href="https://www.theatlantic.com/magazine/archive/2022/01/children-sex-trafficking-conspiracy-epidemic/620845/"> moral panic about the idea of human traffickers lurking in the shadows</a>, ready to kidnap unsuspecting women and children and sell them into sexual slavery.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cCXXvm">
The outsize fear is driven by <a href="https://www.nytimes.com/2020/08/12/technology/qanon-save-the-children-trafficking.html">internet conspiracy theories and misinformation</a>, <a href="https://www.washingtonpost.com/dc-md-va/interactive/2021/wayfair-qanon-sex-trafficking-conspiracy/">social media</a>, <a href="https://www.nytimes.com/2023/07/19/us/politics/trump-sound-of-freedom.html">politicians, and pop culture</a>. But the reality is that the people most at risk of human trafficking are <a href="https://humantraffickinghotline.org/en/human-trafficking#:~:text=Who%20is%20Vulnerable%3F,a%20runaway%20or%20homeless%20youth.">those who are already vulnerable because they live at the margins of society</a>, sometimes as children in the foster care system, or as undocumented immigrants, or as people struggling with addiction or homelessness. They are often forgotten because the authorities <a href="https://nij.ojp.gov/topics/articles/federally-backed-human-trafficking-task-force-model-yields-progress#:~:text=They%20include%20victim%20identification%20challenges,both%20sex%20and%20labor%20trafficking.">don’t always identify them as victims</a>.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nRAFwt">
And in this case, it seems clear that while our culture is <a href="https://www.vox.com/culture/23619617/delphi-murders-updates-reddit-true-crime">obsessed</a> with salacious-sounding crimes, we’re also, whatever the truth of this case turns out to be, <a href="https://www.vox.com/22979866/bad-vegan-netflix-inventing-anna-dropout-scammer">deeply fascinated by the idea of scam artists</a>.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jRpWiB">
There are, unfortunately, countless real stories of missing Black women and children, like Relisha Rudd, <a href="https://www.npr.org/podcasts/959614430/through-the-cracks">an 8-year-old who went missing in Washington, DC, in 2014 and still hasn’t been found</a>. As the Black and Missing Foundation <a href="https://www.blackandmissinginc.com/black-and-missing-foundation-statement-on-the-carlethia-carlee-russell-investigation/">stated this week</a>: “We must remain vigilant and not lose sight of the bigger picture while we await additional information.” For years, the foundation “has been sounding the alarm on the plight of missing Black and Brown people, from around the country, and their stories rarely go viral … Let’s keep hope alive for these families and channel our efforts to bringing them home.”
</p>
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The public, and <a href="https://www.vox.com/media">the media</a>, will likely move on from Russell’s story soon. Finding Rudd, and other missing children and adults, remains just as urgent as it was before social media discovered the Russell case, and will remain just as important once it moves on.
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<em><strong>Update, July 24, 6 pm ET: </strong></em><em>This story was originally published on July 22 and has been updated with a new statement from Russell’s attorney.</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>Vinesh, Bajrang could be withdrawn from Asian Games squad if they lose Worlds trials: Ad-hoc panel member</strong> - IOA ad-hoc panel then decided to conduct trials but exempted both Punia and Phogat, triggering angry reactions from the wrestling fraternity, which alleged bias in the decision.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>No. 2 seed Adrian Mannarino wins at Newport, ending great week for American Alex Michelsen</strong> - Second-seeded Adrian Mannarino defeated teenager Alex Michelsen, 6-2, 6-4, to win the Hall of Fame Open final on Sunday</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Morning Digest | Home Minister Amit Shah tells Lok Sabha that government is ready for discussion on Manipur; government approves 8.15% interest rate for PF deposits, and more</strong> - Here is a select list of stories to start the day</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 men’s and women’s hockey teams aim to excel in Spain</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>Saudi Arabian football team Al-Hilal makes world record $332 million bid for France striker Kylian Mbappe</strong> - Saudi Arabian soccer team Al-Hilal has made a record $332 million bid for France striker Kylian Mbappe after missing out on Lionel Messi</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>Bhatti launches selfie with ‘Free power Signature’ to counter BRS’s claims</strong> - Congress leaders to take selfies at all irrigation and infrastructure projects to show people what they did for the State</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Karnataka CM Siddaramaiah suspends engineer for leaking ceiling in Haveri district hospital</strong> - Patients in the children and maternity wards were being treated under a leaking ceiling</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>Data | In Telangana, districts near capital have flourished, while those in periphery lag behind</strong> - An analysis of eight socio­economic indicators shows a deep divide in development between core districts and periphery areas</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 Christian ashram in Rajasthan recalls how Oommen Chandy saved it from allegation of proselytising</strong> - Former Kerala Chief Minister’s prompt intervention during a quandary ensured the functioning of the ashram</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 and written by Nalme Nachiyar.</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>Rhodes wildfires are ‘like a biblical catastrophe’</strong> - As tourists evacuate, the wildfires have come at great personal cost to the Greek island’s residents.</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>Estonia sinking: Ramp from ferry wreck raised after 29 years</strong> - Survivors hope a new inquiry will give a definitive explanation of why the ship went down in 1994.</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>Paris to bring back swimming in Seine after 100 years</strong> - Banned for a century because of filthy water, bathing is to resume in parts of the river.</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>Kylian Mbappe: Al-Hilal make £259m offer for PSG and France forward</strong> - Saudi Arabian side Al-Hilal are given permission to speak to Kylian Mbappe after making a world record £259m bid for the Paris St-Germain forward.</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>Denmark Quran burning: Muslim nations condemn far right group’s action</strong> - Crowds in Iraq and Yemen protest against the acts of a far-right group in Copenhagen.</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>Borax is the new Tide Pods and poison control experts are facepalming</strong> - Borax is used in laundry detergent and is not safe to ingest. - <a href="https://arstechnica.com/?p=1956311">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SpaceX teases another application for Starship</strong> - “SpaceX could itself become a large commercial LEO destination.” - <a href="https://arstechnica.com/?p=1956125">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>After bopping an asteroid 3 years ago, NASA will finally see the results</strong> - “Every sample here has a story to tell.” - <a href="https://arstechnica.com/?p=1956175">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Jury orders Google to pay $339M for patent-infringing Chromecast</strong> - Google plans on appealing. - <a href="https://arstechnica.com/?p=1956208">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ChatGPT’s new personalization feature could save users a lot of time</strong> - Beta feature allows ChatGPT to remember key details with less prompt repetition. - <a href="https://arstechnica.com/?p=1956160">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 young couple felt they were having sex too often, so they visited Father O’Reilly for some counseling.</strong> - <!-- SC_OFF --></p>
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The priest recommended they take a vow to not have sex for a year, and the couple reluctantly agreed.
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Eleven months later, the couple visited Father O’Reilly again.
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“Father,” said the wife, “you need to throw us out of the church. We broke our vow of celibacy.”
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“What happened?” asked the priest.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well,” explained the husband, “my wife dropped a dime on the floor. When she bent down to pick it up, I saw a tiny part of her butt cheek. It turned me on so much that I couldn’t stand it any longer. I threw her on the floor and had sex with her right then and there.”
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“Oh, I see.” Said the priest. “You did break your vow a month early. But you are a married couple and you were celibate a long time. Why do you think I should throw you out of the church?”
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“I don’t know,” replied the wife, “but they threw us out of Safeway.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Yorkie_Mom_2"> /u/Yorkie_Mom_2 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/158wo7j/a_young_couple_felt_they_were_having_sex_too/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/158wo7j/a_young_couple_felt_they_were_having_sex_too/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man was riding the train across the country when suddenly everything started rocking violently.</strong> - <!-- SC_OFF --></p>
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People were being thrown out of their seats and luggage was flying everywhere. Then, as suddenly as it started, everything is back to the calm, smooth ride he was used to. Everyone sorted themselves out and found seats again.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
When they reach the next stop, the man went forward to the engine car and asked the conductor what had happened. The conductor replied “We hit a lawyer.” The man couldn’t believe it. “You mean hitting a person cause that?!” The conductor looked at him and explained “Well he was in the ditch, but we got him anyways.”
</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/brother_p"> /u/brother_p </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/158scrk/a_man_was_riding_the_train_across_the_country/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/158scrk/a_man_was_riding_the_train_across_the_country/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I tried jabbing a hole in my condom to get my girlfriend pregnant…</strong> - <!-- SC_OFF --></p>
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Now I just need to figure out how to get my dick to stop bleeding
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/ControlSuspicious348"> /u/ControlSuspicious348 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/158tx2w/i_tried_jabbing_a_hole_in_my_condom_to_get_my/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/158tx2w/i_tried_jabbing_a_hole_in_my_condom_to_get_my/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man goes to his friend’s house and knocks on the door.</strong> - <!-- SC_OFF --></p>
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The wife responds and only had a towel on her.
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The man looks at her and says: is your husband here?
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She said: yes, he’s taking a bath.
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The man: I’ll give you $100 if you drop the towel.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wife: you are crazy, I would never do that.
</p>
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The man: I’ll give you $250 if you drop it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wife: I told you no. what do you want?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man: okay, $500!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wife thinks and says: okay but fast.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She drops the towel, and the man gives her the $500 and tells her. Thank you, tell your husband I’ll be back later.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The wife walks in, and the husband asks who it was.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wife: It was John looking for you, but he says he’s coming later.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Husband: oh! did he give you the $500 that he owes me.
</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/elyuma"> /u/elyuma </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/158mih7/a_man_goes_to_his_friends_house_and_knocks_on_the/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/158mih7/a_man_goes_to_his_friends_house_and_knocks_on_the/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man walks into a magic forest and tries to cut down a talking tree. “You can’t cut me down!,” the tree complains, “I’m a talking tree!”</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man responds, “You may be a talking tree, but you will dialogue.”
</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/masterbrand44"> /u/masterbrand44 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/158yn89/a_man_walks_into_a_magic_forest_and_tries_to_cut/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/158yn89/a_man_walks_into_a_magic_forest_and_tries_to_cut/">[comments]</a></span></p></li>
</ul>
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