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<title>12 August, 2023</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Additive Manufacturing Leveraged Microfluidic Setup for Sample to Answer Colorimetric Detection of Pathogens</strong> -
<div>
Colorimetric readout for the detection of infectious diseases is gaining traction at the point of care/need owing to its ease of analysis and interpretation, and integration potential with highly specific Loop-mediated amplification (LAMP) assays. However, coupling colorimetric readout with LAMP is rife with challenges including, rapidity, inter-user variability, colorimetric signal quantification, and user involvement in sequential steps of the LAMP assay, hindering its application. To address these challenges, for the first time, we propose a remotely smartphone-operated automated setup consisting of (i) an additively manufactured microfluidic cartridge, (ii) a portable reflected-light imaging setup with controlled epi-illumination (PRICE) module, and (iii) a control and data analysis module. The microfluidic cartridge facilitates sample collection, lysis, mixing of amplification reagents stored on-chip, and subsequent isothermal heating for initiation of amplification in a novel way by employing tunable elastomeric chambers and auxiliary components (heaters and linear actuators). PRICE offers a new imaging setup that captures the colorimetric change of the amplification media over a plasmonic nanostructured substrate in a controlled and noise-free environment for rapid minute-scale nucleic acid detection. The control and data analysis module employs microprocessors to automate cartridge operation in tandem with the imaging module. The different device components were characterized individually and finally, as a proof of concept, SARS-CoV-2 wild-type RNA was detected with a turnaround time of 13 minutes, showing the clinical feasibility. The suggested automated device can be adopted in future iterations for other detection and molecular assays that require sequential fluid handling steps.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.10.552726v1" target="_blank">Additive Manufacturing Leveraged Microfluidic Setup for Sample to Answer Colorimetric Detection of Pathogens</a>
</div></li>
<li><strong>Pretrainable Geometric Graph Neural Network for Antibody Affinity Maturation</strong> -
<div>
In the realm of antibody therapeutics development, increasing the binding affinity of an antibody to its target antigen is a crucial task. This paper presents GearBind, a pretrainable deep neural network designed to be effective for in silico affinity maturation. Leveraging multi-level geometric message passing alongside contrastive pretraining on protein structural data, GearBind capably models the complex interplay of atom-level interactions within protein complexes, surpassing previous state-of-the-art approaches on SKEMPI v2 in terms of Pearson correlation, mean absolute error (MAE) and root mean square error (RMSE). In silico experiments elucidate that pretraining helps GearBind become sensitive to mutation-induced binding affinity changes and reflective of amino acid substitution tendency. Using an ensemble model based on pretrained GearBind, we successfully optimize the affinity of CR3022 to the spike (S) protein of the SARS-CoV-2 Omicron strain. Our strategy yields a high success rate with up to 17-fold affinity increase. GearBind proves to be an effective tool in narrowing the search space for in vitro antibody affinity maturation, underscoring the utility of geometric deep learning and adept pre-training in macromolecule interaction modeling.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.10.552845v1" target="_blank">Pretrainable Geometric Graph Neural Network for Antibody Affinity Maturation</a>
</div></li>
<li><strong>Waning of post-vaccination neutralizing antibody responses against SARS-CoV-2, a systematic literature review and meta-analysis</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Mass COVID-19 vaccination and the continuous introduction of new viral variants of SARS-CoV-2, especially of Omicron subvariants, has resulted in an increase in the proportion of the population with hybrid immunity at various stages of waning protection. We systematically reviewed waning of post-vaccination neutralizing antibody titers in different immunological settings to investigate potential differences. Methods We searched for studies providing data for post-vaccination neutralizing antibody responses against SARS-CoV-2 in PubMed, bioRxiv, and medRxiv from Dec 15, 2021, to Jan 31, 2023, using keywords related to COVID-19, vaccination, and antibody neutralization. We used random effects meta-regression to estimate the average fold-reduction in post-vaccination neutralizing antibody titers against the Index strain or Omicron BA.1. from month 1 to month 6 post last dose, stratified by vaccination regimen (primary or booster) and infection-naive vs hybrid-immune status. Findings In total, 26 studies reporting longitudinal post-vaccination neutralizing antibody titers were included. Neutralization titers against the Index variant were available from all studies for infection-naive participants, and from nine for hybrid-immune participants. Against Omicron BA.1, nine and eight studies were available for infection-naive and hybrid-immune cohorts, respectively. In infection-naive cohorts, post-vaccination neutralization titers against the Index strain waned 5.1-fold (95% CI 3.4-7.8) from month 1 to month 6 following primary regimen and 3.8-fold (95% CI 2.4-5.9) following the booster. Titers against Omicron BA.1 waned 5.9-fold (95% CI 3.8-9.0) in infection-naive, post-booster cohorts. In hybrid-immune, post-primary vaccination cohorts, titers waned 3.7-fold (95% CI 1.7-7.9) against the Index strain and 5.0-fold (95% CI 1.1-21.8) against Omicron BA.1. Interpretation No obvious differences in waning between post-primary or post-boost vaccination were observed for vaccines used widely to date, nor between infection-naive and hybrid-immune participants. Titers against Omicron BA.1 may wane faster compared to Index titers, which may worsen for more recent Omicron sub-variants and should be monitored. Relatively small datasets limit the precision of our current analysis; further investigation is needed when more data become available. However, based on our current findings, striking differences in waning for the analyzed and future comparisons are unlikely.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.08.23293864v1" target="_blank">Waning of post-vaccination neutralizing antibody responses against SARS-CoV-2, a systematic literature review and meta-analysis</a>
</div></li>
<li><strong>Iterative In Silico Screening for Optimizing Stable Conformation of Anti-SARS-CoV-2 Nanobodies</strong> -
<div>
Abstract–Nanobodies (Nbs or VHHs) are single-domain antibodies (sdAbs) derived from camelid heavy-chain antibodies. The variable region of these nanobodies has special and unique characteristics, such as small size, good tissue penetration, and cost-effective production, making nanobodies a good candidate for the diagnosis and treatment of viruses. Identifying effective nanobodies against the COVID-19 would help us defeat this dangerous virus or other unknown variants in future. Herein, we introduce an in silico screening strategy for optimizing stable conformation of anti-SARS-CoV-2 nanobodies. Firstly, various complexes containing nanobodies were downloaded from the RCSB database, which were identified from immunized llamas. The primary docking between nanobodies and the SARS-CoV-2 spike protein receptor-binding domain was performed through ClusPro program, with the manually screening that leaving the reasonable conformation to the next step. Then, the binding distances of atoms between the antigen-antibody interfaces was measured through the Neighbor Search algorithm. Finally, filtered nanobodies were acquired according to HADDOCK scores through HADDOCK docking the Covid spike protein with nanobodies under restrictions of calculated molecular distance between active residues and antigenic epitopes less than 4.5 A. In this way, those nanobodies which with more reasonable conformation and with stronger neutralizing efficacy were acquired. This three-steps screening strategy iteratively in Silico greatly improved the accuracy of screening desired nanobodies compared to using only ClusPro docking or default HADDOCK docking settings. It provides new ideas for the screening of novel antibodies and computer-aided screening methods.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.09.552633v1" target="_blank">Iterative In Silico Screening for Optimizing Stable Conformation of Anti-SARS-CoV-2 Nanobodies</a>
</div></li>
<li><strong>Development and Analytical Evaluation of a Point-of-Care Electrochemical Biosensor for Rapid and Accurate SARS-CoV-2 Detection</strong> -
<div>
The COVID-19 pandemic has underscored the critical need for rapid and accurate screening and diagnostic methods for potential respiratory viruses. Existing COVID-19 diagnostic approaches face limitations either in terms of turnaround time or accuracy. In this study, we present an electrochemical biosensor that offers nearly instantaneous and precise SARS-CoV-2 detection, suitable for point-of-care and environmental monitoring applications. The biosensor employs a stapled hACE-2 N-terminal alpha helix peptide to functionalize an in-situ grown polypyrrole conductive polymer on a nitrocellulose membrane backbone through a chemical process. We assessed the biosensor's analytical performance using heat-inactivated omicron and delta variants of the SARS-CoV-2 virus in artificial saliva (AS) and nasal swabs (NS) samples diluted in a strong ionic solution. Virus identification was achieved through electrochemical impedance spectroscopy (EIS) and frequency analyses. The assay demonstrated a limit of detection of 40 TCID50/mL, with 95% sensitivity and 100% specificity. Notably, the biosensor exhibited no cross-reactivity when tested against the influenza virus. The entire testing process using the biosensor takes less than a minute. In summary, our biosensor exhibits promising potential in the battle against pandemic respiratory viruses, offering a platform for the creation of rapid, compact, portable, and point-of-care devices capable of multiplexing various viruses. This groundbreaking development has the capacity to significantly bolster our readiness and response to future viral outbreaks.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.08.552470v1" target="_blank">Development and Analytical Evaluation of a Point-of-Care Electrochemical Biosensor for Rapid and Accurate SARS-CoV-2 Detection</a>
</div></li>
<li><strong>Enhanced Deep Convolutional Neural Network for SARS-CoV-2 Variants Classification</strong> -
<div>
High-throughput sequencing techniques and sequence analysis have enabled the taxonomic classification of pathogens present in clinical samples. Sequencing provides an unbiased identification and systematic classification of pathogens and this is generally achieved by comparing novel sequences to pre-existing annotated reference databases. However, this approach is limited by large-scale reference databases which require considerable computational resources and skills to compare against. Alternative robust methods such as machine learning are currently employed in genome sequence analysis and classification, and it can be applied in classifying SARS-CoV-2 variants, whose continued evolution has resulted in the emergence of multiple variants. We developed a deep learning Convolutional Neural Networks-Long Short Term Memory (CNN-LSTM) model to classify dominant SARS-CoV-2 variants (omicron, delta, beta, gamma and alpha) based on gene sequences from the surface glycoprotein (spike gene). We trained and validated the model using &gt; 26,000 SARS-CoV-2 sequences from the GISAID database. The model was evaluated using unseen 3,057 SARS-CoV-2 sequences. The model was compared to existing molecular epidemiology tool, nextclade. Our model achieved an accuracy of 98.55% on training, 99.19% on the validation and 98.41% on the test dataset. Comparing the proposed model to nextclade, the model achieved significant accuracy in classifying SARS-CoV-2 variants from unseen data. Nextclade identified the presence of recombinant strains in the evaluation data, a mechanism that the proposed model did not detect. This study provides an alternative approach to pre-existing methods employed in the classification of SARS-CoV-2 variants. Timely classification will enable effective monitoring and tracking of SARS-CoV-2 variants and inform public health policies in the control and management of the COVID-19 pandemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.09.552643v1" target="_blank">Enhanced Deep Convolutional Neural Network for SARS-CoV-2 Variants Classification</a>
</div></li>
<li><strong>Open-source milligram-scale, four channel, automated protein purification system</strong> -
<div>
Liquid chromatography purification of multiple recombinant proteins, in parallel, could catalyze research and discovery if the processes are fast and approach the robustness of traditional, "one-protein-at-a-time" purification. Here, we report an automated, four channel chromatography platform that we have designed and validated for parallelized protein purification at milligram scales. The device can purify up to four proteins (each with its own single column), has inputs for up to eight buffers or solvents that can be directed to any of the four columns via a network of software-driven valves, and includes an automated fraction collector with ten positions for 1.5 or 5.0 mL collection tubes and four positions for 50 mL collection tubes for each column output. The control software can be accessed either via Python scripting, giving users full access to all steps of the purification process, or via a simple-to-navigate touch screen graphical user interface that does not require knowledge of the command line or any programming language. Using our instrument, we report milligram-scale, parallelized, single-column purification of a panel of mammalian cell expressed coronavirus (SARS-CoV-2, HCoV-229E, HCoV-OC43, HCoV-229E) trimeric Spike and monomeric Receptor Binding Domain (RBD) antigens, and monoclonal antibodies targeting SARS-CoV-2 Spike (S) and Influenza Hemagglutinin (HA). We include a detailed hardware build guide, and have made the controlling software open source, to allow others to build and customize their own protein purifier systems.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.09.552685v1" target="_blank">Open-source milligram-scale, four channel, automated protein purification system</a>
</div></li>
<li><strong>Parental intention, attitudes, beliefs, trust and deliberation towards childhood vaccination in the Netherlands in 2022: Indications of change compared to 2013</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<b>Background and aim</b> Vaccine uptake within the Dutch National Immunisation Programme (NIP) has slightly declined since the COVID-19 pandemic. We studied psychosocial factors of vaccine uptake, namely parental intention, attitudes, beliefs, trust and deliberation (i.e. self-evidence), before (2013) and two years into the pandemic (2022). <b>Methods</b> In 2022 and 2013, parents with a young child (aged &lt;3.5 years) participated in online surveys on vaccination (n=1,000 and 800, (estimated) response=12.2% and 37.2%, respectively). Psychosocial factors were measured on 7-point Likert scales. Multivariate logistic regression analysis was used to study differences between parents in 2022 and 2013 in 9negative9 scores (≤2) of psychosocial factors. <b>Results</b> In both 2022 and 2013, most parents with a young child expressed positive intention (2022=83.1%, 2013=87.0%), attitudes (3 items: 2022=66.7%-70.9%, 2013=62.1%-69.8%) and trust (2022=51.8%, 2013=52.0%) towards the NIP and felt that vaccinating their child was self-evident (2022=57.2%, 2013=67.3%). Compared to parents with a young child in 2013, parents with a young child in 2022 had significantly higher odds of reporting negative attitudes towards vaccination (3 items combined: OR=2.84), believing that vaccinations offer insufficient protection (OR=4.89), that the NIP is not beneficial for the protection of their child9s health (OR=2.23), that vaccinating their child does not necessarily protect the health of other children (OR=2.24) or adults (OR=2.22) and that vaccinations could cause severe side effects (OR=2.20), preferring natural infection over vaccination (OR=3.18) and reporting low trust towards the NIP (OR=1.73). <b>Conclusions</b> Although most parents had positive intention, attitudes and trust towards vaccination and perceived vaccinating their child as self-evident, proportions of parents with negative scores were slightly larger in 2022 compared to 2013. Monitoring these determinants of vaccine uptake and developing appropriate interventions could contribute to sustaining high vaccine uptake.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.24.23291934v2" target="_blank">Parental intention, attitudes, beliefs, trust and deliberation towards childhood vaccination in the Netherlands in 2022: Indications of change compared to 2013</a>
</div></li>
<li><strong>Contact patterns of older adults with and without frailties in the Netherlands during the COVID-19 pandemic</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background During the COVID-19 pandemic social distancing measures were imposed to protect the population from exposure, especially older adults and persons with frailties who have the highest risk for severe outcomes. These restrictions greatly reduced contacts in the general population, but little is known about behaviour changes among older adults and persons with frailties themselves. Our aim was to quantify how COVID-19 measures affected contact behaviour of older adults and how this differed between older adults with and without frailties. Methods In 2021 a contact survey was carried out among persons aged 70 years and older in the Netherlands. A random sample of persons per age group (70-74, 75-79, 80-84, 85-89, 90+) and gender was invited to participate, either during a period with stringent (April 2021) or moderate (October 2021) measures. Participants provided general information on themselves including their frailty, and they reported characteristics of all persons with whom they had face-to-face contact on a given day over the course of a full week. Results In total 720 community-dwelling elderly persons were included (overall response rate of 15%), who reported 16,505 contacts. During the survey period with moderate measures, participants without frailties had significantly more contacts outside their household than participants with frailties. Especially for females, frailty was a more informative predictor for number of contacts than age. During the survey period with stringent measures, participants with and without frailties had significantly lower numbers of contacts compared to the survey period with moderate measures. The reduction of number of contacts was largest for the eldest participants without frailties. As they interact mostly with adults of a similar high age who likely have frailties, this reduction of number of contacts indirectly protects older adults with frailties from SARS-CoV-2 exposure. Conclusions The results of this study reveal that social distancing measures during the COVID-19 pandemic differentially affected the contact patterns of older adults with and without frailties. The reduction of contacts may have led to direct protection of older adults in general but also to indirect protection of older adults with frailties.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.09.23289550v2" target="_blank">Contact patterns of older adults with and without frailties in the Netherlands during the COVID-19 pandemic</a>
</div></li>
<li><strong>An Energizing Role for Motivation in Information-Seeking During the Early Phase of the COVID- 19 Pandemic</strong> -
<div>
Curiosity is a powerful determinant of behavior. The past decade has seen a surge of scientific research on curiosity, an endeavor recently imbibed with urgency by the WHO, which set managing information-seeking as a public health goal during pandemics. And yet, a fundamental aspect of curiosity has remained unresolved: its relationship to utility. Is curiosity a drive towards information simply for the sake of obtaining that information, or is it a rational drive towards optimal learning? We leveraged people’s curiosity about COVID-19 to study information-seeking and learning in a large sample (n=5376) during the spring of 2020. Our findings reveal that curiosity is goal-rational in that it maximizes the personal utility of learning. Personal utility, unlike normative economic utility, is contingent on a person’s motivational state. On the basis of these findings, we explain information-seeking during the pandemic with a rational theoretical framework for curiosity.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/hcta4/" target="_blank">An Energizing Role for Motivation in Information-Seeking During the Early Phase of the COVID- 19 Pandemic</a>
</div></li>
<li><strong>Verification Theatre at Borders and in Pockets</strong> -
<div>
To appear in: Colleen M. Flood, Y.Y. Brandon Chen, Raywat Deonandan, Sam Halabi, and Sophie Thériault (eds.) Pandemics, Public Health, and the Regulation of Borders: Lessons from COVID-19 (Routledge, forthcoming). This version: August 2023. Abstract The COVID-19 pandemic saw the creation of a wide array of digital infrastructures, underpinning both digital and paper systems, for proving attributes such as vaccination, test results or recovery. These systems were hotly debated. Yet this debate often failed to connect their social, technical and legal aspects, focussing on one area to the exclusion of the others. In this paper, I seek to bring them together. I argue that fraud-free “vaccination certificate” systems were a technical and social pipe-dream, but one that was primarily advantageous to organisations wishing to establish and own infrastructure for future ambitions as verification platforms. Furthermore, attempts to include features to ostensibly reduce fraud had, and risks further, broader knock-on effects on local digital infrastructures around the world, particularly in countries with low IT capacities easily captured by large firms and de facto excluded from and by global standardisation processes. The paper further reflects on the role of privacy in these debates, and how privacy, and more specifically confidentiality, was misconstrued as a main design aim of these systems, when the main social problems could manifest even in a system built with state of the art privacy-enhancing technologies. The COVID-19 pandemic should sharpen our senses towards the importance of infrastructures, and more broadly, how to use technologies in societies in crises.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/h24uv/" target="_blank">Verification Theatre at Borders and in Pockets</a>
</div></li>
<li><strong>Transformative Effects of COVID-19 on Healthcare Systems</strong> -
<div>
The global healthcare landscape has undergone an unprecedented metamorphosis due to the COVID-19 pandemic, revealing vulnerabilities, sparking innovation, and necessitating adaptive strategies. This crisis’s impact extends beyond immediate health concerns, influencing healthcare delivery, policy, and infrastructure. Healthcare systems faced overwhelming strain, resulting in improvised medical units and resource allocation shifts. The pandemic prompted the deferral of non-urgent medical procedures, while telehealth integration surged, reshaping patient-doctor interactions. Fragile supply chains underscored the need for enhanced resilience measures. Mental health challenges highlighted the importance of comprehensive care, and healthcare workers exhibited remarkable resilience. Collective efforts accelerated scientific advancements, yielding swift vaccine development. Existing health inequalities were exacerbated, underscoring the urgency of equitable healthcare provision. Policy reforms and global cooperation played pivotal roles. A paradigm shift emerged, emphasizing digital innovation in healthcare. The pandemic’s repercussions underscore the significance of adaptability, collaboration, and ensuring fair access to care.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/8x53a/" target="_blank">Transformative Effects of COVID-19 on Healthcare Systems</a>
</div></li>
<li><strong>Cell cycle regulation of the psoriasis associated gene CCHCR1 by transcription factor E2F1</strong> -
<div>
The coiled-coil alpha-helical rod protein 1 (CCHCR1) was first identified as a candidate gene in psoriasis and has lately been associated with COVID-19 susceptibility. Located within P-bodies and centrosomes, its exact cellular role and transcriptional control remain largely unknown. Here, we showed that CCHCR1 shares a bidirectional promoter with its neighboring gene, TCF19. This bidirectional promoter is activated by the G1/S-regulatory transcription factor E2F1, and both genes are co-induced during the G1/S transition of the cell cycle. A luciferase reporter assay suggests that the short intergenic sequence, only 287 bp in length, is sufficient for the G1/S induction of both genes, but the expression of CCHCR1 is further enhanced by the presence of exon 1 from both TCF19 and CCHCR1. This research uncovers the transcriptional regulation of the CCHCR1 gene, offering new perspectives on its function. These findings contribute to the broader understanding of diseases associated with CCHCR1 and may serve as a foundational step for future research in these vital medical fields.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.08.535951v3" target="_blank">Cell cycle regulation of the psoriasis associated gene CCHCR1 by transcription factor E2F1</a>
</div></li>
<li><strong>In silico thermodynamic evaluation of the effectiveness of RT-LAMP primers to SARS-CoV-2 variants detection</strong> -
<div>
Viral mutations are the primary cause of mismatches in primer-target hybridisation, affecting the sensibility of molecular techniques, potentially leading to detection dropouts. Despite its importance, little is known about the quantitative effect of mismatches in primer-target hybridisation. We use up-to-date and highly detailed thermodynamic model parameters of DNA mismatches to evaluate the sensibility to variants of SARS-CoV-2 RT-LAMP primers. We aligned 18 RT-LAMP primer sets, which were underwent clinical validation, to the genomes of Wuhan strain (ws), 7 variants and 4 subvariants, and calculated hybridisation temperatures allowing up to three consecutive mismatches. We calculate the coverage when the mismatched melting temperature falls by more than 5C in comparison to the matched alignments. If no mismatches are considered, the average coverage found would be 94% for ws, falling the lowest value for Omicron: 84%. However, considering mismatches the coverage is much higher: 97% (ws) to 88% (Omicron). Stabilizing mismatches (higher melting temperatures), account for roughly 1/3 of this increase. The number of primer dropouts increases for new each variant, however the effect is much less severe if mismatches are considered. We suggest using melting temperature calculations to continuously assess the trend of primer dropouts.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.08.552530v1" target="_blank">In silico thermodynamic evaluation of the effectiveness of RT-LAMP primers to SARS-CoV-2 variants detection</a>
</div></li>
<li><strong>Heart-on-a-chip model of immune-induced cardiac dysfunction reveals the involvement of free mitochondrial DNA and therapeutic effects of endothelial exosomes</strong> -
<div>
Cardiovascular disease continues to take more human lives than all cancer combined, prompting the need for improved research models and treatment options. Despite a significant progress in development of mature heart-on-a-chip models of fibrosis and cardiomyopathies starting from induced pluripotent stem cells (iPSCs), human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip system with circulating immune cells to model SARS-CoV-2-induced acute myocarditis. Briefly, we observed hallmarks of COVID-19-induced myocardial inflammation in the heart-on-a-chip model, as the presence of immune cells augmented the expression levels of proinflammatory cytokines, triggered progressive impairment of contractile function and altered intracellular calcium transient activities. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the in vitro heart-on-a-chip model and then validated in COVID-19 patients with low left ventricular ejection fraction (LVEF), demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2 induced myocardial inflammation, we established that administration of human umbilical vein-derived EVs effectively rescued the contractile deficit, normalized intracellular calcium handling, elevated the contraction force and reduced the ccf- mtDNA and chemokine release via TLR-NF-kB signaling axis.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.09.552495v1" target="_blank">Heart-on-a-chip model of immune-induced cardiac dysfunction reveals the involvement of free mitochondrial DNA and therapeutic effects of endothelial exosomes</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 2/3 Study to Evaluate the Safety and Immunogenicity of an (Omicron Subvariant) COVID-19 Vaccine Booster Dose of Previously Vaccinated Participants.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: XBB.1.5 Vaccine (Booster);   Biological: XBB.1.5 Vaccine (single dose)<br/><b>Sponsor</b>:   Novavax<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Dietary Supplement: Freeze-dried Mare Milk (Saumal)<br/><b>Sponsor</b>:   Asfendiyarov Kazakh National Medical University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>EFFECT OF COGNITIVE BEHAVIORAL THERAPY ON DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH POST COVID-19</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Intervention</b>:   Behavioral: rehacom<br/><b>Sponsor</b>:   Cairo University<br/><b>Enrolling by invitation</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>Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly</strong> - <b>Conditions</b>:   Vaccination; Infection;   COVID-19<br/><b>Intervention</b>:   Biological: Comirnaty<br/><b>Sponsor</b>:   Radboud University Medical Center<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 Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: mRNA-CR-04 vaccine 10μg;   Biological: mRNA-CR-04 vaccine 30μg;   Biological: mRNA-CR-04 vaccine 100μg;   Drug: Placebo<br/><b>Sponsor</b>:   GlaxoSmithKline<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine;   Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)<br/><b>Sponsor</b>:   Novavax<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hyperbaric on Pulmonary Functions in Post Covid -19 Patients.</strong> - <b>Condition</b>:   Post COVID-19 Patients<br/><b>Interventions</b>:   Device: hyperbaric oxygen therapy;   Device: breathing exercise;   Drug: medical treatment<br/><b>Sponsor</b>:   Cairo University<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome</strong> - <b>Conditions</b>:   Post-Acute COVID-19 Syndrome;   Fatigue<br/><b>Interventions</b>:   Other: Dietary intervention to mitigate Post-Acute COVID-19 Syndrome;   Other: Attention Control<br/><b>Sponsor</b>:   University of Maryland, Baltimore<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19</strong> - <b>Conditions</b>:   SARS CoV 2 Infection;   Influenza, Human<br/><b>Interventions</b>:   Biological: BIMERVAX;   Biological: SIIV<br/><b>Sponsor</b>:   Hipra Scientific, S.L.U<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>Directed Topical Drug Delivery for Treatment for PASC Hyposmia</strong> - <b>Condition</b>:   Post Acute Sequelae Covid-19 Hyposmia<br/><b>Interventions</b>:   Drug: Beclomethasone;   Other: Placebo;   Device: Microsponge<br/><b>Sponsor</b>:   Duke University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Supported Employment COVID-19 Rapid Testing for PWID</strong> - <b>Condition</b>:   Health Behavior<br/><b>Intervention</b>:   Behavioral: Supported Employment<br/><b>Sponsor</b>:   University of Oregon<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>Telerehabilitation for Post COVID-19 Condition</strong> - <b>Conditions</b>:   Long COVID;   Chronic Fatigue Syndrome<br/><b>Intervention</b>:   Other: Telerehabilitation program based on cardiorespiratory principles<br/><b>Sponsors</b>:   Université de Sherbrooke;   Hotel Dieu Hospital<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>Study of Tixagevimab/Cilgavimab and Regdanvimab Efficacy for Treatment of COVID-19</strong> - <b>Condition</b>:   Coronavirus Infections<br/><b>Interventions</b>:   Drug: tixagevimab/cilgavimab 150+150 mg;   Drug: tixagevimab/cilgavimab 300+300 mg;   Drug: regdanvimab<br/><b>Sponsors</b>:   City Clinical Hospital No.52 of Moscow Healthcare Department;   Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety of Concomitant Administration of Bivalent COVID-19 Vaccines With Influenza Vaccines</strong> - <b>Conditions</b>:   Immune Response;   Safety<br/><b>Interventions</b>:   Biological: bivalent BNT162b2 mRNA original/omicron BA.4-5 vaccine;   Biological: quadrivalent influenza vaccine<br/><b>Sponsors</b>:   Catholic Kwandong University;   Korea University Guro Hospital<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Getting INFORMED and Living Well Among Asian Americans in California</strong> - <b>Conditions</b>:   COVID-19;   Well-Being, Psychological<br/><b>Interventions</b>:   Behavioral: INFORMED-Living Well;   Behavioral: Text Messaging Only<br/><b>Sponsors</b>:   University of California, San Francisco;   Chinese Community Health Resource Center;   University of California, Davis;   University of California, Merced;   California Department of Public Health<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mechanism and antibacterial synergies of poly(Dabco-BBAC) nanoparticles against multi-drug resistant Pseudomonas aeruginosa isolates from human burns</strong> - Multi-drug resistant bacteria are a major problem in the treatment of infectious diseases, such as pneumonia, meningitis, or even coronavirus disease 2019 (COVID-19). Cationic nanopolymers are a new type of antimicrobial agent with high efficiency. We synthesized and characterized cationic polymer based on 1,4-diazabicyclo [2.2.2] octane (DABCO) and Bis (bromoacetyl)cystamine (BBAC), named poly (DABCO-BBAC) nanoparticles(NPs), and produced 150 nm diameter NPs. The antibacterial activity of poly…</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>Targeting RdRp of SARS-CoV-2 with De Novo Molecule Generation</strong> - Viruses are known for their extremely high mutation rates, allowing them to evade both the human immune system and many forms of standard medicine. Despite this, the RNA dependent RNA polymerase (RdRp) of the RNA viruses has been largely conserved, and any significant mutation of this protein is unlikely. The recent COVID-19 pandemic presents a need for therapeutics. We have designed a de novo drug design algorithm that generates strong binding ligands from scratch, based on only the structure…</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>Regadenoson for the treatment of COVID-19: A five case clinical series and mouse studies</strong> - CONCLUSIONS: Infused RA is safe and produces rapid anti-inflammatory effects mediated by A2A adenosine receptors on iNKT cells and possibly in part by A2ARs on other immune cells and platelets. We speculate that iNKT cells are activated by release of injury-induced glycolipid antigens and/or alarmins such as IL-33 derived from virally infected type II epithelial cells which in turn activate iNKT cells and secondarily other immune cells. Adenosine released from hypoxic tissues, or RA infused 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>Shedding light into the biological activity of aminopterin, <em>via</em> molecular structural, docking, and molecular dynamics analyses</strong> - In this study, the structural and anticancer properties of aminopterin, as well as its antiviral characteristics, were elucidated. The preferred conformations of the title molecule were investigated with semiempirical AM1 method, and the obtained the lowest energy conformer was then optimized by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational frequencies of the optimized structure were calculated by the same level of theory and were compared with the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Soluble wild-type ACE2 molecules inhibit newer SARS-CoV-2 variants and are a potential antiviral strategy to mitigate disease severity in COVID-19</strong> - SARS-CoV-2, the virus responsible for COVID-19, has caused havoc around the world. While several COVID-19 vaccines and drugs have been authorised for use, these antiviral drugs remain beyond the reach of most low- and middle-income countries. Rapid viral evolution is reducing the efficacy of vaccines and monoclonal antibodies and contributing to deaths of some fully vaccinated persons. Others with normal immunity may have chosen not be vaccinated and remain at risk if they contract the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In vitro</em> and <em>in vivo</em> effects of <em>Pelargonium sidoides DC.</em> root extract EPs<sup>®</sup> 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2</strong> - The occurrence of immune-evasive SARS-CoV-2 strains emphasizes the importance to search for broad-acting antiviral compounds. Our previous in vitro study showed that Pelargonium sidoides DC. root extract EPs^(®) 7630 has combined antiviral and immunomodulatory properties in SARS-CoV-2-infected human lung cells. Here we assessed in vivo effects of EPs^(®) 7630 in SARS-CoV-2-infected hamsters, and investigated properties of EPs^(®) 7630 and its functionally relevant constituents in context of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Stabilization of RNA G-quadruplexes in the SARS-CoV-2 genome inhibits viral infection via translational suppression</strong> - The G-quadruplex (G4) formed in single-stranded DNAs or RNAs plays a key role in diverse biological processes and is considered as a potential antiviral target. In the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 25 putative G4-forming sequences are predicted; however, the effects of G4-binding ligands on SARS-CoV-2 replication have not been studied in the context of viral infection. In this study, we investigated whether G4-ligands suppressed SARS-CoV-2 replication…</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>Author Correction: Cell-impermeable staurosporine analog targets extracellular kinases to inhibit HSV and SARS-CoV-2</strong> - No abstract</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of Toll-like receptor 4 and Interleukin-1 receptor prevent SARS-CoV-2 mediated kidney injury</strong> - Acute kidney injury (AKI) is a common and severe complication of the coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly affects the glomerular and tubular epithelial cells to induce AKI; however, its pathophysiology remains unclear. Here, we explored the underlying mechanisms and therapeutic targets of renal involvement in COVID-19. We developed an in vitro human kidney cellular model, including immortalized tubular epithelial and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PRO-2000 exhibits SARS-CoV-2 antiviral activity by interfering with spike-heparin binding</strong> - Here, we report on the anti-SARS-CoV-2 activity of PRO-2000, a sulfonated polyanionic compound. In Vero cells infected with the Wuhan, alpha, beta, delta or omicron variant, PRO-2000 displayed EC(50) values of 1.1 μM, 2.4 μM, 1.3 μM, 2.1 μM and 0.11 μM, respectively, and an average selectivity index (i.e. ratio of cytotoxic versus antiviral concentration) of 172. Its anti-SARS-CoV-2 activity was confirmed by virus yield assays in Vero cells, Caco2 cells and A549 cells overexpressing ACE2 and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Diketo acid inhibitors of nsp13 of SARS-CoV-2 block viral replication</strong> - For RNA viruses, RNA helicases have long been recognized to play critical roles during virus replication cycles, facilitating proper folding and replication of viral RNAs, therefore representing an ideal target for drug discovery. SARS-CoV-2 helicase, the non-structural protein 13 (nsp13) is a highly conserved protein among all known coronaviruses, and, at the moment, is one of the most explored viral targets to identify new possible antiviral agents. In the present study, we present six diketo…</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>Heterologous vaccination (ChAdOx1 and BNT162b2) induces a better immune response against the omicron variant than homologous vaccination</strong> - CONCLUSION: In conclusion, our findings suggest that heterologous booster vaccination after primary vaccination produces higher nAb titers and provides a higher level of protection against the omicron variant compared to primary vaccination alone. This protective effect was similar to that observed in patients with severe COVID-19.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Systematic Survey of Reversibly Covalent Dipeptidyl Inhibitors of the SARS-CoV-2 Main Protease</strong> - SARS-CoV-2, the COVID-19 pathogen, relies on its main protease (M^(Pro)) for replication and pathogenesis. M^(Pro) is a demonstrated target for the development of antivirals for SARS-CoV-2. Past studies have systematically explored tripeptidyl inhibitors such as nirmatrelvir as M^(Pro) inhibitors. However, dipeptidyl inhibitors especially those with a spiro residue at their P2 position have not been systematically investigated. In this work, we synthesized about 30 dipeptidyl M^(Pro) inhibitors…</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>Observing inhibition of the SARS-CoV-2 helicase at single-nucleotide resolution</strong> - The genome of SARS-CoV-2 encodes for a helicase (nsp13) that is essential for viral replication and highly conserved across related viruses, making it an attractive antiviral target. Here we use nanopore tweezers, a high-resolution single-molecule technique, to gain detailed insight into how nsp13 turns ATP-hydrolysis into directed motion along nucleic acid strands. We measured nsp13 both as it translocates along single-stranded DNA or unwinds double-stranded DNA. Our data reveal nsp13’s…</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>Greener approach for the isolation of oleanolic acid from <em>Nepeta leucophylla Benth</em>. Its derivatization and their molecular docking as antibacterial and antiviral agents</strong> - In the present study bioactive methanolic extract along with chloroform and hexane extracts obtained from shade dried leaves of the Himalayan aromatic medicinal plant Nepeta leucophylla Benth. Were screened for the presence of triterpenoids, especially oleanolic acid (OA). Total three compounds oleanolic acid, squalene and linoleic methyl ester were isolated from methanol extract. The percentage yield of OA was 0.11%. Out of these three, OA is more bioactive and was further subjected to…</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>2024 Preview: Bidenomics Versus the Trump Freak Show</strong> - The President’s feel-good tour offers a stark contrast to his predecessor’s summer of conspiracies and criminal indictments. But will it work? - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/2024-preview-bidenomics-versus-the-trump-freak-show">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How Ohio Voters Defeated an Effort to Thwart Abortion Rights</strong> - Opponents of the measure capitalized on fears of a Republican power grab. - <a href="https://www.newyorker.com/news/daily-comment/how-ohio-voters-defeated-an-effort-to-thwart-abortion-rights">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The End of Legacy Admissions Could Transform College Access</strong> - After the fall of affirmative action, liberals and conservatives want to eliminate benefits for children of alumni. Could their logic lead to reparations? - <a href="https://www.newyorker.com/news/daily-comment/the-end-of-legacy-admissions-could-transform-college-access">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can “Cop City” Be Stopped at the Ballot Box?</strong> - The fight over a massive police-training complex, set to be built outside Atlanta, has lasted more than two years. Now many people hope the proposal will be put to a vote. - <a href="https://www.newyorker.com/news/letter-from-the-south/can-cop-city-be-stopped-at-the-ballot-box">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Future of Legacy Admissions, and a Conversation with Esmeralda Santiago</strong> - The U.S. Education Secretary, Miguel Cardona, and the contributor Jeannie Suk Gersen on the movement to end legacy admissions. Plus, Santiago speaks with Vinson Cunningham. - <a href="https://www.newyorker.com/podcast/the-new-yorker-radio-hour/the-future-of-legacy-admissions-and-a-conversation-with-esmeralda-santiago">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Publishing scammers are using AI to scale their grifts</strong> -
<figure>
<img alt="A yellow and blue illustration shows a pair of robot hands typing on a typewriter." src="https://cdn.vox-cdn.com/thumbor/J09AlZYQj-LSNzPA1DacM8VFGmQ=/339x0:2776x1828/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72537675/GettyImages_1466243153.0.jpg"/>
<figcaption>
Getty Images/iStockphoto
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Large language models are disrupting the publishing industry, from spam submissions to garbage books.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Sg6JNx">
AI is, in theory, poised to disrupt work as we know it now. But it’s still facing the same problem every buzzy new tech product before it has faced: The VC funding is there, but the long-term business model is not, particularly for individuals. What do you do with a large language model AI at this stage, when all you know for sure is that it will produce text to order, in varying degrees of accuracy?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="s1mqcd">
One fairly straightforward response is to try to sell that text. Preferably, you would want to sell it someplace where it doesn’t matter whether it’s accurate or not, or even where inaccuracy could become fiction and hence valuable: the book market. The book market is also, conveniently, the last textual medium where users are still in the habit of paying directly (even just a tiny bit). Publishing is currently the weak point that bad-faith AI users are trying to infiltrate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="flyoP1">
Legally speaking, you can’t sell AI-generated text, because text generated by machines is not subject to copyright (<a href="https://mashable.com/article/us-copyright-law-ai-generated-content">with some exceptions</a>). Nevertheless, the scammers and grifters who circulate along publishing’s underbelly are integrating AI into their existing scams and grifts. Publishers are reportedly investigating ways of using AI in discreet, closed-door meetings. And authors are on the alert for anything that looks like a smoking gun to take down what many of them believe to be an existential threat to their craft.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dTioyu">
It started in January, when <a href="https://www.theverge.com/2023/2/25/23613752/ai-generated-short-stories-literary-magazines-clarkesworld-science-fiction">science fiction magazines reported</a> that they were being flooded with AI-generated submissions. Editors believed “side hustle” influencers were recommending that their followers use AI to generate short stories and then sell them, apparently under the belief that short story writers pull in big bucks. In December 2022, <a href="http://neil-clarke.com/a-concerning-trend/">explained Clarkesworld editor Neil Clarke</a>, the magazine received 50 fraudulent submissions; in the first half of February 2023, they received almost 350.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="R3yv8o">
By July, the Author’s Guild was becoming concerned. Large language models are trained off large piles of text. A <a href="https://arxiv.org/pdf/2302.13971.pdf">Meta white paper</a> named one popular corpus used to train large language models; that corpus includes text scraped from so-called “<a href="https://www.vice.com/en/article/v7vnn4/shadow-libraries-are-moving-their-pirated-books-to-the-dark-web-after-fed-crackdowns">shadow libraries</a>,” large collections of pirated books. How was that not copyright infringement?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="F1x6c3">
“We understand that many of the books used to develop AI systems originated from notorious piracy websites,” the Author’s Guild wrote in <a href="https://actionnetwork.org/petitions/authors-guild-open-letter-to-generative-ai-leaders">an open letter to the CEOs of various AI companies</a>. “It is only fair that you compensate us for using our writings, without which AI would be banal and extremely limited.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="13gewD">
The letter went on to call for the CEOs to get permission for their use of copyrighted material for AI programming, compensate writers for past and ongoing use of their work in training AI, and compensate them further for the use of their work under AI output.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nfptdu">
The Guild had reason to be concerned. The same kind of side-hustle influencer who advised their audience to start sending AI-generated stories to literary magazines has also begun advising their audience to start selling AI-generated ebooks on Amazon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qgx3Lf">
“Making money with Amazon KDP is a numbers game,” <a href="https://sidehustlescience.org/ai-side-hustles/">advises one such post</a>. “Clever side hustlers can target a particular niche, and leverage AI to produce multiple books quickly while slowly racking in those sweet royalties.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zco6jU">
“Targeting a particular niche” can sometimes get very specific — as specific as, say, “targeting the niche of people interested in a particular author’s books by pretending to be that author.” In August, <a href="https://janefriedman.com/i-would-rather-see-my-books-pirated/">the writer Jane Friedman reported</a> that “garbage books” she’d never seen before were getting sold on Amazon under her name and had been added to her Goodreads profile. The books read, she said, exactly like what ChatGPT spits out when prompted with her name. If it was, that means an AI trained on Friedman’s corpus (without compensating her) was now generating new text to be sold under her name (again without compensating her).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rvrGm8">
“Whoever’s doing this is obviously preying on writers who trust my name and think I’ve actually written these books,” Friedman wrote.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IDvH5Z">
Neither of these schemes is precisely new. There have been “garbage books” for sale on Amazon for a long time: plagiarized books and books with stolen text run through Google Translate a few times and books with straight gobbledygook as the text. It’s not unheard of for those books to have the byline of a legitimate author, all the better to trick unsuspecting readers into buying them. Likewise, people have sent plagiarized submissions to literary magazines for a long time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tlKgHp">
What’s new right now is the scale of the operation. AI makes it easy for scammers and side hustlers to do their work in massive quantities.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OUkuRM">
In July, authors Christopher Golden and Richard Kadrey joined Sarah Silverman in filing <a href="https://www.nytimes.com/2023/07/10/arts/sarah-silverman-lawsuit-openai-meta.html">a class action lawsuit against OpenAI and Meta</a>, alleging that the companies used multiple books, including Silverman’s memoir, as part of their training sets.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Fwk8YG">
Authors, Geraldine Brooks <a href="https://www.semafor.com/newsletter/08/06/2023/new-york-times-is-investigating-its-baghdad-bureau-chief">declared at the Martha’s Vineyard Book Festival this month</a>, “are the ones who should be going on strike.” She was increasingly concerned that none of her contracts had any language in them about AI.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iD2YkG">
It was in the midst of this increasingly agitated atmosphere that the website Prosecraft emerged into the spotlight in early August. A product of software company Shaxpir that went live in 2019, Prosecraft ranks books based on how many words they have, how often they use passive voice, how often they use adjectives, and the vividness of their language. Its database includes analytics for many books already under copyright, although it does not include their text.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="waR75R">
“This company Prosecraft appears to have stolen a lot of books, trained an AI, and are now offering a service based on that data,” <a href="https://twitter.com/harikunzru/status/1688544605325725696">wrote novelist Hari Kunzru</a> on Twitter.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A5rp3o">
Prosecraft doesn’t use AI. It uses an algorithm without any generative AI properties. It’s also not particularly profitable. <a href="https://blog.shaxpir.com/taking-down-prosecraft-io-37e189797121">According to creator Benji Smith</a>, it “has never generated any income.” Still, authors en masse saw it as just more of the same urgent threat they were already facing: a slick tech interface no one asked for, all its value scraped from their own work, without their permission. Facing a virulent outcry on social media, <a href="https://blog.shaxpir.com/taking-down-prosecraft-io-37e189797121">Smith took Prosecraft down</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oiehBn">
Meanwhile, <a href="https://www.nytimes.com/2023/08/02/books/ais-inroads-in-publishing-touch-off-fear-and-creativity.html">the New York Times reports</a> that about 50 companies that actually do use AI to create, package, edit, and market books have launched over the past year. An irony here is that publishing is a business of notoriously low margins, and those margins are getting smaller. <a href="https://authorsguild.org/news/authors-guild-survey-shows-drastic-42-percent-decline-in-authors-earnings-in-last-decade/">A 2018 Authors Guild survey</a> found that the median annual income for authors was $6,080, down from $12,850 in 2007. It also found that only 21 percent of full-time published authors derived 100 percent of their individual income from book-related income, and for those who did, the median income was $20,300.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M0jHeL">
The people who tell our stories are already stretched very, very thin. As a culture, we have spent decades undervaluing their labor, treating writing as a passion project that does not deserve remuneration rather than skilled labor that ought to come with a paycheck.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TsBL6D">
Now, AI has become a powerful tool for grifters to use to try to vacuum up the little money we do award to writers. The side hustle hustles on.
</p></li>
<li><strong>What’s going on with your lightbulbs?</strong> -
<figure>
<img alt="Closeup of the filaments inside a lightbulb." src="https://cdn.vox-cdn.com/thumbor/LfVgJy0M7HmnSU-G6yBUk-6L3zc=/357x0:6081x4293/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72537610/1245076201.0.jpg"/>
<figcaption>
Rolf Vennenbernd/picture alliance via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
No, incandescent lightbulbs aren’t banned.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pJumGd">
Last week, a series of flashy headlines announced the start of a “ban” on incandescent light bulbs — the classic round bulbs you most likely imagine floating above someone’s head when they have a brilliant idea. These pieces <a href="https://thehill.com/policy/energy-environment/4131945-4-things-to-know-as-full-enforcement-of-incandescent-bulb-ban-begins/">offered advice</a> on how to prepare, <a href="https://www.cnn.com/2023/08/01/business/incandescent-light-bulb-ban/index.html">outlined</a> exceptions, and <a href="https://www.cbsnews.com/news/incandescent-bulb-ban-goes-into-effect-led-save-money-environment/">pointed</a> out how the change would save money and the environment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j4ZayI">
Yet, for all the useful and accurate information out there, most of these stories got one essential fact wrong, the experts Vox spoke to agreed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c4rqkz">
“It’s not a ban,” Mark Lien, an industry relations consultant for the nonprofit <a href="https://www.ies.org/">Illuminating Engineering Society</a>, and Andrew deLaski, the executive director of the advocacy organization <a href="https://appliance-standards.org/">Appliance Standards Awareness Project</a>, told Vox in separate conversations. Both went on to describe the incandescent lightbulb-limiting guidelines as an “efficiency standard.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kU0r0l">
The roots of the modern incandescent bulb can be <a href="https://www.energy.gov/articles/history-light-bulb">traced back to the 1800s</a> and, by the <a href="https://americanhistory.si.edu/blog/rural-electrification">1920s</a>, most American homes in urban areas were illuminated with them. But, given incandescents emit light by heating a wire filament until it glows, the average bulb converts around <a href="https://www.mrsec.psu.edu/content/light-bulb-efficiency#:~:text=As%20the%20electrons%20move%2C%20they,90%25%20is%20lost%20as%20heat.">90 percent</a> of the electricity it consumes into heat, not light — meaning they’re not very efficient.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0U7D5t">
In contrast, light-emitting diodes (LEDs) use the electricity fueling them more efficiently. This type of lighting uses a <a href="https://www.energystar.gov/products/lighting_fans/light_bulbs/learn_about_led_bulbs#:~:text=incandescent%20light%20bulbs.-,How%20do%20they%20work%3F,absorbed%20into%20a%20heat%20sink.">microchip</a> and was first developed in the 1960s. It wasn’t until 1994, however, that Nobel Physics honorees Isamu Akasaki, Hiroshi Amano, and Shuji Nakamura <a href="https://www.nobelprize.org/prizes/physics/2014/press-release/">developed</a> a bright blue LED light, which would pave the way for further developments in the space. Today, LEDs exist in a range of colors and brightness levels.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tbem02">
The standard now requires light bulbs to emit at least 45 lumens (a measure of brightness) per watt. An average LED light emits at least <a href="https://www.voltlighting.com/learn/lumens-to-watts-conversion-led-bulb#:~:text=Depending%20on%20the%20bulb%20and,to%20replace%20an%20incandescent%20bulb.">75 lumens per watt</a>, while incandescent bulbs only <a href="https://www.voltlighting.com/learn/lumens-to-watts-conversion-led-bulb">emit 12 to 18 lumens per watt</a> while using more energy. Switching from the classic incandescent to the new-age LEDs may sound like a big change, but, at the end of the day, most consumers probably didn’t notice anything different when the efficiency standard went into effect <a href="https://www.cnn.com/2023/08/01/business/incandescent-light-bulb-ban/index.html">earlier this month.</a>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KlVAHt">
“Most major retailers <a href="https://www.nema.org/analytics/lamp-indices">stopped selling incandescent light bulbs</a> earlier this year,” said deLaski. “Most people didn’t notice, but you really haven’t seen incandescent light bulbs on most store shelves for a long time.”
</p>
<h3 id="HcRBps">
The history of the standard
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sqnWg8">
In 2007, Congress enacted — with President George W. Bush’s signature — the <a href="https://georgewbush-whitehouse.archives.gov/news/releases/2007/12/20071219-1.html">Energy Independence and Security Act</a>, which mandated the phaseout of inefficient bulbs in two stages.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gCfp2X">
The first stage, between 2012 and 2014, <a href="https://www.theverge.com/2014/1/1/5263826/the-incandescent-light-bulb-isnt-dead">required freshly sold bulbs</a> to be about 25 percent more efficient than the market standard at the time. That first year, the <a href="https://www.nationalgeographic.com/environment/article/u-s-phase-out-of-incandescent-light-bulbs-continues-in-2014-with-40-60-watt-varieties">100-watt incandescent bulb</a> had to be taken off the market (businesses were allowed to <a href="https://www.nationalgeographic.com/environment/article/u-s-phase-out-of-incandescent-light-bulbs-continues-in-2014-with-40-60-watt-varieties">sell any remaining inventory</a> but could not buy and sell the bulbs from manufacturers). In 2013, the efficiency regulations booted out the 75-watt incandescent bulb, and by 2014, 40- and 60-watt bulbs were also out, leaving LEDs, and the less popular <a href="https://www.theverge.com/2014/1/1/5263826/the-incandescent-light-bulb-isnt-dead">43, 72, and 150-watt</a> incandescent bulbs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SSbgC5">
“It just happens that the really inefficient lamps can’t meet the efficiency requirements, but they never banned incandescence,” said Lien, who as the director of government-industry relations for lighting manufacturer Osram and a member of the <a href="https://www.nema.org/">National Electrical Manufacturers Association</a> helped develop the future energy efficiency benchmarks in 2015.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8pmIih">
The Department of Energy planned to release the final efficiency standard by the start of 2017. While the department couldn’t do so for <a href="https://thehill.com/policy/energy-environment/4131945-4-things-to-know-as-full-enforcement-of-incandescent-bulb-ban-begins/">bureaucratic reasons</a>, the interim “backstop” standard required that all bulbs had to emit at least 45 lumens per watt, said deLaski. The Trump administration blocked this backstop from taking effect, hence delays in the final phaseout.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="422LF0">
However, in April 2022, President Biden’s Department of Energy <a href="https://www1.eere.energy.gov/buildings/appliance_standards/standards.aspx?productid=4">reinstated the guidelines</a>, saying the backstop was valid. It took a little over a year to push out the final (and current) efficiency standard where any manufactured and sold bulbs must have at least 45 lumens per watt. Since businesses knew since last April the standard would go into effect, they had months to <a href="https://www.cnbc.com/2023/08/02/biden-rule-banning-incandescent-light-bulbs-now-fully-in-effect.html">sell off any inventory</a> that did not meet these guidelines.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L900zX">
A misconception about this regulation and its history is that it was always aimed at cutting incandescents out of the market. In 2007, when the guidelines were first made, there was hope that incandescents, fluorescents, and LEDs could reach and exceed the future efficiency standard, said deLaski.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UgEO8J">
“The standard was set at a level that any of those three technologies could have met it,” deLaski added. As a result, manufacturers invested in all three technologies in what deLaski called a “technological foot race” to create the most efficient bulbs. In the mid-2010s, it became clear that LEDs were far better than their counterparts, he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S3VPJb">
“[Efficiency standards] drive innovation. This is a great story about innovation here that’s kind of been untold,” said deLaski. “When Congress set that standard back in 2007 … it unleashed a wave of investments and innovation on the part of manufacturers to develop that low-cost, high-quality LED that we have on the shelves today.”
</p>
<h3 id="dL86sC">
What the standard does and does not do
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZzK6GQ">
Consumers don’t need to rush to the store to replace any incandescent bulbs currently in use in their homes. The standard only applies to the <a href="https://www.energy.gov/sites/default/files/2022-05/GSL%20Backstop%20Enforcement%20Webinar%20May%204%202022.pdf">sale</a> (not use) of bulbs, and there are some notable exceptions (although President Biden did <a href="https://www.energy.gov/articles/biden-administration-implements-new-cost-saving-energy-efficiency-standards-light-bulbs">expand</a> the scope of the regulation to include more light sources).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xe7l2c">
Types of incandescent lights excluded from the standard <a href="https://www.cnbc.com/2023/08/02/biden-rule-banning-incandescent-light-bulbs-now-fully-in-effect.html">include</a> but are not limited to appliance lamps, black lights, bug lamps, infrared lamps, plant lights, flood lights, reflector lamps, and traffic signals.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iAzEsV">
Overall, the standard is set to save consumers <a href="https://www.energy.gov/articles/biden-administration-implements-new-cost-saving-energy-efficiency-standards-light-bulbs">$3 billion on utility bills annually</a> and cut 222 million metric tons of carbon emissions over the next three decades.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qIkWCW">
Still, some people aren’t happy about the standard. Consumers’ concerns stem from two places, said Lien. There are those that dislike LEDs because “it’s change,” and those who hold a “stigma” against the lights because of the low quality of early models, he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sG29ek">
“LED, it’s turning into a wonderful general light source, it’s evolving to that point, but there are still things that it’s not capable of doing well,” said Lien. For example, while LEDs perform well in <a href="https://sitlersledsupplies.com/leds-perform-well-cold-weather/">cool environments</a>, they don’t perform well in heat, so they can’t be used as oven lights.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="urkUwv">
Misconceptions and fallacies about LED’s propensity to flicker and the unsubstantiated claims that they can be harmful prosper in some circles. “There are still a few people that are just absolutely opposed to LEDs,” said Lien. “And they have some misconceptions about how LEDs give off a tremendous amount of blue light at night that hurts people. Those stories get a lot of attention, but they’re not accurate.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="42qtuu">
These LED haters would <a href="https://nymag.com/strategist/article/led-light-bulbs-investigation.html">appear to be in the minority</a>. While some manufacturers may take issue with the efficiency standard, Lien says at the time the 45-lumen watt standard was set years ago, there was consensus among the major players that this was an achievable benchmark.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cBbIzG">
“I think what’s been misunderstood somewhat is that LEDs were winning in the marketplace, even before this standard took effect,” said deLaski. “And that’s because consumers liked them. They prefer them because they save them money, they provide the same or better light as the bulbs they replace, and they last 10 to 25 times longer.”
</p></li>
<li><strong>The constitutional case that Donald Trump is already banned from being president</strong> -
<figure>
<img alt="Donald Trump Holds A Campaign Rally In Erie, Pennsylvania" src="https://cdn.vox-cdn.com/thumbor/0pEwLEtjgDj0qWh9VivsbLo7eFU=/0x0:3900x2925/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72535947/1563677308.0.jpg"/>
<figcaption>
Trump enters Erie Insurance Arena in Erie, Pennsylvania, on July 29, 2023. | Jeff Swensen/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Two conservative lawyers make a strong 14th Amendment argument. But the politics of their theory are very, very dicey.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QpRAI4">
Two conservative legal scholars, <a href="https://www.nytimes.com/2023/08/10/us/trump-jan-6-insurrection-conservatives.html?utm_source=substack&amp;utm_medium=email">members of the Federalist Society in good standing</a>, have just published <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4532751">an audacious argument</a>: that <a href="https://www.vox.com/donald-trump">Donald Trump</a> is constitutionally prohibited from running for president, and that state election officials have not only the authority but the legal obligation<em> </em>to prevent his name from appearing on the ballot.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="phSV37">
The legal paper, authored by University of Chicago professor William Baude and University of St. Thomas professor Michael Stokes Paulsen, centers on <a href="https://constitution.findlaw.com/amendment14/annotation15.html#:~:text=Section%203%20of%20the%20Fourteenth%20Amendment%20prohibits%20anyone%20who%20has,rebellion%22%20against%20the%20United%20States.">Section 3 of the 14th Amendment</a> — a provision that limits people from returning to public office if they have since “engaged in insurrection or rebellion” or “given aid or comfort” to those who have. Baude and Paulsen argue that this clearly covers Trump’s behavior between November 2020 and January 2021.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Hx9L3x">
“The most politically explosive application of Section Three to the events of January 6, is at the same time the most straightforward,” Baude and Paulsen write. “Former President Donald J. Trump is constitutionally disqualified from again being President (or holding any other covered office) because of his role in the attempted overthrow of the <a href="https://www.vox.com/2020-presidential-election">2020 election</a> and the events leading to the January 6 attack.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZdVRFP">
The consequences of this argument are astonishing. On Baude and Paulsen’s read, Section 3 is “self-executing” — meaning it does not require an act of <a href="https://www.vox.com/congress">Congress</a> to enter force and binds those public officials in the position to act on its dictates. Basically, if a single official anywhere in the US electoral system finds their constitutional analysis compelling, Baude and Paulsen urge them to act on it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ms4KhQ">
“No official should shrink from these duties. It would be wrong — indeed, arguably itself a breach of one’s constitutional oath of office — to abandon one’s responsibilities of faithful interpretation, application, and enforcement of Section Three,” they write.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xl8IvN">
As a matter of law, I find their arguments quite compelling. If you look at Section 3 in light of the historical evidence and how restrictions on eligibility for office work elsewhere in the Constitution, it’s hard to disagree with Baude and Paulen’s application of its text to Trump.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="icTwxZ">
But as a matter of politics, encouraging state election officials to go rogue and kick Trump off the ballot is a recipe for disaster. And that disconnect, between what the law says and the practical barriers to implementing it, speaks to some deep problems in American democracy that led to Trump’s insurrection in the first place.
</p>
<h3 id="B4Vu00">
The (very strong) argument that Trump is ineligible for office
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ssIaZv">
Baude and Paulsen’s <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4532751">paper</a>, set to be published in the <em>University of Pennsylvania Law Review</em>, focusing on plain-language readings on Section 3 of the 14th Amendment and the way its key terms were used in political discussion around the time of enactment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="l4QxbJ">
To get what they’re trying to do, it’s worth reading the text of Section 3 in full:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HCxzTi">
No person shall be a Senator or Representative in Congress, or elector of President and Vice President, or hold any office, civil or military, under the United States, or under any State, who, having previously taken an oath, as a member of Congress, or as an officer of the United States, or as a member of any State legislature, or as an executive or judicial officer of any State, to support the Constitution of the United States, shall have engaged in insurrection or rebellion against the same, or given aid or comfort to the enemies thereof. But Congress may by a vote of two-thirds of each House, remove such disability.
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cUgbK7">
Using historical and dictionary sources, Baude and Paulsen establish clear definitions for key terms. “Insurrection” and “rebellion,” in their view, “cover pretty much the entire terrain of large-scale unlawful resistance to government authority.” To have “engaged in” such conduct, they claim, means being “actively involved in the planning or execution of intentional acts of insurrection or rebellion” or “knowingly provided active, meaningful, voluntary, direct support for, material assistance to, or specific encouragement of such actions.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2H1aox">
If this interpretation is correct, then the legal case against Trump is fairly straightforward — all established by facts in public reporting, evidence from the January 6 committee, and <a href="https://www.vox.com/policy/2023/8/2/23816616/trump-indictment-january-6-jack-smith-orange-man-bad">the recent federal indictment</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="csOiwz">
In this well-known story, Trump was “actively involved” in an extralegal scheme to send fake electors to the Congress, and urged the vice president to unlawfully accept these fake electors over the real ones and crown Trump president. In service of his scheme, he provided “direct support for” and “specific encouragement” of the mob that ransacked the Capitol on January 6 in his speech, <a href="https://www.presidency.ucsb.edu/documents/tweets-january-6-2021">his tweets</a>, private statements, and refusal to take actions (like <a href="https://apnews.com/article/fact-check-trump-order-national-guard-156055113284">calling in the National Guard</a>) that could have stopped the mob.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AGRrmQ">
“The bottom line is that Donald Trump both ‘engaged in’ ‘insurrection or rebellion’ and gave ‘aid or comfort’ to others engaging in such conduct, within the original meaning of those terms as employed in Section Three of the Fourteenth Amendment,” Baude and Paulsen write. “If the public record is accurate, the case is not even close.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mlC4JQ">
Normally, this kind of argument feels like a purely abstract exercise. Maybe there’s a strong case that Trump running for president is unconstitutional, but who’s actually going to stop him?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OyX0Xv">
The answer, according to Baude and Paulsen, is literally anybody in a legal position to do so.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oI467B">
“Section Three’s language is language of automatic legal effect: ‘No person shall be’ directly enacts the officeholding bar it describes where its rule is satisfied,” they explain. “It does not grant a power to Congress (or any other body) to enact or effectuate a rule of disqualification. It enacts the rule itself.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1cpxNU">
To underscore the point, they compare Section 3’s prohibition to other constitutional restrictions on running for office. Article II, for example, says that “No Person…shall be eligible” for the presidency until they’ve turned 35. If a 20-year-old filed paperwork to run for the presidency, no one would object to state election officials keeping them off the ballot for being too young.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="saNymV">
More than that: They’d be legally obligated to block the 20 year old. Even if (let’s say) the members of a state board of elections think someone below the drinking age would make the best president in American history, the law is clear that such a person can’t hold office and thus can’t be permitted to run.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wOlP61">
The “shall be” language of Section 3 is identical to Article II’s, Baude and Paulsen note, and thus entails a similar obligation. Every official involved in the US election system, from a local registrar to members of Congress, has an obligation to determine if candidates for the presidency and other high office are prohibited from running under Section 3.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vYJjNO">
“In principle: Section Three’s disqualification rule may and must be followed — applied, honored, obeyed, enforced, carried out — by anyone whose job it is to figure out whether someone is legally qualified to office,” they write.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7YfJTM">
The fact that’s it easier to tell someone’s age than if they “engaged in” an act of “insurrection” shouldn’t matter. For Baude and Paulsen, the law is the law; if you don’t like it, pass a constitutional amendment to change it. The legal system provides a remedy if a person is wrongly disqualified under the 14th Amendment, just as it does if they are wrongly disqualified on any other grounds.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o3nQiS">
The practical upshot of this analysis, they emphasize, is that officials need to start applying 14th Amendment analysis to candidates <em>now</em>. Trump, and any others found to have previously sworn an oath to uphold the Constitution and then engage in the plot to overturn the 2020 election, can and should be barred from running immediately.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IrFKA2">
“It is not for us to say who all is disqualified by virtue of Section Three’s constitutional rule. That is the duty and responsibility of many officials, administrators, legislators, and judges throughout the country,” Baude and Paulsen conclude. “Where they are called on to decide eligibility to office, they are called on to enforce Section Three, applying the Constitution’s legal standard to the facts before them in a given instance.”
</p>
<h3 id="sgmLcL">
The (very strong) practical objection to their argument, and why it matters
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CVjRLn">
There is, Baude and Paulsen admit, a “small problem” with their argument: There’s legal precedent to the controversy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="50HeOo">
In 1869’s <em>In re Griffin </em>(a.k.a. <em>Griffin’s Case)</em>, a circuit court judge named Salmon Chase (who would later go on to be the chief justice of the United States) <a href="https://freespeechforpeople.org/wp-content/uploads/2023/03/14.3-fsfp-magliocca-report-mar-2023.pdf">ruled on a criminal appeal</a> by a Black man, Caesar Griffin, convicted of attempted murder. Griffin did not contest the facts of the case, but argued that the judge who presided in the case, Hugh W. Sheffey, was not legally empowered to make a ruling.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8Oc1ni">
Before becoming a judge in 1866, Sheffey had served in the Virginia state legislature and then (subsequently) its Confederate equivalent. Griffin argued that Sheffey could not legally hold public office under Section 3 of the 14th Amendment, and therefore his conviction should be vacated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1ktRqq">
Chase disagreed. In his telling, stripping Sheffey and other former Confederates of their office and nullifying cases like Griffin’s would cause chaos throughout the Reconstruction South — and would be unfair to the former Confederates themselves. Therefore, the 14th Amendment simply can’t be read literally in the way Baude and Paulsen suggest.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G7mdnO">
“Surely a construction which fails to accomplish the main purpose of the amendment, and yet necessarily works the mischief and inconveniences which have been described, and is repugnant to the first principles of justice and right embodied in other provisions of the constitution, is not to be favored, if any other reasonable construction can be found,” Chase <a href="https://law.resource.org/pub/us/case/reporter/F.Cas/0011.f.cas/0011.f.cas.0007.html">held</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dTrHUz">
This, Baude and Paulsen show, is a very bad argument. There is no other “reasonable construction” of Section 3 beyond the literal read, nor does Chase offer one that’s at all possible to square with the plain text of the amendment. Chase’s ruling simply decides that the law cannot possibly be what it looks like it is, because he thinks it’s bad and unfair to Confederates, and thus should be ignored.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LoG4Wi">
For this reason, Baude and Paulsen conclude that “<em>Griffin’s Case</em> is a case study in how not to go about the enterprise of faithful constitutional interpretation,” one that should be “hooted down the pages of history [and] purged from our constitutional understanding of Section Three.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VPpK0u">
This is all well and good as a matter of legal argumentation, but the problem is that <em>Griffin’s Case</em> exists as a matter of fact. Though <em>Griffin </em>was not a <a href="https://www.vox.com/scotus">Supreme Court</a> case, and thus Chase’s ruling is not binding on higher federal courts in the same manner as a ruling by the justices, Baude and Paulsen themselves admit that “Chase’s tendentious construction of Section Three has gone on to a surprisingly serious career as a precedent.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OToavv">
Moreover, state election officials are not federal judges; the very existence of <em>Griffin’s Case</em>, however poorly reasoned, creates real doubt as to whether they are legally empowered to do what Baude and Paulsen are telling them they have to do.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lsDUDZ">
This means that any serious attempt to implement the paper’s findings would give rise to significant legal challenge and political chaos. Imagine — <em>just imagine</em> — that local election administration officials in states like Georgia, Wisconsin, or Arizona acted on Baude and Paulsen’s advice and knocked Trump off the general election ballot.
</p>
<figure class="e-image">
<img alt="Protesters in a crowd on the steps of the Capitol, with smoke in the air." src="https://cdn.vox-cdn.com/thumbor/I035Ji6If2pCwNwaGySuYkoJBog=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24845198/GettyImages_1236804079.jpg"/> <cite>Victor J. Blue/Bloomberg via Getty Images</cite>
<figcaption>
Demonstrators attempt to breach the US Capitol after they earlier stormed the building in Washington, DC, on January 6, 2021.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n0G9Mm">
Even if these hypothetical officials’ actions were upheld by the Supreme Court, and that’s a very big if, Trump and his supporters would be unlikely to accept the ruling. Instead, they would be likely to see it as more proof that the system is rigged against them — and to act extralegally to install Trump in office.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wjCxW8">
Best case, there’s a write-in campaign to put Trump in the presidency, giving rise to a constitutional crisis if he won (since the Supreme Court would have ruled him ineligible in upholding the state officials’ actions). Worst case<em> — </em>well, the January 6 riot could have been a lot bloodier than it already was.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cd7DXi">
What this illustrates is that the Trump problem is very hard to solve through the law alone.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S5yLvU">
The New York and federal indictments <a href="https://www.theguardian.com/us-news/2023/aug/05/trump-indictment-republican-voter-base">seem to have strengthened</a> his hold on the Republican primary electorate rather than weakened it because a large percentage of the American electorate trusts Trump over neutral arbiters, like nonpartisan election officials and judges. So long as he commands this level of support, the law’s ability to bind Trump will be limited: Even if he’s convicted on federal charges, he could still win the election from his prison cell.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OOdIAS">
Similarly, a serious effort to render Trump ineligible would run up against the practical problem that he is a near-lock to be the candidate of one of the two major parties — which, in a highly polarized system, means he’ll be the candidate of roughly half of the electorate. There is little reason to believe courts enjoy enough legitimacy among Republicans (or Democrats, for that matter) to be in a position to kick a major-party candidate off the ballot. The systemic consequences of such an attempt could well be devastating.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wvQj6T">
This is not a healthy state of affairs. Democracies depend on the rule of law, on the words on the page being respected as the rules of the game. Baude and Paulsen make a very compelling case that those rules render Trump as ineligible as a wide receiver who stepped out of bounds during his route.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QDjIXw">
But in a football game, the players feel obligated to respect the refs. In our fractured political system, it’s not obvious that the refs — be they election administrators or Supreme Court justices — enjoy the same level of legitimacy. We’ve already seen the consequences of this legitimacy deficit during the 2020 election; we could very well see them again in 2024.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QdVkWI">
</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>Panshul Uboveja and Manshi Singh win titles</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>Tamanna Takoria clinches women’s title</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>FIFA Women World Cup | Australia beats France in penalty thriller to reach semifinals</strong> - Australia now go to Sydney on Wednesday to face the winners of the final last-eight tie between England and Colombia.</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>Mbappe, Neymar and Verratti left out of PSG squad for season opener</strong> - Mbappe is among a number of players tipped to leave the Parc des Princes in the transfer window, which closes on Sept. 1.</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>England captain Harry Kane leaves Tottenham for Bayern Munich in search for trophies</strong> - England captain Harry Kane has completed his move to Bayern Munich from Tottenham in soccer’s biggest transfer of the summer as the striker goes in search of the first major trophies in his career</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>St John’s to soon start comprehensive geriatric and palliative care services</strong> - St. John’s Medical College is celebrating its 60th year of existence this year; Chief Postmaster General, Karnataka Circle released an India Post special cover with insignia of St. John’s</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>First India-made MRI scanner by Bengaluru-based Voxelgrids Innovations, to be launched for clinical work in October, will potentially cut the cost of scanning by 30%</strong> - The indigenously developed machine is characterised by several innovations, including avoiding reliance on scarcely available liquid helium, bottom-up software design, and customised hardware</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>Foxconn gets board nod for $400 million investment in Telangana</strong> - Once again proves Telangana speed, Minister KTR posted, saying with the previously announced $150 million, the firm is poised to invest $550 million</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>ED files charge sheet against Senthilbalaji, court sends him to judicial custody till August 25</strong> - The Minister, who was arrested by the ED on June 14, will continue to be lodged at the Puzhal central jail in Chennai</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>‘Ustaad’ movie review: An imperfect yet warm coming-of-age story of a boy and his bike</strong> - Debut director Phanideep, actors Simha Koduri and Kavya Kalyanram make an impression in the Telugu film ‘Ustaad’, a slightly overdrawn story of a boy, his dreams, and his bike</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>Migrant boat sinks in Channel killing six people</strong> - A rescue operation by the British and French coastguards has rescued around 50 people, authorities said.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Sex lives in focus for Ukraine’s injured veterans</strong> - The charity ReSex is providing guidance for wounded soldiers looking for help with their sex lives.</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>K2: Climbers deny walking by dying guide in bid to break record</strong> - Footage has emerged appearing to show Kristin Harila’s team climbing over Mohammed Hassan on Pakistan’s K2.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine fires military conscription officials for taking bribes</strong> - Officials took cash and cryptocurrency and helped people to leave Ukraine, President Zelensky says.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Russian convicts released to fight with Wagner accused of new crimes</strong> - Victims’ families are distraught that Russian prisoners released to fight in Ukraine are reoffending.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The “Shove” mechanic in Baldur’s Gate 3 can ruin an encounter, and I love it</strong> - What my brave warrior’s death to a lowly goblin taught me about dice anarchy. - <a href="https://arstechnica.com/?p=1960409">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-magnetizing-vaccine doctor loses medical license</strong> - Tenpenny lost her license for refusing to cooperate with a board investigation. - <a href="https://arstechnica.com/?p=1960598">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sites scramble to block ChatGPT web crawler after instructions emerge</strong> - Restrictions don’t apply to current OpenAI models, but will affect future versions. - <a href="https://arstechnica.com/?p=1960108">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Microsoft finds vulnerabilities it says could be used to shut down power plants</strong> - Exploitation is hard and patches are already out, but the potential risk is great. - <a href="https://arstechnica.com/?p=1960538">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sam Bankman-Fried is going to jail</strong> - Judge also denied SBF’s request to delay jail time. - <a href="https://arstechnica.com/?p=1960540">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Doctor tells the 90 Year Old Man that he needs a semen sample. “Bring back the specimen tomorrow.”</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The next day the old man comes back with the jar in hand. It’s as clean and empty as it was the previous day. “Did you have a little trouble?” asked the doctor. A pause, then he says, “When I got home I tried, you know? First, with the right hand. Next, with the left hand. Nothing. That I asked my wife for some help. She tried too. With her left hand, with the right hand, with her mouth, she even put it under her armpit. Nothing.”Now we got us a friend, down the street. She helps us with things now and again from time to time, seeing as how we’re getting on in age, and she’s trying with her left, with her right…" “Hold on,” the doctor says, “you asked your neighbor for help?” “Yeah, but none of us could get that jar open.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/2BallsInTheHole"> /u/2BallsInTheHole </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15oluge/the_doctor_tells_the_90_year_old_man_that_he/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15oluge/the_doctor_tells_the_90_year_old_man_that_he/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>One day a man, who had been stranded on a desert island for over ten years sees an unusual speck on the horizon.“It’s certainly not a ship”, he thinks to himself. As the speck gets closer Suddenly, emerging from the surf, comes a drop dead gorgeous blonde woman wearing a wet suit and scuba gear.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She approaches the stunned guy and says: “Tell me, how long has it been since you’ve had a cigarette?” “Ten years,” replies the stunned man. With that she reaches over and unzips a waterproof pocket on her left sleeve and pulls out a pack of cigarettes. He takes one, lights it, takes a long drag and says: “Man, oh man! Is that good!” “And how long has it been since you’ve had a sip of bourbon?” she asks him. Trembling the castaway replies: “Ten years.” She reaches over, unzips her right sleeve, pulls out a flask and hands it to him. He opens the flask, takes a long swig and says: “WOW, that’s absolutely fantastic!” At this point she starts slowly unzipping the long zipper that runs down the front of her wet suit, looks at the man seductively, and asks: “And how long has it been since you’ve had some real fun?” With tears in his eyes, the guy falls to his knees and sobs: “Oh good Lord! Don’t tell me you’ve got a laptop?”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15oj29b/one_day_a_man_who_had_been_stranded_on_a_desert/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15oj29b/one_day_a_man_who_had_been_stranded_on_a_desert/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why did my girlfriend leave?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
My girlfriend said we had to have a serious talk. She had enough of me constantly singing “I want it that way” by the Backstreet Boys. She said if I didn’t stop singing that song, she was done with the relationship and would leave.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I said, “Tell me why?”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Tazmerican"> /u/Tazmerican </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15ow1xu/why_did_my_girlfriend_leave/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15ow1xu/why_did_my_girlfriend_leave/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A mechanic was secretly drinking brake fluid at the garage where he worked. On some days he would even drink a whole pint of the stuff. One day his boss found out and confronted him about it.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The mechanic said “It won’t become a problem, boss, I swear I can stop whenever I want!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/RayBans0306"> /u/RayBans0306 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15os5bt/a_mechanic_was_secretly_drinking_brake_fluid_at/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15os5bt/a_mechanic_was_secretly_drinking_brake_fluid_at/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A penis has a sad life.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
His hair is a mess; his family is nuts; his next-door neighbor is an arsehole; his best friend is a pussy, and his owner beats him habitually..
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/jflipside"> /u/jflipside </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15ovpx8/a_penis_has_a_sad_life/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15ovpx8/a_penis_has_a_sad_life/">[comments]</a></span></p></li>
</ul>
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