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<title>05 October, 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>Funding Solutions in Real Estate: The Influence of the COVID-19 Pandemic on Lending</strong> -
<div>
The global real estate industry has always been closely tied to economic fluctuations, and the COVID-19 pandemic has been no exception. One of the most significant aspects affected by this crisis is real estate lending. In this article, we will explore the evolving landscape of funding solutions in the real estate sector and how the pandemic has reshaped the lending environment.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/n6vm5/" target="_blank">Funding Solutions in Real Estate: The Influence of the COVID-19 Pandemic on Lending</a>
</div></li>
<li><strong>SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia</strong> -
<div>
Age is a major risk factor for coronavirus disease (COVID-19)-associated severe pneumonia and mortality; however, the underlying mechanism remains unclear. Herein, we investigated whether age-related deregulation of RNAi components and RNA splicing factors affects COVID-19 severity. Decreased expression of RNAi components (Dicer and XPO5) and splicing factors (SRSF3 and hnRNPA3) correlated with increased severity of COVID-19 and SARS-CoV-2 nucleocapsid (N) protein-induced pneumonia. N protein induced autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, repressing miRNA biogenesis and RNA splicing and inducing DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 were downregulated with age in mouse lung tissues. Older mice experienced more severe N protein-induced pneumonia than younger mice. However, treatment with a poly(ADP-ribose) polymerase inhibitor (PJ34) or aromatase inhibitor (anastrozole) relieved N protein-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.03.560426v1" target="_blank">SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia</a>
</div></li>
<li><strong>Comparative single-cell analysis reveals IFN-γ as a driver of respiratory sequelae post COVID-19</strong> -
<div>
Post-acute sequelae of SARS-CoV-2 infection (PASC) represents an urgent public health challenge, with its impact resonating in over 60 million individuals globally. While a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood studies, with few focusing on samples derived from post-COVID affected tissues. Further, clinical studies alone often provide correlative insights rather than causal relationships. Thus, it is essential to compare clinical samples with relevant animal models and conduct functional experiments to truly understand the etiology of PASC. In this study, we have made comprehensive comparisons between bronchoalveolar lavage fluid (BAL) single-cell RNA sequencing (scRNAseq) data derived from clinical PASC samples and relevant PASC mouse models. This revealed a strong pro-fibrotic monocyte-derived macrophage response in respiratory PASC (R-PASC) in both humans and mice, and abnormal interactions between pulmonary macrophages and respiratory resident T cells. IFN-g emerged as a key node mediating the immune anomalies in R-PASC. Strikingly, neutralizing IFN-g post the resolution of acute infection reduced lung inflammation, tissue fibrosis, and improved pulmonary gas-exchange function in two mouse models of R-PASC. Our study underscores the importance of performing comparative analysis to understand the root cause of PASC for developing effective therapies.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.03.560739v1" target="_blank">Comparative single-cell analysis reveals IFN-γ as a driver of respiratory sequelae post COVID-19</a>
</div></li>
<li><strong>mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting</strong> -
<div>
To address the limitations of whole-spike COVID vaccines, we explored mRNA vaccines encoding membrane-anchored receptor-binding domain (RBD-TMs), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail (CT) fragments of the SARS-CoV-2 spike protein. In naive mice, RBD-TM mRNA vaccines against ancestral SARS-CoV-2, Beta, Delta, Delta-plus, Kappa, Omicron BA.1 or BA.5, all induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays indicated broad neutralizing activity against a range of variant RBDs. In the setting of a heterologous boost, against the background of exposure to ancestral whole spike vaccines, sVNT studies suggested that RBD-TM vaccines were able to overcome the detrimental effects of immune imprinting. Omicron BA.1 and BA.5 RBD-TM booster vaccines induced serum antibodies with 12 and 22-fold higher neutralizing activity against the target RBD than their equivalent whole spike variants. Boosting with BA.1 or BA.5 RBD-TM provided good protection against more recent variants including XBB and XBB.1.5. Each RBD-TM mRNA is 28% of the length of its whole-spike equivalent. This advantage will enable tetravalent mRNA vaccines to be developed at well-tolerated doses of formulated mRNA.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.04.560777v1" target="_blank">mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting</a>
</div></li>
<li><strong>Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors</strong> -
<div>
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant global morbidity and mortality. A crucial viral protein, the non-structural protein 14 (nsp14), catalyzes the methylation of viral RNA and plays a critical role in viral genome replication and transcription. Due to the low mutation rate in the nsp region among various SARS-CoV-2 variants, nsp14 has emerged as a promising therapeutic target. However, discovering potential inhibitors remains a challenge. In this work, we introduce a computational pipeline for the rapid and efficient identification of potential nsp14 inhibitors by leveraging virtual screening and the NCI open compound collection, which contains 250,000 freely available molecules for researchers worldwide. The introduced pipeline provides a cost-effective and efficient approach for early-stage drug discovery by allowing researchers to evaluate promising molecules without incurring synthesis expenses. Our pipeline successfully identified seven promising candidates after experimentally validating only 40 compounds. Notably, we discovered NSC620333, a compound that exhibits a strong binding affinity to nsp14 with a dissociation constant of 427 {+/-} 84 nM. In addition, we gained new insights into the structure and function of this protein through molecular dynamics simulations. We identified new conformational states of the protein and determined that residues Phe367, Tyr368, and Gln354 within the binding pocket serve as stabilizing residues for novel ligand interactions. We also found that metal coordination complexes are crucial for the overall function of the binding pocket. Lastly, we present the solved crystal structure of the nsp14-MTase complexed with SS148, a potent inhibitor of methyltransferase activity at the nanomolar level (IC50 value of 70 {+/-} 6 nM). Our computational pipeline accurately predicted the binding pose of SS148, demonstrating its effectiveness and potential in accelerating drug discovery efforts against SARS-CoV-2 and other emerging viruses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.03.560722v1" target="_blank">Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors</a>
</div></li>
<li><strong>Post-acute immunological and behavioral sequelae in mice after Omicron infection</strong> -
<div>
Progress in understanding long COVID and developing effective therapeutics is hampered in part by the lack of suitable animal models. Here we used ACE2-transgenic mice recovered from Omicron (BA.1) infection to test for pulmonary and behavioral post-acute sequelae. Through in-depth phenotyping by CyTOF, we demonstrate that naive mice experiencing a first Omicron infection exhibit profound immune perturbations in the lung after resolving acute infection. This is not observed if mice were first vaccinated with spike-encoding mRNA. The protective effects of vaccination against post-acute sequelae were associated with a highly polyfunctional SARS-CoV-2-specific T cell response that was recalled upon BA.1 breakthrough infection but not seen with BA.1 infection alone. Without vaccination, the chemokine receptor CXCR4 was uniquely upregulated on multiple pulmonary immune subsets in the BA.1 convalescent mice, a process previously connected to severe COVID-19. Taking advantage of recent developments in machine learning and computer vision, we demonstrate that BA.1 convalescent mice exhibited spontaneous behavioral changes, emotional alterations, and cognitive-related deficits in context habituation. Collectively, our data identify immunological and behavioral post-acute sequelae after Omicron infection and uncover a protective effect of vaccination against post-acute pulmonary immune perturbations.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.05.543758v2" target="_blank">Post-acute immunological and behavioral sequelae in mice after Omicron infection</a>
</div></li>
<li><strong>Time warping between main epidemic time series in epidemiological surveillance</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The most common reported epidemic time series in epidemiological surveillance are the daily or weekly incidence of new cases, the hospital admission count, the ICU admission count, and the death toll, which played such a prominent role in the struggle to monitor the Covid-19 pandemic. We show that pairs of such curves are related to each other by a generalized renewal equation depending on a smooth time varying delay and a smooth ratio generalizing the reproduction number. Such a functional relation is also explored for pairs of simultaneous curves measuring the same indicator in two neighboring countries. Given two such simultaneous time series, we develop, based on a signal processing approach, an efficient numerical method for computing their time varying delay and ratio curves, and we verify that its results are consistent. Indeed, they experimentally verify symmetry and transitivity requirements and we also show, using realistic simulated data, that the method faithfully recovers time delays and ratios. We discuss several real examples where the method seems to display interpretable time delays and ratios. The proposed method generalizes and unifies many recent related attempts to take advantage of the plurality of these health data across regions or countries and time, providing a better understanding of the relationship between them. An implementation of the method is publicly available at the EpiInvert CRAN package.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.07.23285605v2" target="_blank">Time warping between main epidemic time series in epidemiological surveillance</a>
</div></li>
<li><strong>Behavioural and Social Predictors of COVID-19 Vaccine Uptake among Persons with Disabilities in Kenya.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The uptake of the COVID-19 vaccine by persons with disabilities remains largely unknown in low-and middle-income countries. This evidence gap necessitates disability-focused research to inform improvements in access and inclusion in the last mile of COVID-19 vaccination programs and to support future programs for other vaccine-preventable diseases. We aimed to identify behavioural and social predictors of COVID-19 uptake among persons with disabilities in Kenya. This was a convergent parallel mixed method study that involved questionnaires (792), key informants interviews, and focus group discussions among persons with disabilities and key stakeholders (government actors and professional associations). Data were analysed using STATA statistical analysis software (version 14). Chi-square (X2) and Fisher’s exact tests were used to test for differences in categorical variables; multivariate regression analysis was employed to ascertain the factors that influence uptake of COVID-19 among persons with disabilities (PWDs) in Kenya. Approximately 59% of persons with disabilities reported to be fully vaccinated, with significant disparities noted among those with cognition (34.2%) and self-care (36.6%) impairments. Confidence in vaccine benefits (Adjusted odds ration [OR]; 11.3, 95% CI; 5.2-24.2), health worker recommendation (OR; 2.6, 95% CI; 1.8-3.7), employment (OR; 2.1, 95% CI; 1.4-3.1), perceived risk (OR; 2.0, 95% CI; 1.3-3.1), age and area of residence were statistically significant predictors of vaccine uptake among PWDs. The primary reasons for low uptake included perceived negative vaccine effects and lack of adequate information. No association was found between having a primary caregiver and/or assistive device, with COVID-19 vaccine uptake. Subsequent vaccination deployments should map and reach PWDs through relevant institutions of PWDs, and localized vaccination campaigns. Related communication strategies should leverage on behaviour change techniques that inspire confidence in vaccines, and on the credibility and trust in health workers to improve vaccine uptake.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296513v1" target="_blank">Behavioural and Social Predictors of COVID-19 Vaccine Uptake among Persons with Disabilities in Kenya.</a>
</div></li>
<li><strong>United States Marijuana Legalization and Opioid Mortality Trends Before and During the First Year of the COVID-19 Pandemic</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
To determine if marijuana legalization reduced opioid mortality, the U.S. opioid and fentanyl subset death trends during the 2010-2019 decade were compared in states and District of Columbia (D.C.) (jurisdictions) that had implemented marijuana legalization with states that had not. Acceleration of opioid mortality during 2020, first year of the COVID-19 pandemic, was also compared in recreational and medicinal-only legalizing jurisdictions. Joinpoint methodology was applied to Centers for Disease Control and Prevention WONDER data. Trends in legalizing jurisdictions were cumulative aggregates. The overall opioid and fentanyl death rates and percentage of opioid deaths due to fentanyl increased more during 2010-2019 in jurisdictions that legalized marijuana than in those that did not (pairwise comparison p=0.007, 0.05, and 0.006, respectively). By 2019, the opioid and fentanyl death rates were 44% and 50% greater in the legalizing than non-legalizing jurisdictions, respectively. When the COVID-19 pandemic hit in 2020, jurisdictions that implemented recreational marijuana legalization before 2019 had significantly greater increases in both overall opioid and fentanyl death rates than jurisdictions with medicinal-only legalization. For all opioids, the mean (95% confidence interval [CI]) 2019-to-2020 increases were 46.5% (95% CI, 36.6% to 56.3%) and 29.1% (95% CI 20.2% to 37.9%), respectively (p=0.02). For fentanyl, they were 115.6% (95% CI, 80.2% to 151.6%) and 55.4% (95% CI, 31.6% to 79.2%), respectively (p=0.01). Marijuana legalization is correlated with worsening of the U.S. opioid epidemic, and especially during the COVID-19 pandemic with recreational legalization.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296502v1" target="_blank">United States Marijuana Legalization and Opioid Mortality Trends Before and During the First Year of the COVID-19 Pandemic</a>
</div></li>
<li><strong>Moral Judgments Impact Perceived Risks from COVID-19 Exposure</strong> -
<div>
The COVID-19 pandemic has created enormously difficult decisions for individuals trying to navigate both the risks of the pandemic and the demands of everyday life. Good decision making in such scenarios can have life and death consequences. For this reason, it is important to understand what drives risk assessments during a pandemic, and, in particular, to investigate the ways that these assessments might deviate from ideal risk assessments. Two studies (N = 841) investigate risk judgments related to COVID-19. The results indicate that risk judgments are sensitive to factors unrelated to the objective risks of infection. In particular, activities that are morally justified are perceived as safer while those that might subject people to blame, or culpability, are seen as riskier.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/59s2g/" target="_blank">Moral Judgments Impact Perceived Risks from COVID-19 Exposure</a>
</div></li>
<li><strong>Prevalence and factors associated with fear of COVID-19 in military personnel during the second epidemic wave in Peru</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
There is few research in military members that provided protection and security during the COVID-19 crisis. We aimed to determine the prevalence and factors associated with fear of COVID-19 in military members. A cross-sectional study was conducted between November 02 and 09, 2021, during the second wave of the COVID-19 pandemic in the region of Lambayeque, Peru. The outcome was fear of COVID-19, measured with the Fear of COVID-19 Scale. The association with resilience (abbreviated CD-RISC), food insecurity (HFIAS), physical activity (IPAQ-S), eating disorder (EAT-26), and other socio-labor variables were assessed. Of 525 participants, the median age was 22, 95.8% were male, and 19.2% experienced fear of COVID-19. A higher prevalence of fear of COVID-19 was associated with age (PR=1.03; 95% CI: 1.01-1.06), religion (PP=2.05; 95% CI: 1.04-4.05), eating disorder (PR=2.95; 95% CI: 1.99-4.36), and having a relative with mental disorder (PR=2.13; 95% CI: 1.09-4.17). Overweight (PR=0.58; 95% IC: 0.37-0.90) and a high level of resilience (PR=0.63; 95% IC: 0.43-0.93) were associated with a lower prevalence of fear of COVID-19. Two out of ten military personnel were afraid of COVID-19. We recommend special attention to the factors associated with the development of suicide risk in military personnel.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296474v1" target="_blank">Prevalence and factors associated with fear of COVID-19 in military personnel during the second epidemic wave in Peru</a>
</div></li>
<li><strong>Mendelian Randomization Reveals the Role of HMGCR in Pulmonary Arterial Hypertension Treatment, Independent of LDL Cholesterol Concentration</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Introduction: Specific lipid-reducing therapeutics, including statins, are known for mitigating cardiovascular diseases due to their comprehensive benefits including anti-inflammatory properties, antioxidative stress response, and enhancement of endothelial function. The objective of our study was to determine the causative impact of lipid-reducing agents (HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitor) on the outcomes of pulmonary hypertension via a two-sample Mendelian randomization (MR) analysis.   Methods: Two types of genetic tools were employed to estimate the exposure to lipid-lowering drugs, comprising expression quantitative trait loci of the drug9s target genes and genetic variations close to or within the target genes related to low-density lipoprotein (LDL cholesterol derived from a genome-wide association study). We utilized summary-data-based MR (SMR) and inverse-variance-weighted MR (IVWMR) methodologies for estimating effect sizes.   Results: SMR analysis indicated that elevated HMGCR expression correlates with increased pulmonary hypertension risk (β=-0.964, se=0.276). Yet, no evident causative link between HMGCR-regulated LDL cholesterol and COVID-19 hospitalization was observed in the IVW-MR analysis (β = -0.21, se= 0.17).   Conclusions:  Our Mendelian randomization investigation unveiled a possible positive impact of lipid-lowering therapeutics on the prognosis of pulmonary hypertension. Importantly, no causal relation was established between LDL cholesterol and pulmonary hypertension.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.02.23295606v1" target="_blank">Mendelian Randomization Reveals the Role of HMGCR in Pulmonary Arterial Hypertension Treatment, Independent of LDL Cholesterol Concentration</a>
</div></li>
<li><strong>Modeling spillover dynamics: understanding emerging pathogens of public health concern</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The emergence of infectious diseases with pandemic potential is a major public health threat worldwide. According to the World Health Organization, around 60% of the reported emerging infectious diseases are zoonoses and have been triggered by spillover events. Although the dynamics of spillover events are not yet well understood, mathematical modeling has the potential to characterize the highly complex interactions among pathogens, wildlife, humans, and the environment where they coexist. In this work, motivated by discussions on the introductory phase of SARS-CoV-2 towards a pandemic scenario, we address the so far unexplored emergence of novel infectious agents. Aiming at gaining insights into the dynamics of spillover events and the final outcome of an eventual disease outbreak in a population, we propose a continuous time stochastic modeling framework to describe a cross-species disease transmission by coupling the dynamics of animal reservoirs and human hosts. A complete analysis of the system is conducted, followed by numerical experiments where we investigate different scenarios of spillover events. Applied to the emergence of SARS-CoV-2 and monkeypox viruses, our results provide insights into the emergence of new infectious diseases able to cause not only local outbreaks but eventually explosive epidemics towards a pandemic.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.02.23296428v1" target="_blank">Modeling spillover dynamics: understanding emerging pathogens of public health concern</a>
</div></li>
<li><strong>Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false- negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive analytical sensitivity in the lab, the assessment of clinical accuracy with IACs is often overlooked. In some cases, the IACs were run spatially, complicating assay workflow. Therefore, the multiplex assay for pathogen and IAC is needed. Results: We developed a one-pot duplex reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for saliva samples, a non-invasive and simple collected specimen for POC NAATs. The ORF1ab gene of SARS-CoV-2 was used as a target and a human 18S ribosomal RNA in human saliva was employed as an IAC to ensure clinical reliability of the RT-LAMP assay. The optimized assay could detect SARS-CoV-2 viral particles down to 100 copies/μL of saliva within 30 minutes without RNA extraction. The duplex RT-LAMP for SARS-CoV-2 and IAC is successfully amplified in the same reaction without cross-reactivity. The valid results were easily visualized in triple-line lateral flow immunoassay, in which two lines (flow control and IAC lines) represent valid negative results and three lines (flow control, IAC, and test line) represent valid positive results. This duplex assay demonstrated a clinical sensitivity of 95%, specificity of 100%, and accuracy of 96% in 30 clinical saliva samples. Significance: IACs play a crucial role in ensuring user confidence with respect to the accuracy and reliability of at-home and POC molecular diagnostics. We demonstrated the multiplex capability of SARS-COV-2 and human18S ribosomal RNA RT-LAMP without complicating assay design. This generic platform can be extended in a similar manner to include human18S ribosomal RNA IACs into different clinical sample matrices.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296477v1" target="_blank">Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing</a>
</div></li>
<li><strong>Some principles for using epidemiologic study results to parameterize transmission models</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Infectious disease models, including individual based models (IBMs), can be used to inform public health response. For these models to be effective, accurate estimates of key parameters describing the natural history of infection and disease are needed. However, obtaining these parameter estimates from epidemiological studies is not always straightforward. We aim to 1) outline challenges to parameter estimation that arise due to common biases found in epidemiologic studies and 2) describe the conditions under which careful consideration in the design and analysis of the study could allow us to obtain a causal estimate of the parameter of interest. In this discussion we do not focus on issues of generalizability and transportability. Methods: Using examples from the COVID-19 pandemic, we first identify different ways of parameterizing IBMs and describe ideal study designs to estimate these parameters. Given real-world limitations, we describe challenges in parameter estimation due to confounding and conditioning on a post-exposure observation. We then describe ideal study designs that can lead to unbiased parameter estimates. We finally discuss additional challenges in estimating progression probabilities and the consequences of these challenges. Results: Causal estimation can only occur if we are able to accurately measure and control for all confounding variables that create non-causal associations between the exposure and outcome of interest, which is sometimes challenging given the nature of the variables we need to measure. In the absence of perfect control, non-causal parameter estimates should still be used, as sometimes they are the best available information we have. Conclusions: Identifying which estimates from epidemiologic studies correspond to the quantities needed to parameterize disease models, and determining whether these parameters have causal interpretations, can inform future study designs and improve inferences from infectious disease models. Understanding the way in which biases can arise in parameter estimation can inform sensitivity analyses or help with interpretation of results if the magnitude and direction of the bias is understood.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296455v1" target="_blank">Some principles for using epidemiologic study results to parameterize transmission models</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>Study of the Vector Vaccine GamCovidVac-M (Altered Antigenic Composition)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac-M vector vaccine for the prevention of COVID-19 with altered antigenic composition <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Vector Vaccine GamCovidVac for the Prevention of COVID-19 With Altered Antigenic Profile With Participation of Adult Volunteers</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac vector vaccine for the prevention of COVID-19 (with altered antigenic profile) <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <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>Effects of Cacao FLAvonoids in LOng Covid Patients (FLALOC)</strong> - <b>Conditions</b>: Long Covid19; Fatigue Syndrome, Chronic <br/><b>Interventions</b>: Dietary Supplement: Flavonoids <br/><b>Sponsors</b>: Guillermo Ceballos Reyes; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exercise Interventions in Post-acute Sequelae of Covid-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Exercise <br/><b>Sponsors</b>: University of Virginia <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Efficacy of the 2023-2024 Updated COVID-19 Vaccines Against COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Vaccine-Preventable Diseases; SARS CoV 2 Infection; Upper Respiratory Tract Infection; Upper Respiratory Disease <br/><b>Interventions</b>: Biological: Novavax COVID-19 vaccine (2023-2024 formula XBB containing); Biological: Pfizer COVID-19 mRNA vaccine (2023-2024 formula XBB containing) <br/><b>Sponsors</b>: Sarang K. Yoon, DO, MOH; Westat; 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>Motivational Interviewing for Vaccine Uptake in Latinx Adults</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Other: EHR alert; Behavioral: Motivational Interviewing; Behavioral: Warm hand off to nurse <br/><b>Sponsors</b>: Boston College; East Boston Neighborhood Health Center; Harvard School of Public Health (HSPH); Boston Children’s Hospital; National Institute of Nursing Research (NINR) <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>Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects</strong> - <b>Conditions</b>: COVID-19; Infectious Disease; Symptomatic COVID-19 Infection Laboratory-Confirmed; SARS CoV 2 Infection <br/><b>Interventions</b>: Combination Product: RQ-001; Other: Placebo <br/><b>Sponsors</b>: Red Queen Therapeutics, Inc.; PPD <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of “Sputnik Lite” for the Prevention of COVID-19 With Altered Antigenic Composition.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: “Sputnik Lite” vaccine for the prevention of COVID-19 with altered antigenic composition <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19</strong> - <b>Conditions</b>: COVID-19, SARS-CoV-2 <br/><b>Interventions</b>: Biological: Biological: AZD3152; Biological: Biological: Placebo <br/><b>Sponsors</b>: AstraZeneca <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>Examining the Function of Cs4 on Post-COVID-19 Disorders</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Other: Chinese medicine nutritional supplement Cs4 <br/><b>Sponsors</b>: The University of Hong Kong <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Amantadine Therapy for Cognitive Impairment in Long COVID</strong> - <b>Conditions</b>: Long COVID; Post-COVID19 Condition; Post-Acute COVID19 Syndrome <br/><b>Interventions</b>: Drug: Amantadine <br/><b>Sponsors</b>: Ohio State 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>Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia</strong> - <b>Conditions</b>: Parosmia <br/><b>Interventions</b>: Procedure: Stellate Ganglion Block; Other: Placebo <br/><b>Sponsors</b>: Lawson Health Research Institute <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>CPAP Efficacy in Post-COVID Patients With Sleep Apnea</strong> - <b>Conditions</b>: COVID-19; Sleep Apnea <br/><b>Interventions</b>: Device: Continuous positive airway pressure <br/><b>Sponsors</b>: University of Pittsburgh <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>Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 (THYTECH2)</strong> - <b>Conditions</b>: Systemic Inflammatory Response Syndrome <br/><b>Interventions</b>: Biological: Allogeneic thyTreg 5.000.000; Biological: Allogeneic thyTreg 10.000.000 <br/><b>Sponsors</b>: Hospital General Universitario Gregorio Marañon; Instituto de Salud Carlos III <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SA55 Injection; Other: Placebo for SA55 injection <br/><b>Sponsors</b>: Sinovac Life Sciences Co., Ltd. <br/><b>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>What do we know about the function of SARS-CoV-2 proteins?</strong> - The COVID-19 pandemic has highlighted the importance in the understanding of the biology of SARS-CoV-2. After more than two years since the first report of COVID-19, it remains crucial to continue studying how SARS-CoV-2 proteins interact with the host metabolism to cause COVID-19. In this review, we summarize the findings regarding the functions of the 16 non-structural, 6 accessory and 4 structural SARS-CoV-2 proteins. We place less emphasis on the spike protein, which has been the subject 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>High-affinity binding to the SARS-CoV-2 spike trimer by a nanostructured, trivalent protein-DNA synthetic antibody</strong> - Multivalency enables nanostructures to bind molecular targets with high affinity. Although antibodies can be generated against a wide range of antigens, their shape and size cannot be tuned to match a given target. DNA nanotechnology provides an attractive approach for designing customized multivalent scaffolds due to the addressability and programmability of the nanostructure shape and size. Here, we design a nanoscale synthetic antibody (“nano-synbody”) based on a three-helix bundle DNA…</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>Bioactive metabolites identified from Aspergillus terreus derived from soil</strong> - Aspergillus terreus has been reported to produce many bioactive metabolites that possess potential activities including anti-inflammatory, cytotoxic, and antimicrobial activities. In the present study, we report the isolation and identification of A. terreus from a collected soil sample. The metabolites existing in the microbial ethyl acetate extract were tentatively identified by HPLC/MS and chemically categorized into alkaloids, terpenoids, polyketides, γ-butyrolactones, quinones, 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>Effects of tea, catechins and catechin derivatives on Omicron subvariants of SARS-CoV-2</strong> - The Omicron subvariants of SARS-CoV-2 have multiple mutations in the S-proteins and show high transmissibility. We previously reported that tea catechin (-)-epigallocatechin gallate (EGCG) and its derivatives including theaflavin-3,3’-di-O-digallate (TFDG) strongly inactivated the conventional SARS-CoV-2 by binding to the receptor binding domain (RBD) of the S-protein. Here we show that Omicron subvariants were effectively inactivated by green tea, Matcha, and black tea. EGCG and TFDG strongly…</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>AMPK inhibitor, compound C, inhibits coronavirus replication in vitro</strong> - The coronavirus disease (COVID-19) pandemic has resulted in more than six million deaths by October 2022. Vaccines and antivirals for severe acute respiratory syndrome coronavirus 2 are now available; however, more effective antiviral drugs are required for effective treatment. Here, we report that a potent AMP-activated protein kinase (AMPK) inhibitor, compound C/dorsomorphin, inhibits the replication of the human coronavirus OC43 strain (HCoV-OC43). We examined HCoV-OC43 replication in control…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A First-In-Human Phase 1 Study of Simnotrelvir, a 3CL-like Protease Inhibitor for Treatment of COVID-19, in Healthy Adult Subjects</strong> - Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier:…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An in-vitro evaluation of antifungal, anti-lungcancer (A549), and anti-hyperglycemic activities potential of Andrographis paniculata (Burm. f.) flower extract</strong> - The medical plant research has received more attention among researchers especially after the Covid-19 pandemic. This research performed to evaluate the antifungal, anti-lung cancer (A549), and anti-hyperglycemic activities of aqueous extract of Andrographis paniculata flower. Interestingly, A. paniculata flower aqueous extract contains pharmaceutically valuable phytochemicals such as alkaloid, phenolics, terpenoids, tannins, flavonoids, and protein. It also showed fine antifungal activity…</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>Development in biomarkers of breast cancer: a bibliometric analysis from 2011 to 2020</strong> - CONCLUSIONS: In the past decade, most research has focused on basic and clinical studies, of which microRNAs (miRNAs) and circulating tumor DNAs (ctDNAs) associated with the inhibition and attenuation of BC have become the focus of recent research.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The effect of loneliness on depression in young people: a multiple mediated effects model</strong> - CONCLUSIONS: The findings indicate that the inability to alleviate negative emotions through socialization and interpersonal companionship during COVID-19 contributed to increased loneliness and subsequent depression. Reduced resilience due to loneliness may lead individuals to project unfavorable interpersonal experiences onto other aspects of life and believe they are incapable of overcoming challenges, thereby deteriorating depression conditions. Enhancing an individual’s resilience may help…</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>Virus on surfaces: Chemical mechanism, influence factors, disinfection strategies, and implications for virus repelling surface design</strong> - While SARS-CoV-2 is generally under control, the question of variants and infections still persists. Fundamental information on how the virus interacts with inanimate surfaces commonly found in our daily life and when in contact with the skin will be helpful in developing strategies to inhibit the spread of the virus. Here in, a critically important review of current understanding of the interaction between virus and surface is summarized from chemistry point-of-view. 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>The role of cross-reactive immunity to emerging coronaviruses: Implications for novel universal mucosal vaccine design</strong> - Host immune response to coronaviruses and the role of cross-reactivity immunity among different coronaviruses are crucial for understanding and combating the continuing COVID-19 outbreak and potential subsequent pandemics. This review paper explores how previous exposure to common cold coronaviruses and more pathogenic coronaviruses may elicit a protective immune response against SARS-CoV-2 infection, and discusses the challenges posed by some variants of concern that may escape current…</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>Multi-structural molecular docking (MOD) combined with molecular dynamics reveal the structural requirements of designing broad-spectrum inhibitors of SARS-CoV-2 entry to host cells</strong> - New variants of SARS-CoV-2 that can escape immune response continue to emerge. Consequently, there is an urgent demand to design small molecule therapeutics inhibiting viral entry to host cells to reduce infectivity rate. Despite numerous in silico and in situ studies, the structural requirement of designing viral-entry inhibitors effective against multiple variants of SARS-CoV-2 has yet to be described. Here we systematically screened the binding of various natural products (NPs) to six…</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 monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome</strong> - Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms….</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>Antibacterial and anti-corona virus (229E) activity of Nigella sativa oil combined with photodynamic therapy based on methylene blue in wound infection: in vitro and in vivo study</strong> - Microbial skin infections, antibiotic resistance, and poor wound healing are major problems, and new treatments are needed. Our study targeted solving this problem with Nigella sativa (NS) oil and photodynamic therapy based on methylene blue (MB-PDT). Antibacterial activity and minimum inhibitory concentration (MIC) were determined via agar well diffusion assay and broth microdilution, respectively. Transmission electron microscopy (TEM) proved deformations in Staphylococcus aureus ATCC 6538….</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>N-linked glycoproteins and host proteases are involved in swine acute diarrhea syndrome coronavirus entry</strong> - Swine acute diarrhea syndrome coronavirus (SADS-CoV) is highly pathogenic to piglets and poses a major threat to the swine industry. SADS-CoV has a wide cell tropism and pathogenic potential in younger animals. Therefore, understanding how SADS-CoV enters cells is essential for curbing its re-emergence and spread. Here, we report that tunicamycin, an N-linked glycoprotein inhibitor, inhibited the attachment of SADS-CoV to host cells, suggesting that the SADS-CoV receptor may be an N-linked…</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>McCarthy’s Ouster Is Proof, Once Again, That Appeasement Doesn’t Work</strong> - The political-obituary writers will not be kind to one of the weakest House Speakers ever. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/mccarthys-ouster-is-proof-once-again-that-appeasement-doesnt-work">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Trump’s Bloody Campaign Promises</strong> - It’s tempting to ignore the former President’s expressions of rage, but the stakes for American democracy demand that attention be paid. - <a href="https://www.newyorker.com/news/daily-comment/trumps-bloody-campaign-promises">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why Obama’s “Car Czar” Thinks Biden Should Stay Out of the U.A.W. Strike</strong> - Last week, Steve Rattner called the President’s trip to the picket line “outrageous.” Whom did he help—or harm—by going? - <a href="https://www.newyorker.com/news/q-and-a/why-obamas-car-czar-thinks-biden-should-stay-out-of-the-uaw-strike">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Should the West Threaten the Putin Regime Over Ukraine?</strong> - The historian Stephen Kotkin on the state of the war and the dangers of a Russian Tet Offensive. - <a href="https://www.newyorker.com/news/q-and-a/should-the-west-threaten-the-putin-regime-over-ukraine">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Trump Legal Show Might Be in Town Until Christmas</strong> - On Monday, the former President appeared at the first day of his three-month civil trial in Manhattan, determined to exploit the case for his political ends. - <a href="https://www.newyorker.com/news/our-columnists/the-trump-legal-show-might-be-in-town-until-christmas">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The lifesaving, Nobel Prize-winning discovery that almost didn’t happen</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/lHqxFTLsApbzOHMbJj_QmAbBD5Q=/0x0:6803x5102/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72723491/GettyImages_1701994937.0.jpg"/>
<figcaption>
Katalin Karikó and Drew Weissman speak during a press conference after being awarded the Nobel Prize in Medicine on October 2, 2023 in Philadelphia. | Mark Makela/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Katalin Karikó co-won a Nobel Prize this week for her groundbreaking work on mRNA vaccines — but she had to fight against professional science to do it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="T9M5Rh">
The Nobel Prize for Medicine was awarded on Monday to Katalin Karikó and Drew Weissman, for discoveries that led to the development of mRNA vaccinations, including those developed during the Covid-19 pandemic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bdzC9H">
Arguably few Nobelists had a hand in saving more lives than Karikó and Weissman. One study estimates that in the US alone, the vaccines <a href="https://www.cidrap.umn.edu/covid-19/report-covid-19-vaccines-saved-us-115-trillion-3-million-lives">prevented over 3 million deaths and 18 million hospitalizations and saved more than $1 trillion</a>. Worldwide, of course, the effect was <a href="https://www.cidrap.umn.edu/covid-19-vaccines-saved-estimated-20-million-lives-1-year">even larger</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TJSw87">
By far the most effective vaccines against Covid-19 were the mRNA vaccines developed by Pfizer and Moderna, and both companies benefited from the discoveries of Weissman and Karikó about how to change the body’s immune response to mRNA. Their Nobel Prize, obviously, is richly deserved.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lzHtDE">
It’s also a bit of a warning sign.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aJbSJe">
In hindsight, little medical research was of more importance than Karikó’s work at Weissman’s lab on making mRNA vaccines a reality. But at every stage, the research community that should have embraced this research instead stymied it, because of powerful incentives in science toward work that is more fundable and more publishable.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="phH44u">
It’s hard to escape the impression that mRNA vaccines reached production despite the system, rather than because of it. And that raises the question: What other extraordinary, world-changing research programs are our current research lab system not equipped to nourish?
</p>
<h3 id="18LH7U">
We nearly missed out on this huge line of research
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="g0xAag">
Karikó was hired by the University of Pennsylvania in 1989 in a role that put her on track to become a full tenured professor. But she struggled to get grant funding for her work on mRNA. “She was too committed to the promise of mRNA to switch to other, perhaps more easily fundable projects,” David Scales, a junior researcher who worked in her lab at Penn, <a href="https://www.wbur.org/news/2021/02/12/brutal-science-system-mrna-pioneer">told WBUR</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZdsTgg">
And in roles like Karikó’s, bringing in grant funding was everything. In 1995, Penn demoted her. “Anyone of less grit and determination would have just given up long before the groundwork for today’s vaccines was laid,” Scales said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Slw3Fe">
But Karikó persevered. She had to hop from lab to lab at Penn and eventually joined Weissman’s lab, which was working on an HIV vaccine. Together, they ended up taking a closer look at a key barrier to creating mRNA vaccines: the body’s strong immune response to mRNA. mRNA would be unusable for vaccines if the body identified it as a foreign agent and destroyed it. Together, they worked out a way of altering the chemical bonds in mRNA in a way that appeared to allow it to escape the immune system’s notice.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hX72Os">
A key scientific hurdle to mRNA vaccination had been cleared. But the hurdles that were a product of our broken academic science system remained.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rGS2kH">
“We couldn’t get funding. We couldn’t get publications. We couldn’t get people to notice RNA as something interesting,” Weissman <a href="https://www.npr.org/sections/health-shots/2023/10/02/1202941256/nobel-prize-goes-to-scientists-who-made-mrna-covid-vaccines-possible">said in an interview on Monday</a>. “Pretty much everybody gave up on it.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9lFNul">
They tried working toward mRNA vaccination outside academia, <a href="https://www.bu.edu/articles/2021/how-drew-weissman-and-katalin-kariko-developed-mrna-technology-inside-covid-vaccines/">founding a small company called RNARx</a>. That too ran into problems. In 2006, Penn applied for and received two patents for Karikó’s and Weissman’s work. But RNARx struggled to come to a licensing agreement with Penn for the patents.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0RanMs">
So, <a href="https://www.nature.com/articles/d41586-021-02483-w">according to 2021 reporting in <em>Nature</em></a>, Penn sold the patents for $300,000 to a small lab-reagents supplier in Madison. When the funder backing the vaccine company Moderna called Karikó to ask to license the patents, she had to tell them <a href="https://www.nature.com/articles/s41591-018-0183-7">she didn’t have them</a>. They were eventually sublicensed to both Moderna and BioNTech (which partnered with Pfizer), for hundreds of millions of dollars.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dul7uS">
“I was kicked out, from Penn, was forced to retire,” Karikó <a href="https://www.nobelprize.org/prizes/medicine/2023/kariko/interview/">told</a> Adam Smith, interviewing her on behalf of the Nobel Prize committee after she got her award. She eventually found a place at BioNTech, which required her commuting to and from Germany.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lnjyac">
So in other words, a researcher with a world-changing discovery was for so long unable to get sustained funding to do further research — a clear failure of our institutions for deciding what merits funding.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IXpVy2">
It’s hard to guess exactly what went wrong in Karikó’s case, but there are some obvious possibilities. Researchers have <a href="https://publichealth.jhu.edu/2016/researchers-peer-review-system-for-awarding-nih-grants-is-flawed">long complained</a> that a single objection on the committee considering a grant can effectively kill it, making the process highly subjective and leading it to strongly favor incremental, conservative research rather than bold ideas. Even worse, it can end up favoring work that is already halfway done.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6RYUdI">
One of the best strategies to get a grant is to not apply until you already have very impressive results data, but this strategy highly rewards having a well-funded lab. That makes it very difficult for new researchers to break in — like Karikó, who immigrated to the US at age 30, without many financial resources.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W9GU7Q">
Then, because of Karikó’s struggle to get grants, she was demoted by her institution. It’s a fate many scientists are deeply afraid of, and which therefore discourages them from doing work that may not get grants — even if they know it has important world-changing potential. And she wasn’t able to get other institutional jobs. Thankfully, Karikó had a supportive husband who could enable her commute to BioNTech in <em>Germany</em> to continue her work at a company that saw its potential.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JfqMHl">
(I should note here that mRNA vaccines were the work of countless people, and that no new vaccine is developed by a lone hero — that’s simply not how modern biology works. Many, many other people have worked on mRNA vaccines, and there are probably other routes around the immune system response problem. But if the technology had been even a few years delayed, millions of lives would have been lost, which means that Karikó and Weissman’s work, employed in both the Moderna and Pfizer vaccines, was indeed a huge deal.)
</p>
<h3 id="HwACSL">
What we may be missing
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U8ZyCF">
This is not a triumphant story about the successful functioning of our systems for R&amp;D and scientific discovery. Those systems appear to have basically failed. This is a story about how through sheer stubbornness, and a few strokes of luck, the mRNA technology made it to market, where it saved millions of lives and trillions of dollars. That makes it a great fit for a Nobel Prize, which celebrates individuals who made extraordinary contributions that changed the face of their fields. But it also makes it a cautionary tale.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tYQq9h">
How many people like Karikó and Weissman are out there, confident that they’re on to something world-changing and yet unable to get the funding to keep researching it? How many scientists quietly change careers toward something more fundable?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="x3iJ7P">
There are a lot of different ideas for how we could make scientific funding more flexible and responsive, and let scientists pursue projects without immediate payoffs. I’ve written about <a href="https://www.vox.com/future-perfect/2021/12/18/22838746/biomedicine-science-grants-arc-institute">the Arc Institute, a philanthropic effort to do just that</a>, as well as about zany-but-legitimately-valuable ideas like <a href="https://www.vox.com/future-perfect/2019/1/18/18183939/science-funding-grant-lotteries-research">allocating some funding by lottery</a>. But while we can debate the best solution, I don’t think we can debate any longer that there’s a problem.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cEeJuj">
There’s too much at stake in scientific research for us to set grant and tenure policies that systematically fail our researchers and then hope they overcome adversity and succeed anyway. Karikó’s untouchable conviction and decades-long labor in obscurity until she was at last vindicated is a beautiful story of the triumph of the human spirit, and it should never happen again.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nlZ0Sg">
<em>A version of this newsletter originally appeared in the </em><a href="https://www.vox.com/future-perfect"><em><strong>Future Perfect</strong></em></a><em> newsletter. </em><a href="https://www.vox.com/pages/future-perfect-newsletter-signup"><em><strong>Sign up here!</strong></em></a>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="98kknI">
</p></li>
<li><strong>Rental cars, where the fees are limitless and a reservation is a little bit fake</strong> -
<figure>
<img alt="A figure stands at one end of a long, winding ribbon of printed paper next to an empty signature line. At the other end, in the distance, a person stands in front of a pink SUV with a clipboard." src="https://cdn.vox-cdn.com/thumbor/7vpQf-lcFncx-FXq2FLotDOMdX8=/0x0:1440x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72723413/BigSqueeze_RentalCars_PaigeVickers.0.png"/>
<figcaption>
Paige Vickers/Vox
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The baffling structure of rental car taxes and fees, explained.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mVLSVl">
The experience of renting a car can give you some trust issues. You’re booking on some travel website, where you start at Price A. Then, by the time you get to the checkout, you’re at a higher Price B that wasn’t the one you saw prominently advertised — maybe it was in small letters, but you didn’t notice. When you go to pick up the car, you’ve got to make a deliberate effort to avoid the even higher Price C, which the guy at the counter is pretty intent on selling you on. Even if Price B sticks, you find yourself staring at your receipt, wondering what in the world all those extra charges are. That’s assuming that the vehicle you intended to rent is even available. That’s assuming any vehicle is available.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="m0UPnC">
We all know <a href="https://www.vox.com/money/23862850/flights-travel-delays-fees-nightmares-compensation-airlines">flying sucks</a>. Airlines <a href="https://www.vox.com/the-goods/23410970/flight-fees-airlines-frontier-spirit-baggage-pick-seat">squeeze every penny they can out</a> of us with add-ons and fees, and airports are <a href="https://www.vox.com/23460965/airport-restaurant-flight-prices-lounge-bar-expensive">wildly overpriced</a>. The experience of renting a car often flies under the radar, but it can be similarly terrible.
</p>
<aside id="JsZbOR">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="djzRoe">
The pandemic <a href="https://www.nytimes.com/2020/07/17/nyregion/car-rental-nyc-shortage-coronavirus.html">was an absolute nightmare</a> for renting a car, and <a href="https://www.washingtonpost.com/technology/2021/12/01/hertz-customer-kate-klonick-rental-car/">horror stories were not hard to come by</a>. (To be fair to the companies here, a business where your inventory may be taken very very far away and not returned to its initial location is inherently complicated, and the pandemic <a href="https://www.washingtonpost.com/business/2021/05/01/rental-car-shortage-economy/">was a doozy</a> for the industry in a lot of ways.) Even though some of the dust has settled, it’s hardly smooth sailing now. The customer service experience remains exhausting. The concept of a reservation still comes with a bit of a wink — there’s a whole <a href="https://www.youtube.com/watch?v=4T2GmGSNvaM">Seinfeld scene</a> about it. The fees and tax scheme is incomprehensible.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7Ak4GV">
“The fees in the car rental sector, in many ways, are worse than fees in the airline sector because there’s a factor of sticker shock,” said <a href="https://www.economicliberties.us/william-mcgee/">William J. McGee</a>, senior fellow for aviation and travel at the American Economic Liberties Project, an anti-monopoly think tank.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xn8CRY">
There’s a specific and daunting element of surprise that comes with the price and logistics of renting a car. And yet, the rental car rodeo is often an inevitable part of travel: It’s expensive, it’s annoying, and it’s not clear it’s getting better anytime soon.
</p>
<h3 id="qz4r1k">
Don’t just be mad about rental car companies for the fees
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MIpaw5">
A family friend recently reached out about the cost of their rental car from Budget at the Denver airport. They sent over the receipt, and it’s really something to behold. The base rate for an eight-day rental is $555.19; the total they owe is more than $400 higher.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="me49DF">
Deciphering what each line item corresponds to requires navigating a ton of jargon. A “concession recovery fee” costs $77.74; the “Colorado road safety fee” is $19.17; an “energy recovery fee” is $7.11. A look at Budget’s <a href="https://www.budget.com/en/customer-care/faqs/global/glossary">glossary</a> and some googling provide an explanation of the fees, especially where they come from. The concession fee is a kickback to the airport. The state fee <a href="https://www.dollar.com/AboutUs/FEESLanding.aspx">helps pay</a> for Colorado’s roads. The energy fee is because customers are supposed to chip in to keep the company’s lights on, which seems like it could be rolled up into the base rate but okay.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RZCfw5">
It’s ridiculous that consumers would need to look in a glossary to decipher the list of charges they’re faced with. More importantly, it’s representative of the issue with rental car fees and taxes: They’re coming at you from every which way, and many of them you can’t avoid. The guy at the counter trying to sell you on insurance is someone you can hopefully say no to (more on that later), but the locality that’s figured out that a rental car tax is <a href="https://www.azcentral.com/story/news/local/arizona/2019/10/07/proposition-302-rental-car-tax-stadium-holds-us-supreme-court-dismisses-case/3904307002/">a nice way to pay for a new sports stadium</a>, not so much.
</p>
<div class="c-float-right">
<aside id="Kk4rby">
<q>It’s sort of like consumers are walking down the street, and state and local governments, airports, and car rental companies are all picking cash out of their pockets at every step</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VI0e5L">
“People are not wrong to hate all the fees that they’re hit with, but we distinguish between fees that are unavoidable and those you can potentially do something about,” said <a href="https://www.consumerreports.org/cro/about-us/our-people/our-experts/chuck-bell/index.htm">Chuck Bell</a>, director of financial services policy at Consumer Reports.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4E6TEa">
It’s sort of like consumers are walking down the street, and state and local governments, airports, and car rental companies are all picking cash out of their pockets at every step.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jbxu17">
Airports can charge different fees that add up quickly, such as <a href="https://www.theflightexpert.com/glossary/airport-concession-fee/">concession fees</a>, which amounts to the rent companies are supposed to pay for being allowed to do business on their premises. That’s generally passed on to the consumer. The same goes for <a href="https://images.hertz.com/pdfs/chargeexplained.pdf">facility fees</a>, which are supposed to go toward new car rental facilities. If you pick your car up at the airport, those fees are unavoidable.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qTISAQ">
Many state and local governments across the country <a href="https://blog.autoslash.com/states-with-highest-car-rental-taxes-and-fees/">levy a number of fees and taxes on rental cars</a>, too, whether it’s for <a href="https://www.mass.gov/info-details/surcharge-on-vehicle-rental-transactions-for-police-training-in-massachusetts#:~:text=Vendors%20will%20collect%20a%20%242,Trucks">police training</a> or miscellaneous projects or (I was being serious earlier) <a href="https://lithub.com/youre-paying-for-sports-stadiums-you-dont-even-go-to/">sports arenas</a>. The reasoning on the part of lawmakers is that it’s easier to raise taxes on out-of-towners than it is on locals, and state and local governments want and need the money. “In some cities and states, there are politicians that say, ‘Well, if we try and put in a tax for this big project … the people that vote for us are all going to be upset, and they’re not going to want to pay this tax,’” McGee said. “But if you have tourists coming through, they don’t vote for you.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bXYZe6">
One question you might be asking yourself here is why any of these fees and taxes are even broken out. If it’s an unavoidable part of the total cost, who cares who the money’s going to? One simple answer is it is a way for rental car companies to offer full disclosure to consumers — and to show them their bill is more expensive in part because of mandated extra charges outside of their control. From the consumer’s perspective, it’s a bit of a wash.
</p>
<h3 id="xHLbcC">
But also do be mad at the companies for the fees
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6WZonx">
There’s probably a discussion to be had about whether governments and airports should account for so much of the rental car receipt pie. But what can be a bigger pain point for consumers — and one that’s within the industry’s control — is the extra charges the companies themselves add on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WP6sPi">
The industry will say a lot of the extra fees are your choice, which is true. You decide whether you want to pay that extra driver fee, and you pick if you want that insurance. Still, some of it isn’t up to you, like <a href="https://www.hertz.com/rentacar/reservation/reviewmodifycancel/templates/rentalTerms.jsp?KEYWORD=FEES&amp;EOAG=YQB">having to pay</a> the company for parking and licensing the vehicle, or being hit with some random penalty for smoking in the car even though you swear you did not. Regardless, a lot of it is confusing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BVTujv">
In the summer of 2022, Brittany Miller, who works for a nonprofit in Seattle, got duped by a Hertz location in Las Vegas on what was and was not her choice. The agent there told her she had to purchase additional insurance (in rental car parlance, a collision damage waiver) even though she and her boyfriend had insurance of their own — your regular car insurance usually covers rentals. She says the agent made it seem as though they wouldn’t be able to walk out of the lot if they didn’t agree, telling them it was Nevada state law. So, they relented.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QAEBqe">
Once they later realized they’d been tricked, they decided to try to get their $300 back — an endeavor that took over a year. Hertz at one point told her it would be $25 to even investigate the case because six months had passed since the original rental date. Eventually, she found an email address on Reddit that got her results. Hertz returned the money and apologized for the “misinformation” the couple was given at the lot. “It was kind of gratifying but also frustrating to hear,” Miller said. “It shouldn’t be pulling teeth to get them to admit wrongdoing.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lMTQhV">
Hertz did not respond to a request for comment for this story.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8yIuQb">
While Miller’s experience is perhaps an extreme one, it’s not entirely novel. Once you’re at the counter trying to pick up your car, you’re faced with a barrage of questions that can be tough to decipher, especially as the agent tries to upsell you. A few years ago, I found myself in a back-and-forth with a rental car agent over whether I should get the <em>extra</em> extra insurance. He warned me the coverage I had wouldn’t pay for damages … if a tree fell on my car.
</p>
<div class="c-float-right">
<aside id="2WCXkR">
<q>“The devil’s really in the details with a lot of these things”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3v8IFy">
“There’s a lot of fine print, so if you’re not prepared for it when you walk up to the counter, you can be persuaded to take it because you’re afraid,” Bell said. “The devil’s really in the details with a lot of these things, and I think people get bamboozled into accepting add-on charges that they don’t need.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qDpG46">
Car rentals, relative to other services, have more discretionary and add-on services that they try to induce people to accept. There are all sorts of levels of protections for the car, for liability, for possessions, and accompanying fees consumers have to sort through. Do you need a car seat? What about GPS? Will someone under 25 be driving? Really, have you thought about the insurance? What about transponders for tolls? There can also be penalties for canceling, for dropping off a car too late, or for dropping it off too early.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3IAKde">
Your mileage may vary on which of these is fair and which isn’t, but some of it does feel, at the very least, mildly unfair. Rental companies sometimes push consumers to pay extra for toll transponders, even though there aren’t tolls in the area. If people forgo a transponder and do hit some tolls, <a href="https://www.nytimes.com/2020/01/23/travel/rental-cars-and-cashless-tolls.html">the add-on charges can be much higher than the tolls themselves</a>. There <a href="https://www.wthr.com/article/news/investigations/13-investigates/how-few-40-cent-tolls-your-rental-car-can-result-90-bill/531-9a3dde85-caf0-4b7b-be90-4e63b8bdfc35">have been lawsuits</a> around the issue, and some rental car <a href="https://www.cnet.com/personal-finance/use-avis-or-budget-you-could-be-owed-part-of-45-million-hidden-fee-settlement/">companies have reached settlements</a> to repay consumers over hidden fees around tolls. This is all likely disclosed somewhere in rental agreements, but who has time to pore through contracts to see where they may or may not get gouged?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4hyzR1">
“There’s a lot of confusion at the front desk, and there’s that huge rental document that they’re scrolling through on an iPad and getting you to sign,” said <a href="https://www.linkedin.com/in/mjmcgovern12/">Melanie McGovern</a>, a spokesperson for the Better Business Bureau.
</p>
<h3 id="dqTvvL">
Why are we — or rather, rental cars — like this?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="en3ADT">
Reporting for this story, I heard all sorts of terrible tales from consumers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JqPB7p">
Shoshana Weissman, a Washington, DC, strategist, was charged some $2,000 by Budget after her rental because the company claimed she hadn’t returned the car to the Salt Lake City airport. She sent the company all sorts of proof she had, going as far as to request security footage from the airport. Eventually, Budget sent her an email saying the car had been re-rented in Minneapolis and returned the money, no further explanation offered. “They accused me of stealing a car,” she said. (This is a problem Hertz <a href="https://www.npr.org/2022/12/06/1140998674/hertz-false-accusation-stealing-cars-settlement">has made headlines for</a>, too.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZVozkn">
Budget didn’t respond to a request for comment for this story.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aSzXLa">
One man couldn’t get ahold of the company’s tow service when his rental car broke down, so he had to hire an outside service and then fight to be reimbursed even though it was the company’s car that was defective. Another man spent days going from location to location trying to find something comparable to the van he’d reserved, eventually realizing that the agent at the first office had lied about the vehicle’s availability elsewhere. Another customer was in an accident that wasn’t his fault while driving a rental car. He has insurance through his credit card; the rental car company tried to charge him for forgoing its insurance anyway.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="71jDEY">
I don’t want to malign the car rental industry here, which did go through quite a roller coaster ride in terms of <a href="https://www.theatlantic.com/technology/archive/2021/12/car-rental-shortage-covid/621068/">inventories and demand as a result of the pandemic</a>. But it feels fairly clear there is much to be desired in the consumer experience. As to why it’s like this, there’s no one specific answer, though there are some issues in play.
</p>
<div class="c-float-right">
<aside id="rDnnYQ">
<q>“It’s an oligopoly, really, between the big three”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iFnjsh">
For one thing, there isn’t much competition in the car rental industry. Enterprise, Avis, and Hertz run some 86 percent of the show, McGee said. “There are only three car rental companies in the United States, which is kind of shocking when you think about it. Because Enterprise owns National and Alamo, and Hertz owns Dollar and Thrifty, and Avis owns Budget,” he said. “It’s an oligopoly, really, between the big three. And so that’s problematic in terms of service, in terms of cost.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DINQ6K">
McGee said he believes the industry needs more regulation and attention. “Problems with car rental companies just don’t seem to get the sort of media coverage that other problems do with <a href="https://www.vox.com/travel">airlines</a> and hotels and whatnot,” he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0bd1C6">
Some efforts to address “<a href="https://www.vox.com/policy-and-politics/2023/2/15/23599953/biden-junk-fee-protection-act-white-house-ticketmaster-resort">junk fees</a>” in rental cars, among other sectors, may be underway as part of the <a href="https://www.vox.com/joe-biden">Biden administration</a>’s efforts to broadly take on hidden charges and drip pricing, where companies draw consumers in with one price and then slowly add on extra charges. (I will note here that the rental car websites are generally pretty good about telling you at least the base unavoidable total cost upfront. The travel websites are not so great; the total cost might show up on the search page, but in much smaller print than the lower advertised price they’d like you to notice.) The FTC is currently <a href="https://www.ftc.gov/news-events/news/press-releases/2022/10/federal-trade-commission-explores-rule-cracking-down-junk-fees">exploring a rule</a> on junk fees. It also has <a href="https://consumer.ftc.gov/articles/renting-car">resources for consumers</a> on navigating the rental car industry.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aocGRa">
Part of the issue here is that there’s nobody advocating for the consumer in the web of rental car fees. “There’s nobody at the table telling the airport or state and local government, ‘Don’t tax people for this,’” Bell said. “That also just reflects interest-group-based politics where consumers are underrepresented.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="noPhc9">
You could imagine a government that would say it wants to hold down costs for people when they go on vacation and would regulate the fees that are charged by providers, but our system doesn’t really do that. “You can charge extra fees to consumers because you can,” Bell said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="q5aZ4c">
<a href="https://www.internationalcarrentalshow.com/speakers/gregory-m-scott">Greg Scott</a>, a spokesman for the American Rental Car Association, said that every rental car company he is aware of “is aware of and in complete compliance” with the National Association of Attorneys General guidelines on disclosure to consumers. “There’s no question that at the counter, you’re asked a series of questions and you have to make a series of decisions,” he said. “We’re in the customer service business. We rent cars, we want you to be happy with it.”
</p>
<h3 id="c4eSpT">
Good luck and Godspeed next time you’re at the rental car counter
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N7ZOC5">
The fact of the matter is that when it comes to rental cars, a lot is out of consumers’ hands. There really is no getting around a lot of the fees, whether it be from states or airports or the companies themselves. The whole which-car-will-you-even-get situation is frustrating but inevitable. Prices, while they’re coming down, <a href="https://www.nerdwallet.com/article/travel/car-rental-price-increase">are still much higher than they were in 2019</a>. But there are some limited measures consumers can take.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ETITuW">
<a href="https://www.consumerreports.org/fees-billing/how-to-avoid-sneaky-car-rental-fees/">Do your homework</a> before you get to the counter so that when you get there you know what you’re going to do. Check if you’ve already got some sort of insurance coverage on the rental so you’re ready to say no on the collision damage waiver. Figure out the closest gas station so you’ll be able to fill up before returning the car instead of paying the prepaid fuel fee, which is almost always more expensive. You can bring your own toll transponder if you have one. If you don’t, look up whether the route you’re going to take has tolls and how hard it is to avoid them. Avoid picking your car up at the airport and choose a non-airport location. Call ahead to make sure your reservation really is there. Note any potential damage to the car and how many miles it has on it before you leave the lot.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QQ6ZxP">
If you’re not sure about something at the counter, press the agent on it, even if you feel pressured to move fast. “BBB encourages consumers to read the fine print and take the time to ask questions to understand the full agreement before they sign anything,” McGovern said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Cl3elk">
If something does go awry, complain, not only to the company but also to the FTC and CFPB and Better Business Bureau. “I would encourage people to fight back if they’re having problems,” Bell said. McGee noted that people can appeal to their credit card companies, specifically invoking the <a href="https://www.experian.com/blogs/ask-experian/what-is-the-fair-credit-billing-act/">Fair Credit Billing Act</a> that limits liability for unfair billing practices, and ask them to put a hold on the charge and investigate it. “It often works,” he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LsBUY9">
Comparison shopping can be tricky because the initial price you see often has little to do with the final cost. There are other options, like <a href="https://www.theverge.com/2022/1/11/22878329/turo-car-sharing-ipo-s1-stock-price-losses">Turo</a>, which is sort of like <a href="https://www.vox.com/airbnb">Airbnb</a> for cars, said Charles Leocha, president and co-founder of Travelers United, a traveler advocacy group. “There’s different levels of car rentals, and they all have different pricing,” he said. He also recommends looking at budget brands, even if many of them are owned by the big three. “They take care of the car the same way, it’s just they’re maybe a year older.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yn9azC">
The catch in all of this is that it puts a lot of onus on consumers to do what they can to make sure they don’t get tripped up at every turn.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oaf1Do">
And yet, many of us have found ourselves there before and will likely be there once again: Standing at the rental car counter, ready to get moving, and wondering what on God’s green earth is going on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5G5qzT">
<em>We live in a world that’s constantly trying to sucker us and trick us, where we’re always surrounded by scams big and small. It can feel impossible to navigate. Each month, join Emily Stewart to look at all the little ways our economic systems control and manipulate the average person. Welcome to </em><a href="https://www.vox.com/the-big-squeeze"><em>The Big Squeeze</em></a><em>.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NF25sR">
<a href="http://vox.com/big-squeeze-newsletter"><em>Sign up to get this column in your inbox</em></a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fEmYHz">
<em>Have ideas for a future column or thoughts on this one? Email </em><a href="mailto:emily.stewart@vox.com"><em>emily.stewart@vox.com</em></a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="d7mm6q">
</p></li>
<li><strong>How TikTok monetizes dangerous health trends in real time</strong> -
<figure>
<img alt="Illustration of five sets of eyes focusing on a TikTok logo. You can see darkened silhouettes of people talking and passing money to others within the logo." src="https://cdn.vox-cdn.com/thumbor/pLAfCxSsw_b4zQd3ekcUtOlTmNc=/240x0:1680x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72723379/Vox_TikTok_PaigeVickers.0.png"/>
<figcaption>
Paige Vickers/Vox
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</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Castor oil won’t dissolve cysts and tumors. Some creators on TikTok Shop are earning commissions by suggesting otherwise.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C0GU7p">
For the past few weeks, TikTok creator Busy Belle has been telling her nearly 30,000 followers that castor oil, if applied to the belly button, can fight bacterial infections and dissolve tumors. She’s posted several videos to TikTok Shop, the platform’s new e-commerce tool, promoting Aliver Jamaican Black Castor Oil. One of these videos has more than 1.5 million views and the product she links to lists more than 33,000 total sales. Belle presumably got a cut from more than a few of these.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="q3Z291">
“The people who are like, ‘Eh, blah blah blah, TikTok people are just lying,’” Belle says in one video. “No, we are not. Why would I be posting about it? I’m a Taurus, I don’t lie, okay?” She said her routine involves “lathering” herself with castor oil once a week, adding, “I’m telling everybody to do it. It’s natural and why not.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="J6o7M1">
Although castor oil has been sold (with little evidence) as a cure-all for ages, it’s recently become trendy, and its sales are getting a boost from influencers and stores claiming that it can relieve a wide range of ailments. Its popularity spans several social platforms. But on TikTok, creators like Busy Belle can make you feel as though you were fated to discover a new trend that promises to make you feel or look better.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XnocB9">
Recommendation algorithms can feel magical when they deliver what you want. And when they work, you might be tempted to interpret the eerie insights as evidence that the algorithm knows you better than you know yourself. Get a steady stream of posts and videos about a certain topic and you might start to wonder if your feed is trying to tell you something about yourself. So in the land of wellness influencers on TikTok — and the diaspora of niches that draw from this space — you might feel as though a promised treatment or cure “found” you just when you needed it most.
</p>
<aside id="Vw9Z3W">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pIAdt3">
Social media platforms like TikTok have always been filled with snake oil salesmen and wellness influencers pushing questionable cleanses and protocols. But <a href="https://www.vox.com/technology/2023/9/14/23872449/tiktok-shop-for-you-page-ads">the US rollout of the TikTok Shop in September</a> has shined a spotlight on how dubious online wellness advice and TikTok’s trend cycles work together to find new audiences, and how they repackage ineffective or dangerous health remedies that have been around for years. Creators shilling <a href="https://www.rollingstone.com/culture/culture-features/tiktok-shop-parasite-cleanse-ban-1234826112/">parasite cleanses</a>, detox drinks, miracle cures, and promoting oils and tinctures with overbroad health claims have all been pushed onto the For You Pages of TikTok users in recent weeks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9uk6N8">
TikTok Shop is an in-app marketplace selling an unfathomable amount of products that have become, or aspire to become, viral must-haves. Its listings are a river of offerings from verified brands, to scammy or counterfeit copies of popular items, to the sort of cheap apparel and household goods you might expect on Wish or Temu. It’s designed to help the company make money off the #TikTokMadeMeBuyIt phenomenon, where viral attention drives viewers to buy everything from <a href="https://www.foodandwine.com/lifestyle/kitchen/fullstar-vegetable-chopper-tiktok-review">vegetable choppers</a> to <a href="https://www.dailydot.com/irl/psychology-of-tiktok-shopping-ordinary/">beauty products</a> to <a href="https://www.vice.com/en/article/epxyyz/the-best-tik-tok-items">portable carpet steamers</a>. Instead of jumping to Amazon or another third-party online store, TikTok Shop incentivizes users to buy products directly in the app.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vOda9m">
The Shop also provides a revenue stream for creators, who can make “affiliate” videos promoting products found in the shop. Instead of a paid sponsorship arrangement, affiliates make a commission from sales. Some influencers and companies have been able to use the Shop to monetize trends by targeting TikTok’s young users in order to sell ineffective, dangerous, or unethical products.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O2zUIg">
The mechanisms for this sort of targeting predate the Shop launch. Earlier this year, some wellness TikTok creators <a href="https://www.vox.com/technology/2023/7/29/23811639/tiktok-borax-challenge-dangerous-laundry-detergent">popularized the dangerous and ineffective</a> practice of drinking borax diluted in water. Fitness influencers have also previously <a href="https://health.clevelandclinic.org/dry-scooping-tiktok-trend/">promoted “dry scooping” protein powder</a>, which experts say is not a good idea. Merchants have even used TikTok’s popularity with younger viewers to push steroids and steroid-like drugs, according to a recent report from the <a href="https://counterhate.com/wp-content/uploads/2023/09/TikToks-Toxic-Trade-Steroids-and-Steroid-Like-Drugs.pdf">Center for Countering Digital Hate</a>. Researchers found that videos promoting these substances, at times appearing to target teenagers, were viewed more than 500 million times on TikTok, mostly by people younger than 24. Those videos shill products on behalf of third-party merchant sites, and the influencers making the content get a commission for sales. (The report’s data precedes the launch of TikTok Shop in the US.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Aseydx">
“Alternative” health trends do well on TikTok because they provide recommendations that are “cheap, accessible, and explained through a scientific-adjacent explanation that feels familiar,” Rachel Moran, who studies health misinformation as a postdoc scholar at the University of Washington, <a href="https://www.vox.com/technology/2023/7/29/23811639/tiktok-borax-challenge-dangerous-laundry-detergent">told Vox earlier this year</a>. But there’s another factor at play here: Personal anecdotes, a powerful marketing tool on TikTok, have long been a core evangelizing tool for dubious wellness and health advice. And even TikTok influencers with apparent credentials and large followings might be giving out compromised advice. A recent <a href="https://www.washingtonpost.com/wellness/2023/09/13/dietitian-instagram-tiktok-paid-food-industry/">Washington Post investigation</a> found that American Beverage, a lobbying group for the soft drink industry, had paid 10 registered dietitians to promote the benefits of artificial sweeteners on social media in response to the <a href="https://www.vox.com/2023/7/1/23780348/aspartame-cancer-carcinogenic-health-risk-who-iarc-fda-efsa-diet-coke-sugar-free">World Health Organization’s warning</a> that aspartame might cause cancer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ytsnjn">
What’s happening on TikTok Shop is an extension of these trends, for those who can get their products past the platform’s moderation tools. While steroids and borax “detox” mixes aren’t necessarily showing up in the Shop tab, some dubious wellness trends are finding success there by offering products that have some legitimate uses, just perhaps not those being promoted by those getting paid to sell them. Castor oil, for example, has been surging in popularity this summer as a wellness hack, but it’s also an FDA-approved laxative and an ingredient in some skin care products and eye drops. Creators advertising on behalf of castor oil merchants on TikTok Shop, however, are making much broader claims, ones often not backed by any scientific evidence.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IAoNqv">
Which brings us back to influencers, like Busy Belle, who have been pushing castor oil’s health benefits and encouraging people to buy products that influencers will get a commission for selling. While castor oil may help moisturize your skin and hair, claims about stimulating hair growth or reversing wrinkles are not supported by research. Claims about castor oil’s ability to improve eye health also aren’t backed up by any high-quality research, according to a recent close look at the oil’s new status as a wellness trend in the <a href="https://www.nytimes.com/2023/08/08/well/castor-oil-benefits-hair-growth-tumor.html">New York Times</a>. And while it’s unlikely that applying castor oil to your skin will cause any serious issues, it won’t penetrate your body and dissolve tumors and cysts.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E3yend">
By early October, #CastorOil had at least 925 million views on TikTok, according to the platform’s page for the hashtag, and many of the top videos specifically promote applying the oil to your belly button. In one TikTok Shop video advertising Aliver’s castor oil, a beauty creator with 99,000 followers who goes by <span class="citation" data-cites="mtagbeauty">@mtagbeauty</span> tells viewers to “start slow” with castor oil, claiming that it’s such an effective detox regime that some people might feel a bit sick if starting too strong. Other Shop videos about castor oil claim that it can treat anxiety, boost the immune system, and treat arthritis.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bHoydh">
Some sponsored videos use audio from a popular lecture from Barbara O’Neill, an Australian activist who has promoted treating cancer with baking soda and claims that all vaccines are harmful. In it, O’Neill says that if castor oil is applied on or around the belly button, “it will heal any problems in the abdomen,” that the oil will “penetrate” and break up cysts and fibroids in the uterus, and heal constipation and diarrhea by “penetrating” into the colon. In the same lecture, she claims it can cure cancer in the abdomen and brain (<a href="https://www.logicallyfacts.com/en/fact-check/false-no-castor-oil-compresses-cannot-cure-tumors-bone-spurs-cysts-and-uterine-fibroids">none of these things are true</a>). O’Neill is not permitted to provide health services in Australia, after a <a href="https://www.theguardian.com/lifeandstyle/2019/oct/03/naturopath-who-said-bicarbonate-soda-cures-cancer-banned-for-life-by-health-watchdog">health care watchdog investigation</a> found in 2019 that she was not accredited, had not earned any health-related degrees or diplomas, and was, under the guise of a naturopathic medical practitioner, providing her patients with false, potentially deadly advice and encouraging them to forgo chemotherapy in favor of her preferred, ineffective, cancer “cures.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TwQ4CD">
Some of the recent castor oil videos appear to violate <a href="https://seller-us.tiktok.com/university/essay?identity=1&amp;role=1&amp;knowledge_id=1399532709988097&amp;from=policy">TikTok Shop’s policies</a> against selling “unlicensed medicines, herbal or homeopathic products, and those making health claims,” weight loss supplements, and “beauty and personal care products that claim to have medical applications but are not verified by the United States Food and Drug Administration.” But it’s not clear whether these rules apply to the TikTok Shop listing, the TikTokers being paid to advertise these products, or both — even when an item’s popularity seems to be tied directly to a questionable health practice that has become a trend.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zBmpMz">
This current castor oil trend on TikTok can feel like a multimedia assault on the For You page of anyone who has indicated to the algorithm that they’re interested in the topic or even wellness trends in general. See enough videos advertising Aliver’s castor oil — of which there are many — and you might start getting videos shilling the <a href="https://trademarks.justia.com/870/70/aliver-87070240.html">company</a>’s other beauty offerings, including its aphrodisiacs and skin-lightening products, which are also against Shop rules.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0hkVBA">
Whenever a new bad trend gets attention — whether it’s drinking borax, pushing ineffective cancer “cures,” or selling vaccine “detox” concoctions — social media platforms eventually swoop in, enforce their rules, and emphasize that the majority of users on the platform aren’t seeing the content in question. The attention fades, the influencers regroup, and the cycle begins again.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7SWBo6">
TikTok Shop is a new era for the platform, one that makes it even easier for the company to monetize trends in real time instead of being outpaced by the astonishing speed of TikTok fame. But rule enforcement, context, and caution continue to lag behind.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fxorbx">
<em>A version of this story was also published in the Vox Technology newsletter. </em><a href="https://www.vox.com/pages/newsletters"><em><strong>Sign up here</strong></em></a><em> so you don’t miss the next one!</em>
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rasputin and Sky Fall shine</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ravishing Form, Queenstown, Artemis Ignacia, Monteverdi and Stellar Gold excel</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>Pat Cummins on World Cup 2023: Australians get a lot of love when we play in India</strong> - As World Cup 2023 gets underway, Australian captain Pat Cummins chats about the India-Australia cricketing rivalry and why he watches sports documentaries</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Asian Games | Compound archers secure men, women team gold, make it three in a row</strong> - India is assured of at least five medals in archery at the ongoing Asian Games</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>Australian players have a plan for Indian spinners, says Pat Cummins</strong> - Cummins will banking on his “aggressive” opener David Warner, “key player” Glenn Maxwell to guide Australia to victory in their opening World Cup match against India in Chennai</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>Here are the big stories from Karnataka today</strong> - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated by Nalme Nachiyar.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nanded hospital deaths | Dean, paediatrician booked for culpable homicide</strong> - 37 patients, including 18 newborns, died in a span of four days.</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 day to celebrate the birds in Bengaluru</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>‘Chaaver’ movie review: Tinu Pappachan’s craft fails to save a poorly-written film</strong> - Tinu Pappachan’s ‘Chaaver,’ starring Kunchacko Boban and Arjun Ashokan, suffers from the sketchily-defined characters and a one-sided political narrative</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>TNSTC conductor placed under suspension in the Nilgiris</strong> -</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Abkhazia: Russia to build naval base in Georgian separatist region, says local leader</strong> - The claim comes from the separatist region as Kyiv steps up attacks on Moscow’s Black Sea fleet.</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>Tenerife: Evacuations as fire flares up again in high temperatures</strong> - Efforts are under way to extinguish a blaze that first ravaged part of the island in August.</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: US gives 1.1 million rounds of ammunition seized from Iran to Kyiv</strong> - The US military says the rounds were confiscated from a ship taking arms to Yemeni rebels last year.</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>Migrant crisis: Sunak to urge ‘Europe-wide solutions’ at summit in Granada</strong> - At a summit in Spain, Europe’s leaders will discuss how to lower irregular migration to the continent.</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>Venice bus crash: The heroes who pulled survivors from burning wreck</strong> - The two men say they have not slept since the tourist bus plunged off a bridge and caught fire.</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>Japan is studying a reusable rocket, but it won’t fly before 2030</strong> - This launcher would replace the H3 rocket, which hasn’t yet become operational. - <a href="https://arstechnica.com/?p=1973400">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Vulnerabilities in Supermicro BMCs could allow for unkillable server rootkits</strong> - With the ability to manage huge fleets of servers, BMCs are ideal places to stash malware. - <a href="https://arstechnica.com/?p=1973415">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Colorful quantum dots snag 2023 Nobel Prize in Chemistry</strong> - Moungi G. Bawendi, Louis E. Brus, and Alexei I. Ekimov laid a vital nanotech foundation. - <a href="https://arstechnica.com/?p=1973096">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Report: Amazon made $1B with secret algorithm for spiking prices Internet-wide</strong> - Report reveals details about Amazon’s secret algorithm redacted in FTC complaint. - <a href="https://arstechnica.com/?p=1973347">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Apple fixes overheating problems and 0-day security flaw with iOS 17.0.3 update</strong> - Some third-party apps will also need to be updated to address overheating issue. - <a href="https://arstechnica.com/?p=1973341">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>During the USSR regime a communist governor is visiting one of the small towns in his district</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The mayor of the town is excited to show the governor how dedicated his people are to the communist party, so as they are walking through the town bazaar, he pulls one of the farmers aside<br/> to ask him a couple of questions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He asked “Comrade, if you had two apartments, wouldn’t you be happy to donate one to the communist party?” and the guy replied “Off course comrade mayor, I would be happy contribute to the motherland”. The mayor went on “And if you had two automobiles, wouldn’t you be happy to donate one of them to the communist party?” and the guy said “Off course, it would be an honor”. The governor is very impressed, but the mayor decided to keep going “And comrade, if you had two cows, wouldn’t you also happily donate one back to the people?”. At this the farmer hesitated and with a dismayed look said “No, that I would not donate”. Puzzled, the mayor asks him “But if you would donate an apartment and a car, why wouldn’t you donate a cow?” The farmer looks back at him and says “Well, I actually have two cows…”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/crypto_junkie2040"> /u/crypto_junkie2040 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/17046vs/during_the_ussr_regime_a_communist_governor_is/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/17046vs/during_the_ussr_regime_a_communist_governor_is/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A business man sees a fisherman laying down on the shore, looking at the sky</strong> - <!-- SC_OFF --></p>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Hi, why aren’t you fishing?
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Well, I caught the fishes we plan on eating
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
But if you caught more, you could sell them.
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And then what?
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Then you could buy a motor for the boat to catch even more fish
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And then what?
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Then you can sell more fish, get more boats, and even more fish, and sell that as well
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And then what?
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Then you can enjoy life!
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And what do you think I’m doing right now?
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</ul>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/crazy4llama"> /u/crazy4llama </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/170dkce/a_business_man_sees_a_fisherman_laying_down_on/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/170dkce/a_business_man_sees_a_fisherman_laying_down_on/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cruise ship drive by</strong> - <!-- SC_OFF --></p>
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I was on a cruise recently.
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One morning, the ship was passing very close to a small island. As I was admiring the serenity of this far off place, a ruckus occurred.
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On the island, a man came running out from the thickness of the brush. His hair was down to his waist and his beard almost the same. His clothes were tattered straps, barely covering his beet red skin. He was frantically waving his arms around as he jumped up and down. And he seemed to be yelling something.
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The captain of the ship happened to be on a morning stroll around the deck, so I grabbed his attention and brought him to my spot on the rail.
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“Captain, there, on that island. There’s a man over there. What do you think he’s yelling?” I asked.
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“Oh, don’t mind him”, the captain replied. “He does this every 3 months when we pass by”.
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Spaceace91478"> /u/Spaceace91478 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/17031x5/cruise_ship_drive_by/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/17031x5/cruise_ship_drive_by/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Five Jewish Women Go Out for Dinner</strong> - <!-- SC_OFF --></p>
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After their meals arrive, the waiter comes over and asks, “Ladies, is anything alright?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/kinshane227"> /u/kinshane227 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16zokfo/five_jewish_women_go_out_for_dinner/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16zokfo/five_jewish_women_go_out_for_dinner/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I went for a circumcision and the surgeon forgot his scalpel.</strong> - <!-- SC_OFF --></p>
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Still managed to pull it off though
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Cunt_Puffin"> /u/Cunt_Puffin </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/170cum4/i_went_for_a_circumcision_and_the_surgeon_forgot/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/170cum4/i_went_for_a_circumcision_and_the_surgeon_forgot/">[comments]</a></span></p></li>
</ul>
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