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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants</strong> -
<div>
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional NSP14 enzyme, possessing exonuclease and mRNA capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscores the dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.28.559966v1" target="_blank">SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants</a>
</div></li>
<li><strong>Plasma of COVID-19 patients does not alter electrical resistance of human endothelial blood-brain barrier in vitro.</strong> -
<div>
The pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) instigated the most serious global health crisis. Clinical presentation of COVID-19 frequently includes severe neurological and neuropsychiatric symptoms. However, it is presently unknown whether and to which extent pathological impairment of blood-brain barrier (BBB) contributes to the development of neuropathology during COVID-19 progression. In the present study we used human induced pluripotent stem cells-derived brain endothelial cells (iBECs) to study the effects of blood plasma derived from COVID-19 patients on the BBB integrity in vitro. We also performed a comprehensive analysis of the cytokine and chemokine profiles in the plasma of COVID-19 patients, healthy and recovered individuals. We found significantly increased levels of interferon {gamma}-induced protein 10 kDa (IP-10), hepatocyte growth factor (HGF), and interleukin-18 (IL-18) in the plasma of COVID-19 patients. However, blood plasma from COVID-19 patients did not affect transendothelial electrical resistance (TEER) in iBEC monolayers. Our results demonstrate that COVID-19-associated blood plasma inflammatory factors do not impair BBB integrity directly and suggest that pathological remodelling of BBB during COVID-19 may occur through indirect mechanisms.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.28.559927v1" target="_blank">Plasma of COVID-19 patients does not alter electrical resistance of human endothelial blood-brain barrier in vitro.</a>
</div></li>
<li><strong>Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike</strong> -
<div>
Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding domain of spike protein. In contrast, whether antigenic drift occurs in the S2 domain remains largely elusive. Here, we perform a deep mutational scanning experiment to identify S2 mutations that affect binding of SARS-CoV-2 spike to three S2 apex public antibodies. Our results indicate that spatially diverse mutations, including D950N and Q954H, which are observed in Delta and Omicron variants, respectively, weaken the binding of spike to these antibodies. Although S2 apex antibodies are known to be non-neutralizing, we show that they confer partial protection in vivo. We further demonstrate that such in vivo protection activity is diminished by the natural mutation D950N. Overall, this study indicates that the S2 domain of SARS-CoV-2 spike can undergo antigenic drift, which represents a potential challenge for the development of more universal coronavirus vaccines.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.27.559757v1" target="_blank">Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike</a>
</div></li>
<li><strong>Efficient inhibition of fusion inhibitor HY3000 peptide to SARS-CoV-2 emerging EG.5, EG.5.1 and BA.2.86 variants</strong> -
<div>
SARS-CoV-2 continues to evolve and spread. Recently, the Omicron EG.5 lineage, bearing an additional F456L mutation in spike (S) protein compared to its ancestor XBB.1.9.2, and its sub-variant EG.5.1, which carries a further Q52H mutation, have raised concerns due to their increased prevalence and extended immune escape properties. Additionally, an alarming variant, BA.2.86, has also garnered global concern because it contains over 30 amino acid mutations in its S protein compared to BA.2, including more than 10 changes in receptor-binding domain (RBD), reminiscent of the appearance of the Omicron variant in late 2021. Therefore, there is an urgent need to assess the effectiveness of current vaccines and therapeutics against EG.5, EG.5.1 and BA.2.86. In our previous work, we reported the design and broad-spectrum antiviral activity of a peptide fusion inhibitor HY3000 against SARS-CoV-2 and its variants including XBB.1.5. Here, we continued to evaluate the inhibitory potency of the HY3000 peptide against the prevailing EG.5 and EG.5.1, as well as XBB.1.16, FL.1.5.1, FY.3 and BA.2.86. Our data indicated that the peptide retained its potent inhibitory activities against these variants, indicating its potential as a good virus fusion inhibitor with broad-spectrum therapeutic effect against current and future SARS-CoV-2 variants. Currently, the HY3000 has been finished in Phase II clinical trial in China and has also been approved to conduct clinical investigation by U.S. Food and Drug Administration (FDA), suggesting a good application prospect against the ongoing COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.28.559747v1" target="_blank">Efficient inhibition of fusion inhibitor HY3000 peptide to SARS-CoV-2 emerging EG.5, EG.5.1 and BA.2.86 variants</a>
</div></li>
<li><strong>Inhibiting Glutamine Metabolism Blocks Coronavirus Replication in Mammalian Cells</strong> -
<div>
Developing therapeutic strategies against COVID-19 has gained widespread interest given the likelihood that new viral variants will continue to emerge. Here we describe one potential therapeutic strategy which involves targeting members of the glutaminase family of mitochondrial metabolic enzymes (GLS and GLS2), which catalyze the first step in glutamine metabolism, the hydrolysis of glutamine to glutamate. We show three examples where GLS expression increases during coronavirus infection of host cells, and another in which GLS2 is upregulated. The viruses hijack the metabolic machinery responsible for glutamine metabolism to generate the building blocks for biosynthetic processes and satisfy the bioenergetic requirements demanded by the "glutamine addiction" of virus-infected host cells. We demonstrate how genetic silencing of glutaminase enzymes reduces coronavirus infection and that newer members of two classes of small molecule allosteric inhibitors targeting these enzymes, designated as SU1, a pan-GLS/GLS2 inhibitor, and UP4, which is specific for GLS, block viral replication in mammalian epithelial cells. Overall, these findings highlight the importance of glutamine metabolism for coronavirus replication in human cells and show that glutaminase inhibitors can block coronavirus infection and thereby may represent a novel class of anti-viral drug candidates.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.27.559756v1" target="_blank">Inhibiting Glutamine Metabolism Blocks Coronavirus Replication in Mammalian Cells</a>
</div></li>
<li><strong>Inhibition of SARS-CoV-2 Infection in Human Airway Epithelium with a Xeno-Nucleic Acid Aptamer</strong> -
<div>
Background: SARS-CoV-2, the agent responsible for the COVID-19 pandemic, enters cells through viral spike glycoprotein binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2). Given the lack of effective antivirals targeting SARS-CoV-2, we previously utilized systematic evolution of ligands by exponential enrichment (SELEX) and selected fluoro-arabino nucleic acid (FANA) aptamer R8-9 that was able to block the interaction between the viral receptor-binding domain and ACE2. Methods: Here, we further assessed FANA-R8-9 as an entry inhibitor in contexts that recapitulate infection in vivo. Results: We demonstrate that FANA-R8-9 inhibits spike-bearing pseudovirus particle uptake in cell lines. Then, using an in-vitro model of human airway epithelium (HAE) and SARS-CoV-2 virus, we show that FANA-R8-9 significantly reduces viral infection when added either at the time of inoculation, or several hours later. These results were specific to the R8-9 sequence, not the xeno-nucleic acid utilized to make the aptamer. Importantly, we also show that FANA-R8-9 is stable in HAE culture secretions and has no overt cytotoxic effects. Conclusions: Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.27.559799v1" target="_blank">Inhibition of SARS-CoV-2 Infection in Human Airway Epithelium with a Xeno-Nucleic Acid Aptamer</a>
</div></li>
<li><strong>An extended catalytic model to assess changes in risk for multiple reinfections with SARS-CoV-2</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The SARS-CoV-2 pandemic has illustrated that monitoring trends in multiple infections can provide insight into the biological characteristics of new variants. Following several pandemic waves, many people have already been infected and reinfected by SARS-CoV-2 and therefore methods are needed to understand the risk of multiple reinfections. Objectives: In this paper, we extended an existing catalytic model designed to detect increases in the risk of reinfection by SARS-CoV-2 to detect increases in the population-level risk of multiple reinfections. Methods: The catalytic model assumes the risk of reinfection is proportional to observed infections and uses a Bayesian approach to fit model parameters to the number of nth infections among individuals whose nth infection was observed at least 90 days before. Using a posterior draw from the fitted model parameters, a 95% projection interval of daily nth infections is calculated under the assumption of a constant nth infection hazard coefficient. An additional model parameter was introduced to consider the increased risk of reinfection detected during the Omicron wave. Validation was performed to assess the model9s ability to detect increases in the risk of third infections. Key Findings: The model parameters converged when applying the model9s fitting and projection procedure to the number of observed third SARS-COV-2 infections in South Africa. No additional increase in the risk of third infection was detected after the increase detected during the Omicron wave. The validation of the third infections method showed that the model can successfully detect increases in the risk of third infections under different scenarios. Limitations: Even though the extended model is intended to detect the risk of nth infections, the method was only validated for detecting increases in the risk of third infections and not for four or more infections. The method is very sensitive to low numbers of nth infections, so it might not be usable in settings with small epidemics, low coverage of testing or early in an outbreak. Conclusions: The catalytic model to detect increases in the risk of reinfections was successfully extended to detect increases in the risk of nth infections and could contribute to future detection of increases in the risk of nth infections by SARS-CoV-2 or other similar pathogens.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.27.23296231v1" target="_blank">An extended catalytic model to assess changes in risk for multiple reinfections with SARS-CoV-2</a>
</div></li>
<li><strong>Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<b>Objective</b> Vaccination reduces the risk of acute COVID-19 in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. <b>Methods </b> This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record (EHR) Program for visits between vaccine availability, and October 29, 2022. Conditional logistic regression was used to estimate VE against long COVID with matching on age group (5 to 11, 12 to 17) and time period and adjustment for sex, ethnicity, health system, comorbidity burden, and pre-exposure health care utilization. We examined both probable (symptom-based) and diagnosed long COVID in the year following vaccination. <b>Results </b> The vaccination rate was 56% in the cohort of 1,037,936 children. The incidence of probably long COVID was 4.5% among patients with COVID-19, while diagnosed long COVID was 0.7%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5 44.5) against probable long COVID and 41.7% (15.0 60.0) against diagnosed long COVID. VE was higher for adolescents 50.3% [36.3 61.0]) than children aged 5-11 (23.8% [4.9 39.0]). VE was higher at 6 months (61.4% [51.0 69.6]), but decreased to 10.6% (26.8 37.0%) at 18 months. <b>Discussion </b> This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data. <b>Discussion </b> This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.27.23296100v2" target="_blank">Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort</a>
</div></li>
<li><strong>Model-based impact evaluation of new tuberculosis vaccines in aging populations under different modeling scenarios: the case of China.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The slow descent in TB burden, the COVID-19 pandemic, along the rise of multidrug-resistant strains of Mycobacterium tuberculosis, seriously threaten TB control and the goals of the End TB strategy. To fight back, several vaccine candidates are under development, with some of them undergoing phases 2B and 3 of the development pipeline. The impact of these vaccines on the general population needs to be addressed using disease-transmission models, and, in a country like China, which last year ranked third in number of cases worldwide, and where the population is undergoing a fast process of demographic aging, the impact of TB vaccination campaigns may depend heavily upon the age of targeted populations and with the mechanistic descriptions of the TB vaccines. For these reasons, transmission models need to capture the coupling between TB dynamics and demographic evolution, as well as to be able to accommodate different mechanistic descriptions of TB vaccine protection. In this work, we studied the potential impact of a new TB vaccine in China targeting adolescents (15-19 y.o.) or elderly people (60-64 y.o.), according to varying vaccine descriptions that represent reasonable mechanisms of action leading to prevention of disease (PoD), or prevention of recurrence (PoR), each of them targetting specific routes to TB disease. To measure the influence of the description of the coupling between transmission dynamics and aging in TB transmission models, we explored two different approaches to compute the evolution of the contact matrices, which relate to the spreading among different age strata. Our results show that the magnitude of model-based impact estimates substantially depends upon the vaccine profile, and it is also strongly related to the modeling approach chosen to describe the time evolution of contact matrices. In spite of these sources of uncertainty, our results also show, in line with previous modeling works, that elder vaccination is a suitable option in China to reduce the incidence of TB.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.27.23296224v1" target="_blank">Model-based impact evaluation of new tuberculosis vaccines in aging populations under different modeling scenarios: the case of China.</a>
</div></li>
<li><strong>Time trends and modifiable factors of contact tracing coverage in Geneva, Switzerland, June 2020 to February 2022</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Contact tracing has been one of the central non-pharmaceutical interventions implemented worldwide to try to control the spread of Sars-CoV-2, but its effectiveness strongly depends on its ability to detect contacts. Methods: We analysed 1669892 concomitant infections occurring at the same address from June 2020 until February 2022 using an extensive operational database of SARS-CoV-2 tests in Geneva and used permutations statistics to compare the total number of secondary infections occurring at the address with those reported through contact tracing. Results: Manual contact tracing captured on average 41% of the secondary infections, with variation in time from 23% during epidemic peaks to 60% during low epidemic activity. People living in wealthy neighbourhoods were less likely to report contacts (adjusted odds ratio (aOR): 1.6). People living in buildings, compared to people living in single house, were also less likely to report contacts than those living in houses, with an aOR of 1.1 to 3.1 depending on the variant, the size of the building and the presence of shops. This under-reporting of contacts in buildings decreased during periods of mandatory face masking and restriction of private gathering. Conclusions: Contact tracing alone does not detect enough secondary infections to efficiently reduce the propagation of Sars-CoV-2. Public messages and outreach campaigns targeting specific populations, such as those in affluent areas, could enhance coverage. Additionally, measures like wearing face masks, improving ventilation, and implementing gathering restrictions should also be considered to reduce the number of infections occurring during interactions that may not be perceived as high risk.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.22.23287577v3" target="_blank">Time trends and modifiable factors of contact tracing coverage in Geneva, Switzerland, June 2020 to February 2022</a>
</div></li>
<li><strong>Scientifically led response plan for future global open-source initiatives related to emergency intervention.</strong> -
<div>
The modern era of interconnectedness and rapid technological advancements has ushered in a new paradigm of collaborative problem-solving. Open-source initiatives stand at the helm of this paradigm, driving a culture of shared innovation to tackle global challenges. The global response to the COVID-19 pandemic has magnified the pivotal role of open-source solutions, especially in times of emergency interventions. This guide is designed to assist governmental bodies and organizations in understanding, supporting, and leveraging open-source initiatives to effectively respond to future emergencies. It encapsulates valuable insights and actionable recommendations derived from a thorough examination of past open-source engagements, particularly during the COVID-19 pandemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/3nvus/" target="_blank">Scientifically led response plan for future global open-source initiatives related to emergency intervention.</a>
</div></li>
<li><strong>A Phase 2, randomized, double-blind, placebo-controlled multi-center trial sub-study for the clinical effects of paridiprubart treatment in hospitalized critically ill patients with COVID-19 ARDS</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Coronavirus disease 2019 (COVID-19) mortality is predominantly due to acute respiratory distress syndrome (ARDS). There are currently limited treatment options for ARDS, a life-threatening condition with different etiologies, secondary to inflammation-induced lung injury. Paridiprubart is a monoclonal antibody that inhibits Toll-like Receptor 4 (TLR4), a key player in ARDS pathophysiology. Methods: This was a prespecified sub-study of a randomized, double-blind, placebo-controlled, Phase 2 trial evaluating the efficacy and safety of paridiprubart in COVID-19 patients with ARDS receiving invasive mechanical ventilation and additional organ support. Efficacy outcomes were 28- and 60-day all-cause mortality, and improvement in COVID-19 severity and ventilation-free days at 28-days post-treatment. Results: Thirteen (13) and twenty (20) patients received paridiprubart and placebo, respectively. The groups were comparable for demographics and baseline parameters, except for higher kidney failure incidence and use of immune modulators and antivirals, and lower corticosteroids use in the paridiprubart group. Mortality at 28-days post-treatment was 7.7% (1/13) in the paridiprubart group versus 40.0% (8/20) for placebo (OR=0.125; 95% CI, 0.013-1.160; P=0.067; P[bootstrap]=0.011). 60-day mortality was 23.1% (3/13) in paridiprubart-treated patients and 45.0% (9/20) in placebo patients (OR=0.367; 95% CI, 0.077-1.749; P=0.208; P[bootstrap]=0.162). Mean survival time was 55.78 days for paridiprubart recipients compared to 41.44 days for placebo patients (HR=0.386; 95% CI, 0.077-1.436; P=0.156; P[bootstrap]=0.083). Although not statistically significant, results for other efficacy measures favored paridiprubart. Incidence of adverse events was similar in both groups. Conclusions: In COVID-19 patients with ARDS requiring invasive ventilation and organ support, paridiprubart was efficacious in preventing mortality and improving clinical outcomes, with no safety concerns.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.21.23295853v1" target="_blank">A Phase 2, randomized, double-blind, placebo-controlled multi-center trial sub-study for the clinical effects of paridiprubart treatment in hospitalized critically ill patients with COVID-19 ARDS</a>
</div></li>
<li><strong>Genomic evolution of SARS-CoV-2 variants of concern under in vitro neutralising selection pressure following two doses of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine</strong> -
<div>
Aims: To explore viral evolution during in vitro neutralisation using next generation sequencing, and to determine whether sera from individuals immunised with two doses of the Pfizer BioNTech vaccine (BNT162b2) are as effective at neutralising the SARSCoV2 variant of concern (VOC) Delta (B 1.617.2) compared to the earlier lineages Beta (B.1.351) and wildtype (lineage A.2.2) virus. Methods: Using a live virus SARSCoV2 neutralisation assay in Vero E6 cells we determined neutralising antibody titres (nAbT) in 14 participants (vaccine naive (n=2) and post second dose of BNT162b2 vaccination (n=12), median age 45 years [IQR 29 to 65], median time after second dose = 21 days [IQR 19 to 28] against three SARSCoV2 strains: wild-type, Beta and Delta. The determination of nAbT was performed by visual inspection of cytopathic effect (CPE) and inhouse quantitative reverse transcriptase real time quantitative polymerase chain reaction (RTqPCR) to confirm SARS-CoV-2 replication. A total of 110 representative samples including inoculum, neutralisation breakpoints at 72 hrs, negative and positive controls underwent genome sequencing using the Respiratory Viral Oligo Panel version 2 (RVOP) (Illumina Inc. (San Diego, United States of America)) viral enrichment and short read sequencing using (Illumina Inc. (San Diego, United States of America)),(Figure 1). Results: There was a significant reduction in nAbT observed against the Delta and Beta VOC compared with wildtype, 4.4 fold (p = &gt;0.0006) and 2.3 fold (p = 0.0140), respectively (Figure 2). Neutralizing antibodies were not detected in one vaccinated immunosuppressed participant nor the vaccine naive participants (n=2). The highest nAbT against the SARS-CoV-2 variants investigated was obtained from a participant who was vaccinated following SARSCoV2 infection 12 months prior (Table S1). Limited consensus level mutations occurred in the SARS-CoV-2 genome of any lineage during in vitro neutralisation, however, consistent minority allele frequency variants (MFV) were detected in the SARS-CoV-2 polypeptide, spike (S) and membrane protein. Discussion: Significant reductions in nAbT post vaccination were identified, with Delta demonstrating a 4.4 fold reduction. The reduction in nAbT for the VOC Beta has been previously documented, however, limited data is available on vaccine evasion for the Delta VOC, the predominant strain currently circulating worldwide at the time. Studies in high incidence countries may not be applicable to low incidence settings such as Australia as nAbT may be significantly higher in vaccine recipients previously infected with SARSCoV2, as seen in our cohort. Monitoring viral evolution is critical to evaluate the impact of novel SARSCoV2 variants on vaccine effectiveness as mutational profiles in the sub-consensus genome could indicate increases in transmissibility, virulence or allow the development of antiviral resistance.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.24.558921v1" target="_blank">Genomic evolution of SARS-CoV-2 variants of concern under in vitro neutralising selection pressure following two doses of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine</a>
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<li><strong>p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein</strong> -
<div>
The inhibition of p38 mitogen-activated protein kinase (p38-MAPK) by small molecule chemical inhibitors was previously shown to impair severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, however, mechanisms underlying antiviral activity remains unexplored. In this study, reduced growth of SARS-CoV-2 in p38- knockout Vero cells, together with enhanced viral yield in cells transfected with construct expressing p38, suggested that p38-MAPK is essential for the propagation of SARS-CoV-2. The SARS-CoV-2 was also shown to induce phosphorylation (activation) of p38, at time when transcription/translational activities are considered to be at the peak levels. Further, we demonstrated that p38 supports viral RNA/protein synthesis without affecting viral attachment, entry, and budding in the target cells. In addition, we demonstrated that long-term culture of SARS-CoV-2 in the presence of p38 inhibitor SB203580 does not easily select resistant viral mutants. In conclusion, we provide mechanistic insights on the regulation of SARS-CoV-2 replication by p38 MAPK.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.27.559660v1" target="_blank">p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein</a>
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<li><strong>Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera</strong> -
<div>
The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.27.559689v1" target="_blank">Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera</a>
</div></li>
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<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 “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>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mind Body Intervention for Long COVID</strong> - <b>Conditions</b>: Long COVID; Post-Acute Sequelae of COVID-19; COVID Long-Haul <br/><b>Interventions</b>: Behavioral: Mind Body Intervention #1 <br/><b>Sponsors</b>: Beth Israel Deaconess Medical Center <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: STI-1558 <br/><b>Sponsors</b>: Zhejiang ACEA Pharmaceutical Co. Ltd. <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin)</strong> - <b>Conditions</b>: Covid19 <br/><b>Interventions</b>: Other: Placebo; Drug: Metformin <br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center <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>Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells); Biological: Placebo <br/><b>Sponsors</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SA55 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SA55 nasal spray <br/><b>Sponsors</b>: Sinovac Life Sciences Co., Ltd. <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>Tele-physiotherapy on Post-stroke Hemiplegia Patients</strong> - <b>Conditions</b>: Hemiplegia; Muscle Spasticity <br/><b>Interventions</b>: Other: Conventional Physiotherapy + telephysiotherapty <br/><b>Sponsors</b>: Universidad Católica San Antonio de Murcia; Hermanas Hospitalarias del Sagrado Corazón de Jesús; Hospital Universitario Virgen de la Arrixaca <br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise Therapy; Behavioral: Psychotherapy <br/><b>Sponsors</b>: Hannover Medical School; Health Insurance Audi BKK; occupational health service Volkswagen AG; Helmholtz Centre for Infection Research <br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In-silico</em> investigation of 4-nitro-N-1H-pyrazol-3-ylbenzamide towards its potential use against SARS-CoV-2: a DFT, molecular docking and molecular dynamics study</strong> - In the present research work, we report the synthesis and characterization of novel pyrazole derivative obtained by the condensation reaction of 4-nitro benzaldehyde group with one equivalent of the 2-amino pyrazole yielding 4-nitro-N-1H-pyrazol-3-ylbenzamide with high yield. The two symmetry-independent molecules (molecule A and molecule B) differ about the central C-N bond, with the dihedral angles between the pyrazole ring system and the nitrobenzene ring being 13.90° and 18.64°,…</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>Dimeric ACE2-FC Is Equivalent to Monomeric ACE2 in the Surrogate Virus Neutralization Test</strong> - Angiotensin-converting enzyme 2 (ACE2) is the main cellular receptor for the dangerous sarbecoviruses SARS-CoV and SARS-CoV-2. Its recombinant extracellular domain is used to monitor the level of protective humoral immune response to a viral infection or vaccine using the surrogate virus neutralization test (sVNT). Soluble ACE2 is also considered as an option for antiviral therapy potentially insensitive to the changes in the SARS-CoV-2 spike protein. Extensive testing of the samples 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>Ancestral, Delta, and Omicron (BA.1) SARS-CoV-2 strains are dependent on serine proteases for entry throughout the human respiratory tract</strong> - CONCLUSIONS: Our findings demonstrate that entry of Omicron BA.1 SARS-CoV-2 is dependent on serine proteases for entry throughout the respiratory tract.</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>DETECTION OF SARS-COV-2 NEUTRALIZING ANTIBODIES IN RETROPHARYNGEAL LYMPH NODE EXUDATES OF WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) FROM NEBRASKA, USA</strong> - Disease surveillance testing for emerging zoonotic pathogens in wildlife is a key component in understanding the epidemiology of these agents and potential risk to human populations. Recent emergence of SARS-CoV-2 in humans, and subsequent detection of this virus in wildlife, highlights the need for developing new One Health surveillance strategies. We used lymph node exudate, a sample type that is routinely collected in hunter-harvested white-tailed deer (WTD, Odocoileus virginianus) for…</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>Physiological effects of ivabradine in heart failure and beyond</strong> - Ivabradine is a pharmacologic agent that inhibits the funny current responsible for determining heart rate in the sinoatrial node. Ivabradines clinical potential has been investigated in the context of heart failure since it is associated with reduced myocardial oxygen demand, enhanced diastolic filling, stroke volume, and coronary perfusion time; however, it is yet to demonstrate definitive mortality benefit. Alternative effects of ivabradine include modulation of the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The REEP5/TRAM1 complex binds SARS-CoV-2 NSP3 and promotes virus replication</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like other coronaviruses, replicates their genome in virus-induced cytosolic membrane-bound replication organelles (ROs). SARS-CoV-2 promotes the biogenesis of ROs by inducing the rearrangement of endoplasmic reticulum (ER) membranes. NSP3, NSP4, and NSP6 are transmembrane viral non-structural proteins (NSPs) and essential players in the formation of ROs. To understand how these three NSPs work synergistically with host-binding…</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>Pupillographic Analysis of COVID-19 Patients: Early and Late Results After Recovery</strong> - CONCLUSION: PDs were significantly larger in COVID-19 patients in all light intensities in the 1^(st) month after COVID-19. However, pupillary dilation was transient, and no significant difference was found in the 6^(th) month. We suggest that the transient pupillary dilation may be secondary to the autonomic nervous system dysfunction and/or optic nerve and visual pathways alterations following COVID-19.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An In Silico Design of Peptides Targeting the S1/S2 Cleavage Site of the SARS-CoV-2 Spike Protein</strong> - SARS-CoV-2, responsible for the COVID-19 pandemic, invades host cells via its spike protein, which includes critical binding regions, such as the receptor-binding domain (RBD), the S1/S2 cleavage site, the S2 cleavage site, and heptad-repeat (HR) sections. Peptides targeting the RBD and HR1 inhibit binding to host ACE2 receptors and the formation of the fusion core. Other peptides target proteases, such as TMPRSS2 and cathepsin L, to prevent the cleavage of the S protein. However, research has…</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>microRNA-185 Inhibits SARS-CoV-2 Infection through the Modulation of the Hosts Lipid Microenvironment</strong> - With the emergence of the novel betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there has been an urgent need for the development of fast-acting antivirals, particularly in dealing with different variants of concern (VOC). SARS-CoV-2, like other RNA viruses, depends on host cell machinery to propagate and misregulate metabolic pathways to its advantage. Herein, we discovered that the immunometabolic microRNA-185 (miR-185) restricts SARS-CoV-2 propagation by…</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>Protective versus Pathogenic Type I Interferon Responses during Virus Infections</strong> - Following virus infections, type I interferons are synthesized to induce the expression of antiviral molecules and interfere with virus replication. The importance of early antiviral type I IFN response against virus invasion has been emphasized during COVID-19 as well as in studies on the microbiome. Further, type I IFNs can directly act on various immune cells to enhance protective host immune responses to viral infections. However, accumulating data indicate that IFN responses can be harmful…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting SARS-CoV-2 Macrodomain-1 to Restore the Innate Immune Response Using In Silico Screening of Medicinal Compounds and Free Energy Calculation Approaches</strong> - Among the different drug targets of SARS-CoV-2, a multi-domain protein known as NSP3 is a critical element of the translational and replication machinery. The macrodomain-I, in particular, has been reported to have an essential role in the viral attack on the innate immune response. In this study, we explore natural medicinal compounds and identify potential inhibitors to target the SARS-CoV-2-NSP3 macrodomain-I. Computational modeling and simulation tools were utilized to investigate 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>Mannose-Binding Lectins as Potent Antivirals against SARS-CoV-2</strong> - The SARS-CoV-2 entry into host cells is mainly mediated by the interactions between the viral spike protein (S) and the ACE-2 cell receptor, which are highly glycosylated. Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the in vitro anti-SARS-CoV-2 activity of two mannose-binding lectins isolated from the Brazilian plants Canavalia brasiliensis and Dioclea violacea (ConBR and DVL). These lectins inhibited SARS-CoV-2…</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>Atovaquone and Pibrentasvir Inhibit the SARS-CoV-2 Endoribonuclease and Restrict Infection In Vitro but Not In Vivo</strong> - The emergence of SARS-CoV-1 in 2003 followed by MERS-CoV and now SARS-CoV-2 has proven the latent threat these viruses pose to humanity. While the SARS-CoV-2 pandemic has shifted to a stage of endemicity, the threat of new coronaviruses emerging from animal reservoirs remains. To address this issue, the global community must develop small molecule drugs targeting highly conserved structures in the coronavirus proteome. Here, we characterized existing drugs for their ability to inhibit 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>Synthetic Frog-Derived-like Peptides: A New Weapon against Emerging and Potential Zoonotic Viruses</strong> - Given the emergence of the coronavirus disease 2019 (COVID-19), zoonoses have raised in the spotlight of the scientific community. Animals have a pivotal role not only for this infection, but also for many other recent emerging and re-emerging viral diseases, where they may represent both intermediate hosts and/or vectors for zoonoses diffusion. Today, roughly two-thirds of human infections are derived from animal origins; therefore, the search for new broad-spectrum antiviral molecules is…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2</strong> - The S-protein is the major antigen of the SARS-CoV-2 virus, against which protective antibodies are generated. The S-protein gene was used in adenoviral vectors and mRNA vaccines against COVID-19. While the primary function of antibodies is to bind to antigens, catalytic antibodies can hydrolyze various substrates, including nucleic acids, proteins, oligopeptides, polysaccharides, and some other molecules. In this study, antibody fractions with affinity for RBD and S-protein (RBD-IgG and S-IgG)…</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>The Latino Question at the Second Republican Debate</strong> - At an event featuring Univisions Ilia Calderón, the candidates showed little interest in speaking to Latino concerns. - <a href="https://www.newyorker.com/news/daily-comment/the-latino-question-at-the-second-republican-debate">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>“Thank You for Speaking While Im Interrupting”: The Crosstalk Chaos of the Second Republican Debate</strong> - The event, which was billed as a chance for Donald Trumps rivals to change their fortunes, only reinforced the confusion and aimlessness of their candidacies. - <a href="https://www.newyorker.com/news/our-columnists/thank-you-for-speaking-while-im-interrupting-the-crosstalk-chaos-of-the-second-republican-debate">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Peter Daous Theory of Election Interference—by Democrats</strong> - The former Clinton aide, now running the third-party Presidential campaign of Cornel West, on his recent political awakening. - <a href="https://www.newyorker.com/news/q-and-a/peter-daous-theory-of-election-interference-by-democrats">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Violent End of Nagorno-Karabakhs Fight for Independence</strong> - In less than a day, indiscriminate shelling in the region killed hundreds, displaced tens of thousands, and wiped out a thirty-five-year battle for political autonomy. - <a href="https://www.newyorker.com/news/our-columnists/the-violent-end-of-nagorno-karabakhs-fight-for-independence">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Joe Bidens Visit to a U.A.W. Picket Line Was a Powerful Political Gesture</strong> - By joining striking workers in Michigan, the President sent a message that cant be delivered from a White House lectern. - <a href="https://www.newyorker.com/news/our-columnists/joe-bidens-visit-to-a-uaw-picket-line-was-a-powerful-political-gesture">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The prices hospitals post online can be wildly different than what they tell patients over the phone</strong> -
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<figcaption>
Getty Images/iStockphoto
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
University of Texas researchers, with help from Mark Cuban, find price transparency still has a long way to go.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uSn5f7">
When Dr. Peter Cram, the University of Texas Medical Branchs chair of internal medicine, heard billionaire Mark Cuban bemoaning how difficult it is to figure out the cost of routine medical services, he thought he had good news to share.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="usMoHI">
Cram was listening to <a href="https://podcasts.apple.com/us/podcast/jon-talks-to-mark-cuban-billionaires-basketball-and/id1583132133?i=1000547744894">Cubans interview on Jon Stewarts podcast</a>, explaining his difficulty in pinning down a price for his own colonoscopy. So Cram reached out to let Cuban know about the <a href="https://www.cms.gov/priorities/key-initiatives/hospital-price-transparency#:~:text=Starting%20January%201%2C%202021%2C%20each,with%20all%20items%20and%20services.">new federal price transparency rules</a> for hospitals. According to those rules, hospitals must post online prices for many or all of their services. But Cuban said he was skeptical that hospitals would give the same price when a patient called to check the price.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cjXBiE">
At that moment, Cram said, “a lightbulb went off in my head.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qOj66Y">
We already know that shopping, ahead of time, for <a href="https://www.vox.com/health-care">health care</a> is <a href="https://www.vox.com/2015/10/19/9567991/health-care-shopping-mri">harder than it should be</a>. But despite the recent federal efforts to force more transparency for hospital prices, a new study to which both Cram and Cuban contributed reveals that its as difficult as ever to get a clear answer to what seems like it should be an easy question: How much is my MRI going to cost?
</p>
<h3 id="fAANTk">
A simple study asked hospitals how much their services cost. The answer: chaos.
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vaE3SH">
<a href="https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2809589">The new study</a>, led by University of Texas medical student Merina Thomas and Cram and published in <em>JAMA</em>, compared the prices hospitals posted online (as required under new federal regulations) with the prices obtained in phone calls conducted by the team posing as potential patients.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CjD6w3">
They contacted 60 hospitals across the country, a mix of top-ranked facilities, hospitals that primarily serve low-income people, and the other hospitals in between. They asked about two procedures for which comparison shopping is more common: vaginal childbirth and a brain MRI.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oUIQNl">
The researchers went into their study optimistic, as Cram had been when he contacted Cuban, that things had changed since the price transparency rules took effect.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZaZut3">
“I had hoped that perhaps things were improving with the new requirements around price transparency,” Cram told me over email. But: “Our results seem to show that we still have a long way to go.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hrvlK6">
It was rare for the advertised price on the web to be the same as the price quoted over the phone. Less than 20 percent of hospitals provided the same price through an online price estimator as they did when someone spoke to a member of the billing department. In many cases, the disparity was significant, with more than a 50 percent price difference depending on whether you checked on a website or called for a quote.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="f3Lifp">
And in a handful of cases, the price more than doubled depending on how you asked. At two hospitals, MRIs were listed online at $2,000, but “patients” were given a price of more than $5,000 when they called. Five hospitals offered a price of $10,000 for vaginal childbirth over the phone, but the price posted online were twice that much.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LcyiyE">
There didnt seem to be a clear pattern of which quotes were higher. Sometimes they were higher over the phone, sometimes higher on the website.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ys6SNV">
The researchers said they took pains to make sure they were getting apples-to-apples comparisons, going so far as to give specific billing codes during their scripted calls with hospital staff. It didnt matter.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5oNOB4">
They could not identify why exactly they found such a significant disparity. The authors theorized that, because a single “service” may involve multiple different billing codes, it was still difficult even under the transparency rules to communicate to the billing staff exactly what they were inquiring about. They also speculated hospitals are not adequately training their staff, though the authors noted a lack of research on that question.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lltOs4">
The findings add to the evidence that US hospitals may not have “a cogent pricing strategy,” as the researchers put it, meaning hospitals set prices in a somewhat arbitrary manner.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qswCiQ">
Research <a href="https://www.healthsystemtracker.org/brief/price-transparency-and-variation-in-u-s-health-services/">had already found</a> prices for the same services vary wildly at different hospitals. The top-line findings of this new study reveal that it can be difficult to even determine what the price for a given service is at a given hospital. That is a problem both for the 10 percent of the US population that is uninsured as well as people enrolled in high-deductible health plans, which are becoming more common.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LR4AEi">
On top of that, the researchers made one other note in their study: They found poor correlation between brain MRI and vaginal childbirth prices within an individual hospital. In other words, some facilities would have high MRI prices compared to others but low prices for delivering babies — with no discernible economic reason for that disparity. Its chaos.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OBbTJc">
“This lack of correlation raises further questions about whether hospitals have a cogent pricing strategy akin to other businesses … or whether this lack of correlation simply reflects a chaotic and disorganized pricing structure,” the researchers wrote.
</p>
<h3 id="8TAqFZ">
Mark Cuban continues his quest for more transparent medical costs
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xNamqr">
These conclusions are familiar for another one of the studys other coauthors: Cuban, entrepreneur, NBA owner, and founder of the Mark Cuban Cost Plus Drugs Company. Here, he continues to buff his bona fides as a health care provocateur by helping to conceive of the new study, and provide technical and material assistance to make it happen.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3b3Cct">
Cuban has been fixated on market failures in the health care industry for the better part of a decade, particularly for prescription drug prices.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Crc2kE">
Though he <a href="https://www.statnews.com/2016/07/13/mark-cuban-drug-prices-interview/">told me in 2016</a> that he did not have an interest in entering the market himself, he did start a drug company six years later, offering generic drugs directly to patients at a flat 15 percent markup. The companys aim is to reduce the costs faced by uninsured people and people with higher out-of-pocket obligations under their insurance plan (a problem that can be exacerbated by the industrys notorious middlemen, <a href="https://www.vox.com/2023/5/10/23709448/what-are-pbms-pharmacy-benefit-managers-bernie-sanders">pharmacy benefits managers</a>). Experts have <a href="https://priceschool.usc.edu/news/mark-cuban-amazon-pharmacy-drug-costs/">compared it</a> to a Costco business model.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zFMNYg">
The company has gotten a toehold in the market since its launch last year, selling <a href="https://www.forbes.com/sites/joshuacohen/2023/01/01/mark-cubans-cost-plus-drug-company-continues-to-revolutionize-generic-drug-pricing/?sh=678609247919">350 drugs to a customer base of about 1.5 million people</a>. It is planning to begin manufacturing some generic drugs itself, similar to plans by the hospital nonprofit Civica Rx and states like <a href="https://www.vox.com/policy-and-politics/23574178/insulin-cost-california-biden-medicare-coverage">California</a>. Its <a href="https://www.beckershospitalreview.com/pharmacy/8-recent-moves-from-mark-cuban-cost-plus-drugs.html">added</a> pharmacy services, including mail orders. Researchers <a href="https://news.vumc.org/2023/06/08/study-finds-mark-cubans-cost-plus-drug-company-could-save-taxpayers-millions-on-medicare-generic-oncology-drugs/">think</a> it could save Medicare up to $1 billion a year if people start getting certain cancer drugs through Cubans company. It was named <a href="https://time.com/collection/time100-companies-2023/6285143/cost-plus-drugs/">one of Times most influential companies of 2023</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3hHgX4">
Selling generic drugs at minimal markup is not a silver bullet for fixing Americas high drug costs, as <a href="https://www.pharmacytimes.com/view/expert-mark-cuban-s-pharmacy-has-shown-there-s-no-silver-bullet-to-disrupt-the-pharmacy-value-chain">experts</a> are <a href="https://www.cnbc.com/2022/07/28/mark-cuban-pharmacy-cost-plus-drugs-struggling-with-brand-name-drugs.html">happy</a> to point out. For one, that has no effect on new breakthrough medicines that are expensive but protected by patents. Still, most credit the company for offering genuine low-price options that particularly help people who face exorbitant costs otherwise.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yNIhya">
Now with this hospital study, Cuban has lent support to exposing absurdities in another sector of the health care industry. Since he first started speaking out on drug prices during <a href="https://www.vox.com/2015/12/17/10436618/martin-shkreli-arrest-explained">the scandals of the mid-2010s</a>, as costs and public anger grew, <a href="https://www.vox.com/congress">Congress</a> has finally started taking <a href="https://www.vox.com/policy/2023/8/30/23850979/medicare-drug-price-negotiations-10-prescription-list">serious action to address the cost of medicine</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8yBfa8">
Hospital prices are another frontier for reform. Many experts see price transparency — a work in progress as Cram put it — as only the beginning. As the <em>JAMA</em> studys authors observed in their paper, “absent improvements in customer service, public frustration with hospitals is likely to grow.”
</p></li>
<li><strong>A program that saved child care for millions is expiring. What now?</strong> -
<figure>
<img alt="Seen from above, three children in yellow shirts play with brightly colored puzzle pieces on a tiled floor. " src="https://cdn.vox-cdn.com/thumbor/LXu0Vf-lEKHwFa7XGDH7ECIWLzc=/870x157:7834x5380/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72700912/GettyImages_1232619181.0.jpg"/>
<figcaption>
Young children play at Little Flowers Early Childhood and Development Center in Baltimore in 2021. | The Washington Post via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The “child care cliff” marks the end of one of the last pandemic-era safety nets.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RFnrAQ">
This weekend, parents and <a href="https://www.vox.com/child-care">child care</a> providers across the nation are bracing for the end of an instrumental federal program that has stabilized child care programs and reduced costs for families over the past three years.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BTNFDP">
Some $24 billion worth of child care funding — one of the last remaining Covid-19 emergency relief programs still in effect — is set to expire Saturday. Issued as part of the $1.9 trillion <a href="https://www.vox.com/policy-and-politics/2021/3/10/22320350/biden-sign-stimulus-bill-covid-19">American Rescue Plan</a>, the program marked the largest investment in child care in US history and allowed fragile businesses to cover rent and maintenance and raise wages for their notoriously <a href="https://www.epi.org/publication/higher-wages-for-child-care-and-home-health-care-workers/">underpaid staff</a>. The <a href="https://www.vox.com/joe-biden">Biden administration</a> has reported that the grants helped <a href="https://www.acf.hhs.gov/occ/map/arp-act-stabilization-funding-state-territory-fact-sheets#:~:text=In%20the%20United%20States%3A,with%20a%20persistent%20poverty%20rate.">80 percent of US licensed child care centers</a> stay afloat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="InhIVl">
Frequently referred to as the “child care cliff,” the expiration of the grants is expected to renew strain on the child care sector, which already runs on tight margins, struggles to recruit and retain staff from higher-paying industries, and charges most parents far more than they can comfortably afford.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wxmws9">
Many news organizations, including <a href="https://www.nytimes.com/2023/06/21/upshot/child-care-daycare-disruptions.html">the New York Times</a>, the <a href="https://www.washingtonpost.com/opinions/2023/08/27/child-care-funding-crisis/">Washington Post</a>, <a href="https://www.axios.com/2023/09/20/child-care-cliff">Axios</a>, <a href="https://www.bloomberg.com/news/articles/2023-09-06/child-care-funding-expiration-risks-disrupting-women-s-work-force-gains?embedded-checkout=true&amp;sref=qYiz2hd0">Bloomberg</a>, the <a href="https://www.wsj.com/us-news/education/as-pandemic-funds-expire-child-care-centers-struggle-to-survive-6cefdf5b">Wall Street Journal</a>, and <a href="https://www.msnbc.com/opinion/msnbc-opinion/biden-child-care-cliff-us-economy-rcna103631">MSNBC</a>, have cited an estimate from the liberal think tank the Century Foundation stating that 70,000 child care programs will likely close, resulting in 3.2 million children losing access to care.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2xP8iU">
That figure was derived from an <a href="https://www.naeyc.org/state-survey-briefs">October 2022 survey</a> of 12,000 early childhood educators that found 34 percent of child care programs reported that they would have closed during the pandemic if not for the emergency grants. The grants covered 220,000 programs and 9.6 million kids, so the Century Foundation multiplied those figures by 0.34 to arrive at its estimate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4erAXZ">
Experts in child care policy told Vox, however, that the “cliff” may prove far less of a tumble for providers and families than that popular statistic suggests — partly due to <a href="https://www.vox.com/policy/2023/4/17/23667770/child-care-crisis-prek-family-immigration">poor data</a> on industry supply and demand and partly because <a href="https://earlysuccess.org/2022-progress-and-landscape">most states have made</a> <a href="https://info.childcareaware.org/blog/state-session-round-up-summer-2023">unprecedented investments</a> in their child care systems over the last two years.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S3frfV">
The federal grants were authorized to help child care programs during the extraordinary circumstances of the pandemic, after lawmakers deemed the child care sector <a href="https://www.help.senate.gov/imo/media/doc/the_need_for_ongoing_support_for_the_nations_child_care_sector_report.pdf">“uniquely vulnerable”</a> to the crisis, and less able to access relief loans through methods available to other small businesses. In a US Senate HELP Committee <a href="https://www.help.senate.gov/imo/media/doc/the_need_for_ongoing_support_for_the_nations_child_care_sector_report.pdf">report</a> issued this past spring, Sens. Bernie Sanders (I-VT) and Patty Murray (D-WA) noted that emergency relief was needed because child care providers began “hemorrhaging money during pandemic shutdowns” as fewer children attended and they faced unexpected costs to comply with reduced group sizes, cleaning materials, and personal protective equipment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bvjpP8">
Today, programs are no longer struggling to enroll students nor needing to cover the costs of pandemic safety regulations. “Saying you would have closed during Covid if not for the grants is not the same thing, that you will close after Covid if the grants dont continue,” said Matt Bruenig, founder of another left-wing think tank, the <a href="https://www.peoplespolicyproject.org/">Peoples Policy Project</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LOqCtv">
One leading child care expert declined to comment on the widely cited Century Foundation estimate (“We didnt do the number and I dont want to speak directly to that,” Sarah Rittling, of the <a href="https://www.ffyf.org/">First Five Years Fund</a>, told Vox), while another said that they knew no one who expected the loss of programs to reach anywhere near 70,000, but did not want to say so on the record for fear of alienating other leaders in their child care advocacy coalition.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4ZS0Rz">
“Will there be some adjustments [when the funds expire]? Yes, obviously, thats fairly true, but you see estimates that a quarter of American kids will lose their child care spots and I will gladly take any bet that anyone at the Century Foundation wants to place,” said Patrick T. Brown, a child care policy analyst at the <a href="https://eppc.org/">Ethics and Public Policy Center</a>, a conservative think tank. “I do not think 25 percent of kids are going to lose their child care. People have a vested interest in using strong frames and narratives to say we have a broken market.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gJ1P5M">
Julie Kashen, director for womens economic justice at The Century Foundation, defended her organizations analysis but acknowledged that the estimate of program closures is unlikely to come to pass, telling Vox its more like a “worst-case scenario.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qanlgX">
“A number of states have put forward their own state funding and our analysis did not account for that,” she said. “We dont have numbers yet of how much will be mitigated by state investments, but from Alaska to Maine to Illinois, they have put their own funding in, and that will make a decent difference in reducing the losses.”
</p>
<h3 id="mR6fhE">
Why Congress isnt extending the Covid-19 child care grants
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hVtgjR">
The federal pandemic grants were objectively successful in helping to stabilize the child care sector over the last three years, leaving many people baffled that <a href="https://www.vox.com/congress">Congress</a> would choose not to renew the funding now. The Department of Labor recently reported that the price of child care rose 6 percent in July over the previous year, nearly double <a href="https://www.wsj.com/economy/child-care-prices-are-rising-at-nearly-twice-the-overall-inflation-rate-2c279c61?mod=article_inline">the rate of inflation</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mVqkbA">
From Republicans perspective, the child care grants, like other Covid-19 safety net programs, were passed as an emergency relief measure, and now that the emergency is over, the pandemic level of spending should not become the new federal baseline. A strong current among conservatives supports “going back to normal” and <a href="https://www.nytimes.com/2023/06/01/us/politics/debt-limit-senate.html">reining in spending</a> more broadly to address inflation and the deficit.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wIhctB">
Democrats and progressives argue that funding for child care was woefully low before the pandemic, and returning to the status quo now, amid a tighter labor market and fierce hiring competition from other industries, would be untenable. Reduced federal funding could mean pay cuts or hiring freezes, or hikes in costs that families cant afford, leading to fewer children served and, ultimately, closure of some programs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lXf7gN">
In response to the impending deadline, congressional Democrats earlier this month <a href="https://www.murray.senate.gov/wp-content/uploads/2023/09/The-Child-Care-Stabilization-Act-One-Pager.pdf">proposed a bill</a> to give $16 billion to child care providers each year for the next five years. It has no Republican co-sponsors and <a href="https://www.politico.com/news/2023/08/31/biden-child-care-system-00113613">even its own authors concede</a> that its unlikely to go anywhere. The Biden administration has <a href="https://www.politico.com/news/2023/08/31/biden-child-care-system-00113613">declined to lobby for</a> additional child care funding in the fraught ongoing budget negotiations, arguing that it needs to bargain with Republicans only over emergency priorities to stave off a government shutdown.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HIH7Zu">
One recurring challenge for Democrats is that because they have so many areas they want to see new big investments in, and because they work within broad advocacy coalitions, leaders <a href="https://www.slowboring.com/p/the-real-reason-bidens-child-poverty?utm_source=profile&amp;utm_medium=reader2">often struggle</a> to home in on a few specific priorities, instead championing lots of big social investments at once.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oymMYY">
This dynamic was on display during the failed Build Back Better negotiations and amid <a href="https://www.vox.com/2022/8/8/23296951/inflation-reduction-act-biden-democrats-climate-change">Inflation Reduction Act</a> talks. Child care investments were in competition with new spending on preschool, affordable housing, paid medical and family leave, and the expanded child tax credit. In the end, virtually none won out.
</p>
<h3 id="dDHt4w">
Child care programs face tougher staff recruitment. Parents face higher costs.
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="saKtsa">
Over the last two years <a href="https://info.childcareaware.org/blog/state-session-round-up-summer-2023">many states passed new legislation</a> to support child care access, affordability, and quality, including red states such as <a href="https://www.alabamaschoolreadiness.org/alabama-advocates-celebrate-historic-42-million-increase-in-state-early-childhood-education-investments/#:~:text=Home-,Alabama%20advocates%20celebrate%20historic%20%2442%20million%20increase%20in%20state%20early,for%20early%20care%20and%20education.">Alabama</a>, <a href="https://info.childcareaware.org/hubfs/Geaux%20Far%20LA%20Legislative%20Recap-2.pdf">Louisiana</a>, <a href="https://legiscan.com/MT/bill/HB648/2023">Montana</a> and <a href="https://ndkidscount.org/2023-legislative-session-childrens-well-being-bills">North Dakota</a>, as well as blue and purple states like <a href="https://info.childcareaware.org/hubfs/Final-2023-Legislative-Update-FINAL.pdf">Minnesota</a>, <a href="https://www.vox.com/policy-and-politics/2022/10/18/23404090/new-mexico-election-result-child-care-early-childhood-prek">New Mexico</a>, <a href="https://new-futures.org/issues/child-care-working-families">New Hampshire</a>, <a href="https://www.startearly.org/post/our-response-to-the-approved-illinois-fiscal-year-2024-state-budget/#:~:text=Start%20Early%20is%20thrilled%20that,with%20disabilities%20and%20developmental%20delays.">Illinois</a>, <a href="https://sd09.senate.ca.gov/news/20230719-ca%E2%80%99s-largest-date-investment-child-care-increasing-provider-pay-and-lowering-fees#:~:text=California's%20investment%20in%20child%20care,Gavin%20Newsom.">California</a>, <a href="https://www.threadalaska.org/thread-blog/ccpo-broadcast-child-care-relief-funding-update-provider-town-hall-follow-up/">Alaska</a> and <a href="https://www.vox.com/politics/2023/5/22/23726703/childcare-investments-vermont-ece-economy-parents-kids">Vermont</a>. Most states were in strong fiscal positions and built on the political momentum for child care investments that coalesced during the pandemic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7GlXsM">
Linda Smith, who heads early childhood research at the <a href="https://bipartisanpolicy.org/">Bipartisan Policy Center</a>, told Vox that the impact of the expiring pandemic funds will vary by state, but she expects that broadly, retaining child care workers will become harder. In 2019, the median child care worker earned <a href="https://cscce.berkeley.edu/workforce-index-2020/the-early-educator-workforce/early-educator-pay-economic-insecurity-across-the-states/">$11.65 per hour</a>. Today their pay averages <a href="https://www.bls.gov/oes/current/oes399011.htm">$14.22</a>, but without public subsidy, programs may have to raise rates for families to continue paying workers those higher wages. The <a href="https://www.naeyc.org/state-survey-briefs">survey released last October</a> and cited by the Century Foundation found that 43 percent of child care centers and 37 percent of home-based providers expected that theyd have to raise rates when federal relief dollars dry up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="opbQhc">
“In lower-income working families, passing those costs on to parents is not going to be an option,” said Smith. These increased costs will also overlap with the <a href="https://www.vox.com/even-better/23755273/prepare-return-student-loan-payments-servicer-budget">resumption of student loan payments</a> in October after a three-year pause, and <a href="https://www.wsj.com/personal-finance/interest-rates-investing-mortgage-banks-real-estate-debt-ca87c251">higher interest rates</a> on credit cards, mortgages, and car loans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SX2zGr">
Some states are already starting to see the effects of diminished funding. In June, the Republican-controlled legislature in Wisconsin started <a href="https://wisconsinexaminer.com/2023/08/07/child-care-providers-are-reeling-as-they-await-for-state-to-try-again-for-financial-support/">reducing</a> its federal stabilization grants from $20 million a month to $10 million, and the remaining funds are expected to end completely in January. Ruth Schmidt, the executive director of the Wisconsin Early Childhood Association, <a href="https://www.cbsnews.com/minnesota/news/wisconsin-child-care-industry-on-verge-of-crisis-as-pandemic-era-subsidy-comes-to-end/">told CBS</a> that nearly 90 percent of day care centers are raising tuition in response. Some programs <a href="https://wisconsinexaminer.com/2023/07/10/child-care-advocates-will-try-again-for-state-money-to-support-providers/">have closed</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3G8Qee">
Whitney Evans, the California director for <a href="https://parentchildplus.org/">ParentChild+</a>, said she expects the decline in federal funding will affect low-income parents who are least able to work remotely. “For middle-income families, this is going to be a huge pain in the ass but theyll figure out a way,” she told Vox. “But for children with the least access to resources, who wont be able to pay more for slots if rates go up, there will be even less space available.”
</p>
<h3 id="WHHbWh">
Could this affect female workforce participation?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QOzjhK">
A big question looming over the expiring child care funds is whether a major disruption to the child care ecosystem would force parents — and mothers in particular — out of their <a href="https://www.vox.com/labor-jobs">jobs</a>. Child care advocates have been saying for years that a failure to invest more in the nations child care system will result in that outcome; this was a <a href="https://www.nytimes.com/2021/01/18/us/biden-stimulus-package-shecession.html">key argument</a> during the fight for the Build Back Better Act.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DbhHYc">
However, despite the failure of Congress to pass those new child care investments, workforce participation among moms, and even moms of very young children, has continued to rise. The <a href="https://www.axios.com/2023/09/21/jobs-working-moms-remote-wfh-statistics">latest data</a> showed 66.6 percent of women who gave birth in the previous 12 months were working in 2022, up from 66.5 percent in 2021, and 61.6 percent in 2010. And more than <a href="https://www.hamiltonproject.org/publication/post/prime-age-women-are-going-above-and-beyond-in-the-labor-market-recovery/">70 percent of mothers</a> with kids under five were working this past summer — more than even before the pandemic. The expansion of <a href="https://www.vox.com/remote-work">remote work</a>, which makes it easier for parents to juggle their jobs and child care responsibilities, is likely one major contributing factor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NglLdy">
Kashen, of the Century Foundation, credits the <a href="https://www.vox.com/22310269/third-stimulus-update-2021-package">American Rescue Plan</a> investments for staving off female workforce fallout, and said that the “reality is most parents have to work,” so even if moms are employed, it doesnt mean they arent making hard trade-offs behind the scenes, including working later hours, facing declining mental and physical health, or spending less time with family.
</p>
<h3 id="3Bg4tX">
Is there any chance child care funding will return?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6cFdnn">
The politics are challenging right now. Congressional Republicans are currently engaged in a fierce battle over cutting federal spending and have expressed little appetite for new social investments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gwwWQn">
Still, the news isnt all bad. Among parents, the child care issue is far less polarized. A recent poll of Kentucky voters and parents found <a href="https://www.uwgc.org/sites/default/files/2023-08/2023_Poll_Report-KY_Child_Care_Crisis.pdf">strong support</a> for investing more taxpayer money into child care programs, and a <a href="https://www.ffyf.org/july23poll/">national poll</a> conducted for the First Five Years Fund this summer found that 74 percent of voters, including 61 percent of Republican voters, back increased federal spending for child care.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xDzD0k">
Moreover, during the <a href="https://www.vox.com/2024-elections/2023/9/27/23893654/republican-debate-second-winners-losers-vivek-ramaswamy-fox-news">second Republican presidential debate</a> earlier this week, the moderators pressed candidates on how they would expand access to care — <a href="https://www.youtube.com/watch?v=4twMG75z8tk">even citing</a> the expiring pandemic-era funds. South Carolina Sen. <a href="https://www.vox.com/2023/5/22/23731910/tim-scott-2024-presidential-candidate">Tim Scott</a> blasted the Biden administration for allowing day care costs to exceed $15,000 per child, and Doug Burgum, the GOP governor of North Dakota, stressed that “child care is workforce infrastructure.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Q12qNL">
That bipartisan support for affordable child care is likely why Republicans, after rebuffing Democrats $400 billion child care proposal during the Build Back Better fight, agreed to a <a href="https://www.collins.senate.gov/newsroom/more-than-8-billion-secured-for-child-care-by-senator-collins-in-fy23-funding-law">30 percent increase</a> last year of the Child Care and Development Block Grant, a federal program aimed at reducing child care costs for low-income families. And this past summer, Reps. Ro Khanna (D-CA) and Nancy Mace (R-SC) announced the launch of a new <a href="https://khanna.house.gov/media/press-releases/icymi-khanna-and-mace-announce-new-bipartisan-childcare-caucus-congress">Bipartisan Affordable Childcare Caucus</a> in Congress, and Reps. Salud Carbajal (D-CA) and Lori Chavez-DeRemer (R-OR) introduced a bipartisan bill to <a href="https://www.congress.gov/bill/118th-congress/house-bill/4571?q=%7B%22search%22%3A%5B%22H.R.4571%22%5D%7D&amp;s=3&amp;r=1">improve federal child care tax credits</a>, legislation endorsed by <a href="https://www.ffyf.org/bipartisan-bill-seeks-to-leverage-existing-tax-credits-to-support-working-parents-and-employers-in-accessing-child-care/">advocacy groups</a> and the <a href="https://carbajal.house.gov/news/documentsingle.aspx?DocumentID=1659">US Chamber of Commerce</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LooteW">
Some Republican lawmakers remain ideologically against government involvement in child-rearing and oppose efforts such as increased spending on non-religious day care centers. This is partly why some Republicans <a href="https://rollcall.com/2023/08/10/some-republicans-crack-open-door-to-child-tax-credit-compromise/">are more open to expanding</a> the federal child tax credit, which gives money directly to families to spend how they see fit. Expanding the tax credit is also a priority for Democrats, though it might be tough for lawmakers to secure new investments for child care and the child tax credit at the same time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oBtnd5">
Progressives, for their part, are hopeful that theyll have another opportunity to push new child care investments during the end-of-the-year omnibus tax package negotiations. Last year advocates secured new funding in this period for a maternal and child health home visiting program, <a href="https://www.finance.senate.gov/chairmans-news/wyden-cheers-significant-health-care-provisions-in-end-of-year-bill">doubling the amount</a> of federal spending and reauthorizing the program for five years.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZQuGQT">
“The pandemic gave us all a better sense of what it means to have more money in the child care system,” said Rittling, of the First Five Years Fund. “We know that money needs to be sustained beyond Covid, and well be looking at every possible way we can to make that happen.”
</p></li>
<li><strong>9 questions about the governments effort to break up Amazon</strong> -
<figure>
<img alt="An Amazon delivery worker with packages coming out of an Amazon van." src="https://cdn.vox-cdn.com/thumbor/kncfMAy8UCvyc99Yb-mu7aF0xV0=/251x0:4256x3004/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72700814/GettyImages_1232149494.0.jpg"/>
<figcaption>
An Amazon driver delivers some Prime packages. Amazons shipping service is one of several things the FTC says Amazon uses to squeeze sellers and raise prices for customers. | Tom Williams/CQ-Roll Call, Inc. via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Why the FTC is going after your Prime subscription (and a few other things).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="275RWb">
The <a href="https://www.vox.com/big-tech">Big Tech</a> <a href="https://www.vox.com/antitrust">antitrust</a> reform movement has come for <a href="https://www.vox.com/amazon">Amazon</a>. On September 26, the Federal Trade Commission and 17 states <a href="https://www.vox.com/technology/2023/9/26/23835959/ftc-amazon-antitrust-lawsuit-prime-lina-khan">sued the Everything Store</a> for “<a href="https://www.ftc.gov/news-events/news/press-releases/2023/09/ftc-sues-amazon-illegally-maintaining-monopoly-power">illegally maintaining monopoly power</a>.” This comes after <a href="https://www.vox.com/technology/2023/9/11/23864514/google-search-antitrust-trial">two</a> <a href="https://www.vox.com/recode/21524710/google-antitrust-lawsuit-doj-search-trump-bill-barr">different</a> antitrust lawsuits against <a href="https://www.vox.com/google">Google</a> from the Department of Justice — one of which is <a href="https://www.vox.com/technology/2023/9/11/23864514/google-search-antitrust-trial">currently on trial</a> — and <a href="https://www.vox.com/2021/8/19/22632826/facebook-ftc-lawsuit-antitrust-monopoly-lina-khan-instagram-whatsapp-path-circle">another one</a> against <a href="https://www.vox.com/meta">Meta</a> from the FTC.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QiDjVR">
Like the others, this lawsuit gets at the heart of some of the defendants business practices and how they work in concert to reinforce its dominance. In this case, Amazon is accused of using its monopoly on online shopping to make it impossible for other platforms to compete; force the many companies that sell products through Amazon to pay various fees and follow rules designed to enrich Amazon and disadvantage everyone else; and inflate prices on Amazon and beyond. Something called “Project Nessie” is thrown in there, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nT7bvZ">
It will be years before the case goes to trial and even longer before we get a final resolution, assuming it isnt dropped or settled first, so were only at the beginning of a long process. If the FTC wins, Amazon may be forced to do business differently or even be broken up. That might mean some changes to how you shop, too. If youre wondering what exactly Amazon is accused of doing wrong and how all of this could affect you, we have some answers.
</p>
<h3 id="gEuRSX">
<ol type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Why is the FTC suing Amazon?
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AMeLPy">
The FTC is accusing Amazon of abusing its monopoly, harming competition, businesses that sell products through Amazons platform, and consumers. (The FTC is one of two agencies that enforces antitrust laws in the US. The other is the Department of Justice, which has its own Big Tech antitrust cases to fight.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="w9WiQs">
The FTCs main argument targets Amazon Marketplace, where outside businesses, or third-party sellers, sell their products to Amazon customers. This platform has vastly increased the number of products Amazon can offer to consumers and accounts for the majority of Amazons sales. And Amazon, the FTC says, has implemented various rules and fees that sellers have no choice but to follow and pay. That has enriched Amazon at the expense of the sellers and consumers, who are paying inflated prices not just on Amazon but everywhere else, too. —<em>Sara Morrison</em>
</p>
<h3 id="h4TdTd">
<ol start="2" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">What? How could I be paying higher prices on Amazon, a company that famously offers the lowest prices?
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wqI896">
The FTCs case is that the low prices on Amazon are a mirage, and the company is using several interconnected business lines to create it. There are two parts to this.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mapJVy">
The first is that Amazon knows it has tremendous leverage over third-party businesses, whose survival depends on being allowed on the platform and having visibility to their customers. Over time, it has <a href="https://www.vox.com/recode/22810795/amazon-marketplace-prime-report">implemented rules and fees</a> that sellers feel compelled to follow and pay. Those include search ads, commissions on sales, and using Amazons warehouses and shipping services.
</p>
<aside id="1JRFFq">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="diFrIY">
Amazon has put <a href="https://www.vox.com/recode/2022/11/10/23450349/amazon-advertising-everywhere-prime-sponsored-products">more and more ads</a> on search results pages, which means sellers feel compelled to buy ads if they want to get in front of customers. It has also <a href="https://www.vox.com/recode/2019/5/3/18511544/amazon-prime-oral-history-jeff-bezos-one-day-shipping">made Prime</a> an integral part of the shopping and selling experience. Lots of customers have Prime, so they look for products sold through Prime to save on shipping and get their subscription moneys worth. Amazon gives Prime products much more prominent placement on product pages, so sellers have to qualify for Prime if they want people to see and buy their products. But Amazon also makes sellers use its warehouse and shipping service, Fulfillment by Amazon, to qualify for Prime. This has resulted in sellers paying as much as 50 cents on every dollar in sales to Amazon, the suit says. To maintain their profit margin or make any profit at all, sellers have to pass those costs onto consumers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dqVupj">
But heres the second part of all this: Amazons <a href="https://www.vox.com/recode/22453561/amazon-antitrust-dc-attorney-general-lawsuit">“fair pricing” policies</a> say that sellers cant really offer their products for less anywhere else. Sellers are afraid to run afoul of Amazon, which could mean their listings are suppressed or theyre kicked off the platform entirely. So even if a seller incurred fewer expenses and could price their products for less and maintain the same profit margin on another platform, they wont.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GOk5hJ">
The lawsuit also alleges Amazon makes it difficult for first-party sellers, or retailers that sell products to Amazon that Amazon then sells to consumers, to offer lower prices elsewhere. But its less clear how Amazon is allegedly doing this, as those sections are heavily redacted.
</p>
<figure class="e-image">
<img alt="An Amazon delivery person pulling a large amount of packages on a wheeled cart on New York City sidewalk." src="https://cdn.vox-cdn.com/thumbor/Yrv10Wla6A0UViXb7SuTSD95NFc=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24960589/GettyImages_1563112878.jpg"/> <cite>Kena Betancur/VIEWpress/Corbis via Getty Images</cite>
<figcaption>
The FTC says that Amazon pressures sellers to use its shipping service, leading to higher prices and hurting competition. Amazon says sellers can choose whether to use its shipping service and that its policies are in the customers best interests.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BsV8WL">
All these factors combined, the lawsuit says, mean that customers are paying more everywhere, sellers are being squeezed, other stores cant compete with Amazon on prices, and Amazon doesnt have to lower the various fees it charges sellers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2xtq0i">
So while Amazon may have the lowest prices out there, those arent necessarily the lowest prices possible. <em>—SM </em>
</p>
<h3 id="O9kAfR">
<ol start="3" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">What does Amazon say about all this?
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wYMYZL">
David Zapolsky, Amazons general counsel and senior vice president of global public policy, <a href="https://www.aboutamazon.com/news/company-news/amazon-ftc-antitrust-lawsuit-full-response">released a statement</a> in response to the FTC lawsuit, calling the suit “misguided” and arguing that, if successful, the lawsuit would increase prices, lead to slower deliveries, and hurt the small businesses that use Amazon Marketplace.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OUN5OA">
The statement responds to a couple of the FTC complaints arguments directly. One repeated theme throughout Amazons response is this: While Amazon might encourage sellers to, say, sign up for their Fulfillment by Amazon service or create listings that meet certain conditions in order to be prominently featured, they dont actually require<em> </em>sellers to do any of those things in order to list there. And, they argue, giving merchants multiple ways to sell on Amazon increases competition and is good for businesses.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mKJIJm">
Amazon also argues that the FTCs characterization of Amazons market share is too large because it doesnt include physical retail stores as competition. —<em>A.W. Ohlheiser </em>
</p>
<h3 id="i2UMR8">
<ol start="4" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Who is Lina Khan and why does she matter?
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LwZdh2">
Lina Khan is the current FTC chair, a position shes held since 2021. As <a href="https://www.vox.com/recode/2022/6/9/23160578/lina-khan-ftc-interview">Vox has previously explained,</a> Khan was best known at the time of her appointment for her law school paper titled “Amazons Antitrust Paradox,” and was a prominent advocate for antitrust reform who was known, specifically, for criticizing Amazons business practices.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NE9ssE">
If youre wondering how Amazon feels about Khans tenure as FTC chair, well … after Khans appointment, <a href="https://www.theverge.com/2021/6/30/22557456/amazon-lina-khan-recusal-petition-federal-trade-commission-antitrust">Amazon petitioned the FTC</a> with a complaint, arguing that Khan should recuse herself from participating in any actions that regulate Amazon as a company due to her past criticism. —<em>AO</em>
</p>
<figure class="e-image">
<img alt="FTC chair Lina Khan." src="https://cdn.vox-cdn.com/thumbor/zItHmjz1tJA1KN0n7jqhFOZibeo=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24960552/GettyImages_1690670544.jpg"/> <cite>Ting Shen/Bloomberg via Getty Images</cite>
<figcaption>
FTC chair Lina Khan at a recent media appearance.
</figcaption>
</figure>
<h3 id="26etIO">
<ol start="5" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">What is “Project Nessie?” I love cryptozoology, so how can something that sounds so cool be bad?
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EULKfz">
Project Nessie is some kind of algorithm, and thats about all we know. It appears several times in the complaint, only to vanish before we can really determine what it is, much like the <a href="https://www.visitinvernesslochness.com/the-lochness-monster">more famous Nessie</a>. Thats because Amazon was able to get most parts of the complaint surrounding Project Nessie redacted, leaving big black boxes over what is presumably the explanation of the project and why the FTC thinks its bad. All we know right now is that its an algorithm and that the FTC believes it somehow gives Amazon more money at the expense of consumers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eTXjzZ">
It may not be redacted forever. Amazon will have to justify these redactions to a judge, who will ultimately decide what should be kept from the public. Nessie may surface after all. —<em>SM</em>
</p>
<h3 id="J1VYTa">
<ol start="6" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">What does “Fulfillment by Amazon” mean? And what the heck is a “buy box?”
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TRpmvM">
As the lawsuit indicates, there are a couple of different ways products are sold on Amazon. There are things sold and shipped by Amazon — whether they are products produced under an Amazon brand or purchased wholesale by Amazon from another company — and there are products sold by third parties <a href="https://www.vox.com/recode/22810795/amazon-marketplace-prime-report">through Amazon Marketplace</a>.
</p>
<aside id="eZQhiK">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SjyAXk">
Third-party sellers are exactly what you might guess: people or businesses that are not directly affiliated with Amazon using the retail sites enormous platform to sell their products. Generally, third-party sellers control their own listings. Some third-party merchants on Amazon ship their products directly to customers. Others tap into Amazons infrastructure a little more deeply.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="b00FqE">
Enter the Fulfillment by Amazon service, where sellers can, for a fee, send their inventory directly to an Amazon warehouse and let Amazon process and ship the order. These products are generally eligible for Prime shipping. (Its exceedingly difficult to get Prime shipping without using Fulfillment by Amazon.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1fNzjl">
Being a third-party seller on Amazon doesnt necessarily mean that your products will be visible to a wide audience of Amazon shoppers. Amazon encourages sellers to list their products in specific ways in order to maximize visibility. For instance: Third-party sellers who list the same item for purchase in Amazon Marketplace are competing with each other to show up in the “buy box” (also called the “featured offer”). The buy box is the box on an Amazon listing that contains the “add to cart” and “buy now” buttons, a.k.a. where you are generally going to click as a consumer if you want to buy the product.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mlSWtA">
In Amazons <a href="https://sell.amazon.com/blog/buy-box-featured-offer">guide</a> to getting a product featured in the buy box, it encourages sellers to price “competitively” or “at or below the lowest priced alternatives,” and to offer “fast and free shipping,” either through their own merchant shipping process or by signing up for the Fulfilled by Amazon service. A product is also more likely to show up in the buy box if its eligible for Prime shipping. —<em>AO</em>
</p>
<h3 id="fumDL7">
<ol start="7" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Why should I care what Amazon does to third-party sellers?
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RVU6vs">
Its important to remember that Marketplace sales <a href="https://s2.q4cdn.com/299287126/files/doc_financials/2021/ar/Amazon-2020-Shareholder-Letter-and-1997-Shareholder-Letter.pdf">account for</a> the majority of sales on Amazon and that these third-party sellers are paying fees to Amazon in order to sell there. Signing up for Fulfillment by Amazon comes with additional costs to the merchant. When Amazon raises those fees, consumers will generally have to pay more for that item going forward.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AdFZiO">
Amazons policies can also raise the prices of items on other sites. Because the companys fair pricing policy <a href="https://www.vox.com/technology/2023/9/26/23835959/ftc-amazon-antitrust-lawsuit-prime-lina-khan">gives them leeway to punish merchants</a> who list a product on Amazon at a higher price than they might elsewhere — say, on a platform that does not charge the same fees Amazon does — sellers are incentivized to raise their prices everywhere in order to account for Amazons fees. —<em>AO</em>
</p>
<figure class="e-image">
<img alt="Interior of an Amazon warehouse." src="https://cdn.vox-cdn.com/thumbor/31rVt61JKuPjaWq4LvHdQLs8HjY=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24960597/GettyImages_459987396.jpg"/> <cite>Peter Macdiarmid/Getty Images</cite>
<figcaption>
One of the many warehouses Amazon has all over the world.
</figcaption>
</figure>
<h3 id="VnJgqP">
<ol start="8" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">What will happen to Amazon if it loses the FTC lawsuit? How will it affect <em>me</em>?
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="euA8if">
In interviews with the press, Khan has been careful not to say much about what remedies the FTC will pursue if it wins the case. But the agency is asking the court to stop Amazon from engaging in illegal practices, issue monetary penalties, and provide any relief necessary to prevent Amazon from violating the law again in the future — up to structural relief, which means breaking the company up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NWlKqZ">
That doesnt mean that an FTC win will break up Amazon, and we dont know what that breakup would look like even if it did. A judge would make that decision, and were a long way away from even the possibility of it. The fact that the FTC played up the interconnected and interlocking nature of Amazons alleged violations in its complaint, though, indicates that the agency would say theres no way to truly solve the problem if the company remains in one piece.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JWj3lZ">
This also means its impossible to say, right now, how things would change for you, the customer. If Amazon isnt broken up, it may well have to stop or significantly change its Prime service, which is one of the alleged weapons Amazon wields over sellers. The FTC will say that an agency victory will mean lower prices for you and more competition that will force Amazon to have to offer a better product or give you more or better shopping options elsewhere. The very fact that Amazon is now fighting a lawsuit could have a chilling effect on some of the ways it does (or wants to do) business, as was the case for <a href="https://www.vox.com/microsoft">Microsoft</a> in the late 90s and early 00s. That said, Amazon isnt going to do anything drastic unless it absolutely has to. —<em>SM</em>
</p>
<h3 id="h4DpY0">
<ol start="9" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">But will Amazon lose? I mean, come on. Really?
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pM0ZDw">
We here at Vox dont have a crystal ball, but history shows that antitrust cases are hard to win. Courts are business-friendly and have only become more so since the last Big Tech antitrust case <a href="https://www.vox.com/recode/22893117/microsoft-activision-antitrust-big-tech">against Microsoft</a>. Khans FTC has had some <a href="https://www.axios.com/2023/02/24/ftc-meta-within-case-dismissed">high</a>-<a href="https://www.vox.com/technology/2023/7/11/23785775/microsoft-activision-ftc-antitrust-decision">profile</a> losses with Big Tech so far. But those were about acquisitions and not, as this case is about, existing business practices.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IDHr5c">
This case does have something other cases against Meta and Google dont: physical goods that, the FTC says, consumers are paying more for than they should. Thats something that courts, which have come to embrace the “consumer welfare standard” as a deciding factor in whether or not a companys monopoly is harmful, will pay attention to. That still doesnt mean the FTC will be able to convince them that Amazon is doing anything wrong. —<em>SM</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>Hangzhou Asian Games | 18 and counting: Indian shooting has its best ever medal count</strong> - The Indian shooters bagged six gold, seven silver and five bronze with two more days of action remaining.</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>Nikhat Zareen secures Paris Olympic quota; assures of medal at Asian Games</strong> - Fighting in her third bout of the tournament, Nikhat needed less than three minutes to notch a facile RSC (referee stops contest) win over Nassar Hanan of Jordan in the quarterfinal.</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>Hangzhou Asian Games | Indian mens badminton team assured of medal, womens team bows out</strong> - Taking the court first, Lakshya Sen defeated Prince Dahal 21-5 21-8 before Kidambi Srikanth beat Sunil Joshi 21-4 21-13 in the second match. In the third match, Mithun Manjunath edged past Bishnu Katuwal 21-2 21-17 to clinch the tie</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>2023 ODI World Cup venues | Ekana Stadium, Lucknow — capacity, pitch info, tickets and more</strong> - The Uttar Pradesh Cricket Association believes hosting World Cup matches will boost cricket in the region and encourage young talent</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>ICC World Cup preview | Afghanistans primary goal will be to improve its poor record</strong> - The squad boasts of a strong spin attack, comprising Rashid Khan, Mohammad Nabi, Mujeeb Ur Rahman and Noor Ahmad.</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>State registers significant rise in non tax revenue in August</strong> - Slow pace of overall growth in revenue receipts continues for fifth month in a row; States revenue deficit at the end of August stood at ₹3,715 crore against surplus of ₹4,881 crore estimated for the 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>Punnapra set to become first beach ecotourism destination in Kerala</strong> - Government contemplating setting up ecotourism directorate, says Forests Minister A.K. Saseendran</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>Two held with country-made guns near Piler in Andhra Pradesh</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>Work on new PHC in Kavanur village near Arcot town begins</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>Womens reservation bill gets Presidents assent</strong> - Now, it will be officially known as the Constitution (106th Amendment) Act.</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>Rotterdam shootings: Hospital was warned of psychotic suspect</strong> - Dutch prosecutors had raised concerns about the man accused of killing three people in Rotterdam.</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>Putin meets former Wagner commander Andrei Troshev</strong> - The Kremlin says Andrei Troshev, ex-aide to Yevgeny Prigozhin, now works for the defence ministry.</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>Death toll in Nagorno-Karabakh fuel depot blast jumps to 170</strong> - The sharp rise comers as more than two-thirds of the regions ethnic Armenians have left for Armenia.</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>Gulnara Karimova: Swiss say Uzbekistan ex-leaders daughter ran huge crime network</strong> - Switzerland seizes $857m of assets as the daughter of Uzbekistans ex-leader is charged with fraud.</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>Slovakia elections: The populist ex-PM vowing to cut Ukraine support</strong> - Robert Fico says if his party returns to power in Saturdays vote, military aid to Ukraine will end.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rocket Report: Iran launches satellite; Artemis II boosters get train ride</strong> - Is ArianeGroup finally getting more serious about a reusable rocket? - <a href="https://arstechnica.com/?p=1972044">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>$5,000 Google Jamboard dies in 2024—cloud-based apps will stop working, too</strong> - Googles digital whiteboard for schools and businesses lasted 8 years. - <a href="https://arstechnica.com/?p=1972006">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>US may pay 3x more than EU for Modernas US-funded COVID shot</strong> - Moderna developed its vaccine with the NIH and got $1.7 billion in federal grant money. - <a href="https://arstechnica.com/?p=1972056">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A new Chrome 0-day is sending the Internet into a new chapter of Groundhog Day</strong> - If your software package involves VP8 video encoding, its likely vulnerable to attack. - <a href="https://arstechnica.com/?p=1972043">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Losing subscribers, Disney+ starts fighting password sharing, too</strong> - The enforcement is starting with Canada. - <a href="https://arstechnica.com/?p=1971954">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man escapes from prison where he has been for 15 years. He breaks into a house to look for money and guns and finds a young couple in bed.</strong> - <!-- SC_OFF --></p>
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He orders the guy out of bed and ties him to a chair, while tying the girl to the bed he gets on top of her, kisses her neck, then gets up and goes into the bathroom. While hes in there, the husband tells his wife: “Listen, this guys an escaped convict, look at his clothes! He probably spent lots of time in jail and hasnt seen a woman in years. I saw how he kissed your neck. If he wants s<em>x, dont resist, dont complain, do whatever he tells you. Satisfy him no matter how much he nauseates you. This guy is probably very dangerous. If he gets angry, hell k</em>ll us. Be strong, honey. I love you.” To which his wife responds: “He wasnt kissing my neck. He was whispering in my ear. He told me he was gay, thought you were cute, and asked me if we had any vaseline. I told him it was in the bathroom. Be strong honey. I love you too!”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16v5h80/a_man_escapes_from_prison_where_he_has_been_for/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16v5h80/a_man_escapes_from_prison_where_he_has_been_for/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A husband and a wife are waiting at the bus stop..</strong> - <!-- SC_OFF --></p>
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A Husband and a wife are waiting at the bus stop with their 10 children. A blind man joins them after a few minutes.<br/> Soon, the bus arrives, but it is overloaded and only the wife and the nine kids are able to fit onto the bus. So the husband and the blind man decide to walk.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After a while, the husband gets irritated by the ticking of the stick of the blind man as he taps it on the sidewalk, and says to him, “Why dont you put a piece of rubber at the end of your stick? That ticking sound is driving me crazy.”
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The blind man replies, “If you had put a rubber at the end of YOUR stick, wed be riding the bus, so shut up.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/whyamihere999"> /u/whyamihere999 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16utnjs/a_husband_and_a_wife_are_waiting_at_the_bus_stop/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16utnjs/a_husband_and_a_wife_are_waiting_at_the_bus_stop/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why is Santa always smiling?</strong> - <!-- SC_OFF --></p>
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Because he knows where all the naughty girls are.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Ravenclaw_Student_"> /u/Ravenclaw_Student_ </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16v701z/why_is_santa_always_smiling/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16v701z/why_is_santa_always_smiling/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A good looking man walked into an agents office in Hollywood and said “I want to be a movie star.”</strong> - <!-- SC_OFF --></p>
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Tall, handsome and with experience on Broadway, he had the right credentials.
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The agent asked, “Whats your name?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The guy said, “My name is Penis van Lesbian.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The agent said, “Sir, I hate to tell you, but in order to get into Hollywood, you are going to have to change your name.”
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"I will NOT change my name!
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The van Lesbian name is centuries old.
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I will not disrespect my grandfather by changing my name. Not ever."
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The agent said, "Sir, I have worked in Hollywood for years.. you will NEVER go far in Hollywood with a name like Penis van Lesbian!
</p>
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Im telling you, you will HAVE TO change your name or I will not be able to represent you."
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“So be it! I guess we will not do business together” the guy said and he left the agents office.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
FIVE YEARS LATER… The agent opens an envelope sent to his office.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Inside the envelope is a letter and a check for $50,000.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The agent is awe-struck, who would possibly send him $ 50,000? He reads the letter enclosed:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
"Dear Sir, Five years ago, I came into your office wanting to become an actor in Hollywood, you told me I needed to change my name.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Determined to make it with my God-given birth name, I refused.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
You told me I would never make it in Hollywood with a name like Penis van Lesbian.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After I left your office, I thought about what you said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I decided you were right.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I had to change my name.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I had too much pride to return to your office, so I signed with another agent.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I would never have made it without changing my name, so the enclosed check is a token of my appreciation.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Thank you for your advice.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Sincerely,
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Dick van Dyke
</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/orgasmic2021"> /u/orgasmic2021 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16uaala/a_good_looking_man_walked_into_an_agents_office/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16uaala/a_good_looking_man_walked_into_an_agents_office/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Brakes</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A Boy was having sex with a girl on a Railway track.
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The train driver spots them and starts hooting but they ignore it.
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He applies brakes hard and the train stops just a few yards away from the couple. The train driver jumps and walks to the boy who had just finished and was standing up and zipping up his pants.
</p>
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The driver shouts at the boy "Do you realize that if I had not seen you, this would have been ur last f…!!!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Boy -Listen dude, you were coming… She was coming…. and I was coming…. then I realized ….only You have Brakes.
</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/njman10"> /u/njman10 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16uir5u/brakes/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16uir5u/brakes/">[comments]</a></span></p></li>
</ul>
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