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<title>16 October, 2023</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Did long COVID increase road deaths in the U.S.?</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Objective To examine data on COVID-19 disease associated with a 10 percent increase in U.S. road deaths from 2020 to 2021 that raises the question of the potential effect of pandemic stress and neurological damage from COVID-19 disease. Methods Poisson regression was used to estimate the association of recent COVID-19 cases, accumulated cases, maximum temperatures, truck registrations, and gasoline prices with road deaths monthly among U.S. states in 2021. Using the regression coefficients, changes in each risk factor from 2020 to 2021 were used to calculate expected deaths in 2021 if each factor had remained the same as in 2020. Results Corrected for the other risk factors, road deaths were associated with accumulated COVID-19 cases but not cases in the previous month More than 20,700 road deaths were associated with the changes in accumulated COVID-19 cases but were substantially offset by about 19,100 less-than-expected deaths associated with increased gasoline prices. Conclusions While more research is needed, the data are sufficient to warn people with long COVID to minimize driving.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.11.23296868v1" target="_blank">Did long COVID increase road deaths in the U.S.?</a>
</div></li>
<li><strong>Repression of mRNA translation initiation by GIGYF1 via blocking the eIF3-eIF4G1 interaction</strong> -
<div>
Viruses commonly interfere with the function of the eukaryotic translation initiation factor 4G1 (eIF4G1), a pivotal factor in the recruitment of the eIF3 complex and ribosome to the mRNA. This results in the inhibition of general host protein synthesis and redirecting ribosomes toward viral mRNAs. Certain viruses also selectively repress the translation of mRNAs involved in the host antiviral response. GIGYF2 and its interacting cap-binding protein 4EHP enable the transcript-specific repression of mRNA translation mediated by microRNAs and RNA-binding proteins (RBPs). RNA viruses, such as SARS-CoV-2, exploit the GIGYF2/4EHP complex to selectively repress the translation of transcripts such as Ifnb1 mRNA, which encodes the antiviral cytokine Interferon {beta} (IFN-{beta}). Herein, we reveal that GIGYF1, a paralogue of GIGYF2, robustly represses cellular mRNA translation through a distinct mechanism independent of 4EHP. Upon recruitment to a target mRNA by RBPs, the C-terminal region of GIGYF1 binds to subunits of eIF3 at the interaction interface of eIF3-eIF4G1. This disrupts the recruitment of eIF3 to the mRNA by eIF4G1, resulting in mRNA-specific translational repression. This mechanism exerts profound influences on the host cell's response to viral infection. Depletion of GIGYF1 induces a robust immune response by derepressing Ifnb1 mRNA translation. Overall, our study highlights a unique mechanism of translational regulation by GIGYF1 that involves sequestering eIF3 and abrogating its binding to eIF4G1. This mechanism can be utilized by RBPs that interact with GIGYF1 to specifically repress the translation of their target mRNAs, significantly affecting critical biological processes, including host-pathogen interactions.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.14.562322v1" target="_blank">Repression of mRNA translation initiation by GIGYF1 via blocking the eIF3-eIF4G1 interaction</a>
</div></li>
<li><strong>Inferring Viral Transmission Pathways from Within-Host Variation</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Genome sequencing can offer critical insight into pathogen spread in viral outbreaks, but existing transmission inference methods use simplistic evolutionary models and only incorporate a portion of available genetic data. Here, we develop a robust evolutionary model for transmission reconstruction that tracks the genetic composition of within-host viral populations over time and the lineages transmitted between hosts. We confirm that our model reliably describes within-host variant frequencies in a dataset of 134,682 SARS-CoV-2 deep-sequenced genomes from Massachusetts, USA. We then demonstrate that our reconstruction approach infers transmissions more accurately than two leading methods on synthetic data, as well as in a controlled outbreak of bovine respiratory syncytial virus and an epidemiologically-investigated SARS-CoV-2 outbreak in South Africa. Finally, we apply our transmission reconstruction tool to 5,692 outbreaks among the 134,682 Massachusetts genomes. Our methods and results demonstrate the utility of within-host variation for transmission inference of SARS-CoV-2 and other pathogens, and provide an adaptable mathematical framework for tracking within-host evolution.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.14.23297039v1" target="_blank">Inferring Viral Transmission Pathways from Within-Host Variation</a>
</div></li>
<li><strong>Evaluation of Stroke Risk Following COVID-19 mRNA Bivalent Vaccines Among U.S. Adults Aged ≥65 Years</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In January 2023, the United States Food and Drug Administration and the Centers for Disease Control and Prevention noted a safety concern for ischemic stroke in adults 65 years of age or older receiving the BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine. This self-controlled case series analysis evaluated stroke risk among Medicare fee-for-service beneficiaries aged 65 years of age or older receiving: 1) a Pfizer-BioNTech (BNT162b2; WT OMI BA.4 and BA.5) or Moderna (mRNA 1273.222) COVID-19 bivalent vaccine, 2) high-dose/adjuvanted influenza vaccines, and 3) concomitant COVID-19 bivalent vaccines and influenza vaccines, from August 31 to November 6, 2022. The primary analysis did not find elevated stroke risk following COVID-19 bivalent vaccines. In the age subgroup analyses, only the 85+ year age group had a risk of NHS (Incident Rate Ratio (IRR)=1.36, 95% CI 1.09 to 1.69 [1 to 21 days]) and NHS/TIA (IRR=1.28, 95% CI 1.08 to 1.52 [1 to 21 days]) with BNT162b2 Bivalent WT OMI BA.4 and BA.5. Among beneficiaries receiving a concomitant COVID-19 bivalent vaccine and a high-dose/adjuvanted influenza vaccine, an increased risk was observed for NHS (IRR=1.20, 95% CI 1.01 to 1.42 [22 to 42 days]) with BNT162b2 Bivalent WT OMI BA.4 and BA.5 and for TIA (IRR=1.35, 95% CI 1.06 to 1.74 [1 to 21 days]) with mRNA 1273.222. Results of the secondary analyses showed a small increased risk of NHS following high-dose or adjuvanted influenza vaccines (IRR=1.09, 95% CI 1.02 to 1.17 [22 to 42 days]).
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.10.23296624v1" target="_blank">Evaluation of Stroke Risk Following COVID-19 mRNA Bivalent Vaccines Among U.S. Adults Aged ≥65 Years</a>
</div></li>
<li><strong>Omicron COVID-19 Immune Correlates Analysis of a Third Dose of mRNA-1273 in the COVE Trial</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In the coronavirus efficacy (COVE) phase 3 efficacy trial of the mRNA-1273 vaccine, IgG binding antibody (bAb) concentration against Spike (BA.1 strain) and neutralizing antibody (nAb) titer against Spike (BA.1 strain) pseudovirus were assessed as correlates of risk of Omicron COVID-19 and as correlates of relative boost efficacy in per-protocol recipients of a third (booster) dose. Markers were measured on the day of the boost (BD1) and 28 days later (BD29). For SARS-CoV-2 naive individuals, BD29 Spike IgG-BA.1 strain bAbs and BD29 BA.1-strain nAbs inversely correlated with Omicron COVID-19: hazard ratio (HR) per 10-fold marker increase [95% confidence interval (CI)] = 0.16 (0.03, 0.79); P=0.024 and 0.31 (0.10, 0.96); P = 0.042, respectively. These markers also inversely correlated with Omicron COVID-19 in non-naive individuals: HR = 0.15 (0.04, 0.63); P = 0.009 and 0.28 (0.07, 1.08); P = 0.06, trend. Fold-rise in markers from BD1 to BD29 had similarly strong inverse correlations. For SARS-CoV-2 naive individuals, overall booster relative (three-dose vs two-dose) efficacy was 46% (95% CI: 20%, 64%) and correlated with BA.1 strain nAb titer at exposure. At 56, 251, and 891 arbitrary units (AU)/ml (10th, 50th, and 90th percentile), the booster relative efficacies were -8% (95% CI: -126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), respectively. Similar relationships were observed for Spike IgG-BA.1 strain bAbs and for the markers measured at BD29. The performance of bAb and nAb markers as correlates of protection against Omicron COVID-19 supports their continued use as surrogate endpoints for mRNA vaccination against Omicron COVID-19.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.15.23295628v1" target="_blank">Omicron COVID-19 Immune Correlates Analysis of a Third Dose of mRNA-1273 in the COVE Trial</a>
</div></li>
<li><strong>IFIH1 loss-of-function predisposes to inflammatory and SARS-CoV-2-related infectious diseases</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The IFIH1 gene, encoding melanoma differentiation-associated protein 5 (MDA5), is an indispensable innate immune regulator involved in the early detection of viral infections. Previous studies described MDA5 dysregulation linking it to weakened immunological responses, and increased susceptibility to microbial infections and autoimmune disorders. Monoallelic gain-of-function of the IFIH1 gene has been associated with multisystem disorders, namely Aicardi-Goutieres and Singleton-Merten syndromes, while biallelic loss of this gene causes immunodeficiency. In this study, nine patients suffering from different cases of recurrent infections, inflammatory diseases, severe COVID-19, or multisystem inflammatory syndrome in children (MIS-C) were identified with putative loss-of-function IFIH1 variants by whole exome sequencing. All patients revealed signs of lymphopenia and an increase in inflammatory markers, including CRP, amyloid A, ferritin, and IL-6. One patient with a pathogenic homozygous variant c.2807+1G&gt;A was the most severe case showing immunodeficiency and glomerulonephritis. The c.1641+1G&gt;C variant was identified in the heterozygous state in patients suffering from periodic fever, COVID-19, or MIS-C, while the c.2016delA variant was identified in two patients with inflammatory bowel disease or MIS-C. Expression analysis showed that PBMCs of one patient with a c.2016delA variant had a significant decrease in ISG15, IFNA and IFNG transcript levels, compared to normal PBMCs, upon stimulation with poly(I:C), suggesting that MDA5 receptor truncation disrupts the immune response. Our findings accentuate the implication of rare monogenic IFIH1 loss-of-function variants in altering the immune response, and severely predisposing patients to inflammatory and infectious diseases, including SARS-CoV-2 related disorders.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.13.23297034v1" target="_blank">IFIH1 loss-of-function predisposes to inflammatory and SARS-CoV-2-related infectious diseases</a>
</div></li>
<li><strong>Surveillance and Stability of SARS-CoV-2 Wastewater Samples in Minnesota</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wastewater-based epidemiology provides an approach for assessing the prevalence of pathogens such as COVID-19 in a sewer service area. In this study, SARS-CoV-2 RNA was measured serially in 44 wastewater treatment plants of varying service capacities comprising approximately 67% of the population of Minnesota, from September 2020 through December 2022. We employed linear regression models to establish a predictive relationship between the weekly SARS‐CoV‐2 RNA concentrations in wastewater and clinical case counts. Metrics were assessed under specified transformation and normalization methods which we confirmed by cross-validation averaged across the enrolled treatment plants. We report that the relationship between COVID-19 incidence and SARS-CoV-2 RNA in wastewater may be treatment plant-specific. Toward establishing guidelines for pathogen surveillance, we further studied storage and time-to-analysis for RNA wastewater data and observed large effects of storage temperature, indicating that collection methods may have an important effect on the utility and validity of wastewater data for infectious disease monitoring. Our findings are additive for any large-scale wastewater surveillance program.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.14.23296666v1" target="_blank">Surveillance and Stability of SARS-CoV-2 Wastewater Samples in Minnesota</a>
</div></li>
<li><strong>Ischemic Stroke after Bivalent COVID-19 Vaccination: A Self-Controlled Case Series Study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Introduction The potential association between bivalent COVID-19 vaccination and ischemic stroke remains uncertain, despite several studies conducted thus far. The purpose is to evaluate the risk of ischemic stroke following bivalent COVID-19 vaccination. Methods A self-controlled case series study was conducted among members aged 12 years and older who experienced ischemic stroke between September 1, 2022 and March 31, 2023 in a large California health care system. Ischemic strokes were identified using ICD-10 codes in Emergency Department and inpatient settings. Exposures were Pfizer-BioNTech or Moderna bivalent COVID-19 vaccination. Risk intervals were pre-specified as 1-21 days and 1-42 days after bivalent COVID-19 vaccination; all non-risk-interval person-time served as control interval. We conducted overall and subgroup analyses by age, history of SARS-CoV-2 infection, and co-administration of influenza vaccine. When an elevated risk was detected, we performed chart review of ischemic strokes, and re-evaluated the risk. RESULTS With 4933 cases, we found no increased risk within 21-day risk interval across vaccines and by subgroups. However, an elevated risk emerged within 42-day risk interval among individuals &lt;65 years who received co-administration of Pfizer-BioNTech bivalent vaccine and influenza vaccine on the same day; relative incidence (RI) was 2.14 (95% CI, 1.02-4.49). Among those who also had history of SARS-CoV-2 infection, RI was 3.94 (95% CI, 1.10-14.16). After chart review, RIs were 2.35 (95% CI, 0.98-5.65) and 4.33 (95% CI, 0.98-19.11), respectively. Among individuals &lt;65 years who received Moderna bivalent vaccine and had history of SARS-CoV-2 infection, RI was 2.62 (95% CI, 1.13-6.03) before chart review and 2.24 (95% CI, 0.78-6.47) after chart review. CONCLUSIONS The potential association between bivalent COVID-19 vaccination and ischemic stroke in the 1-42-day analysis warrants further investigation among individuals &lt;65 years with influenza vaccine co-administration and prior SARS-CoV-2 infection.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.12.23296968v1" target="_blank">Ischemic Stroke after Bivalent COVID-19 Vaccination: A Self-Controlled Case Series Study</a>
</div></li>
<li><strong>Longitudinal viscosity of blood plasma for rapid COVID-19 prognostics</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Blood Plasma Viscosity (PV) is an established biomarker for numerous diseases. While PV colloquially refers to the shear viscosity, there is a second viscosity component–the bulk viscosity–that describes the irreversible fluid compressibility on short time scales. The bulk viscosity is acutely sensitive to solid-like suspensions, and obtainable via the longitudinal viscosity from acoustic attenuation measurements. Whether it has diagnostic value remains unexplored yet may be pertinent given the association of diverse pathologies with the formation of plasma suspensions, such as fibrin-microstructures in COVID-19 and long-COVID. Here we show that the longitudinal PV measured using Brillouin Light Scattering (BLS) can serve as a proxy for the shear PV of blood plasma, and exhibits a temperature dependence consistent with increased suspension concentrations in severe COVID-patient plasma. Our results open a new avenue for PV diagnostics based on the longitudinal PV, and show that BLS can provide a means for its clinical implementation.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.13.23297016v1" target="_blank">Longitudinal viscosity of blood plasma for rapid COVID-19 prognostics</a>
</div></li>
<li><strong>Hyperglycemia-induced cathepsin L maturation: Implications for diabetic comorbidities and COVID-19 susceptibility</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Diabetes is the second most frequent chronic comorbidity for COVID-19 mortality, yet the underlying mechanism remains unclear. Previous studies suggest that Cathepsin L (CTSL) is implicated in diabetic complications such as nephropathy and retinopathy. Our previous research identified CTSL as a critical protease that promotes SARS-CoV-2 infection and a potential drug target. Here, we show that individuals with diabetes have elevated blood CTSL levels, which facilitates SARS-CoV-2 infection. Chronic hyperglycemia, as indicated by HbA1c levels, is positively correlated with CTSL concentration and activity in diabetic patients. Acute hyperglycemia induced by a hyperglycemic clamp in healthy individuals increases CTSL activity. <i>In vitro, </i>high glucose, but not high insulin, promotes SARS-CoV-2 infection in wild-type (WT) cells, while <i>CTSL</i> knockout (KO) cells show reduced susceptibility to high glucose-promoted effects. Using lung tissue samples from diabetic and non-diabetic patients, as well as db/db diabetic and control mice, our findings demonstrate that diabetic conditions increase CTSL activity in both humans and mice. Mechanistically, high glucose levels promote CTSL maturation and CTSL translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. This study emphasizes the significance of hyperglycemia-induced cathepsin L maturation in the development of diabetic comorbidities and complications.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.15.23297013v1" target="_blank">Hyperglycemia-induced cathepsin L maturation: Implications for diabetic comorbidities and COVID-19 susceptibility</a>
</div></li>
<li><strong>Hidden evolutionary constraints dictate the retention of coronavirus accessory genes</strong> -
<div>
Genetic innovation is fundamental to the ability of viruses to adapt in the face of host immunity. Coronaviruses exhibit many mechanisms of innovation given flexibility in genomic composition relative to most RNA virus families (1-5). Examples include the acquisition of unique accessory genes that can originate by capture of cellular genes or through duplication and divergence of existing viral genes (6-8). Accessory genes may be influential in dictating viral host range and cellular tropism, but little is known about how selection acts on these variable regions of virus genomes. We used experimental evolution of mouse hepatitis virus (MHV) with an inactive native phosphodiesterase, NS2, that encodes a complementing cellular AKAP7 gene (9), to simulate the capture of a host gene and found hidden patterns of constraint that determine the fate of coronavirus accessory genes. After courses of serial infection, AKAP7 was retained under strong selection but rapidly lost under relaxed selection. In contrast, the gene encoding inactive NS2, ORF2, remained intact, suggesting it is under cryptic evolutionary constraint. Guided by the retention of ORF2 and hints of similar patterns in related betacoronaviruses, we analyzed the evolution of SARS-CoV-2 ORF8, which arose via gene duplication (6) and contains premature stop codons in several globally successful lineages. As with MHV ORF2, the coding-defective SARS-CoV-2 ORF8 gene remains largely intact, mirroring patterns observed during MHV experimental evolution and extending these findings to viruses currently adapting to humans. Retention of inactive genes challenges assumptions on the dynamics of gene loss in virus genomes and can help guide evolutionary analysis of emerging and pandemic coronaviruses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.12.561935v1" target="_blank">Hidden evolutionary constraints dictate the retention of coronavirus accessory genes</a>
</div></li>
<li><strong>Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein driving the genesis of Omicron variants</strong> -
<div>
Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralising public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidences to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.12.561995v1" target="_blank">Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein driving the genesis of Omicron variants</a>
</div></li>
<li><strong>Threat awareness and counter-terrorism preparedness of Dutch hospitals: a cross-sectional survey</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
ABSTRACT Background Workplace violence, including violent extremism, is a growing concern in the healthcare environment. Furthermore, there has been a disproportionate rise in the rate of terrorist attacks on hospitals during the past two decades. Hospitals are vulnerable targets due to their easy accessibility and their high density of patients, staff and visitors. Nonetheless, little is known about the hospitals awareness of these risks, and to which extent these facilities protect themselves from violent extremism and terrorist attacks. Methods This was a cross-sectional survey study among emergency managers of acute care hospitals in the Netherlands. The questionnaire included 42 items across six themes: demographic (hospital) data; general and emergency department (ED) access control; ED security and preparedness; online security and offline transparency; violence, terrorism and warfare; and impact of the COVID-19 pandemic. Responses were collected and stored in a secured online database, and subsequently exported to an Excel spreadsheet for descriptive analysis. Continuous data were reported as means or as medians with interquartile ranges (IQR), using SPSS. Categorical data were reported as absolute numbers and as valid percentages. Results The questionnaire was completed on behalf of 33 out of 71 hospital organizations (46%), representing 38 out of 82 EDs (46%). Hospitals had broadly different policies with regards to patient and visitor registration, and the presence of security guards. Most hospitals had controlled vehicle access for the parking lot and ambulance bay, but this was not 24/7 in all hospitals. A paragraph on terrorist attacks was included in 34% of hospital disaster plans. Eighteen percent of hospitals had previous experience with acts of violent extremism and 55% of hospitals had sustained (attempted) cyberattacks. Whilst the likelihood of a physical terrorist attack was deemed low at 3.6 (median 4, IQR 2.6) on a 10-point Likert scale, the likelihood of a cyberattack was considered high at 7.3 (median 8, IQR 2.3). A significant proportion of emergency managers reported to experience an increased risk of violence since the onset of the COVID-19 pandemic. Conclusion Practice variation with regards to counter-terrorism defence measures in Dutch hospitals is high. The preparedness of hospitals for terrorist attacks or acts of violent extremism could be improved and may benefit from uniform, evidence based hospital security policies.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.14.23297038v1" target="_blank">Threat awareness and counter-terrorism preparedness of Dutch hospitals: a cross-sectional survey</a>
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<li><strong>Nanobodies against SARS-CoV-2 non-structural protein Nsp9 inhibit viral replication by targeting innate immunity</strong> -
<div>
Nanobodies are emerging as critical tools for drug design. Several have been recently created to serve as inhibitors of SARS-Cov-2 entry in the host cell by targeting surface-exposed Spike protein. However, due to the high frequency of mutations that affect Spike, these nanobodies may not target it to their full potential and as a consequence, inhibition of viral entry may not be efficient. Here we have established a pipeline that instead targets highly conserved viral proteins that are made only after viral entry into the host cell when the SARS-Cov-2 RNA-based genome is translated. As proof of principle, we designed nanobodies against the SARS-CoV-2 non-structural protein Nsp9, required for viral genome replication. To find out if this strategy efficiently blocks viral replication, one of these anti-Nsp9 nanobodies, 2NSP23, previously characterized using immunoassays and NMR spectroscopy for epitope mapping, was encapsulated into lipid nanoparticles (LNP) as mRNA. We show that this nanobody, hereby referred to as LNP-mRNA-2NSP23, is internalized and translated in HEK293 cells. We next infected HEK293-ACE2 cells with multiple SARS-CoV-2 variants and subjected them to LNP-mRNA-2NSP23 treatment. Analysis of total RNA isolated from infected cells treated or untreated with LNP-mRNA-2NSP23 using qPCR and RNA deep sequencing shows that the LNP-mRNA-2NSP23 nanobody protects HEK293-ACE2 cells and suppresses replication of several SARS-CoV-2 variants. These observations indicate that following translation, the nanobody 2NSP23 inhibits viral replication by targeting Nsp9 in living cells. We speculate that LNP-mRNA-2NSP23 may be translated into an innovative technology to generate novel antiviral drugs highly efficient across coronaviruses.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.12.561992v1" target="_blank">Nanobodies against SARS-CoV-2 non-structural protein Nsp9 inhibit viral replication by targeting innate immunity</a>
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<li><strong>Akaluc bioluminescence offers superior sensitivity to track in vivo dynamics of SARS-CoV-2 infection</strong> -
<div>
Monitoring in vivo viral dynamics can improve our understanding of pathogenicity and tissue tropism. For positive-sense, single-stranded RNA viruses, several studies have attempted to monitor viral kinetics in vivo using reporter genomes. The application of such recombinant viruses can be limited by challenges in accommodating bioluminescent reporter genes in the viral genome. Conventional luminescence also exhibits relatively low tissue permeability and thus less sensitivity for visualization in vivo. Here we show that unlike NanoLuc bioluminescence, the improved method, termed AkaBLI, allows visualization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Syrian hamsters. By successfully incorporating a codon-optimized Akaluc luciferase gene into the SARS-CoV-2 genome, we visualized in vivo infection, including the tissue-specific differences associated with particular variants. Additionally, we could evaluate the efficacy of neutralizing antibodies and mRNA vaccination by monitoring changes in Akaluc signals. Overall, AkaBLI is an effective technology for monitoring viral dynamics in live animals.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.12.561993v1" target="_blank">Akaluc bioluminescence offers superior sensitivity to track in vivo dynamics of SARS-CoV-2 infection</a>
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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>Food Effects of GST-HG171 Tablets Combined With Ritonavir in Healthy Chinese Participants</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection <br/><b>Interventions</b>: Drug: GST-HG171/ritonavir; Drug: ritonavir <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 3 Open-Label Controlled Trial of Convalescent Plasma in Early COVID-19 Infection</strong> - <b>Conditions</b>: Covid19 <br/><b>Interventions</b>: Drug: Convalescent Plasma; Other: Standard of Care <br/><b>Sponsors</b>: Larkin Community Hospital <br/><b>Withdrawn</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Education of Medical Staff to Post Acute Covid susTained sYmptoms</strong> - <b>Conditions</b>: Post-acute COVID-19 Syndrome <br/><b>Interventions</b>: Other: Training in the management of functional disorders; Other: Reimbursement of 3 long consultations <br/><b>Sponsors</b>: Assistance Publique - Hôpitaux de Paris; ANRS, Emerging Infectious Diseases <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>Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments</strong> - <b>Conditions</b>: Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome; COVID-19; Fatigue; Fatigue Syndrome, Chronic <br/><b>Interventions</b>: Device: Monoplace Hyperbaric Chamber (Class III medical device). <br/><b>Sponsors</b>: Sunnybrook Health Sciences Centre <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>Pharmacist Management of Paxlovid eVisits</strong> - <b>Conditions</b>: COVID-19; Quality of Care <br/><b>Interventions</b>: Other: Pharmacist Care; Other: AFM Pool Care <br/><b>Sponsors</b>: Kaiser Permanente <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>Equity Evaluation of Fact Boxes on Informed COVID-19 and Influenza Vaccination Decisions - Study Protocol</strong> - <b>Conditions</b>: COVID-19; Influenza <br/><b>Interventions</b>: Other: Fact box <br/><b>Sponsors</b>: Harding Center for Risk Literacy <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>tDCS in the Management of Post-COVID Disorders</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training; Behavioral: Cognitive Training <br/><b>Sponsors</b>: Universidade Federal de Pernambuco; São Paulo State University <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>Early Awake Alterning Prone Positioning Combined With Non-invasive Oxygen Therapy in Patients With COVID-19.</strong> - <b>Conditions</b>: COVID-19 Pneumonia <br/><b>Interventions</b>: Other: Prone position; Other: Standard treatment <br/><b>Sponsors</b>: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran <br/><b>Terminated</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>ACTIVATE in Public Housing</strong> - <b>Conditions</b>: Pneumonia; Influenza; Varicella Zoster; Meningitis; COVID-19; Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Increasing Willingness and Uptake of Influenza, Pneumonia, Meningitis, HZV, and COVID-19 Vaccination <br/><b>Sponsors</b>: Charles Drew University of Medicine and Science <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of a Home-Based Exercise Intervention in Subjects With Long COVID</strong> - <b>Conditions</b>: Long COVID-19; Post-COVID-19 Syndrome <br/><b>Interventions</b>: Other: home-based concurrent exercise <br/><b>Sponsors</b>: University of Vienna <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Vector Vaccine GamCovidVac-M (Altered Antigenic Composition)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac-M vector vaccine for the prevention of COVID-19 with altered antigenic composition <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Vector Vaccine GamCovidVac for the Prevention of COVID-19 With Altered Antigenic Profile With Participation of Adult Volunteers</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac vector vaccine for the prevention of COVID-19 (with altered antigenic profile) <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exercise Interventions in Post-acute Sequelae of Covid-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Exercise <br/><b>Sponsors</b>: University of Virginia <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Cacao FLAvonoids in LOng Covid Patients (FLALOC)</strong> - <b>Conditions</b>: Long Covid19; Fatigue Syndrome, Chronic <br/><b>Interventions</b>: Dietary Supplement: Flavonoids <br/><b>Sponsors</b>: Guillermo Ceballos Reyes; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Efficacy of the 2023-2024 Updated COVID-19 Vaccines Against COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Vaccine-Preventable Diseases; SARS CoV 2 Infection; Upper Respiratory Tract Infection; Upper Respiratory Disease <br/><b>Interventions</b>: Biological: Novavax COVID-19 vaccine (2023-2024 formula XBB containing); Biological: Pfizer COVID-19 mRNA vaccine (2023-2024 formula XBB containing) <br/><b>Sponsors</b>: Sarang K. Yoon, DO, MOH; Westat; Novavax <br/><b>Not yet recruiting</b></p></li>
</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>Autoantibodies against Angiotensin-converting enzyme 2 and immune molecules are associated with COVID-19 disease severity</strong> - Increased inflammation caused by SARS-CoV-2 infection can lead to severe coronavirus disease 2019 (COVID-19) and long-term disease manifestations referred to as post-acute sequalae of COVID (PASC). The mechanisms of this variable long-term immune activation are poorly defined. Autoantibodies targeting immune factors such as cytokines, as well as the viral host cell receptor, angiotensin-converting enzyme 2 (ACE2), have been observed after SARS-CoV-2 infection. Autoantibodies to immune factors…</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>Point of care detection of SARS-CoV-2 antibodies and neutralisation capacity-lateral flow immunoassay evaluation compared to commercial assay to inform potential role in therapeutic and surveillance practices</strong> - CONCLUSION: High sensitivity, specificity, and PPV were demonstrated for the POC LFA for the detection of anti-S-RBD antibodies in comparison to the commercial assay. The LFA was not a reliable determinant of the neutralisation capacity of identified antibodies. POC LFA are useful tools in sero-epidemiology settings, pandemic preparedness and may act as supportive tools in treatment decisions through the rapid identification of anti-Spike antibodies.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The clinical relevance of OSM in inflammatory diseases: a comprehensive review</strong> - Oncostatin M (OSM) is a pleiotropic cytokine involved in a variety of inflammatory responses such as wound healing, liver regeneration, and bone remodeling. As a member of the interleukin-6 (IL-6) family of cytokines, OSM binds the shared receptor gp130, recruits either OSMRβ or LIFRβ, and activates a variety of signaling pathways including the JAK/STAT, MAPK, JNK, and PI3K/AKT pathways. Since its discovery in 1986, OSM has been identified as a significant contributor to a multitude 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>Synthesis and Biological Evaluation of Benzothiazolyl-pyridine Hybrids as New Antiviral Agents against H5N1 Bird Flu and SARS-COV-2 Viruses</strong> - A novel series of benzothiazolyl-pyridine hybrids 8a-h and 14a-e were produced from the reaction of enamine derivative 4 with each of the arylcyanoacetamides 5a-h and cyanoacetohydrazides 9a-e. The new products were characterized by spectral techniques (IR, ¹H NMR, ^(13)C NMR, and MS). Biological evaluation of 8a-h and 14a-e in vitro against H5N1 and SARS-COV-2 viruses showed that several compounds had significant activity. Compounds 8f-h, which contain fluorine atoms, have better activity…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploration of 1,2,3-triazolo fused triterpenoids as inhibitors of human coronavirus 229E targeting the viral nsp15 protein</strong> - The coronavirus disease-19 (COVID-19) pandemic has raised major interest in innovative drug concepts to suppress human coronavirus (HCoV) infections. We previously reported on a class of 1,2,3-triazolo fused betulonic acid derivatives causing strong inhibition of HCoV-229E replication via the viral nsp15 protein, which is proposedly related to compound binding at an intermonomer interface in hexameric nsp15. In the present study, we further explored the structure-activity relationship (SAR), 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>Anti-SARS-CoV-2 activity of cyanopeptolins produced by Nostoc edaphicum CCNP1411</strong> - Despite the advances in contemporary medicine and availability of numerous innovative therapies, effective treatment and prevention of SARS-CoV-2 infections pose a challenge. In the search for new anti-SARS-CoV-2 drug candidates, natural products are frequently explored. Here, fifteen cyanopeptolins (CPs) were isolated from the Baltic cyanobacterium Nostoc edaphicum and tested against SARS-CoV-2. Of these depsipeptides, the Arg-containing structural variants showed the strongest inhibition 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>Discovery of druggable potent inhibitors of serine proteases and farnesoid X receptor by ligand-based virtual screening to obstruct SARS-CoV-2</strong> - The coronavirus, a subfamily of the coronavirinae family, is an RNA virus with over 40 variations that can infect humans, non-human mammals and birds. There are seven types of human coronaviruses, including SARS-CoV-2, is responsible for the recent COVID-19 pandemic. The current study is focused on the identification of drug molecules for the treatment of COVID-19 by targeting human proteases like transmembrane serine protease 2 (TMPRSS2), furin, cathepsin B, and a nuclear receptor named…</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>Decoding Sepsis-Induced Disseminated Intravascular Coagulation: A Comprehensive Review of Existing and Emerging Therapies</strong> - Disseminated intravascular coagulation (DIC) is a recurrent complication of sepsis. Since DIC not only promotes organ dysfunction but also represents a strong prognostic factor, it is important to diagnose DIC as early as possible. When coagulation is activated, fibrinolysis is inhibited, blood thinners are consumed, and a condition is created that promotes blood clotting, making it more difficult for the body to remove fibrin or prevent it from being deposited in the blood vessels. This leads…</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>Plant Cell-Engineered Gold Nanoparticles Conjugated to Quercetin Inhibit SARS-CoV-2 and HSV-1 Entry</strong> - Recent studies have revealed considerable promise in the antiviral properties of metal nanomaterials, specifically when biologically prepared. This study demonstrates for the first time the antiviral roles of the plant cell-engineered gold nanoparticles (pAuNPs) alone and when conjugated with quercetin (pAuNPsQ). We show here that the quercetin conjugated nanoparticles (pAuNPsQ) preferentially inhibit the cell entry of two medically important viruses-severe acute respiratory syndrome coronavirus…</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>Phenotypic Test of Benzo[4,5]imidazo[1,2-c]pyrimidinone-Based Nucleoside and Non-Nucleoside Derivatives against DNA and RNA Viruses, Including Coronaviruses</strong> - Emerging and re-emerging viruses periodically cause outbreaks and epidemics around the world, which ultimately lead to global events such as the COVID-19 pandemic. Thus, the urgent need for new antiviral drugs is obvious. Over more than a century of antiviral development, nucleoside analogs have proven to be promising agents against diversified DNA and RNA viruses. Here, we present the synthesis and evaluation of the antiviral activity of nucleoside analogs and their deglycosylated derivatives…</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>Functionalized Fullerene Potentially Inhibits SARS-CoV-2 Infection by Modulating Spike Protein Conformational Changes</strong> - The disease of SARS-CoV-2 has caused considerable morbidity and mortality globally. Spike proteins on the surface of SARS-CoV-2 allow it to bind with human cells, leading to infection. Fullerenes and their derivatives are promising SARS-CoV-2 inhibitors and drug-delivery vehicles. In this study, Gaussian accelerated molecular dynamics simulations and the Markov state model were employed to delve into the inhibitory mechanism of Fullerene-linear-polyglycerol-b-amine sulfate (F-LGPS) on spike…</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>BNT162b2 vaccine induced variant-specific immunity, safety and risk of Omicron breakthrough infection in children aged 5 to 11 years: a cohort study</strong> - There is little information on BNT162b2 vaccine-induced variant-specific immunogenicity, safety data and dynamics of breakthrough infections in pediatric populations. We addressed these questions using a prospective two dose BNT162b2 (10 mcg) vaccination cohort study of healthy children 5-11 years in Singapore. Follow up included blood samples at scheduled visits, daily vaccination symptom diary and confirmation of SARS-CoV-2 infection. Surrogate virus neutralization test (sVNT) and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Author Correction: Calcium dobesilate reduces SARS-CoV-2 entry into endothelial cells by inhibiting virus binding to heparan sulfate</strong> - No abstract</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structure-based development and preclinical evaluation of the SARS-CoV-2 3C-like protease inhibitor simnotrelvir</strong> - The persistent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants accentuates the great demand for developing effective therapeutic agents. Here, we report the development of an orally bioavailable SARS-CoV-2 3C-like protease (3CL^(pro)) inhibitor, namely simnotrelvir, and its preclinical evaluation, which lay the foundation for clinical trials studies as well as the conditional approval of simnotrelvir in…</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 community effort in SARS-CoV-2 drug discovery</strong> - The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the “Billion molecules against Covid-19 challenge”, to identify small-molecule inhibitors against SARS-CoV-2 or relevant human…</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 Luxury Office Development That Became a Horrific Migrant Shelter</strong> - In Brooklyn, hundreds of men have languished in a city-run facility, taking cold showers, eating bad food, and sleeping inches from one another. - <a href="https://www.newyorker.com/news/our-local-correspondents/the-luxury-office-development-that-became-a-horrific-migrant-shelter">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Chaos Party on the Hill Keeps On Chaos-ing</strong> - Even after Hamas’s attack on Israel, House Republicans are too busy fighting with themselves to get serious about the rest of the world. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/the-chaos-party-on-the-hill-keeps-on-chaos-ing">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Keir Starmer, the Man Who Would Be Britain’s Next Prime Minister</strong> - At the annual conference of the Labour Party this week, Keir Starmer laid out his plans to rebuild the United Kingdom after thirteen years of Conservative misrule. - <a href="https://www.newyorker.com/news/our-columnists/the-man-who-would-be-britains-next-prime-minister-keir-starmer-labour">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Humanitarian Catastrophe in Gaza</strong> - International law obligations are nonreciprocal: one war crime doesn’t excuse another. - <a href="https://www.newyorker.com/news/q-and-a/the-humanitarian-catastrophe-in-gaza">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can White House Diplomacy Help Prevent Escalation in Gaza and Beyond?</strong> - It is not a simple matter for the Biden Administration to be, on the one hand, the backstop for Israel’s looming actions in Gaza and, on the other, a voice for strategic caution and the initiator of a diplomatic track. - <a href="https://www.newyorker.com/news/daily-comment/can-white-house-diplomacy-help-prevent-escalation-in-gaza-and-beyond">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Elon Musk wants to merge humans with AI. How many brains will be damaged along the way?</strong> -
<figure>
<img alt="An illustration of Elon Musk attempting to guide a man using a wheelchair into a mysterious, dark tunnel. The man has glowing threads that run from his hand to his head." src="https://cdn.vox-cdn.com/thumbor/Bb1ydRSBcX7qq7KnATsPM8fqxkQ=/353x0:1793x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72760001/231006_xinmei_Vox_Neuralink_final.0.jpg"/>
<figcaption>
Xinmei Liu for Vox
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The brain implant company Neuralink is pushing a needlessly risky approach, former employees say.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ogf1fT">
Of all Elon Musk’s exploits — the Tesla cars, the SpaceX rockets, the Twitter takeover, the plans to colonize Mars — his secretive brain chip company Neuralink may be the most dangerous.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9TK8ak">
What is Neuralink for? In the short term, it’s for helping people with paralysis. But that’s not the whole answer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c66XhN">
Launched in 2016, the company revealed in 2019 that it had created<a href="https://www.vox.com/future-perfect/2019/7/17/20697812/elon-musk-neuralink-ai-brain-implant-thread-robot"> flexible “threads” that can be implanted into a brain</a>, along with a sewing-machine-like robot to do the implanting. The idea is that these threads will read signals from a paralyzed patient’s brain and transmit that data to an iPhone or computer, enabling the patient to control it with just their thoughts — no need to tap or type or swipe.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hNN9yM">
So far, Neuralink has only done testing on animals. But in May, the company announced it had won FDA approval to run its<a href="https://www.reuters.com/science/elon-musks-neuralink-gets-us-fda-approval-human-clinical-study-brain-implants-2023-05-25/"> first clinical trial in humans</a>. Now, it’s<a href="https://neuralink.com/blog/first-clinical-trial-open-for-recruitment/"> recruiting</a> paralyzed volunteers to study whether the implant enables them to control external devices. If the technology works in humans, it could improve quality of life for millions of people. Approximately<a href="https://www.christopherreeve.org/living-with-paralysis/stats-about-paralysis"> 5.4 million people</a> are living with paralysis in the US alone.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nOjwgO">
But helping paralyzed people is not Musk’s end goal. That’s just a step on the way to achieving a much wilder long-term ambition.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zhickz">
That ambition, in<a href="https://www.vox.com/future-perfect/2019/7/17/20697812/elon-musk-neuralink-ai-brain-implant-thread-robot"> Musk’s own words</a>, is “to achieve a symbiosis with artificial intelligence.” His goal is to develop a technology that helps humans “merg[e] with AI” so that we won’t be “left behind” as AI becomes more sophisticated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CSNxQv">
This fantastical vision is not the sort of thing for which the FDA greenlights human trials. But work on helping people with paralysis? That can get a warmer reception. And so it has.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EdstSB">
But it’s important to understand that this technology comes with staggering risks. Former Neuralink employees as well as experts in the field alleged that the company pushed for an unnecessarily invasive, potentially dangerous approach to the implants that can damage the brain (and apparently <a href="https://www.wired.com/story/neuralink-uc-davis-monkey-photos-videos-secret/">has done so in animal test subjects</a>) to advance Musk’s goal of merging with AI.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cDxUuP">
Neuralink did not respond to a request for comment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dEaeIz">
There are also ethical risks for society at large that go beyond just Neuralink. A number of companies are developing tech that plugs into human brains, which can<a href="https://www.vox.com/future-perfect/2023/5/4/23708162/neurotechnology-mind-reading-brain-neuralink-brain-computer-interface"> decode what’s going on in our minds</a> and has the potential to erode mental privacy and supercharge authoritarian surveillance. We have to prepare ourselves for what’s coming.
</p>
<h3 id="PR7ykb">
Why Elon Musk wants to merge human brains with AI
</h3>
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Neuralink is a response to one big fear: that AI will take over the world.
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This is a fear that’s increasingly widespread among AI leaders, who worry that we may create machines that are smarter than humans and that have the ability to<a href="https://www.vox.com/the-highlight/23447596/artificial-intelligence-agi-openai-gpt3-existential-risk-human-extinction"> deceive us and ultimately seize control from us</a>.
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In March, many of them, including Musk, signed<a href="https://www.vox.com/future-perfect/2023/3/29/23660833/ai-pause-musk-artificial-intelligence-moratorium-chatgpt-gpt4"> an open letter</a> calling for a six-month pause on developing AI systems more powerful than OpenAI’s GPT-4. The <a href="https://futureoflife.org/open-letter/pause-giant-ai-experiments/">letter</a> warned that “AI systems with human-competitive intelligence can pose profound risks to society and humanity” and went on to ask: “<em>Should</em> we develop nonhuman minds that might eventually outnumber, outsmart, obsolete and replace us? <em>Should</em> we risk loss of control of our civilization?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h91ip4">
Although Musk is not alone in warning about<a href="https://www.nbcnews.com/politics/congress/big-tech-ceos-ai-meeting-senators-musk-zuckerberg-rcna104738"> “civilizational risk”</a> posed by AI systems, where he differs from others is in his plan for warding off the risk. The plan is basically: If you can’t beat ’em, join ’em.
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Musk foresees a world where AI systems that can communicate information at a trillion bits per second will look down their metaphorical noses at humans, who can only communicate at <a href="https://www.science.org/content/article/human-speech-may-have-universal-transmission-rate-39-bits-second">39 bits per second</a>. To the AI systems, we’d seem useless. Unless, perhaps, we became just like them.
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A big part of that, in Musk’s view, is being able to think and communicate at the speed of AI. “It’s mostly about the bandwidth, the speed of the connection between your brain and the digital version of yourself, particularly output,” he<a href="https://www.cnbc.com/2017/02/13/elon-musk-humans-merge-machines-cyborg-artificial-intelligence-robots.html"> said</a> in 2017. “Some high bandwidth interface to the brain will be something that helps achieve a symbiosis between human and machine intelligence and maybe solves the control problem and the usefulness problem.”
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Fast forward a half-dozen years, and you can see that Musk is still obsessed with this notion of bandwidth — the rate at which computers can read out information from your brain. It is, in fact, the idea that drives Neuralink.
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<img alt=" " src="https://cdn.vox-cdn.com/thumbor/w3db8fRW1FQGzOYju98jOlvpvYs=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24970919/Screen_Shot_2023_10_02_at_1.05.20_PM.png"/>
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The Neuralink device is a brain implant, outfitted with 1,024 electrodes, that can pick up signals from a whole lot of neurons. The more electrodes you’ve got, the more neurons you can listen in on, and the more data you’ll get. Plus, the closer you can get to those neurons, the higher quality your data will be.
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And the Neuralink device gets <em>very </em>close to the neurons. The company’s procedure for implanting it requires drilling a hole in the skull and penetrating the brain.
</p>
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But there are less extreme ways to go about this. Other companies are proving it. Let’s break down what they’re doing — and why Musk feels the need to do something different.
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There are other ways to make a brain-computer interface. Why is Neuralink choosing the most extreme one?
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Neuralink isn’t the only company exploring brain-computer interfaces (BCIs) for restoring people’s physical capabilities. Other companies like <a href="https://synchron.com/">Synchron</a>, <a href="https://blackrockneurotech.com/">Blackrock Neurotech</a>, <a href="https://paradromics.com/">Paradromics</a>, and <a href="https://precisionneuro.io/">Precision Neuroscience</a> are also working in this space. So is <a href="https://www.darpa.mil/news-events/2019-05-20">the US military</a>.
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In recent years, a lot of the research that’s made headlines has focused on brain implants that would <a href="https://www.statnews.com/2018/11/15/brain-computer-interface-translate-thoughts-speech/">translate paralyzed people’s thoughts into speech</a>. Mark Zuckerberg’s Meta, for example, is working on BCIs that could <a href="https://www.vox.com/future-perfect/2019/8/5/20750259/facebook-ai-mind-reading-brain-computer-interface">pick up thoughts directly from your neurons and translate them into words</a> in real time. (In the long term, the company <a href="https://tech.facebook.com/reality-labs/2020/3/imagining-a-new-interface-hands-free-communication-without-saying-a-word/">says</a> it aims to give everyone the ability to control keyboards, augmented reality glasses, and more, using just their thoughts.)
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Earlier success in the BCI field focused not on speech, but on movement. In 2006, Matthew Nagle, a man with spinal cord paralysis, <a href="https://www.nytimes.com/2006/07/13/science/13brain.html">received a brain implant</a> that allowed him to control a computer cursor. Soon Nagle was playing Pong using only his mind.
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Nagle’s brain implant, developed by the research consortium <a href="https://www.braingate.org/">BrainGate</a>, contained a “Utah” array, a cluster of <a href="https://www.theguardian.com/science/2019/sep/22/brain-computer-interface-implants-neuralink-braingate-elon-musk">100 spiky electrodes</a> that is surgically embedded into the brain. That’s only around one-tenth of the electrodes in Neuralink’s device. But it still enabled a paralyzed person to move a cursor, check email, adjust the volume or channel on a TV, and control a robotic limb. Since then, others with paralysis have achieved <a href="https://www.theverge.com/2015/5/21/8639905/brain-control-robot-arm-paralyzed-quadriplegic">similar feats</a> with BCI technology.
</p>
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While early technologies like the Utah array protruded awkwardly from the skull, newer BCIs are invisible to the outside observer once they’re implanted, and some are much less invasive.
</p>
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Synchron’s BCI, for example, builds on stent technology that’s been around since the 1980s. A stent is a metal scaffold that you can introduce into a blood vessel; it can be safely left there for decades (and has been in many cardiac patients, keeping their arteries open). Synchron uses a catheter to send a stent up into a blood vessel in the motor cortex of the brain. Once there, the stent unfurls like a flower, and sensors on it pick up signals from neurons. This has already <a href="https://www.ted.com/talks/tom_oxley_a_brain_implant_that_turns_your_thoughts_into_text">enabled several paralyzed people to tweet and text with their thoughts</a>.
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No open brain surgery necessary. No drilling holes in the skull.
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Musk himself has said that BCIs wouldn’t necessarily require open brain surgery, in <a href="https://www.youtube.com/watch?v=ZrGPuUQsDjo">a telling five-minute video at Recode’s Code Conference in 2016</a>. “You could go through the veins and arteries, because that provides a complete roadway to all of your neurons,” he said. “You could insert something basically into the jugular and…”
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After the audience laughed nervously, he added, “It doesn’t involve chopping your skull off or anything like that.”
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In Neuralink’s early years, before the company had settled on its current approach — which <em>does </em>involve drilling into the skull — one of its research teams allegedly looked into the tamer intravascular approach, four former Neuralink employees told me. This team explored the option of delivering a device to the brain through an artery and demonstrated that it was feasible.
</p>
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But by 2019, Neuralink had rejected this option, choosing instead to go with the more invasive surgical robot that implants threads directly into the brain.
</p>
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Why? If the intravascular approach can restore key functioning to paralyzed patients, and also avoids some of the safety risks that come with crossing the blood-brain barrier, such as inflammation and scar tissue buildup in the brain, why opt for something more invasive than necessary?
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The company isn’t saying. But according to Hirobumi Watanabe, who led Neuralink’s intravascular research team in 2018, the main reason was the company’s obsession with maximizing bandwidth.
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“The goal of Neuralink is to go for more electrodes, more bandwidth,” Watanabe said, “so that this interface can do way more than what other technologies can do.”
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After all, Musk has suggested that a seamless merge with machines could enable us to do everything from <a href="https://www.businessinsider.com/neuralink-elon-musk-microchips-brains-ai-2021-2#elon-musk-also-says-that-in-the-long-term-neuralinks-chip-could-be-used-to-meld-human-consciousness-with-artificial-intelligence-though-experts-are-skeptical-of-this-15">enhancing our memory</a> to <a href="https://www.cnbc.com/2022/04/08/elon-musk-humans-could-eventually-download-their-brains-into-robots.html">uploading our minds and living forever</a> — staples of <a href="https://www.vox.com/the-highlight/23779413/silicon-valleys-ai-religion-transhumanism-longtermism-ea">Silicon Valley’s transhumanist fantasies</a>. Which perhaps helps make sense of the company’s dual <a href="https://neuralink.com/">mission</a>: to “create a generalized brain interface to restore autonomy to those with unmet medical needs today and unlock human potential tomorrow.”
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“Neuralink is explicitly aiming at producing general-purpose neural interfaces,” the Munich-based neuroethicist <a href="https://www.professoren.tum.de/en/ienca-marcello">Marcello Ienca</a> told me. “To my knowledge, they are the only company that is currently planning clinical trials for implantable medical neural interfaces while making public statements about future nonmedical applications of neural implants for cognitive enhancement. To create a general-purpose technology, you need to create a seamless interface between humans and computers, enabling enhanced cognitive and sensory abilities. Achieving this vision may indeed require more invasive methods to achieve higher bandwidth and precision.”
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Watanabe believes Neuralink prioritized maximizing bandwidth because that serves Musk’s goal of creating a generalized BCI that lets us merge with AI and develop all sorts of new capacities. “That’s what Elon Musk is saying, so that’s what the company has to do,” he said.
</p>
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The intravascular approach didn’t seem like it could deliver as much bandwidth as the invasive approach. Staying in the blood vessels may be safer, but the downside is that you don’t have access to as many neurons. “That’s the biggest reason they did not go for this approach,” Watanabe said. “It’s rather sad.” He added that he believed Neuralink was too quick to abandon the minimally invasive approach. “We could have pushed this project forward.”
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For Tom Oxley, the CEO of Synchron, this raises a big question. “The question is, does a clash emerge between the short-term goal of patient-oriented clinical health outcomes and the long-term goal of AI symbiosis?” he told me. “I think the answer is probably yes.”
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“It matters what you’re designing for and if you have a patient problem in mind,” Oxley added. Synchron could theoretically build toward increasing bandwidth by miniaturizing its tech and going into deeper branches of the blood vessels; <a href="https://www.science.org/doi/10.1126/science.adh3916">research</a> shows this is viable. “But,” he said, “we chose a point at which we think we have enough signal to solve a problem for a patient.”
</p>
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Ben Rapoport, a neurosurgeon who left Neuralink to found Precision Neuroscience, emphasized that any time you’ve got electrodes penetrating the brain, you’re doing some damage to brain tissue. And that’s unnecessary if your goal is helping paralyzed patients.
</p>
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“I don’t think that tradeoff is required for the kind of neuroprosthetic function that we need to restore speech and motor function to patients with stroke and spinal cord injury,” Rapoport told me. “One of our guiding philosophies is that building a high-fidelity brain-computer interface system can be accomplished without damaging the brain.”
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To prove that you don’t need Muskian invasiveness to achieve high bandwidth, Precision has designed a thin film that coats the surface of the brain with 1,024 electrodes — the same number of electrodes in Neuralink’s implant — that deliver signals similar to Neuralink’s. The film has to be inserted through a slit in the skull, but the advantage is that it sits on the brain’s surface without penetrating it. Rapoport calls this the “Goldilocks solution,” and it’s already been <a href="https://www.globenewswire.com/news-release/2023/06/06/2682588/0/en/Precision-Neuroscience-Begins-First-in-Human-Study-of-its-Neural-Interface-Technology.html">implanted</a> in a handful of patients, recording their brain activity at high resolution.
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“It’s key to do a very, very safe procedure that doesn’t damage the brain and that is minimally invasive in nature,” Rapoport said. “And furthermore, that as we scale up the bandwidth of the system, the risk to the patient should not increase.”
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This makes sense if your most cherished ambition is to help patients improve their lives as much as possible without courting undue risk. But Musk, we know, has other ambitions.
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“What Neuralink doesn’t seem to be very interested in is that while a more invasive approach might offer advantages in terms of bandwidth, it raises greater ethical and safety concerns,” Ienca told me. “At least, I haven’t heard any public statement in which they indicate how they intend to address the greater privacy, safety, and mental integrity risks generated by their approach. This is strange because according to international research ethics guidelines it wouldn’t be ethical to use a more invasive technology if the same performance can be achieved using less invasive methods.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EbibZg">
More invasive methods, by their nature, can do real damage to the brain — as Neuralink’s experiments on animals have shown.
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<h3 id="Z0PLVg">
Ethical concerns about Neuralink, as illustrated by its animals
</h3>
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Some Neuralink employees have come forward to speak on behalf of the pigs and monkeys used in the company’s experiments, saying they suffered and died at higher rates than necessary because the company was <a href="https://www.reuters.com/technology/musks-neuralink-faces-federal-probe-employee-backlash-over-animal-tests-2022-12-05/">rushing and botching surgeries</a>. Musk, they alleged, was pushing the staff to get FDA approval quickly after he’d repeatedly predicted the company would soon start human trials.
</p>
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One example of a grisly error: In 2021, Neuralink implanted 25 out of 60 pigs with devices that were the wrong size. Afterward, the company killed all the affected pigs. Staff told Reuters that the mistake could have been averted if they’d had more time to prepare.
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Veterinary reports indicate that <a href="https://www.wired.com/story/elon-musk-pcrm-neuralink-monkey-deaths/">Neuralink’s monkeys also suffered gruesome fates</a>. In one monkey, a bit of the device “broke off” during implantation in the brain. The monkey scratched and yanked until part of the device was dislodged, and infections took hold. Another monkey developed bleeding in her brain, with the implant leaving parts of her cortex “tattered.” Both animals were euthanized.
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Last December, the US Department of Agriculture’s Office of Inspector General launched an <a href="https://www.reuters.com/technology/musks-neuralink-faces-federal-probe-employee-backlash-over-animal-tests-2022-12-05/">investigation</a> into possible animal welfare violations at Neuralink. The company is also facing a <a href="https://www.reuters.com/technology/elon-musks-neuralink-may-have-illegally-transported-pathogens-animal-advocates-2023-02-09/">probe</a> from the Department of Transportation over worries that implants removed from monkeys’ brains may have been packaged and moved unsafely, potentially exposing people to pathogens.
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“Past animal experiments [at Neuralink] revealed <a href="https://pcrm.widen.net/s/llzr7cg57q/request-for-glp-investigation-re-neuralink---with-enclosures---12.13.22">serious safety concerns</a> stemming from the product’s invasiveness and rushed, sloppy actions by company employees,” said the Physicians Committee for Responsible Medicine, a nonprofit that opposes animal testing, in a May <a href="https://www.pcrm.org/news/news-releases/physicians-committees-statement-neuralink-reportedly-receiving-approval-human">statement</a>. “As such, the public should continue to be skeptical of the safety and functionality of any device produced by Neuralink.”
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Nevertheless, the FDA has cleared the company to begin human trials.
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“The company has provided sufficient information to support the approval of its IDE [investigational device exemption] application to begin human trials under the criteria and requirements of the IDE approval,” the FDA said in a statement to Vox, adding, “The agency’s focus for determining approval of an IDE is based on assessing the safety profile for potential subjects, ensuring risks are appropriately minimized and communicated to subjects, and ensuring the potential for benefit, including the value of the knowledge to be gained, outweighs the risk.”
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<h3 id="2QJDiB">
What if Neuralink’s approach works too well?
</h3>
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Beyond what the surgeries will mean for the individuals who get recruited for Neuralink’s trials, there are ethical concerns about what BCI technology means for society more broadly. If high-bandwidth implants of the type Musk is pursuing really do allow unprecedented access to what’s happening in people’s brains, that could make dystopian possibilities more likely. Some neuroethicists argue that the potential for misuse is so great that <a href="https://www.vox.com/2019/8/30/20835137/facebook-zuckerberg-elon-musk-brain-mind-reading-neuroethics">we need revamped human rights laws to protect us</a> before we move forward.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9kFmNk">
For one thing, our brains are the final privacy frontier. They’re the seat of our personal identity and our most intimate thoughts. If those precious three pounds of goo in our craniums aren’t ours to control, what is?
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In China, the government is already mining data from some workers’ brains by having them wear <a href="https://www.scmp.com/news/china/society/article/2143899/forget-facebook-leak-china-mining-data-directly-workers-brains">caps that scan their brainwaves</a> for emotional states. In the US, <a href="https://www.theatlantic.com/magazine/archive/2018/11/the-pentagon-wants-to-weaponize-the-brain-what-could-go-wrong/570841/">the military is looking into neurotechnologies</a> to make soldiers more fit for duty — more alert, for instance.
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And some police departments around the world have been exploring <a href="https://www.theverge.com/2015/2/2/7951549/brain-fingerprinting-technology-unproven-courtroom-science-farwell-p300">“brain fingerprinting” technology</a>, which analyzes automatic responses that occur in our brains when we encounter stimuli we recognize. (The idea is that this could enable police to interrogate a suspect’s brain; their brain responses would be more negative for faces or phrases they don’t recognize than for faces or phrases they do recognize.) Brain fingerprinting tech is <a href="https://www.researchgate.net/publication/344526903_Brain_Fingerprinting_A_Warning_Against_Early_Implementation">scientifically questionable</a>, yet India’s police have used it since 2003, Singapore’s police bought it in 2013, and the Florida state police <a href="https://www.bbc.com/future/article/20160125-is-it-wise-that-the-police-have-started-scanning-brains">signed a contract to use it in 2014</a>.
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Imagine a scenario where your government uses BCIs for surveillance or interrogations. The right to not self-incriminate — enshrined in the US Constitution — could become meaningless in a world where the authorities are empowered to eavesdrop on your mental state without your consent.
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Experts also worry that devices like those being built by Neuralink may be vulnerable to hacking. What happens if you’re using one of them and a malicious actor intercepts the Bluetooth connection, changing the signals that go to your brain to make you more depressed, say, or more compliant?
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Neuroethicists refer to that as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290799/#CR51">brainjacking</a>. “This is still hypothetical, but the possibility has been demonstrated in proof-of-concept studies,” Ienca <a href="https://www.vox.com/2019/8/30/20835137/facebook-zuckerberg-elon-musk-brain-mind-reading-neuroethics">told me</a> in 2019. “A hack like this wouldn’t require that much technological sophistication.”
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Finally, consider how your psychological continuity or fundamental sense of self could be disrupted by the imposition of a BCI — or by its removal. In one <a href="https://voxcom.cmail20.com/t/d-l-xlkdhkd-jytjceij-o/">study</a>, an epileptic woman who’d been given a BCI came to feel such a radical symbiosis with it that, she said, “It became me.” Then the company that implanted the device in her brain went bankrupt and she was forced to have it removed. She cried, saying, “I lost myself.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HPy5qU">
To ward off the risk of a hypothetical all-powerful AI in the future, Musk wants to create a symbiosis between your brain and machines. But the symbiosis generates its own very real risks — and they are upon us now.
</p>
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</p>
<ul>
<li><strong>The Vox guide to open enrollment</strong> -
<figure>
<img alt="A drawing of a person looking at a hospital building covered in boxes, some of which are checked." src="https://cdn.vox-cdn.com/thumbor/4uo9Q0yBfSyLSAyi_tyQ71cRLT8=/0x0:1440x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72748337/231011_vox_open_enrollment_lead__1_.0.jpg"/>
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Sebastian König for Vox
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Every year, picking a health plan is a frustrating guessing game. Here’s how to navigate your choices — and understand the system that built them.
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It’s time for one of the most confusing, frustrating rituals of the year: <a href="https://www.vox.com/health-care">health care</a> open enrollment. Over the coming weeks and months, people across the country will consider questions that we try to avoid the other 11 months of the year: Is it better to have a high premium and a low deductible, or the other way around? How are you supposed to guess how much money to put in a flexible spending account? Does dental insurance actually, you know, do anything? Please remind me, what is “coinsurance” again?
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The whole annual ordeal raises a bigger question, too: Why is all of this so complicated?
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It turns out that understanding open enrollment goes a long way to helping understand the convoluted American health insurance system. The choices you face at this time of year about next year’s insurance plans are the result of quirks in the tax code and accidents of history. Nobody would build a health care system this way on purpose. But it’s the one that, for now, we’re stuck with. We hope these stories help you navigate the choices you face — while helping you understand why they exist in the first place.
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<em>— Libby Nelson</em>
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<small><em><strong>Editorial Lead: </strong></em></small><small><em>Libby Nelson | </em></small><small><em><strong>Editors:</strong></em></small><small><em> Meredith Haggerty, Alanna Okun | </em></small><small><em><strong>Reporters: </strong></em></small><small><em>Dylan Scott, Emily Stewart, Allie Volpe | </em></small><small><em><strong>Style &amp; Standards: </strong></em></small><small><em>Tanya Pai, Caity PenzeyMoog, Kim Eggleston, Elizabeth Crane, Sarah Schweppe, Anouck Dussaud | </em></small><small><em><strong>Art Director: </strong></em></small><small><em>Paige Vickers | </em></small><small><em><strong>Illustrator: </strong></em></small><small><em>Sebastian König | </em></small><small><em><strong>Audio:</strong></em></small><small><em> A. Hall, Jonquilyn Hill, Sofi LaLonde | </em></small><small><em><strong>Audience Lead:</strong></em></small><small><em> Shira Tarlo | </em></small><small><em><strong>Managing Editors: </strong></em></small><small><em>Natalie Jennings, Nisha Chittal | </em></small><small><em><strong>Special Thanks: </strong></em></small><small><em>Blair Hickman, Andrew Losowsky, Sam Hankins, Amani Orr</em></small>
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<li><strong>The subtle privatization of Medicare</strong> -
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Sebastian König for Vox
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More than half of seniors will sign up for a private version of Medicare this open enrollment. What happened?
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If you’re signing up for Medicare benefits this <a href="https://www.vox.com/e/23678392">open enrollment</a>, odds are you aren’t actually enrolling in the traditional government program that people may envision. More than half of Medicare beneficiaries are now choosing an alternative version of the program administered by private companies.
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Medicare, the paragon of America’s welfare state, is undergoing a subtle but fundamental transformation from government program to public benefit provided by private companies, a shift with major implications for both patients and taxpayers. This alternative version of Medicare, known as Medicare Advantage, now covers more than half of the program’s 60 million enrollees, or about <a href="https://khn.org/morning-breakout/medicare-advantage-enrollment-reaches-31-million-though-is-slowing/">31 million Americans</a> — nearly double its share 10 years ago.
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<img alt=" " src="https://cdn.vox-cdn.com/thumbor/dYEE9rqFC-N-RTiICiJZmkWFCiI=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24970542/total_medicare_advantage_enrollment_2007_2023.png"/> <cite>KFF</cite>
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That explosive growth has invited fresh scrutiny. <a href="https://www.vox.com/joe-biden">President Joe Biden</a> and House Republicans bickered over the administration’s <a href="https://www.kff.org/policy-watch/is-the-biden-administration-proposing-cuts-to-medicare-advantage/">proposed changes to payments</a> for the private insurers that sell Medicare Advantage plans earlier this year. Fears over <a href="https://www.vox.com/policy/2023/3/9/23630856/joe-biden-budget-medicare-trust-fund-taxes">Medicare’s solvency</a> have renewed the debate about how much the plans <a href="https://www.healthaffairs.org/do/10.1377/forefront.20220223.736815/">cost the federal government</a>. And <a href="https://www.statnews.com/2023/03/13/medicare-advantage-plans-denial-artificial-intelligence/">recent investigations</a> have added to concerns about how private companies oversee the public benefits they are supposed to provide.
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If you’re choosing between traditional Medicare and an Advantage plan, here’s what you should know about the two versions of the program — how we got here, the potential drawbacks, and what could be in store for the program going forward.
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What is Medicare Advantage?
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Medicare has traditionally been a government-run insurance program for people over 65 and those with long-term disabilities. Medicare Advantage allows private insurers to offer their own plans that provide Medicare benefits, as well as some additional perks not available in the original program. The secret to the program’s success is simplicity. Traditional Medicare is a fragmented program: Part A covers hospital care, and Part B covers outpatient services. Patients must enroll in a separate Part D plan for prescription drug coverage that is administered by private insurers. Most people also purchase supplemental coverage, extra insurance that helps reduce their out-of-pocket costs.
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Medicare Advantage, also known as Part C, combines those benefits into one insurance plan that also includes an annual limit on out-of-pocket costs, something that does not technically exist in regular Medicare.
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But the benefits to patients seem to come at a cost to taxpayers. Though the health insurance industry <a href="https://www.ahip.org/news/press-releases/new-study-medicare-advantage-costs-less-than-original-medicare">disputes</a> these findings, MedPAC, the independent committee tasked with overseeing Medicare on <a href="https://www.vox.com/congress">Congress</a>’s behalf, <a href="https://www.medpac.gov/wp-content/uploads/import_data/scrape_files/docs/default-source/reports/mar21_medpac_report_to_the_congress_sec.pdf#page=401">found</a> Medicare Advantage plans cost the federal government more money per patient than the original program would have if those same people had stuck with the traditional benefits.
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Private companies are also making healthy margins on their Medicare business. <a href="https://www.kff.org/medicare/issue-brief/health-insurer-financial-performance/">A Kaiser Family Foundation analysis</a> found that insurers were making more money per patient in Medicare Advantage than with their individual or employer-sponsored plans. Humana, which covers 5 million beneficiaries, or roughly one in five people who have elected to go with the Medicare alternative, <a href="https://www.ajmc.com/view/humana-leaving-commercial-business-will-focus-on-government-funded-programs">announced this year</a> it was dropping the rest of its portfolio to focus exclusively on the Medicare Advantage market and Medicaid managed care, a version of that government program that is similarly run by private insurers with state supervision.
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Patients have clearly found something to like in what Medicare Advantage offers. The program was established in 1997 to give people a streamlined alternative, a private option less overt than <a href="https://khn.org/morning-breakout/gop-platform/">more recent GOP voucher proposals</a>.
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But scholarly research and media investigations have revealed notable downsides in turning over a program that covers America’s seniors, the people who need and use the most <a href="https://www.vox.com/health-care">health care</a>, to private companies. Medicare Advantage enrollees are more likely to report trouble affording health care than people on traditional Medicare. Some of the behavior by Medicare Advantage plans, such as using <a href="https://www.vox.com/2023/4/28/23702644/artificial-intelligence-machine-learning-technology">AI</a> to decide when to stop covering services for their enrollees, may be becoming more common in the private sector but is still unheard of for public programs.
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The trade-off the United States seems to be making is accepting more administrative bloat and more stringent provision of benefits in exchange for a more navigable Medicare plan. The trade-off is one other countries have made as they designed universal health care programs. (A similar trend is <a href="https://www.kff.org/medicaid/issue-brief/10-things-to-know-about-medicaid-managed-care/">underway in Medicaid</a>.)
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But as concern grows about Medicare facing a potential financial cliff, and evidence mounts about the costs of Medicare Advantage, the risks of the trade-off are becoming clearer. Medicare is no longer what it used to be: Once the epitome of government-run health insurance, its benefits are on the verge of being primarily funneled through private companies. Any attempts to change the program will have to wrestle with that reality.
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How Medicare Advantage got so popular
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Pilot programs for private insurers’ administration of Medicare date to the 1970s, but the Medicare Advantage program was created by the Balanced Budget Act of 1997, at a time when concerns about Medicare’s solvency ran high. Originally known as Medicare Choice or Part C, it was renamed Medicare Advantage in 2003, when Medicare was expanded to cover prescription drugs.
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The idea was to provide patients with a simpler Medicare plan. If you have <a href="https://www.medicare.gov/basics/costs/medicare-costs">traditional Medicare</a>, you are combining Part A, for which most people don’t pay a premium, and B, for which most people do, with a separate Part D drug plan, and potentially supplemental coverage, too. With Medicare Advantage, people can enroll in a single insurance plan that provided the full menu of benefits.
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Some Medicare Advantage plans also include dental, hearing, and vision benefits, services that are not covered by the traditional program but can be critical for seniors. Medicare Advantage plans also set annual caps on out-of-pocket costs, which don’t apply in traditional Medicare. (Supplemental coverage or Medicaid instead lowers costs for most — but not all — Americans who opt for the original version of the program.)
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Beneficiaries pay monthly premiums to purchase a Medicare Advantage plan; people with lower incomes qualify for subsidies. There are notable limitations in coverage. In traditional Medicare, for example, patients can go to any doctor or hospital that accepts Medicare; Medicare Advantage has more limited provider networks, and patients can be on the hook for higher costs if they are treated at an out-of-network doctor or hospital.
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The federal government pays Medicare Advantage plans a flat rate for the expected cost of covering their particular customers and the insurers are required to adhere to certain rules about benefits and costs. But companies still have flexibility about how to run their plans and have a financial incentive to limit expenses. The less money they spend, the more they get to keep for themselves.
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Still, customers will vote with their feet and, after <a href="https://www.cbo.gov/sites/default/files/105th-congress-1997-1998/reports/bba-97.pdf">slower-than-expected initial uptake</a>, Medicare Advantage is now growing so quickly that it has become the dominant form of Medicare.
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Why the movement? In <a href="https://www.healthaffairs.org/do/10.1377/forefront.20210304.136304/full/">a 2021 analysis published in Health Affairs</a>, Ken Terry and David Muhlestein observed that “we’re witnessing the rapid privatization of Medicare” and offered an explanation: Medicare Advantage plans “offer beneficiaries a better deal than traditional Medicare.”
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The premiums people pay for a Medicare Advantage plan can be significantly lower than the combined cost of supplemental coverage and a Part D plan — less than $50 compared to more than $200 on average, per Terry and Muhlestein — with the added benefit of having only a single insurance card. According to <a href="https://www.commonwealthfund.org/publications/issue-briefs/2022/oct/traditional-medicare-or-advantage-how-older-americans-choose">a 2022 Commonwealth Fund survey</a>, the additional benefits offered by Medicare Advantage plans (such as dental or vision) and the limits on out-of-pocket costs were the most common reasons seniors gave for choosing the alternative over the original program.
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In general, patients with traditional Medicare and people with Medicare Advantage say they have similar satisfaction with their benefits. On some metrics, the latter group excels; people with a Medicare Advantage plan are more likely to have a regular doctor and to say they have received preventive health care services. With a few exceptions for particular medicines, Medicare Advantage customers report fewer problems accessing their prescription drugs, too.
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But people enrolled in Medicare Advantage also experience a unique set of problems compared to people who choose the original program.
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The potential downsides of Medicare Advantage’s growth
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Those problems, based on the available research, start with cost. A higher percentage of Medicare Advantage enrollees report having problems affording care (about 19 percent, per <a href="https://www.kff.org/medicare/issue-brief/cost-related-problems-are-less-common-among-beneficiaries-in-traditional-medicare-than-in-medicare-advantage-mainly-due-to-supplemental-coverage/">a 2021 KFF analysis</a>) than those on traditional Medicare (15 percent), though people on the original program without supplemental coverage had the most problems with affordability (30 percent). (Most people on Medicare do purchase this coverage.) Black Americans and people with lower incomes were more likely to report having trouble paying for health care while enrolled in Medicare Advantage.
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Other findings appear worrisome, too. Medicare Advantage patients are <a href="https://www.ajmc.com/view/comparison-of-the-use-of-top-ranked-cancer-hospitals-between-medicare-advantage-and-traditional-medicare">less likely to receive medical care at the highest-rated facilities</a> for their particular needs, compared to people with traditional Medicare, a reflection of more restrictive provider networks. Families also <a href="https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2771443">reported</a> more satisfaction with end-of-life care when using traditional Medicare.
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Specific business practices by Medicare Advantage plans, and their consequences for patients, have also been called into question by investigative reporting and government inquiries over the past few years, practices that seem to run counter to Medicare’s function as an entitlement program for Americans over 65 and those with long-term disabilities.
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Earlier this year, STAT <a href="https://www.statnews.com/2023/03/13/medicare-advantage-plans-denial-artificial-intelligence/">reported</a> on the increasing use of AI algorithms by these plans to determine when to cut off benefits for a customer. The lead example of their reporting was an 85-year-old woman with a broken left shoulder, whose insurer followed an algorithm that said she should be ready to leave a nursing facility and return home within 17 days.
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On the 17th day of her stay, the insurer said it would no longer cover the bills for her stay, even though her doctors and nurses observed that the woman was still in extreme pain and incapable of doing basic activities, such as dressing herself or going to the bathroom. It took more than a year, and a federal judge’s order, for the patient to receive payments for the three additional weeks she needed to stay in the nursing facility. Doctors shared other stories of patients who saw benefits withdrawn at the end of their life, leaving their families to fight over the leftover bills for years after their loved one had died.
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A <a href="https://oig.hhs.gov/oei/reports/OEI-09-18-00260.pdf">report from federal investigators published in April 2022</a> found that tens of thousands of Medicare Advantage customers were denied coverage for services they should have been entitled to. A significant number of prior authorization denials (13 percent) and payment denials (19 percent) reviewed by the investigators were for services that should have been covered by the program but were not.
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“Denied requests that meet Medicare coverage rules may prevent or delay beneficiaries from receiving medically necessary care and can burden providers,” they wrote. “Even when denials are reversed, avoidable delays and extra steps create friction in the program.”
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In addition, as <a href="https://www.nytimes.com/2022/10/08/upshot/medicare-advantage-fraud-allegations.html">the New York Times reported last October</a>, most of the largest Medicare Advantage insurers have been the subject of federal audits that found they improperly billed the program and of litigation that accused them of fraud. Taken together, the plans overbilled Medicare by between $12 billion and $25 billion in 2020, depending on the estimate.
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Though Medicare Advantage was first established as a tool for reining in spending, these private plans instead seem to be perpetuating the program’s solvency crisis.
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According to MedPac, since 2004, Medicare has always paid more to Medicare Advantage insurers for the cost of covering their customers than the program would have spent if the same beneficiaries had instead been enrolled in traditional Medicare. Some years, the private plans were receiving a nearly 20 percent markup compared to the original benefit structure.
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<img alt=" " src="https://cdn.vox-cdn.com/thumbor/9qUQDxqyYiqx9XYWBXg227Eafiw=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24509619/Screen_Shot_2023_03_14_at_1.00.11_PM.png"/> <cite>MedPAC</cite>
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Those high payments are drawing more attention with an insolvency crisis for Medicare Part A, which covers hospital bills, on the horizon. Part A is funded almost entirely through the program’s dedicated payroll taxes. If those benefits cost more than the government receives in Medicare payroll taxes in a given year, as can happen in an economic downturn, the difference comes out of a trust fund earmarked specifically for Part A. The Medicare trustees, who issue <a href="https://www.cms.gov/files/document/2022-medicare-trustees-report.pdf">annual reports on the program’s finances</a>, project that Medicare spending will begin outpacing revenue again in 2024, requiring the program to dip into the trust fund. The trust fund is projected to be fully depleted by 2028 without further policy changes.
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The growth of Medicare Advantage is contributing to the financial crunch. Those plans receive funding based on the type of service provided to their customer, which means money for hospital care comes from Part A. Annual Part A payments to Medicare Advantage plans are expected to increase from about $176 billion in 2022 to $336 billion by 2030.
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With revived concerns over Medicare’s solvency and evidence of excess spending in Medicare Advantage, policymakers are starting to look at making changes to the program. But that won’t be easy.
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The health insurance industry will resist big changes or cuts to Medicare Advantage
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Health insurers are going to fiercely defend their Medicare Advantage business against any proposed cuts, as the flap over the Biden administration’s proposed payment changes reveals. That’s because Medicare Advantage is now the industry’s most profitable line of business. United Healthcare, the nation’s largest health insurer and the largest seller of Medicare Advantage plans, has been <a href="https://www.healthcarefinancenews.com/news/unitedhealthcare-expand-medicare-advantage-footprint-2022">aggressively expanding</a> its offerings for people in the program.
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That has made insurers very protective of their Medicare Advantage business. Insurers are not quite the lobbying force they were before the <a href="https://www.vox.com/obamacare">Affordable Care Act</a>, but they remain highly influential and they have found allies among Republicans who have always preferred to see Medicare become more of a private operation.
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Earlier this year, that alliance successfully targeted proposed payment changes by the Biden administration. As KFF analysts <a href="https://www.kff.org/policy-watch/is-the-biden-administration-proposing-cuts-to-medicare-advantage/">explained</a>, the White House wanted to crack down on overpayments with adjustments to the complicated formula that determines when Medicare Advantage plans need to pay back the federal government for improper billing. The insurance industry painted that proposal as a cut, even though the Biden administration estimated that, when the entirety of their proposed payment plan is taken into consideration, Medicare Advantage plans would still see a 1 percent increase in payments from the federal government in 2024.
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Health insurers warned of premium increases and benefit cuts, “though there is no clear evidence to suggest that,” according to the KFF analysts. They were joined by Republicans, who sought to turn the tables on Biden by accusing him of proposing Medicare cuts after the president had criticized Republican plans to cut spending for the program.
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“Joe Biden is trying to gut Medicare benefits. Seniors can’t trust Democrats to protect Medicare,” one Republican campaign spokesperson <a href="https://rollcall.com/2023/02/22/insurers-republicans-square-off-with-biden-on-medicare-cuts/">told Roll Call</a> in February. The Better Medicare Alliance, a lobbying group for Medicare Advantage plans, has started running TV ads asking seniors to petition the White House to reverse the proposed payment changes.
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Though independent fact-checkers <a href="https://khn.org/news/article/tom-cotton-medicare-advantage-biden-fact-check/">concluded</a> that calling the Biden proposal a cut is inaccurate, the private insurers still won. The payment rates that the administration finalized in April after this brouhaha <a href="https://www.reuters.com/world/us/us-softens-cut-medicare-advantage-2024-payments-2023-04-01/">ended up being more favorable to the Medicare Advantage plans</a>. The entire episode demonstrated Medicare Advantage’s growing political clout and previewed the fight that would likely meet any efforts to seriously alter the program.
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The policy structure of Medicare Advantage is not without precedent. States have outsourced much of the administration of Medicaid to managed care plans. <a href="https://www.vox.com/policy-and-politics/2020/1/17/21046874/netherlands-universal-health-insurance-private">Countries like the Netherlands</a> have set up health systems that use private insurers, operating under strict government oversight, to provide insurance benefits to their citizens. Giving people more choice and a more streamlined experience can have its benefits, as evidenced by the popularity of Medicare Advantage in the US.
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But asking private actors, with profit motivations, to administer government benefits to which people are supposed to be entitled brings risks. People are more likely to have trouble affording health care, and their claims are more likely to be denied; that is true in places like the Netherlands, compared to other countries with more direct government administration, and that is true of Medicare Advantage when compared to the traditional Medicare program.
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To date, policymakers have seemed content to let Medicare Advantage grow without much moderation. Medicare beneficiaries have been attracted to its comparative simplicity. But the costs of funding the program, amid the political environment’s shift toward more fiscal restraint, and the problems experienced by patients have put the program under the microscope.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rIgcUm">
It is difficult, at this point, to imagine the Medicare program without Medicare Advantage. The question is whether policymakers can make it more cost-effective and crack down on insurer behavior that runs counter to the program’s objectives. Recent events suggest that if they try, they will have a fight on their hands.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qVEF9G">
<em><strong>Update, October 16, 6 am ET: </strong></em><em>This story was originally published on March 17 and has been updated for 2023’s open enrollment process.</em>
</p>
<hr class="p-entry-hr" id="j1ExsS"/>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jWyBxY">
<em>Still have questions? Vox health care reporter Dylan Scott will be chatting with Vox contributors on Thursday, October 19. To sign up, </em><a href="https://www.vox.com/pages/support-now?itm_campaign=coral-chat&amp;itm_medium=site&amp;itm_source=sidebar"><em>make a monthly or annual contribution to Vox before Wednesday afternoon</em></a><em>.</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>BCCI welcomes cricket’s inclusion in 2028 Los Angeles Olympics</strong> - Shah was the chief of ICC’s working group that dealt with the International Olympic Committee before cricket was formally inducted into the Los Angeles Olympics 2028 on Monday</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>Rohit Sharma on par with AB de Villiers and Viv Richards in World Cup performances | Data</strong> - Rohit’s ODI record is superlative, but his World Cup performances have been even more other-worldly — he has scored 1,195 runs in 20 matches with an average of 66.4 and strike rate of 101.96</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>Cricket, squash among 5 sports included in 2028 Los Angeles Olympic programme</strong> - The final choice of which sports are on the 2028 programme was voted today at the IOC session in Mumbai</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>Eng vs Afg | This win will put a smile on faces of my people back in Afghanistan: Rashid</strong> - Rashid said that many Afghans were struggling after the recent earthquakes</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Morning Digest | One million Gazans displaced in a week, says UN; SP to contest M.P. election in alliance with Congress, and more</strong> - Here is a select list of stories to start the day</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>KCR asks people to make an informed decision before casting vote</strong> - He cautions voters that parties try to confuse, mislead them in different ways</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>It will be a hat-trick for BRS, says Telangana Minister Srinivas Goud</strong> - The BRS government has already introduced several programs and schemes for the welfare of people and would further do its best to secure top position among the developed States in the country, he says</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I-T Department seizes cash and valuables worth ₹102 crore</strong> - Searches were conducted against against some government contractors, real estate developers, and their associates across four States</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>Bhadrachalam former MLA Kunja Satyavathi dies at 52</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>Israel matters more than Manipur for PM Modi: Rahul in poll-bound Mizoram</strong> - The Congress leader took part in a padayatra in Aizawl on Monday as part of the party’s Bharat Jodo Yatra programme</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>Polish election: Right-wing ruling party to lose majority - exit poll</strong> - Donald Tusk’s centrist opposition has a better chance of forming a coalition if the poll is right.</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>France raises security level after school knife attack</strong> - France is put on its highest counter-terrorism alert, following the death of a teacher stabbed at a high school.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Germany migrants: Seven dead after vehicle crashes in Bavaria</strong> - Authorities said the driver of a “suspected smuggling vehicle” attempted to evade police before losing control.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Putin denies Russia behind Finland gas pipeline damage</strong> - Finnish officials say they cannot rule out a state actor being responsible for the rupture.</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>French police break up pro-Palestinian demo after ban</strong> - Tear gas is used after pro-Palestinian rallies are banned as a possible threat to public order.</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>Air purifiers aren’t enough to clean your home from wildfire smoke</strong> - There are ways to clean it up, however. - <a href="https://arstechnica.com/?p=1976176">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plant-based cheese may be getting more appetizing</strong> - Can we skip the dairy and still get a cheese that doesn’t taste like plants? - <a href="https://arstechnica.com/?p=1976155">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>This exoplanet might literally be the most metal planet out there</strong> - It’s likely that something stripped the outer layers off a once-rocky exoplanet. - <a href="https://arstechnica.com/?p=1976025">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CEO Bobby Kotick will leave Activision Blizzard on January 1, 2024</strong> - Schreier: Kotick will depart after 33 years, employees are “very excited.” - <a href="https://arstechnica.com/?p=1976154">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hydro dams are struggling to handle the world’s intensifying weather</strong> - Climate change is robbing some hydro dams of water while oversupplying others. - <a href="https://arstechnica.com/?p=1976129">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>God Has a Sense of Humor</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
God told men they would find faithful and obedient wives in all the corners of the Earth. Then men discovered that the Earth is round, and God laughed and laughed.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MergingConcepts"> /u/MergingConcepts </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/17923zc/god_has_a_sense_of_humor/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/17923zc/god_has_a_sense_of_humor/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Omar Epps moved next to Chris Hemsworth.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Initially they didn’t talk much, but after a little time they started having family get-togethers. They became good friends for a while, even going so far as to have little decoration challenges every holiday.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Omar always pulled out all the stops come Christmas, and he seemed to enjoy it so much that, often, Chris would concede and just admire his neighbor’s over-the-top yuletide spirit.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
But one year, Chris felt like upping the ante and properly competing. So instead of doing a large spread of house decor, Chris commissioned the construction of an enormous lawn ornament.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The next evening, Omar looked across the lawn and gasped–there, standing taller than a house, was a towering statue of Thor, colorfully lit and dressed like an elf.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He laughed it off as ridiculous and tacky, but to his surprise it was drawing much more attention, from strangers and neighbors alike, than his own festive manor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
More than a little disgruntled that he was no longer the talk of the HOA, he made his irritation known at dinner. Curious, his oldest daughter went over to see this titan in person.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Later that night, Chris awoke to his children’s shouts. He ran to the window and saw his beautiful Elf Thor flaming. The fire department came, but too late, as the damage was done and the magnificent creature destroyed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Chris checked the cameras and saw what looked like a teenager approaching the statue, but before he could make out who it was, the feed cut. All footage past this point was corrupted.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Distraught, he reached out to Omar and admitted how important it was to him to win the decor war just one year, and he just wished he could find out who this kid was. Omar consoled him as best he could, but now worried he was going to have to confront his daughter….
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He knocked on her door and asked her to be honest with him. She scoffed, and pulled up the house security on her laptop. Sure enough, there she was, walking back to the house only 10 minutes after leaving to see the statue. According to the CFI, the fire started over an hour later.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
We may never learn the truth, but we know one thing for certain: <span class="md-spoiler-text">Epps’ teen didn’t kill Hems’ elf.</span>
</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/KairuSmairukon"> /u/KairuSmairukon </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/178olhp/omar_epps_moved_next_to_chris_hemsworth/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/178olhp/omar_epps_moved_next_to_chris_hemsworth/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The naked runner</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A couple of lovers were in the midst of action in bed when suddenly they heard a noise at the door. The woman panicked and said to her lover, ‘My husband, my husband is here! Jump out of the window!’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Without thinking twice, the lover jumped naked out of the window and landed in some bushes. He quickly got up and joined a marathon that was happening on the street. He ran alongside the other runners, trying to blend in despite his total nudity.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In the middle of the race, another runner noticed and asked, ‘Hey, buddy, what’s your participant number?’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The lover, with a serious expression, replied, ‘Well, I don’t actually have a number today…’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The other runner, surprised, continued, ‘Why are you running barefoot then?’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The lover responded, ‘Well, I need to air out my feet; the doctor recommended staying cool because of my hypertension. If I don’t, I start feeling unwell.’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The runner was still amazed, ‘But why aren’t you wearing a shirt?’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The lover explained, ‘The breeze on my body is good for circulation. It helps with my hypertension. But don’t worry, we’ll reach the finish line together!’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The other runner finally said, ‘But what about the lack of pants or underwear?’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The lover, without losing his composure, replied, ‘Oh, that’s because I need to keep this area well-ventilated. If not, my hypertension could cause stomach problems and other inconveniences…’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The incredulous runner said, ’<span class="md-spoiler-text">I see, so the condom is in case it rains, right?’"</span>
</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/BudapestDoha"> /u/BudapestDoha </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/178ghx5/the_naked_runner/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/178ghx5/the_naked_runner/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>genie and the wish</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A woman walking along the beach when she stumbled upon a Genie’s lamp. She picked it up and rubbed it, and lo-and-behold a Genie appeared. The amazed woman soon came back to her senses and asked if she got three wishes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Genie said, “Nope. . . due to inflation, constant downsizing, fierce global competition, and low wages in third-world countries, I can only grant you one wish. So, . . . what shall it be?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The woman didn’t hesitate. She said, “I want peace in the Middle East. See this map? I want these countries to stop fighting with each other.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Genie looked at the map and exclaimed, “Good Lady! These countries have been at war for thousands of years. I’m out of shape after being in a bottle for centuries. I’m good but not THAT good! I don’t think it can be done. Make another wish.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The woman thought for a few minutes and said, “Well, I’ve never been able to find the right man. You know, one that’s considerate and fun, likes to cook and helps with the house cleaning, is good in bed and gets along with my family, doesn’t watch sports all the time, and is faithful. That’s what I wish for — a good mate.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Genie let out a long sigh, shook his head and said, “Let me see that map again!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/bohogirl1"> /u/bohogirl1 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/178ly2s/genie_and_the_wish/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/178ly2s/genie_and_the_wish/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man enters a pet shop</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He spots a parrot with a higher than normal price tag.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Why is this bird so expensive?” he asked the shop owner
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Oh well, it’s a very special parrot you see” the owner replied “if you lift its right leg, it will sing a you hymn. And if you lift its left leg, it will recite a psalm”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Wow!” the man was clearing impressed “what would it say if i lift both its legs?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I will fall down, you moron” the parrot said from behind.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Des-You-color"> /u/Des-You-color </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/178hms0/a_man_enters_a_pet_shop/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/178hms0/a_man_enters_a_pet_shop/">[comments]</a></span></p></li>
</ul>
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