Revisit the Inhibitory Effects of Glucocorticoids on Immunocytes -
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+Glucocorticoids (GCs) are efficacious agents for reducing inflammation and suppressing immune responses, exerting various effects on immune cells through the intracellular glucocorticoid receptor (GR), and impacting both innate and adaptive immunity. In the context of COVID-19, glucocorticoids are often used to treat severe cases of patients by reducing inflammation, suppressing immune responses, and ameliorating the severity of COVID-19. However, the precise inhibitory effects on immune cells have yet to be comprehensively delineated. In this study, we extensively examined the inhibitory effects of treating Balb/c mice with dexamethasone (DEX) on lymphoid and myeloid cells. We observed that high doses of DEX treatment resulted in a reduction in the number of immunocytes and an attenuation of their activity. Particularly noteworthy, macrophages, DC cells, and monocytes were diminished by approximately 90% following high doses of DEX, while B cells experienced a reduction of about 70% and CD3 T cells were less affected. Furthermore, our findings demonstrated that DEX induces the inhibition of immune cells by engaging in high-affinity binding to GR. Consequently, we conclude that DEX treatments affect a broad range of immune cells, encompassing both lymphoid and myeloid cells, through depletion or the down-regulation of immune function, potentially acting via the GR signaling pathway. These findings may enhance the clinical applicability of DEX in achieving transient immune deficiency.
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Stably-Inverted Apical-Out Human Upper Airway Organoids for SARS-CoV-2 Infection and Therapeutic Testing -
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+Apical-out organoids produced through eversion triggered by extra-organoid extracellular matrix (ECM) removal or degradation are generally small, structurally variable, and limited for viral infection and therapeutics testing. This work describes ECM-encapsulating, stably-inverted apical-out human upper airway organoids (AORBs) that are large (~500 um diameter), consistently spherical, recapitulate in vivo-like cellular heterogeneity, and maintain their inverted morphology for over 60 days. Treatment of AORBs with IL-13 skews differentiation towards goblet cells and the apical-out geometry allows extra-organoid mucus collection. AORB maturation for 14 days induces strong co-expression of ACE2 and TMPRSS2 to allow high-yield infection with five SARS-CoV-2 variants. Dose-response analysis of three well-studied SARS-CoV-2 antiviral compounds [remdesivir, bemnifosbuvir (AT-511), and nirmatrelvir] shows AORB antiviral assays to be comparable to gold-standard air-liquid interface cultures, but with higher throughput (~10-fold) and fewer cells (~100-fold). While this work focuses on SARS-CoV-2 applications, the consistent AORB shape and size, and one-organoid-per-well modularity broadly impacts in vitro human cell model standardization efforts in line with economic imperatives and recently updated FDA regulation on therapeutic testing.
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A speed limit on serial strain replacement from original antigenic sin -
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+Many pathogens evolve to escape immunity, yet it remains difficult to predict whether immune pressure will lead to diversification, serial replacement of one variant by another, or more complex patterns. Pathogen strain dynamics are mediated by cross-protective immunity, whereby exposure to one strain partially protects against infection by antigenically diverged strains. There is growing evidence that this protection is influenced by early exposures, a phenomenon referred to as original antigenic sin (OAS) or imprinting. In this paper, we derive new constraints on the emergence of the pattern of successive strain replacements demonstrated by influenza, SARS-CoV-2, seasonal coronaviruses, and other pathogens. We find that OAS implies that the limited diversity characteristic of successive strain replacement can only be maintained if R0 is less than a threshold set by the characteristic antigenic distances for cross-protection and for the creation of new immune memory. This bound implies a "speed limit" on the evolution of new strains and a minimum variance of the distribution of infecting strains in antigenic space at any time. To carry out this analysis, we develop a theoretical model of pathogen evolution in antigenic space that implements OAS by decoupling the antigenic distances required for protection from infection and strain-specific memory creation. Our results demonstrate that OAS can play an integral role in the emergence of strain structure from host immune dynamics, preventing highly transmissible pathogens from maintaining serial strain replacement without diversification.
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Lethal Infection of Human ACE2-Transgenic Mice Caused by SARS-CoV-2-related Pangolin Coronavirus GX_P2V(short_3UTR) -
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+SARS-CoV-2-related pangolin coronavirus GX_P2V(short_3UTR) can cause 100% mortality in human ACE2-transgenic mice, potentially attributable to late-stage brain infection. This underscores a spillover risk of GX_P2V into humans and provides a unique model for understanding the pathogenic mechanisms of SARS-CoV-2-related viruses.
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A Murine Model of Post-acute Neurological Sequelae Following SARS-CoV-2 Variant Infection -
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+Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. Surviving mice showed no detectable viral RNA in the brain and minimal neuroinflammation post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and reduced levels of genes associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent T helper 1 prone cellular immune responses and high neutralizing antibodies against Delta and Omicron variants in the periphery for months post-acute infection. Overall, infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long COVID patients and may be useful for future assessment of the efficacy of vaccines and therapeutics against SARS-CoV-2 variants.
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Prototype mRNA vaccines imprint broadly neutralizing human serum antibodies after Omicron variant-matched boosting -
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+Immune imprinting is a phenomenon in which an individual's prior antigenic experiences influence responses to subsequent infection or vaccination. Here, using antibody depletion and multiplexed spike-binding assays, we characterized the type-specificity and cross-reactivity of serum antibody responses after mRNA vaccination in mice and human clinical trial participants. In mice, a single priming dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike minimally imprinted serum responses elicited by Omicron boosters, enabling a robust generation of type-specific antibodies. However, substantial imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron mRNA vaccine. In humans who received two BA.5 or XBB.1.5 Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with circulating Omicron variants as well as more distantly related sarbecoviruses. Because the serum neutralizing response against Omicron strains and other sarbecoviruses was completely abrogated after pre-clearing with the Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes shaped and shared by the antecedent mRNA-1273 primary series. Our depletion analysis also identified cross-reactive neutralizing antibodies that recognize distinct epitopes in the receptor binding domain (RBD) and S2 proteins with differential inhibitory effects on members of the sarbecovirus subgenus. Thus, although the serum antibody response to Omicron-based boosters in humans is dominantly imprinted by prior immunizations with prototype mRNA-1273 vaccines, this outcome can be beneficial as it drives expansion of multiple classes of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and extend activity to distantly related sarbecoviruses.
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Change in Anti-COVID-19 Behavior and Prejudice against Minorities during the COVID-19 Pandemic: Longitudinal Evidence from Five European Countries -
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+In the COVID-19 pandemic, it is vital to identify factors increasing behaviors that limit the transmission of COVID-19 (i.e., anti-COVID-19 behavior) and factors protecting against the negative consequences of the pandemic on societies (i.e., prejudice). A simultaneous investigation of a change in anti-COVID behavior and prejudice during the pandemic is essential because some factors (e.g., fear of COVID-19) could increase both outcomes, whilst other factors (e.g., norms in anti-COVID behavior or intergroup contact in prejudice) could bring desirable changes in one outcome without negatively affecting the other. In a three-wave longitudinal study (NT1 = 4275) in five European countries from April to October 2020, we employed a latent change score model to distinguish between intra- and inter-individual changes in anti-COVID-19 behavior and prejudice. On the intra-individual level, anti-COVID-19 behavior was increased by anti-COVID-19 norms; and prejudice against migrants from the Middle East was influenced by positive and negative direct and mass-media intergroup contact.
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Mutation of highly conserved residues in loop 2 of the coronavirus macrodomain demonstrates that enhanced ADP-ribose binding is detrimental to infection -
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+All coronaviruses (CoVs) encode for a conserved macrodomain (Mac1) located in nonstructural protein 3 (nsp3). Mac1 is an ADP-ribosylhydrolase that binds and hydrolyzes mono-ADP-ribose from target proteins. Previous work has shown that Mac1 is important for virus replication and pathogenesis. Within Mac1, there are several regions that are highly conserved across CoVs, including the GIF (glycine-isoleucine-phenylalanine) motif. To determine how the biochemical activities of these residues impact CoV replication, the isoleucine and the phenylalanine residues were mutated to alanine (I-A/F-A) in both recombinant Mac1 proteins and recombinant CoVs, including murine hepatitis virus (MHV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The F-A mutant proteins had ADP-ribose binding and/or hydrolysis defects that led to attenuated replication and pathogenesis in cell culture and mice. In contrast, the I-A mutations had normal enzyme activity and enhanced ADP-ribose binding. Despite increased ADP-ribose binding, I-A mutant MERS-CoV and SARS-CoV-2 were highly attenuated in both cell culture and mice, indicating that this isoleucine residue acts as a gate that controls ADP-ribose binding for efficient virus replication. These results highlight the function of this highly conserved residue and provide unique insight into how macrodomains control ADP-ribose binding and hydrolysis to promote viral replication and pathogenesis.
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BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population. -
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+Background: During the current COVID 19 pandemic, the rate of morbidity and mortality was considerably lower in BCG vaccinated countries like Pakistan. BCG has been shown to provide cross protection to both disseminated TB as well as non related viral infections in BCG vaccinated children which is consistent with COVID 19 morbidity in the younger age group. Recently, this cross protection was attributed to trained immunity (TI) associated with BCG recall responses in the innate arm of the immune system. Little is known about the longevity of BCG Trained Immunity (TI) beyond early childhood. Objective: To assess the BCG induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross protection against COVID 19 and other viral infections. Study Design: In this cross sectional study, healthy young adults and adolescents (n=20) were recruited from 16-40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition. Methods: BCG induced cytokine responses were assessed using prototypic markers for cells of the TI network macrophages [M1 (TNF alpha, IFN gamma), M2 (IL10)], NK (IL2), Gamma delta (gamma delta]) T (IL17, IL4)} and SARS CoV2 IgG antibodies against RBD using short term (12 hours) cultures assay. Results: Significant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNF alpha (9148 pg/ml) followed by IL10 (488 pg/ml) and IFN gamma(355 pg/ml). The ratio of unstimulated vs BCG stimulated cytokines was 132 fold higher for TNF alpha, 40 fold for IL10, and 27 fold for IFN gamma. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG. Conclusion: The presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro and anti inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID 19 pandemic in the younger age groups resulting in lower morbidity and mortality.
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VLP-Based Model for Study of Airborne Viral Pathogens -
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+The recent COVID-19 pandemic has underscored the danger of airborne viral pathogens. The lack of model systems to study airborne pathogens limits the understanding of airborne pathogen distribution, as well as potential surveillance and mitigation strategies. In this work, we develop a novel model system to study airborne pathogens using virus like particles (VLP). Specifically, we demonstrate the ability to aerosolize VLP and detect and quantify aerosolized VLP RNA by Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) in real-time fluorescent and colorimetric assays. Importantly, the VLP model presents many advantages for the study of airborne viral pathogens: (i) similarity in size and surface components; (ii) ease of generation and noninfectious nature enabling study of BSL3 and BSL4 viruses; (iii) facile characterization of aerosolization parameters; (iv) ability to adapt the system to other viral envelope proteins including those of newly discovered pathogens and mutant variants; (v) the ability to introduce viral sequences to develop nucleic acid amplification assays.
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Antigen non-specific CD8+ T cells accelerate cognitive decline in aged mice following respiratory coronavirus infection -
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+Primarily a respiratory infection, numerous patients infected with SARS-CoV-2 present with neurologic symptoms, some continuing long after viral clearance as a persistent symptomatic phase termed long COVID. Advanced age increases the risk of severe disease, as well as incidence of long COVID. We hypothesized that perturbations in the aged immune response predispose elderly individuals to severe coronavirus infection and post-infectious sequelae. Using a murine model of respiratory coronavirus, mouse hepatitis virus strain A59 (MHV-A59), we found that aging increased clinical illness and lethality to MHV infection, with aged animals harboring increased virus in the brain during acute infection. This was coupled with an unexpected increase in activated CD8+ T cells within the brains of aged animals but reduced antigen specificity of those CD8+ T cells. Aged animals demonstrated spatial learning impairment following MHV infection, which correlated with increased neuronal cell death and reduced neuronal regeneration in aged hippocampus. Using primary cell culture, we demonstrated that activated CD8+ T cells induce neuronal death, independent of antigen-specificity. Specifically, higher levels of CD8+ T cell-derived IFN-{gamma} correlated with neuronal death. These results support the evidence that CD8+ T cells in the brain directly contribute to cognitive dysfunction following coronavirus infection in aged individuals.
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Four Years of COVID-19: Saudi Arabia, Egypt and Pakistan Have the Highest Research Growth Rates From 2020-2023 -
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+We tried to assess the global research scholarly output after COVID-19 (from 2020 to 2023). Based on Scopus record, the world has produced 15, 041, 579 publications with 86, 165, 933 citations. We analyzed those countries, which have published at least 150, 000 research papers. For each country, we retrieved total number of publications, % growth rate, total citations, citations per paper, Field Weighted Citation Impact (FWCI), and % international collaboration. Twenty-seven (n=27) countries were found to be highly productive, with China leading the way in number of publications. Citation metrics are dominated by the USA, China, and European countries. Specifically, Switzerland, Netherlands, and Australia are notable for their high impact and influence. Saudi Arabia achieved the highest growth rate of 53.5%, and highest international collaboration (76.5%). Infact Saudi Arabia also attained high citations per article (8.8), and an FWCI of 1.63. While, Pakistan exhibited an 8.4 citations per article, FWCI of 1.54, growth rate of 34.9%, and collaborative percentage of 64.9%. Egypt also attained the 2nd highest growth rate (n=36.1). Based on four (n=4) distinct performance metrics, Pakistan and Saudi Arabia were in the top ten group.
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Complex changes in serum protein levels in COVID-19 convalescents -
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+The COVID-19 pandemic, triggered by severe acute respiratory syndrome coronavirus 2, has affected millions of people worldwide. Much research has been dedicated to our understanding of COVID-19 disease heterogeneity and severity, but less is known about recovery associated changes. To address this gap in knowledge, we quantified the proteome from serum samples from 29 COVID-19 convalescents and 29 age-, race-, and sex-matched healthy controls. Samples were acquired within the first months of the pandemic. Many proteins from pathways known to change during acute COVID-19 illness, such as from the complement cascade, coagulation system, inflammation and adaptive immune system, had returned to levels seen in healthy controls. In comparison, we identified 22 and 15 proteins with significantly elevated and lowered levels, respectively, amongst COVID-19 convalescents compared to healthy controls. Some of the changes were similar to those observed for the acute phase of the disease, i.e. elevated levels of proteins from hemolysis, the adaptive immune systems, and inflammation. In contrast, some alterations opposed those in the acute phase, e.g. elevated levels of CETP and APOA1 which function in lipid/cholesterol metabolism, and decreased levels of proteins from the complement cascade (e.g. C1R, C1S, and VWF), the coagulation system (e.g. THBS1 and VWF), and the regulation of the actin cytoskeleton (e.g. PFN1 and CFL1) amongst COVID-19 convalescents. We speculate that some of these shifts might originate from a transient decrease in platelet counts upon recovery from the disease. Finally, we observed race-specific changes, e.g. with respect to immunoglobulins and proteins related to cholesterol metabolism.
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Rapid and specific detection of single nanoparticles and viruses in microfluidic laminar flow via confocal fluorescence microscopy -
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+Mainstream virus detection relies on the specific amplification of nucleic acids via polymerase chain reaction, a process that is slow and requires extensive laboratory expertise and equipment. Other modalities, such as antigen-based tests, allow much faster virus detection but have reduced sensitivity. In this study, we report the development of a flow virometer for the specific and rapid detection of single nanoparticles based on confocal microscopy. The combination of laminar flow and multiple dyes enable the detection of correlated fluorescence signals, providing information on nanoparticle volumes and specific chemical composition properties, such as viral envelope proteins. We evaluated and validated the assay using fluorescent beads and viruses, including SARS-CoV-2. Additionally, we demonstrate how hydrodynamic focusing enhances the assay sensitivity for detecting clinically-relevant virus loads. Based on our results, we envision the use of this technology for clinically relevant bio-nanoparticles, supported by the implementation of the assay in a portable and user-friendly setup.
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DNA origami vaccine (DoriVac) nanoparticles improve both humoral and cellular immune responses to infectious diseases -
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+Current SARS-CoV-2 vaccines have demonstrated robust induction of neutralizing antibodies and CD4+ T cell activation, however CD8+ responses are variable, and the duration of immunity and protection against variants are limited. Here we repurposed our DNA origami vaccine platform, DoriVac, for targeting infectious viruses, namely SARS-CoV-2, HIV, and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific HR2 peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induced neutralizing antibodies, Th1 CD4+ T cells, and CD8+ T cells in naive mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validated that DoriVac, when conjugated with antigenic peptides or proteins, induced promising cellular immune responses in human cells. These results suggest that DoriVac holds potential as a versatile, modular vaccine platform, capable of inducing both humoral and cellular immunities. The programmability of this platform underscores its potential utility in addressing future pandemics.
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SARS-CoV-2 and Influenza A/B in Point-of-Care and Non-Laboratory Settings - Conditions: SARS-CoV-2 Infection; Influenza A; Influenza B Interventions: Diagnostic Test: Aptitude Medical Systems Metrix COVID/Flu Test Sponsors: Aptitude Medical Systems; Biomedical Advanced Research and Development Authority Recruiting
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Effect of Aerobic Exercises Versus Incentive Spirometer Device on Post-covid Pulmonary Fibrosis Patients - Conditions: Lung Fibrosis Interstitial; Post-COVID-19 Syndrome Interventions: Other: Aerobic Exercises; Device: Incentive Spirometer Device; Other: Traditional Chest Physiotherapy Sponsors: McCarious Nahad Aziz Abdelshaheed Stephens; Cairo University Active, not recruiting
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Can Doctors Reduce COVID-19 Misinformation and Increase Vaccine Uptake in Ghana? A Cluster-randomised Controlled Trial - Conditions: COVID-19 Interventions: Behavioral: Motivational Interviewing, AIMS; Behavioral: Facility engagement Sponsors: London School of Economics and Political Science; Innovations for Poverty Action; Ghana Health Services Not yet recruiting
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Long COVID Ultrasound Trial - Conditions: Long Covid Interventions: Device: Splenic Ultrasound Sponsors: SecondWave Systems Inc.; University of Minnesota; MCDC (United States Department of Defense) Not yet recruiting
Could Wearing Face Mask Have Affected Demodex Parasite - Conditions: Pandemic, COVID-19; Demodex Infestation Interventions: Diagnostic Test: standard superficial skin biopsy (SSSB) Sponsors: Nurhan Döner AktaĆ Completed
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TDCS Stimulation After Covid-19 Infection - Conditions: COVID-19 Interventions: Procedure: Transcranial Direct Stimulation Sponsors: Istanbul Medipol University Hospital; Alanya Alaaddin Keykubat University Recruiting
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Safety and Immunogenicity of a Booster Vaccination With an Adapted Vaccine - Conditions: SARS-CoV2 Infection Interventions: Biological: PHH-1V81; Biological: Comirnaty Omicron XBB1.5 Sponsors: Hipra Scientific, S.L.U Active, not recruiting
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From PubMed
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Evaluation of the humoral and mucosal immune response of a multiepitope vaccine against COVID-19 in pigs - INTRODUCTION: This study evaluated the immune response to a multiepitope recombinant chimeric protein (CHIVAX) containing B- and T-cell epitopes of the SARS-CoV-2 spikeâs receptor binding domain (RBD) in a translational porcine model for pre-clinical studies.
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In Silico Study on Natural Chemical Compounds from Citric Essential Oils as Potential Inhibitors of an Omicron (BA.1) SARS-CoV-2 Mutantsâ Spike Glycoprotein - CONCLUSION: The outcomes of this investigation hold significant potential for the utilization of a homology modeling approach for the prediction of RBDâs secondary structure based on its sequence when the 3D structure of a mutated protein is not available. This opens the opportunities for further advancing the drug discovery process, offering novel avenues for the development of multifunctional, non-toxic natural medications.
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A Comprehensive Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Nirmatrelvir/Ritonavir - Nirmatrelvir is a potent and selective inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease that is used as an oral antiviral coronavirus disease 2019 (COVID-19) treatment. To sustain unbound systemic trough concentrations above the antiviral in vitro 90% effective concentration value (EC(90)), nirmatrelvir is coadministered with 100 mg of ritonavir, a pharmacokinetic enhancer. Ritonavir inhibits nirmatrelvirâs cytochrome P450 (CYP) 3A4-mediated metabolismâŠ
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A stapled lipopeptide platform for preventing and treating highly pathogenic viruses of pandemic potential - The continued emergence of highly pathogenic viruses, which either thwart immune- and small molecule-based therapies or lack interventions entirely, mandates alternative approaches, particularly for prompt and facile pre- and post-exposure prophylaxis. Many highly pathogenic viruses, including coronaviruses, employ the six-helix bundle heptad repeat membrane fusion mechanism to achieve infection. Although heptad-repeat-2 decoys can inhibit viral entry by blocking six-helix bundle assembly, theâŠ
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ACE2 Receptor-Targeted Inhaled Nanoemulsions Inhibit SARS-CoV-2 and Attenuate Inflammatory Responses - Three kinds of coronaviruses are highly pathogenic to humans, and two of them mainly infect humans through Angiotensin-converting enzyme 2 ïŒACE2ïŒreceptors. Therefore, specifically blocking ACE2 binding at the interface with the receptor-binding domain is promising to achieve both preventive and therapeutic effects of coronaviruses. Alternatively, drug-targeted delivery based on ACE2 receptors can further improve the efficacy and safety of inhalation drugs. Here, these two approaches areâŠ
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TRIM28-mediated nucleocapsid protein SUMOylation enhances SARS-CoV-2 virulence - Viruses, as opportunistic intracellular parasites, hijack the cellular machinery of host cells to support their survival and propagation. Numerous viral proteins are subjected to host-mediated post-translational modifications. Here, we demonstrate that the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is SUMOylated on the lysine 65 residue, which efficiently mediates SARS2-NPâs ability in homo-oligomerization, RNA association, liquid-liquid phase separation (LLPS). Thereby the innate antiviralâŠ
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Plant extracts modulate cellular stress to inhibit replication of mouse Coronavirus MHV-A59 - The Covid-19 infection outbreak led to a global epidemic, and although several vaccines have been developed, the appearance of mutations has allowed the virus to evade the immune response. Added to this is the existing risk of the appearance of new emerging viruses. Therefore, it is necessary to explore novel antiviral therapies. Here, we investigate the potential in vitro of plant extracts to modulate cellular stress and inhibit murine hepatitis virus (MHV)-A59 replication. L929 cells wereâŠ
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A randomized double-blind placebo-controlled trial of an inhibitor of plasminogen activator inhibitor-1 (TM5614) in mild to moderate COVID-19 - An inhibitor of plasminogen activator inhibitor (PAI)-1, TM5614, inhibited thrombosis, inflammation, and fibrosis in several experimental mouse models. To evaluate the efficacy and safety of TM5614 in human COVID-19 pneumonia, phase IIa and IIb trials were conducted. In an open-label, single-arm trial, 26 Japanese COVID-19 patients with mild to moderate pneumonia were treated with 120-180 mg of TM5614 daily, and all were discharged without any notable side effects. Then, a randomized,âŠ
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Antiviral effect of palmatine against infectious bronchitis virus through regulation of NF-ÎșB/IRF7/JAK-STAT signalling pathway and apoptosis - 1. Infectious bronchitis virus (IBV), a gamma-coronavirus, can infect chickens of all ages and leads to an acute contact respiratory infection. This study evaluated the anti-viral activity of palmatine, a natural non-flavonoid alkaloid, against IBV in chicken embryo kidney (CEK) cells.2. The half toxic concentration (CC(50)) of palmatine was 672.92 ÎŒM, the half inhibitory concentration (IC(50)) of palmatine against IBV was 7.76 ÎŒM and the selection index (SI) was 86.74.3. Mode of action assayâŠ
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One-step silver coating of polypropylene surgical mask with antibacterial and antiviral properties - Face masks can filter droplets containing viruses and bacteria minimizing the transmission and spread of respiratory pathogens but are also an indirect source of microbes transmission. A novel antibacterial and antiviral Ag-coated polypropylene surgical mask obtained through the in situ and one-step deposition of metallic silver nanoparticles, synthesized by silver mirror reaction combined with sonication or agitation methods, is proposed in this study. SEM analysis shows Ag nanoparticles fusedâŠ
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A novel inhibitor of SARS-CoV infection: Lactulose octasulfate interferes with ACE2-Spike protein binding - The ongoing challenge of managing coronaviruses, particularly SARS-CoV-2, necessitates the development of effective antiviral agents. This study introduces Lactulose octasulfate (LOS), a sulfated disaccharide, demonstrating significant antiviral activity against key coronaviruses including SARS-CoV-2, SARS-CoV, and MERS-CoV. We hypothesize LOS operates extracellularly, targeting the ACE2-S-protein axis, due to its low cellular permeability. Our investigation combines biolayer interferometryâŠ
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IFN-Îł-mediated control of SARS-CoV-2 infection through nitric oxide - INTRODUCTION: The COVID-19 pandemic has highlighted the need to identify mechanisms of antiviral host defense against SARS-CoV-2. One such mediator is interferon-g (IFN-Îł), which, when administered to infected patients, is reported to result in viral clearance and resolution of pulmonary symptoms. IFN-Îł treatment of a human lung epithelial cell line triggered an antiviral activity against SARS-CoV-2, yet the mechanism for this antiviral response was not identified.
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HDAC1-3 inhibition increases SARS-CoV-2 replication and productive infection in lung mesothelial and epithelial cells - CONCLUSION: This study highlights a previously unrecognized effect of HDAC1-3 inhibition in increasing SARS-CoV-2 cell entry, replication and productive infection correlating with increased expression of ACE2 and TMPRSS2. These data, while adding basic insight into COVID-19 pathogenesis, warn for the use of HDAC inhibitors in SARS-CoV-2 patients.
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Should Virtual Objective Structured Clinical Examination (OSCE) Teaching Replace or Complement Face-to-Face Teaching in the Post-COVID-19 Educational Environment: An Evaluation of an Innovative National COVID-19 Teaching Programme - Background The COVID-19 pandemic brought about drastic changes to medical education and examinations, with a shift to online lectures and webinars. Additionally, social restrictions in the United Kingdom (UK) inhibited studentsâ ability to practice for objective structured clinical examination (OSCE) with their peers. Methods The Virtual OSCE buddy scheme (VOBS) provided a means to practice OSCE skills virtually by linking groups of 2-6 final-year medical students with a junior doctor who hadâŠ
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Valorizing pomegranate wastes by producing functional silver nanoparticles with antioxidant, anticancer, antiviral, and antimicrobial activities and its potential in food preservation - The food sector generates massive amounts of waste, which are rich in active compounds, especially polyphenols; therefore, valorizing these wastes is a global trend. In this study, we produce silver nanoparticles from pomegranate wastes, characterized by enhanced antioxidant, anticancer, antiviral, and antimicrobial properties and investigated their potential to maintain the fruit quality for sixty days in market. The pomegranate waste-mediated silver nanoparticles (PPAgNPs) were spherical shapeâŠ
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From Patent Search
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The California Town Owned by a New York Investment Firm - Scotia was created, a century and a half ago, so that lumberjacks could live near the trees they cut down. Its current owners have been trying for more than a decade to bring new residents to town. - link
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Joe Biden Makes Saving Democracy the Center of His Campaign - The President and his team are framing the 2024 race as a binary choice between him and an authoritarian Donald Trump. - link
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Gaza Is Starving - The chief economist of the World Food Program explains how the scarcity of food may tip the territory into famine. - link
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Whatâs Behind Israelâs Crackdown in the West Bank? - The Palestinian political analyst Ibrahim Dalalsha on the politics behind the violence and settlement expansion since October 7th. - link
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The Ghost of January 6th Haunts 2024 - The impending Biden-vs.-Trump rematch already has one dominant theme. - link
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From Vox
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The Golden Globes are (just barely) making a comeback. Hereâs what to expect. -
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+A Golden Globe statue at the Golden Globe Awards Preview held at the Beverly Hilton Hotel on December 13, 2023, in Beverly Hills, California. | River Callaway/Penske Media via Getty Images
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+This yearâs Golden Globes boasts new faces, new voters, new categories, and a new network. Is it enough?
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+When the 81st Golden Globes arrive on Sunday, January 7, it may look a lot like the award show you remember: informal, mildly erratic, with caustic self-roasts and some nominees that cause a few spit takes.
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+But beneath its tipsy exterior, a lot has changed for the show. It has a new owner, a new network (CBS), a new host in comedian Jo Koy, new voting requirements, and crucially, more than triple the number of voting members.
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+Most importantly, after barely surviving a watershed scandal that nearly brought an end to our favorite quirky awards night, the Golden Globes have a lot to prove about what kind of awards show they want to become in the future.
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+What does that mean for the show? Mainly that, despite a return to relative normalcy â Barbenheimer and Succession lead this yearâs nominations â no one is entirely sure what the new Golden Globes will be.
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+A year of firsts
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+This yearâs Golden Globes are poised to be a fresh start on multiple fronts. Among the yearâs nods are nearly 30 first-time nominees, including industry veterans like Chris Rock and Trevor Noah and newcomers like Finnish actress Alma Pöysti, nominated for Best Actress for her turn in the rom-dramedy Fallen Leaves.
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+The traditional â and sometimes confusing â split between genres has also gotten a shake-up, with the addition of two new categories for TV standup comedy performance and cinematic and box office achievement. (Though you might think the latter category is a strictly Billboard-style award based on metrics, itâs not entirely objective; the profitable but much-maligned conservative rallying point Sound of Freedom wasnât on the list.)
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+Koy will likely also bring a different tone to the role of host. The Globes historically indulge in self-mockery, with hosts often taking aim at their guests and the entire Hollywood apparatus. In its past life, the production rarely feared courting controversy and daring to offend. This time, however, producers have vowed to keep things relentlessly positive and to keep the party vibes going above all else. Koy has declared the evening âa celebration,â not just for the Globes but for an industry thatâs battled its way back, first from a global pandemic and then the most intense industry strikes in recent memory.
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+Whether they can pull the party off, though, especially given the pressure the event is under, will be easier said than done.
+
+
+What happened to the old Golden Globes again?
+
+
+Among the pantheon of Hollywood awards shows, the Golden Globes have always felt a bit like the boozy cousin living in the basement of the Oscars. Careening from controversy to controversy, the Globes are usually saved, certainly not by their taste, but by their quirks, attendeesâ irreverence, and the high likelihood of at least one drunken acceptance speech thanks to the ceremonyâs open bar.
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+In recent years, however, not even soused Emma Thompson has been able to save them. The 2021 Globes seemed to sink under the weight of their increasing irrelevance. Just how irrelevant became clear in a major months-long scandal over longstanding corruption and entrenched racism in the Globesâ organizing body, the Hollywood Foreign Press Association (HFPA).
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+Last year, the HFPA finally came to an end â and with it, presumably, the decades of scandal that tainted the awards. In its place, the Globesâ longstanding producer, Dick Clark Productions, took over the show with the goal of turning things around for the beleaguered awards.
+
+
+The HFPA was historically a small, select, and non-public body of around 90 people, all of whom were supposed to be entertainment journalists. For decades, the industry had chafed over the sentiment that this tiny, secretive club used its unearned privilege â unearned because who the heck even were these people? â to garner access to Hollywoodâs elite. In exchange, the HFPA grew notorious for nominating, not based on artistic merit, but based on whichever marketing campaign wooed voters the hardest.
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+And thanks to the perception that the Globes can influence the Oscars, woo they did. Since the Academy has over 10,000 voting members, the logic held, it was easier to directly influence 90 people to give your movie attention for the Globes and then hope that momentum carried through to Oscar night. At various points in the past, the Oscars have attempted to circumvent this trap by cutting off voting before the Globes ceremony occurs. Meanwhile, the Globes have sometimes changed their schedule to be closer to the Oscars, presumably to keep the tag-team impression (and thus their relevance) alive.
+
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+All that changed in 2021 when, under increasing scrutiny from the industry, an investigation by the Los Angeles Times found that, in addition to its long and well-documented history of alleged corruption, the organization was allegedly rife with sexism and systemic racism: None of its 87 members was Black. Not only that, but the HFPA hadnât had a Black member in at least 20 years.
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+After so many years of resentment against the HFPA, the industry backlash after this revelation was so fierce that the HFPA collapsed. First, the awards show fell apart, with celebrities refusing to attend or present awards and longtime network NBC refusing to air the ceremony. After the organization promised to expand and change, for a brief moment things looked up. The Globes were acquired by Eldridge Industries, a business management firm co-founded and run by billionaire sports investor Todd Boehly, with the initial goal of creating a new private firm to control the HFPA and run the Globes. But even though the 2023 Globes were a relative success, viewership was abysmal at an average of just 6.3 million, NBC declined to renew its longstanding partnership with the awards, and despite its promise to change, the HFPA continued to flounder.
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+The final death knell for the HFPA came in June 2023. Instead of creating an independent company to oversee the awards, Eldridge sold the Globes to a subsidiary, the Globesâ longtime production partner, Dick Clark Productions (DCP). The sale went through with the provision that DCP would completely dissolve the 80-year-old press association and turn the Globes into a for-profit enterprise.
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+Will all that change impact the awards? Yes and no!
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+Dick Clark Productions is perhaps best known for producing the annual New Yearâs Eve live celebration in Times Square, but itâs also been producing the Golden Globes since the â80s. Named after the late popular event host, DCP has a long resume of awards shows under its belt, as well as reality shows like So You Think You Can Dance.
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+Because of DCPâs longstanding production of the Globes, its acquisition of the show shouldnât make much of a difference in the overall aesthetic and format of this yearâs ceremony. The voting membership, however, has undergone a much-needed overhaul. Eligibility requirements have expanded and membership has tripled to 300 members. The basic premise of membership â you have to be a journalist writing for a media outlet outside of the US â remains the same.
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+Already, the nominations feel less out of step with the culture than they have in years past â less inconsistent with fewer head-turning and baffling nominees. While there are some snubs in the lineup, most of the choices make sense. The frontrunners, including Barbie, Oppenheimer, and Succession, are all mainstream critical favorites, and so far, predictions for who will take home the acting prizes seem to align squarely with the rest of the critical establishment.
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+Still, if thereâs one thing the Globes have taught us, itâs that thereâs always room for the unexpected. After all, itâs not quite clear that the strange, co-dependent relationship that once existed between the voters and the industry has entirely ended. Add to that the fresh possibilities afforded by this yearâs blank slate and the odds are good that at least one or two shocking upsets could well be on the menu.
+
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+But then, those record-scratch moments are why we love the Globes: Even when theyâre serving us a quizzical trainwreck, we just canât look away.
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+
Could this obscure tax idea reshape American housing? -
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+With over 50,000 vacant or abandoned homes in the City of Detroit, some houseless individuals find these buildings as a refuge in the cold winter months in Detroit. | Adam J. Dewey/Anadolu Agency via Getty Images
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+Detroit may put the land-value tax to the test
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+Over the last six months, an obscure housing policy idea has emerged as one of the most talked about proposals to revive Detroit, Michigan â an idea that could potentially spur development on the cityâs vast amount of vacant property as well as lower the cityâs punishingly high taxes on homeowners. Economists are buzzingwith interest, and the cityâs mayor, Mike Duggan, is all in.
+
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+Meet the land-value tax, a form of taxation rarely tried in the United States despite being popularized globally by an American political economist in the 19th century. Versions of the tax have been implemented in countries all over the world, including Mexico, Denmark, Singapore, Russia, and Taiwan.
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+For nearly all of US history, American property taxes have taken a pretty standard form. Individuals pay a tax based on the assessed value of their land, buildings, and any other improvements to their property combined. If you renovate your house and make it nicer, for example, your overall property tax could go up. The proposed land-value tax in Detroit, by contrast, would effectively tax land at a higher rate than any buildings or amenities on the property.
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+Mayor Duggan, who is spearheading the effort, hopes this land-value tax idea will incentivize development on blighted property as well as offer some tax relief to homeowners, who bear some of the highest rates in the country. The Duggan administration estimates that under his proposal 97 percent of Detroit homeowners will see an average decrease of 17 percent in property tax. The proposal is not about lowering taxes generally, but about increasing taxes on those who own vacant land (a big problem in the city) and decreasing future taxes on people who develop their land.
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+âI think it is an important idea for any place where people are holding onto valuable land that could be used for more productive purposes,â James Hohman, the director of fiscal policy at the Mackinac Center for Public Policy in Michigan, told Vox.
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+Duggan had hoped to put the idea before Detroit voters in February, during Michiganâs presidential primary, but proponents say their best hope at this point is the November ballot, after constituents have had more time to learn about what exactly theyâre voting on. First, the Michigan legislature must pass a law permitting Detroit to levy a âsplit-rateâ property tax at all. While a Detroit state representative introduced a bill to do just that in September, other Democratic lawmakers felt the whole thing was moving too fast. âI believe in proper process. I believe in democracy, and quite frankly, not enough of us are voting on primaries,â said Detroit City Council Member Gabriela Santiago-Romero, in October.
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+The Duggan administration still hopes to implement the land-value tax in 2025. âUltimately it will be the voters who decide for themselves,â John Roach, a mayoral spokesperson, told Vox.
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+If it passes, Detroit would become the largest American city to enact a land-value tax, a fact that could spur other communities in the US to follow suit. A land-value tax could help address the nationâs housing crisis by encouraging more housing development â like building new accessory dwelling units in backyards or brand-new multistory apartment buildings on vacant property. A land-value tax could also help other communities reverse their declining fortunes through more equitable growth. Itâs a lot of ifs, but policymakers, researchers, and housing activists say the chance to test the theory has never been closer in reach.
+
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+Why now?
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+Property taxes have long been a critical source of local public funding in the US, making up 48 percent of local government self-sourced revenue across the country in 2021. While many communities factor the value of land into their overall property tax rate, only a handful have had taxes on land specifically.
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+âProperty taxes are [some of] the oldest taxes levied by state and local governments and thereâs a lot of protections for property tax in state constitutions,â said Hohman. âBecause itâs been a reliable source of local revenue most governments havenât felt the need to experiment.â
+
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+But a number of factors in Detroit, in addition to the cityâs steep property tax rate on homeowners, have helped make the city a more ripe candidate for a land-value tax. Detroit has had a declining population for decades â peaking in the 1950s at 1.85 million â and has been grappling with large amounts of vacant land under private, public, and nonprofit ownership. (About 17 percent of Detroitâs 138 square miles is vacant.) Advocates say a land-value tax could also offer something of a fiscal buffer to Detroit, which continues to see the strength of its once more powerful auto and manufacturing industries decline.
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+The mayor threw his backing behind the concept this past May, and though the specific details have changed somewhat in recent months, the basic idea of taxing land at a higher rate than buildings remains intact. According to the Detroit Free Press, those who would be hit the hardest under the proposal are land speculators who own vacant lots, owners of empty and decrepit buildings, owners of scrap yards and auto salvage yards, and parking lot owners. Owners of urban farms, community gardens, and side lots would be protected. Some supporters of the land-value tax idea think the Duggan administrationâs proposal doesnât even go far enough.
+
+
+Economists are in support of the idea. In November, the University of Chicagoâs Kent A. Clark Center for Global Markets published a poll of 41 leading economists around the world, including four Nobel laureates, and 83 percent agreed or strongly agreed that the land-value tax would boost Detroitâs local growth over the next decade. Fifty-three percent agreed or strongly agreed that Detroitâs proposal would enhance incentives for owners to develop land.
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+One reason Detroit may be able to take a more radical-seeming step on land taxation is that Detroitâs status quo is not working very well for the city government. The study conducted by the Lincoln Institute of Land Policy found that in 1959, Detroitâs property tax raised over $1 billion, when adjusted for inflation. Sixty years later, that number was just $119 million. âIf this was 80% of our revenues, weâd be a lot more nervous,â Jay Rising, Detroitâs chief financial officer, told the Economist.
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+Despite raising less overall from property taxes compared to the past, the cityâs high rate has been brutal on low-income homeowners, who also often suffer from inaccurate assessments of their propertyâs value. One study published in 2019 found that 1 in 4 city properties went into tax foreclosure between 2011 and 2015 due to owners falling behind on their bills. The land-value tax would in theory offer relief to homeowners, and reduce the amount of foreclosures in the city.
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+Advocates point to the experience in Pittsburgh as the strongest evidence in the US that this is worth trying. Pennsylvania broadly has the longest history of implementing split-rate land-value taxes with more than a dozen Pennsylvania cities and school districts having adopted it. Pittsburgh, however, which had a split-rate tax from 1913 until 2001, is the most prominent example. One study from 1997 found the land-value tax played a significant role in boosting investment in downtown Pittsburgh, and helped the city avoid tax increases overall. Other research found that split-rate taxes in Pennsylvania encouraged denser housing development and influenced business formation decisions.
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+Pittsburgh abandoned its split-rate tax in 2001 following a countywide reassessment that dramatically increased land values, prompting a voter backlash. Pittsburgh had failed to keep up with accurate and routine tax assessments for decades, so then when they finally did one, homeowners were not pleased to see a massive spike in their property tax liabilities.
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+âThe policy was seen as unfair because it went up all of a sudden, and policymakers abandoned it and used the split-rate tax as a scapegoat for bad execution,â said Andrew Justus, a housing policy analyst at the Niskanen Center. âPittsburghâs experience shows the importance of administrative competence in implementing good ideas.â
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+Some Democratic lawmakers in Michigan say theyâre concerned about taking a policy gamble on a majority-Black city. Other Detroit constituents have expressed general distrust of the cityâs mayor and ideas heâs enthusiastic about, arguing there are other reforms needed to stave off eviction and foreclosure.
+
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+Roach, Dugganâs spokesperson, said Michiganâs Democratic House Speaker Joe Tate indicated he will bring up the Detroit land-value tax idea for a vote in January. The next step after that would be for the Detroit City Council to approve language for the proposal to be on the November 2024 ballot.
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+Detroit has more problems than just one tax can solve
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+Given the experience in Pittsburgh and other Pennsylvania municipalities, few think a land-value tax will be some sort of silver bullet for Detroit. Yet most experts believe it will still be ultimately a smart move for the city, and make Detroit more enticing to business, investors, and new residents.
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+Alex Alsup, the vice president of research and development at Regrid, a land parcel data company, said itâs possible that speculators absorb the higher taxes and continue to leave their land vacant â an outcome that would be relatively disappointing. A better outcome would be for the owner to either invest in their land or sell the lot to someone else who wants to. Itâs also possible, Alsup said, that the speculator gives up on paying their higher tax and the lot ends up in foreclosure.
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+âTax foreclosure may not be the worst thing for speculator-owned vacant homes and land, so long as the city is prepared to exercise its right to take control of these properties before they actually reach the annual tax foreclosure auction,â Alsup wrote recently in the Detroit Free Press. âThe next job would be a more thoughtful approach to getting properties into the hands of people who will put them into productive use.â
+
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+Some Detroit activists argue that a land-value tax will fail if not paired with fixing the cityâs notoriously broken property assessment process, which often undervalues expensive homes and over-values less valuable ones. âLike a lot of American cities Detroit has historically struggled with accurate and frequent assessments and particularly at the low-end of the value spectrum,â said Justus, of the Niskanen Center. âI think critics have a legitimate concern that the city will need to keep up with accurate and fair assessments, but itâs not insurmountable.â
+
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+Though a land-value tax might prove to be a political winner in Detroit, advocates acknowledge the political calculus might not be so optimistic everywhere. In some cases, it could seem very unfair to people who budgeted and invested under certain assumptions, and not every city will be able to tout a solid tax break to more than 95 percent of homeowners.
+
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+âThere are some places where the political cost may be too high, making it not worth it to incite backlash,â said Hohman, of the Mackinac Center. Still land-value tax proponents have their eyes on more than just Detroit, and the Motor City might just be the proof point they need.
+
+Even before their release, the documents reignited long-gestating conspiracy theories about prominent figures who were once in Epsteinâs orbit, including former President Bill Clinton and GOP presidential frontrunner Donald Trump, while providing both Democrats and Republicans with a new opportunity to attempt to link their opponents with Epsteinâs crimes.
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+Because the documents were misrepresented on social media as a âlistâ of potential Epstein clients or co-conspirators, there was a major focus on who and what they would expose and whether prominent Epstein associates would be explicitly tied to his trafficking of minors. In reality, many people referenced in these documents are not accused of wrongdoing, and the filings are not a âclient listâ as some surmised.
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+Instead, the âlistâ is actually dozens of documents from a 2015 court case filed by Epstein accuser Virginia Giuffre against his co-conspirator Ghislaine Maxwell, who has been convicted of child sex trafficking. These documents reference roughly 150 of Epsteinâs associates, including Clinton and Trump, but donât provide significant new information so much as they offer a more in-depth look at the people in Epsteinâs circles.
+
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+Despite the lack of revelations thus far, political actors, particularly those on the right, remain eager to utilize the information in these filings to continue amplifying the conspiracy theories theyâve long promoted.
+
+
+What is the âEpstein listâ?
+
+
+Following a request from the Miami Herald, the judge in the Maxwell case, Loretta Preska, ruled in favor of unsealing the documents from a defamation case against Maxwell, arguing that much of the information was already public.
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+Epstein, a millionaire businessman charged with sex trafficking, and Maxwell, a former socialite and longtime confidant of Epstein, have faced numerous allegations they contributed to the sexual abuse and assault of minors and helped other powerful individuals do the same. Epsteinâs death, which was ruled a suicide by federal authorities, occurred in prison while he was awaiting trial.
+
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+The unsealed documents (which retain some redactions) come from a variety of court filings and depositions with figures key to the case, including former employees and victims of Epstein and Maxwell.
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+The depositions in particular contain accusations of sexual misconduct by figures in Epstein and Maxwellâs circles, narratives on how Maxwell recruited girls and young women to work at Epsteinâs properties, and details of sex acts at least some of those recruited were coerced into, often under the guise of giving massages.
+
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+Whoâs mentioned and what did we learn about them?
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+
+There are a number of famous politicians and celebrities who are mentioned. In addition to Clinton and Trump, the UKâs Prince Andrew, former New Mexico Gov. Bill Richardson, and former Sen. George Mitchell, among others, make appearances. Clinton and Trump have also fielded allegations of sexual misconduct unrelated to Epstein, though not everyone mentioned has.
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+Bill Clinton, who is known to have taken several plane trips with Epstein, is mentioned, though the references do not detail wrongdoing. Epstein accuser Johanna Sjoberg testified as part of the case and said that Epstein told her that âClinton likes them young,â but that she wasnât aware of Clinton engaging in any sexual contact with minors at Epsteinâs invitation.
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+A Clinton spokesperson has said that the former president had no knowledge of Epsteinâs crimes and that he had not contacted Epstein in more than a decade.
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+Donald Trump is mentioned. Sjoberg testified that Epstein once discussed going to a casino in Atlantic City with him, though the references do not detail wrongdoing. In 2002, Trump previously said that he had known Epstein for â15 yearsâ and that he was a âterrific guyâ who âlikes beautiful women as much as I do, and many of them are on the younger side.â In 2019, he later distanced himself from Epstein after allegations of sex trafficking came out, saying he was ânot a fan.â
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+Prince Andrew appears in Sjobergâs deposition; she accused him of groping her breast, allegations that Buckingham Palace has previously denied. Sjoberg added that someone took a photograph of the groping and that she was ushered out of the room after it happened, while Giuffre remained with Andrew.
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+Prince Andrew has also separately settled a case with Giuffre, who has accused him of sexual abuse which he denied.
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+Attorney and former Trump impeachment counsel Alan Dershowitz is mentioned and accused of having sexual relations with a minor referred to as Jane Doe #3 in the documents and witnessing the abuse of additional girls. Dershowitz has posted a video denying these allegations.
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+Previously, Giuffre had also accused Dershowitz of sexual misconduct toward her, though she later changed her statement and stated that she âmay have made a mistakeâ identifying Dershowitz. Dershowitz has also pointed to this development in response to the allegations.
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+Other famous names mentioned include magician David Copperfield, who allegedly spoke with Sjoberg about Epstein and is not accused of any wrongdoing. Jean-Luc Brunel, a deceased modeling scout, is another individual Giuffre said she was forced to have sexual relations with and is cited as someone who helped Epstein acquire girls for trafficking. Richardson and Mitchell are also listed as people who Giuffre says she was forced to have sexual relations with; both have denied these allegations.
+
+
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+What is the significance of the âlistâ and does it matter?
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+The documents refocus the spotlight on Epstein as well as the powerful men associated with him, raising fresh questions about their involvement with his crimes. That other documents remain sealed and Epstein isnât available to offer his firsthand account only add to the uncertainty inherent in these questions and offer new fuel to conspiracy theories.
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+On the right, Epsteinâs death by suicide has been a central source of conspiracy fodder, including in bolstering unfounded claims that Epstein is an example of the Clintons having their political enemies killed. Additionally, the far right has tried to use Epsteinâs ties to various Democrats to push unsubstantiated claims about the party promoting a pedophilia ring, a conspiracy theory known as QAnon, which has been used to boost support for Trump.
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+As Voxâs Anna North has explained, those on the left have linked Epsteinâs death to unfounded claims of Trump orchestrating the deaths of his political foes as well. Additionally, there have been efforts to use Trumpâs history of sexual assault and rape allegations to suggest he was a direct participant in Epsteinâs crimes.
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+The conspiracies have even ensnared those with nothing to do with the Epstein case. In a Tuesday appearance on ESPN, football player Aaron Rodgers suggested Jimmy Kimmel could be named in the documents. Rodgersâs Kimmel reference followed a joke the late-night host had previously made calling Rodgers a âtin-foil hatterâ for fueling speculation about the Epstein list.
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+Kimmel was quick to claim Rodgersâs comments had serious fallout. âYour reckless words put my family in danger,â Kimmel said in a social media statement.
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+As the Pizzagate situation in 2016 highlighted, these conspiracy theories can have real-world consequences and implications. That year, internet trolls on the right also promoted a false conspiracy theory that prominent Democrats had formed a sex-trafficking ring targeting children and that they used pizza establishments like Comet Ping Pong in Washington, DC, to do so. Because of this, the restaurant suffered significant harassment and saw a gunman visit its premises and fire inside.
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+Thus far, the Epstein conspiracies have yet to result in comparable consequences, though there are concerns they could fuel misinformation and similarly charged scenarios amid the highly polarized political environment of the 2024 election.
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From The Hindu: Sports
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Kohli, Jadeja to vie for Sobers Trophy; Ashwin in race for ICC Test Cricketer of Year - Kohli made 2048 runs in 35 matches across Tests and ODIs in 2023, including the 50th one-day hundred to go past the iconic Sachin Tendulkar during the World Cup.
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Praggnanandhaa receives backing from Adani Group -
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South African athlete Oscar Pistorius is freed on parole after serving 9 years in girlfriendâs death - Serious offenders in South Africa are eligible for parole after serving at least half their sentence.
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ICC Test rankings | Australia topples India as worldâs No 1 Test side - Australiaâs impressive effort to take an unassailable 2-0 lead over Pakistan at home in the on-going three-match series has helped them move up in the rankings.
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AUS vs PAK | Josh Hazlewood has Pakistan reeling after Jamalâs third Test heroics - Paceman Hazlewood ripped through to reduce the tourists from 67 for four to go to the close on the third day at 68 for seven, a lead of 82
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From The Hindu: National News
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Potential-linked credit plan envisages priority sector lending of âč22,075 cr. in 2024-25 in Thiruvananthapuram - Banks carry out priority sector lending on the basis of the plan prepared by NABARD
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âč100 crore sanctioned for Kuttanad package -
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Kerala Orthodox priest who joined BJP removed from Church positions temporarily - According to an official statement, an inquiry commission has been constituted for probing the complaints lodged against Fr. Kurien by a few members of the diocese within two months. The priest will stand down from all his positions in the church till the inquiry is completed
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Cabinet approves naming Ayodhya airport after Maharishi Valmiki; gives international airport status - At the Cabinet meeting chaired by Prime Minister Narendra Modi, it was also decided to declare the airport as an international airport.
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Odisha man, whose death news drove his wife to end life, is actually alive - Goof-ups in identifying body not only led to chaos and the womanâs suicide but also denied the family of the wrongly identified man the chance to bid a proper farewell.
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From BBC: Europe
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Ukraine war: US says Russia using North Korea ballistic missiles - The US promises to raise what it calls a significant and concerning escalation at the UN Security Council.
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Hamburg hospital fire kills four patients - The blaze reportedly broke out on Thursday evening on the third floor of the Helios Clinic in Uelzen.
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Can Denmarkâs world-beating drugs maker stay ahead? - Thanks to its weight loss drug, Novo Nordisk briefly became Europeâs most valuable firm in 2023.
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Swedish snow chaos leaves 1,000 vehicles trapped on main E22 road - The army is called in to help drivers in southern Sweden amid a big freeze across the Nordic countries.
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Queen Margrethe II of Denmark embarks on final ride in gold carriage before abdication - Queen Margrethe II will formally step down next Sunday, after announcing her abdication last month.
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From Ars Technica
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Rocket Report: SpaceXâs record year; Fireflyâs Alpha rocket falls short - Living downrange from one of Chinaâs launch sites sure doesnât seem safe. - link
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Elon Musk: SpaceX needs to build Starships as often as Boeing builds 737s - âShip production needs to be roughly an order of magnitude higher than booster production.â - link
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A âridiculously weakâ password causes disaster for Spainâs No. 2 mobile carrier - BGP tampering caused by poor security hygiene causes major outage for Orange España. - link
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1D Pac-Man is the best game Iâve played in 2024 (so far) - An appreciation of âsmall gamesâ and the people who make them. - link
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How to avoid the cognitive hooks and habits that make us vulnerable to cons - Psychologists behind âinvisible gorillaâ study are back with a new book: Nobodyâs Fool. - link
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From Jokes Subreddit
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A blonde woman deicdes to dye her hair brunette so people would stop calling her stupid -
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+After doing so she decides to take a stroll and reaches the home of a shepherd.
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+Woman: âGood day too you, sir!â
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+Shepherd: âHowdy maâam!â
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+Woman: âSay, if I can guess how many sheep you have can I get one for myself ?â
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+Shepherd: âSure, go ahead!â
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+Woman: âYou have exactly 300 sheepâ
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+Shepherd: âWow, thatâs amazing! Go ahead, choose a sheep, you deserve it!â
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+The woman chooses a sheep and is about to leave before the shepherd stops her
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+Shepherd: âSay, If I can guess your natural hair color would you give me back my dog ?â
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