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<title>19 January, 2024</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>Revealing the drivers of antibiotic resistance trends in Streptococcus pneumoniae amidst the 2020 COVID-19 pandemic: Insights from mathematical modeling</strong> -
<div>
Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built in into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.08.503267v4" target="_blank">Revealing the drivers of antibiotic resistance trends in Streptococcus pneumoniae amidst the 2020 COVID-19 pandemic: Insights from mathematical modeling</a>
</div></li>
<li><strong>Persistence and Free Chlorine Disinfection of Human Coronaviruses and Their Surrogates in Water</strong> -
<div>
The COVID-19 pandemic illustrates the importance of understanding the behavior and control of human pathogenic viruses in the environment. Exposure via water (drinking, bathing, and recreation) is a known route of transmission of viruses to humans, but the literature is relatively void of studies on the persistence of many viruses, especially coronaviruses, in water and their susceptibility to chlorine disinfection. To fill that knowledge gap, we evaluated the persistence and free chlorine disinfection of human coronavirus OC43 (HCoV-OC43) and its surrogates, murine hepatitis virus (MHV) and porcine transmissible gastroenteritis virus (TGEV), in drinking water and laboratory buffer using cell culture methods. The decay rate constants of human coronavirus and its surrogates in water varied depending on virus and water matrix. In drinking water prior to disinfectant addition, MHV showed the largest decay rate constant (2.25 day-1) followed by HCoV-OC43 (0.99 day-1) and TGEV (0.65 day-1); while in phosphate buffer, HCoV-OC43 (0.51 day-1) had a larger decay rate constant than MHV (0.28 day-1) and TGEV (0.24 day-1). Upon free chlorine disinfection, the inactivation rates of coronaviruses were independent of free chlorine concentration and not affected by water matrix, though they still varied between viruses. TGEV showed the highest susceptibility to free chlorine disinfection with the inactivation rate constant of 113.50 mg-1 min-1 L, followed by MHV (81.33 mg-1 min-1 L) and HCoV-OC43 (59.42 mg-1 min-1 L).
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.16.575911v1" target="_blank">Persistence and Free Chlorine Disinfection of Human Coronaviruses and Their Surrogates in Water</a>
</div></li>
<li><strong>A Bacteriophage Cocktail Targeting Yersinia pestis Provides Strong Post-Exposure Protection in a Rat Pneumonic Plague Model</strong> -
<div>
Yersinia pestis, one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded history. Due to high genomic plasticity, Y. pestis is amenable to genetic mutations as well as genetic engineering that can lead to the emergence or intentional development of pan-drug resistant strains. The dissemination of such Y. pestis strains could be catastrophic, with public health consequences far more daunting than those caused by the recent COVID-19 pandemic. Thus, there is an urgent need to develop novel, safe, and effective treatment approaches for managing Y. pestis infections. This includes infections by antigenically distinct strains for which vaccines, none FDA approved yet, may not be effective, and those that cannot be controlled by approved antibiotics. Lytic bacteriophages provide one such alternative approach. In this study, we examined post-exposure efficacy of a bacteriophage cocktail, YPP-401, to combat pneumonic plague caused by Y. pestis CO92. YPP-401 is a four-phage preparation with a 100% lytic activity against a panel of 68 genetically diverse Y. pestis strains. Using a pneumonic plague aerosol challenge model in gender-balanced Brown Norway rats, YPP-401 demonstrated ~88% protection when delivered 18 hours post-exposure for each of two administration routes (i.e., intraperitoneal and intranasal) in a dose-dependent manner. Our studies suggest that YPP-401 could provide an innovative, safe, and effective approach for managing Y. pestis infections, including those caused by naturally occurring or intentionally developed strains that cannot be managed by vaccines in development and antibiotics.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.17.576055v1" target="_blank">A Bacteriophage Cocktail Targeting Yersinia pestis Provides Strong Post-Exposure Protection in a Rat Pneumonic Plague Model</a>
</div></li>
<li><strong>GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern</strong> -
<div>
Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and to structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work we show through over 45 s of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by N-glycosylation at N343 and how the structural role of this glycan changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2) and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the N-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.05.570076v2" target="_blank">GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern</a>
</div></li>
<li><strong>Phase 1 of the NIH Preprint Pilot: Testing the viability of making preprints discoverable in PubMed Central and PubMed</strong> -
<div>
Introduction: The National Library of Medicine (NLM) launched a pilot in June 2020 to 1) explore the feasibility and utility of adding preprints to PubMed Central (PMC) and making them discoverable in PubMed and 2) to support accelerated discoverability of NIH-supported research without compromising user trust in NLM’s widely used literature services. Methods: The first phase of the Pilot focused on archiving preprints reporting NIH-supported SARS-CoV-2 virus and COVID-19 research. To launch Phase 1, NLM identified eligible preprint servers and developed processes for identifying NIH-supported preprints within scope in these servers. Processes were also developed for the ingest and conversion of preprints in PMC and to send corresponding records to PubMed. User interfaces were modified for display of preprint records. NLM collected data on the preprints ingested and discovery of preprint records in PMC and PubMed and engaged users through focus groups and a survey to obtain direct feedback on the Pilot and perceptions of preprints. Results: Between June 2020 and June 2022, NLM added more than 3,300 preprint records to PMC and PubMed, which were viewed 4 million times and 3 million times, respectively. Nearly a quarter of preprints in the Pilot were not associated with a peer-reviewed published journal article. User feedback revealed that the inclusion of preprints did not have a notable impact on trust in PMC or PubMed. Discussion: NIH-supported preprints can be identified and added to PMC and PubMed without disrupting existing operations processes. Additionally, inclusion of preprints in PMC and PubMed accelerates discovery of NIH research without reducing trust in NLM literature services. Phase 1 of the Pilot provided a useful testbed for studying NIH investigator preprint posting practices, as well as knowledge gaps among user groups, during the COVID-19 public health emergency, an unusual time with heightened interest in immediate access to research results.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.12.520156v2" target="_blank">Phase 1 of the NIH Preprint Pilot: Testing the viability of making preprints discoverable in PubMed Central and PubMed</a>
</div></li>
<li><strong>Deciphering the Molecular Mechanism of Post-Acute Sequelae of COVID-19 through Comorbidity Network Analysis</strong> -
<div>
Introduction: The post-acute sequelae of COVID-19 presents a significant health challenge in the post-pandemic world. Our study aims to analyze longitudinal electronic health records to determine the impact of COVID-19 on disease progression, provide molecular insights into these mechanisms, and identify associated biomarkers. Method: We included 58,710 patients with COVID-19 records from 01/01/2020 to 31/08/2022 and at least one hospital admission before and after the acute phase of COVID-19 (28 days) as the treatment group. A healthy control group of 174,071 individuals was established for comparison using propensity score matching based on pre-existing diseases (before COVID-19). We built a comorbidity network using Pearson correlation coefficient differences between pairs of pre-existing disease and post-infection disease in both groups. Disease-protein mapping and protein-protein interaction network analysis revealed the impact of COVID-19 on disease trajectories through protein interactions in the human body. Results: The disparity in the weight of prevalent disease comorbidity patterns between the treatment and control groups highlights the impact of COVID-19. Certain specific comorbidity patterns show a more pronounced influence by COVID-19. For each comorbidity pattern, overlapping proteins directly associated with pre-existing diseases, post-infection diseases, and COVID-19 help to elucidate the biological mechanism of COVID-19's impact on each comorbidity pattern. Proteins essential for explaining the biological mechanism can be identified based on their weights. Conclusion: Disease comorbidity associations influenced by COVID-19, as identified through longitudinal electronic health records and disease-protein mapping, can help elucidate the biological mechanisms of COVID-19, discover intervention methods, and decode the molecular basis of comorbidity associations. This analysis can also yield potential biomarkers and corresponding treatments for specific disease patterns.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.17.575851v1" target="_blank">Deciphering the Molecular Mechanism of Post-Acute Sequelae of COVID-19 through Comorbidity Network Analysis</a>
</div></li>
<li><strong>Changes in wild meat hunting and use by rural communities during the COVID-19 socio-economic shock</strong> -
<div>
There has been limited quantitative research into the effects of socio-economic shocks on biological resource use. Focusing on wild meat hunting, a substantial livelihood and food source in tropical regions, we evaluated the impacts of the shock from Nigeria’s COVID-19 lockdown on species exploitation around a global biodiversity hotspot. Using a three-year quantitative dataset collected during and after the lockdown (covering 1,008 hunter-months) and matching by time of year, we found that successful hunting trip rates were more frequent during lockdown, with a corresponding increase in the monthly number, mass, and value of animals caught. Moreover, hunters consumed a larger proportion of wild meat and sold less during lockdown compared to non-lockdown periods. These results suggest that local communities relied on wild meat to supplement reduced food and income during lockdown, buffering COVID-19’s socio-economic shock. Our findings also indicate that wild species may be especially vulnerable to increased hunting pressure during such shocks.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/ezyr7/" target="_blank">Changes in wild meat hunting and use by rural communities during the COVID-19 socio-economic shock</a>
</div></li>
<li><strong>Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection</strong> -
<div>
Inflammation-induced thrombosis is a common consequence of bacterial and viral infections, such as those caused by Salmonella Typhimurium (STm) and SARS-CoV-2. The identification of multi-organ thrombosis and the chronological differences in its induction and resolution raise significant challenges for successfully targeting multi-organ infection-associated thrombosis. Here, we identified specific pathways and effector cells driving thrombosis in the spleen and liver following STm infection. Thrombosis in the spleen is independent of IFN-{gamma} or the platelet C-type lectin-like receptor CLEC-2, while both molecules were previously identified as key drivers of thrombosis in the liver. Furthermore, we identified platelets, monocytes, and neutrophils as core constituents of thrombi in both organs. Depleting neutrophils or monocytic cells independently abrogated thrombus formation. Nevertheless, blocking TNF, which is expressed by both myeloid cell types, diminished both thrombosis and inflammation which correlates with reduced endothelial expression of E-selectin and leukocyte infiltration. Moreover, tissue factor and P-selectin glycoprotein ligand 1 inhibition impairs thrombosis in both spleen and liver, identifying multiple common checkpoints to target multi-organ thrombosis. Therefore, organ-specific, and broad mechanisms driving thrombosis potentially allow tailored treatments based on the clinical need and to define the most adequate strategy to target both thrombosis and inflammation associated with systemic infections.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.16.575813v1" target="_blank">Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection</a>
</div></li>
<li><strong>Impact of SARS-CoV-2 spike efficacy on tolerability of spike-based Covid-19 Vaccinations</strong> -
<div>
Abstract: Knowledge about the efficacy of vaccine spikes has multiplied in recent years. The purpose of this review is to update the key findings from the scientific literature that provide explanations for many of the reported and analysed adverse effects associated with the spike-based Covid-19 vaccination. Principle results: An overwhelming body of evidence supports the main mode of action of spike-based Covid-19 vaccines, namely the downregulation of ACE2 by spikes. Direct spike effects, synergisms and RAAS-independent responses complement and multiply the already deleterious effects on tolerability. It has been repeatedly confirmed that the SARS-CoV spike protein alone is not only able to downregulate ACE2, but also to induce cell fusion, activation of TLR4, of co-receptors and gastrointestinal responses. The systemic and long-lasting detection of spikes after vaccination disproves the claimed regionally limited and short-lasting spike production and efficacy. The production volume of spikes, their dependencies and the non-neutralised spike proportion have so far remained unknown for unknown reasons. Conclusions: The exceptionally broad spectrum, frequency and severity of the reported side effects associated with spike-based Covid-19 vaccination exceed the known level of conventional vaccinations. According to my side effect analyses, the spike-based vaccines possess an unacceptable class-specific, unique side effect profile. From a pharmacological point of view, spikes are highly active substances, but not tolerable simple antigens. For this reason, they are not suitable for preventive immunisation to avoid comparatively harmless infections.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/pw8zr/" target="_blank">Impact of SARS-CoV-2 spike efficacy on tolerability of spike-based Covid-19 Vaccinations</a>
</div></li>
<li><strong>Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody</strong> -
<div>
Three coronaviruses have spilled over from animal reservoirs into the human population and caused deadly epidemics or pandemics. The continued emergence of coronaviruses highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using LIBRA-seq, we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these antibodies, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryo-EM structure of 54043-5 bound to the pre-fusion S2 subunit of the SARS-CoV-2 spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses, including ADCC and ADCP. In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.15.575741v1" target="_blank">Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody</a>
</div></li>
<li><strong>Adsorption-driven deformation and landing-footprints of the RBD proteins in SARS-CoV-2 variants onto biological and inanimate surfaces</strong> -
<div>
Respiratory viruses, carried through airborne microdroplets, frequently adhere to surfaces, including plastics and metals. However, our understanding of the interactions between viruses and materials remains limited, particularly in scenarios involving polarizable surfaces. Here, we investigate the role of receptor-binding domain (RBD) mutations on the adsorption of SARS-CoV-2 to hydrophobic and hydrophilic surfaces employing molecular simulations. To contextualize our findings, we contrast the interactions on inanimate surfaces with those on native-biological interfaces, specifically the ACE2 receptor. Notably, we identify a twofold increase in structural deformations for the protein's receptor binding motif onto the inanimate surfaces, indicative of enhanced shock-absorbing mechanisms. Furthermore, the distribution of amino acids (landing-footprints) on the inanimate surface reveals a distinct regional asymmetry relative to the biological interface. In spite of the H-bonds formed at the hydrophilic substrate, the simulations consistently show a higher number of contacts and interfacial area with the hydrophobic surface, with the WT RBD adsorbed more strongly to than the delta or omicron RBDs. In contrast, the adsorption of delta and omicron to hydrophilic surfaces was characterized by a distinctive hopping-pattern. The novel shock-absorbing mechanisms identified in the virus adsorption on inanimate surfaces could lead current experimental efforts in the design of virucidal surfaces.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.15.575706v1" target="_blank">Adsorption-driven deformation and landing-footprints of the RBD proteins in SARS-CoV-2 variants onto biological and inanimate surfaces</a>
</div></li>
<li><strong>Reference materials for SARS-CoV-2 molecular diagnostic quality control: validation of encapsulated synthetic RNAs for room temperature storage and shipping</strong> -
<div>
The Coronavirus pandemic unveiled the unprecedented need for diagnostic tests to rapidly detect the presence of pathogens in the population. Real-time RT-PCR and other nucleic acid amplification techniques are accurate and sensitive molecular techniques that necessitate positive controls. To meet this need, Twist Bioscience has developed and released synthetic RNA controls. However, RNA is an inherently unstable molecule needing cold storage, costly shipping, and resource-intensive logistics. Imagene provides a solution to this problem by encapsulating dehydrated RNA inside metallic capsules filled with anhydrous argon, allowing room temperature and eco-friendly storage and shipping. Here, RNA controls produced by Twist were encapsulated (RNAshells) and distributed to several laboratories that used them for COVID-19 detection tests by amplification. One RT-LAMP procedure, four different RT-PCR devices and 6 different PCR kits were used. The amplification targets were genes E, N; RdRp, Sarbeco-E and Orf1a/b. RNA retrieval was satisfactory, and the detection was reproducible. RNA stability was checked by accelerated aging. The results for a 10-year equivalent storage time at 25 {degrees}C were not significantly different from those for unaged samples. This room temperature RNA stability allows the preparation and distribution of large strategic batches which can be stored for a long time and used for standardization processes between detection sites. Moreover, it makes it also possible to use these controls for single use and in the field where large temperature differences can occur. Consequently, this type of encapsulated RNA controls, processed at room temperature, can be used as reference materials for the SARS-Cov-2 virus as well as for other pathogens detection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.28.555008v3" target="_blank">Reference materials for SARS-CoV-2 molecular diagnostic quality control: validation of encapsulated synthetic RNAs for room temperature storage and shipping</a>
</div></li>
<li><strong>Lineage frequency time series reveal elevated levels of genetic drift in SARS-CoV-2 transmission in England</strong> -
<div>
Genetic drift in infectious disease transmission results from randomness of transmission and host recovery or death. The strength of genetic drift for SARS-CoV-2 transmission is expected to be high due to high levels of superspreading, and this is expected to substantially impact disease epidemiology and evolution. However, we don’t yet have an understanding of how genetic drift changes over time or across locations. Furthermore, noise that results from data collection can potentially confound estimates of genetic drift. To address this challenge, we develop and validate a method to jointly infer genetic drift and measurement noise from time-series lineage frequency data. Our method is highly scalable to increasingly large genomic datasets, which overcomes a limitation in commonly used phylogenetic methods. We apply this method to over 490,000 SARS-CoV-2 genomic sequences from England collected between March 2020 and December 2021 by the COVID-19 Genomics UK (COG-UK) consortium and separately infer the strength of genetic drift for pre-B.1.177, B.1.177, Alpha, and Delta. We find that even after correcting for measurement noise, the strength of genetic drift is consistently, throughout time, higher than that expected from the observed number of COVID-19 positive individuals in England by 1 to 3 orders of magnitude, which cannot be explained by literature values of superspreading. Our estimates of genetic drift will be informative for parameterizing evolutionary models and studying potential mechanisms for increased drift.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.21.517390v3" target="_blank">Lineage frequency time series reveal elevated levels of genetic drift in SARS-CoV-2 transmission in England</a>
</div></li>
<li><strong>De novo-designed minibinders expand the synthetic biology sensing repertoire</strong> -
<div>
Synthetic and chimeric receptors capable of recognizing and responding to user-defined antigens have enabled "smart" therapeutics based on engineered cells. These cell engineering tools depend on antigen sensors which are most often derived from antibodies. Advances in the de novo design of proteins have enabled the design of protein binders with the potential to target epitopes with unique properties and faster production timelines compared to antibodies. Building upon our previous work combining a de novo-designed minibinder of the Spike protein of SARS-CoV-2 with the synthetic receptor synNotch (SARSNotch), we investigated whether minibinders can be readily adapted to a diversity of cell engineering tools. We show that the Spike minibinder LCB1 easily generalizes to a next-generation proteolytic receptor SNIPR that performs similarly to our previously reported SARSNotch. LCB1-SNIPR successfully enables the detection of live SARS-CoV-2, an improvement over SARSNotch which can only detect cell-expressed Spike. To test the generalizability of minibinders to diverse applications, we tested LCB1 as an antigen sensor for a chimeric antigen receptor (CAR). LCB1-CAR enabled CD8+ T cells to cytotoxically target Spike-expressing cells. Our findings suggest that minibinders represent a novel class of antigen sensors that have the potential to dramatically expand the sensing repertoire of cell engineering tools.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.12.575267v1" target="_blank">De novo-designed minibinders expand the synthetic biology sensing repertoire</a>
</div></li>
<li><strong>mRNA-LNP COVID-19 vaccine lipids induce low level complement activation and production of proinflammatory cytokines: Mechanisms, effects of complement inhibitors, and relevance to adverse reactions</strong> -
<div>
Messenger RNA-containing lipid nanoparticles (mRNA-LNPs) enabled widespread COVID-19 vaccination with a small fraction of vaccine recipients displaying acute or sub-acute inflammatory symptoms. The molecular mechanism of these adverse events (AEs) remains undetermined. Here we report that the mRNA-LNP vaccine, Comirnaty, triggers low-level complement (C) activation and production of inflammatory cytokines, which may be key underlying processes of inflammatory AEs. In serum, Comirnaty and the control PEGylated liposome (Doxebo) caused different rises of C split products, C5a, sC5b-9, Bb and C4d, indicating stimulation of the classical pathway of C activation mainly by the liposomes, while a stronger stimulation of the alternative pathway was equal with the vaccine and the liposomes. Spikevax had similar C activation as Comirnaty, but viral or synthetic mRNAs had no such effect. In autologous serum-supplemented peripheral blood mononuclear cell (PBMC) cultures, Comirnaty caused increases in the levels of sC5b-9 and proinflammatory cytokines in the following order: IL-1 &lt; IFN-{gamma} &lt; IL-1{beta} &lt; TNF- &lt; IL-6 &lt; IL-8, whereas heat-inactivation of serum prevented the rises of IL-1, IL-1{beta}, and TNF-. Clinical C inhibitors, Soliris and Berinert, suppressed vaccine-induced C activation in serum but did not affect cytokine production when applied individually. These findings suggest that the PEGylated lipid coating of mRNA-LNP nanoparticles can trigger C activation mainly via the alternative pathway, which may be causally related to the induction of some, but not all inflammatory cytokines. While innate immune stimulation is essential for the vaccine's efficacy, concurrent production of C- and PBMC-derived inflammatory mediators may contribute to some of the AEs. Pharmacological attenuation of harmful cytokine production using C inhibitors likely requires blocking the C cascade at multiple points.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.12.575122v1" target="_blank">mRNA-LNP COVID-19 vaccine lipids induce low level complement activation and production of proinflammatory cytokines: Mechanisms, effects of complement inhibitors, and relevance to adverse reactions</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effectiveness of a Health Promotion Program for Older People With Post-Covid-19 Sarcopenia</strong> - <b>Conditions</b>: Post COVID-19 Condition <br/><b>Interventions</b>: Other: Protein powder and Resistance exercise <br/><b>Sponsors</b>: Mahidol University; National Health Security Office, Thailand <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>Chronic-disease Self-management Program in Patients Living With Long-COVID in Puerto Rico</strong> - <b>Conditions</b>: Long Covid19 <br/><b>Interventions</b>: Other: “Tomando control de su salud” (Spanish Chronic Disease Self-Management) <br/><b>Sponsors</b>: University of Puerto Rico; National Institutes of Health (NIH) <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>Treatment of Persistent Post-Covid-19 Smell and Taste Disorders</strong> - <b>Conditions</b>: Post-covid-19 Persistent Smell and Taste Disorders <br/><b>Interventions</b>: Drug: Cerebrolysin; Other: olfactory and gustatory trainings <br/><b>Sponsors</b>: Sherifa Ahmed Hamed <br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evealuate Safety and Immunogenicity of TI-0010 SARS-CoV-2 Vaccine in Healthy Adults</strong> - <b>Conditions</b>: COVID-19; COVID-19 Immunisation <br/><b>Interventions</b>: Biological: TI-0010; Biological: Placebo <br/><b>Sponsors</b>: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College; Therorna <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>Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction</strong> - <b>Conditions</b>: Long Haul COVID-19; Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders <br/><b>Interventions</b>: Drug: Sodium Citrate; Drug: Normal Saline; Other: Olfactory Training Kit - “The Olfactory Kit, by AdvancedRx” <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill <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>Phase II, Double Blind, Randomized Trial of CX-4945 in Viral Community Acquired Pneumonia</strong> - <b>Conditions</b>: Community-acquired Pneumonia; SARS-CoV-2 -Associated Pneumonia; Influenza With Pneumonia <br/><b>Interventions</b>: Drug: CX-4945 (SARS-CoV-2 domain); Drug: Placebo (SARS-CoV-2 domain); Drug: CX-4945 (Influenza virus domain); Drug: Placebo (Influenza virus domain) <br/><b>Sponsors</b>: Senhwa Biosciences, Inc. <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>Edge AI-deployed DIGItal Twins for PREDICTing Disease Progression and Need for Early Intervention in Infectious and Cardiovascular Diseases Beyond COVID-19 - Investigation of Biomarkers in Dermal Interstitial Fluid</strong> - <b>Conditions</b>: Heart Failure <br/><b>Interventions</b>: Device: Use of the PELSA System for dISF extraction <br/><b>Sponsors</b>: Charite University, Berlin, Germany <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase III Clinical Study Evaluating the Efficacy and Safety of WPV01 in Patients With Mild/Moderate COVID-19</strong> - <b>Conditions</b>: Mild to Moderate COVID-19 <br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo <br/><b>Sponsors</b>: Westlake Pharmaceuticals (Hangzhou) Co., Ltd. <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Integrated Mindfulness-based Health Qigong Intervention for COVID-19 Survivors and Caregivers</strong> - <b>Conditions</b>: COVID-19 Infection <br/><b>Interventions</b>: Other: Mindfulness-based Health Qigong Intervention <br/><b>Sponsors</b>: The Hong Kong Polytechnic 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>SARS-CoV-2 and Influenza A/B in Point-of-Care and Non-Laboratory Settings</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Aptitude Medical Systems Metrix COVID/Flu Test <br/><b>Sponsors</b>: Aptitude Medical Systems; Biomedical Advanced Research and Development Authority <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>Effect of Aerobic Exercises Versus Incentive Spirometer Device on Post-covid Pulmonary Fibrosis Patients</strong> - <b>Conditions</b>: Lung Fibrosis Interstitial; Post-COVID-19 Syndrome <br/><b>Interventions</b>: Other: Aerobic Exercises; Device: Incentive Spirometer Device; Other: Traditional Chest Physiotherapy <br/><b>Sponsors</b>: McCarious Nahad Aziz Abdelshaheed Stephens; Cairo University <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>Can Doctors Reduce COVID-19 Misinformation and Increase Vaccine Uptake in Ghana? A Cluster-randomised Controlled Trial</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Motivational Interviewing, AIMS; Behavioral: Facility engagement <br/><b>Sponsors</b>: London School of Economics and Political Science; Innovations for Poverty Action; Ghana Health Services <br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<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 Anxious Precision of Jacqueline Novak’s Comedy</strong> - “Get on Your Knees,” her new Netflix special, is a ninety-minute reflection on the blow job. - <a href="https://www.newyorker.com/magazine/2024/01/22/jacqueline-novak-profile">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Drug-Decriminalization Fight Erupts in Oregon</strong> - An ambitious law set forth a more humane way to address addiction. Then came the backlash. - <a href="https://www.newyorker.com/magazine/2024/01/22/a-new-drug-war-in-oregon">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Birth of My Daughter, the Death of My Marriage</strong> - Now that I was doing little besides keeping this tiny creature alive, it was impossible to ignore my desire to wander the streets with our baby, in ever-widening loops away from home. - <a href="https://www.newyorker.com/magazine/2024/01/22/the-birth-of-my-daughter-the-death-of-my-marriage">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Price of Netanyahu’s Ambition</strong> - Amid war with Hamas, a hostage crisis, the devastation of Gaza, and Israel’s splintering identity, the Prime Minister seems unable to distinguish between his own interests and his country’s. - <a href="https://www.newyorker.com/magazine/2024/01/22/benjamin-netanyahu-israel-gaza-hamas-war-hostages">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How Ten Middle East Conflicts Are Converging Into One Big War</strong> - The U.S. is enmeshed in wars among disparate players in Israel, Iraq, Lebanon, Syria, and Yemen. - <a href="https://www.newyorker.com/news/daily-comment/how-ten-middle-east-conflicts-are-converging-into-one-big-war">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Why have our winters gotten so weird?</strong> -
<figure>
<img alt="Children are sledding in front of the Capitol Building in Washington, DC, on January 16, after the region received 2-4 inches of snow, marking the first significant snowstorm in over two years for the city." src="https://cdn.vox-cdn.com/thumbor/JAhTvWxkQ6kfbJ9psUjd25PMUrc=/781x0:7056x4706/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73068135/GettyImages_1931227878.0.jpeg"/>
<figcaption>
Much of the US is experiencing frigid cold temperatures, but winters have been warming across the country in recent decades. | Aaron Schwartz/NurPhoto via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Yes, it’s freezing now. But winters are actually warming dangerously fast.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CAlYdW">
Bitter cold continues to grip the United States as unusual freezing temperatures stretch <a href="https://www.wesh.com/article/florida-cold-wind-chill-wednesday-temperatures/46421158">as far south as Florida</a> this week. Even <a href="https://www.foxweather.com/weather-news/deadly-cold-continues">more chilly weather</a> is in store through the weekend, putting more than 80 percent of the US population under some type of cold weather advisory.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ClZLu0">
But this jarring cold snap is sandwiched between the end of what was the <a href="https://www.vox.com/23969523/climate-change-cop28-paris-1-5-c-uae-2023-record-warm">hottest year on record</a> and the start of another year that <a href="https://www.reuters.com/business/environment/us-scientists-say-one-in-three-chance-2024-another-year-record-heat-2024-01-12/">could be even hotter</a>. And even as temperatures <a href="https://www.reuters.com/world/us/arctic-blast-ends-new-york-snow-drought-brings-record-cold-west-2024-01-16/">plunge to new depths</a>, the recent weather isn’t remotely enough to derail an ominous trend.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MwQHoC">
As the climate changes, the bottom of the temperature scale is rising faster than the top. This pronounced winter warming is often less palpable than the triple-digit summer heat waves that have become all the more frequent across much of the country, but no less profound.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QxlXJ1">
According to <a href="https://www.climatecentral.org/climate-matters/fewer-frigid-nights-2023">Climate Central</a>, more than 200 locations around the United States have lost almost two weeks of below-freezing nights since 1970. By 2050, 23 states are projected to lose upward of a month of freezing days.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DSks3u">
“In general, winters have been getting warmer across the country, and really across the world,” said <a href="https://cropsoil.uga.edu/people/faculty/pam-knox.html">Pamela Knox</a>, an agricultural climatologist at the University of Georgia extension. “It turns out that the colder seasons are warming up more quickly than the warmer seasons.” Warmer winters are one of the strongest examples of how humanity has changed the world with its ravenous appetite for fossil fuels, which emit greenhouse gases into the atmosphere and drive up global temperatures.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6KFe9M">
That doesn’t just mean <a href="https://www.theguardian.com/environment/2023/dec/26/ski-resorts-battle-for-a-future-as-snow-declines-in-climate-crisis">fewer good ski days</a> or the end of <a href="https://www.vox.com/culture/24001256/snow-winter-climate-change-solastalgia-warming">white Christmases</a> for some regions; cold weather is an important, essential signal for plants and animals, and losing it has far-reaching effects on the economy, food production, and health.
</p>
<h3 id="pSDTnr">
Why winters in particular are heating up
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7Pd8V0">
Though Earth is warming on average, those changes aren’t distributed evenly across the planet or throughout the year. The Arctic, for example, is warming about <a href="https://www.nature.com/articles/s43247-022-00498-3">four times as fast</a> as the rest of the world as the sunlight-reflecting ice yields to the darker, heat-absorbing ocean below.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fhfxrK">
The cold seasons are also heating up disproportionately further south, albeit at a slower pace than the North Pole. According to the fifth <a href="https://www.vox.com/climate/23959402/national-climate-assessment-nca-report-biden-trump">National Climate Assessment</a>, a report by 14 US government agencies published last year, “Winter is <a href="https://nca2023.globalchange.gov/chapter/2/#key-message-1">warming nearly twice as fast</a> as summer in many northern states.”
</p>
<figure class="e-image">
<img alt="Maps showing changes in hot and cold extremes across the US. " src="https://cdn.vox-cdn.com/thumbor/-etY8O__BdIfduR_nqcMyLhXnbM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25234579/figure2_7.jpeg"/> <cite><a class="ql-link" href="https://nca2023.globalchange.gov/chapter/2/#key-message-1" target="_blank">National Climate Assessment</a></cite>
<figcaption>
The number of hot extreme days has increase over the past 20 years across the US while cold extremes are declining.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5O7qzX">
Why? Winters, it turns out, tend to have a stronger response to heat-trapping gases than summers. That’s not just due to carbon dioxide and methane, but also water vapor. For every 1.8 degrees Fahrenheit increase in temperature, air can hold on to 7 percent more moisture. “Cold atmospheres are especially sensitive to the additional moisture because the air is usually dry to start with, and a little more water vapor means a lot more heat is trapped near the surface,” <a href="https://www.woodwellclimate.org/staff/jennifer-francis/">Jennifer Francis</a>, a senior scientist at the Woodwell Climate Research Center, an independent team of climate scientists, wrote in an email.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jyuena">
In places where winter temperatures are rising above the freezing point, that’s leading to more rain than snow. But in areas where winter is warming but not yet above 32 degrees Fahrenheit, that extra moisture in the air can lead to more snowfall.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="enAbeK">
“Snowfall is generally declining except where it’s still plenty cold enough for snow (rather than rain) to fall,” Francis said. “There is also a clear increased frequency of heavy precipitation events in all seasons.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="e9FLBP">
Warming winters could also have some paradoxical effects and may even contribute to sudden cold snaps like the one underway across the US, although scientists are <a href="https://www.vox.com/22287295/texas-uri-climate-change-cold-polar-vortex-arctic">debating the mechanisms at work</a>. One idea is that the rapid warming in the Arctic is destabilizing the polar vortex, the band of fast-moving air that typically contains frigid air to the far north. The National Climate Assessment <a href="https://nca2023.globalchange.gov/chapter/2/#key-message-1">notes</a> that “some recent studies suggest that Arctic warming results in increasing disruptions of the stratospheric polar vortex that cause cold air from the Arctic to spill down over the United States, as seen in recent severe winter weather events such as the February 2021 cold snap that affected large parts of the country.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="riTGEX">
However, with more greenhouse gases accumulating in the atmosphere, more heating is in store for the coldest regions of the world, which in turn will raise sea levels, alter ocean currents, and warp weather patterns around the globe. This is already having far-reaching effects near the equator, from reshaping shorelines to hampering harvests of prized fruit.
</p>
<h3 id="KFiD98">
You’ll miss this cold when it’s gone
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5RVQz8">
Consider the peach. For the state of Georgia, it’s kind of its thing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OPavEZ">
Georgia’s official nickname is “<a href="https://www.usatoday.com/story/news/2023/01/29/official-state-nicknames-50-united-states/11032943002/">The Peach State</a>.” “George peach” is a <a href="https://www.benjaminmoore.com/en-us/paint-colors/color/031/georgia-peach">trademarked paint color</a>. They’re on the <a href="https://mvd.dor.ga.gov/motor/plates/PlateDetails.aspx?pcode=AA">license plate</a>. The Atlanta metro area has <a href="https://www.atlantamagazine.com/news-culture-articles/the-somewhat-definitive-ranking-of-atlantas-peachtree-streets/">more than 70 Peachtree streets</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5iUuPI">
These perfect, pinkish, plump, pulpy, pitted produce are products of pride for the state (despite Georgia ranking <a href="https://www.ers.usda.gov/data-products/chart-gallery/gallery/chart-detail/?chartId=107215">a distant third</a> in peach production). So, the <a href="https://www.npr.org/2023/05/30/1178773390/weather-is-to-blame-for-roughly-90-of-georgias-peach-crop-being-destroyed">loss of 90 percent of the crop</a> last year — the worst harvest since at least 1955 — hit Georgians hard. Even as <a href="https://www.cbsnews.com/miami/news/georgia-the-peach-state-is-out-of-peaches-heres-why-and-how-locals-are-coping/">prices tripled</a>, many farmers didn’t have any peaches to sell, leaving picky connoisseurs to scramble for what was left.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tQTT4K">
“Buying peaches from any other state is completely out of the question,” Henryk Kumar, director of operations at the Butter &amp; Cream ice cream shops in Georgia, <a href="https://www.cnn.com/2023/07/15/business/georgia-peach-shortage/index.html">told CNN last year</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3AtYTi">
Like much of the country, Georgia was hammered by severe and often hot weather in 2023. The extremes proved to be an <a href="https://www.walb.com/2023/07/19/peach-state-saw-90-its-namesake-crop-destroyed/">especially deadly combination</a> for the state’s precious fruit. A heat wave in February followed by two back-to-back cold snaps then heat waves again in the summer devastated the crop.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lLciFV">
The string of weather last year was especially unlucky, but warmer temperatures from November through February are posing a long-term threat to the future of Georgia peaches.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="131H2C">
Georgia isn’t known for chilly winters, but what little cool weather it gets is precious. To produce ample fruit, peach trees require a minimum number of chill hours at temperatures below 45 degrees Fahrenheit. Depending on the variety, that requirement can range from <a href="https://newswire.caes.uga.edu/story/6157/peach-crop.html">500 to 800 hours</a>. The cool weather signals the tree to save up energy and resources. Once a tree reaches its minimum cold exposure, it can suspend its dormancy and resume growing in the spring.
</p>
<figure class="e-image">
<img alt="A road sign with a peach on it welcomes travelers to Georgia on July 24, 2023, in Fort Valley, Georgia. It reads, “Welcome to Georgia. We’re glad Georgia’s on your mind.”" src="https://cdn.vox-cdn.com/thumbor/vmJd0wZndS5zqkhqNvgIvI_5Fdg=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25234718/GettyImages_1568145839.jpeg"/> <cite>Joe Raedle/Getty Images</cite>
<figcaption>
Peaches are Georgia’s iconic fruit, but warming winters are threatening harvests.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E7Fw6J">
However, with warmer winters, peach trees are experiencing seasonal insomnia. It’s disrupting the timing of when they blossom, making it harder for farmers to ensure they’re pollinated and end up bearing fruit. “A lot of times they bring in bees, so they want to have the maximum amount of pollination in a certain amount of time,” Knox said. “What happens when you don’t get enough chill hours is that the plants will still produce buds, but they’re not all ready to bloom at the same time.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RREC58">
If warming continues at its current pace, Georgia will face <a href="https://www.mdpi.com/2225-1154/7/8/94">more frequent seasons</a> where it won’t be cold enough to grow many common peach varieties. The optimal growing regions for fruit like peaches and apples are going to shift northward, according to Knox: “Maybe they’ll grow more in north Georgia rather than in central Georgia where they do now.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xnw884">
This is just one example of how much the world as we know it counts on cool weather and the stakes of losing it. Another critical winter threshold is the freezing point of water. In places like the Sierra Nevada, snow serves as a water battery, charging up in the winter to power streams and rivers in the western US throughout the year. Warmer winters can thus fuel a <a href="https://www.vox.com/energy-and-environment/23550073/california-floods-rainfall-weather-climate-change-whiplash">weather whiplash</a> with flooding in the winter and drought in the summer, even if overall precipitation doesn’t change very much.
</p>
<figure class="e-image">
<img alt="Graph showing the number of unfrozen days across the US since 1979. " src="https://cdn.vox-cdn.com/thumbor/vovxdwLHw1HmR3q6FX9NJF8aFbI=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25234565/freeze_thaw_download1_2023.png"/> <cite><a class="ql-link" href="https://www.epa.gov/climate-indicators/climate-change-indicators-freeze-thaw-conditions" target="_blank">Environmental Protection Agency</a></cite>
<figcaption>
The number of days with unfrozen ground is rising across the continental US.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Uno0Eh">
The loss of cold weather in the winter can also amplify warming through the spring and summer. “Earlier loss of spring snow cover more generally means that the strong spring sun can dry out the soil earlier, and when the soil dries out, it can warm up much faster,” Francis said. “This is contributing to summer heat waves, droughts, and more intense fire seasons.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ryAzKf">
Warmer winters do have some upsides. Since the beginning of the 20th century, warming has <a href="https://www.epa.gov/climate-indicators/climate-change-indicators-length-growing-season">extended the growing season by two weeks</a>. For farmers growing annual crops like corn or wheat, that can let them squeeze in more plantings in a year. Last year, the US saw increases in soy and wheat production, as well as a <a href="https://www.vox.com/climate/23971356/thanksgiving-2023-food-steak-olive-oil-record-heat-climate-change">record corn harvest</a>. But for orchards that bear fruit once a year, that longer season doesn’t offer much help.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RrZAqm">
Rising winter temperatures also mean that severe chills and sudden frost events may be less likely in some areas. A dip below freezing after plants begin to awaken from their winter slumber can damage fragile leaves, stems, and roots, thereby hurting crop yields. But even in a warmer climate, frost events can still occur within the ordinary chaos of weather — as it did with Georgia’s peaches last year — though their timing may change. “The national climate system is like a bowl of jello,” Knox said. “It’s always jiggling.”
</p></li>
<li><strong>Congress averted a shutdown. Here’s what’s next.</strong> -
<figure>
<img alt="Mike Johnson, tieless in a blue suit and shirt, holds a hand up as he speaks, paintings and statues behind him." src="https://cdn.vox-cdn.com/thumbor/OFwRri1nLZ6ju-BEvVrB6XmjtIY=/388x0:3500x2334/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73067281/GettyImages_1930882826.0.jpg"/>
<figcaption>
House Speaker Mike Johnson speaks at the US Capitol ahead of the government funding deal. | Valerie Plesch/Bloomberg/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Congress’s interminable shutdown cycle, explained.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MKUQ0L">
On Thursday, <a href="https://www.vox.com/congress">Congress</a> <a href="https://www.vox.com/videos/22808675/us-government-shutdown-appropriations-bill-spending">narrowly averted</a> a <a href="https://www.vox.com/politics/2023/9/28/23894486/government-shutdown-federal-employees-services-closed">government shutdown</a>, one day before a January 19 funding deadline.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eDX8cF">
That’s welcome news: Government employees won’t be furloughed and programs won’t be delayed — but only for now. The deal does nothing to resolve the spending disagreements that put the government in danger of a shutdown in the first place, and could threaten the House’s ability to function if far-right Republicans unhappy with the deal manage to oust Speaker Mike Johnson over what they see as intolerable compromises with Democrats.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zTEs49">
The short-term spending bill Congress passed — known as a continuing resolution, or CR — will only keep the government funded until early March. At that point, Congress, and the country, will have to navigate questions about a potential shutdown all over again.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UHeEJQ">
In recent years, shutdowns — or the threat of one — have become more common as Congress has become more polarized and as lawmakers, particularly Republicans, have sought to leverage these must-pass annual spending bills to send a message to their base. Conservatives, for instance, have recently threatened to shut down the government if the spending deal didn’t include more <a href="https://thehill.com/homenews/house/4390204-5-things-to-know-about-border-bill-hr2-gop-shutdown-threats/">aggressive border security policies</a> that make it harder to seek asylum.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8S5aOA">
This week, Democrats jumped in to help the House GOP pass the CR without the assistance of these hardliners, but it’s this kind of partisan grandstanding that leads to the government feeling like it’s <a href="https://www.vox.com/videos/22808675/us-government-shutdown-appropriations-bill-spending">constantly on the verge of a shutdown</a> and that Congress is unable to complete even its most basic tasks.
</p>
<h3 id="pviozg">
Why are we talking about a potential shutdown again?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O5iPq1">
Each year, lawmakers have to pass either 12 full-year spending bills or a CR by the end of September in order to keep the government open.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="q3rCjL">
Because Congress tends to procrastinate, lawmakers are often working up until that deadline on these bills, heightening concerns that they might not finish the job.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DT85JZ">
That’s exactly what happened <a href="https://www.vox.com/politics/2023/9/30/23897597/shutdown-congress-kevin-mccarthy-ukraine">last September</a> when Congress approved a short-term spending bill that gave them until mid-November to finish the full-year spending bills. At the time, then-House Speaker Kevin McCarthy had to rely on Democrats to help keep the government open since the right flank of his caucus was refusing to do so.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XLoWDe">
That dynamic ultimately led to complete chaos in House Republican leadership. Because of a new rule that McCarthy agreed to this term, any single lawmaker is able to force a vote removing the speaker if they’re unhappy with that person. McCarthy’s decision to work with Democrats, which conservatives slammed, ultimately led to a vote on his removal as speaker, which succeeded.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W0k60k">
McCarthy’s removal, however, didn’t mean Congress’s approach to the funding bills changed. With the November deadline fast approaching, House Republicans once again worked with Democrats to approve <a href="https://www.vox.com/politics/2023/11/15/23962996/house-funding-bill-government-shutdown-mike-johnson">another short-term spending bill,</a> this time giving them two new deadlines to pass legislation: Funding for some agencies expired on January 19, while funding for other agencies expired on February 2.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y6Run7">
To prevent the latest batch of funding from expiring, Congress scrambled this week to try to find a deal. Really, they only had one option: a short-term spending bill, as they didn’t leave themselves enough time for the negotiations involved with a full-year spending package — especially given the conservative demands around the border that are nonstarters with most Democrats.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qxuAE0">
Such CRs are unpopular with Republicans and have been criticized by Johnson, too, fueling concerns that the government could shut down this winter. In order to avoid that scenario, Johnson ultimately relied on Democratic votes just like McCarthy did to ensure a short-term funding bill could pass.
</p>
<h3 id="Telh9E">
What does it mean that Democrats are bailing out the House GOP?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JLI3kk">
In a sign of the ongoing fracturing among House Republicans — and opposition to spending by the party’s right flank — 106 GOP members voted against the short-term spending legislation backed by their leadership on Thursday.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OeZU9B">
This dynamic underscores how divided House Republicans continue to be, and the power that Democrats have to make or break certain votes. Democrats did not reportedly extract any major concessions from Johnson in exchange for their support to keep the government open, since lawmakers were hoping to avoid a shutdown. If Johnson continues to rely on their backing, however, it’s possible that they could make such demands.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tC3Kft">
By working with Democrats, Johnson, like his predecessor, also jeopardizes his support from his own conference, particularly from more conservative members who are irked about the partnership. If they were to abandon him, that would plunge the House (and the government funding process) into chaos. Again.
</p>
<h3 id="0DMYeQ">
What’s next?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sas2BK">
The short-term spending bill sets new spending deadlines for Congress with funding for some agencies — including the Agriculture Department, Transportation Department, and Energy Department — expiring on March 1 and funding for the remaining agencies expiring on March 8. We’ll probably revisit the question of whether there will be a government shutdown once more around that time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a0fOJe">
Lawmakers have said they hope to wrap the full-year spending bills by then. Thus far, the House and Senate have reached a deal on how much non-defense and defense spending levels should be for 2024, <a href="https://www.npr.org/2024/01/08/1223445221/up-first-briefing-congress-avoids-government-shutdown-lloyd-austins-hospital-sta">$886 billion and $704 billion respectively</a>, but they still need to hammer out the specifics for how much particular agencies and programs should receive.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZDV8ps">
Congress also has the potential to do yet another CR ahead of the March deadline, but it runs the risk of activating a 1 percent across-the-board spending cut if it hasn’t passed full-year spending bills by April 30. An agreement lawmakers previously inked on the <a href="https://www.vox.com/2023/5/9/23715753/debt-ceiling-limit-default-deal-crisis">debt ceiling</a> included this spending cut in order to motivate Congress to get its work done more quickly. If lawmakers don’t approve full-year spending bills by April 30, agencies will have to navigate how they’d cut back on their spending to meet the 1 percent threshold.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gw38U0">
Complicating all of this is that Johnson could face threats to his speakership.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ULqmRi">
It doesn’t appear that most Republicans want to wade back into the mess caused by McCarthy’s ouster, and there’s no clear candidate to replace Johnson if the party got rid of him. But <a href="https://www.politico.com/live-updates/2024/01/10/congress/conservatives-blast-johnson-00134782">conservatives are very angry with him</a> over his decision to use a CR and to work with Democrats. And some in his caucus, including <a href="https://thehill.com/homenews/house/4416370-shutdown-funding-house-biden/">Texas Rep. Chip Roy and Georgia Rep. Marjorie Taylor Greene</a> have signaled willingness to depose him, just like McCarthy.
</p>
<h3 id="i1Mak0">
Can we stop this cycle of almost shutting down?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aqoc14">
Congress absolutely has the tools to prevent future shutdowns but is hesitant to use them, in part because some of the options have their own downsides.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UH5L7y">
First, lawmakers could simply pass spending legislation on time and stop using it as a political cudgel, an unlikely prospect. Second, there have been bills proposed that would impose an automatic continuing resolution if Congress doesn’t manage to approve full-year bills in time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qONRqh">
A past measure from Sen. Mark Warner (D-VA), for example, would have guaranteed the automatic institution of a new CR any time Congress missed a deadline and simultaneously halted funding to the executive and legislative branches in order to incentivize lawmakers to take action on full-year bills.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mLVLpL">
The disadvantage of an approach like this is that the knowledge that there’s a CR waiting in the wings could deter lawmakers from negotiating on annual spending levels and providing resources to new programs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1Q5PIZ">
Because Congress is forced to compromise on spending bills under the current system, lawmakers have to engage with how government programs are being funded on an annual basis, something that could be lost if the approval of such measures is automated.
</p></li>
<li><strong>Vox podcasts tackle the Israel-Hamas war</strong> -
<figure>
<img alt="Orange glowing lights blaze in the night sky over a dark city skyline." src="https://cdn.vox-cdn.com/thumbor/szI7HHbPMHFKWkg3MZu8sG8kXdc=/107x0:1814x1280/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72847308/AP23310764413057.0.jpg"/>
<figcaption>
Israeli forces’ flares light up the night sky in Gaza City on November 6, 2023. | Abed Khaled/AP
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Looking to understand the Israel-Hamas war? Start with these Vox podcast episodes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hruIUo">
The Israel-Palestine conflict goes back decades, but this <a href="https://www.vox.com/2023/10/7/23907683/israel-hamas-war-news-updates-october-2023">latest war</a> has taken <a href="https://apnews.com/article/israel-hamas-war-news-11-6-2023-51286d15dddd77ae0dd7ea76ee52bc71">an unprecedented toll in terms of the number of people killed</a>, and represents a significant step back from any hopes of securing a two-state solution and a permanent peace. <a href="https://www.vox.com/pages/podcasts">Vox podcasts</a> are covering the conflict in depth, offering our listeners context and clarity about the history of the conflict, a deeper understanding of the players in Israel and Palestine and on the world stage, and the toll of Hamas’s attack and Israel’s retaliation on the people in the region.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MnBYNc">
<a href="https://vox.com/todayexplained"><em>Today, Explained</em></a>,<strong> </strong>Vox’s daily news explainer podcast, has been covering the conflict since it began,<strong> </strong>with an episode posted right after Hamas’s <a href="https://www.vox.com/2023/10/7/23907683/israel-hamas-war-news-updates-october-2023">October 7 attack on Israel</a> that took the lives of around 1,200 people and resulted in the kidnapping of an estimated 240 hostages. The show has since continued to cover many threads in this story, from<strong> </strong>where Hamas comes from to<strong> </strong>how false information about the conflict has spread on social media and how information warfare is used in the Middle East. Vox podcasts <a href="https://www.vox.com/the-weeds"><em>The Weeds</em></a> and <a href="https://www.vox.com/the-gray-area"><em>The Gray Area</em></a> have also been covering the unfolding crisis, its stakes, and its impact.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2kKr31">
You can find those and all our other episodes on the topic below; we’ll continue to add more as new episodes are published.
</p>
<hr class="p-entry-hr" id="RGqWVo"/>
<h3 id="woPdiu">
How the war in Gaza ends
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wK2sNB">
<a href="https://podcasts.apple.com/us/podcast/how-the-war-in-gaza-ends/id1346207297?i=1000642138582">January 18, 2024</a> | Israel’s war against Hamas has now been raging for over 100 days. According to Ian Lustick, professor emeritus at the University of Pennsylvania, history tells us what it will take to end it.
</p>
<div id="SJLUcy">
</div>
<h3 id="asQmed">
Israel’s next move
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QBV4Pr">
<a href="https://link.chtbl.com/IsraelsNextMove">January 3, 2023</a> | Israeli Prime Minister Benjamin Netanyahu faces trouble at home and abroad. AP correspondent Tia Goldenberg and scholar Hussein Ibish explain the significance of a high-profile killing in Lebanon.
</p>
<div id="oVyQ9x">
</div>
<h3 id="sEM2EX">
The fight over campus antisemitism
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vPOwm3">
<a href="https://link.chtbl.com/TEXCampusAntisemitism">December 12, 2023</a> | Three elite university presidents walk into Congress for a hearing on antisemitism. Only two still have their jobs. New York magazine reporter Nia Prater tells us what happened, and a Harvard professor of Jewish history explains why he thinks resignations won’t make campuses safer.
</p>
<div id="6iFn6a">
</div>
<h3 id="00z9DI">
How Palestine went global
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M1KvMn">
<a href="https://link.chtbl.com/TEX124">December 4, 2023</a> | People with no direct connection to the Middle East have taken to seeing the Palestinian cause as an anti-colonial struggle connected to their own experience. Columbia historian Rashid Khalidi explains why “decolonization” is resonating worldwide.
</p>
<div id="FJHviO">
</div>
<h3 id="7YHBXd">
The American politics of Israel
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VFRGF2">
<a href="https://link.chtbl.com/TEXIsraelPolitics">November 29, 2023</a> | The Israel-Hamas war is dividing the previously united Democrats and uniting the recently fractured Republican Party. Semafor’s David Weigel explains what that means going into 2024.
</p>
<div id="Iwx2oi">
</div>
<h3 id="01MAY0">
The hostage deal (brought to you by Qatar)
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GRrFTr">
<a href="https://link.chtbl.com/TEXHostageDeal">November 27, 2023</a> | After 50 days of the Israel-Hamas war, both sides took a breather to save lives. And it couldn’t have happened without Qatar.
</p>
<div id="2NKTTW">
</div>
<h3 id="XW3Wm8">
Inside the occupied West Bank
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8hpwWy">
<a href="https://link.chtbl.com/TEXWestBank">November 20, 2023</a> | With the world focused on Gaza, Israeli settlers and soldiers are increasing attacks on Palestinians in the West Bank. Writer Nathan Thrall and journalist Dalia Hatuqa explain the decades of tension that shape life in the West Bank.
</p>
<div id="mgBn6Z">
</div>
<h3 id="UtoCGa">
A call from Gaza
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="faJMeF">
<a href="https://link.chtbl.com/TEXCallFromGaza">November 14, 2023</a> | People are desperately trying to escape Gaza as the siege on the strip continues. Mohammed Ghalaieny, a Palestinian British man, tells us why he is choosing to stay, even as other foreign nationals escape through the Rafah border crossing with Egypt.
</p>
<div id="YjDHNi">
</div>
<h3 id="eAjDEC">
A Jew and a Muslim get honest about Israel and Gaza
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WCxb8i">
<a href="https://link.chtbl.com/GrayArea1113">November 13, 2023</a> | <a href="https://www.vox.com/authors/zack-beauchamp">Zack Beauchamp</a>, a Vox senior correspondent who writes about democracy and Israel, speaks with Shadi Hamid, a columnist at the Washington Post, research professor of Islamic studies at Fuller Seminary, and author of<em> The Problem of Democracy: America, the Middle East, and the Rise and Fall of an Idea</em>. They discuss the October 7 attack, the subsequent war in Gaza, what it means for Israelis and Palestinians, and how Jews and Muslims in the United States can find common ground amid their communities’ grief. This conversation was recorded on November 2, 2023.
</p>
<div id="VYKxSV">
</div>
<h3 id="EHONIG">
BDS and the history of the boycott
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BmwHyD">
<a href="https://link.chtbl.com/WeedsBDS">November 8, 2023</a> | If you turn on the news or scroll through your social media feed of choice, there’s a good chance you’ll see the latest on the Israel-Hamas war — and the reaction to it. But there’s one call to action making its way down social media feeds that feels different from all these other responses. It’s called <a href="https://www.vox.com/world-politics/23935054/boycott-movement-palestine-against-israel-bds">BDS, short for boycott, divest, and sanction</a>. And like just about everything related to this conflict, it’s complicated and controversial. <a href="https://www.vox.com/the-weeds"><em>The Weeds</em></a> host <a href="https://www.vox.com/authors/jonquilyn-hill">Jonquilyn Hill</a> sits down with Vox senior reporter <a href="https://www.vox.com/authors/whizy-kim">Whizy Kim</a> to explain the controversial movement, and with Cornell professor and author of <em>Buying Power: A History of Consumer Activism in America</em> Lawrence B. Glickman to discuss the history of boycotts and whether they even work.
</p>
<div id="W9bkwx">
</div>
<h3 id="eCQMxj">
Ceasefire?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0njnUb">
<a href="https://link.chtbl.com/TEXCeasefire">November 8, 2023</a> | Protesters, politicians, and the pope are <a href="https://www.vox.com/world-politics/2023/11/9/23953714/biden-campaign-alumni-want-gaza-ceasefire-state-department-dissent-memo">calling for a ceasefire in the Israel-Hamas war</a>, but the US and Israeli governments remain opposed. Vox’s Jonathan Guyer and Jon B. Alterman from the Center for Strategic and International Studies explain what happens next.
</p>
<div id="qI0QXG">
</div>
<h3 id="7PpXDq">
The view from Israel
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nWyxFA">
<a href="https://link.chtbl.com/TEXviewfromisrael">November 2, 2023</a> | Israelis overwhelmingly disapprove of their government’s handling of the October 7 attacks, but their desire for unity keeps Prime Minister <a href="https://www.vox.com/23910085/netanyahu-israel-right-hamas-gaza-war-history">Benjamin Netanyahu</a> in power. Michael Koplow of the Israel Policy Forum explains what Israel’s government should do next, and professor Noah Efron of Bar-Ilan University describes the mood among Israelis.
</p>
<div id="VUWe5b">
</div>
<h3 id="LW92hD">
Gaza’s humanitarian crisis
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="X9Ru7m">
<a href="https://link.chtbl.com/TEXgazacrisis">October 30, 2023</a> | Cut off from water and power and recovering from a communications blackout, Gaza is plunged deeper into crisis. It’s not just a humanitarian problem, says leading human rights attorney Kenneth Roth — it’s a violation of international law.
</p>
<div id="PIruUH">
</div>
<h3 id="YuKMW7">
Why does the US always side with Israel?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cKU4E4">
<a href="https://link.chtbl.com/TEXisraellistenerQs">October 25, 2023</a> | This was the top question we got when we asked <a href="https://www.vox.com/today-explained-podcast"><em>Today, Explained</em></a> listeners hat they wanted to know about this conflict. Joel Beinin, Middle East history professor emeritus at Stanford, has answers.
</p>
<div id="vAxsQA">
</div>
<h3 id="tUX2Xg">
Hearts, minds, and likes
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sufAJi">
<a href="https://link.chtbl.com/TEXheartsmindslikes">October 23, 2023</a> | False information about what is happening in Israel and Gaza is taking over social media faster than journalists like BBC Verify’s Shayan Sardarizadeh can check it. That’s exactly how digital propagandists want it, says professor and social media expert Marc Owen Jones.
</p>
<div id="IFsoiN">
</div>
<h3 id="u8x3t1">
Biden goes to Israel
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ubWEil">
<a href="https://link.chtbl.com/TEXbidenisrael">October 18, 2023</a> | It’s been 11 days since Hamas attacked Israel, killing civilians and taking hostages. Israel’s retaliation has killed hundreds of Palestinians and created a humanitarian crisis in Gaza. Senior fellow at the Carnegie Endowment Aaron David Miller and Middle East analyst Michael Wahid Hanna explain what role diplomacy will play in the coming days.
</p>
<div id="YOjqzu">
</div>
<h3 id="zsE1x2">
How Palestinians view Hamas
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gvB3t6">
<a href="https://link.chtbl.com/TEXpalestiniansviewhamas">October 16, 2023</a> | The US along with Israel and many of its allies have long considered Hamas a terrorist group. Khaled Al-Hroub, a professor at Northwestern University in Qatar, explains how its reputation is a lot murkier among Palestinians, who elected the group to political power in 2006.
</p>
<div id="Uc1VlQ">
</div>
<h3 id="8vk1M3">
Israel, Hamas, and how we got here
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="56kmG2">
<a href="https://link.chtbl.com/TEXIsraelHamas">October 10, 2023</a> | This Israel-Hamas war is unlike the ones that came before it, says Haaretz’s Allison Kaplan Sommer. But it was years in the making, says Vox’s Zack Beauchamp.
</p>
<div id="SWtk9m">
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cuDbml">
</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>AIFF league committee suggests promotion-relegation system in IWL</strong> - The committee also examined the proposed calendar for the AIFF Club competitions starting from the 2024-25 season</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>Mother-daughter duo guns for glory beyond Meghalaya Games</strong> - Daughter Toiaibha’s bronze in the 10m air pistol event has made Marbarisha target a podium finish at the next event</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two ex-Indian footballers from Kerala to set off on odyssey across tribal pockets with the goal of kick-starting academies</strong> - Campaign ‘Soccer Safari – Exploring India’s Football Heartlands’, jointly organised by Thirteenth Foundation and Plan D Trips, is likely to be flagged off by actor Mammootty later in January</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Australian Open | Defending champ Sabalenka crushes Tsurenko to reach 4th round</strong> - The second-seeded Belarusian, who won her first Grand Slam title at the same venue 12 months ago, needed just 52 minutes for victory over the Ukranian Lesia Tsurenko</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>AFC Asian Cup | Uzbekistan brushes aside a lacklustre India with 3-0 win</strong> - The loss leaves India’s chances of progressing past the group stage to a miracle</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MEDISEP: Finance department issues new orders on deducting ‘arrears on premium’</strong> - For new employees, the ‘arrears on premium’ from July 1, 2022, will be deducted in equal installments from their first salary onwards</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>Govt. teachers take out rally seeking payment of arrears</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>Here are the big stories from Karnataka today</strong> - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated and written by Nalme Nachiyar.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Srikakulam artist showcases talent with a miniature painting of Ayodhya Ram’s temple</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>NASA spacecraft pings India’s Chandrayaan-3 lander on the moon</strong> - “We’ve showed that we can locate our retroreflector on the surface from the moon’s orbit.“</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Russian oil depot hit in Ukrainian drone attack</strong> - Fire breaks out over a large area in the Bryansk region, a day after another oil facility is targeted.</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>Bay of Biscay: France temporarily bans fishing to protect dolphins</strong> - The move comes after pressure from conservation groups, but local fishermen have called it “absurd”.</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>Georgia: Stalin Icon removed from Tbilisi church</strong> - The icon showed the Soviet dictator being blessed by a saint, but the Church says it has to be changed.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Russian dog-lovers fight to save strays from cull in Siberia’s Ulan-Ude</strong> - Eighteen have been put down in Siberia’s UIan-Ude but hundreds are sent on trains to safety.</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>Olympic Finnish sauna in Kent given Grade II listed status</strong> - Historic England says the sauna, gifted after the 1948 Olympic Games, is a “remarkable survival”.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Axiom, SpaceX launch third all-private crew mission to space station</strong> - A US-Spanish dual citizen commands a crew of Italian, Swedish, and Turkish astronauts. - <a href="https://arstechnica.com/?p=1997288">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DeepMind AI rivals the world’s smartest high schoolers at geometry</strong> - DeepMind solved 25 out of 30 questions—compared to 26 for a human gold medalist. - <a href="https://arstechnica.com/?p=1997186">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Zuckerberg’s AGI remarks follow trend of downplaying AI dangers</strong> - Zuckeberg and Altman both tamp down fear and hype with casual statements about AGI. - <a href="https://arstechnica.com/?p=1997158">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Amazon plans to charge for Alexa in June—unless internal conflict delays revamp</strong> - Report claims Amazon is struggling to build a subscription version of Alexa. - <a href="https://arstechnica.com/?p=1997184">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Indiana Jones and the Great Circle is a new first-person Nazi-whipping journey</strong> - Modern action/FPS is set inside Indy’s classic post-<em>Ark</em>, pre-<em>Crusade</em> era. - <a href="https://arstechnica.com/?p=1997200">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>Five pigs walk into a bar. The first pig orders one beer, the second pig orders two beers, the third pig orders three beers, the fourth pig orders four beers, and the fifth pig orders five beers.</strong> - <!-- SC_OFF --></p>
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The first pig drinks his beer, goes to the bathroom, and leaves. The second pig drinks both his beers, goes to the bathroom, and leaves. The third pig drinks all three of his beers, goes to the bathroom, and leaves. The fourth pig drinks all four of his beers, goes to the bathroom, and leaves. The fifth pig drinks all five of his beers, and then leaves without going to the bathroom.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Wait a minute!” says the bartender. “Why aren’t you going to the bathroom like your four friends did? I mean, you drank more beer than any of them!”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Because,” says the pig. “I’m the pig that goes wee wee wee all the way home.”
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/wimpykidfan37"> /u/wimpykidfan37 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/199xx4q/five_pigs_walk_into_a_bar_the_first_pig_orders/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/199xx4q/five_pigs_walk_into_a_bar_the_first_pig_orders/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Roosevelt, Churchill, and Stalin, meet on a skyscraper…</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
My father told me this joke today, thought I’d share:
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Roosevelt, Churchill, and Stalin want to prove that their generals have a larger sense of duty and tenacity compared to the other nations’ soldiers. So they all meet on top of a skyscraper.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Roosevelt goes first, and orders his finest general to jump off the ledge, stating that it was for God and country. The general, states " Sir, you are the greatest president this country has seen, but I cannot jump over the ledge, I have a family to think of!"
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Churchill goes second, and orders his finest general to jump off the ledge, stating that it was for God and country. The general, states " Sir, you are the greatest prime minister and have bravely led us through hell and back, but I cannot jump over the ledge, I have a family to think of!"
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Stalin goes last, and orders his finest general to jump off the ledge, stating that it was for the greater good of the Soviet state. The general immediately jumps off the ledge, and is caught by a net a few stories down, where he is met by the three leaders.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Roosevelt and Churchill ask the Soviet general, “Why’d you jump?” The soldier grimly replies: “I have a family to think of.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Playful-Arm-674"> /u/Playful-Arm-674 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/19a9tgs/roosevelt_churchill_and_stalin_meet_on_a/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/19a9tgs/roosevelt_churchill_and_stalin_meet_on_a/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A woman and a dress</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A woman was cleaning her closet and came across her old wedding dress. The dress was custom-made and very ornate - it was also one of the only items the woman had kept after her husband passed away.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
While cleaning, a hangar caught on one of the hems of the dress and ripped a large hole. Horrified, the woman dropped what she was doing, grabbed the dress, and ran to the tailor to have it fixed.
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Upon arriving at the tailor, she tells him she will pay any cost to repair the dress. The tailor replies, “Ah, I am so sorry but this dress is quite the work of art and repairing it is beyond my skill set. In fact, I know of only one man in the world equal to the task. However, you likely won’t want to go to him, as he lives in Greece.”
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Frantic and distressed that she may have ruined such a sentimental item, she demanded to know how she could find this legendary tailor.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man told her that he was named Euripides and lived on the Isle of Crete, but that he was reclusive and did not have any modern means of communication. He only serviced customers who came to his store - in person.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Frustrated but determined, the woman bought a plane ticket to Greece and caught a ferry to Crete. She asked locals where she could find the legendary tailor and eventually, after many days of searching, arrived at what she was sure was his humble storefront.
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Upon entering, she nearly shouts at the man, “Please… PLEASE tell me you are the legendary tailor, Euripides.”
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In a heavy Greek accent he replies, “Ahhh, I do believe I am who you seek, child. However, that is not my name. I am Iamenides”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
At this, the woman becomes hysterical. Sobbing, she replies, “No. NO! I was told only ONE man could fix my dress and THAT man is EURIPIDES!”
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Calmly, the man replies, "You misunderstand, my friend…
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
YOU-rip-a-dese, and I-a-mend-a-dese."
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Tjohn184"> /u/Tjohn184 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/19a8wha/a_woman_and_a_dress/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/19a8wha/a_woman_and_a_dress/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A world championship of pickpockets.</strong> - <!-- SC_OFF --></p>
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The final round. A pavillion is full of people wanting to see the three sets of finalists in action.
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The first two go on stage:
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<strong>Pickpocket</strong>: Bonjour everyone. We are Jean and Alain, the best pickpockets in France. Please turn off the lights for one minute.
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The lights go off for one minute.
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<strong>Jean</strong>: Gentleman at row eight, seat twelve, please come here to take back your pocketwatch and your pen.
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A round of applause.
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The next two contestants go on stage.
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<strong>Pickpocket</strong>: Good day everyone. We are Tommy and Joe, the best pickpockets in USA. Turn off the lights for half a minute.
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Once the lights come back:
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<strong>Tommy</strong>: Lady at row ten, seat six, come here for your purse, your necklace, you earrings and your wristwatch.
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A wild and long round of applause.
</p>
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The final two contestants go on stage:
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<strong>Pickpocket</strong>: Hello guys. We are the best pickpockets in Russia. I am Petya. No need to turn off the lights. Vasya, give everyone their socks back.
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Omeganian"> /u/Omeganian </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/19ab3em/a_world_championship_of_pickpockets/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/19ab3em/a_world_championship_of_pickpockets/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Stuttering</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A man had a bad case of stuttering. He went to many doctors over the years, but none of them could help him. Finally, one doctor said to him, ‘I believe I found the reason for your stuttering.’
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man asked, ‘Waah.. waaah.. waah.. what is my pro… proo… problem?’
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The doctor replied, ‘Your penis is very, very large. The weight of your penis is causing a strain on your larynx, and this results in your stuttering. The only solution to this is to perform a penis transplant.’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man was really tired of his stuttering, so he agreed to a transplant. Several days later, the doctor called the man up and informed him that they had found a suitable donor. The transplant operation was successfully performed and the man could speak without any stutter.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
At first, he was happy, but after a while, he began to miss his large penis, and how the girls used to love it.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He finally went back to his doctor and said, ‘Doctor, I am grateful for the opportunity you have given me to speak without a stutter, but I miss my old penis. Please find the transplant donor and tell him that we have to exchange penises back.’
</p>
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The doctor shook his head and replied, ‘N…n…no w…w…way!’
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Just_Sarah82"> /u/Just_Sarah82 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/19ag5a4/stuttering/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/19ag5a4/stuttering/">[comments]</a></span></p></li>
</ul>
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