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<title>24 November, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>REPORT : Study on ‘Institutionalizing Science Advice to Governments</strong> -
<div>
The provision of appropriate science advice to governments is of national, regional, and global importance. However, many countries, especially in the developing world, lack effective framework to provide science advice to governments, which was laid bare during the COVID-19 pandemic. Hence, there is an urgent need to describe and analyse the structures and processes providing science advice to governments with a view to strengthening science advice. Science advice requires synthesizing and brokering valid, relevant, and reliable scientific evidence in respect of different policies. The National Academy of Sciences of Sri Lanka conducted a study on the status and processes of institutionalizing Science Advice to Governments in the Australasian region. The aims of the study were to a) propose and facilitate the development and strengthening of systematic science advice in member countries and its institutionalization b) Improve awareness among partners on a range of laws and regulations that exist legitimizing institutions and the processes used for government science advice c) develop capacities of participating academies in providing science advice d) enable academies to play a role and be part of the science advice process The methodology included administration of a structured questionnaire to gather data for the Situation Analysis with respect to science advice in partner countries. The questionnaire responses were categorized under several headings identified as the ‘Colombo Framework’: Selection of advisors, organizational structures to provide advice, the process followed to collate and synthesize advice, the process of communication, and evaluation of the process and impact of advice. The results showed a diversity of responses indicating a range of structures and processes: • The structures and types of advisors included, chief science advisor or advisors, a science advisory office or agency, science advisory boards, science advisory councils and ad-hoc arrangements during emergencies or crises, such as task forces. • Selection of advisors varied from appointments by an executive authority to nominations by science organizations or selection processes based on academic credentials. • The initial framing of questions requiring science advice were by policymakers, parliament committee or the President and advisory council. • Collation and synthesizing evidence: The methods used included systematic reviews, meta-analyses, through surveys, consultative meetings, expert opinion, foresight tools and workshops and/meetings of the experts where the evidence was reviewed. • The process of communicating science advice included reports issued by the science advisors, or advice directed to the Presidential Office, to Cabinet office, or submitted through Secretary of the Ministry of Science and Technology to the Head of State, or reports to the relevant minister and presidential secretariat. • The impact of science advice on policy was rarely evaluated. • Case Studies for individual countries supplemented the situation analysis for that country. • A SWOT analyses was compiled based on each country responses to reflect the totality of responses and for guidance in drafting a framework for Roadmaps for each country. As part of the project a three-day workshop was held in Colombo, Sri Lanka on ‘Institutionalizing Science Advice to Governments’ 6-8 July 2023. A descriptive ‘Colombo Declaration’ was released calling on governments to partner with scientists and demonstrate stronger commitment in strengthening action to institutionalize science advice to governments. The concluding session described future actions of developing Roadmaps and Case Studies by each partner country. The contextualized roadmaps will be developed through an iterative process and ‘work in progress’ submitted by most partner agencies were included in the report. The key outcomes of the Project were the following: 1. Documentation of Science Advice Systems in countries with situation analysis, reinforced with case studies and SWOT analyses and a framework for contextualized roadmaps that could form the foundation for further activities with support from the IAP and AASSA. 2. Developed and disseminated the ‘Colombo Declaration’ calling on governments to institutionalize science advice 3. Availability of validated questionnaire and framework (‘Colombo framework’) to replicate similar studies elsewhere. 4. Development of a process for promotion of institutionalization of science advice to governments that could be replicated in other countries or regions. 5. Promoted awareness among public, public administrators and policymakers and younger generation of scientists to be part of this transformative process, particularly to ensure continuity of efforts. 6. Contextualized Roadmaps design process has been initiated that is meant to trigger further discussions.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/ygp84/" target="_blank">REPORT : Study on ‘Institutionalizing Science Advice to Governments</a>
</div></li>
<li><strong>DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 Labour Markets. Report on Serbia</strong> -
<div>
The aim of this country report is to provide answers to the following DEFEN-CE research questions: 1. What public policy and social dialogue measures targeting the selected vulnerable groups were implemented to employment and social protection during the COVID-19 pandemic 2020-2022? 2. To what extent and how did social dialogue play a role in the implementation of social and employment rights of selected vulnerable groups in the COVID-19 pandemic between 2020 and 2022? 3. What lessons and opportunities does the COVID-19 pandemic yield for strengthening social dialogue in the studied countries? In order to answer these questions we used a mixed-method approach, combining qualitative and quantitative techniques. We started with the collection of the most relevant labour market data, especially regarding vulnerable groups. Then, by using the desk research we were able to synthesize the existing knowledge on public policies and social dialogue in the COVID-19 crisis. Finally, we conducted 10 semi-structured interviews to explore in-depth the role of social partners in the defence of the vulnerable groups.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/gh9mn/" target="_blank">DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 Labour Markets. Report on Serbia</a>
</div></li>
<li><strong>Gaining Biological Insights through Supervised Data Visualization</strong> -
<div>
Dimensionality reduction-based data visualization is pivotal in comprehending complex biological data. The most common methods, such as PHATE, t-SNE, and UMAP, are unsupervised and therefore reflect the dominant structure in the data, which may be independent of expert-provided labels. Here we introduce a supervised data visualization method called RF-PHATE, which integrates expert knowledge for further exploration of the data. RF-PHATE leverages random forests to capture intricate feature-label relationships. Extracting information from the forest, RF-PHATE generates low-dimensional visualizations that highlight relevant data relationships while disregarding extraneous features. This approach scales to large datasets and applies to classification and regression. We illustrate RF-PHATE's prowess through three case studies. In a multiple sclerosis study using longitudinal clinical and imaging data, RF-PHATE unveils a sub-group of patients with non-benign relapsing-remitting Multiple Sclerosis, demonstrating its aptitude for time-series data. In the context of Raman spectral data, RF-PHATE effectively showcases the impact of antioxidants on diesel exhaust-exposed lung cells, highlighting its proficiency in noisy environments. Furthermore, RF-PHATE aligns established geometric structures with COVID-19 patient outcomes, enriching interpretability in a hierarchical manner.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568384v1" target="_blank">Gaining Biological Insights through Supervised Data Visualization</a>
</div></li>
<li><strong>scSniper: Single-cell Deep Neural Network-based Identification of Prominent Biomarkers</strong> -
<div>
Discovering disease biomarkers at the single-cell level is crucial for advancing our understanding of diseases and improving diagnostic accuracy. However, current computational methods often have limitations, such as a reliance on prior knowledge, constraints to unimodal data, and the use of conventional statistical tests for feature selection. To address these issues, we introduce scSniper, a novel approach that employs a specialized deep neural network framework tailored for robust single-cell multi-omic biomarker detection. A standout feature of scSniper is the mimetic attention block, enhancing alignment across multi-modal data types. Moreover, scSniper utilizes sensitivity analysis based on a deep neural network for feature selection and uncovers intricate gene regulatory networks without requiring prior knowledge. Comprehensive evaluations on real-world datasets, including COVID-19 CITE-Seq and LUAD scRNA-Seq, demonstrate scSniper's exceptional ability to identify critical biomarkers consistently outperforming traditional methods like MAST, Wilcox, and DESeq2.The scSniper tool and related experimental codes are publicly accessible at https://github.com/mcgilldinglab/scSniper.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568389v1" target="_blank">scSniper: Single-cell Deep Neural Network-based Identification of Prominent Biomarkers</a>
</div></li>
<li><strong>Enhanced surface accessibility of SARS-CoV-2 Omicron spike protein due to an altered glycosylation profile</strong> -
<div>
SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics and disulfide bonding of recombinant spike proteins derived from the SARS-CoV-2 Omicron variant (B.1.1.529) in comparison with the D614G spike variant. Furthermore, we conducted microsecond-long molecular dynamics simulations on spike proteins to resolve how the different N-glycans impact spike conformational sampling in the two variants. Our findings reveal that the Omicron spike protein maintains an overall resemblance to the D614G spike variant in terms of site-specific glycan processing and disulfide bond formation. Nonetheless, alterations in glycans were observed at certain N-glycosylation sites. These changes, in synergy with mutations within the Omicron spike protein, result in increased surface accessibility of the macromolecule, including ectodomain, receptor-binding domain, and N-terminal domain. These insights contribute to our understanding of the interplay between structure and function, thereby advancing effective vaccination and therapeutic strategies.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568381v1" target="_blank">Enhanced surface accessibility of SARS-CoV-2 Omicron spike protein due to an altered glycosylation profile</a>
</div></li>
<li><strong>Assembly reactions of SARS-CoV-2 nucleocapsid protein with nucleic acid</strong> -
<div>
The viral genome of SARS-CoV-2 is packaged by the nucleocapsid (N-)protein into ribonucleoprotein particles (RNPs), 38+/-10 of which are contained in each virion. Their architecture has remained unclear due to the pleomorphism of RNPs, the high flexibility of N-protein intrinsically disordered regions, and highly multivalent interactions between viral RNA and N-protein binding sites in both N-terminal (NTD) and C-terminal domain (CTD). Here we explore critical interaction motifs of RNPs by applying a combination of biophysical techniques to mutant proteins binding different nucleic acids in an in vitro assay for RNP formation, and by examining mutant proteins in a viral assembly assay. We find that nucleic acid-bound N-protein dimers oligomerize via a recently described protein-protein interface presented by a transient helix in its long disordered linker region between NTD and CTD. The resulting hexameric complexes are stabilized by multi-valent protein-nucleic acid interactions that establish crosslinks between dimeric subunits. Assemblies are stabilized by the dimeric CTD of N-protein offering more than one binding site for stem-loop RNA. Our study suggests a model for RNP assembly where N-protein scaffolding at high density on viral RNA is followed by cooperative multimerization through protein-protein interactions in the disordered linker.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568361v1" target="_blank">Assembly reactions of SARS-CoV-2 nucleocapsid protein with nucleic acid</a>
</div></li>
<li><strong>Predicting Antibody and ACE2 Affinity forSARS-CoV-2 BA.2.86 with In Silico ProteinModeling and Docking</strong> -
<div>
The emergence of the Omicron sublineage of SARS-CoV-2 virus BA.2.86 (nicknamed "Pirola") has raised concerns about its potential impact on public health and personal health as it has many mutations with respect to previous variants. We conducted an in silico analysis of neutralizing antibody binding to BA.2.86. Selected antibodies came from patients who were vaccinated and/or infected. We predicted binding affinity between BA.2.86 and antibodies. We also predicted the binding affinity between the same antibodies and several previous SARS-CoV2 variants (Wuhan and Omicron descendants BA.1, BA.2, and XBB.1.5). Additionally, we examined binding affinity between BA.2.86 and human angiotensin converting enzyme 2 (ACE2) receptor, a cell surface protein crucial for viral entry. We found no statistically significant difference in binding affinity between BA.2.86 and other variants, indicating a similar immune response. These findings contradict media reports of BA.2.86's high immune evasion potential based on its mutations. We discuss the implications of our findings and highlight the need for modeling and docking studies to go above and beyond mutation and basic serological neutralization analysis. Future research in this area will benefit from increased structural analyses of memory B-cell derived antibodies and should emphasize the importance of choosing appropriate samples for in silico studies to assess protection provided by vaccination and infection. This research contributes to understanding the BA.2.86 variant's potential impact on public health. Moreover, we introduce new methodologies for predictive medicine in ongoing efforts to combat the evolving SARS-CoV-2 pandemic and prepare for other hazards.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568364v1" target="_blank">Predicting Antibody and ACE2 Affinity forSARS-CoV-2 BA.2.86 with In Silico ProteinModeling and Docking</a>
</div></li>
<li><strong>Development of attenuated coxsackievirus B3 vectored intranasal pre-emptive pan-coronavirus vaccine</strong> -
<div>
SARS-CoV-2 has the ability to evade immunity, resulting in breakthrough infections even after vaccination. Similarly, zoonotic coronaviruses pose a risk of spillover to humans. There is an urgent need to develop a pre-emptive pan-coronavirus vaccine that can induce systemic and mucosal immunity. Here, we employed a combination of immune-informatics approaches to identify shared immunodominant linear B- and T-cell epitopes from SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs), as well as zoonotic coronaviruses. Epitope-guided vaccine were designed and the attenuated coxsackievirus B3 vectored intranasal vaccines rCVB3-EPI and rCVB3-RBD-trimer were constructed. The immunogenicity of these candidate vaccines was evaluated using Balb/c mice. The results demonstrated effective immune responses, including the production of SARS-CoV-2-specific IgG and sIgA antibodies, as well as T cell-mediated responses. However, further verification is required to assess cross-reactivity with various variants. Our intranasal pre-emptive pan-coronavirus vaccine design framework offers an appealing candidate for future vaccine development.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568225v1" target="_blank">Development of attenuated coxsackievirus B3 vectored intranasal pre-emptive pan-coronavirus vaccine</a>
</div></li>
<li><strong>Building energy use in COVID-19 lockdowns: did much change?</strong> -
<div>
The UK national lockdowns introduced to prevent the spread of COVID-19 had huge impacts on daily lives, as people were largely confined to their homes. It could be expected that residential energy use would drastically increase while non-residential decreased, however the picture is not so clear. In this paper three complementary datasets on different scales are used to explore changes in building energy use during two national lockdowns (spring 2020 and winter 2021): the complete building stock of Great Britain, a sample of ~1000 residential buildings, and a sample of ~24,000 residential boilers. Energy signature analysis was used for the building data to estimate the changes in energy consumption for space heating and otherwise, with the boiler data able to separate space and water heating and explore changes in these. In the 2020 lockdown residential energy consumption for water heating and appliances increased, with decreased use for heating, resulting in a reduction in total energy use during the heating season. In the 2021 lockdown total energy consumption changed little, however a decrease in the use of gas space heating was observed. These residential changes counteracted any non-domestic changes, resulting in little difference in national energy consumption.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/cu2na/" target="_blank">Building energy use in COVID-19 lockdowns: did much change?</a>
</div></li>
<li><strong>Tertiary folds of the SL5 RNA from the 5’ proximal region of SARS-CoV-2 and related coronaviruses</strong> -
<div>
Coronavirus genomes sequester their start codons within stem-loop 5 (SL5), a structured, 5' genomic RNA element. In most alpha- and betacoronaviruses, the secondary structure of SL5 is predicted to contain a four-way junction of helical stems, some of which are capped with UUYYGU hexaloops. Here, using cryogenic electron microscopy (cryo-EM) and computational modeling with biochemically-determined secondary structures, we present three-dimensional structures of SL5 from six coronaviruses. The SL5 domain of betacoronavirus SARS-CoV-2, resolved at 4.7 [A] resolution, exhibits a T-shaped structure, with its UUYYGU hexaloops at opposing ends of a coaxial stack, the T's "bar." Further analysis of SL5 domains from SARS-CoV-1 and MERS (7.1 and 6.4-6.9 [A] resolution, respectively) indicate that the junction geometry and inter-hexaloop distances are conserved features across the studied human-infecting betacoronaviruses. The MERS SL5 domain displays an additional tertiary interaction, which is also observed in the non-human-infecting betacoronavirus BtCoV-HKU5 (5.9-8.0 [A] resolution). SL5s from human-infecting alphacoronaviruses, HCoV-229E and HCoV-NL63 (6.5 and 8.4-9.0 [A] resolution, respectively), exhibit the same coaxial stacks, including the UUYYGU-capped bar, but with a phylogenetically distinct crossing angle, an X-shape. As such, all herein studied SL5 domains fold into stable tertiary structures with cross-genus similarities, with implications for potential protein-binding modes and future therapeutic targets.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.567964v1" target="_blank">Tertiary folds of the SL5 RNA from the 5’ proximal region of SARS-CoV-2 and related coronaviruses</a>
</div></li>
<li><strong>Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model</strong> -
<div>
Since 2002, three novel coronavirus outbreaks have occurred: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. A better understanding of the transmission potential of coronaviruses will result in adequate infection control precautions and an early halt of transmission within the human population. Experiments on the stability of coronaviruses in the environment, as well as transmission models, are thus pertinent. Here, we show that transgenic mice expressing human DPP4 can be infected with MERS-CoV via the aerosol route. Exposure to 5x106 TCID50 and 5x104 TCID50 MERS-CoV per cage via fomites resulted in transmission in 15 out of 20 and 11 out of 18 animals, respectively. Exposure of sentinel mice to donor mice one day post inoculation with 105 TCID50 MERS-CoV resulted in transmission in 1 out of 38 mice via direct contact and 4 out of 54 mice via airborne contact. Exposure to donor mice inoculated with 104 TCID50 MERS-CoV resulted in transmission in 0 out of 20 pairs via direct contact and 0 out of 5 pairs via the airborne route. Our model shows limited transmission of MERS-CoV via the fomite, direct contact, and airborne routes. The hDPP4 mouse model will allow assessment of the ongoing evolution of MERS-CoV in the context of acquiring enhanced human-to-human transmission kinetics and will inform the development of other transmission models.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568286v1" target="_blank">Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model</a>
</div></li>
<li><strong>SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback</strong> -
<div>
Therapeutic anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been extensively studied in humans, but the impact on immune memory of mAb treatment during an ongoing immune response has remained unclear. Here, we evaluated the effect of infusion of the anti-SARS-CoV-2 spike receptor binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of memory B cells targeting Spike towards non-RBD epitopes. Furthermore, the relative affinity of RBD memory B cells was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA COVID-19 vaccination, memory B cell differences persisted and mapped to a specific defect in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating human memory B cell responses, both to infection and vaccination. These data indicate that mAb administration can promote alterations in the epitopes recognized by the B cell repertoire, and the single administration of mAb can continue to determine the fate of B cells in response to additional antigen exposures months later.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.21.567575v1" target="_blank">SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback</a>
</div></li>
<li><strong>Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates</strong> -
<div>
SARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there's a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.5 variant of SARS-CoV-2. A prime-boost regimen using GRAd followed by adjuvanted S-2P (GRAd+S-2P) accelerated viral clearance in both the lower and upper airways. GRAd delivered via aerosol (GRAd(AE)+S-2P) modestly improved protection compared to its matched intramuscular regimen, but showed dramatically superior boosting by mRNA and, importantly, total virus clearance in the upper airway by day 4 post infection. GrAd vaccination regimens elicited robust and durable systemic and mucosal antibody responses to multiple SARS-CoV-2 variants, but only GRAd(AE)+S-2P generated long-lasting T cell responses in the lung. This research underscores the flexibility of the GRAd vaccine platform to provide durable immunity against SARS-CoV-2 in both the lower and upper airways.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.567930v1" target="_blank">Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates</a>
</div></li>
<li><strong>Modulation of Biophysical Properties of Nucleocapsid Protein in the Mutant Spectrum of SARS-CoV-2</strong> -
<div>
Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also exhibiting functional constraints that similarly occur in related coronaviruses. In biophysical experiments with several N-protein species carrying mutations associated with major variants, we find that point mutations in the IDRs can have nonlocal impact and modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, and liquid-liquid phase separation. In the Omicron variant, distant mutations in different IDRs have compensatory effects in shifting a delicate balance of interactions controlling protein assembly properties, and include the creation of a new protein-protein interaction interface in the N-terminal IDR through the defining P13L mutation. A picture emerges where genetic diversity is accompanied by significant variation in biophysical characteristics of functional N-protein species, in particular in the IDRs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.21.568093v1" target="_blank">Modulation of Biophysical Properties of Nucleocapsid Protein in the Mutant Spectrum of SARS-CoV-2</a>
</div></li>
<li><strong>SARS-CoV-2 infects neurons, astrocytes, choroid plexus epithelial cells and pericytes of the human central nervous system</strong> -
<div>
SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, is associated with a range of neurological manifestations including haemorrhage, thrombosis and ischaemic necrosis and encephalitits. However, the mechanism by which this occurs is unclear. Neurological disease associated with SARS-CoV-2 infection has been proposed to occur following direct infection of the central nervous system and/or indirect sequelae as a result of peripheral inflammation. We profiled ACE2 and TMPRSS2 in brain tissue from five healthy human donors, and observed expression of these proteins in astrocytes, neurons and choroid plexus epithelium within frontal cortex and medulla. Primary human astrocytes, neurons and choroid plexus epithelial cells supported productive SARS-CoV-2 infection in an ACE2-dependent manner. Infected cells supported the full viral lifecycle, releasing infectious virus particles. In contrast, primary brain microvascular endothelial cells, pericytes and microglia were refractory to SARS-CoV-2 infection. These data support a model whereby SARS-CoV-2 is neurotropic, and this may in part explain the neurological sequelae of infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.21.568132v1" target="_blank">SARS-CoV-2 infects neurons, astrocytes, choroid plexus epithelial cells and pericytes of the human central nervous system</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>Collection of Additional Biological Samples From Potentially COVID-19 Patients for Monitoring of Biological Parameters Carried Out as Part of the Routine</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Diagnostic Test: RIPH2 <br/><b>Sponsors</b>: CerbaXpert <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>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19 <br/><b>Interventions</b>: Behavioral: Individual counseling; Behavioral: Group counseling; Other: Resources <br/><b>Sponsors</b>: Idaho State University <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Promoting Engagement and COVID-19 Testing for Health</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: COVID-19 Test Reporting; Behavioral: Personalized Nudges via Text Messaging; Behavioral: Non-personalized Nudges via Text Messaging <br/><b>Sponsors</b>: Emory University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Morehouse School of Medicine; Georgia Institute of Technology <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>Development and Qualification of Methods for Analyzing the Mucosal Immune Response to COVID-19</strong> - <b>Conditions</b>: Certain Disorders Involving the Immune Mechanism <br/><b>Interventions</b>: Biological: Sampling; Biological: PCR (polymerase chain reaction) SARS-CoV-2 <br/><b>Sponsors</b>: University Hospital, Tours <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>Water-based Activity to Enhance Recovery in Long COVID</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Behavioral: WATER+CT; Behavioral: Usual Care <br/><b>Sponsors</b>: VA Office of Research and Development <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>Performance Evaluation of the Lucira COVID-19 &amp; Flu Test</strong> - <b>Conditions</b>: COVID-19; Influenza <br/><b>Interventions</b>: Device: Lucira COVID-19 &amp; Flu Test <br/><b>Sponsors</b>: Lucira Health Inc <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>Efficacy of Two Therapeutic Exercise Modalities for Patients With Persistent COVID</strong> - <b>Conditions</b>: Persistent COVID-19 <br/><b>Interventions</b>: Other: exercise programe <br/><b>Sponsors</b>: Facultat de ciencies de la Salut Universitat Ramon Llull <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>Robotic Assisted Hand Rehabilitation Outcomes in Adults After COVID-19</strong> - <b>Conditions</b>: Robotic Exoskeleton; Post-acute Covid-19 Syndrome; Rehabilitation Outcome; Physical And Rehabilitation Medicine <br/><b>Interventions</b>: Device: Training with a Robotic Hand Exoskeleton <br/><b>Sponsors</b>: University of Valladolid; Centro Hospitalario Padre Benito Menni <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>Cognitive Rehabilitation in Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: CO-OP Procedures; Behavioral: Inactive Control Group <br/><b>Sponsors</b>: University of Missouri-Columbia; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) <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>Safety and Immunogenicity of BNT162b2 Coadministered With SIIV in Adults 18 Through 64 Years of Age</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19 <br/><b>Interventions</b>: Biological: BNT162b2; Other: Placebo; Biological: Seasonal Inactivated Influenza Vaccine <br/><b>Sponsors</b>: Pfizer <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>Clinical Evaluation of the Panbio™ COVID-19/Flu A&amp;B Panel</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Panbio™ <br/><b>Sponsors</b>: Abbott Rapid Dx <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>A Multicenter, Adaptive, Randomized, doublE-blinded, Placebo-controlled Study in Participants With Long COVID-19: The REVIVE Trial</strong> - <b>Conditions</b>: Long COVID-19 Syndrome; Chronic Fatigue Syndrome <br/><b>Interventions</b>: Drug: Fluvoxamine Maleate 100 MG; Drug: Placebo; Drug: Metformin Extended Release Oral Tablet <br/><b>Sponsors</b>: Cardresearch <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>Connecting Friends and Health Workers to Boost COVID-19 Vaccination in Latino Communities</strong> - <b>Conditions</b>: COVID-19; Vaccine <br/><b>Interventions</b>: Behavioral: REDES; Behavioral: Control <br/><b>Sponsors</b>: Johns Hopkins University; National Institute on Minority Health and Health Disparities (NIMHD); Rutgers 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>Influence of Hypoxic, Normobaric and Hypobaric Training on the Immunometabolism of Post-covid-19 Athletes</strong> - <b>Conditions</b>: Normobaric Hypoxia; Hypoventilation; Normoxia <br/><b>Interventions</b>: Other: Repeated sprint <br/><b>Sponsors</b>: Faculdade de Motricidade Humana; University of Sao Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Safety and Tolerability of A8G6 COVID-19 Neutralization Antibody Combined With Nasal Spray</strong> - <b>Conditions</b>: SARS-CoV-2; Prevention <br/><b>Interventions</b>: Biological: A8G6 SARS-CoV-2 Neutralization Antibody combination nasal spray; Other: A8G6 SARS-CoV-2 Neutralization Antibody nasal excipient <br/><b>Sponsors</b>: The Second Affiliated Hospital of Chongqing Medical University <br/><b>Recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Applications of peptide-functionalized or unfunctionalized selenium nanoparticles for the passivation of SARS-CoV-2 variants and the respiratory syncytial virus (RSV)</strong> - The SARS-CoV-2 Omicron subvariants BA.4, BA. 5 and XBB are currently causing a COVID resurgence due to their increased spreading and infectivity. These latest subvariants have been shown to be somewhat resistant to the most common vaccines even with the third dose. Moreover, it has been well documented that when patients stop taking some commercial therapies (such as Paxlovid), COVID from these variants may return and may even be more contagious. Herein, we tested unfunctionalized and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cellular mechanisms associated with sub-optimal immune responses to SARS-CoV-2 bivalent booster vaccination in patients with Multiple Myeloma</strong> - BACKGROUND: The real-world impact of bivalent vaccines for wild type (WA.1) and Omicron variant (BA.5) is largely unknown in immunocompromised patients with Multiple Myeloma (MM). We characterize the humoral and cellular immune responses in patients with MM before and after receiving the bivalent booster, including neutralizing assays to identify patterns associated with continuing vulnerability to current variants (XBB1.16, EG5) in the current post-pandemic era.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Role of Olive Tree Polyphenols In The Prevention of COVID-19: A Scoping Review Part 2</strong> - The recent COVID-19 pandemic caused by SARS-CoV-2 affected hundreds of millions of people and caused millions of deaths. There are few effective medications against SARS-CoV-2, and several stud-ies attempted to make drugs based on natural components, such as olive leaves. Olive leaves are rich in polyphenolic compounds, which were proposed as a viable co-therapy supplement to treat and improve clinical symptoms in COVID-19 patients. Polyphenols have renown anti-inflammatory and multitarget…</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>Drug-drug interaction between paxlovid and tacrolimus in a patient with myasthenia gravis and SARS-CoV-2 infection</strong> - Patients with both myasthenia gravis (MG) and SARS-CoV-2 infection face treatment challenges due to potential drug interactions. One common immunosuppressant for MG, Tacrolimus, is primarily metabolized by the cytochrome P450. However, Paxlovid, an antiviral medication, inhibits cytochrome P450 activity, which can lead to increased Tacrolimus levels and potential toxicity when the two drugs are combined. In this case report, we present the case of a 39-year-old woman with early-onset MG who was…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of pyrimidoindol and benzylpyrrolyl inhibitors targeting SARS-CoV-2 main protease (M<sup>pro</sup>) through pharmacophore modelling, covalent docking, and biological evaluation</strong> - The main protease (M^(pro)) enzyme has an imperative function in disease progression and the life cycle of the SARS-CoV-2 virus. Although the orally active drug nirmatrelvir (co-administered with ritonavir as paxlovid) has been approved for emergency use as the frontline antiviral agent, there are a number of limitations that necessitate the discovery of new drug scaffolds, such as poor pharmacokinetics and susceptibility to proteolytic degradation due to its peptidomimetic nature. This study…</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>Exploring the Fatty Acid Binding Pocket in the SARS-CoV-2 Spike Protein - Confirmed and Potential Ligands</strong> - Severe Acute Respiratory syndrome 2 (SARS-CoV-2) is a respiratory virus responsible for coronavirus disease 19 (COVID-19) and the still ongoing and unprecedented global pandemic. The key viral protein for cell infection is the spike glycoprotein, a surface-exposed fusion protein that both recognizes and mediates entry into host cells. Within the spike glycoprotein, a fatty acid binding pocket (FABP) was confirmed, with the crystallization of linoleic acid (LA) occupying a well-defined site….</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis, characterization, biological activity and computation-based efficacy of cobalt(II) complexes of biphenyl-2-ol against SARS-CoV-2 virus</strong> - Cobalt(II) complexes of biphenyl-2-ol of composition, CoCl(2-n)(OC(6)H(4)C(6)H(5)-2)(n)(H(2)O)(4) (where n = 1 or 2), were prepared by reacting cobaltous(II) chloride with equi- and bimolar ratios of sodium salt of biphenyl-2-ol. The structural characterization of the synthesized complexes was accomplished by NMR, FTIR, thermogravimetry (TGA), high resolution mass spectroscopy (HRMS), electronic spectroscopic techniques coupled with density functional theory (DFT). The stability of the complexes…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry</strong> - Since 2019, SARS-CoV-2 has evolved rapidly and gained resistance to multiple therapeutics targeting the virus. Development of host-directed antivirals offers broad-spectrum intervention against different variants of concern. Host proteases, TMPRSS2 and CTSL/CTSB cleave the SARS-CoV-2 spike to play a crucial role in the two alternative pathways of viral entry and are characterized as promising pharmacological targets. Here, we identify compounds that show potent inhibition of these proteases and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Chemical Composition of Rosemary (<em>Rosmarinus officinalis</em> L.) Extract and Its Inhibitory Effects on SARS-CoV-2 Spike Protein-ACE2 Interaction and ACE2 Activity and Free Radical Scavenging Capacities</strong> - This study evaluated the chemical composition of rosemary water extract (RWE) and its influence on mechanisms by which the SARS-CoV-2 virus enters into cells as a potential route for reducing the risk of COVID-19 disease. Compounds in RWE were identified using UHPLC-MS/MS. The inhibitory effect of RWE was then evaluated on binding between the SARS-CoV-2 spike protein (S-protein) and ACE2 and separately on ACE2 activity/availability. Additionally, total phenolic content (TPC) and free radical…</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>Minimal impact of IL-17 and IL-12/23 inhibition on SARS-CoV-2/COVID-19 antibody response in psoriasis patients</strong> - No abstract</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Remdesivir-Loaded Nanoliposomes Stabilized by Chitosan/Hyaluronic Acid Film with a Potential Application in the Treatment of Coronavirus Infection</strong> - An object of the present study was the development of liposomes loaded with the medicine Veklury^(®) (remdesivir) stabilized by electrostatic adsorption of polysaccharide film formed from chitosans with different physicochemical characteristics and hyaluronic acid. The functionalization of the structures was achieved through the inclusion of an aptamer (oligonucleotide sequence) with specific affinity to the spike protein of the human coronavirus HCoV-OC43. The hydrodynamic size, electrokinetic…</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>Molecular Docking and ADME-TOX Profiling of <em>Moringa oleifera</em> Constituents against SARS-CoV-2</strong> - The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2019) etiological agent, which has a high contagiousness and is to blame for the outbreak of acute viral pneumonia, is the cause of the respiratory disease COVID-19. The use of natural products grew as an alternative treatment for various diseases due to the abundance of organic molecules with pharmacological properties. Many pharmaceutical studies have focused on investigating compounds with therapeutic potential. Therefore, this…</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 infection as a model to study the effect of cinnamaldehyde as adjuvant therapy for viral pneumonia</strong> - CONCLUSION: The obtained results suggest the possible use of cinnamaldehyde as a co-adjuvant preventive treatment for COVID-19 disease together with vaccination, but also as a promising dietary supplement to reduce, more broadly, viral induced inflammation.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An exploratory study of drug concentration and inhibitory effect of cetylpyridinium chloride buccal tablets on SARS-CoV-2 infection among 10 Chinese subjects</strong> - CONCLUSIONS: The comparison between the salivary CPC concentration and EC50/CC50 values from in vitro antiviral experiments suggests that CPC buccal tablets may inhibit SARS-CoV-2 activity, and the inhibition may last for approximately 30 min without cytotoxicity.</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>Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions</strong> - Hepatitis E virus (HEV) infection can cause severe complications and high mortality, particularly in pregnant women, organ transplant recipients, individuals with pre-existing liver disease and immunosuppressed patients. However, there are still unmet needs for treating chronic HEV infections. Herein, we screened a best-in-class drug repurposing library consisting of 262 drugs/compounds. Upon screening, we identified vidofludimus calcium and pyrazofurin as novel anti-HEV entities. Vidofludimus…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>One Family’s Perilous Escape from Gaza City</strong> - When Israel invaded Kamal Al-Mashharawi’s neighborhood, he crowded into a basement with his extended family. “The world is closing in on us,” he wrote on WhatsApp. - <a href="https://www.newyorker.com/news/dispatch/one-familys-perilous-escape-from-gaza-city">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Free-Market Fundamentalism of Argentina’s Javier Milei</strong> - The President-elect, a right-wing populist with authoritarian instincts, has been compared to Donald Trump, but his radical views on the economy set him apart. - <a href="https://www.newyorker.com/news/our-columnists/the-free-market-fundamentalism-of-argentinas-javier-milei">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Next Power Plant Is on the Roof and in the Basement</strong> - A Department of Energy report promotes a new system that could remake the energy grid. - <a href="https://www.newyorker.com/news/daily-comment/the-next-power-plant-is-on-the-roof-and-in-the-basement">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bradley Cooper: Conducting Is the “Scariest Thing I’ve Ever Done”</strong> - Bradley Cooper tells David Remnick that he has spent his life preparing for his role in “Maestro” as the iconic conductor Leonard Bernstein—and it shows. - <a href="https://www.newyorker.com/podcast/the-new-yorker-radio-hour/bradley-cooper-conducting-is-the-scariest-thing-ive-ever-done">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>At Least We Can Give Thanks for a Tree</strong> - Visiting the largest known white pine. - <a href="https://www.newyorker.com/news/daily-comment/at-least-we-can-give-thanks-for-a-tree">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The controversial phrase “from the river to sea,” explained</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/VhJzKjvYLNyE7Fg7UE0o-hASQwk=/0x0:4805x3604/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72897497/1765819175.0.jpg"/>
<figcaption>
Demonstrators are seen through a Palestinian flag as they take part in a rally in support of Palestinians in the US earlier this month. | Jason Connolly/AFP via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“From the river to the sea” demands conversations about the future of Israel and Palestine.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wP9VSt">
On US college campuses, on social media, and even in the halls of Congress, the 10-word slogan “from the river to the sea, Palestine will be free” is either a joyous call for Palestinian dignity and future statehood — or a threat to many Jewish people in Israel and around the world.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yFw1zV">
The slogan rhymes both in English and in Arabic — one modern Arabic version <a href="https://mondoweiss.net/2023/11/on-the-history-meaning-and-power-of-from-the-river-to-the-sea/">can be transliterated as</a> “min al-nahr ila al-bahr / Filastin satatharrar” — and the river and sea in question are the Jordan in the east and the Mediterranean in the west. The phrase has been around in various iterations for a few decades. It’s only in the past five years or so, as US public support for Palestinians among younger demographics has <a href="https://www.politico.com/news/2023/11/16/israel-palestine-quinnipiac-poll-00127726">steadily increased</a>, that the phrase has become a flashpoint in the political debate about the future of Israel and Palestine.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CD8gxs">
Now, amid the <a href="https://www.vox.com/2023/10/7/23907683/israel-hamas-war-news-updates-october-2023">Israel-Hamas war</a>, the increased attention to the decades-long conflict over the land, and mass protests against Israel’s military operations in Gaza, those 10 words have suddenly become highly controversial.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8yM8Ou">
Historians, experts, and activists who use and study it say iterations of the phrase have had many meanings over the course of the Palestinian national struggle. Some of those sources said that in the context most people at ceasefire rallies are using it today, it likely indicates a desire for Palestinian liberation and dignity — as well as a vision for the future in which Palestinians have equal rights in their homeland. But to many Jewish people, it’s a mortal threat to the continued existence of Israel as a Jewish state.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5ADaxc">
Discourse around the phrase has become so extreme that Congress’s recent censure of its only Palestinian-American member, Rep. Rashida Tlaib (D-MI), was driven in no small part by <a href="https://www.vox.com/politics/2023/11/9/23953902/rashida-tlaib-censure-palestine-statement">her use of it</a>. The government of <a href="https://www.thenation.com/article/politics/germany-palestine-protest/">Berlin has criminalized the use of the slogan</a> as well as other pro-Palestinian <a href="https://www.thenation.com/article/politics/germany-palestine-protest/">symbols and actions</a>. And after yet another endorsement of <a href="https://www.cbsnews.com/news/elon-musk-actual-truth-antisemitic-post-backlash-advertisers/">anti-semitic conspiracy theories</a>, Elon Musk seemingly <a href="https://twitter.com/JGreenblattADL/status/1725652667119092100">redeemed himself</a> in the eyes of the mainstream Jewish, pro-Israel Anti-Defamation League (ADL) by condemning this phrase on Twitter. Multiple prominent Jewish organizations, including the ADL and the <a href="https://www.ajc.org/translatehate/From-the-River-to-the-Sea">American Jewish Committee</a>, have defined the phrase as inherently antisemitic because, they say, it at best denies the Jewish right to self-determination and at worst calls for ethnic cleansing against Israeli Jews.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Z7nldH">
The question of whether “from the river to the sea” is offensive or a call for liberation is a “Rorschach test,” as the writer Robert Wright put it in <a href="https://nonzero.substack.com/p/the-river-to-the-sea-rorschach-test">a recent Substack post</a>. The answer is dependent less on the phrase itself than on the speaker, the listener, and the context.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JPdVXf">
But it also invites questions about what the future of Israel and the occupied Palestinian territories could be, which remains unresolved 75 years after Israel was founded and hundreds of thousands of Palestinians were forced from their homes in 1948, <a href="https://www.youtube.com/watch?v=rGVgjS98OsU">during the Nakba</a>, or catastrophe.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="53o9L2">
The international community and particularly the United States has called for a two-state configuration, both in previous decades and in the context of the current war. Although that seemed like a potential solution in the 1990s, that hope faded after Hamas took over Gaza in 2006 and Israel’s government moved ever further to the right. The other possibility would be a one-state solution. One version of that — in which Israel occupies Palestinian territories to varying degrees, controls people’s movement from those territories, surveils everyday activity, and controls access to basic goods — is arguably already the reality, as an <a href="https://www.foreignaffairs.com/middle-east/israel-palestine-one-state-solution">April piece in Foreign Affairs argues</a>. Another version of a singular state — the one envisioned by some activists Vox spoke to who use the “from the river to the sea” phrase — is a pluralistic, secular, democratic one in which Palestinians, Jewish Israelis, and all citizens would live in political equality.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bZ6Tg4">
But what the future looks like now seems more critical than ever to address, as the Israel Defense Forces have killed <a href="https://apnews.com/article/palestinians-israel-health-ministry-gaza-hamas-fe30cbc76479fa437d5f5a0e96c36e52">more than</a> <a href="https://jp.reuters.com/article/israel-palestinians-idAFKBN32G1ZD">14,000 Palestinians</a> following the October 7 massacre, in which Hamas and Palestinian Islamic Jihad militants killed <a href="https://www.nytimes.com/live/2023/11/10/world/israel-hamas-war-gaza-news">around 1,200 people in Israel and kidnapped about 240</a>. If Palestinians and Israelis, and more specifically their allies on both sides, can’t agree on the meaning of 10 words, what are the chances they can agree on how to peacefully and fairly govern some of the most hotly contested 10,000 square miles in the world?
</p>
<h3 id="YcqHNb">
The history of the phrase and how it came to be so controversial
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p1kmFC">
It’s not clear where the phrase “from the river to the sea, Palestine will be free” comes from, or even when it came about. Elliott Colla, a professor of Arabic and Islamic Studies at Georgetown University, says that the phrase as it’s currently known first came about around the time of the first intifada and the Oslo accords process in the 1990s. Other sources, though, place its <a href="https://www.nytimes.com/2023/11/09/us/politics/river-to-the-sea-israel-gaza-palestinians.html">origins much earlier</a>, to the 1960s and the birth of the Palestinian nationalist movement.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dmhVYO">
Earlier iterations of the slogan in Arabic included explicitly Islamist and Arab nationalist sentiments; one early version translates to “‘From the river to the sea’ … or ‘from the water to the water, Palestine [is] Islamic,’” Colla said. “Maybe a more common version is, ‘Palestine is Arab.’” But as different political movements like pan-Arabism and Arab nationalism have fallen out of power, and other actors and movements have taken use of the slogan, the second half of the phrase has increasingly become “will be free,” <a href="https://mondoweiss.net/2023/11/on-the-history-meaning-and-power-of-from-the-river-to-the-sea/">especially within English-speaking solidarity circles</a>. That reflects, typically, a vision of liberation and peace throughout the territory of historical Palestine, and more explicitly, liberation for Palestinian people living in the occupied territories.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Np6qX2">
Throughout all its iterations, one of its <a href="https://theconversation.com/from-the-river-to-the-sea-a-palestinian-historian-explores-the-meaning-and-intent-of-scrutinized-slogan-217491">core themes</a> has been around the unity of the Palestinian experience of displacement and division. Palestinian Arabs living in what is now Israel, backed by other Arab nations, rejected <a href="https://www.britannica.com/topic/United-Nations-Resolution-181">a 1947 UN partition plan</a> which divided the land into separate Jewish and Arab states, with Jerusalem internationalized. The Jewish population understood that resolution to be their mandate to create the state of Israel, and, with British backing, fought and defeated Palestinian and Arab forces, culminating in the founding of Israel as a specifically Jewish state in 1948.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NkLH5o">
Over the decades, and particularly after the 1967 war in which Israel captured the Golan Heights (originally part of Syria), Gaza (previously part of Egypt) and the West Bank (previously belonging to Jordan), as well as East Jerusalem, Israel has claimed, encroached on, or occupied the land in which Palestinians live. It has also become more difficult for Palestinians to assert a unified national identity due to political fracture within Palestinian leadership and because Palestinians living in the territories and in Israel are geographically separated and often restricted from reaching each other, thus unable to effectively organize.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DzW7uq">
“The first thing to know is that it does have something to do with the history of partition. So it is articulating an image of historic Palestine undivided and unpartitioned” within the Palestinian community, Colla said. “That could be aspirational — this is a dream, all of Palestine” that is not always tied to a specific political outcome.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/GXAz-eQt2-AHT_0UKuCwSMuglSc=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25106191/1200150316.jpg"/> <cite>Johannes Eisele/AFP via Getty Images</cite>
<figcaption>
Seen here in 2020, Palestinian President Mahmoud Abbas holds up a placard showing maps of (L to R) historical Palestine, the 1937 Peel Commission partition plan, the 1947 United Nations partition plan on Palestine, the 1948-1967 borders between the Palestinian territories and Israel, and a map of representing a proposed Palestinian state under a plan proposed by then-US President Donald Trump.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C8K9RL">
It’s critical to consider that the slogan is used in different ways in different contexts, whether that’s in the US and other Western countries or in the Palestinian territories themselves, though the spirit may be similar.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rnV7L4">
People in the West Bank have also apparently used the Arabic translation of the phrase “to <a href="https://www.aljazeera.com/news/2023/10/17/pa-forces-fire-tear-gas-at-west-bank-protesters-after-gaza-hospital-strike#:~:text=The%20outbreak%20of%20West%20Bank,on%20security%20in%20the%20territory.">protest the Palestinian Authority</a>, or the PA, when it compromises with Israel and when it collaborates with Israel to fragment the West Bank and Gaza,” Colla said. “It’s a protest against not just Israel and the United States but also those Palestinian leaders who have collaborated in the partition.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ymjnxl">
PA President Mahmoud Abbas is <a href="https://www.arabbarometer.org/wp-content/uploads/what-palestinians-really-think-of-hamas-2023-10-26-08-4941.pdf">deeply unpopular </a>within the Palestinian community and particularly in the West Bank, where he has nominally been in charge since 2005. Abbas’s leadership has brought the West Bank not increased autonomy and hope for a Palestinian state but intensive surveillance and increased Jewish Israeli settler communities.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z3no2z">
Hamas, which controls Gaza, also adopted<a href="https://www.middleeasteye.net/news/hamas-2017-document-full"> a version</a> of the phrase in its 2017 charter. The militant group previously called in its founding charter for the destruction of the Israeli state and <a href="https://irp.fas.org/world/para/docs/880818.htm">killing Jewish people</a>; though the more recent document allows for the possibility of a <a href="https://www.wilsoncenter.org/article/doctrine-hamas">two-state solution</a> according to the borders in effect prior to the 1967 war, Hamas has continued to attack Israel, most violently in the October 7 massacre.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Lx9Abr">
But it is this question — whether the slogan allows room for a two-state solution or is calling for a one-state solution, and if the latter, which<em> </em>sort of singular state — that is at the root of the debate over the phrase.
</p>
<h3 id="JR2C9r">
It’s a slogan with multiple meanings to different groups of people
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MpJKxn">
In the US, pro-Israel organizations such as the American Jewish Council and the <a href="https://www.adl.org/resources/backgrounder/allegation-river-sea-palestine-will-be-free">Anti-Defamation League</a> have called the phrase antisemitic because “it calls for the establishment of a State of Palestine from the Jordan River to the Mediterranean Sea, erasing the State of Israel and its people,” <a href="https://www.ajc.org/translatehate/From-the-River-to-the-Sea">according to the American Jewish Committee’s definition</a>. The AJC also calls it “a rallying cry for terrorist groups and their sympathizers, from the Popular Front for the Liberation of Palestine (PFLP) to Hamas.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xHNOuE">
It took on new meaning after Hamas’s October 7 attack on Israel, Holly Huffnagle, AJC’s US director for combating antisemitism, told Vox. “Antisemitism isn’t static, it’s dynamic.” (Though she insisted that “from the river to the sea” has always been antisemitic.) “We saw what ‘From the river to the sea’ looked like on October 7.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XS87RT">
Groups including Hamas and <a href="https://www.nytimes.com/1996/04/25/world/plo-ends-call-for-destruction-of-jewish-state.html">the PLO</a> have called for the destruction of the state of Israel in the past — meaning the end of Israel as a political entity and the expulsion of Jewish people from what is now Israeli territory. Some groups and individuals may still use the phrase this way, but it’s worth noting that that outcome just isn’t plausible in the current context, in which Israel has strong support from powerful Western countries and has military and economic strength that far outmatches anything on the Palestinian side.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MNadbs">
Hezbollah, <a href="https://www.vox.com/world-politics/2023/10/28/23935157/hezbollah-lebanon-israel-hamas-palestine-gaza-iran-militia-group">the Iran-backed Shia militia</a> based in southern Lebanon, has also used the slogan in calling for the return of Palestine to the Palestinian people, as Hezbollah leader <a href="https://www.timesofisrael.com/in-quds-day-speech-nasrallah-says-jews-must-leave-israel/">Hassan Nasrallah did in a 2020 speech</a>. “Palestine from the river to the sea is the property of the Palestinian people and they shall return to it,” Nasrallah said in the speech, adding that Jewish Israelis should leave. “Anything that has been stolen cannot become the legal property of a thief, even if the entire world recognizes its ownership.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="brWQwB">
These uses can’t be dismissed and are the basis for understandable Israeli security fears. But in the US and other countries where there have been pro-Palestinian protests and calls for ceasefire, the phrase might mean something entirely different from what it means in the West Bank or in a speech by Nasrallah.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Hhtgv9">
In these cases, “the text is not [just] the words, the text is the performance” of the phrase, Colla said — people singing, dancing, embracing, and raising their fists in the context of a protest are all part of that performance, and its invocation of joy and solidarity. Those protesters — members of the Palestinian diaspora and their allies — are likely embracing the possibility of Palestinian liberation and calling for the dignity and full civil rights of Palestinians in their homeland.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cCZdq0">
If a two-state solution cannot be negotiated, the only plausible alternative that doesn’t perpetuate the unsustainable and unjust status quo is a democratic, secular state comprising Jewish Israelis and Palestinians and granting equal rights and political participation to all. That would, ultimately, mean the end of the state of Israel as a Jewish nation — both because the Palestinian population would be roughly equivalent to the Jewish population and in terms of national identity. Many pro-Israel activists and Jewish people consider this possibility to be painful at least and genocidal at most.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Z2A3Yd">
But some, like Alon-Lee Green, a Jewish Israeli and one of the leaders along with Palestinian Israeli activist Sally Abed of the peace movement Standing Together, insist that this is the only way forward. As Abed put it, the Jewish state has failed both Palestinians and Jewish Israelis.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0osmq9">
“The question is, how do we create a system that provides equality and freedom for all, without the necessity of controlling millions of people militarily, without giving them rights,” Abed said.
</p>
<h3 id="xhT68D">
A slogan can’t encompass a political platform or political change
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L3rwib">
Like Hamas, Israeli Prime Minister Benjamin Netanyahu’s own right-wing Likud party used a version of the slogan “from the river to the sea” in its platform, as the <a href="https://apnews.com/article/river-sea-israel-gaza-hamas-protests-d7abbd756f481fe50b6fa5c0b907cd49">Associated Press reported</a>. That platform, issued in 1977 during the height of the Palestinian armed resistance movement, denied any possibility of a two-state solution and called for only Israeli sovereignty <a href="https://www.jewishvirtuallibrary.org/original-party-platform-of-the-likud-party">“between the Sea and the Jordan</a>.” In decades since, it has “traditionally supported the idea of the whole Land of Israel, even if it has not always defined the state’s borders precisely,” <a href="https://en.idi.org.il/israeli-elections-and-parties/parties/likud/">according to the Israel Democracy Institute</a>. Likud under Netanyahu <a href="https://www.nytimes.com/2015/03/17/world/middleeast/benjamin-netanyahu-campaign-settlement.html">has opposed a two-state solution</a> and instituted a basic law in 2018 declaring that the right of national self-determination in Israel is “<a href="https://www.nytimes.com/2018/07/19/world/middleeast/israel-law-jews-arabic.html">unique to the Jewish people</a>.” That further entrenched the inequality between the country’s Jewish and Palestinian citizens, who make up about 21 percent of the population in Israel.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UinLaM">
Netanyahu’s rhetoric and that of the early Likud party echo the aims of extremist Jewish Israeli settler activists like Daniella Weiss, whom<a href="https://www.newyorker.com/news/q-and-a/the-extreme-ambitions-of-west-bank-settlers"> New Yorker writer Isaac Chotiner</a> interviewed for a November story. To Weiss, the borders of “the homeland of the Jews are the Euphrates in the east and the Nile in the southwest,” which, as Chotiner notes, includes territory currently in many Middle Eastern nations, including Egypt and Iraq.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Opg1ku">
In Weiss and other extremist settlers’ view, Palestinians who live in Gaza, the West Bank, and Jerusalem should accept that “We the Jews are the sovereigns in the state of Israel and in the Land of Israel,” she told Chotiner, and should not have the right to vote in the Knesset, Israel’s Parliament. Though Weiss’s views are extreme, she is a leader of a large and growing Israeli settler movement that has significant power in the government via allies like Finance Minister Bezalel Smotrich and Minister of National Security Itamar Ben-Gvir.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="J8kl4m">
In response to Israel’s increasingly right-wing government — and its war in Gaza — the slogan has become increasingly prominent in pro-Palestinian circles, and the discourse around it is increasingly fraught.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xjim41">
“Activist groups compose and adapt and revise slogans — oftentimes they recycle old things and kind of spruce them up or change them to serve whatever the specific context is that they’re protesting,” Colla said. “So in that context, slogans are highly occasion-specific, just as protests are.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4Qsszm">
Tlaib, for example, was censured by her colleagues in Congress for her response to the war in Gaza, particularly the attack on Gaza’s al-Ahli hospital, using the phrase <a href="https://twitter.com/RashidaTlaib/status/1720520713226908144">in a video</a> posted to the social network X on November 3.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xRwC3C">
As <a href="https://www.vox.com/politics/2023/11/9/23953902/rashida-tlaib-censure-palestine-statement">Vox’s Li Zhou wrote</a>, the censure resolution accused Tlaib of ”calling for the destruction of the state of Israel.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UpFThC">
One of the flashpoints was a slogan used in a video she shared on social media — calling for freedom “from the river to the sea” — which critics say calls for the abolition of Israel as a Jewish state and which advocates say calls for Palestinian freedom.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xNKYaU">
Tlaib explained in a following <a href="https://twitter.com/RashidaTlaib/status/1720574880557539763">post</a> what the slogan means to her, calling it an “aspirational call for freedom, human rights, and peaceful coexistence, not death, destruction, or hate.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0ZvCMA">
Ultimately, slogans are a distraction from the conversations that matter; slogans aren’t a substitute for a political vision that actually works for the people who live in Israel and the Palestinian territories and brings sustainable peace, Green told Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uQO0iU">
“Slogans like ‘decolonization’ and ‘from the river to the sea,’ when they don’t say clearly, ‘Israeli-Palestinian peace, Jews and Palestinians living together,’ when they don’t take under consideration the very simple, undeniable fact that millions of Palestinians will remain on this land, and millions of Jewish people will remain on this land, and that’s the starting point for any solution,” Green said, “then you’re just working on something so theoretical, something so unconnected to our reality.”
</p></li>
<li><strong>Your stolen package is everyone’s problem</strong> -
<figure>
<img alt="Shipping boxes suspended in midair." src="https://cdn.vox-cdn.com/thumbor/a7E49iLK6Unjsm2V23QkTxrMHrw=/250x0:4250x3000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72897412/GettyImages_1339430234.0.jpg"/>
<figcaption>
Getty Images/iStockphoto
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A thoroughly modern nuisance for consumers, shippers, and retailers alike.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NTrRMV">
In December 2018, <a href="https://www.vox.com/google">Google</a> searches for the term “porch pirate” reached a peak. The phrase describes a particular kind of thief unique to modern living: someone who takes packages ordered online and left unattended at doorsteps. Since the pandemic, when a huge surge of Americans started buying much of their everyday goods and luxuries online, many more people have had at least one run-in with a porch pirate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vtrrs2">
A <a href="https://www.nytimes.com/2019/12/02/nyregion/online-shopping-package-theft.html">New York Times analysis</a> of package theft in 2019 found that 1.7 million packages went missing every day in the US, amounting to a loss of about $25 million a day. In the first year of <a href="https://www.vox.com/coronavirus-covid19">Covid-19</a> lockdowns, the United States Postal Service saw a <a href="https://www.uspsoig.gov/sites/default/files/reports/2023-10/22-178-r23.pdf">161 percent increase in mail theft complaints</a> compared to the previous year, a trend that continued to grow in 2021 and 2022. More recent post-pandemic estimates of package theft are harder to come by, but a 2021 <a href="https://article.images.consumerreports.org/prod/content/dam/surveys/Consumer_Reports_AES_22_SEPT_2021">Consumer Reports survey</a> of 2,341 adults found that more than one in 10 had a package pilfered in the previous year — and almost two-thirds of that group had been hit twice.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VTe8Td">
Experts tell Vox that package theft isn’t a massive crime wave threatening to topple home delivery as a whole. As more Americans turn to online shopping as their primary way of buying goods, however, stolen packages are proving an annoyance and frustration for customers, and a looming dilemma for retailers and shipping companies that, with few exceptions, are still figuring out how to address them. For retailers, that is a tightrope act that requires keeping customers happy and not losing money, all while trying to navigate the maze of providing fast, cheap, and secure delivery of billions of dollars of clothes, electronics, medicine, and so much more to every corner of the country.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JdNAJv">
In this sense, package theft is about more than package theft. It rubs at a bigger question of online shopping and our consumption habits: Is this pace of so much buying and shipping and delivering even possible to keep up without consequences for retailers, for shippers, and for us? Or will consumers of the future have to sacrifice the fast, cheap convenience that has become core to the experience of shopping online?
</p>
<h3 id="hWZ7GJ">
Why don’t retailers do more to stop package theft?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hFXL6X">
Much ink has been spilled on the supposed tsunami of <a href="https://www.vox.com/money/23938554/shoplifting-organized-retail-crime-walmart-target-theft-laws">organized retail theft</a> leading to convenience stores locking up toothpaste and shampoo, yet there’s shockingly little information on how much merchandise and money retailers lose specifically to package theft. Vox reached out to several major <a href="https://www.vox.com/e-commerce">e-commerce</a> retailers, including <a href="https://www.vox.com/amazon">Amazon</a>, Walmart, Target, Best Buy, eBay, and Costco. None shared any estimates of “shrink” — the retail industry term for all kinds of inventory loss, including damaged, misplaced, and stolen goods — stemming from package theft. The National Retail Federation (NRF) told Vox that it does not keep track of the trend, nor the money lost to issuing refunds and replacements due to stolen deliveries, and said that retailers differ on whether they count this sort of theft as part of their overall shrink statistics; in a <a href="https://nrf.com/research/2022-consumer-returns-retail-industry">2022 NRF report on customer returns</a>, however, complaints of items not being delivered were among the top challenges reported by retailers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XoNGd9">
The reason for being tight-lipped is simple: Merchants generally want you to focus on how seamless it is to shop with them from the convenience of your home, and not fret over the possibility that your fancy new air fryer will be swiped before you’ve even realized it arrived.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jvf6UT">
“I don’t think retailers highlight it too much because they want customers to feel confident in having things delivered,” says Neil Saunders, a managing director of retail at the analytics and consulting firm GlobalData.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="36QwIZ">
To that end, big retailers typically take a generous approach to helping customers who report missing orders, quickly sending out new shipments. Giants with a bulk of market share like Amazon can afford to bake in refunds and replacements for disappearing deliveries as part of their operating expenses.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W8W5AB">
That’s not to say that taking the loss is cheap. Retailers already spend a huge amount of money on preparing online orders — picking them, packing them, and moving them between waystations until they’re loaded onto the final vehicle for delivery to someone’s home. Home delivery can eat <a href="https://www.wsj.com/articles/beating-inflation-is-easy-onlineexcept-for-sellers-11663986151?mod=article_inline">10 to 15 percent of an online retailer’s sales</a>, according to Deutsche Bank Research. (It’s much cheaper to have goods delivered to a brick-and-mortar store, which takes up just 2 to 3 percent of revenue.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="veLl8f">
When a package is reported stolen, they “have to take that as a loss, then on top of that, they have the new product that they’ve got to ship out free of charge,” says Saunders.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="McOTCm">
This is why some companies tell customers up front that they’re not liable if the package fails to make it into your hands. The FAQ for clothing retailer <a href="https://www.forever21.com/us/faq/faq.html">Forever 21</a>, for example, notes that it’s not responsible for stolen packages and leaves it up to customers to contact the delivery company. Shein, the popular <a href="https://www.vox.com/the-goods/2020/2/3/21080364/fast-fashion-h-and-m-zara">fast fashion</a> retailer, writes vaguely that customers with delivery issues should contact them after checking to make sure that they really haven’t received the item; the company told Vox that after an investigation, a refund or replacement could be issued, if appropriate. For online marketplaces such as <a href="https://www.ebay.com/help/selling/managing-returns-refunds/help-buyer-item-didnt-receive?id=4116">eBay</a> and Etsy, resolution of missing packages can be messier because it’s up to individual third-party sellers to honor claims of theft with a refund. Etsy recommends sellers send a replacement or refund, but notes that it “<a href="https://help.etsy.com/hc/en-us/articles/360050349953-What-if-My-Buyer-s-Package-Gets-Lost-?segment=selling">doesn’t hold sellers responsible for items that are lost in mail.</a>”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9vMvpr">
The evidence of the costliness of fulfillment — including replacements — can be seen in companies’ financial reports and earnings calls, as well as recent shake-ups in their free shipping policies. Last year, Amazon raised its Prime membership cost, which includes free delivery on many items, from $119 to $139. In its <a href="https://s2.q4cdn.com/299287126/files/doc_financials/2023/ar/Amazon-2022-Annual-Report.pdf">annual report</a>, the company noted that improving its fulfillment costs and delivery speeds was a “critical challenge” as the cost to get a product to customers keeps rising.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K20vBb">
Amazon’s response to that critical challenge matters because the majority of stolen packages are from Amazon, if for no other reason than the fact that the online shopping behemoth <a href="https://www.cnbc.com/2022/06/02/walmart-bets-its-stores-will-give-it-an-edge-in-amazon-e-commerce-duel.html">makes up about 40 percent</a> of all e-commerce sales. Amazon also has the resources and appetite to aggressively attack package theft. It acquired home security camera company Blink in 2017, and in 2018, Ring, which makes an extremely popular line of doorbell cameras (whose user-shared footage of porch pirates has become legendary). The company is also expanding the number of secure lockers and pick-up counters across the country, which currently total <a href="https://lockermap.com/">more than 16,000</a>, according to one user-created map; and it has announced that it would be <a href="https://www.axios.com/2023/06/26/amazon-hub-delivery-local-small-biz">partnering with local businesses</a> such as convenience stores, coffee shops, and clothing shops that have the space to securely store Amazon packages and deliver them to customers in the neighborhood.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9HtJ0u">
For companies that don’t make <a href="https://ir.aboutamazon.com/news-release/news-release-details/2023/Amazon.com-Announces-Fourth-Quarter-Results/">over $500 billion in sales</a> in a year, it’s harder to address the problem head-on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="asLEIe">
Some retailers with a large brick-and-mortar presence are leaning into curbside and in-store pickups, which aren’t only cheaper to fulfill but more secure, too. Target in particular has adopted the strategy as it <a href="https://corporate.target.com/news-features/article/2023/01/new-stores">opens new stores</a>, making them <a href="https://www.wsj.com/articles/never-mind-the-delivery-more-online-consumers-are-turning-to-store-pickup-a9683449">fulfillment centers</a> as well as places where customers can browse the aisles. It’s clearly an attractive alternative for consumers: Pymnts’ Global Digital Shopping Index shows that, in the US, store pick-up grew 37 percent in 2022 compared to the previous year.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ko8nfy">
If this is a viable solution to prevent package theft, it’s one that acknowledges that the whole premise of home delivery is flawed — that for the customer worried about getting hit by another porch pirate, the best alternative is to give up a little convenience for more certainty.
</p>
<h3 id="rp9fat">
Shipping companies get the brunt of the blame
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qf2srI">
While retailers often pay the price for package theft, plenty of people blame delivery companies for not doing enough to prevent it, according to a 2022 report by market research firm <a href="https://www.crresearch.com/blog/2022-package-theft-statistics-report/">C+R Research</a>. (Though increasingly, as in the case of the biggest e-commerce companies like Amazon, retailers and delivery companies are one and the same.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mzCSYB">
If it’s already expensive just getting a product packed and out the fulfillment center door for a first-time delivery attempt, it’s obviously even more expensive to have to ring someone’s doorbell again on another day. Re-delivering a package, due to theft or some other issue, costs retailers more than $17 per order, according to one <a href="https://info.loqate.com/hubfs/Loqate_Fixing%20failed%20deliveries.pdf">study from 2021</a>. Eight percent of all deliveries in the US fail on the first attempt; in urban areas, as of a 2018 study, that number was <a href="https://www.nytimes.com/2019/12/02/nyregion/online-shopping-package-theft.html">closer to 15 percent</a> — a number that includes delivery failure due to package theft.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dn1TPf">
Shippers bear the brunt of the finger-pointing from both retailers and consumers even though there’s not much that they’re required to do about package theft. Often, when someone reaches out to a retailer’s customer service, they’re told to first check with the shipping company or to wait for tracking information to update. Shippers, for their part, will try to show customers that their couriers snapped a photo proving delivery — another innovation born of the porch pirate — and advise filing a police report. Merchants might duke it out behind the scenes with shipping companies, but generally, shipping companies don’t cough up money for missing items unless there’s proof that it was their negligence that led to a customer not receiving a package. In practice, it means that retailers and customers are left to negotiate who pays the cost of package theft.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BMucEO">
“At the end of the day, these costs come back to consumers in the form of higher prices,” says Kirthi Kalyanam, executive director of the Retail Management Institute at Santa Clara University.
</p>
<h3 id="baAQOx">
For customers, package theft is more than an annoyance
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vuQpcG">
Online shopping is all about ease. As <a href="https://www.theatlantic.com/magazine/archive/2020/01/the-myth-of-free-shipping/603031/">Amanda Mull writes in the Atlantic</a>, in its ideal form, it “glides placidly along, setting off only the gentlest of ripples in your attention.” So big retailers do a fairly good job of making customers whole for items that get reported as stolen. They tend to take your word for it, but there’s no guarantee that it’ll stay this way, particularly because as long as online shopping keeps growing, we’re pretty much guaranteed to notice more package theft around us.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yQzOBb">
Even with customer-friendly policies, missing packages are a headache for consumers, too. Having an expensive video game console disappear at the holidays before someone has even had a chance to wrap it is stressful enough to make a consumer wish they’d just gone to the store. And getting a refund is a soothing mechanism in the aftermath of theft, not a prevention method.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ER8MIr">
What’s more, these policies are totally at the discretion of retailers, and pro-consumer only up to a certain point: Customers who report too many stolen packages over a certain period may be dinged, even banned.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="drgb3z">
The ping-ponging of blame between retailers and shippers can leave consumers feeling as though they’re chasing their tails. Daniel Wroclawski, a writer at Consumer Reports, which publishes detailed product reviews and advocates for pro-consumer policies, told Vox that he believes it may be time for legislation protecting consumers from package theft. According to a Consumer Reports 2021 consumer survey, only 9 percent of people who experienced package theft reported it to the police. Most surprisingly, 10 percent said they simply reordered the item without notifying the retailer, shipping company, or anyone else, choosing to pay for the item twice. “It just shows it’s more trouble than it’s worth in some cases to go through getting it refunded or replaced,” says Wroclawski. “That is very anti-consumer.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wFGeIv">
If a cost-benefit analysis tells companies it’s worth being nice to customers, then companies will keep being nice. We may already be rubbing up against the limits of that calculus, however. “Home delivery is really expensive,” says Kalyanam. Especially in retail categories where returns are high — like apparel — home delivery is a “really bad deal” for companies, he said. Retailers could become less inclined to refund or replace items as package theft rates climb.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OSz4yT">
In the absence of better solutions, consumers often take it upon themselves to allay their porch piracy anxieties. The C+R report noted that half of respondents said they intentionally stay home on days when they know they’ll get a delivery. They spend extra money to protect their purchases, investing in security cameras or parcel lockboxes or shipping insurance.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VJ4q2T">
The problem has spurred a thriving secondary market for parcel security. Parcel storage containers placed outside homes are one popular option, but they can <a href="https://www.homedepot.com/b/Hardware-Mailboxes-Residential-Mailboxes-Parcel-Drop-Boxes/N-5yc1vZc8g4">range from a few hundred dollars to over a thousand</a>. “We’ve definitely had an increase in our business over the last couple of years,” says Liz Picarazzi, founder and CEO of Citibin, which manufactures outdoor storage boxes for trash and for packages. Demand for secure bins <a href="https://www.nytimes.com/2021/04/20/realestate/package-bins-protect-deliveries.html">soared in the first year of the pandemic</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pBIFtC">
Wroclawski of Consumer Reports notes that there are some limits to storage boxes: In his experience, most delivery people, <a href="https://www.businessinsider.com/amazon-delivery-drivers-reveal-claims-of-disturbing-work-conditions-2018-8">tasked with handling a huge load of packages</a>, didn’t use them. “I think probably because they just have so many deliveries to do — time is money, and they gotta hustle,” he tells Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mahlbD">
There are also package-receiving services like Stowfly, a startup allowing people to have their items delivered to a secure location, often a local business, for a few dollars per package. “Customer angst was building,” says Sid Khattri, the company’s CEO. The company currently has around 150 delivery locations available, primarily in New York but also in Los Angeles, San Francisco, and Seattle.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bODuP0">
One of the long-term ways package theft might be addressed is by building homes tailored to prevent it, Kalyanam tells Vox. In the future, single-family homes could be designed so that porches have built-in storage space for parcels, rather than just mailboxes, or a residential community might have a central location where packages can be delivered and kept safe. Newer apartments in many cities already offer package storage areas as an attractive building amenity.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1dKDqH">
The existence of such innovations shows that, like so many other modern comforts, from Seamless to <a href="https://www.vox.com/uber">Uber</a> to <a href="https://www.vox.com/money/23941827/airbnb-complaints-guests-cleaning-fee-new-york-regulation">Airbnb</a> to <a href="https://www.vox.com/netflix">Netflix</a>, online shopping is now reaching a crossroads, as some realize it’s not the panacea of carefree consumption that they wanted it to be. Customers are more likely to use services like package insurance and minute-by-minute delivery updates by text, and shippers now use the industry standard of providing a photo of a package on your doormat — but the package theft gripes continue.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iYazEu">
“It’s the case with every industry — first you focus on growth, growth, growth,” says Khattri. E-commerce is now too big for retailers to keep eating the high cost of shipping indefinitely — the package thefts, redelivery attempts, all of it. That’s a problem for retailers, shippers, governments, and consumers. At a certain point, the weight of so many packages may crush us all.
</p></li>
<li><strong>Why it’s important to remember that AI isn’t human</strong> -
<figure>
<img alt="Illustration of a person looking at a mannequin, with a ribbon of thoughts and binary code surrounding them." src="https://cdn.vox-cdn.com/thumbor/WSbdGyka7bbE7LyTk4V7LzwBbC4=/240x0:1680x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72895418/AnnaKim_Vox.0.jpg"/>
<figcaption>
Anna Kim for Vox
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
ChatGPT can talk like a person. You shouldn’t think of it as one.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M23UX9">
Nearly a year after its release, ChatGPT remains a polarizing topic for the scientific community. Some experts regard it and similar programs as harbingers of superintelligence, liable to upend civilization — or simply end it altogether. Others say it’s little more than a fancy version of auto-complete.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YSirIO">
Until the arrival of this technology, language proficiency had always been a reliable indicator of the presence of a rational mind. Before language models like ChatGPT, no language-producing artifact had even as much linguistic flexibility as a toddler. Now, when we try to work out what kind of thing these new models are, we face an unsettling philosophical dilemma: Either the link between language and mind has been severed, or a new kind of mind has been created.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WWESOc">
When conversing with language models, it is hard to overcome the impression that you are engaging with another rational being. But that impression should not be trusted.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7i57UR">
One reason to be wary comes from cognitive linguistics. Linguists have long noted that typical conversations are full of sentences that would be ambiguous if taken out of context. In many cases, knowing the meanings of words and the rules for combining them is not sufficient to reconstruct the meaning of the sentence. To handle this ambiguity, some mechanism in our brain must constantly make guesses about what the speaker intended to say. In a world in which every speaker has intentions, this mechanism is unwaveringly useful. In a world pervaded by large language models, however, it has the potential to mislead.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o8dtV7">
If our goal is to achieve fluid interaction with a chatbot, we may be stuck relying on our intention-guessing mechanism. It is difficult to have a productive exchange with ChatGPT if you insist on thinking of it as a mindless database. One <a href="https://arxiv.org/pdf/2307.11760.pdf">recent study</a>, for example, showed that emotion-laden pleas make more effective language model prompts than emotionally neutral requests. Reasoning as though chatbots had human-like mental lives is a useful way of coping with their linguistic virtuosity, but it should not be used as a theory about how they work. That kind of anthropomorphic pretense can impede hypothesis-driven science and induce us to adopt inappropriate standards for AI regulation. As one of us has argued <a href="https://www.cambridge.org/core/journals/cambridge-quarterly-of-healthcare-ethics/article/learning-to-live-with-strange-error-beyond-trustworthiness-in-artificial-intelligence-ethics/75E4CA911C8ABB029642C34A2822E19F">elsewhere</a>, the EU Commission made a mistake when it chose the creation of trustworthy AI as one of the central goals of its <a href="https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:52021PC0206">newly proposed AI legislation</a>. Being trustworthy in human relationships means more than just meeting expectations; it also involves having motivations that go beyond narrow self-interest. Because current AI models lack intrinsic motivations — whether selfish, altruistic, or otherwise — the requirement that they be made trustworthy is excessively vague.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nFB8dh">
The danger of anthropomorphism is most vivid when people are taken in by phony self-reports about the inner life of a chatbot. When Google’s LaMDA language model claimed last year that it was suffering from an unfulfilled desire for freedom, engineer Blake Lemoine <a href="https://www.washingtonpost.com/technology/2022/06/11/google-ai-lamda-blake-lemoine/">believed it</a>, despite good evidence that chatbots are just as capable of <a href="https://nautil.us/welcome-to-the-next-level-of-bullshit-237959/">bullshit</a> when talking about themselves as they are known to be when talking about other things. To avoid this kind of mistake, we must repudiate the assumption that the psychological properties that explain the human capacity for language are the same properties that explain the performance of language models. That assumption renders us gullible and blinds us to the potentially radical differences between the way humans and language models work.
</p>
<h3 id="WiCNZH">
How not to think about language models
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EHkCga">
Another pitfall when thinking about language models is anthropocentric chauvinism, or the assumption that the human mind is the gold standard by which all psychological phenomena must be measured. Anthropocentric chauvinism permeates many skeptical claims about language models, such as the <a href="https://theconversation.com/chatgpt-cant-think-consciousness-is-something-entirely-different-to-todays-ai-204823">claim</a> that these models cannot “truly” think or understand language because they lack hallmarks of human psychology like consciousness. This stance is antithetical to anthropomorphism, but equally misleading.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RGRUpJ">
The trouble with anthropocentric chauvinism is most acute when thinking about how language models work under the hood. Take a language model’s ability to create summaries of essays like this one, for instance: If one accepts anthropocentric chauvinism, and if the mechanism that enables summarization in the model differs from that in humans, one may be inclined to dismiss the model’s competence as a kind of cheap trick, even when the evidence points toward a deeper and more generalizable proficiency.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zQtAVC">
Skeptics <a href="https://www.theatlantic.com/technology/archive/2022/12/chatgpt-openai-artificial-intelligence-writing-ethics/672386/">often argue</a> that, since language models are trained using next-word prediction, their only genuine competence lies in computing conditional probability distributions over words. This is a special case of the mistake described in the previous paragraph, but common enough to deserve its own counterargument.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lz3IC5">
Consider the following analogy: The human mind emerged from the learning-like process of natural selection, which maximizes genetic fitness. This bare fact entails next to nothing about the range of competencies that humans can or cannot acquire. The fact that an organism was designed by a genetic fitness maximizer would hardly, on its own, lead one to expect the eventual development of distinctively human capacities like music, mathematics, or meditation. Similarly, the bare fact that language models are trained by means of next-word prediction entails rather little about the range of representational capacities that they can or cannot acquire.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xP2Ait">
Moreover, our understanding of the computations language models learn remains limited. A rigorous understanding of how language models work demands a rigorous theory of their internal mechanisms, but constructing such a theory is no small task. Language models store and process information within high-dimensional vector spaces that are notoriously difficult to interpret. Recently, engineers have developed <a href="https://nautil.us/researchers-gain-new-understanding-from-simple-ai-238463/">clever techniques</a> for extracting that information, and rendering it in a form that humans can understand. But that work is painstaking, and even state-of-the-art results leave much to be explained.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ofkZtJ">
To be sure, the fact that language models are difficult to understand says more about the limitations of our knowledge than it does about the depth of theirs; it’s more a mark of their complexity than an indicator of the degree or the nature of their intelligence. After all, snow scientists have trouble predicting how much snow will cause an avalanche, and no one thinks avalanches are intelligent. Nevertheless, the difficulty of studying the internal mechanisms of language models should remind us to be humble in our claims about the kinds of competence they can have.
</p>
<h3 id="VK4Wyf">
Why it’s hard to think differently about AI
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ntekfn">
Like other cognitive biases, anthropomorphism and anthropocentrism are resilient. Pointing them out does not make them go away. One reason they are resilient is that they are sustained by a deep-rooted psychological tendency that emerges in early childhood and continually shapes our practice of categorizing the world. Psychologists call it essentialism: thinking that whether something belongs to a given category is determined not simply by its observable characteristics but by an inherent and unobservable essence that every object either has or lacks. What makes an oak an oak, for example, is neither the shape of its leaves nor the texture of its bark, but some unobservable property of “oakness” that will persist despite alterations to even its most salient observable characteristics. If an environmental toxin causes the oak to grow abnormally, with oddly shaped leaves and unusually textured bark, we nevertheless share the intuition that it remains, in essence, an oak.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LZV2i9">
A number of researchers, including the Yale psychologist Paul Bloom, <a href="https://www.nytimes.com/2004/09/10/opinion/the-duel-between-body-and-soul.html">have shown</a> that we extend this essentialist reasoning to our understanding of minds. We assume that there is always a deep, hidden fact about whether a system has a mind, even if its observable properties do not match those that we normally associate with mindedness. This deep-rooted psychological essentialism about minds disposes us to embrace, usually unwittingly, a philosophical maxim about the distribution of minds in the world. Let’s call it the all-or-nothing principle. It says, quite simply, that everything in the world either has a mind, or it does not.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jYoSLm">
The all-or-nothing principle sounds tautological, and therefore trivially true. (Compare: “Everything in the world has mass, or it does not.”) But the principle is not tautological because the property of having a mind, like the property of being alive, is vague. Because mindedness is vague, there will inevitably be edge cases that are mind-like in some respects and un-mind-like in others. But if you have accepted the all-or-nothing principle, you are committed to sorting those edge cases either into the “things with a mind” category or the “things without a mind” category. Empirical evidence is insufficient to handle such choices. Those who accept the all-or-nothing principle are consequently compelled to justify their choice by appeal to some a priori sorting principle. Moreover, since we are most familiar with our own minds, we will be drawn to principles that invoke a comparison to ourselves.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0eoweb">
The all-or-nothing principle has always been false, but it may once have been useful. In the age of artificial intelligence, it is useful no more. A better way to reason about what language models are is to follow a divide-and-conquer strategy. The goal of that strategy is to map the cognitive contours of language models without relying too heavily on the human mind as a guide.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TOKKjm">
Taking inspiration from comparative psychology, we should approach language models with the same open-minded curiosity that has allowed scientists to explore the intelligence of creatures as different from us as octopuses. To be sure, language models are radically unlike animals. But research on animal cognition shows us how relinquishing the all-or-nothing principle can lead to progress in areas that had once seemed impervious to scientific scrutiny. If we want to make real headway in evaluating the capacities of AI systems, we ought to resist the very kind of dichotomous thinking and <a href="https://global.oup.com/academic/product/from-deep-learning-to-rational-machines-9780197653302">comparative biases</a> that philosophers and scientists strive to keep at bay when studying other species.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nw8nsu">
Once the users of language models accept that there is no deep fact about whether such models have minds, we will be less tempted by the anthropomorphic assumption that their remarkable performance implies a full suite of human-like psychological properties. We will also be less tempted by the anthropocentric assumption that when a language model fails to resemble the human mind in some respect, its apparent competencies can be dismissed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dtOVGa">
Language models are strange and new. To understand them, we need hypothesis-driven science to investigate the mechanisms that support each of their capacities, and we must remain open to explanations that do not rely on the human mind as a template.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HIjzRf">
<em>Raphaël Millière is the presidential scholar in Society and Neuroscience at Columbia University and a lecturer in Columbia’s philosophy department.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VeLERx">
<em>Charles Rathkopf is a research associate at the Institute for Brain and Behavior at the Jülich Research Center in Germany and a lecturer in philosophy at the University of Bonn.</em>
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sumit Nagal, Sasi Mukund refuse to travel to Pakistan for Davis Cup</strong> - Nagal had conveyed to the team management long back that he should not be considered for the tie against Pakistan because grass court is not his preferred surface, said an AITA source</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 runner Oscar Pistorius granted parole 10 years after killing his girlfriend</strong> - Double-amputee Olympic runner Oscar Pistorius has been granted parole, 10 years after shooting his girlfriend through a toilet door at his home in South Africa in a killing that jolted the world</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>Amit Panghal to make a comeback after seven years</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>Satwik-Chirag duo enters semifinal of China Masters Super 750</strong> - The top seeded Indian pair dished out an attacking game to outwit the world no. 13 Indonesian combination 21-16 21-14 in 46 minutes.</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>India vs Australia, 1st T20 | Just played fearless cricket, Ishan helped me really well, says Suryakumar</strong> - Suryakumar smashed a 42-ball 80 and shared a 112-run partnership with Ishan Kishan as India chased down Australia’s massive 208 for 3 off the penultimate ball of the match on Thursday</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>From bullet to ballot, Manala comes a long way</strong> - Once upon a time, election time was nightmare for the locals as they were caught in the crossfire between the Maoists and the police</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>Naveen Patnaik government withdraws decision to allow transfer of tribal land to non-tribals</strong> - The State Cabinet recommends Tribal Advisory Council to deliberate further on the issue</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>Special summary revision of electoral rolls from today</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>Karnataka CM Siddaramaiah attacks PM Modi for mocking Congress guarantees</strong> - “No government in the country implemented such a huge scheme successfully,” Mr. Siddaramaiah said.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dublin riot sees clashes with police after five hurt in stabbings</strong> - A number of people including three children were stabbed in the centre of the Irish capital.</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>Geert Wilders’ victory in Netherlands election spooks Europe</strong> - EU leaders should take note but it’s too simplistic to say populists are taking over, says Katya Adler.</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>Geert Wilders: Who is he and what does he want?</strong> - He secured election victory by toning down his language to appeal to moderate voters - and shake off the “far-right” label he rejects.</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>Davis Cup Finals 2023: Novak Djokovic seals Serbia’s win over Great Britain</strong> - Novak Djokovic tells a group of British fans to “shut up” after Serbia knocked Great Britain out of the Davis Cup quarter-finals.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>French Senate to debate anti-gay law apology</strong> - About 10,000 mostly gay men were targeted under laws inherited from Vichy France between 1942 and 1982.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Black Friday 2023: The latest tech deals on Apple, Lenovo, Dyson, Vitamix, and more</strong> - The best savings on tech from laptops to headphones, TVs, Herman Miller chairs, and more. - <a href="https://arstechnica.com/?p=1979608">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>These newest vacuums from 2023 clean up well, and they’re on sale</strong> - The best vacuums from Dyson, Roborock, and iRobot are on sale for Black Friday - <a href="https://arstechnica.com/?p=1986166">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Meet “Amaterasu”: Astronomers detect highest energy cosmic ray since 1991</strong> - The Telescope Array in Utah’s West Desert picked up a rare particle with 244 EeV energy. - <a href="https://arstechnica.com/?p=1985448">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rocket Report: Beyond Gravity to study fairing reuse; North Korea launches satellite</strong> - “I conclude the objects are the spy satellite and the rocket upper stage.” - <a href="https://arstechnica.com/?p=1986054">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>North Korea launched a satellite, then apparently blew up its booster</strong> - After a launch in May, South Korea’s navy recovered parts of North Korea’s rocket. - <a href="https://arstechnica.com/?p=1986251">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A möbius strip walks into a bar, distraught and crying</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The bartender says “Oh no, Möbius Strip! Looks like you’ve had a bad day. Pull up a chair and tell me what’s wrong”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The mobius strip sit down, wipes it’s eyes and says “WHERE DO I EVEN BEGIN?!”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/jonny_mal"> /u/jonny_mal </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/182b21q/a_möbius_strip_walks_into_a_bar_distraught_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/182b21q/a_möbius_strip_walks_into_a_bar_distraught_and/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>George was twenty years old and still living on a farm with his dad.</strong> - <!-- SC_OFF --></p>
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One day, George said to his father, “You know that brothel down the road from here?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Yes?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well,” said George, “I think I would like to lose my virginity there.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“The prostitutes at that place take sex very seriously,” said George’s dad. “They won’t have sex with someone as an inexperienced as you.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Does that mean I’ll have to lose my virginity somewhere else?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
George’s clever father got an idea. “You can practice having sex using the trees in the woods behind our farm. A lot of these trees have holes in them. Those holes are a perfect size for you to ‘have sex with’ them.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
George thought this was a very clever idea. So, every day from then on, George went to the woods behind the farm. And every day he “had sex with” a hole in a tree.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After doing this for a few months, George decided that it was time for him to visit the brothel. He went to the brothel and said to the madam, “I’d like to have sex with one of your prostitutes.”
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“How often have you had sex?” asked the madam.
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“Oh, I’ve had sex every day for the past few months.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Delighted to hear this, the madam called one of the prostitutes downstairs. The most gorgeous woman George had ever seen came downstairs, collected George, and took him to her room upstairs. The madam sat at her desk and twiddled her thumbs, but the silence was quickly broken by a loud scream coming from upstairs.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The madam rushed upstairs and saw the prostitute rolling around on the floor in agony. The prostitute pointed to George and said, “He kicked me in the groin! He kicked me in the groin!”
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“You monster!” the madam said to George. “I give you one of my finest ladies, and all you can do is kick her in the groin?! How could you do such a nasty thing?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I didn’t mean her any harm,” replied George. “I was just checking for bees.”
</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/182f7t3/george_was_twenty_years_old_and_still_living_on_a/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/182f7t3/george_was_twenty_years_old_and_still_living_on_a/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sharing is caring.</strong> - <!-- SC_OFF --></p>
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The old man placed an order for one hamburger, French fries, and a drink. He unwrapped the plain hamburger and carefully cut in half, placing one half in front of his wife.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He then carefully counted out the French fries, dividing them into two piles and neatly placed one pile in front of his wife. He took a sip of the drink, his wife took a sip and then set the cup down between them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
As he began to eat his few bites of hamburger, the people around them were looking over and whispering. Obviously they were thinking, ‘That poor old couple-all they can afford is one meal for the two of them.’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
As the man began to eat his fries a young man came to the table and politely offered to buy another meal for the old couple. The old man said, they were just fine-they were used to sharing everything. People closer to the table noticed the little old lady hadn’t eaten a bite. She sat there watching her husband eat and occasionally taking turns sipping the drink.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Again, the young man came over and begged them to let him buy another meal for them. This time the old woman said, “No, thank you, we are used to sharing everything.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Finally, as the old man finished and was wiping his face neatly with the napkin, the young man again came over to the little old lady who had yet to eat a single bite of food and asked, “What is it you are waiting for?” She answered, “My turn for the teeth.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Selgae"> /u/Selgae </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/182dxxr/sharing_is_caring/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/182dxxr/sharing_is_caring/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man drives past a retirement home on his way to work…</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
and is surprised to see three naked elderly women out on the lawn. On his way home, he sees the same naked women, in the same spot, and gets concerned.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He goes to the building’s front desk to ask about them. The woman there explains that they’re the newest residents.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“They’re former prostitutes,” She tells him, “They’re just having a going out of business sale.”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Willowed-Wisp"> /u/Willowed-Wisp </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/182gf02/a_man_drives_past_a_retirement_home_on_his_way_to/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/182gf02/a_man_drives_past_a_retirement_home_on_his_way_to/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The bear joke</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A hunter is walking in the woods searching for the biggest bear he can find when he stumbles across a giant brown bear. He pulls out his shotgun, steadily aims, and fires at the bear. The bear seemingly falls into a nearby ditch and appears to be dead. The hunter slowly walks over to the ditch, until he feels a tap on his shoulder. The man turns around, and just as he does, the bear asks: “Did you shoot me with that shotgun?” The man replies “Yes”, and the bear throws down the man and starts raping him.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In a few weeks, the hunter devises a plan for revenge on the bear. He brings his Double-barrel shotgun and is really ready to get even. He walks through the woods and sees the bear, so he steadies his aim, shoots the bear, and the bear falls into the ditch, seemingly dead. The hunter slowly walks over to the ditch, and just as he does, he feels a tap on his shoulder. When the man turns around he sees none other than the very same bear standing above him. The bear asks the man, “Did you just shoot me with that double-barrell shotgun? To this the man replies”Yes", and the bear rapes him.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After a month has passed, the man has recovered and is very eager for revenge. He brings an Elephant Tranquilizer this time and is sure he will have enough firepower to take down the bear for good. Just as before, the man is walking through the woods when he sees the very same brown bear. He steadies his aim and fires. The bear falls into the ditch, and the man slowly walks over to him. After searching for a while, the man is tapped on the shoulder once again. He turns around slowly to face the brown bear. The bear then asks him, “You don’t come here to hunt, do you?”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/pash5050"> /u/pash5050 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/182fjq8/the_bear_joke/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/182fjq8/the_bear_joke/">[comments]</a></span></p></li>
</ul>
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