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<title>31 December, 2023</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Improve Vaccine Immunomodulation</strong> -
<div>
Over the past few decades, the development of potent and safe immune-activating adjuvant technologies has become the heart of intensive research in the constant fight against highly mutative and immune evasive viruses such as influenza, SARS-CoV-2, and HIV. Herein, we developed a highly modular saponin-based nanoparticle platform incorporating toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, TLR7/8a adjuvants and their mixtures. These various TLRa-SNP adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific Th-responses that could be of interest depending on the target disease for prevention. In a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform which could improve the design of vaccines for and dramatically impact modern vaccine development.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.16.549249v2" target="_blank">Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Improve Vaccine Immunomodulation</a>
</div></li>
<li><strong>The Double-Edged Sword Mediatized Integration Processes during the COVID-19 Pandemic</strong> -
<div>
The issue of media appropriation by refugees experienced a boom in 2015, but since then the topic has received less attention over the years. In addition, refugees have faced significant challenges since the appearance of COVID-19. In this paper, I discuss how Syrian migrants and refugees who have lived in Germany for at least four years used media technologies during COVID-19. I present findings from twelve guided interviews conducted in a northern German city. In summary, media use in general has increased, as has that of the majority society. On the other hand, media use during the pandemic has proven to be a double-edged sword: Some refugees had great(er) problems coping with the situation, while others gained self-empowerment and agency through using media during the pandemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/yjt23/" target="_blank">The Double-Edged Sword Mediatized Integration Processes during the COVID-19 Pandemic</a>
</div></li>
<li><strong>Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response</strong> -
<div>
Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. It also imposes a substantial economic burden through increased absenteeism during periods of active pathogen circulation. Vaccination is generally accepted as the most effective strategy for influenza prevention. As both influenza A and B viruses circulate and cause seasonal epidemics, vaccines need to include multiple antigens derived from different viral subtypes. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains. Additionally, the rapid variability of the virus poses challenges in providing extended protection beyond a single season. Therefore, mRNA technology is particularly promising for influenza prevention, as it enables the rapid development of multivalent vaccines and allows for quick updates of their antigenic composition. mRNA vaccines have already proven successful in preventing COVID-19 by eliciting rapid cellular and humoral immune responses. In this study, we present the development of a trivalent mRNA vaccine candidates, evaluate its immunogenicity using the hemagglutination inhibition assay, and assess its efficacy in animals. We demonstrate the higher immunogenicity of the mRNA vaccine candidates compared to the inactivated split influenza vaccine and its enhanced ability to generate a cross-specific humoral immune response. These findings highlight the potential mRNA technology in overcoming current limitations of influenza vaccines and hold promise for ensuring greater efficacy in preventing seasonal influenza outbreaks.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.30.573722v1" target="_blank">Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response</a>
</div></li>
<li><strong>Tying the Knot: Unraveling the Intricacies of the Coronavirus Frameshift Pseudoknot</strong> -
<div>
Understanding and targeting functional RNA structures towards treatment of coronavirus infection can help us to prepare for novel variants of SARS-CoV-2 (the virus causing COVID-19), and any other coronaviruses that could emerge via human-to-human transmission or potential zoonotic (inter-species) events. Leveraging the fact that all coronaviruses use a mechanism known as -1 programmed ribosomal frameshifting (-1 PRF) to replicate, we apply algorithms to predict the most energetically favourable secondary structures (each nucleotide involved in at most one pairing) that may be involved in regulating the -1 PRF event in coronaviruses, especially SARS-CoV-2. We compute previously unknown most stable structure predictions for the frameshift site of coronaviruses via hierarchical folding, a biologically motivated framework where initial non-crossing structure folds first, followed by subsequent, possibly crossing (pseudoknotted), structures. Using mutual information from 181 coronavirus sequences, in conjunction with the algorithm KnotAli, we compute secondary structure predictions for the frameshift site of different coronaviruses. We then utilize the Shapify algorithm to obtain most stable SARS-CoV-2 secondary structure predictions guided by frameshift sequence-specific and genome-wide experimental data. We build on our previous secondary structure investigation of the singular SARS-CoV-2 68 nt frameshift element sequence, by using Shapify to obtain predictions for 132 extended sequences and including covariation information. Previous investigations have not applied hierarchical folding to extended length SARS-CoV-2 frameshift sequences. By doing so, we simulate the effects of ribosome interaction with the frameshift site, providing insight to biological function. We contribute in-depth discussion to contextualize secondary structure dual-graph motifs for SARS-CoV-2, highlighting the energetic stability of the previously identified 3_8 motif alongside the known dominant 3_3 and 3_6 (native-type) -1 PRF structures. Integrating experimental data within minimum free energy (MFE) hierarchical folding algorithms provides novel structure predictions to distill the relationship between RNA structure and function. In particular, fully categorizing most stable secondary structure predictions via hierarchical folding supports our identification of motif transitions and critical site targets for future therapeutic research.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.28.573501v1" target="_blank">Tying the Knot: Unraveling the Intricacies of the Coronavirus Frameshift Pseudoknot</a>
</div></li>
<li><strong>CParty: Conditional partition function for density-2 RNA pseudoknots</strong> -
<div>
RNA molecules fold into biologically important functional structures. Efficient dynamic programming RNA (secondary) structure prediction algorithms restrict the search space to evade NP-hardness of general pseudoknot prediction. While such prediction algorithms can be extended to provide a stochastic view on RNA ensembles, they are either limited to pseudoknot-free structures or extremely complex. To overcome this dilemma, we provide the theoretical framework and implementation for our algorithm, CParty, that follows the hierarchical folding hypothesis, i.e., the bio-physically well-motivated assumption that non-crossing structures fold relatively fast prior to the formation of pseudoknot interactions. Thus, we efficiently compute the conditional partition function (CPF) given a non-crossing structure G for a subset of pseudoknotted structures, i.e., density-2 structures G U G’ for non-crossing disjoint structure G’. Notably, this can enable sampling from the hierarchical distribution P(G’|G). With CParty we develop for the first time an unambiguous scheme based on HFold, i.e., the minimum free energy hierarchical folding algorithm based on a realistic pseudoknot energy model. Thus, we develop the first partition function variant for density-2 structures. Compared to the only other available pseudoknot partition function algorithm, which covers simple pseudoknots (and follows a different strategy, mapped from a pure minimum free energy structure prediction), our method covers a much larger structure class; at the same time, it is significantly more efficient—reducing the time as well as the space complexity by a quadratic factor. Summarizing, we provide an efficient, cubic time, algorithm for the stochastic analysis of pseudoknotted RNAs, which enables novel applications. We discuss one such application, i.e., how the CPF for a pseudoknotted therapeutic target in SARS-CoV-2 can provide insight into RNA structure formation.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.541023v2" target="_blank">CParty: Conditional partition function for density-2 RNA pseudoknots</a>
</div></li>
<li><strong>The 8C model of vaccination readiness: A common framework to facilitate cross-study comparisons.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Several factors can potentially influence an individual’s vaccination readiness. To facilitate cross-study comparisons, it is essential that researchers use a shared framework to measure these factors. This would not only help determine their relative importance cross different contexts but also would aid in tailoring interventions to enhance vaccine uptake. Historically, five psychological antecedents of vaccination were identified: confidence, complacency, constraints, calculation, and collective responsibility. This 5C scale was later expanded to a 7C model by incorporating two additional components: compliance and conspiracy. Building upon this framework, we propose an eighth component, certification, defined as the person’s self-report that, in the past, they have had to provide evidence of vaccination. This component addresses a significant gap in the 7C model, as some individuals reported taking the COVID-19 vaccine primarily to obtain proof of vaccination, a motivation not captured by the 7C model. Our confirmatory factor analysis (N = 406) of a bifactor model of US citizens9 self-reported COVID-19 vaccination status showed that this eighth component had good psychometric properties and the 8C model had slightly higher criterion validity than the 7C model. We present the 8C model as a framework that provides a richer and more complete descriptions of the factors that determine vaccination readiness and encourage future studies of vaccination readiness to utilise it.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.22.23300464v1" target="_blank">The 8C model of vaccination readiness: A common framework to facilitate cross-study comparisons.</a>
</div></li>
<li><strong>BNT162b2 XBB1.5-adapted Vaccine and COVID-19 Hospital Admissions and Ambulatory Visits in US Adults</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Importance Data describing the early additional protection afforded by recently recommended XBB1.5-adapted COVID-19 vaccines are limited. Objective We estimated the association between receipt of BNT162b2 XBB1.5-adapted vaccine (Pfizer-BioNTech 2023-2024 formulation) and medically attended COVID-19 outcomes among adults &gt;=18 years of age. Design, Setting, and Participants We performed a test-negative case-control study to compare the odds of BNT162b2 XBB1.5-adapted vaccine receipt between COVID-19 cases and test-negative controls among adults in the Kaiser Permanente Southern California health system between October 11 and December 10, 2023. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models that were adjusted for patient demographic and clinical characteristics. Exposure The primary exposure was receipt of BNT162b2 XBB1.5-adapted vaccine compared to not receiving an XBB1.5-adapted vaccine of any kind, regardless of prior COVID-19 vaccination or SARS-CoV-2 infection history. We also compared receipt of prior (non-XBB1.5-adapted) versions of COVID-19 vaccines to the unvaccinated to estimate remaining protection from older vaccines. Main Outcomes and Measures Cases were those with a positive SARS-CoV-2 polymerase chain reaction test, and controls tested negative. Analyses were done separately for COVID-19 hospital admissions, emergency department (ED) and urgent care (UC) encounters, and outpatient visits. Results Among 4232 cases and 19,775 controls with median age of 54 years, adjusted ORs for testing positive for SARS-CoV-2 among those who received BNT162b2 XBB1.5-adapted vaccine a median of 30 days ago (vs not having received an XBB1.5-adapted vaccine of any kind) were 0.37 (95% CI: 0.20-0.67) for COVID-19 hospitalization, 0.42 (0.34-0.53) for ED/UC visits, and 0.42 (0.27-0.66) for outpatient visits. Compared to the unvaccinated, those who had received only older versions of COVID-19 vaccines did not show significantly reduced risk of COVID-19 outcomes, including hospital admission. Conclusions and Relevance Our findings reaffirm current recommendations for broad age-based use of annually updated COVID-19 vaccines given that (1) XBB1.5-adapted vaccines provided significant additional protection against a range of COVID-19 outcomes and (2) older versions of COVID-19 vaccines offered little, if any, additional protection, including against hospital admission, regardless of the number or type of prior doses received.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.24.23300512v1" target="_blank">BNT162b2 XBB1.5-adapted Vaccine and COVID-19 Hospital Admissions and Ambulatory Visits in US Adults</a>
</div></li>
<li><strong>Dengue Virus Serotype 2 Cosmopolitan C Genotype Reemerges with a New Subclade in Southwest Region of Bangladesh</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In 2023, the Dengue virus (DENV) outbreak infected over 0.3 million cases and 1500 deaths in Bangladesh. Although the the serotype and genotype data were unavailable. Our study conducted serotyping and genomic surveillance in four districts of Southwest Bangladesh between September and October 2023. The surveillance data from 2019 to 2023 extracted from the Directorate General of Health Services in Bangladesh indicated a significant increase of Dengue infections in 2023, particularly during September-November. The two-layered hypothesis examination confirmed that, despite endemic months, 2023 dengue outbreak had a higher morbidity rate compared to previous years (2019-2022) in Southwest of Bangladesh. Serotyping and E gene sequence analysis of 25 randomly selected positive samples reveals that DENV-2 was the sole serotype circulating in this region during the study period. Genomic analysis exposed a new subclade of DENV-2, classified under Cosmopolitan genotype within C clade, distinct from previous years Bangladeshi variants until 2022. This subclade, possibly migrating from India, might be emerged during COVID-19 pandemic years and exhibited higher morbidity rates, thus challenging our existing mitigation strategies. This investigation provides valuable insights for public health interventions and underscores the importance of continuous genomic surveillance in managing Dengue outbreaks. Key words: Dengue serotype 2, Bangladesh, New Subclade, Cosmopolitan C, Phylogenetic tree
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.24.23300504v1" target="_blank">Dengue Virus Serotype 2 Cosmopolitan C Genotype Reemerges with a New Subclade in Southwest Region of Bangladesh</a>
</div></li>
<li><strong>Learning the fitness dynamics of pathogens from phylogenies</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The dynamics of pathogen genetic diversity, including the emergence of lineages with increased fitness, is a foundational concept of disease ecology with key public health implications. However, the identification of distinct lineages and estimation of associated fitness remain challenging, and are rarely done outside densely sampled systems. Here, we present a scalable framework that summarizes changes in population composition in phylogenies, allowing for the automatic detection of lineages based on shared fitness and evolutionary relationships. We apply our approach to a broad set of viruses and bacteria (SARS-CoV-2, H3N2 influenza, Bordetella pertussis and Mycobacterium tuberculosis) and identify previously undiscovered lineages, as well as specific amino acid changes linked to fitness changes, the findings of which are robust to uneven and limited observation. This widely-applicable framework provides an avenue to monitor evolution in real-time to support public health action and explore fundamental drivers of pathogen fitness.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.23.23300456v1" target="_blank">Learning the fitness dynamics of pathogens from phylogenies</a>
</div></li>
<li><strong>Associations between COVID-19 and putative markers of neuroinflammation: A diffusion basis spectrum imaging study.</strong> -
<div>
COVID-19 remains a significant international public health concern. Yet, the mechanisms through which symptomatology emerges remain poorly understood. While SARS-CoV-2 infection may induce prolonged inflammation within the central nervous system, the evidence primarily stems from limited small-scale case investigations. To address this gap, our study capitalized on longitudinal UK Biobank neuroimaging data acquired prior to and following COVID-19 testing (N=416 including n=224 COVID-19 cases; Mage=58.6). Putative neuroinflammation was assessed in gray matter structures and white matter tracts using non-invasive Diffusion Basis Spectrum Imaging (DBSI), which estimates inflammation-related cellularity (DBSI-restricted fraction; DBSI-RF) and vasogenic edema (DBSI-hindered fraction; DBSI-HF).We hypothesized that COVID-19 case status would be associated with increases in DBSI markers after accounting for potential confound (age, sex, race, body mass index, smoking frequency, and data acquisition interval) and multiple testing. COVID-19 case status was not significantly associated with DBSI-RF (all |B|&lt;0.28, pFDR &gt;0.05), but with greater DBSI-HF in left pre- and post-central gyri and right middle frontal gyrus (all B&gt;0.3, all pFDR=0.03). Intriguingly, the brain areas exhibiting increased putative vasogenic edema had previously been linked to COVID-19-related functional and structural alterations, whereas brain regions displaying subtle differences in cellularity between COVID-19 cases and controls included regions within or functionally connected to the olfactory network, which has been implicated in COVID-19 psychopathology. Nevertheless, our study might not have captured acute and transitory neuroinflammatory effects linked to SARS-CoV-2 infection, possibly due to symptom resolution before the imaging scan. Future research is warranted to explore the potential time- and symptom-dependent neuroinflammatory relationship with COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.20.549891v3" target="_blank">Associations between COVID-19 and putative markers of neuroinflammation: A diffusion basis spectrum imaging study.</a>
</div></li>
<li><strong>The double bind of communicating about zoonotic origins: Describing exotic animal sources of COVID-19 increases both healthy and discriminatory avoidance behaviors</strong> -
<div>
Many novel diseases are of zoonotic origin, likely including COVID-19. Describing diseases as originating from diverse exotic animals can increase risk perceptions and protective avoidance behaviors, but may also activate stereotypes, increasing discriminatory behaviors and disease stigma. Data from the first several weeks of the US COVID-19 pandemic tested how communications about zoonotic disease origins affect people’s risk perceptions, health behaviors, and stigma. Participants (N = 677) who read news articles describing exotic animals (e.g., snakes) as sources of COVID-19 viewed the virus as riskier and reported stronger intentions to engage in preventative behaviors (e.g., handwashing), relative to those who read about a familiar source (pigs). Reading exotic origin descriptions was associated with stronger intentions to avoid Asian individuals and animal products, both of which contributed to greater stigma for COVID-19. Results have implications for public health communicators who aim to increase risk perceptions without activating stigma or prejudice.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/948qn/" target="_blank">The double bind of communicating about zoonotic origins: Describing exotic animal sources of COVID-19 increases both healthy and discriminatory avoidance behaviors</a>
</div></li>
<li><strong>Discovery of 2-amide-3-methylester thiophenes that target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an anti-viral target</strong> -
<div>
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has made it clear that further development of antiviral therapies will be needed to combat additional SARS-CoV-2 variants or novel CoVs. Here, we describe small molecule inhibitors for SARS-CoV-2 Mac1, which counters ADP-ribosylation mediated innate immune responses. The compounds inhibiting Mac1 were discovered through high-throughput screening (HTS) using a protein FRET-based competition assay and the best hit compound had an IC50 of 14 M. Three validated HTS hits have the same 2-amide-3-methylester thiophene scaffold and the scaffold was selected for structure-activity relationship (SAR) studies through commercial and synthesized analogs. We studied the compound binding mode in detail using X-ray crystallography and this allowed us to focus on specific features of the compound and design analogs. Compound 27 (MDOLL-0229) had an IC50 of 2.1 M and was generally selective for CoV Mac1 proteins after profiling for activity against a panel of viral and human ADP-ribose binding proteins. The improved potency allowed testing of its effect on virus replication and indeed, 27 inhibited replication of both MHVa prototype CoV, and SARS-CoV-2. Furthermore, sequencing of a drug-resistant MHV identified mutations in Mac1, further demonstrating the specificity of 27. Compound 27 is the first Mac1 targeted small molecule demonstrated to inhibit coronavirus replication in a cell model. This, together with its well-defined binding mode, makes 27 a good candidate for further hit/lead-optimization efforts.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.28.555062v2" target="_blank">Discovery of 2-amide-3-methylester thiophenes that target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an anti-viral target</a>
</div></li>
<li><strong>Effect of Heparin and Tocilizumab in Patients with Severe COVID-19: The HEPMAB Randomized Clinical Trial</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Clinical presentation of severe Coronavirus disease 2019 (COVID-19) is associated to an intense inflammatory response and thrombogenesis. The benefits of the association of interleukin-6 receptor blockade (tocilizumab) and therapeutic-dose anticoagulation remains unclear. We aimed to assess whether heparin and tocilizumab could effectively reduce inflammation and thrombogenesis in severe COVID-19 patients. Methods This is an open-label, multicenter, randomized, clinical trial, involving patients with severe COVID-19 infection. Eligible patients were randomly assigned in a 1:1:1:1 ratio to receive either therapeutic or prophylactic anticoagulation with heparin, with or without an intravenous single dose of tocilizumab. The participants in the study were assigned to one of the four distinct arms: 1) therapeutic anticoagulation; 2) prophylactic anticoagulation; 3) therapeutic anticoagulation plus a single intravenous dose of tocilizumab; and 4) prophylactic anticoagulation plus a single intravenous dose of tocilizumab. The primary outcome was clinical improvement at day 30, defined as a composite of hospital discharge and/or a reduction of at least 2 points of the modified ordinal scale of 7 points recommended by the World Health Organization. Results We enrolled 308 patients. Patients randomized to receive therapeutic anticoagulation more frequently had clinical improvement at day 30 when compared to the prophylactic anticoagulation patients [64/75 (85%) versus 51/80 (64%), odds ratio, 3.31; 95% confidence interval, 1.51; 7.26 P=0.003]. Major bleeding was more frequent in the therapeutic anticoagulation group (6.7%) and in the therapeutic anticoagulation plus tocilizumab group (5.0%), compared to the prophylactic anticoagulation group (P=0.02). All-cause mortality at day 30 was significantly lower in therapeutic anticoagulation group (9.3%), when compared to prophylactic anticoagulation group (28.7%), therapeutic anticoagulation plus tocilizumab group (21.5%) and prophylactic anticoagulation plus tocilizumab group (25.7%), P=0.02. Conclusions In this randomized clinical trial involving severe COVID-19 patients, therapeutic anticoagulation resulted in clinical improvement at 30 days. Even if therapeutic anticoagulation increased bleeding, it was associated with a reduced overall mortality. Tocilizumab did not provide additional benefits to heparin in COVID-19 patients.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.22.23300466v1" target="_blank">Effect of Heparin and Tocilizumab in Patients with Severe COVID-19: The HEPMAB Randomized Clinical Trial</a>
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<li><strong>Synthesis and Assembly of mRNA-Bifunctional Lipid Nanoparticle (BLNP) for Selective Delivery of mRNA Vaccines to Dendritic Cells</strong> -
<div>
The fight against COVID-19 pandemic has gained a strong consensus about the importance of developing mRNA vaccines to rapidly respond to an outbreak. Several studies have shown that mRNA vaccines formulated as mRNA-lipid nanoparticles (LNPs) for vaccination can elicit a robust and efficient immune response. In this study, we report the preparation of mRNA-bifunctional lipid nanoparticles (mRNA-BLNPs) as vaccines for targeted delivery to dendritic cells (DCs) to improve safety and enhance immune response. Using this DC-targeted delivery system, mice immunized with SARS-CoV-2 spike mRNA-BLNP vaccine elicited a stronger immune response with higher titer of neutralizing IgG antibody response than the LNP-formulated vaccine against SARS-CoV-2. In addition, the spike mRNA-BLNP vaccine with deletion of glycosites in the stem elicited a broadly protective immune response against SARS-CoV-2 and variants. These findings suggest the importance and potential of developing DC-targeted mRNA vaccines to elicit broadly protective immune responses against human viruses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.26.572282v1" target="_blank">Synthesis and Assembly of mRNA-Bifunctional Lipid Nanoparticle (BLNP) for Selective Delivery of mRNA Vaccines to Dendritic Cells</a>
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<li><strong>Inferring the sensitivity of wastewater metagenomic sequencing for pathogen early detection</strong> -
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Detecting novel pathogens at an early stage requires robust early warning that is both sensitive and pathogen-agnostic. Wastewater metagenomic sequencing (W-MGS) could meet these goals, but its sensitivity and financial feasibility depend on the relative abundance of novel pathogen sequences in W-MGS data. Here we collate W-MGS data from a diverse range of studies to characterize the relative abundance of known viruses in wastewater. We then develop a Bayesian statistical model to integrate these data with epidemiological estimates for 13 human-infecting viruses, and use it to estimate the expected relative abundance of different viral pathogens for a given prevalence or incidence in the community. Our results reveal pronounced variation between studies, with estimates differing by one to three orders of magnitude for the same pathogen: for example, the expected relative abundance of SARS-CoV-2 at 1% weekly incidence varied between 10^-7 and 10^-10. Integrating these estimates with a simple cost model highlights similarly wide inter-study and inter-pathogen variation in the cost of W-MGS-based early detection, with a mean yearly cost estimate of roughly $19,000 for a Norovirus-like pathogen and $2.9 million for a SARS-CoV-2-like pathogen at 1% incidence. The model and parameter estimates presented here represent an important resource for future investigation into the performance of wastewater MGS, and can be extended to incorporate new wastewater datasets as they become available.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.22.23300450v1" target="_blank">Inferring the sensitivity of wastewater metagenomic sequencing for pathogen early detection</a>
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</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>Could Wearing Face Mask Have Affected Demodex Parasite</strong> - <b>Conditions</b>: Pandemic, COVID-19; Demodex Infestation <br/><b>Interventions</b>: Diagnostic Test: standard superficial skin biopsy (SSSB) <br/><b>Sponsors</b>: Nurhan Döner Aktaş <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>TDCS Stimulation After Covid-19 Infection</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Procedure: Transcranial Direct Stimulation <br/><b>Sponsors</b>: Istanbul Medipol University Hospital; Alanya Alaaddin Keykubat 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>Safety and Immunogenicity of a Booster Vaccination With an Adapted Vaccine</strong> - <b>Conditions</b>: SARS-CoV2 Infection <br/><b>Interventions</b>: Biological: PHH-1V81; Biological: Comirnaty Omicron XBB1.5 <br/><b>Sponsors</b>: Hipra Scientific, S.L.U <br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Combined Modified RNA Vaccine Candidate Against COVID-19 and Influenza.</strong> - <b>Conditions</b>: Influenza; COVID-19 <br/><b>Interventions</b>: Biological: Influenza and COVID-19 Combination A; Biological: Licensed influenza vaccine; Biological: COVID-19 Vaccine; Biological: Influenza and COVID-19 Combination B; Biological: Placebo <br/><b>Sponsors</b>: BioNTech SE; Pfizer <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>Transcranial Pulse Stimulation (TPS) in Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Fatigue <br/><b>Interventions</b>: Device: Transcranial pulse stimulation Verum; Device: Transcranial pulse stimulation Sham <br/><b>Sponsors</b>: Medical University of Vienna; Campus Bio-Medico 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>Evaluate the Efficacy and Safety of “Formosa 1-Breath Free (NRICM101)” in Subjects With the Symptoms of COVID-19 or Influenza-like Disease</strong> - <b>Conditions</b>: Influenza Viral Infections; COVID-19 <br/><b>Interventions</b>: Drug: Formosa 1-Breath Free (NRICM101); Drug: Placebo control drug <br/><b>Sponsors</b>: China Medical University Hospital; Tian-I Pharmaceutical,. Co. Ltd.; China Medical University, China; Qualitix Clinical Research Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 3 Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of Booster Vaccination With Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell); Biological: Recombinant COVID-19 Variant Vaccine (Sf9 Cell); Biological: Placebo <br/><b>Sponsors</b>: WestVac Biopharma Co., Ltd.; WestVac Biopharma (Guangzhou) Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In silico</em> study of inhibition activity of boceprevir drug against 2019-nCoV main protease</strong> - Boceprevir drug is a ketoamide serine protease inhibitor with a linear peptidomimetic structure that exhibits inhibition activity against 2019-nCoV main protease. This paper reports electronic properties of boceprevir and its molecular docking as well as molecular dynamics simulation analysis with protein receptor. For this, the equilibrium structure of boceprevir has been obtained by DFT at B3LYP and ωB97XD levels with 6-311+G(d,p) basis set in gas and water mediums. HOMO-LUMO and absorption…</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>Novel sofosbuvir derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective</strong> - The human coronavirus, SARS-CoV-2, had a negative impact on both the economy and human health, and the emerging resistant variants are an ongoing threat. One essential protein to target to prevent virus replication is the viral RNA-dependent RNA polymerase (RdRp). Sofosbuvir, a uridine nucleotide analog that potently inhibits viral polymerase, has been found to help treat SARS-CoV-2 patients. This work combines molecular docking and dynamics simulation (MDS) to test 14 sofosbuvir-based…</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>Differential Roles of Interleukin-6 in Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Cardiometabolic Diseases</strong> - Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can lead to a cytokine storm, unleashed in part by pyroptosis of virus-infected macrophages and monocytes. Interleukin-6 (IL-6) has emerged as a key participant in this ominous complication of COVID-19. IL-6 antagonists have improved outcomes in patients with COVID-19 in some, but not all, studies. IL-6 signaling involves at least 3 distinct pathways, including classic-signaling, trans-signaling, and trans-presentation…</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>Excessive daytime sleepiness is associated with impaired antibody response to influenza vaccination in older male adults</strong> - CONCLUSION: Our results provide an additional and easily measured variable explaining poor vaccine effectiveness in older adults. Our results support that gaining sufficient sleep is a simple non-vaccine interventional approach to improve influenza immune responses in older adults. Our findings extend the literature on the negative influence of excessive daytime sleepiness on immune responses to influenza vaccination in older male adults.</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>Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS)</strong> - CONCLUSIONS: Ferritin is a clinically useful biomarker in ARDS and is associated with worse patient outcomes. These results provide support for prospective interventional trials of immunomodulatory agents targeting IL-18 in this hyperferritinaemic subgroup of patients with ARDS.</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>Sutimlimab suppresses SARS-CoV-2 mRNA vaccine-induced hemolytic crisis in a patient with cold agglutinin disease</strong> - Cold agglutinin disease (CAD) is a rare form of acquired autoimmune hemolytic anemia driven mainly by antibodies that activate the classical complement pathway. Several patients with CAD experience its development or exacerbation of hemolysis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or after receiving the SARS-CoV-2 mRNA vaccine. Therefore, these patients cannot receive an additional SARS-CoV-2 mRNA vaccination and have a higher risk of severe SARS-CoV-2…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of host proteins interacting with non-structural protein nsp9 of porcine epidemic diarrhea virus on viral replication</strong> - Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic virus that can cause acute intestinal infectious diseases in both piglets and fattening pigs. The virus encodes at least 16 non-structural proteins, including nsp9, which has been shown to bind to single-stranded RNA. However, its function and mechanism remain unclear. In this study, we aimed to identify potential host proteins that interact with PEDV nsp9 using immunoprecipitation combined with mass spectrometry. The interactions…</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>COVID-19 in Dental Practice Is Prevented by Eugenol Responsible for the Ambient Odor Specific to Dental Offices: Possibility and Speculation</strong> - Dental professionals routinely work in proximity to patients even when either or both of them have suspected or confirmed COVID-19. The oral cavity also serves as a reservoir for SARS-CoV-2 because the virus is present in and replicates in oral secretions (saliva and gingival crevicular fluid), oral tissues (salivary gland and periodontal tissue), and oral microenvironments (gingival sulcus and periodontal pocket). Despite a high risk of SARS-CoV-2 infection, the prevalence of COVID-19 in…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of Porcine Deltacoronavirus Entry and Replication by Cepharanthine</strong> - Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that mainly causes acute diarrhea/vomiting, dehydration, and mortality in piglets, possessing economic losses and public health concerns. However, there are currently no proven effective antiviral agents against PDCoV. Cepharanthine (CEP) is a naturally occurring alkaloid used as a traditional remedy for radiation-induced symptoms, but its underlying mechanism of CEP against PDCoV has remained elusive. The…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Does denosumab exert a protective effect against COVID-19? Results of a large cohort study</strong> - CONCLUSION: Our study confirms that denosumab may be safely continued in COVID-19 patients. RANK/RANKL inhibition seems associated with a reduced incidence of symptomatic COVID-19, particularly among the elderly.</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>Intranasal murine pneumonia virus-vectored SARS-CoV-2 vaccine induces mucosal and serum antibodies in macaques</strong> - Next-generation SARS-CoV-2 vaccines are needed that induce systemic and mucosal immunity. Murine pneumonia virus (MPV), a murine homolog of respiratory syncytial virus, is attenuated by host-range restriction in nonhuman primates and has a tropism for the respiratory tract. We generated MPV vectors expressing the wild-type SARS-CoV-2 spike protein (MPV/S) or its prefusion-stabilized form (MPV/S-2P). Both vectors replicated similarly in cell culture and stably expressed S. However, only S-2P 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>Efficacies of S-nitrosoglutathione (GSNO) and GSNO reductase inhibitor in SARS-CoV-2 spike protein induced acute lung disease in mice</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially surfaced in late 2019, often triggers severe pulmonary complications, encompassing various disease mechanisms such as intense lung inflammation, vascular dysfunction, and pulmonary embolism. Currently, however, there’s no drug addressing all these mechanisms simultaneously. This study explored the multi-targeting potential of S-nitrosoglutathione (GSNO) and N6022, an inhibitor of GSNO reductase (GSNOR) on markers…</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>Comparative transcriptome analysis of SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E identifying potential IFN/ISGs targets for inhibiting virus replication</strong> - INTRODUCTION: Since its outbreak in December 2019, SARS-CoV-2 has spread rapidly across the world, posing significant threats and challenges to global public health. SARS-CoV-2, together with SARS-CoV and MERS-CoV, is a highly pathogenic coronavirus that contributes to fatal pneumonia. Understanding the similarities and differences at the transcriptome level between SARS-CoV-2, SARS-CoV, as well as MERS-CoV is critical for developing effective strategies against these viruses.</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>Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity</strong> - The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development</strong> - Antiphospholipid antibodies (aPL) in primary or secondary antiphospholipid syndrome (APS) are a major cause for acquired thrombophilia, but specific interventions preventing autoimmune aPL development are an unmet clinical need. While autoimmune aPL cross-react with various coagulation regulatory proteins, lipid-reactive and COVID-19 patient-derived aPL recognize the endo-lysosomal phospholipid lysobisphosphatidic acid (LBPA) presented by the cell surface expressed endothelial protein C receptor…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Border Crisis</strong> - Dexter Filkins reports on the chaotic situation at the southern border. Plus, a poet whose writing on the DeafBlind experience is full of humor and life. - <a href="https://www.newyorker.com/podcast/the-new-yorker-radio-hour/the-crisis-at-the-border">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why the Noise of L.A. Helicopters Never Stops</strong> - The L.A.P.D. says it has the largest local airborne law-enforcement unit in the world. A recent audit found little evidence that its choppers deter crime. - <a href="https://www.newyorker.com/news/letter-from-los-angeles/why-the-noise-of-la-helicopters-never-stops">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Colorado’s Top Court Kicked Trump Off the Ballot. Will the Supreme Court Agree?</strong> - A legal scholar analyzes how the nine Justices are likely to view the blockbuster decision. - <a href="https://www.newyorker.com/news/q-and-a/colorados-top-court-kicked-trump-off-the-ballot-will-the-supreme-court-agree">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>When Americans Are the Threat at the Border</strong> - Many people charged with trafficking in Tucson are U.S. citizens, suffering from the same problems of poverty and addiction that plague the rest of the country. - <a href="https://www.newyorker.com/news/daily-comment/when-americans-are-the-threat-at-the-border">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How Netanyahu’s Right-Wing Critics See Israel’s Future</strong> - Danny Danon, the former Israeli Ambassador to the United Nations, believes there’s no path forward for a Palestinian state. - <a href="https://www.newyorker.com/news/q-and-a/how-netanyahus-right-wing-critics-see-israels-future">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The best advice we got in 2023</strong> -
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<img alt="An illustration of a blue background with a white cartoonish man with a hole in his mid-section. A hand holding a flower reaches out from the hole." src="https://cdn.vox-cdn.com/thumbor/p02u1wJodLh15f7UE01BqmIJzt8=/0x0:8164x6123/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73011481/GettyImages_1389716481.0.jpg"/>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Expert-approved tips — both big and small — to take you into 2024 and beyond.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dArvB7">
For those looking for a quick fix on <a href="https://www.vox.com/life">how to live</a> better, here’s the bad news: There’s no one right way to experience life. We’re all doing our best to get by and treat others with respect in a world that’s flawed, messy, and unequal. The good news: With no one-size-fits-all approach to happiness, anything that brings joy to others and ourselves is worth pursuing. How we make meaning in our lives, despite the challenges we face, can help bring us closer to that ideal “best” life.
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WjxKyD">
At Vox, much of my reporting centers on helping people live better, offering insight on how to have stronger relationships, a deeper understanding of the self, and how to be a little kinder to ourselves (and everyone else) in the process. As I look back on the advice shared with <a href="https://www.vox.com/even-better">Even Better</a> in 2023 — lessons from academics and authors to therapists and <a href="https://www.vox.com/parenting">parenting</a> gurus — the biggest takeaway I gleaned was how little effort it takes to imbue life with a bit more meaning. Whether that means effectively connecting with friends and loved ones or getting a little closer to finding your life’s purpose, experts have offered insights that have informed our work all year.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BRZWIp">
After combing through all the many words of wisdom shared with readers this year, here are some of the most poignant pieces of advice on how to live a more meaningful life.
</p>
<h3 id="dlAqlK">
Have one meaningful face-to-face conversation every day
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EbPKSf">
There’s no magic formula for how much social interaction one needs to feel fulfilled, but <a href="https://coms.ku.edu/people/jeffrey-hall">Jeffrey Hall</a>, a professor of communication studies and the director of the <a href="https://randtlab.ku.edu/">Relationships and Technology Lab</a> at the University of Kansas has one bit of advice: “The most impactful thing to do is have a meaningful conversation with someone you really like, face-to-face” every day, he says. The second best is having a daily conversation that fits any of the following criteria: The chat is face-to-face, it’s with someone you’re close with, or it’s a quality discussion (meaning you’re catching up, laughing, or getting deep).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dEUT3V">
<a href="https://www.vox.com/even-better/23744304/how-much-social-interaction-do-you-need-loneliness-burnout"><strong>Read more: How much social interaction do you actually need?</strong></a>
</p>
<h3 id="ul99Gj">
Send the text already
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ciLqBz">
You’re thinking of a friend whom you haven’t talked to in a while and want to send them some well wishes. Or maybe you want to compliment a stranger’s jacket on the street. Will your friend respond? Will the stranger think you’re weird? We often talk ourselves out of offering low-lift kindnesses to others due to fear we’ll be rejected or embarrassed. Plenty of studies show that doing the nice thing — sending the text or the thank-you note, extending the compliment — is well received <em>and</em> makes you feel good, too. “Being kind to other people, doing nice things for others — those are the activities that tend to improve our well-being,” says <a href="http://www.kumar-amit.com/">Amit Kumar</a>, assistant professor of marketing and <a href="https://www.vox.com/psychology">psychology</a> at the University of Texas at Austin. “Folks have lots of opportunities for acting in these other-oriented ways that they don’t take advantage of.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JYME2Y">
<a href="https://www.vox.com/even-better/23670005/small-acts-kindness-matter-liking-gap"><strong>Read more: Small acts of kindness matter more than you think</strong></a>
</p>
<h3 id="BkacgX">
Capture memories with simple reflections
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rz34xq">
If you wake up every morning with little recollection of what you did the day prior, take a few minutes before bed to think back on moments you want to remember. Whether you choose to look at photos or videos on your phone, write in a gratitude journal, or recap the day with your partner or roommate, the more you reflect on your life, “over time you realize you’ll actually be able to remember more details of your life,” says five-time USA Memory Champion and memory coach <a href="https://www.nelsondellis.com/">Nelson Dellis</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LDwPqr">
<a href="https://www.vox.com/even-better/23537229/improve-your-memory-concentration-tips"><strong>Read more: Want to improve your memory? Try these unexpected tips.</strong></a><strong> </strong>
</p>
<h3 id="EeOuxS">
Start a niche, ritualized social activity
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TN4pVo">
A potential answer to the eternal question of “how do I make more friends in adulthood?” per Vox’s Rebecca Jennings: Join a club. “It’s a lot less risky to ask someone — or all of your <a href="https://www.vox.com/instagram-news">Instagram</a> followers — if they want to join your book club or pizza club or whatever club than to ask them to hang out one-on-one,” she writes. “When there’s a schedule and an activity, there’s less room for either party to feel as though they’re contributing too much or not enough, to convince themselves every uncomfortable silence equals imminent humiliation.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Mkpzdh">
<a href="https://www.vox.com/even-better/23837430/how-to-make-friends-start-a-club"><strong>Read more: Want to make more friends? Start a club.</strong></a><strong> </strong>
</p>
<h3 id="WD6INJ">
Just being there for someone who’s going through a hard time is enough
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YGcVRX">
When tragedy strikes and we’re called upon to support those we love, we often freeze. We’re afraid of doing or saying the wrong thing and further upsetting our already grieving friend. However, simply calling or texting a loved one and offering time is enough, says <a href="https://faculty.sites.uci.edu/rsilver/">Roxane Cohen Silver</a>, a distinguished professor of psychological science, <a href="https://www.vox.com/public-health">public health</a>, and medicine at the University of California Irvine. Don’t overthink it: Ask, “How are you feeling today?” or say, “I’m thinking of you,” “You crossed my mind today,” and “I’m just checking in.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j630Do">
<a href="https://www.vox.com/even-better/23589570/offer-help-support-validation"><strong>Read more: How to offer help when you don’t know what to say</strong></a>
</p>
<h3 id="s3GOLD">
When speaking with kids, let them lead the conversation
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mG6ugp">
Children are some of the most interesting conversation partners once you get them going. To get there, resist the urge to fill the space and let them guide the conversation. “Ask questions and let the kid direct the flow; they’ll naturally lead the conversation toward what interests them most,” contributor <a href="https://www.vox.com/even-better/23818627/how-to-talk-to-kids-adult-conversation">Charley Locke writes</a>. Ask kiddos about their hobbies and favorite subjects in school, and “don’t try to show off how much you know — encourage them to share instead,” writes Locke.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8g3i9E">
<a href="https://www.vox.com/even-better/23818627/how-to-talk-to-kids-adult-conversation"><strong>Read more: How to (actually) talk to kids</strong></a><strong> </strong>
</p>
<h3 id="MkGL97">
Apologizing is more than saying you’re sorry
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zlp2eT">
An effective apology has six (and a half) components, according to Marjorie Ingall and Susan McCarthy, the authors of the book <a href="https://www.simonandschuster.com/books/Sorry-Sorry-Sorry/Marjorie-Ingall/9781982163495"><em>Sorry, Sorry, Sorry: The Case for Good Apologies</em></a>:
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The words “I’m sorry” or “I apologize.”
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The specific reason you’re apologizing; the thing you did.
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An understanding of why your actions hurt another person.
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An explanation for why you did what you did (but don’t make excuses).
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A plan for how you will avoid this infraction again in the future.
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An offer to fix what’s broken.
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Finally, listen to the person or people you hurt — that’s the half-step.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xr0Lsy">
<a href="https://www.vox.com/even-better/23622442/saying-sorry-apologize"><strong>Read more: Everyone messes up. Here’s how to say you’re sorry.</strong></a>
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Make purposeful activities a regular part of your life
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A life’s purpose is something you pursue long-term, are competent in, and that has an impact on the world or your community. If you have no idea what your purpose is, don’t panic: Many people don’t cultivate purpose until well into adulthood. To live more purposefully, think about the activities that you enjoy, and that fulfill and motivate you, then “organize your life in a way that allows for you to make those things more habitual,” says <a href="https://artsci.wustl.edu/faculty-staff/patrick-hill">Patrick Hill</a>, an associate professor of psychological and brain sciences at Washington University in St. Louis. “Ultimately, that can be a way to help people think about developing a purpose from the ground up, eventually.”
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<a href="https://www.vox.com/even-better/23653236/how-to-find-life-purpose-values-talent"><strong>Read more: How to foster your purpose wherever you are in life</strong></a>
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Use more words to describe your emotions
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Therapy-speak offers succinct sound bites for complex terms. In the process, the meanings of these concepts, like gaslighting or trauma, become flattened and misconstrued. Instead of relying on pop psychology terms, try to be more descriptive when discussing your emotions and experiences, says licensed marriage and family therapist <a href="https://theemoeari.com/">Moe Ari Brown</a>. “If you’re wanting to call someone a narcissist,” Brown says, “what is it that I mean? I’m meaning that I experienced them as self-important and not really taking the time to notice other people’s needs. It’s okay to say that because that really clearly expresses what you’re thinking.”
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<a href="https://www.vox.com/even-better/23769973/limits-therapy-speak-narcissist-gaslighting-trauma-toxic"><strong>Read more: The limits of therapy-speak</strong></a><strong> </strong>
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<h3 id="eMLx07">
Give yourself permission to quit
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If you’re considering picking up a new hobby as a New Year’s resolution, first of all: good for you! Second of all: give yourself criteria for when you’ll let yourself quit, also known as “kill criteria,” according to <a href="https://www.annieduke.com/">Annie Duke</a>, author of <a href="https://www.penguinrandomhouse.com/books/692752/quit-by-annie-duke/"><em>Quit: The Power of Knowing When to Walk Away</em></a>.
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For example, “I’m going to run the marathon unless at some point, the medical staff tells me that I really ought to stop,” Duke says. What is the line you’d need to cross to give up on an endeavor?
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NaPlCL">
<a href="https://www.vox.com/the-highlight/23824299/when-to-quit-job-hobby-when-to-keep-going"><strong>Read more: The art of quitting</strong></a><strong> </strong>
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<h3 id="s6U6Pn">
Feel free to ignore all of this advice if it doesn’t align with your life
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Advice is only good advice if it feels applicable. “If the advice just does not gel with your lifestyle, if it’s not practical, it can be good advice for someone but not for you,” says John Paul Brammer, author of the advice column <a href="https://holapapi.substack.com/"><em>¡Hola Papi!</em></a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MAVWmv">
Similarly, parenting advice isn’t one-size-fits-all. What one child responds to may not be successful with another, even within the same family. “If you’re trying to do something, and it’s not working in your family, go ahead and give yourself the freedom to just not do it,” Bethany L. Johnson, a doctoral student in history at the University of South Carolina and co-author of the book <a href="https://www.vox.com/2019/4/23/18508136/pregnancy-mothers-moms-babies-advice-quinlan-johnson"><em>You’re Doing it Wrong! Mothering, Media, and Medical Expertise</em></a>, told Vox’s Anna North.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qYYOd3">
<a href="https://www.vox.com/even-better/23760823/what-is-good-advice"><strong>Read more: How to tell when you’re getting good advice</strong></a>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="17GvYp">
<a href="https://www.vox.com/the-highlight/23700540/parenting-advice-endless-recycling-dr-spock-gentle-parenting"><strong>Read more: From banning hugs to gentle parenting, how are you supposed to raise kids, anyway?</strong></a>
</p></li>
<li><strong>Relationships aren’t always going to be totally balanced. That isn’t a bad thing.</strong> -
<figure>
<img alt="A painted scene shows a woman leaning on her friend’s shoulder. The friend is faced away, looking off to the side." src="https://cdn.vox-cdn.com/thumbor/9lcc5xf2xBEWQgA_CSbI2yvIBjM=/240x0:1680x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72834100/Vox_Reciprocity_Crisis_Final_Stapleton.0.jpg"/>
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Holly Stapleton for Vox
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We shouldn’t give up on others so easily.
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Would you give your mother nearly $10,000 to help her avoid catastrophe?
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6aShLy">
The question wasn’t rhetorical for comedian and writer Ashley Ray-Harris when, in September, the 32-year-old got a call from her mom. The family had a week to come up with close to $10,000 or else Ray-Harris’s mother would lose the house that once belonged to her parents.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xBZAJk">
In a karmic turn of fate, Ray-Harris had the funds. She’d slowly set aside $10,000 for a new car — her dream car, a 2017 Mazda CX-5. Instead of a down payment, Ray-Harris used her savings to keep a roof over her mother’s head.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GndCis">
The choice was never a choice at all. Reciprocating care and support to the woman who raised her was the only option. Throughout her life, Ray-Harris’s mother had spent money on guitar lessons, horseback riding lessons, and private school tuition — not to mention food, clothing, and shelter. “I’m able to help my mom with this because she put me in a place to achieve my dreams,” Ray-Harris says. “Obviously, I would pay that back to her.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ShZOQU">
A not-insignificant number of strangers on the internet would have advised Ray-Harris to do just the opposite. In a moment of frustration, Ray-Harris <a href="https://twitter.com/theashleyray/status/1704659297878388737">posted about her family’s circumstances</a> on X (formerly <a href="https://www.vox.com/twitter">Twitter</a>) and received a wide array of responses. Many people were moved by Ray-Harris’s readiness to come to her mother’s aid; others shared stories of similarly shouldering a large expense for their loved ones. What she wasn’t expecting was the number of replies from people who said they would not have offered the money to a parent. “People have different relationships with their parents,” she says, “but just the number of people who were like, ‘I love my mom, but I would never do this for her,’ seemed to come from a somewhat self-centered place.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="36e3Vh">
The support we’re willing to offer a close intimate (a parent, say) will vary wildly from what we feel we owe a stranger. Constant asks — for time, attention, affection, and money — can wear on a person’s patience, especially if they’re being called upon by multiple people in their lives. Silently keeping score in relationships may lead us to turn away from others when they need us most. From being <a href="https://knowyourmeme.com/memes/im-actually-at-my-emotional-capacity">too “at capacity” to support a friend</a> to permanently <a href="https://www.glamour.com/story/to-all-my-friends-this-is-my-bridesmaid-resignation-letter">resigning from bridesmaid duties</a>, some people are tightening the reins on their emotional output in relationships of all stripes. <a href="https://twitter.com/Codie_Sanchez/status/1629563662200451075?lang=en">Asking a friend for a ride home from the airport</a> could be considered a moral offense. Dedicating a few minutes to <a href="https://twitter.com/snarkeigh/status/1707033402048679939">watch over a stranger’s belongings at a coffee shop</a> is a few minutes too long. Depending on your circumstances, offering time and support is too great a weight to bear without certainty you’ll get something in return.
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As a result, some are sensing a <a href="https://www.thecut.com/article/hola-papi-setting-boundaries-with-friends.html">“lack of reciprocation” with friends</a>, an <a href="https://www.vox.com/23026672/how-to-handle-a-lopsided-friendship">imbalance</a> within relationships, and an <a href="https://www.thecut.com/article/adult-friendships-vs-kids.html">intense focus on</a> <a href="https://www.theatlantic.com/family/archive/2023/09/relationship-balance-love-friendship-autonomy/675321/">the nuclear family</a> over community. People are undeniably spread thin, <a href="https://www.vox.com/money/23770003/economy-job-market-rich-poor-middle-class-stocks">financially</a>, <a href="https://www.vox.com/23144336/emotional-exhaustion-friendships-community">emotionally</a>, and <a href="https://www.pewresearch.org/short-reads/2020/02/05/how-americans-feel-about-the-satisfactions-and-stresses-of-modern-life/">for time</a>, and they’re turning inward to seek reprieve. On a broad scale, this individualistic mindset can contribute to the<a href="https://www.vox.com/even-better/23744304/how-much-social-interaction-do-you-need-loneliness-burnout"> ongoing loneliness epidemic</a> and diminish <a href="https://www.vox.com/22992901/how-to-find-your-community-as-an-adult">avenues for social support</a>. Although we are limited in our resources of time and emotions, we shouldn’t resign from duties of care and in the process relinquish ourselves from a tit-for-tat mentality. We can give of ourselves to those we interact with because we want to, not to even the score or to expect something in return.
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<h3 id="tQV4fP">
Why we all need extra support right now
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If it feels as though more people are in need of something, from the menial to the consequential, it’s because they are. There are more emotionally vulnerable people than ever. Most notably, the <a href="https://www.vox.com/coronavirus-covid19">Covid-19 pandemic</a> wrought suffering for many — the loss of life, employment, and social support led to <a href="https://www.kff.org/mental-health/issue-brief/the-implications-of-covid-19-for-mental-health-and-substance-use/">increased rates of anxiety, depression, and substance use</a>. <a href="https://news.gallup.com/poll/473057/loneliness-subsides-pandemic-high.aspx">Seventeen percent of Americans say they feel lonely daily</a>; 12 percent of Americans <a href="https://www.americansurveycenter.org/research/the-state-of-american-friendship-change-challenges-and-loss/">reported having no close friends at all in 2021</a>, up from 3 percent in 1990. A <a href="https://www.apa.org/news/press/releases/stress/2022/concerned-future-inflation">majority of adults are stressed</a> by inflation, the <a href="https://www.vox.com/economy">economy</a>, and having enough money to buy essentials. <a href="https://www.kff.org/report-section/kff-cnn-mental-health-in-america-survey-findings/">Half of adults say</a> they or a family member experienced a <a href="https://www.vox.com/mental-health">mental health</a> crisis, with <a href="https://publications.aap.org/pediatrics/article/149/5/e2022056611/184904/Epidemic-Rates-of-Child-and-Adolescent-Mental?autologincheck=redirected">mental health disorders reaching “epidemic rates” in children and adolescents</a>.
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During times of heightened emotional demand, there are two choices: leaning into collective care and support or shying away from others. “Where there’s need and stress, you can choose the path of individualism and pushing people away and never being there for anybody else because you’re so consumed with only preserving and protecting yourself,” says connection coach <a href="https://www.katvellos.com/">Kat Vellos</a>, author of <a href="https://weshouldgettogether.com/"><em>We Should Get Together: The Secret to Cultivating Better Friendships</em></a>, “or you can band together with other people and collectively pool your resources, whether those are emotional resources, financial resources, communal respect, social capital resources, and share the things that you have so that you can lift each other up and actually lighten the load for multiple people at one time.”
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Working collaboratively for the betterment of all becomes increasingly difficult in the absence of trust in one another. According to a <a href="https://www.pewresearch.org/politics/2019/07/22/trust-and-distrust-in-america/">2019 Pew Research Center survey</a>, 64 percent of Americans believe their trust in one another has shrunk. Half of Americans attribute this lack of trust to “a belief that people are not as reliable as they used to be,” according to the Pew survey. A lack of faith in others to come to our aid in a time of need supports the idea that we must be self-sustaining. “It’s up to each person to choose the world they want to live in: Is it one where you’re not going to look out for anybody else, but you maybe can’t expect anybody else to look out for you too?” Vellos says. “Or is it a world where you can be generous and compassionate with other people? Even if the amount we’re able to give varies day to day or hour to hour, but you know through investing in those relationships that when you need help and you need support, somebody else is going to be there for you, too.”
</p>
<h3 id="3CUBlN">
Why we shouldn’t “keep score” in relationships
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sen8ej">
A functional relationship requires a few ingredients: trust, consistency, and spending quality time together, says <a href="https://www.kasleykillam.com/">Kasley Killam</a>, an expert in social health and connection and the author of a forthcoming book on social health. But perhaps most crucial is <a href="https://dictionary.apa.org/responsiveness">responsiveness</a>, or how attentive we are to another person’s wants, needs, and goals, according to <a href="https://www.psychology.uga.edu/directory/people/richard-slatcher">Richard Slatcher</a>, a professor in the <a href="https://www.vox.com/psychology">psychology</a> department at the University of Georgia. Responsiveness can take the form of both instrumental support — like helping a friend move — and emotional support, such as listening closely in conversation. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891543/">Research has shown</a> that responsive partners convey warmth, understanding, validation; they strive to make their partners feel valued. When that responsiveness is reciprocated, what results is “upward spirals of responsiveness that ultimately enhance relationship quality for both people,” according to the authors of a 2010 study.
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Sometimes, one party will endure a season of extended giving — perhaps after a friend <a href="https://www.vox.com/even-better/23589570/offer-help-support-validation">loses a job</a> or has a baby — but ideally, both sides will offer just as much as they accept. “A relationship is worth it if the benefits outweigh the costs — if you get as good as you give, so to speak,” says <a href="https://www.uoguelph.ca/psychology/users/pat-barclay">Pat Barclay</a>, a professor of psychology at the University of Guelph. “If the costs start to outweigh the benefits, then people might not want to keep giving if they feel they’re being asked too much.”
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The problem is, we’re notoriously biased when it comes to estimating how much of ourselves we extend to others compared to what we get in return, says <a href="https://www.uwinnipeg.ca/psychology/faculty-staff/beverley-fehr.html">Beverley Fehr</a>, a professor of psychology at the University of Winnipeg. Remembering all of the good deeds you’ve done for your sister comes far easier than recalling the times she brought you groceries when you were sick, cared for your pets while you were on vacation, and listened to you vent about work. “Partly, we have that bias in the interest of self-esteem or self-protection, wanting to feel good about ourselves, like ‘I’m the one who gives all the time,’” Fehr says. “But the other piece of it is that it’s just easier to remember our contributions than to remember another person’s contributions to a relationship.”
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We don’t consciously keep score, Barclay notes. However, if resentment overtakes enthusiasm whenever a friend asks a favor, “that’s a sign your brain has been tracking that maybe they haven’t been pulling their weight,” he says.
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When we feel like we’re the only ones doing the heavy lifting in a relationship, we’re likely to turn away from those connections. A friend may spend all of their emotional reserves worrying about getting their kids to school, making it through the workday, and having enough money for groceries. <a href="https://www.vox.com/even-better/23861234/birthday-week-trip-expensive-celebration-friendship">Attending your birthday party</a> may not be a priority. As a result, both sides are deprived of what could have been a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416486/">rejuvenating</a> <a href="https://link.springer.com/article/10.1007/s10902-022-00506-5">social</a> <a href="https://ourworldindata.org/happiness-and-friends">encounter</a>. The edicts of self-care would have us believe that safeguarding ourselves, not giving more of our energy to others, is the balm to emotional exhaustion.
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But if society is made up of an emotionally tapped populace, there may not be enough support to go around. “The more [emotionally] needy people there are out there, the more demands there will be and it will be harder to meet each one,” Barclay says. “Furthermore, the more needy people there are, people who generally need emotional support, the less capacity each person will have … to be able to help others. So as conditions get worse, you might expect people to have less ability to help simply because there’s too many people to help and they don’t have as much capacity to give.”
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<h3 id="Gbr99H">
Focus on the self encourages individualism
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In the absence of <a href="https://greatergood.berkeley.edu/article/item/can_government_policies_make_us_happier">policy changes</a> <a href="https://www.vox.com/policy/2023/5/3/23707936/surgeon-general-loneliness-epidemic-report">that would provide</a> more of a social and financial safety net, <a href="https://time.com/6269091/individualism-ahead-of-the-common-good-for-too-long/">Americans look internally to</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394986/">improve their circumstances</a>. Since the 1970s, <a href="https://www.atlantisjournal.org/old/ARCHIVE/31.2/2009MurEffing.pdf">self-help media has provided an avenue for people to improve their lives</a> when so much — wages, costs — is out of their control. The rise of the <a href="https://www.vox.com/health">wellness</a> industry <a href="https://www.latimes.com/lifestyle/story/2022-10-18/self-care-needs-to-change">commodified self-care as something that can be purchased</a> and experienced alone as a means of restoration. Even the <a href="https://www.vox.com/even-better/23769973/limits-therapy-speak-narcissist-gaslighting-trauma-toxic">popularization of therapy-speak</a> reinforces the notion of tending to the self above all others. This focus on the individual as the sole determinant of happiness allows people increasingly to look inward for ways to better their lives.
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This individualized approach to emotional fulfillment breeds what <a href="https://blogs.helsinki.fi/kkuurne/in-english/">Kaisa Kuurne</a>, a sociology lecturer at the University of Helsinki, and her colleague refer to as a “<a href="https://www.tandfonline.com/doi/abs/10.1080/21582041.2014.988289">capable actor</a>.” To outsiders, a capable actor is a highly productive member of society, but they find it difficult to ask for help or to express vulnerability. “It’s a side effect,” Kuurne says, “of individualism. That it can be potentially stigmatizing to be needy, so then you’re not really the moral individual.”
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If you consider yourself efficient and independent, you may assume others in your life are, too. The capable actor theory explains the sentiment of those in comedian Ray-Harris’s X replies who encouraged her to leave her mother in the lurch, Kuurne says: that others’ apparent inability to care for themselves leaves them somehow unworthy of support. To think this way is to deny our collective vulnerability, Kuurne says. Sacrificing time and resources for another isn’t wasteful; it can <a href="https://www.vox.com/even-better/23653236/how-to-find-life-purpose-values-talent">imbue meaning and purpose</a> and joy, says Killam, the social health expert. “Connection is a joy,” she says. “It’s not a chore. And if it feels like a chore, then maybe we need to reevaluate what our values are, what our priorities are.”
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<h3 id="CkzASz">
Purposefully prioritizing responsiveness
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There are plenty of valid reasons we might be unable to support those in our life: family demands, work stress, money troubles, a mental health crisis, lost patience for a particularly time-consuming friend. However, we should avoid thinking of our relationships as transactional, but consider them mutually beneficial, connection coach Vellos says. They are people who enrich your life and whom you can count on in a time of need — and vice-versa. “If somebody views every interaction in our capitalist environment as some type of transaction,” she says, “they might unfairly categorize a very natural friendship interaction as some kind of transaction.”
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We have to be motivated to view connections as a wellspring of meaning, says Slatcher, the University of Georgia professor. Considering others’ wants and needs does not mean ignoring your own; it means becoming more discerning in how to offer the appropriate support. Bolstering responsiveness in a relationship involves some trial and error, Fehr, the University of Winnipeg professor, says: You must discern whether a friend wants you to simply be a listening ear or hopes you spring into action to offer practical support. Acting out of self-interest is not particularly motivating, a <a href="https://link.springer.com/article/10.1007/s11031-022-09949-y">2022 study found</a>. Instead, people are more likely to help in personal relationships when they feel like it is a reflection on their character.
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So what, then, do we owe each other? To actually be there for someone, we must spend time together and be open to vulnerability. Among all of life’s demands and responsibilities, we may not have the time to check in with a friend, let alone get together with them. “You’re rarely in the same place as your intimate unless you arranged it intentionally,” Kuurne says. But if we don’t dedicate the time and space to those we love, they won’t know how to support us — and how we can support them — and thus won’t be as responsive.
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Life is not a one-person show, but a company of players in an ensemble act. When someone we love is in need, as was Ray-Harris’s mother, we come to their aid not because we want something in return, but because our well-being depends on theirs. And if life gets too busy, too hectic, too chaotic, too <em>much</em> that we can’t prioritize those we love, it’s time to recalibrate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="P88eIX">
“Because what are we actually living for?” Killam says. “It should be our relationships and the joy that comes from spending time with people you love.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KCpPTT">
</p></li>
<li><strong>Alcohol overuse causes 140,000 American deaths annually. Why is it so undertreated?</strong> -
<figure>
<img alt="An illustrative collage shows a silhouetted person looking downward. A hand reaches for one of several alcohol bottles in the foreground." src="https://cdn.vox-cdn.com/thumbor/ZM5XZ0C6G837_MCh1COmLBvKX1k=/240x0:1680x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72834098/Alcohol_Use_Disorder_Final.0.png"/>
<figcaption>
Vartika Sharma for Vox
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Medications can help the 1 in 12 people who suffer from alcohol use disorder. But most will never be treated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sLQu8G">
There is something that kills more Americans every year than <a href="https://www.cdc.gov/drugoverdose/deaths/index.html">drug overdoses</a>, than <a href="https://www.pewresearch.org/short-reads/2023/04/26/what-the-data-says-about-gun-deaths-in-the-u-s/">guns</a>, than <a href="https://www.iihs.org/topics/fatality-statistics/detail/yearly-snapshot">car accidents</a>. It’s legal, doesn’t require a background check to buy, is widely advertised, and if you’re 21, you can probably buy it at your corner store. It’s called alcohol.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hC4R86">
While cold beers, glasses of wine, and hard liquor cocktails are often treated as end-of-the-workday or weekend indulgences, alcohol is technically a <a href="https://boardwalkrecoverycenter.com/is-alcohol-a-psychoactive-drug/">psychoactive, addictive drug</a>, one linked to over 50 fatal conditions, including heart disease; breast, pancreatic, and stomach cancers; liver disease; hypertension; and stroke. It contributes to the death of <a href="https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-related-emergencies-and-deaths-united-states#:~:text=It%20is%20estimated%20that%20more,physical%20inactivity%2C%20and%20illegal%20drugs.">140,000</a> people in the US annually, making it one of the <a href="https://www.cdc.gov/chronicdisease/resources/publications/factsheets/alcohol.htm">leading causes of preventable death</a> in the country.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3NYMcu">
More and more research supports the conclusion that even light drinking — that is, less than <a href="https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking">15 drinks</a> a week for men or eight drinks a week for women — can contribute to an <a href="https://www.nytimes.com/2023/01/13/well/mind/alcohol-health-effects.html">increased risk</a> for heart disease and cancers. More recent <a href="https://www.bbc.com/news/world-us-canada-64311705">medical recommendations in countries like Canada</a> have increasingly tightened, moving toward the idea that there is no truly safe level of alcohol consumption.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ipJ8f4">
But the dose is the poison, and those who are at the greatest risk are those who consistently binge drink. This group suffers from alcohol use disorder, a condition where someone consumes excessive amounts of alcohol to the point that it impairs their ability to stop or control their use despite negative social, occupational, or health consequences. And that group is larger than you might think: <a href="https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-use-disorder-aud-united-states-age-groups-and-demographic-characteristics#:~:text=Prevalence%20of%20Past%2DYear%20Alcohol%20Use%20Disorder%20(AUD)&amp;text=According%20to%20the%202021%20National,AUD%20in%20the%20past%20year.">more than 1 in 12 people</a> in the US have AUD, and it’s likely that figure underestimates the real breadth of the problem.
</p>
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In the 20th century, binge drinking coupled with its negative repercussions was called alcohol abuse, alcohol dependence, alcohol addiction, or alcoholism. However, such diagnoses carry a shameful stigma and make unhealthy alcohol use seem like purely a bad choice, rather than the result of a brain-altering disease. By not indicating a range in how alcohol overuse can affect a person, these names also fell short of describing the condition of all people who drink in unhealthy ways. In 2013, the American Psychiatric Association began defining all forms of excessive alcohol use as alcohol use disorder, or <a href="https://alcoholtreatment.niaaa.nih.gov/what-to-know/alcohol-use-disorder">AUD</a>.
</p>
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“Decades ago alcohol use, and really all substance use disorders in general, were sort of viewed as personality flaws or moral failings,” <a href="https://psychiatry.wustl.edu/people/carrie-mintz-md/">Carrie Mintz</a>, an assistant professor of psychiatry at <a href="https://medicine.wustl.edu/">Washington University</a> in St. Louis, told Vox. “We really know now — especially from the past 50 years of increasing amounts of research and data — that these are really brain diseases. There are clear neurologic changes that occur with repeated pathologic use of a potentially addictive substance like alcohol.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j0SqsJ">
But while America treats other dangerous substances, such as opioids, as a public health problem, alcohol use is not treated similarly as a crisis — legally, medically, or culturally. Rather, access to alcohol is only growing. The alcoholic beverage industry <a href="https://www.parkstreet.com/alcoholic-beverage-market-overview/">generated $250 billion</a> in revenue in 2021, while the category of hard alcohol spirits <a href="https://www.pbs.org/newshour/economy/spirits-surpass-beer-for-u-s-market-share-supremacy-data-shows">has now surpassed beer</a> in total sales, even as the number of breweries in the US <a href="https://www.fortunebusinessinsights.com/alcoholic-beverages-market-107439">grew</a> from 3,305 in 2017 to 4,493 in 2020. Alcohol is generally taxed higher than other goods in part to limit its consumption, but since 2000, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299191/">these taxes</a> have lost much of their value — and with it, their ability to curb consumption — because they haven’t kept up with inflation rates and beverage costs.
</p>
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“It’s a real blind spot in drug policy, that a huge number of people are not willing to see alcohol as a drug for which we have a pretty serious problem,” said <a href="https://profiles.stanford.edu/keith-humphreys">Keith Humphreys</a>, a professor of psychiatry and behavioral sciences at Stanford University. What this all means is that nearly a <a href="https://www.aa.org/aa-history#:~:text=Since%20its%20beginnings%20in%201935,it%20works%20to%20help%20alcoholics.">century</a> since the founding of Alcoholics Anonymous — a program that studies show is the <a href="https://med.stanford.edu/news/all-news/2020/03/alcoholics-anonymous-most-effective-path-to-alcohol-abstinence.html#:~:text=After%20evaluating%2035%20studies%20%E2%80%94%20involving,than%20psychotherapy%20in%20achieving%20abstinence.">most effective</a> at helping people achieve and maintain abstinence — the problem is only getting <a href="https://www.niaaa.nih.gov/news-events/research-update/alcohol-related-deaths-which-increased-during-first-year-covid-19-pandemic-continued-rise-2021#:~:text=In%20the%20new%20analyses%2C%20a,for%20nearly%20all%20age%20groups.">worse</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OVggGV">
But that may be changing. As researchers continue to delve into how alcohol use can hurt one’s overall health and lead to addiction, more people are looking for solutions — especially for the group of heavy drinkers who need it most. Beyond the therapeutic and social groups like AA that have long existed to support AUD sufferers, there is a trio of FDA-approved drugs that have a history of curbing alcohol abuse. Rumblings of <a href="https://www.npr.org/sections/health-shots/2023/08/28/1194526119/ozempic-wegovy-drinking-alcohol-cravings-semaglutide">Ozempic’s apparent off-label ability</a> to curb alcohol cravings, as well as overeating, have put the spotlight back on the power of medical intervention with the help of a prescription. In the same way that we view medications like Prozac as tools for treating depression, these medications could be a key element in AUD treatment plans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WXQ0HB">
But they remain <a href="https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-treatment-united-states-age-groups-and-demographic-characteristics#:~:text=Prevalence%20of%20Any%20Past%2DYear%20Alcohol%20Use%20Treatment&amp;text=According%20to%20the%202021%20National,treatment%20in%20the%20past%20year.">vastly underused</a>; while 14.1 million adults experienced AUD in the US in 2019, only 223,000 will ever be prescribed existing medications. The reasons for this vary; some patients don’t want to take a drug to treat their addiction, health care professionals lack awareness and training in treating AUD, and the ongoing stigma surrounding the disease makes it difficult for sufferers to seek help.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aTKvPu">
What’s clear is that the cost of failing to effectively treat alcohol abuse is astronomical, adding up to tens of thousands of deaths a year. AUD breaks apart families and disrupts the workplace, causing <a href="https://medicine.wustl.edu/news/in-u-s-alcohol-use-disorder-linked-to-232-million-missed-workdays-annually/">232 million</a> missed work days annually. New treatments and even laws are emerging daily, but it’s important for health care professionals and those with AUD to remember that effective treatment options are already available.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IIWMiP">
“I think it’s great that we have medications,” said Humphreys. “They all can be used much more than they are. None of them is at the level of antibiotics for infections. But they have a role, and it’s too bad we don’t use them more.”
</p>
<h3 id="LFrYqP">
What is AUD?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6wm1jd">
Americans can purchase alcohol at restaurants, bars, liquor shops, grocery stores, gas stations, and in some states, even <a href="https://www.thekitchn.com/the-drive-thru-daiquiri-a-weird-yet-wonderful-new-orleans-tradition-241670">drive-throughs</a>. Alcohol is everywhere. “At the end of the day, it is so baked into our society to use alcohol. Some people are going to drink it and never develop a problem, and other people are going to develop a problem,” said <a href="https://www.mycasat.org/wp-content/uploads/2017/04/PowerPoint-ACT-2.pdf">Mark Disselkoen</a>, the senior project manager at the <a href="https://casat.org/">Center for the Application of Substance Abuse Technologies</a> (CASAT) at the University of Nevada Reno.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MQHDtj">
While AUD and its effects are widespread, those suffering the most from the disease are the most frequent and heaviest drinkers. Data from the late 2000s <a href="https://www.washingtonpost.com/news/wonk/wp/2014/09/25/think-you-drink-a-lot-this-chart-will-tell-you/">showed</a> that the top 10 percent of American drinkers (approximately 24 million people) consumed an average of 74 alcoholic drinks a week, which means those with the most severe form of AUD purchase over half the alcohol bought in the country.
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The research since then only further proves the pervasive influence of alcohol in the US. Americans <a href="https://www.bw166.com/2019/01/13/u-s-beverage-alcohol-spending-hits-253-8-billion-in-2018-5-1-versus-2017/#:~:text=5.1%25%20versus%202017-,U.S.%20Beverage%20Alcohol%20Spending%20Hits%20%24253.8%20Billion%20in%202018%2C%20%2B5.1,%2412.4%20Billion%2C%20%2B5.1%25.">spend billions</a> on alcohol every year, with approximately <a href="https://news.gallup.com/poll/467507/percentage-americans-drink-alcohol.aspx">65 percent</a> of adults of legal drinking age in the US reporting they drink alcohol (the average American consumes <a href="https://thehill.com/policy/healthcare/4043030-hard-liquor-consumption-is-up-60-percent-since-the-1990s/#:~:text=Overall%2C%20the%20average%20American%20consumed,on%20Alcohol%20Abuse%20and%20Alcoholism.">2.51 gallons</a> of the substance annually).
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WjgPy7">
And the numbers only got worse when Covid-19 swept across the country. In 2020, the first year of the pandemic, studies show that overall a <a href="https://covid19.nih.gov/news-and-stories/risky-drinking-alcohol-use-epidemic-inside-covid-19-pandemic#:~:text=It%20was%20really%20no%20surprise,often%20to%20cope%20with%20stress.">quarter of Americans</a> drank more than they usually did due to the stress of the pandemic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AoVADz">
AUD remains most common in men, but the rate of alcohol-related deaths is growing faster for women, partially due to a general uptick in alcohol consumption by the group. This is an unfortunate shift, explained in part by women’s greater <a href="https://www.cdc.gov/alcohol/fact-sheets/womens-health.htm#:~:text=Impact%20on%20the%20Heart%3A%20Women,years%20of%20drinking%20than%20men.&amp;text=Breast%20and%20other%20Cancers%3A%20Alcohol,esophagus%2C%20liver%2C%20and%20colon.">susceptibility</a> to alcohol-related liver and heart disease, and cancers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jIz92J">
Historically, repeated binge drinking episodes — periods where men drink <a href="https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/binge-drinking">five or more</a> alcoholic beverages in two hours, or for women, four or more beverages in two hours — were called alcohol abuse or alcohol dependence. The <a href="https://ajp.psychiatryonline.org/doi/10.1176/ajp.152.8.1228">DSM-IV</a> (a widely used manual published by the <a href="https://www.psychiatry.org/">American Psychiatric Association</a> to help diagnose mental disorders) categorized alcohol use as either abuse — continued alcohol use despite negative consequences — or dependence, an increasing need for consumption to become intoxicated and avoid withdrawal symptoms, <a href="https://www.niaaa.nih.gov/about-niaaa/directors-page">George Koob</a>, director of the <a href="https://www.niaaa.nih.gov/">National Institute on Alcohol Abuse and Alcoholism</a>, told Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1TBxz0">
But these outdated terms perpetuate negative connotations and stereotypes about people who drink, the experts Vox spoke to agreed. “The terms ‘alcohol abuse’ or ‘substance abuse’ are terms that we try to avoid,” said <a href="https://www.buffalo.edu/cria/about-us/contact.html">Kenneth Leonard</a>, the director of the Clinical and Research Institute on Addictions at the University at Buffalo and the former president of the Division of Addictions of the American Psychological Association. “They have the impact of stigmatizing individuals who have an alcohol use or substance use disorder.” Additionally, because the word “abuse” is associated with violence, it leads to people seeking to punish those with AUD, rather than treat them, said Humphreys.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TASoSw">
In <a href="https://www.ncbi.nlm.nih.gov/books/NBK519699/#:~:text=It%20provides%20a%20classification%20system,)%20%5B1%2C2%5D.">2013</a>, the APA replaced the DSM-IV with the <a href="https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-use-disorder-comparison-between-dsm">DSM-5</a>, which recategorized all forms of abuse as AUD, with cases ranging from mild to moderate or severe. The <a href="https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-use-disorder-comparison-between-dsm">DSM-5</a> criteria include a series of yes-or-no questions about a patient’s drinking habits and the repercussions of those habits from the last year.
</p>
<div id="JBR5Rd">
</div></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>India Women’s fielding was below-par against Australia, remains a work in progress: Muzumdar</strong> - The India head coach also defended Deepti who struggled to find quick runs towards the end and her slow approach, perhaps, contributed to the adverse result</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Morning Digest | Census to be delayed till at least October 2024; Ayodhya airport takes off ahead of Ram Temple consecration ceremony in January and more</strong> - Here is a select list of stories to start the day</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>Sakshi Malik | The wrestler who never stopped fighting</strong> - The Olympic medallist, who led the wrestlers’ protest over alleged sexual harassment and other charges against former WFI president Brij Bhushan Sharan Singh, has been vocal in her demand for a safer environment for the girls who take to the sport</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>World blitz chess | Carlsen repeats title-sweep; A first for Gunina; Poor day for Indians</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>Gukesh, Humpy complete Candidates’ fields, join Pragg, Vidit and Vaishali</strong> -</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>As the sun sets on 2023, Karnataka’s year in review</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>Low demand for precautionary dose amid surging COVID-19 cases in Telangana</strong> - In the month of December, a mere 16 individuals opted to receive the additional precautionary dose</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>Telangana proposes to raise ₹13,000 crore open market borrowings during Q4 after exceeding limits fixed by Union Finance Ministry</strong> - OMBs of ₹42,551 crore raised by December end against ₹42,225 crore allowed by Union Ministry for the current fiscal</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>Silent wave of JN.1 Covid virus among the population in Hyderabad and Secunderabad</strong> - The new virus strain JN.1 has clearly transmitted to a majority of population in the twin cities as per the analysis from the waste water sampling being conducted by the scientists</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>Public places in Madurai non-inclusive; no accessibility for the differently-abled</strong> - Many public facilities remain inaccessible to differently-abled people.</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>Ukraine war: Russia hits back after Kyiv attack on border city</strong> - The latest attacks on Kyiv and Kharkiv come after two days of major aerial assaults by both sides.</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>Venice to ban large tourist groups and loudspeakers</strong> - The new rules will come into effect in June and are part of an effort to ease the impact of tourism.</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>PDC World Championship 2024: Luke Littler beats Raymond van Barneveld to reach quarter-finals</strong> - Luke Littler’s historic run at the PDC World Darts Championship continues as the 16-year-old stuns Raymond van Barneveld to reach the 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>Odesa church: Clergyman narrowly avoids roof collapse after Russian attack</strong> - CCTV shows debris falling from the from the building’s ceiling after Russian strikes hit the area.</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>Poland says Russian missile entered airspace then went into Ukraine</strong> - Poland’s air defence system initially detected the object but subsequently lost track of it.</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>Smartphone manufacturers still want to make foldables a thing</strong> - Foldables are barely 1% of the market, but that’s not stopping anyone but Apple. - <a href="https://arstechnica.com/?p=1993084">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Aaarr matey! Life on a 17th century pirate ship was less chaotic than you think</strong> - Ars chats with historian Rebecca Simon about her most recent book, <em>The Pirates’ Code</em>. - <a href="https://arstechnica.com/?p=1993048">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A cat video highlighted a big year for lasers in space</strong> - NASA has invested more than $700 million in testing laser communications in space. - <a href="https://arstechnica.com/?p=1992668">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SpaceX launches two rockets—three hours apart—to close out a record year</strong> - This was the shortest time between orbital launches at Cape Canaveral since 1966. - <a href="https://arstechnica.com/?p=1992995">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>These scientists explored the good vibrations of the bundengan and didgeridoo</strong> - Their relatively simple construction produces some surprisingly complicated physics. - <a href="https://arstechnica.com/?p=1990299">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 guy goes to Las Vegas to gamble and he loses all his money. He doesn’t even have enough for a cab, but he flagged one down anyway. He explained to the driver that he would pay him back next time and gave him his phone number, but the driver told him, “Get the fuck out of my cab.”</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He walked all the way to the airport and got home.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Some times rolls by and he decides to go back to Vegas again and this time he wins BIG.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He gets his bags and is ready for the airport with all his new winnings.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
There are a line of cabs and at the very end he sees the driver from last time that kicked him out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He stood for a moment thinking how can he get his revenge on that driver.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
So, he gets in the first cab.
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“How much is it to the airport?” he asks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The driver says, “$15.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Great, how much is it for a blowjob on the way there?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The cab driver says, “Get the fuck out of my cab.”
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So he goes to the next one and asks the same thing.
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“How much to airport?”
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“$15.”
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“Great, how much for a blowjob on the way there?”
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And that cab driver also tells him to get the fuck out of his cab.
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He does this all the way down the line of drivers, each one kicking him out.
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He finally gets to the last driver, the one from his last trip.
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He asks, “Hey how much to the airport?”
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Driver responds, “$15.”
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The guy hands him $15 and says, “Great let’s go!”
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And so the driver leaves, slowly passing all the other drivers who are staring out their window while the guy in the back smiles back with a thumbs up.
</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/madazzahatter"> /u/madazzahatter </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18v5p3e/a_guy_goes_to_las_vegas_to_gamble_and_he_loses/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18v5p3e/a_guy_goes_to_las_vegas_to_gamble_and_he_loses/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My dad told me I should fuck both of you.</strong> - <!-- SC_OFF --></p>
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Dad and Son are in the living room when dad feet’s get cold. “Get my slippers from upstairs” He says.
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While upstairs he sees two of his sisters friends so he goes up to both of them, “My Dad told me to come up here and fuck both of you”.
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“You’re lying” they retort.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Okay, I’ll prove it then, “Dad, did you say both of them?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“what’s the point of fucking one”.
</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/Nikkere"> /u/Nikkere </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18v40j5/my_dad_told_me_i_should_fuck_both_of_you/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18v40j5/my_dad_told_me_i_should_fuck_both_of_you/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Three friends decided to bet each other 100 dollars on who could make their wives scream more during sex</strong> - <!-- SC_OFF --></p>
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They all went home to have sex with their wives and make them scream. The next day the met up again.
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The first friend said, “I made love to my wife for two hours and she was screaming for at least one-and-a-half hours.”
</p>
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The second friend countered, “That’s nothing. I started licking my wife for two hours and she was screaming the whole time and a half-hour after that.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Then the third friend said, “That’s pathetic. I made love to my wife for ten minutes, I came a couple of times, I wiped my dick in the curtain, and she’s still screaming”
</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/orgasmic2021"> /u/orgasmic2021 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18ugpxu/three_friends_decided_to_bet_each_other_100/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18ugpxu/three_friends_decided_to_bet_each_other_100/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>There’s the rub…</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A married parishioner went into the confessional and told his priest, “I almost had an affair with another woman.”<br/> The priest asked, “What do you mean, almost?”<br/> The man said, “Well, we got undressed and rubbed together, but then I stopped.”<br/> The priest told him, “Rubbing together is the same as putting it in. You’re not to see that woman again.<br/> For your penance, say five Hail Mary’s and put $50 in the poor box.”<br/> The man left the confessional, said his prayers, and then walked over to the poor box. He paused for a moment and then started to leave.<br/> The priest, who was watching, quickly ran over to him saying, “I saw that. You didn’t put any money in the poor box!”<br/> The man replied, “Yeah, but I rubbed the $50 on the box, and according to you, that’s the same as putting it in!”
</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/GANDORF57"> /u/GANDORF57 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18us5ag/theres_the_rub/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18us5ag/theres_the_rub/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I recently ordered a new sail for my boat. A few days later I realized I’d made a mistake and called to change the order. The person that answered said,</strong> - <!-- SC_OFF --></p>
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“Sorry, that sail has shipped!”
</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/timthedriller"> /u/timthedriller </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/18uuir3/i_recently_ordered_a_new_sail_for_my_boat_a_few/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/18uuir3/i_recently_ordered_a_new_sail_for_my_boat_a_few/">[comments]</a></span></p></li>
</ul>
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