navan
/
Daily-Dose
mirror of https://github.com/navanchauhan/Daily-Dose.git
1
0
Fork 0
Code Issues Projects Releases Wiki Activity

Added daily report

This commit is contained in:
Navan Chauhan 2023-07-15 12:47:48 +00:00
parent 9ac5379e7a
commit 0d9aab9018
3 changed files with 829 additions and 2 deletions
Show Stats Download Patch File Download Diff File Expand all files Collapse all files

184
archive-covid-19/15 July, 2023.html Normal file
View File

@ -0,0 +1,184 @@
<!DOCTYPE html>
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
<meta charset="utf-8"/>
<meta content="pandoc" name="generator"/>
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
<title>15 July, 2023</title>
<style>
code{white-space: pre-wrap;}
span.smallcaps{font-variant: small-caps;}
span.underline{text-decoration: underline;}
div.column{display: inline-block; vertical-align: top; width: 50%;}
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
ul.task-list{list-style: none;}
</style>
<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
<body>
<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>Differential laboratory passaging of SARS-CoV-2 viral stocks impacts the in vitro assessment of neutralizing antibodies</strong> -
<div>
Viral populations in natural infections can have a high degree of sequence diversity, which can directly impact immune escape. However, antibody potency is often tested in vitro with a relatively clonal viral populations, such as laboratory virus or pseudotyped virus stocks, which may not accurately represent the genetic diversity of circulating viral genotypes. This can affect the validity of viral phenotype assays, such as antibody neutralization assays. To address this issue, we tested whether recombinant virus carrying SARS-CoV-2 spike (VSV-SARS-CoV-2-S) stocks could be made more genetically diverse by passage, and if a stock passaged under selective pressure was more capable of escaping monoclonal antibody (mAb) neutralization than unpassaged stock or than viral stock passaged without selective pressures. We passaged VSV-SARS-CoV-2-S four times concurrently in three cell lines and then six times with or without polyclonal antiserum selection pressure. All three of the monoclonal antibodies tested neutralized the viral population present in the unpassaged stock. The viral inoculum derived from serial passage without antiserum selection pressure was neutralized by two of the three mAbs. However, the viral inoculum derived from serial passage under antiserum selection pressure escaped neutralization by all three mAbs. Deep sequencing revealed the rapid acquisition of multiple mutations associated with antibody escape in the VSV-SARS-CoV-2-S that had been passaged in the presence of antiserum, including key mutations present in currently circulating Omicron subvariants. These data indicate that viral stock that was generated under polyclonal antiserum selection pressure better reflects the natural environment of the circulating virus and may yield more biologically relevant outcomes in phenotypic assays.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.14.549044v1" target="_blank">Differential laboratory passaging of SARS-CoV-2 viral stocks impacts the in vitro assessment of neutralizing antibodies</a>
</div></li>
<li><strong>Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus</strong> -
<div>
To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As SARS-CoV-2 omicron sublineages account for over 90% of COVID-19 infections, evasion of immune responses generated by vaccination or exposure to previous variants poses a significant challenge. A compelling new therapeutic strategy against SARS-CoV-2 is that of single domain antibodies, termed nanobodies, which address certain limitations of monoclonal antibodies. Here we demonstrate that our high-affinity nanobody repertoire, generated against wild-type SARS-CoV-2 spike protein (Mast, Fridy et al. 2021), remains effective against variants of concern, including omicron BA.4/BA.5; a subset is predicted to counter resistance in emerging XBB and BQ.1.1 sublineages. Furthermore, we reveal the synergistic potential of nanobody cocktails in neutralizing emerging variants. Our study highlights the power of nanobody technology as a versatile therapeutic and diagnostic tool to combat rapidly evolving infectious diseases such as SARS-CoV-2.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.14.549041v1" target="_blank">Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus</a>
</div></li>
<li><strong>A simulation framework for modeling the within-patient evolutionary dynamics of SARS-CoV-2</strong> -
<div>
The global impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to considerable interest in detecting novel beneficial mutations and other genomic changes that may signal the development of variants of concern (VOCs). The ability to accurately detect these changes within individual patient samples is important in enabling early detection of VOCs. Such genomic scans for positive selection are best performed via comparison of empirical data to simulated data wherein evolutionary factors, including mutation and recombination rates, reproductive and infection dynamics, and purifying and background selection, can be carefully accounted for and parameterized. While there has been work to quantify these factors in SARS-CoV-2, they have yet to be integrated into a baseline model describing intra-host evolutionary dynamics. To construct such a baseline model, we develop a simulation framework that enables one to establish expectations for underlying levels and patterns of patient-level variation. By varying eight key parameters, we evaluated 12,096 different model-parameter combinations and compared them to existing empirical data. Of these, 592 models (~5%) were plausible based on the resulting mean expected number of segregating variants. These plausible models shared several commonalities shedding light on intra-host SARS-CoV-2 evolutionary dynamics: severe infection bottlenecks, low levels of reproductive skew, and a distribution of fitness effects skewed towards strongly deleterious mutations. We also describe important areas of model uncertainty and highlight additional sequence data that may help to further refine a baseline model. This study lays the groundwork for the improved analysis of existing and future SARS-CoV-2 within-patient data.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.13.548462v1" target="_blank">A simulation framework for modeling the within-patient evolutionary dynamics of SARS-CoV-2</a>
</div></li>
<li><strong>Multivalent Exosome based protein vaccine: a “mix and match” approach to epidemic viruses’ challenges.</strong> -
<div>
Endemic viruses are becoming increasingly the norm, and the development of a rapid and effective vaccine is emergent. Here, we used our StealthX TM exosome platform to express either Influenza H3 (StealthTM X-Hemagglutinin, STX-H3) or SARS-CoV-2 Delta spike (StealthTM X-Spike, STX-S) protein on the surface and facilitate their trafficking to the exosomes. When administered as single product, both STX-H3 and STX-S induced a strong immunization with the production of a potent humoral and cellular immune response in mice. Interestingly, these effects were obtained with administration of nanograms of protein and without adjuvant. Therefore, we tested the possibility of a multivalent vaccine: STX-H3 and STX-S exosomes were formulated together in a "mix and match" approach and the immune response was further evaluated. We showed that our STX-H3+S cocktail vaccine is as effective as the single components administered separately, resulting in a strong antibody and T-cell response. Our data show that our exosome platform has an enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation, and for therapeutics by enabling cell and tissue specific targeting.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.13.548895v1" target="_blank">Multivalent Exosome based protein vaccine: a “mix and match” approach to epidemic viruses’ challenges.</a>
</div></li>
<li><strong>Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: a cohort study using OpenSAFELY-TPP</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We analysed healthcare services delivered to people with pancreatic cancer from January 2015 to March 2023 to investigate the effect of the COVID-19 pandemic. Methods With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models (GLM) and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to March 2023. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates. Results The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 26,840 people diagnosed with pancreatic cancer from January 2015 to March 2023. The mean age at diagnosis was 72 (11 SD), 48% of people were female, 95% were of White ethnicity and 40% were diagnosed with diabetes. We found a reduction in surgical resections by 25% to 28% during the pandemic. In addition, 20%, 10% and 4% fewer people received BMI, HbA1c and liver function tests respectively before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1 to 2 per person amongst those who made contact. Reporting of jaundice decreased by 28%, but recovered within twelve months into the pandemic. Emergency department visits, hospital admissions and deaths were not affected. Conclusions The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from the services that were resilient and those that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.02.22283026v2" target="_blank">Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: a cohort study using OpenSAFELY-TPP</a>
</div></li>
<li><strong>Mobilisation towards formal employment in the healthcare system: A qualitative study of community health workers in South Africa</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In low and middle-income countries (LMICs), community health workers (CHWs) play a critical role in delivering primary health care (PHC) services to vulnerable populations. In these settings, they often receive low stipends, function with a lack of basic resources and have little bargaining power with which to demand better working conditions. In this article, we examine CHWs’ employment status, their struggle for recognition as health workers, and their activities to establish labour representation in South Africa. Using a case study approach, we studied seven CHW teams located in semi-urban and rural areas of Gauteng and Mpumalanga Provinces, South Africa. We used in-depth interviews, focus group discussions and observations to gather data from CHWs and their representatives, supervisors and PHC facility staff members. The rural and semi-urban sites CHWs were poorly supervised, resourced and received meagre remuneration, their employment outsourced, without employment benefits and protection. The lack of career progression opportunities demotivated the CHWs, particularly those keen to establish a career in health. In the semi-urban sites, CHWs established a task team to represent them that held regular meetings and often used violent and disruptive strategies against clinic, district and provincial management, which often led to tensions and conflicts with facility staff and programme coordinators.  After a meeting with the local provincial legislature, the task team joined a labour union (NEHAWU) in order to be able to participate in the local Bargaining Council. Though they were not successful in getting the government to provide permanent employment, the union negotiated an increase in stipend from R2 500 (136 USD) to R3 500 (192 USD). In contrast, in the rural sites, the CHWs were not actively demanding permanent employment due to their employment contracts being partly managed by non-government organisations (NGOs) managements; they were fearful of being recalled from the government programme. After the study ended, during the height of COVID-19 in 2020, when the need for motivated and effective CHWs became much more obvious to decision makers, the semi-urban-based teams received permanent employment with remuneration between R9-11,000 (500-600 USD). The task team and their protests raised awareness of the plight of the CHWs, and joining a formal union enabled them to negotiate a modest salary increase. However, it was the emergency created by the world-wide COVID-19 pandemic that forced decision-makers to acknowledge their reliance on this community-based cadre. Hopefully this recognition, and the associated gains, will not fade as the pandemic recedes.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.11.23292526v1" target="_blank">Mobilisation towards formal employment in the healthcare system: A qualitative study of community health workers in South Africa</a>
</div></li>
<li><strong>Environmental Surface Monitoring as a Noninvasive Method for SARS-CoV-2 Surveillance in Community Settings: Lessons from a University Campus Study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Environmental testing of high-touch objects is a potential noninvasive approach for monitoring population-level trends of SARS-CoV-2 and other respiratory viruses within a defined setting. We aimed to determine the association between SARS-CoV-2 contamination on high-touch environmental surfaces, community level case incidence, and university student health data. Environmental swabs were collected from January 2022 to November 2022 from high-touch objects and surfaces from five locations on a large university campus in Florida, USA. RT-qPCR was used to detect and quantify viral RNA, and a subset of positive samples was analyzed by viral genome sequencing to identify circulating lineages. During the study period, we detected SARS-CoV-2 viral RNA on 90.7% of 162 tested samples. Levels of environmental viral RNA correlated with trends in community-level activity and case reports from the student health center. A significant positive correlation was observed between the estimated viral gene copy number in environmental samples and the weekly confirmed cases at the university. Viral sequencing data from environmental samples identified lineages contemporaneously circulating in the local community and state based on genomic surveillance data. Further, we detected emerging variants in environmental samples prior to their identification by clinical genomic surveillance. Our results demonstrate the utility of viral monitoring on high-touch environmental surfaces for SARS-CoV-2 surveillance at a community level. In communities with delayed or limited testing facilities, immediate environmental surface testing may considerably inform epidemic dynamics.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.13.23292575v1" target="_blank">Environmental Surface Monitoring as a Noninvasive Method for SARS-CoV-2 Surveillance in Community Settings: Lessons from a University Campus Study</a>
</div></li>
<li><strong>SWAMPy: Simulating SARS-CoV-2 Wastewater Amplicon Metagenomes with Python</strong> -
<div>
Motivation: Tracking SARS-CoV-2 variants through genomic sequencing has been an important part of the global response to the pandemic. As well as whole-genome sequencing of clinical samples, this surveillance effort has been aided by amplicon sequencing of wastewater samples, which proved effective in real case studies. Because of its relevance to public healthcare decisions, testing and benchmarking wastewater sequencing analysis methods is also crucial, which necessitates a simulator. Although metagenomic simulators exist, none are fit for the purpose of simulating the metagenomes produced through amplicon sequencing of wastewater. Results: Our new simulation tool, SWAMPy (Simulating SARS-CoV-2 Wastewater Amplicon Metagenomes with Python), is intended to provide realistic simulated SARS-CoV-2 wastewater sequencing datasets with which other programs that rely on this type of data can be evaluated and improved. Availability: The code for this project is available at https://github.com/goldman-gp-ebi/SWAMPy. It can be installed on any Unix-based operating system and is available under the GPL-v3 license.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.10.519890v2" target="_blank">SWAMPy: Simulating SARS-CoV-2 Wastewater Amplicon Metagenomes with Python</a>
</div></li>
<li><strong>The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions</strong> -
<div>
The Covid-19 pandemic has significantly altered the way sporting events are observed. With the absence or limited presence of spectators in stadiums, the traditional advantage enjoyed by home teams has diminished considerably. This underscores the notion that the support of home fans can often be considered a key factor of the home advantage (HA) phenomenon, wherein teams perform better in front of their own supporters. However, the impact of reduced attendance on games with higher stakes, as opposed to low-stakes friendly matches, remains uncertain. In this study, we investigate the recently concluded European football championship (EURO 20), wherein several teams had the advantage of playing at home in high-stakes games with only one-third of the stadium capacity filled. Firstly, we demonstrate that the Covid-19 restrictions, leading to reduced fan attendance, resulted in a nearly 50% decrease in HA compared to the HA exhibited by the same teams during the qualification stage preceding EURO 20, even after accounting for team strength. Secondly, we show that while low-stakes friendly matches generally exhibit a smaller overall HA compared to high-stakes games, the absence of fans led to a similar reduction in HA during the low-stakes matches. Utilizing the recently developed Home Advantage Mediated (HAM) model (Bilalić et al., 2021, Scientific Reports, 21558), we were able to attribute the reduction in both high- and low-stakes games to poorer team performance, with no significant contribution from referee bias.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/d3xat/" target="_blank">The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions</a>
</div></li>
<li><strong>Death Seasonality, Google Community Mobility Trends, Seropositivity Rates, Comparisons of SINADEF Data with WHO Summary Data, and other Data Items as Useful in Analysis of Excess Deaths During the COVID-19 Pandemic in Peru, 2020-2021</strong> -
<div>
The government of Peru carried out extensive tracking of data for deaths and other public health parameters that allow analysis of potential efficacy of interventions used during the early years of the COVID-19 pandemic. Data from those sources for death seasonality, mobility trends, household composition and seropositivity rates, as well as Google community mobility trends, are provided here as can facilitate such analysis. Also, excess deaths as calculated from Peru’s National Death Information System (SINADEF) are compared with monthy summary data for excess deaths for the period 2020-2021 as reported by the World Health Organization.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/a9ex5/" target="_blank">Death Seasonality, Google Community Mobility Trends, Seropositivity Rates, Comparisons of SINADEF Data with WHO Summary Data, and other Data Items as Useful in Analysis of Excess Deaths During the COVID-19 Pandemic in Peru, 2020-2021</a>
</div></li>
<li><strong>Performance of amplicon and capture based next-generation sequencing approaches for the epidemiological surveillance of Omicron SARS-CoV-2 and other variants of concern.</strong> -
<div>
To control the SARS-CoV-2 pandemic, healthcare systems have focused on ramping up their capacity for epidemiological surveillance through viral whole genome sequencing. In this paper, we tested the performance of two protocols of SARS-CoV-2 nucleic acid enrichment, an amplicon enrichment using different versions of the ARTIC primer panel and a hybrid-capture method using KAPA RNA Hypercap. We focused on the challenge of the Omicron variant sequencing, the advantages of automated library preparation and the influence of the bioinformatic analysis in the final consensus sequence. All 94 samples were sequenced using Illumina iSeq 100 and analysed with two bioinformatic pipelines: a custom-made pipeline and an Illumina-owned pipeline. We were unsuccessful in sequencing six samples using the capture enrichment due to low reads. On the other hand, amplicon dropout and mispriming caused the loss of mutation G21987A and the erroneous addition of mutation T15521A respectively using amplicon enrichment. Overall, we found high sequence agreement regardless of method of enrichment, bioinformatic pipeline or the use of automation for library preparation in eight different SARS-CoV-2 variants. Automation and the use of a simple app for bioinformatic analysis can simplify the genotyping process, making it available for more diagnostic facilities and increasing global vigilance.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.14.549026v1" target="_blank">Performance of amplicon and capture based next-generation sequencing approaches for the epidemiological surveillance of Omicron SARS-CoV-2 and other variants of concern.</a>
</div></li>
<li><strong>Utility of nasal swabs for assessing mucosal immune responses towards SARS-CoV-2</strong> -
<div>
SARS-CoV-2 has caused millions of infections worldwide since its emergence in 2019. Understanding how infection and vaccination induce mucosal immune responses and how they fluctuate over time is important, especially since they are key in preventing infection and reducing disease severity. We established a novel methodology for assessing SARS-CoV-2 cytokine and antibody responses at the nasal epithelium by using nasopharyngeal swabs collected longitudinally before and after either SARS-CoV-2 infection or vaccination. We then compared responses between mucosal and systemic compartments. We demonstrate that cytokine and antibody profiles differ markedly between compartments. Nasal cytokines show a wound healing phenotype while plasma cytokines are consistent with pro-inflammatory pathways. We found that nasal IgA and IgG have different kinetics after infection, with IgA peaking first. Although vaccination results in low nasal IgA, IgG induction persists for up to 180 days post-vaccination. This research highlights the importance of studying mucosal responses in addition to systemic responses to respiratory infections to understand the correlates of disease severity and immune memory. The methods described herein can be used to further mucosal vaccine development by giving us a better understanding of immunity at the nasal epithelium providing a simpler, alternative clinical practice to studying mucosal responses to infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.12.548630v1" target="_blank">Utility of nasal swabs for assessing mucosal immune responses towards SARS-CoV-2</a>
</div></li>
<li><strong>Booster dose of self-amplifying SARS-CoV-2 RNA vaccine vs. mRNA vaccine: a phase 3 comparison of ARCT-154 with Comirnaty</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Licensed mRNA vaccines demonstrated initial effectiveness against COVID-19 but require booster doses to broaden the anti-SARS-CoV-2 response. There is an unmet need for novel highly immunogenic and broadly protective vaccines. We compared immunogenicity and tolerability of ARCT-154, a novel self-amplifying mRNA vaccine with the mRNA vaccine, Comirnaty. Methods We compared immune responses to ARCT-154 and Comirnaty booster doses in healthy 18-77-year-old Japanese adults initially immunised with two doses of mRNA COVID-19 vaccine (Comirnaty or Spikevax) then a third dose of Comirnaty at least 3 months previously. Neutralising antibodies were measured before and 28 days after booster vaccination. The primary objective was to demonstrate non-inferiority of the immune response against Wuhan-Hu-1 SARS-CoV-2 virus as geometric mean titre (GMT) ratios and seroresponse rates (SRR) of neutralising antibodies; key secondary endpoints included the immune response against the Omicron BA.4/5 variant and vaccine tolerability assessed using participant-completed electronic diaries. Findings Between December 13, 2022 and February 25, 2023 we enrolled 828 participants randomised 1:1 to receive ARCT-154 (n = 420) or Comirnaty (n = 408) booster doses. Four weeks after boosting, ARCT-154 induced higher Wuhan-Hu-1 neutralising antibodies GMTs than Comirnaty (5641 [95% CI: 4321-7363] and 3934 [2993-5169], respectively), a GMT ratio of 1.43 (95% CI: 1.26-1.63), with SRR of 65.2% (60.2-69.9) and 51.6% (46.4-56.8) meeting the non-inferiority criteria. Respective anti-Omicron BA.4/5 GMTs were 2551 (1687-3859) and 1958 (1281-2993), a GMT ratio of 1.30 (95% CI: 1.07-1.58), with SRR of 69.9% (65.0-74.4) and 58.0% (52.8-63.1), meeting the superiority criteria for ARCT-154 over Comirnaty. Booster doses of either ARCT-154 or Comirnaty were equally well-tolerated with no causally-associated severe or serious adverse events; 94.8% and 96.8% of ARCT-154 and Comirnaty vaccinees reported local reactions and 65.7% and 62.5% had solicited systemic adverse events. Events were mainly mild in severity, occurring and resolving within 3-4 days of vaccination. Interpretation Immune responses four weeks after an ARCT-154 booster dose in mRNA-immunised adults were higher than after a Comirnaty booster, meeting non-inferiority criteria against the prototype Wuhan-Hu-1 virus, and superiority criteria against the Omicron BA.4/5 variant.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.13.23292597v1" target="_blank">Booster dose of self-amplifying SARS-CoV-2 RNA vaccine vs. mRNA vaccine: a phase 3 comparison of ARCT-154 with Comirnaty</a>
</div></li>
<li><strong>Risk Factors for Admission into COVID-19 General Wards, Sub-Intensive and Intensive Care Units among SARS-CoV-2 Positive Subjects in the Municipality of Bologna, Italy</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
This is a retrospective cohort study aimed at identifying the risk factors for the hospitalization of patients with COVID-19 in the municipality of Bologna. A total of 32500 patients that tested positive for COVID-19 from February 28/2020 to October 13/2021 in the municipality of Bologna were included. The Kaplan-Meier method was used to estimate changes during time of ICU hospitalization for all patients as well as stratifying subjects by sex. A multi-state Cox9s proportional hazard model was fitted to investigate predictors of ICU and non-ICU hospitalization. Age, sex, calendar period of diagnosis, comorbidities and vaccination status of patients at the time of diagnosis were considered as candidate predictors. In general, male sex and advanced age resulted to be poor prognostic factors of COVID-19 outcomes. An exception was found for the over 80 age group which showed a decrease in the risk of ICU hospitalization compared to 70-79 (HR 0.57 95% CI 0.36 - 0.90 for DIAG-&gt;ICU; HR 0.40 95% CI 0.28 - 0.58 for HOSP-&gt;ICU). Having contracted the disease during the first wave was associated with a significant greater risk of hospitalization than during the second wave, while no difference in the risk of ICU admission was found between the second and third waves. Fully immunized patients showed a significant decrease in the risk of ICU and non-ICU hospitalization compared to the unvaccinated patients (HR 0.23 95% CI 0.16 - 0.31 for DIAG-&gt;HOSP; HR 0.10 95% CI 0.01 - 0.73 for DIAG-&gt;ICU). Chronic kidney failure and asthma were risk factors for non-ICU hospitalization. Diabetes and embolism were risk factors for both direct ICU and non-ICU hospitalization. The study of factors associated with a negative course of the COVID-19 disease allows to prevent fatal outcomes, establish priorities in the treatment of the disease and improve the management of hospital resources and the pandemic itself.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.12.23292559v2" target="_blank">Risk Factors for Admission into COVID-19 General Wards, Sub-Intensive and Intensive Care Units among SARS-CoV-2 Positive Subjects in the Municipality of Bologna, Italy</a>
</div></li>
<li><strong>Trends in serotype distribution and disease severity in adults hospitalised with Streptococcus pneumoniae infection in Bristol and Bath: a retrospective cohort study, 2006-2022</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<b>Background</b> Paediatric pneumococcal conjugate vaccination (PCV) has reduced adult PCV-serotype disease: PCV7 has greater indirect effects than PCV13. Ongoing surveillance is required to evaluate current vaccine usage and inform future vaccine deployment, particularly with respiratory infection epidemiology changing following SARS-CoV-2 emergence. <b>Methods and Findings</b> A retrospective cohort study, all adults &gt;16 years admitted to three UK hospitals, 2006-2022, with pneumococcal disease. Medical records were reviewed for each clinical episode and serotype data were obtained from the UK Health Security Agency national reference laboratory. We identified 1,501 (40.3%) cases of invasive pneumococcal disease (IPD) with known serotype, 134 (3.6%) IPD cases without serotype data, and 2,084 (56.0%) non-IPD cases, which are typically missed in national surveillance. Disease incidence increased progressively from 2006-2020, followed by a sudden decline after COVID-19 emergence and then a gradual increase to pre-pandemic levels. Paediatric PCV7 introduction reduced adult PCV7 serotype IPD from 29.4% [24.1-35.4] of IPD in 2006-09 to 7.0% [3.7-12.7] in 2021-22. PCV13 introduction also decreased adult vaccine serotype IPD, but considerable residual adult disease remains, causing 34.3% [28.6-40.4] of IPD in 2006-09 and 21.7% [15.5-29.6] 9 in 2021-22, respectively. Serotype replacement diminished the benefits of PCV introduction: PCV20-13 and non-PCV serotypes represented 27.0% [21.9-32.9] and 9.3% [6.3-13.5] of disease in 2006-2009, and 39.5% [31.5-48.2] and 31.8% [24.4-40.2] in 2021-2022, respectively. Serotype shifts have resulted in increasing disease caused by serotype 3 and 8, and the re-emergence of serotype 19F and 19A. These serotype shifts occurred as clinical disease severity changed, and whilst the COVID-19 pandemic disrupted disease severity trends, these have now largely reverted to previous trajectories. Patient age trended upwards and although CURB65 severity decreased there were increased ICU admission rates. Overall, inpatient mortality decreased and hospitalisation duration remained stable. <b>Conclusions</b> After 17 years of PCV use, residual pneumococcal disease due to the vaccine serotypes among hospitalised adults remains. The sharp decline in pneumococcal disease during the COVID-19 pandemic has now reversed, with increasing cases due to vaccine serotypes, especially serotype 3. Around 68.2% of cases in 2022 were potentially covered by the recently licensed 20-valent PCV.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.30.23287917v2" target="_blank">Trends in serotype distribution and disease severity in adults hospitalised with Streptococcus pneumoniae infection in Bristol and Bath: a retrospective cohort study, 2006-2022</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Homologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: SARS-CoV-2 Subunit Recombinant Protein Vaccine<br/><b>Sponsor</b>:   PT Bio Farma<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>Role of Ivermectin and Colchicine in Treatment of COVID-19: Randomized Controlled Clinical Trial</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Ivermectin Tablets;   Drug: Colchicine 0.5 MG;   Drug: Standared managment<br/><b>Sponsor</b>:   Ain Shams University<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of A Recombinant Protein COVID-19 Vaccine as Booster Vaccines</strong> - <b>Conditions</b>:   COVID-19;   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Biological: SCTV01E-2;   Biological: SCTV01E<br/><b>Sponsor</b>:   Sinocelltech 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>COVID-19 Vaccine Hesitancy Counseling Intervention for Pharmacists</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Behavioral: Standard implementation webinar and online training;   Behavioral: Virtual facilitation<br/><b>Sponsors</b>:   University of North Carolina, Chapel Hill;   University of Arkansas;   University of South Carolina;   National Institute on Minority Health and Health Disparities (NIMHD)<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>Developing an Effective Intervention to Address Post-Corona-Virus-Disease-2019 Balance Disorders, Weakness and Muscle Fatigue in Individuals Aged 65+</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Device: Resistance Training<br/><b>Sponsor</b>:   Józef Piłsudski University of Physical Education<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>Multimodal Long Covid19</strong> - <b>Condition</b>:   Long COVID-19 Syndrome<br/><b>Intervention</b>:   Other: Multimodal intervention in Long Covid19<br/><b>Sponsors</b>:   Universidad de Magallanes;   Teaching Assistance and Research Center of the University of Magallanes CADI-UMAG;   Clinical Hospital Dr. Lautaro Navarro Avaria<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>Immunogenicity and Safety Study of SCB-2023 Vaccine as a Booster in Adults</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: SCB-2023 vaccine (trivalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection;   Biological: SCB-2019 (monovalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection<br/><b>Sponsor</b>:   Clover Biopharmaceuticals AUS Pty 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>The Safety and Immunogenicity Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB002</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: LYB002V14;   Biological: LYB002V14A;   Biological: LYB002CA<br/><b>Sponsors</b>:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.;   Affiliated Hospital of North Sichuan Medical College<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>Treatment of Long COVID (TLC) Feasibility Trial</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Low-dose Naltrexone (LDN);   Drug: Cetirizine;   Drug: Famotidine;   Drug: LDN Placebo;   Drug: Cetirizine Placebo;   Drug: Famotidine Placebo<br/><b>Sponsors</b>:   Emory University;   CURE Drug Repurposing Collaboratory (CDRC)<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>Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease</strong> - <b>Conditions</b>:   COVID-19;   Renal Insufficiency, Chronic<br/><b>Intervention</b>:   Drug: Nirmatrelvir/ritonavir<br/><b>Sponsor</b>:   Chinese PLA General Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Immunogenicity and Safety Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB001</strong> - <b>Conditions</b>:   COVID-19;   Vaccine Reaction<br/><b>Interventions</b>:   Biological: LYB001;   Biological: CoronaVac<br/><b>Sponsors</b>:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.;   Affiliated Hospital of North Sichuan Medical College<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>Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome</strong> - <b>Condition</b>:   Post-Acute COVID-19 Syndrome<br/><b>Interventions</b>:   Drug: Placebo;   Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]<br/><b>Sponsor</b>:   Hellenic Institute for the Study of Sepsis<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Music Combined With Sports Games on Alleviating Psychological Stress, Anxiety and Mental Energy Among Adolescents During COVID-19 Pandemic in Lanzhou Gansu Province China</strong> - <b>Conditions</b>:   Stress;   Anxiety and Fear<br/><b>Interventions</b>:   Behavioral: Music intervention only;   Behavioral: Sports games intervention only;   Behavioral: Music and sports games intervention<br/><b>Sponsor</b>:   Wu Jiarun<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>:   Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)<br/><b>Interventions</b>:   Drug: MBS-COV;   Drug: Placebo<br/><b>Sponsor</b>:   Oneness Biotech 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>Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19</strong> - <b>Conditions</b>:   Asthenia;   COVID-19;   Functional MRI;   Cognitive Impairment<br/><b>Interventions</b>:   Other: Structural and functional MRI;   Drug: Ethyl methyl hydroxypyridine succinate + Meldonium;   Drug: Placebo<br/><b>Sponsor</b>:   Promomed, LLC<br/><b>Completed</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>CHO-produced RBD-Fc subunit vaccines with alternative adjuvants generate immune responses against SARS-CoV-2</strong> - Subunit vaccines feature critical advantages over other vaccine platforms such as stability, price, and minimal adverse effects. To maximize immunological protection of subunit vaccines, adjuvants are considered as main components that are formulated within the subunit vaccine. They can modulate adverse effects and enhance immune outcomes. However, the most suitable formulation providing the best immunological outcomes and safety are still under investigation. In this report, we combined…</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>Determining the clinical and cost-effectiveness of nasal sprays and a physical activity and stress management intervention to reduce respiratory tract infections in primary care: A protocol for the ‘Immune Defence’ randomised controlled trial</strong> - BACKGROUND: Most adults in the UK experience at least one viral respiratory tract infection (RTI) per year. Individuals with comorbidities and those with recurrent RTIs are at higher risk of infections. This can lead to more severe illness, worse quality of life and more days off work. There is promising evidence that using common nasal sprays or improving immune function through increasing physical activity and managing stress, may reduce the incidence and severity of RTIs.</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><em>In</em><em>silico</em> generation of novel ligands for the inhibition of SARS-CoV-2 main protease (3CL<sup>pro</sup>) using deep learning</strong> - The recent emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) has become a global public health crisis, and a crucial need exists for rapid identification and development of novel therapeutic interventions. In this study, a recurrent neural network (RNN) is trained and optimized to produce novel ligands that could serve as potential inhibitors to the SARS-CoV-2 viral protease: 3 chymotrypsin-like protease (3CL^(pro))….</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>Synergistic Effect of Zinc-Chitosan Nanoparticles and Hydroxychloroquine to Inhibit Buffalo Coronavirus</strong> - Zinc ions can hinder the synthesis of proteins required for accomplishing several stages of the viral life cycle. The intracellular zinc concentration can be increased by using zinc ionophores which transport zinc ions into the cells and hinder viral replication. (Hydroxy)chloroquine is an example of a zinc ionophore, but both zinc and (hydroxy)chloroquine can be toxic to the host organism. The nanocarriers may serve as camouflage to evade the adverse effects of drugs, chemicals, and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Auraptene Has Antiviral Activity against Human Coronavirus OC43 in MRC-5 Cells</strong> - Auraptene (7-geranyloxycoumarin) is the abundant prenyloxycoumarin found in the fruits of Citrus spp. Auraptene has a variety of pharmacological and therapeutic functions, such as anticancer, antioxidant, immunomodulatory, and anti-inflammation activities, with excellent safety profiles. In this study, we evaluated the anticoronaviral activity of auraptene in HCoV-OC43-infected human lung fibroblast MRC-5 cells. We found that auraptene effectively inhibited HCoV-OC43-induced cytopathic effects…</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>Potency of Xanthone Derivatives from <em>Garcinia mangostana</em> L. for COVID-19 Treatment through Angiotensin-Converting Enzyme 2 and Main Protease Blockade: A Computational Study</strong> - ACE2 and Mpro in the pathology of SARS-CoV-2 show great potential in developing COVID-19 drugs as therapeutic targets, due to their roles as the “gate” of viral entry and viral reproduction. Of the many potential compounds for ACE2 and Mpro inhibition, α-mangostin is a promising candidate. Unfortunately, the potential of α-mangostin as a secondary metabolite with the anti-SARS-CoV-2 activity is hindered due to its low solubility in water. Other xanthone isolates, which also possess the xanthone…</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>Pharmacological Activity of Cepharanthine</strong> - Cepharanthine, a natural bisbenzylisoquinoline (BBIQ) alkaloid isolated from the plant Stephania Cephalantha Hayata, is the only bisbenzylisoquinoline alkaloid approved for human use and has been used in the clinic for more than 70 years. Cepharanthine has a variety of medicinal properties, including signaling pathway inhibitory activities, immunomodulatory activities, and antiviral activities. Recently, cepharanthine has been confirmed to greatly inhibit SARS-CoV-2 infection. Therefore, we…</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>Aprotinin-Drug against Respiratory Diseases</strong> - Aprotinin (APR) was discovered in 1930. APR is an effective pan-protease inhibitor, a typical “magic shotgun”. Until 2007, APR was widely used as an antithrombotic and anti-inflammatory drug in cardiac and noncardiac surgeries for reduction of bleeding and thus limiting the need for blood transfusion. The ability of APR to inhibit proteolytic activation of some viruses leads to its use as an antiviral drug for the prevention and treatment of acute respiratory virus infections. However, due to…</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>Transcriptome Changes of Hematopoietic Stem and Progenitor Cells in the Peripheral Blood of COVID-19 Patients by scRNA-seq</strong> - Coronavirus disease 2019 (COVID-19) threatens public health all over the world. It is well-accepted that the immune cells in peripheral blood are widely involved in the pathological process of COVID-19. However, hematopoietic stem and progenitor cells (HSPCs), as the main source of peripheral immune cells, have not been well studied during COVID-19 infection. We comprehensively revealed the transcriptome changes of peripheral blood HSPCs after COVID-19 infection and vaccination by single-cell…</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 Multivariant Surrogate Neutralization Assay Identifies Variant-Specific Neutralizing Antibody Profiles in Primary SARS-CoV-2 Omicron Infection</strong> - Primary infection with the Omicron variant of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) can be serologically identified with distinct profiles of neutralizing antibodies (nAbs), as indicated by high titers against the Omicron variant and low titers against the ancestral wild-type (WT). Here, we evaluated whether a novel surrogate virus neutralization assay (sVNT) that simultaneously quantifies the binding inhibition of angiotensin-converting enzyme 2 (ACE2) to the proteins of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>LY6E is a pan-coronavirus restriction factor in the respiratory tract</strong> - LY6E is an antiviral restriction factor that inhibits coronavirus spike-mediated fusion, but the cell types in vivo that require LY6E for protection from respiratory coronavirus infection are unknown. Here we used a panel of seven conditional Ly6e knockout mice to define which Ly6e-expressing cells confer control of airway infection by murine coronavirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Loss of Ly6e in Lyz2-expressing cells, radioresistant Vav1-expressing cells…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and safety of the siRNA JNJ-73763989 and the capsid assembly modulator JNJ-56136379 (bersacapavir) with nucleos(t)ide analogues for the treatment of chronic hepatitis B virus infection (REEF-1): a multicentre, double-blind, active-controlled, randomised, phase 2b trial</strong> - BACKGROUND: JNJ-73763989 (JNJ-3989), a small interfering RNA, targets all hepatitis B virus (HBV) RNAs, reducing all HBV proteins. JNJ-56136379 (JNJ-6379; also known as bersacapavir), a capsid assembly modulator, inhibits HBV replication. We aimed to evaluate the efficacy (ie, antiviral activity) and safety of these therapeutics in combination with nucleos(t)ide analogues in patients with chronic hepatitis 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>Expression of the readthrough transcript CiDRE in alveolar macrophages boosts SARS-CoV-2 susceptibility and promotes COVID-19 severity</strong> - Lung infection during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the angiotensin-I-converting enzyme 2 (ACE2) receptor induces a cytokine storm. However, the precise mechanisms involved in severe COVID-19 pneumonia are unknown. Here, we showed that interleukin-10 (IL-10) induced the expression of ACE2 in normal alveolar macrophages, causing them to become vectors for SARS-CoV-2. The inhibition of this system in hamster models attenuated SARS-CoV-2 pathogenicity. Genome-wide…</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>Circulating Reelin promotes inflammation and modulates disease activity in acute and long COVID-19 cases</strong> - Thromboembolic complications and excessive inflammation are frequent in severe COVID-19, potentially leading to long COVID. In non-COVID studies, we and others demonstrated that circulating Reelin promotes leukocyte infiltration and thrombosis. Thus, we hypothesized that Reelin participates in endothelial dysfunction and hyperinflammation during COVID-19. We showed that Reelin was increased in COVID-19 patients and correlated with the disease activity. In the severe COVID-19 group, we observed a…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 main protease cleaves MAGED2 to antagonize host antiviral defense</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent causing the global pandemic of COVID-19. SARS-CoV-2 genome encodes a main protease (nsp5, also called Mpro) and a papain-like protease (nsp3, also called PLpro), which are responsible for processing viral polyproteins to assemble a functional replicase complex. In this study, we found that Mpro of SARS-CoV-2 can cleave human MAGED2 and other mammalian orthologs at Gln-263. Moreover, SARS-CoV and MERS-CoV Mpro can also…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<script>AOS.init();</script></body></html>

643
archive-daily-dose/15 July, 2023.html Normal file
View File

@ -0,0 +1,643 @@
<!DOCTYPE html>
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
<meta charset="utf-8"/>
<meta content="pandoc" name="generator"/>
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
<title>15 July, 2023</title>
<style>
code{white-space: pre-wrap;}
span.smallcaps{font-variant: small-caps;}
span.underline{text-decoration: underline;}
div.column{display: inline-block; vertical-align: top; width: 50%;}
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
ul.task-list{list-style: none;}
</style>
<title>Daily-Dose</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><style>*{overflow-x:hidden;}</style><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
<body>
<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>Vermont’s Catastrophic Floods and the Spread of Unnatural Disasters</strong> - In parts of the Northeast, two months of rain fell in two days. - <a href="https://www.newyorker.com/news/annals-of-a-warming-planet/vermonts-catastrophic-floods-and-the-spread-of-unnatural-disasters">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Instant Pot and the Miracle Kitchen Devices of Yesteryear</strong> - Preparing meals is a Sisyphean task, and anything that promises to make it faster, or easier, or better, or healthier, or more fun, is irresistible. - <a href="https://www.newyorker.com/news/afterword/the-instant-pot-and-the-miracle-kitchen-devices-of-yesteryear">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Is It Hot Enough Yet for Politicians to Take Real Action?</strong> - The latest record temperatures are driving, again precisely as scientists have predicted, a cascading series of disasters around the world. - <a href="https://www.newyorker.com/news/daily-comment/is-it-hot-enough-yet-for-politicians-to-take-real-action">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Mysterious Third Party Enters the Presidential Race</strong> - No Labels is obscure but well funded. Could it have an outsized impact on the election? Plus, the journalist Donovan Ramsey on his chronicle of the crack-cocaine epidemic. - <a href="https://www.newyorker.com/podcast/the-new-yorker-radio-hour/a-mysterious-third-party-enters-the-presidential-race">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sotol and the Making of the Next Big Drink</strong> - The Mexican spirit has been called the next mezcal. But its newfound popularity has brought problems, too. - <a href="https://www.newyorker.com/news/letter-from-the-southwest/sotol-and-the-making-of-the-next-big-drink">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Even the scientists who build AI can’t tell you how it works</strong> -
<figure>
<img alt="An image of a laptop screen on the Chat GPT website. " src="https://cdn.vox-cdn.com/thumbor/0gsNd8VSs_vHXIdM9WxFEaxWCiM=/0x0:8326x6245/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72454526/1246656790.0.jpg"/>
<figcaption>
Artificial intelligence systems like ChatGPT might disrupt or revolutionize many industries. But that doesn’t mean we understand what they’re doing. | Frank Rumpenhorst/Picture Alliance via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
 “We built it, we trained it, but we don’t know what it’s doing.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fuwmGs">
Artificial intelligence systems like ChatGPT can do a wide range of impressive things: they can write passable essays, they can ace the bar exam, they’ve even been used for scientific research. But ask an <a href="https://www.vox.com/2023/4/28/23702644/artificial-intelligence-machine-learning-technology">AI</a> researcher how it does all this, and they shrug.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gkTuzY">
“If we open up ChatGPT or a system like it and look inside, you just see millions of numbers flipping around a few hundred times a second,” says AI scientist <a href="https://cims.nyu.edu/~sbowman/">Sam Bowman</a>. “And we just have no idea what any of it means.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A6E4Tb">
Bowman is a professor at NYU, where he runs an AI research lab, and he’s a researcher at Anthropic, an AI research company. He’s spent years building systems like ChatGPT, assessing what they can do, and studying how they work.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j3PiMF">
He explains that ChatGPT runs on something called an artificial neural network, which is a type of AI modeled on the human brain. Instead of having a bunch of rules explicitly coded in like a traditional computer program, this kind of AI learns to detect and predict patterns over time. But Bowman says that because systems like this essentially teach themselves, it’s difficult to explain precisely how they work or what they’ll do. Which can lead to unpredictable and even risky scenarios as these programs become more ubiquitous.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a8T6L5">
I spoke with Bowman on <a href="https://www.vox.com/unexplainable"><em>Unexplainable</em></a>, Vox’s podcast that explores scientific mysteries, unanswered questions, and all the things we learn by diving into the unknown. The conversation is included in a new two-part series on AI: The Black Box.
</p>
<div id="UlKid9">
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vnREUU">
<em>This conversation has been edited for length and clarity.</em>
</p>
<h4 id="nnGSTu">
Noam Hassenfeld
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wPDtNX">
How do systems like ChatGPT work? How do engineers actually train them?
</p>
<h4 id="ytBOKK">
Sam Bowman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FFVSE0">
So the main way that systems like ChatGPT are trained is by basically doing autocomplete. We’ll feed these systems sort of long text from the web. We’ll just have them read through a Wikipedia article word by word. And after it’s seen each word, we’re going to ask it to guess what word is gonna come next. It’s doing this with probability. It’s saying, “It’s a 20 percent chance it’s ‘the,’ 20 percent chance it’s ‘of.’” And then because we know what word actually comes next, we can tell it if it got it right.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o5uDb3">
This takes months, millions of dollars worth of computer time, and then you get a really fancy autocomplete tool. But you want to refine it to act more like the thing that you’re actually trying to build, act like a sort of helpful virtual assistant.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kxRr5A">
There are a few different ways people do this, but the main one is reinforcement learning. The basic idea behind this is you have some sort of test users chat with the system and essentially upvote or downvote responses. Sort of similarly to how you might tell the model, “All right, make this word more likely because it’s the real next word,” with reinforcement learning, you say, “All right, make this entire response more likely because the user liked it, and make this entire response less likely because the user didn’t like it.”
</p>
<h4 id="UH5jZa">
Noam Hassenfeld
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KYEa1p">
So let’s get into some of the unknowns here. You wrote a <a href="https://cims.nyu.edu/~sbowman/eightthings.pdf">paper</a> all about things we don’t know when it comes to systems like ChatGPT. What’s the biggest thing that stands out to you?
</p>
<h4 id="6Eng2s">
Sam Bowman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xq1iC0">
So there’s two connected big concerning unknowns. The first is that we don’t really know what they’re doing in any deep sense. If we open up ChatGPT or a system like it and look inside, you just see millions of numbers flipping around a few hundred times a second, and we just have no idea what any of it means. With only the tiniest of exceptions, we can’t look inside these things and say, “Oh, here’s what concepts it’s using, here’s what kind of rules of reasoning it’s using. Here’s what it does and doesn’t know in any deep way.” We just don’t understand what’s going on here. We built it, we trained it, but we don’t know what it’s doing.
</p>
<h4 id="puXd1B">
Noam Hassenfeld
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AHmtk1">
Very big unknown.
</p>
<h4 id="YUj0Zj">
Sam Bowman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G3Wd9T">
Yes. The other big unknown that’s connected to this is we don’t know how to steer these things or control them in any reliable way. We can kind of nudge them to do more of what we want, but the only way we can tell if our nudges worked is by just putting these systems out in the world and seeing what they do. We’re really just kind of steering these things almost completely through trial and error.
</p>
<h4 id="0U1oou">
Noam Hassenfeld
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RnKmZu">
Can you explain what you mean by “we don’t know what it’s doing”? Do we know what normal programs are doing?
</p>
<h4 id="dJOTIL">
Sam Bowman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lZZHGJ">
I think the key distinction is that with normal programs, with Microsoft Word, with Deep Blue [IBM’s chess playing software], there’s a pretty simple explanation of what it’s doing. We can say, “Okay, this bit of the code inside Deep Blue is computing seven [chess] moves out into the future. If we had played this sequence of moves, what do we think the other player would play?” We can tell these stories at most a few sentences long about just what every little bit of computation is doing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HlRcbW">
With these neural networks [e.g., the type of AI ChatGPT uses], there’s no concise explanation. There’s no explanation in terms of things like checkers moves or strategy or what we think the other player is going to do. All we can really say is just there are a bunch of little numbers and sometimes they go up and sometimes they go down. And all of them together seem to do something involving language. We don’t have the concepts that map onto these neurons to really be able to say anything interesting about how they behave.
</p>
<h4 id="mFL4rc">
Noam Hassenfeld
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NctS13">
How is it possible that we don’t know how something works and how to steer it if we built it?
</p>
<h4 id="eLvsGg">
Sam Bowman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dCmsed">
I think the important piece here is that we really didn’t build it in any deep sense. We built the computers, but then we just gave the faintest outline of a blueprint and kind of let these systems develop on their own. I think an analogy here might be that we’re trying to grow a decorative topiary, a decorative hedge that we’re trying to shape. We plant the seed and we know what shape we want and we can sort of take some clippers and clip it into that shape. But that doesn’t mean we understand anything about the biology of that tree. We just kind of started the process, let it go, and try to nudge it around a little bit at the end.
</p>
<h4 id="V6i3b2">
Noam Hassenfeld
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L9bVYd">
Is this what you were talking about in your paper when you wrote that when a lab starts training a new system like ChatGPT they’re basically investing in a mystery box?
</p>
<h4 id="xg1odV">
Sam Bowman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fsRUIa">
Yeah, so if you build a little version of one of these things, it’s just learning text statistics. It’s just learning that ‘the’ might come before a noun and a period might come before a capital letter. Then as they get bigger, they start learning to rhyme or learning to program or learning to write a passable high school essay. And none of that was designed in — you’re running just the same code to get all these different levels of behavior. You’re just running it longer on more computers with more data.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kO5vwQ">
So basically when a lab decides to invest tens or hundreds of millions of dollars in building one of these neural networks, they don’t know at that point what it’s gonna be able to do. They can reasonably guess it’s gonna be able to do more things than the previous one. But they’ve just got to wait and see. We’ve got some ability to predict some facts about these models as they get bigger, but not these really important questions about what they can do.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2z7Pm2">
This is just very strange. It means that these companies can’t really have product roadmaps. They can’t really say, “All right, next year we’re gonna be able to do this. Then the year after we’re gonna be able to do that.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="raiAvm">
And it also plays into some of the concerns about these systems. That sometimes the skill that emerges in one of these models will be something you really don’t want. The paper describing GPT-4 talks about how when they first trained it, it could do a decent job of walking a layperson through building a biological weapons lab. And they definitely did not want to deploy that as a product. They built it by accident. And then they had to spend months and months figuring out how to clean it up, how to nudge the neural network around so that it would not actually do that when they deployed it in the real world.
</p>
<h4 id="OsmX1N">
Noam Hassenfeld
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FjU27K">
So I’ve heard of the field of interpretability. Which is the science of figuring out how AI works. What does that research look like, and has it produced anything?
</p>
<h4 id="OYvCpa">
Sam Bowman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yEGdBC">
Interpretability is this goal of being able to look inside our systems and say pretty clearly with pretty high confidence what they’re doing, why they’re doing it. Just kind of how they’re set up being able to explain clearly what’s happening inside of a system. I think it’s analogous to biology for organisms or <a href="https://www.vox.com/neuroscience">neuroscience</a> for human minds.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="v5kpmf">
But there are two different things people might mean when they talk about interpretability.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ByMybR">
One of them is this goal of just trying to sort of figure out the right way to look at what’s happening inside of something like ChatGPT figuring out how to kind of look at all these numbers and find interesting ways of mapping out what they might mean, so that eventually we could just look at a system and say something about it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ixaLnG">
The other avenue of research is something like interpretability by design. Trying to build systems where by design, every piece of the system means something that we can understand.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M8YSVu">
But both of these have turned out in practice to be extremely, extremely hard. And I think we’re not making critically fast progress on either of them, unfortunately.
</p>
<h4 id="AXidBb">
Noam Hassenfeld
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SRaMVh">
What makes interpretability so hard?
</p>
<h4 id="J4BpVT">
Sam Bowman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LOK3B7">
Interpretability is hard for the same reason that cognitive science is hard. If we ask questions about the human brain, we very often don’t have good answers. We can’t look at how a person thinks and explain their reasoning by looking at the firings of the neurons.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SjP30b">
And it’s perhaps even worse for these neural networks because we don’t even have the little bits of intuition that we’ve gotten from humans. We don’t really even know what we’re looking for.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qaOQdS">
Another piece of this is just that the numbers get really big here. There are hundreds of billions of connections in these neural networks. So even if you can find a way that if you stare at a piece of the network for a few hours, we would need every single person on Earth to be staring at this network to really get through all of the work of explaining it.
</p>
<h4 id="opt7pW">
Noam Hassenfeld
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h3ggVS">
And because there’s so much we don’t know about these systems, I imagine the spectrum of positive and negative possibilities is pretty wide.
</p>
<h4 id="rm9OJu">
Sam Bowman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="shJJrH">
Yeah, I think that’s right. I think the story here really is about the unknowns. We’ve got something that’s not really meaningfully regulated, that is more or less useful for a huge range of valuable tasks, we’ve got increasingly clear evidence that this technology is improving very quickly in directions that seem like they’re aimed at some very, very important stuff and potentially destabilizing to a lot of important institutions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V1VVRM">
But we don’t know how fast it’s moving. We don’t know why it’s working when it’s working.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4PEVxs">
We don’t have any good ideas yet about how to either technically control it or institutionally control it. And if we have no idea what next year’s systems are gonna do, and if next year we have no idea what the systems the year after that are gonna do.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="t3V3yW">
It seems very plausible to me that that’s going to be the defining story of the next decade or so. How we come to a better understanding of this and how we navigate it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HrY9uJ">
</p></li>
<li><strong>Will diet soda, yogurt, and cereal disappear from stores?</strong> -
<figure>
<img alt="Grocery store aisle with shelves full of food products." src="https://cdn.vox-cdn.com/thumbor/b11iPRJtLZq-Ah1QxdJbH1R2rhw=/657x0:6802x4609/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72454475/GettyImages_1412353022.0.jpg"/>
<figcaption>
The grocery shelves are about to get that much more daunting. On July 14, the World Health Organization classified aspartame as “possibly carcinogenic to humans.” It’s in tons of food and beverages. | Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
What the WHO’s aspartame warnings mean for you.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="acMa2U">
Diet soda. Chewing gum. Yogurt. Cereal. No, this isn’t someone’s grocery list — these are everyday consumer products that can contain the popular artificial sweetener aspartame.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="blW03D">
This week, the World Health Organization’s International Agency for Research on Cancer (IARC) <a href="https://www.vox.com/2023/7/1/23780348/aspartame-cancer-carcinogenic-health-risk-who-iarc-fda-efsa-diet-coke-sugar-free">declared aspartame as “possibly carcinogenic</a>.” Another WHO committee, the Joint FAO/WHO Expert Committee on Food Additives (JECFA), independently assessed the ingredient, too, but maintained its existing recommendation — suggesting not that people cut the substance entirely out of their diets but that they limit their daily aspartame consumption to about 40 mg per kilogram (or about 2.2 pounds) of body weight. Diet soda contains <a href="https://www.chhs.colostate.edu/krnc/monthly-blog/the-low-down-on-diet-drinks-how-much-is-okay">about 200 mg of aspartame</a> per 12-ounce can. By that measure, an adult weighing 60 kg, or roughly 132 pounds, would need to drink about 12 cans of diet soda a day to exceed the JECFA’s recommendation, assuming they had nothing else containing aspartame.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kfEzSI">
Making matters more confounding, the Food and Drug Administration had yet another take. It told Vox in an email that it had reviewed the information used in WHO’s assessment and “identified significant shortcomings” in the studies the agency relied on. “Aspartame is one of the most studied food additives in the human food supply,” the agency added.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="klQ7NC">
All this creates a fair amount of confusion for consumers, leaving many of us with questions about whether we should cut out the thousands of products using the sweetener, worry about what we’ve already consumed, or do nothing at all. Vox sought answers to some of the questions you might have right now.
</p>
<h3 id="GiQxMF">
What is aspartame?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5hTo3t">
Aspartame is an artificial sweetener first discovered in 1965, though it really exploded in popularity in the US in the 1980s, after its approval by the FDA, replacing more than a <a href="https://www.saveur.com/artificial-sweeteners/">billion pounds of sugar</a> throughout the decade. As awareness and concern over excessive sugar consumption grew and rates of Type 2 diabetes and obesity in the US rose, artificial sweeteners became a popular low-calorie sugar substitute in food and drinks, with consumers clamoring for “diet” versions of popular products. Aspartame was hardly the first artificial sweetener; cyclamate and saccharin preceded its use, but they were <a href="https://www.nytimes.com/1970/08/23/archives/the-fda-orders-a-total-cyclamate-ban-another-switch.html">both</a> <a href="https://www.nytimes.com/1977/03/10/archives/fda-banning-saccharin-use-on-cancer-links-fda-bans-use-of-saccharin.html">eventually banned</a> for cancer concerns. Today, <a href="https://www.nbcnews.com/health/cancer/foods-contain-aspartame-artificial-sweetener-possible-carcinogen-rcna93913">over 5,000 products</a> sold in the US contain aspartame.
</p>
<h3 id="1o9dWn">
What do the WHO’s findings even mean?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WV5kQX">
You’d be forgiven for thinking that the WHO is saying aspartame might be totally fine for consumption, as long as you don’t overdo it. The fact that JECFA did not change its recommended daily intake also feels like another point for Team No Big Deal, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L4cCyX">
“When you say it’s a ‘possible carcinogen,’ it’s easy for a consumer to gravitate toward the ‘possible’ part and say, ‘Okay, well, it’s not an immediate threat,” says Brian Ronholm, director of food policy at Consumer Reports, which publishes product tests and investigative journalism, and spearheads consumer advocacy campaigns.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Mr79QM">
The big takeaway from the WHO’s conclusion, however, is that we just don’t know enough about aspartame’s cancer risk in humans. IARC relied on just three available studies looking into the carcinogenic effect of aspartame in humans that showed possible links to liver cancer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2IQRCu">
The IARC uses <a href="https://monographs.iarc.who.int/agents-classified-by-the-iarc/">four classification levels</a> when it comes to agents: Substances in Group 1 are classified as cancer-causing in humans because sufficient evidence exists that they are indeed carcinogens; Group 2A, probably causes cancer; Group 2B, possibly causes cancer; and Group 3 encompasses substances unclassifiable as a cancer risk. Tobacco, sulfur mustard (also known as mustard gas), and asbestos are all Group 1. Aspartame is in Group 2B. Other Group 2B agents include aloe vera, talc-based body powder (which can contain asbestos), nickel, and safrole, a chemical in ingredients used to add flavor to root beer. The FDA <a href="https://www.mcgill.ca/oss/article/did-you-know/root-root-beer-sassafras">banned safrole in food</a> in 1960.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TRx40W">
Here’s what’s really important for consumers: Nothing happens automatically based on the WHO’s assessment; it’s up to regulators, companies, and consumers to decide how to respond. But the assessment certainly should raise eyebrows, especially because the WHO’s cancer research arm is a trusted authority. Experts told Vox that a US ban on aspartame isn’t likely, at least not anytime soon, and food and beverage companies aren’t likely to swiftly remove their products from the shelves.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FlrJbR">
That means, of course, that the choice to continue drinking Diet Coke, chewing Trident Gum, eating sugar-free Jell-O, or consuming one of the many other foods and drinks that use aspartame as a sugar substitute, is left up to individual consumers. Consumer protection groups, meanwhile, have been recommending people avoid aspartame, and the American Cancer Society is advising caution, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S7uJy6">
“The science is still evolving, but we recommend people use today’s report by IARC as a time to reflect on their use of aspartame, but also an opportunity to review their overall dietary intake, including processed meat and alcohol, known carcinogens associated with increased risk of cancer,” Dr. William Dahut, the American Cancer Society’s chief scientific officer, said in a press release. He added that the organization “supports the IARC’s call for more research of aspartame and other artificial sweeteners.”
</p>
<h3 id="I540P8">
Should we avoid all aspartame?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1NvOq9">
If only there were a clear-cut answer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="g5YD8z">
“From a consumer perspective, they’ll probably find the mixed messaging confusing and frustrating,” says Ronholm. “Those who already had concerns and serious questions about aspartame, they’ll think more about sharply limiting their consumption. But there’s also going to be a segment that will continue to consume these beverages and thinking that ‘Well, nothing’s happened to me yet.’”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hbLxNk">
Consumer advocates are urging that people be aware of just how many products can contain aspartame. Not just soda, but low- or no-sugar candies, breakfast cereals, instant coffee, gelatin products, and syrups may all use the sweetener.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5PrH2W">
The Center for Science in the Public Interest (CSPI), a consumer watchdog and advocacy group, has been recommending for a long time that consumers avoid aspartame due to its possible links to cancer. “This should be very concerning for consumers, for industry, and for regulators,” says Thomas Galligan, a principal scientist for food additives and supplements for the organization.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yaMWrU">
Galligan urges consumers to avoid it. “But I say that with a really important caveat — that consumers should not switch out aspartame for sugar. Regular sugary-sweet soda poses a greater health risk to consumers than aspartame and other non-nutritive sweeteners.” He recommends using or looking for products that contain the natural sweetener stevia instead. Better yet, drink water.
</p>
<h3 id="tX3j6T">
Will my favorite soda disappear from the shelves?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WLuaoj">
Many companies have been surprisingly quiet in their response to the news. Yesterday, <a href="https://www.reuters.com/business/retail-consumer/pepsico-says-no-plans-change-portfolio-who-set-warn-aspartame-sweeteners-2023-07-13">PepsiCo’s chief financial officer told Reuters</a> that the company had no plans to change its products at this point. The company <a href="https://www.cnbc.com/2023/07/13/who-aspartame-decision-could-hurt-diet-soda-sales.html">uses aspartame in Pepsi Zero Sugar</a>, but not in Diet Pepsi.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xpQDTm">
“Banning these products is not going to be happening anytime soon,” says Ronholm. The CSPI is urging companies to take IARC’s assessment seriously and reformulate their products — or at least increase the availability of unsweetened products. Both Galligan and Ronholm were skeptical that they would do so. “I can’t envision them reformulating any of their products as a result of this announcement, unless there’s some significant consumer backlash that results in a sharp decline in demand,” Ronholm says. The fact that the WHO’s messaging is probably confusing to consumers and the FDA disagrees with its findings make it unlikely that companies will be motivated to change their products.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HpDktO">
The food and beverage industry, well aware that the IARC was looking into aspartame, has been on the defensive for a while. Industry representatives “actually met with the FDA [in] the middle of last year,” says Galligan.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rRGxdY">
“I would say that the beverage industry is going to continue on those tactics, trying to discredit [and] undercut this really important finding,” Galligan says.
</p>
<h3 id="7ABV9K">
Will the FDA do anything?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xCyWho">
The FDA has made clear that it doesn’t see eye to eye with IARC. But that doesn’t necessarily mean the US agency won’t do anything, especially if public and political pressure mounts. Galligan cites a federal statute called the <a href="https://www.canr.msu.edu/news/food-ingredient-safety-food-additives-delaney-clause">Delaney Clause</a>. Part of the Food Additives Amendment of 1958, which empowered the FDA to require all companies to test new food additives before products hit the market, the Delaney Clause “basically expressly prohibits any chemical that’s been shown to cause cancer from being used,” says Galligan. While in other cases the FDA can rate food additives as safe at certain amounts, this clause imposes a <a href="https://www.nytimes.com/1973/01/13/archives/the-conflict-over-the-delaney-clause.html">strict zero-risk policy</a> on additives shown to cause cancer in animals. According to Galligan, the clause could trigger here. But he added that “while [the FDA] have the authority to regularly reevaluate food additives that have been approved for use, they really rarely do.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HxJQDD">
“We believe that Congress made it very clear when they passed the food additive amendment in 1958 that no amount of possible carcinogens, probable carcinogens, et cetera, are allowed in our food,” he says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BY3erH">
As my <a href="https://www.vox.com/2023/7/1/23780348/aspartame-cancer-carcinogenic-health-risk-who-iarc-fda-efsa-diet-coke-sugar-free">colleague Keren Landman has explained</a>, the FDA’s approval of aspartame has a checkered history. Its use was initially denied, then approved in 1981 despite concerns that it might cause brain tumors. Over the past few decades, many scientists have warned of its potential cancer risk — those who disputed these concerns were often backed by groups representing the food and beverage industry.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9wB2nj">
“You look at the uncertain science surrounding it, you look at the dubious evaluation process that was associated with its original approval — based on that, Consumer Reports has long urged caution in consuming aspartame and will continue to do so,” Ronholm says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MSH2dl">
He continued that even with other chemicals and additives, the FDA has “typically been hesitant” to address issues. A <a href="https://www.politico.com/interactives/2022/fda-fails-regulate-food-health-safety-hazards/">Politico investigation</a> last year painted a picture of a sluggish, dysfunctional agency, particularly when it came to food safety, citing that its food branch had “a deep-seated culture of avoiding hard decisions and a near-paralyzing fear of picking serious fights with the food industry.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ix5kx2">
It’s also worth noting that the FDA’s stance on aspartame is echoed by regulatory bodies in other countries. Over <a href="https://www.washingtonpost.com/business/2023/07/13/aspartame-who-carcinogen-sweeteners/">90 countries</a> currently consider it safe to use in food.
</p>
<h3 id="lRMJ0d">
Can anything make a difference to companies still planning to use aspartame in their products?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M0BweV">
Experts told Vox that consumer backlash could be the quickest way to get food and beverage companies to reformulate or provide aspartame-less alternatives. Take the case of talc, a mineral that can <a href="https://www.cancer.org/cancer/risk-prevention/chemicals/talcum-powder-and-cancer.html">sometimes contain asbestos</a>. In 2006, IARC classified talc with asbestos as a Group 2B carcinogen, the same as it has now done with aspartame. It hasn’t been banned by US regulators, but an onslaught of lawsuits from consumers eventually led to Johnson &amp; Johnson voluntarily stopping sales of their talc-based baby powder, first in <a href="https://www.npr.org/2020/05/19/859182015/johnson-johnson-stops-selling-talc-based-baby-powder-in-u-s-and-canada">the US and Canada</a> but now <a href="https://www.cnbc.com/2022/08/11/jj-to-stop-selling-talc-based-baby-powder-globally-in-2023.html">worldwide</a>. Many <a href="https://www.aljazeera.com/economy/2020/6/9/beauty-brands-moving-away-from-talc-as-us-cancer-lawsuits-mount">makeup brands followed</a>, and some now even tout their <a href="https://www.sephora.com/buy/talc-free-makeup">talc-free formulations</a> as a selling point.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fAmLMB">
It’s also technically possible for individual states to get involved. California just passed a bill <a href="https://thehill.com/homenews/state-watch/4006399-california-assembly-passes-first-in-nation-bill-to-ban-five-toxic-chemicals-from-food-products/">banning five “toxic food chemicals,”</a> including <a href="https://www.consumerreports.org/health/food-additives/red-dye-3-banned-in-cosmetics-but-still-allowed-in-food-a3467381365/">Red Dye No. 3</a>, which the FDA banned in cosmetics decades ago but not in food. Consumer Reports was a co-sponsor of this bill. “One of the things that resonated with the California bill is [that] these were five chemicals that were already banned elsewhere in the world,” Ronholm says. “And oh, by the way, the industry was able to find alternatives to continue making these products and sell them overseas.” Ronholm says it’s possible a similar thing could happen here, though he’s not aware of anything in the works yet.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XQv0fO">
“If other states were interested in this issue and wanted to protect their citizens from aspartame, then seemingly that avenue for progress is available to them,” says Galligan.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9geBE0">
In some cases, a good old-fashioned lawsuit can compel companies to stop sales or reformulate products. Glyphosate, a pesticide, is in IARC’s Group 2A classification — a “probable carcinogen.” The compound is banned in several countries, including Germany, Austria, Thailand, and Saudi Arabia, but not in the US. The <a href="https://enveurope.springeropen.com/articles/10.1186/s12302-018-0184-7">Environmental Protection Agency</a> has deemed it “not likely to be carcinogenic to humans.” But Bayer, which uses glyphosate in its weed killer Roundup, was ordered to pay <a href="https://www.npr.org/2020/06/24/882949098/bayer-to-pay-more-than-10-billion-to-resolve-roundup-cancer-lawsuits">$10 billion</a> to settle thousands of lawsuits claiming that glyphosate causes cancer. The company is pulling Roundup from shelves this year.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xYNtP1">
Similarly, in 2015 the IARC classified processed meat — like bacon and hot dogs — as a <a href="https://www.hsph.harvard.edu/nutritionsource/2015/11/03/report-says-eating-processed-meat-is-carcinogenic-understanding-the-findings/">Group 1 carcinogen</a>. In 2016, the CSPI petitioned the USDA to require warning labels on processed meat. It was <a href="https://www.fsis.usda.gov/sites/default/files/media_file/2020-07/16-07-FSIS-Final-Response-071519.pdf">denied</a>. In the immediate aftermath of the IARC report, sales of <a href="https://www.theguardian.com/uk-news/2015/nov/23/bacon-sausage-sales-fall-who-report-cancer-risk-processed-meat">bacon and sausage plummeted in the UK</a>. In the US, however, processed meat sales <a href="https://www.globenewswire.com/en/news-release/2022/08/11/2496313/0/en/The-Processed-Meat-Market-Is-Expected-to-Witness-Steady-Growth-at-A-CAGR-of-4-6-Through-2031-States-Fact-MR.html">remain strong</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jsDdR3">
Unfortunately, the nuance around IARC’s assessment of aspartame, and the fact that regulatory bodies like the FDA disagree, will likely continue to mean frustration and confusion for consumers. As for whether we change our consumption — we’re on our own there.
</p></li>
<li><strong>The Long Island Serial Killer case may finally be solved — but many questions remain</strong> -
<figure>
<img alt="A Suffolk County police van and caution tape." src="https://cdn.vox-cdn.com/thumbor/uBskB_n5KEtkCwvIJOL-WKyOs34=/334x0:5667x4000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72453790/GettyImages_1532510572.0.jpg"/>
<figcaption>
Personnel cordon off the area after a suspect was arrested in the Gilgo Beach serial killings in Massapequa Park, Long Island, New York, on July 14, 2023. | Kyle Mazza/Anadolu Agency via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A surprise arrest after a 13-year investigation shocked the true crime community — and relieved New Yorkers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="veaRFH">
He murdered at least four people, likely 10, and possibly more. His victims, which included an unidentified toddler and her mother, were left discarded like trash along a short stretch of beach highway. Over the last decade, his specter became a pop culture boogeyman.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VfhVHR">
And now, authorities may have finally caught LISK: the Long Island serial killer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hMafFN">
On Friday morning, police on Long Island swarmed tiny Oak Beach, a neighborhood that lies at the far end of Jones Beach Island, the long, narrow strip of land where all of LISK’s assumed victims were recovered between 2010 and 2011. There, they took 59-year-old Rex Heuermann, an architect and building consultant, into custody.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kXFibg">
<a href="https://nypost.com/2023/07/14/gilgo-beach-serial-killings-suspect-rex-heuermann-idd-a-year-ago-after-dna-match-sources/">According to the New York Post</a>, authorities first identified Heuermann as a potential person of interest over a year ago due to a DNA match. Evidence has <a href="https://nypost.com/2023/07/14/gilgo-beach-serial-killings-suspect-rex-heuermann-idd-a-year-ago-after-dna-match-sources/">connected</a> him with the first group of LISK’s confirmed victims, known as “the Gilgo four.” These were the first four victims, who were all discovered in December 2010 around the Gilgo Beach stretch of the island.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LezcXm">
Heuermann was subsequently charged with the murders of three of the original four recovered victims — Melissa Barthelemy, Amber Lynn Costello, and Megan Waterman. He was <a href="https://abc7chicago.com/gilgo-beach-murders-suspect-identified-charged-in-deaths-of-3-women/13502057/">arraigned in court Friday</a>, where he entered a plea of not guilty. Evidence linking him to the crimes according to <a href="https://www.documentcloud.org/documents/23875981-lti-bail-application-form-2023-7-14-23-_final">court documents</a> include phone records, internet searches, and DNA.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p6KOR0">
The news of Heuermann’s arrest sent social media into a frenzy, as the <a href="https://www.vox.com/true-crime">true crime</a> community celebrated a huge win for an investigation many people doubted would ever be closed. That’s because the LISK case, also referred to as the Gilgo Beach murders or the Long Island Ripper case, is one of the most complicated, confusing, and frustrating serial killer cases in recent memory.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BpW5FN">
The reasons for this are complex, but they’re also very familiar. Like many serial killers, LISK targeted sex workers, likely due to the <a href="https://www.vox.com/2019/8/2/20692327/sex-work-decriminalization-prostitution-new-york-dc">myriad factors</a> that can lead to sex workers being marginalized and missing, often going unreported and unidentified. Authorities sometimes fail to take the disappearances of sex workers seriously, which can hinder investigations. In this case, a <a href="https://www.nytimes.com/2019/11/14/nyregion/thomas-spota-corruption-trial.html">jaw-dropping level</a> of alleged corruption and misconduct from the former Suffolk County Police chief further jeopardized the entire investigation. Then we have the killer himself, whose MO may have changed over time, leading to questions about how many murders he committed or whether he was working with a partner.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vK7RKU">
As developments unfold, there are plenty of new and unresolved questions about this case. The biggest is one that has haunted the case since its inception: Are all LISK’s victims the work of one serial killer, or are there multiple perpetrators stalking the wilds of Long Island?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gtCSGb">
Here’s what to know about the murders that became an eerie shadow for a generation of New Yorkers, and what we know so far about the man who may have committed them.
</p>
<h3 id="d8zZ0i">
The LISK case was long and frustrating — and very scary
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vW9QNX">
The LISK case burst into the public’s awareness because of Shannan Gilbert, a 23-year-old aspiring singer who vanished on May 1, 2010. Prior to her death, Gilbert made a <a href="https://nymag.com/news/features/long-island-serial-killer-families-2011-6/">23-minute 911 call</a> in which she wandered, confused and disoriented, around the Oak Beach neighborhood where she’d had an earlier escort appointment, frantically begging for help and claiming to be in danger. Gilbert’s body was eventually discovered in December 2011, in the marshes near Oak Beach. Thirteen years later, the <a href="https://abc7ny.com/gilgo-beach-long-island-victim-serial-killer/431659/">nature</a> of Gilbert’s death remains <a href="https://www.nbcnewyork.com/news/local/shannan-gilbert-family-to-speak-out-for-1st-time-in-years-after-release-of-911-calls/3691837/">a subject of controversy</a>. Her unsolved case has long been considered by authorities to be unrelated to LISK, but we now know she went missing very near Heuermann’s residence in Oak Beach, a fact that could shed new light on her case.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="X4epiV">
In December 2010, the investigation into Gilbert’s death uncovered four bodies, subsequently dubbed “<a href="https://nypost.com/2022/04/14/long-island-gilgo-beach-serial-killer-victims/">the Gilgo four</a>.” All were discovered over a two-day period, all discarded near each other along desolate Ocean Parkway, a two-lane road that spans the length of Jones Beach Island, a long strip of land that forms part of Long Island’s South Shore.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0LzTGi">
First was the body of Melissa Barthelemy, discovered on December 11, 2010. Barthelemy, a 24-year-old cosmetologist, had first <a href="https://www.gilgonews.com/Vics/melissabarthelemy">gone missing</a> in July 2009. The subsequent investigation into Barthelemy’s death quickly located three more bodies. The second located victim was Amber Lynn Costello, 27, who had gone missing in September 2010. Next police located 25-year-old <a href="https://nypost.com/2022/04/14/long-island-gilgo-beach-serial-killer-victims/">Maureen Brainard-Barnes</a>, a single mom who’d <a href="https://www.gilgonews.com/Vics/maureenbrainardbarnes">gone missing</a> in 2007. Finally, <a href="https://archive.longislandpress.com/2010/10/21/lost-girls-when-women-go-missing-on-long-island-some-matter-prostitutes-dont/">Megan Waterman</a>, 22, a single mom who had <a href="https://www.gilgonews.com/vics/MeganWaterman">gone missing</a> in June 2010. All four of the victims were sex workers <a href="https://www.cbsnews.com/news/long-island-serial-killer-lookalike-victims-online/">of similar age, height, and appearance</a>; all four of their bodies were found whole, three wrapped in burlap.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vgS5Vh">
Over the next five months, the partial remains of six other victims, all disposed of along Ocean Parkway, were discovered. Because these bodies were dismembered and their remains scattered in various locations, there is some debate about whether they are related to the Gilgo four.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iGQkeI">
In July 2003, the fifth victim to be discovered, thought to be connected to the others, 20-year-old Jessica Taylor, also went missing from New York City; her partial remains were found in Manorville, Long Island, later that same month. But it wasn’t until March 2011 that authorities recovered her skull along the Gilgo Beach highway.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MGkH3L">
The sixth victim to be discovered, in April 2011, was an Asian trans woman in her late teens or early 20s. Early media reports and true crime blogs frequently misgendered her, though more recently, she has been referred to as “Gilgo Beach Doe” or “Ocean Parkway Doe.” She is believed to have been killed up to <a href="https://www.namus.gov/UnidentifiedPersons/Case#/9355">five years</a> earlier by a blow to the head. <a href="https://www.reddit.com/r/UnresolvedMysteries/comments/129xxwd/trans_day_of_visibility_who_is_the_suspected/">Very little</a> is known about this victim; like most of the other LISK victims, she is believed to have been a sex worker.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/FSufml8e4JASifcBvn8Ov7wSqQE=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24789228/gilgo_doe.jpg"/> <cite>Suffolk County Police/<a class="ql-link" href="https://imgur.com/a/2MKX0mV" target="_blank">Imgur</a></cite>
<figcaption>
A modified police reconstruction sketch, showing what Gilgo Beach Doe might have looked like.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PIBOZK">
In April, the remains of an unidentified toddler, the seventh victim, were found. Subsequently, the partial remains of an eighth victim, a Black woman known as “<a href="https://www.longislandpress.com/2016/12/13/unidentified-murder-victim-dubbed-peaches-linked-to-gilgo-beach-killings/">Peaches</a>” because of a peach tattoo she had, were found in Cedar Beach off Ocean Parkway. Her initial set of remains had previously been located in Hempstead Lake State Park in 1997. This state park is about 45 minutes away from where more of her remains were ultimately located in April 2011. “Peaches” was confirmed through DNA matching to be the mother of the unidentified toddler. Both mother and daughter are believed to be LISK victims. Authorities have recently <a href="https://www.longislandpress.com/2022/10/11/fbi-near-identifying-peaches/">traced Peaches’ possible roots to Alabama</a> but have not yet made an identification.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V9FoGg">
The ninth victim, 24-year-old Valerie Mack, <a href="https://www.newsday.com/long-island/gilgo-serial-killer-valerie-mack-family-jr04dj51">went missing</a> in October 2000. In November 2000, her torso was found in Manorville, 40 minutes away from Gilgo Beach. Known for years as “Jane Doe no. 6,” Mack, who also went by Melissa Taylor, was eventually <a href="https://www.longislandpress.com/2020/05/28/suffolk-police-release-name-of-newly-identified-long-island-serial-killer-victim/">identified</a> in 2020 via <a href="https://www.vox.com/2018/4/27/17290288/golden-state-killer-joseph-james-deangelo-dna-profile-match">forensic genealogy</a>. She had never been reported missing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7DVP66">
The partial remains of the 10th LISK victim, known as “Fire Island Jane Doe,” were first discovered in 1996 on Fire Island. Her skull was discovered in April 2011, just south of Gilgo in Tobay Beach. She is believed to be LISK’s earliest known victim.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/zluQOY-cByxpEitikVu0XdWkTOk=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24789225/fire_island_doe.jpg"/> <cite>Suffolk County Police/<a class="ql-link" href="https://uncovered.com/cases/fire-island-jane-doe" target="_blank">Uncovered</a></cite>
<figcaption>
A reconstruction of <a class="ql-link" href="https://www.reuters.com/article/us-serialkiller-longisland-idUSTRE8070M620120109" target="_blank">Fire Island Jane Doe</a>.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HcM8p5">
It’s easy to see just from this list how confusing and troubling these murders were. The victims were found in a relatively short time but had been murdered over a range of more than a decade. The thought that a serial killer had been operating, undetected, for all of that time rattled the community of Long Island as well as true crime watchers around the globe.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CN2g7c">
As pressure grew to catch the killer, Suffolk County Police Chief James Burke, appointed in 2012, came under fire for <a href="https://nypost.com/2015/12/12/busted-ex-police-chief-blocked-fbi-probe-of-gilgo-beach-murders/">refusing to work with the FBI</a>. But Burke had bigger problems: He was then attempting to <a href="https://www.nytimes.com/2019/11/14/nyregion/thomas-spota-corruption-trial.html">cover up his brutal beating</a> of a suspect who stole a bag of sex toys from his car. His efforts to obstruct the FBI’s investigation into the beating ultimately wound up implicating Burke, the county prosecutor, the deputy prosecutor, and <a href="https://www.longislandpress.com/2016/12/22/several-suffolk-cops-charged-in-burke-beating-cover-up-case-docs-show/">multiple members</a> of the Suffolk police force.
</p>
<h3 id="0aNnzt">
The case heats up — and becomes a true crime linchpin
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="T8PTfj">
All of this directly impacted the LISK case, which languished for years as a result of Burke’s hostility toward the FBI and his ongoing legal problems. But during this time, amid the burgeoning true crime boom of the 2010s, LISK was capturing the attention of the nation. A 2016 Netflix documentary series, <em>The Killing Season</em>, drew widespread attention to the case, as did numerous podcasts and a book, <em>The Lost Girls</em>, which was subsequently adapted in 2020 into a <a href="https://time.com/5801794/lost-girls-netflix-true-story/">fictionalized Netflix drama</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TXVQAf">
The victims’ families weren’t always happy with this increased publicity; in April 2023, a lawyer for two of the victims’ families <a href="https://patch.com/new-york/easthampton/li-serial-killer-panel-pulled-hamptons-mystery-crime-festival">objected</a> to a LISK panel at a local true crime festival.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="80EP39">
In 2018, Burke was replaced by, ironically, a longtime FBI agent. Geraldine Hart was the first female police chief in Suffolk County’s history. She immediately <a href="https://www.nytimes.com/2020/09/25/nyregion/long-island-serial-killer-gilgo-beach.html">resumed full-scale investigation</a> into the LISK case, and in 2020 released an eye-catching piece of <a href="https://www.gilgonews.com/ArticlesRecovered">new evidence</a>: a belt found near one of the crime scenes, believed to belong to the perpetrator. Inscribed upon the belt was what appeared to be an insignia:
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/jjvDxh2JWGUEohTDpxuqNba13V0=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24789305/belt.png"/> <cite>Suffolk County Police / <a class="ql-link" href="https://www.gilgonews.com/ArticlesRecovered" target="_blank">Gilgo News</a></cite>
<figcaption>
Belt believed to belong to LISK.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eNKtMj">
This insignia proved as mysterious as everything else about the case; web sleuths debated what the symbols meant. Were they letters? Symbols? Nothing? As recently as a month ago, one Redditor declared the belt was “<a href="https://www.reddit.com/r/LISKiller/comments/14apofg/the_lisk_belt_is_probably_a_misdirection/">probably a misdirection</a>” and that attempts to track down a killer with the initials “HM” were probably futile. They may have been partly right; after Friday’s arrest, many have pointed out that “HM” might stand for “Heuermann.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XyIgzw">
Hart’s replacement, police commissioner Rodney Harrison, also tackled the case with zeal. In a <a href="https://nypost.com/2022/01/01/suffolk-police-boss-rodney-harrison-vows-to-solve-gilgo-beach-murders/">2022 press conference</a>, he described law enforcement’s “relentless pursuit to identify the individuals and bring them to justice.”
</p>
<h3 id="4Bwu6I">
What we know about the suspect so far
</h3>
<figure class="e-image">
<img alt="Rex Heuermann in a gray suit poses for a photo in front of a brick Manhattan building." src="https://cdn.vox-cdn.com/thumbor/SZLST1vC9WkkUCaPk3i_qtHsdAg=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24789308/heuermann.jpg"/> <cite>RH Architecture</cite>
<figcaption>
Rex Heuermann.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9M2CM6">
Married with two adult children, Heuermann is a lifelong Long Island resident whose <a href="https://rh-architecture.com/about">specialty</a> as an architect seems to be dealing with the New York City building code. In <a href="https://www.youtube.com/watch?v=tbQOcEs3aZg">a 2022 YouTube interview</a>, he spoke about knowing the details of city codes and compared himself to a “hammer.” His architecture firm, R.H. Architecture, has since removed its staff listing, which also included a listing for one of Heuermann’s relatives. <a href="https://www.nytimes.com/2023/07/14/nyregion/gilgo-beach-murders-long-island-suspect.html">According to the New York Times</a>, Heuermann lived in his dilapidated family home and his neighbors largely avoided him. One neighbor <a href="https://nypost.com/2023/07/14/gilgo-beach-suspect-rex-heuermann-was-weird-a-big-talker/">described him</a> to the New York Post as “a big talker,” adding that it “makes sense that he’s a serial killer.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GIwaVu">
Heuermann’s arrest comes less than a day after authorities <a href="https://www.nyspnews.com/skeletal-remains-found-off-southern-state-parkway-near-exit-40.htm">discovered a new set of skeletal remains</a> in the Suffolk County town of Islip (about 20 minutes from Jones Beach Island, where most of the LISK victims’ remains were found), but so far no connection is known.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="b22ILA">
On July 14, <a href="https://twitter.com/Joecasa23/status/1679852408128643075">police went</a> to Heuermann’s Oak Beach neighborhood, where they searched his residence. Authorities were spotted removing a large cooler from Heuermann’s home on Friday, though the significance of this discovery has not been made clear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ewx9Z3">
According to his lawyer, Michael Brown, Heuermann was “<a href="https://nypost.com/2023/07/14/gilgo-beach-murders-suspect-rex-heuermann-in-custody-live-updates/#27893299">in tears</a>” after his arraignment on Friday, insisting that he “did not do this.” But while the case against Heuermann seems to be circumstantial, it’s compelling. For starters, <a href="https://abc7chicago.com/gilgo-beach-murders-suspect-identified-charged-in-deaths-of-3-women/13502057/">according to court documents</a>, Heuermann’s wife was out of town every time each of the three victims Heuermann is charged with killing went missing. Heuermann also had a long history of conducting internet searches for extreme sexual kinks, as well as an interest in serial killers and specifically LISK.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AsgX1L">
And then there’s the DNA: Authorities matched DNA found on the burlap material used to wrap Waterman’s body to a discarded pizza crust from Heuermann obtained by police in January 2023.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zSuhYk">
Still, this case is by no means open and shut. There will be more prosecutions to follow, and more questions to answer. One of the big ones: Are there more victims? Among the list of other potential LISK victims are <a href="https://uncovered.com/cases/tina-foglia">Tina Foglia</a>, whose dismembered remains were found in Gilgo Beach in 1986; <a href="https://twitter.com/Catch_LISK/status/1631640657172332544">Judith Ramona Veloz</a>, who went missing from New York City in 1993; and <a href="https://www.huffpost.com/entry/natasha-jugo-identified-missing-queens-woman-gilgo-beach_n_2905653">Natasha Jugo</a>, whose car was found abandoned in Gilgo Beach in 2013.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="i5I7Xx">
After Heuermann’s arrest, victims’ families expressed their thanks to police and their relief that a killer might finally have been caught. “The suspect deserves to rot in prison for the rest of his life,” Gilbert’s sister Sherre Gilbert <a href="https://www.nbcnews.com/news/us-news/gilgo-beach-murders-suspected-long-island-serial-killer-custody-offici-rcna94228">told NBC News</a>. “He destroyed many lives so while it won’t bring our loved ones back, it does help that one less monster is off the streets and he can’t ever hurt anyone else!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Q7om6Q">
Among the many grateful bystanders was New York Gov. Kathy Hochul, who <a href="https://abc7chicago.com/gilgo-beach-murders-serial-killer-rex-heuermann-massapequa/13501973/#:~:text=%22I%20know%20there%20is%20a,ever%20be%20brought%20to%20justice%3F%22">issued her own statement</a> about the arrest.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="STTAsS">
“I know there is a community out there that, as the facts unfold, will be sleeping a lot easier tonight,” Hochul said.
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Swastik Sharma and Yashika Shokeen triumph</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>Long jumper Sreeshankar qualifies for 2024 Olympics after winning silver medal at Asian meet</strong> - The 24-year-old Sreeshankar achieved the Olympic qualification with his final round jump of 8.37m. The Paris Games mark is 8.27m</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>Wimbledon men’s final preview | Insatiable Djokovic ready for ultimate showdown with Alcaraz</strong> - Novak Djokovic now wants to gobble up a record-equalling 24th Grand Slam title.</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>If Pakistan doesn’t go for World Cup it will be great injustice to fans: Misbah-ul-Haq</strong> - Former captain Misbah-ul-Haq and all-rounder Shahid Afridi expressed their support for Pakistan cricket team to compete in the ODI World Cup in India</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>We let ourselves down with the bat, says Windies skipper Brathwaite</strong> - Brathwaite was particularly critical of his own performance, added that they failed in execution of their batting plans</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>Chinta Mohan demands government intervention in mitigating tomato crisis</strong> - The Congress leader demands the Centre and the State governments arrange the sale of tomatoes on high subsidy, at ₹30 a kg, in open markets.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>India, China should find a mutually acceptable solution to resolve border issue: Wang Yi</strong> - Wang also said that Chinese President Xi Jinping and Prime Minister Narendra Modi have reached an important consensus on stabilising China-India relations</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>Farmers worry over deficit rainfall in Parvatipuram and Vizianagaram districts in Andhra Pradesh</strong> - They have not taken up sowing of paddy and other crops even in the third week of July</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 railway station to come up at Yadadri temple town</strong> - Fresh tenders being called as the State government failed to release its share of funds for the earlier proposal, say officials</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>Azam Khan gets two-year jail in another case of hate speech</strong> - The case was registered against Mr. Khan during the 2019 Lok Sabha general election.</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>Europe heatwave: Red alerts issued in 16 Italian cities</strong> - Health warnings for Rome and elsewhere come as extreme weather scorches southern and central Europe.</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>In pictures: Cerberus heatwave hits parts of Europe</strong> - People in countries including Italy and Spain are struggling to cope with soaring temperatures.</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>How the tide of migration is changing European politics</strong> - A surge in boats carrying migrants from North Africa is changing Europe’s politics, says Nick Robinson.</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>Wagner head Prigozhin rejected offer to join Russia’s army - Putin</strong> - The leader of June’s aborted mutiny did not want his mercenaries to become a regular unit, President Putin says.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Arman Soldin: Journalist killed in Ukraine given top French honour</strong> - Video journalist Arman Soldin was killed in a rocket attack close to Bakhmut in May.</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>Guidemaster: Picking the right tablet for each use case</strong> - Find the right tablet for work, play, and everything else in between. - <a href="https://arstechnica.com/?p=1946193">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The gravitational interactions that have helped us dodge 60-hour days</strong> - An atmospheric effect got various tidal forces to cancel out. - <a href="https://arstechnica.com/?p=1954165">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Game tutorials should be easily skipped. Why is that so hard?</strong> - Let’s talk about replay accessibility, not replay value. - <a href="https://arstechnica.com/?p=1952139">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Viasat’s new broadband satellite could be a total loss</strong> - The mission now in peril is thought to be valued at roughly $700 million. - <a href="https://arstechnica.com/?p=1954185">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Microsoft takes pains to obscure role in 0-days that caused email breach</strong> - Critics also decry Microsoft’s “pay-to-play” monitoring that detected intrusions. - <a href="https://arstechnica.com/?p=1954171">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 monkey is smoking a joint on a tree, when a lizard walks past..</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The lizard looks up and says “Hey, what are you doing?” The monkey says “Smoking a joint. Come up and join me”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
So the lizard climbs up and sits next to the monkey, and they have another joint. After a while, the lizard says his mouth is ‘dry’, and that he’s going to get a drink from the river.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
At the riverbank, the lizard is so stoned that he leans over too far and falls in.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A crocodile sees this and swims over to the stoned lizard, helping him to the side.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He then asks the lizard “What’s the matter with you!?” The lizard explains that he was up in the tree, smoking a joint with the monkey and his mouth got dry, and that he was so wasted that, when he went to get a drink from the river, he fell in!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The inquisitive crocodile says he has to check this out. He walks into the jungle and finds the tree where the monkey is sitting, finishing a joint.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He looks up and says “Hey, MONKEY!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The monkey looks down and says “OMG! DUUUUDE …. How much water did you drink?!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/HelpingHandsUs"> /u/HelpingHandsUs </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/14zy3j8/a_monkey_is_smoking_a_joint_on_a_tree_when_a/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/14zy3j8/a_monkey_is_smoking_a_joint_on_a_tree_when_a/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A wife was making a breakfast of fried eggs for her husband. Suddenly, her husband burst into the kitchen. “Careful,” he said, "CAREFUL! Put in some more butter! Oh my gosh! You’re cooking too many at once.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
TOO MANY! Turn them! TURN THEM NOW! We need more butter. Oh my gosh! WHERE are we going to get MORE BUTTER? They’re going to STICK! Careful. CAREFUL! I said be CAREFUL! You NEVER listen to me when you’re cooking! Never! Turn them! Hurry up! Are you CRAZY? Have you LOST your mind? Don’t forget to salt them. You know you always forget to salt them. Use the! Salt. USE THE SALT! THE SALT!" The wife stared at him. “What in the world is wrong with you? You think I don’t know how to fry a couple of eggs?” The husband calmly replied, “I just wanted to show you what it feels like when I’m driving.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/14zqiqi/a_wife_was_making_a_breakfast_of_fried_eggs_for/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/14zqiqi/a_wife_was_making_a_breakfast_of_fried_eggs_for/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rumour got round that the bear kept a list of all the animals he plans to kill..</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Scared and confused, the wolf went to confront the bear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Bear,” said wolf. “Do you really keep a list of all the animals you plan to kill?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I do.” said the bear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“And… Is my name on it?” asked the wolf.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“It is.” the bear growled. And the following morning, the wolf was found dead on the forest floor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The fox came later that day to confront the bear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Bear,” she said. “Do you really keep a list of all the animals you plan to kill?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I do.” said the bear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“And… Is my name on it?” she asked.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“It is.” the bear growled. And the following morning, fox’s mangled remains were found lying on the forest floor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
That day the rabbit, too, decided to confront the bear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Bear,” he said. “Do you really keep a list of all the animals you plan to kill?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I do.” said the bear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“And… Is my name on it?” asked the rabbit.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“It is.” the bear growled.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Can - can you remove it?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Oh, for sure.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/HelpingHandsUs"> /u/HelpingHandsUs </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/14zquei/rumour_got_round_that_the_bear_kept_a_list_of_all/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/14zquei/rumour_got_round_that_the_bear_kept_a_list_of_all/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My wife challenged me to a game of strip poker, but it turns out she just wanted to do laundry.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
So I folded.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/KairuSmairukon"> /u/KairuSmairukon </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/14zru0z/my_wife_challenged_me_to_a_game_of_strip_poker/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/14zru0z/my_wife_challenged_me_to_a_game_of_strip_poker/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>You gotta hand it to short people.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Because they can’t reach it on their own.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/AdventurousMistake72"> /u/AdventurousMistake72 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1505cfx/you_gotta_hand_it_to_short_people/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1505cfx/you_gotta_hand_it_to_short_people/">[comments]</a></span></p></li>
</ul>
<script>AOS.init();</script></body></html>

4
index.html
View File

File diff suppressed because one or more lines are too long