tbuckley/cabot-search huggingface dataset:
Ductular reaction promotes intrahepatic angiogenesis through Slit2–Roundabout 1 signaling
Authors: Mar Coll, Silvia Ariño, Celia Martínez‐Sánchez, Ester Garcia‐Pras, Javier Gallego, Anna Moles, Beatriz Aguilar‐Bravo, Delia Blaya, Julia Vallverdú, Teresa Rubio‐Tomás, Juan Jose Lozano, Elisa Pose, Isabel Graupera, Andrea Fernández‐Vidal, Albert Pol, Ramón Bataller, Jian‐Guo Geng, Pere Ginès, Mercedes Fernandez, Pau Sancho‐Bru
Journal: Hepatology (2021)

Ductular reaction (DR) expands in chronic liver diseases and correlates with disease severity. Besides its potential role in liver regeneration, DR plays a role in the wound-healing response of the liver, promoting periductular fibrosis and inflammatory cell recruitment. However, there is no information regarding its role in intrahepatic angiogenesis. In the current study we investigated the potential contribution of DR cells to hepatic vascular remodeling during chronic liver disease.In mouse models of liver injury, DR cells express genes involved in angiogenesis. Among angiogenesis-related genes, the expression of Slit2 and its receptor Roundabout 1 (Robo1) was localized in DR cells and neoangiogenic vessels, respectively. The angiogenic role of the Slit2-Robo1 pathway in chronic liver disease was confirmed in ROBO1/2-/+ mice treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine, which displayed reduced intrahepatic neovascular density compared to wild-type mice. However, ROBO1/2 deficiency did not affect angiogenesis in partial hepatectomy. In patients with advanced alcohol-associated disease, angiogenesis was associated with DR, and up-regulation of SLIT2-ROBO1 correlated with DR and disease severity. In vitro, human liver-derived organoids produced SLIT2 and induced tube formation of endothelial cells.Overall, our data indicate that DR expansion promotes angiogenesis through the Slit2-Robo1 pathway and recognize DR cells as key players in the liver wound-healing response.
A Probabilistic Model for Indel Evolution: Differentiating Insertions from Deletions
Authors: Gil Loewenthal, Dana Rapoport, Oren Avram, Asher Moshe, Elya Wygoda, Alon Itzkovitch, Omer Israeli, Dana Azouri, Reed A Cartwright, Itay Mayrose, Tal Pupko
Journal: Molecular Biology and Evolution (2021)

Insertions and deletions (indels) are common molecular evolutionary events. However, probabilistic models for indel evolution are under-developed due to their computational complexity. Here, we introduce several improvements to indel modeling: 1) While previous models for indel evolution assumed that the rates and length distributions of insertions and deletions are equal, here we propose a richer model that explicitly distinguishes between the two; 2) we introduce numerous summary statistics that allow approximate Bayesian computation-based parameter estimation; 3) we develop a method to correct for biases introduced by alignment programs, when inferring indel parameters from empirical data sets; and 4) using a model-selection scheme, we test whether the richer model better fits biological data compared with the simpler model. Our analyses suggest that both our inference scheme and the model-selection procedure achieve high accuracy on simulated data. We further demonstrate that our proposed richer model better fits a large number of empirical data sets and that, for the majority of these data sets, the deletion rate is higher than the insertion rate.
Eviction Moratoria Expiration and COVID-19 Infection Risk Across Strata of Health and Socioeconomic Status in the United States
Authors: Sebastian Sandoval-Olascoaga, Atheendar S. Venkataramani, Mariana C. Arcaya
Journal: JAMA Network Open (2021)

Housing insecurity induced by evictions may increase the risk of contracting COVID-19.To estimate the association of lifting state-level eviction moratoria, which increased housing insecurity during the COVID-19 pandemic, with the risk of being diagnosed with COVID-19.This retrospective cohort study included individuals with commercial insurance or Medicare Advantage who lived in a state that issued an eviction moratorium and were diagnosed with COVID-19 as well as a control group comprising an equal number of randomly selected individuals in these states who were not diagnosed with COVID-19. Data were collected from OptumLabs Data Warehouse, a database of deidentified administrative claims. The study used a difference-in-differences analysis among states that implemented an eviction moratorium between March 13, 2020, and September 4, 2020.Time since state-level eviction moratoria were lifted.The primary outcome measure was a binary variable indicating whether an individual was diagnosed with COVID-19 for the first time in a given week with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code U07.1. The study analyzed changes in COVID-19 diagnosis before vs after a state lifted its moratorium compared with changes in states that did not lift it. For sensitivity analyses, models were reestimated on a 2% random sample of all individuals in the claims database during this period in these states.The cohort consisted of 509 694 individuals (254 847 [50.0%] diagnosed with COVID-19; mean [SD] age, 47.0 [23.6] years; 239 056 [53.3%] men). During the study period, 43 states and the District of Columbia implemented an eviction moratorium and 7 did not. Among the states that implemented a moratorium, 26 (59.1%) lifted their moratorium before the US Centers for Disease Control and Prevention issued their national moratorium, while 18 (40.1%) maintained theirs. In a Cox difference-in-differences regression model, individuals living in a state that lifted its eviction moratorium experienced higher hazards of a COVID-19 diagnosis beginning 5 weeks after the moratorium was lifted (hazard ratio [HR], 1.39; 95% CI, 1.11-1.76; P = .004), reaching an HR of 1.83 (95% CI, 1.36-2.46; P < .001) 12 weeks after. Hazards increased in magnitude among individuals with preexisting comorbidities and those living in nonaffluent and rent-burdened areas. Individuals with a Charlson Comorbidity Index score of 3 or greater had an HR of 2.37 (95% CI, 1.67-3.36; P < .001) at the end of the study period. Those living in nonaffluent areas had an HR of 2.14 (95% CI, 1.51-3.05; P < .001), while those living in areas with a high rent burden had an HR of 2.31 (95% CI, 1.64-3.26; P < .001).The findings of this difference-in-differences analysis suggest that eviction-led housing insecurity may have exacerbated the COVID-19 pandemic.
Covid-19: Government considers mandatory vaccination for healthcare staff in England
Authors: Abi Rimmer
Journal: BMJ (2021)

Covid-19: Government considers mandatory vaccination for healthcare staff in England Abi RimmerHealth and care workers in England may be required to be vaccinated against covid-19 and flu before they can work directly with patients.The Department of Health and Social Care in England has launched a six week consultation 1 asking staff, healthcare providers, and patients to share their views on whether staff, unless exempt, should be required to be vaccinated.1 Department of Health and Social Care.Making vaccination a condition of deployment in the health and wider social care sector. 9 September 2021.www.gov.uk/government/consultations/making-vaccination-a-conditionof-deployment-in-the-health-and-wider-social-care-sector/making-vaccination-a-condition-of-deployment-in-the-health-and-wider-social-care-sector.
Racism, Diminished Returns of Socioeconomic Resources, and Black Middle-Income Children’s Health Paradox
Authors: Shervin Assari, Cleopatra H. Caldwell
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
David Oliver: Soundbites won’t solve a pandemic
Authors: David Oliver
Journal: BMJ (2021)

Enough Said, explored the rise of simplistic, populist rhetoric in politics and public discourse at the expense of complexity, nuance, and professional expertise. 1 We've often experienced this soundbite culture in trite and simplistic statements about our response to the covid crisis.Slogans and quick fixes may sound attractive.They're more digestible than the nuanced, messy, multifaceted reality of a pandemic virus with variables that can't always be controlled or predicted.But a soundbite isn't a logistical, risk assessed plan-something that the hard realities behind "Get Brexit done" have illustrated. 2Just saying something doesn't make it so.
Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Carmine Pinto, Paolo Andrea Zucali, Maria Pagano, Federica Grosso, Giulia Pasello, Marina Chiara Garassino, Marcello Tiseo, Hector Soto Parra, Francesco Grossi, Federico Cappuzzo, Filippo de Marinis, Paolo Pedrazzoli, Maria Bonomi, Letizia Gianoncelli, Matteo Perrino, Armando Santoro, Francesca Zanelli, Candida Bonelli, Antonio Maconi, Stefano Frega, Erika Gervasi, Luca Boni, Giovanni Luca Ceresoli
Journal: The Lancet Oncology (2021)
Comparison of Treatment Retention of Adults With Opioid Addiction Managed With Extended-Release Buprenorphine vs Daily Sublingual Buprenorphine-Naloxone at Time of Release From Jail
Authors: Joshua D. Lee, Mia Malone, Ryan McDonald, Anna Cheng, Kumar Vasudevan, Babak Tofighi, Ann Garment, Barbara Porter, Keith S. Goldfeld, Michael Matteo, Jasdeep Mangat, Monica Katyal, Jonathan Giftos, Ross MacDonald
Journal: JAMA Network Open (2021)

Extended-release buprenorphine (XRB), a monthly injectable long-acting opioid use disorder (OUD) treatment, has not been studied for use in corrections facilities.To compare treatment retention following release from jail among adults receiving daily sublingual buprenorphine-naloxone (SLB) vs those receiving XRB.This open-label, randomized comparative effectiveness study included 52 incarcerated adults in New York City observed for 8 weeks postrelease between June 2019 and May 2020. Participants were soon-to-be-released volunteers from 1 men's and 1 women's jail facility who had OUDs already treated with SLB. Follow-up treatment was received at a primary care clinic in Manhattan. Data were analyzed between June 2020 and December 2020.XRB treatment was offered prior to release and continued monthly through 8 weeks after release. SLB participants continued to receive daily directly observed in-jail SLB administration, were provided a 7-day SLB supply at jail release, and followed up at a designated clinic (or other preferred clinics).Buprenorphine treatment retention at 8 weeks postrelease.A total of 52 participants were randomized 1:1 to XRB (26 participants) and SLB (26 participants). Participants had a mean (SD) age of 42.6 (10.0) years; 45 participants (87%) were men; and 40 (77%) primarily used heroin prior to incarceration. Most participants (30 [58%]) reported prior buprenorphine use; 18 (35%) reported active community buprenorphine treatment prior to jail admission. Twenty-one of 26 assigned to XRB received 1 or more XRB injection prior to release; 3 initiated XRB postrelease; and 2 did not receive XRB. Patients in the XRB arm had fewer jail medical visits compared with daily SLB medication administration (mean [SD] visits per day: XRB, 0.11 [0.03] vs SLB, 1.06 [0.08]). Community buprenorphine treatment retention at week 8 postrelease was 18 participants in the XRB group (69.2%) vs 9 in the SLB group (34.6%), and rates of opioid-negative urine tests were 72 of 130 tests in the XRB group (55.3%) and 50 of 130 tests in the SLB group (38.4%). There were no differences in rates of serious adverse events, no overdoses, and no deaths.XRB was acceptable among patients currently receiving SLB, and patients had fewer in-jail clinic visits and increased community buprenorphine treatment retention when compared with standard daily SLB treatment. These results support wider use and further study of XRB as correctional and reentry OUD treatment.ClinicalTrials.gov Identifier: NCT03604159.
Neural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance
Authors: Jianglan Liu, Vito W. Rebecca, Andrew V. Kossenkov, Thomas Connelly, Qin Liu, Alexis Gutierrez, Min Xiao, Ling Li, Gao Zhang, Anastasia Samarkina, Delaine Zayasbazan, Jie Zhang, Chaoran Cheng, Zhi Wei, Gretchen M. Alicea, Mizuho Fukunaga-Kalabis, Clemens Krepler, Pedro Aza-Blanc, Chih-Cheng Yang, Bela Delvadia, Cynthia Tong, Ye Huang, Maya Delvadia, Alice S. Morias, Katrin Sproesser, Patricia Brafford, Joshua X. Wang, Marilda Beqiri, Rajasekharan Somasundaram, Adina Vultur, Denitsa M. Hristova, Lawrence W. Wu, Yiling Lu, Gordon B. Mills, Wei Xu, Giorgos C. Karakousis, Xiaowei Xu, Lynn M. Schuchter, Tara C. Mitchell, Ravi K. Amaravadi, Lawrence N. Kwong, Dennie T. Frederick, Genevieve M. Boland, Joseph M. Salvino, David W. Speicher, Keith T. Flaherty, Ze'ev A. Ronai, Meenhard Herlyn
Journal: Cancer Research (2021)

Abstract Metastatic melanoma is challenging to clinically address. Although standard-of-care targeted therapy has high response rates in patients with BRAF-mutant melanoma, therapy relapse occurs in most cases. Intrinsically resistant melanoma cells drive therapy resistance and display molecular and biologic properties akin to neural crest-like stem cells (NCLSC) including high invasiveness, plasticity, and self-renewal capacity. The shared transcriptional programs and vulnerabilities between NCLSCs and cancer cells remains poorly understood. Here, we identify a developmental LPAR1-axis critical for NCLSC viability and melanoma cell survival. LPAR1 activity increased during progression and following acquisition of therapeutic resistance. Notably, genetic inhibition of LPAR1 potentiated BRAFi ± MEKi efficacy and ablated melanoma migration and invasion. Our data define LPAR1 as a new therapeutic target in melanoma and highlights the promise of dissecting stem cell–like pathways hijacked by tumor cells. Significance: This study identifies an LPAR1-axis critical for melanoma invasion and intrinsic/acquired therapy resistance.
A Simple Bacterium Links Heart Infection to Inflammatory Liver Disease
Authors: Pierre Isnard, Marion Larue, Aurelia Pitsch, Jean‐Paul Duong Van Huyen, Philippe Seksik, Loic Brot, Sylvain Diamantis, Julie Bruneau, Maxence Rouyer
Journal: Hepatology (2021)

Isnard, Pierre; Larue, Marion; Pitsch, Aurelia; Duong Van Huyen, Jean‐Paul; Seksik, Philippe; Brot, Loic; Diamantis, Sylvain; Bruneau, Julie; Rouyer, Maxence Author Information
WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017–18: a retrospective observational study
Authors: Magnus Unemo, Monica M Lahra, Martina Escher, Sergey Eremin, Michelle J Cole, Patricia Galarza, Francis Ndowa, Irene Martin, Jo-Anne R Dillon, Marcelo Galas, Pilar Ramon-Pardo, Hillard Weinstock, Teodora Wi
Journal: The Lancet Microbe (2021)

Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major health concerns globally. Increased global surveillance of gonococcal AMR is essential. We aimed to describe the 2017-18 data from WHO's global gonococcal AMR surveillance, and to discuss priorities essential for the effective management and control of gonorrhoea.We did a retrospective observational study of the AMR data of gonococcal isolates reported to WHO by 73 countries in 2017-18. WHO recommends that each country collects at least 100 gonococcal isolates per year, and that quantitative methods to determine the minimum inhibitory concentration of antimicrobials, interpreted by internationally standardised resistance breakpoints, are used.In 2017-18, 73 countries provided AMR data for one or more drug. Decreased susceptibility or resistance to ceftriaxone was reported by 21 (31%) of 68 reporting countries and to cefixime by 24 (47%) of 51 reporting countries. Resistance to azithromycin was reported by 51 (84%) of 61 reporting countries and to ciprofloxacin by all 70 (100%) reporting countries. The annual proportion of decreased susceptibility or resistance across countries was 0-21% to ceftriaxone and 0-22% to cefixime, and that of resistance was 0-60% to azithromycin and 0-100% to ciprofloxacin. The number of countries reporting gonococcal AMR and resistant isolates, and the number of examined isolates, have increased since 2015-16. Surveillance remains scarce in central America and the Caribbean and eastern Europe, and in the WHO African, Eastern Mediterranean, and South-East Asian regions.In many countries, ciprofloxacin resistance was exceedingly high, azithromycin resistance was increasing, and decreased susceptibility or resistance to ceftriaxone and cefixime continued to emerge. WHO's global surveillance of gonococcal AMR needs to expand internationally to provide imperative data for national and international management guidelines and public health policies. Improved prevention, early diagnosis, treatment of index patients and partners, enhanced surveillance (eg, infection, AMR, treatment failures, and antimicrobial use or misuse), and increased knowledge on antimicrobial selection, stewardship, and pharmacokinetics or pharmacodynamics are essential. The development of rapid, accurate, and affordable point-of-care gonococcal diagnostic tests, new antimicrobials, and gonococcal vaccines is imperative.None.
Long term exposure to low level air pollution and mortality in eight European cohorts within the ELAPSE project: pooled analysis
Authors: Maciej Strak, Gudrun Weinmayr, Sophia Rodopoulou, Jie Chen, Kees de Hoogh, Zorana J Andersen, Richard Atkinson, Mariska Bauwelinck, Terese Bekkevold, Tom Bellander, Marie-Christine Boutron-Ruault, Jørgen Brandt, Giulia Cesaroni, Hans Concin, Daniela Fecht, Francesco Forastiere, John Gulliver, Ole Hertel, Barbara Hoffmann, Ulla Arthur Hvidtfeldt, Nicole A H Janssen, Karl-Heinz Jöckel, Jeanette T Jørgensen, Matthias Ketzel, Jochem O Klompmaker, Anton Lager, Karin Leander, Shuo Liu, Petter Ljungman, Patrik K E Magnusson, Amar J Mehta, Gabriele Nagel, Bente Oftedal, Göran Pershagen, Annette Peters, Ole Raaschou-Nielsen, Matteo Renzi, Debora Rizzuto, Yvonne T van der Schouw, Sara Schramm, Gianluca Severi, Torben Sigsgaard, Mette Sørensen, Massimo Stafoggia, Anne Tjønneland, W M Monique Verschuren, Danielle Vienneau, Kathrin Wolf, Klea Katsouyanni, Bert Brunekreef, Gerard Hoek, Evangelia Samoli
Journal: BMJ (2021)

To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. Pooled analysis of eight cohorts. Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide, ozone, and black carbon. Deaths due to natural causes and cause specific mortality. Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 µg/m3 in PM2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 µg/m3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 µg/m3 an increase of 5 µg/m3 in PM2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.