tbuckley/cabot-search huggingface dataset:
Multi- and Transgenerational Outcomes of an Exposure to a Mixture of Endocrine-Disrupting Chemicals (EDCs) on Puberty and Maternal Behavior in the Female Rat
Authors: David López-Rodríguez, Carlos Francisco Aylwin, Virginia Delli, Elena Sevrin, Marzia Campanile, Marion Martin, Delphine Franssen, Arlette Gérard, Silvia Blacher, Ezio Tirelli, Agnès Noël, Alejandro Lomniczi, Anne-Simone Parent
Journal: Environmental Health Perspectives (2021)

BACKGROUND:The effects of endocrine-disrupting chemicals (EDCs) on fertility and reproductive development represent a rising concern in modern societies.Although the neuroendocrine control of sexual maturation is a major target of EDCs, little is known about the potential role of the hypothalamus in puberty and ovulation disruption transmitted across generations.OBJECTIVES: We hypothesized that developmental exposure to an environmentally relevant dose of EDC mixture could induce multi-and/or transgenerational alterations of sexual maturation and maternal care in female rats through epigenetic reprograming of the hypothalamus.We investigated the transmission of a disrupted reproductive phenotype via the maternal germline or via nongenomic mechanisms involving maternal care.METHODS: Adult female Wistar rats were exposed prior to and during gestation and until the end of lactation to a mixture of the following 13 EDCs: di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), bisphenol A (BPA), vinclozolin, prochloraz, procymidone, linuron, epoxynaxole, dichlorodiphenyldichloroethylene, octyl methoxynimmate, 4-methylbenzylidene camphor (4-MBC), butylparaben, and acetaminophen.Perinatally exposed offspring (F1) were mated with unexposed males to generate germ cell (F2) and transgenerationally exposed (F3 and F4) females.Sexual maturation, maternal behavior, and hypothalamic targets of exposure were studied across generations.RESULTS: Germ cell (F2) and transgenerationally (F3) EDC-exposed females, but not F1, displayed delayed pubertal onset and altered folliculogenesis.We reported a transgenerational alteration of key hypothalamic genes controlling puberty and ovulation (Kiss1, Esr1, and Oxt), and we identified the hypothalamic polycomb group of epigenetic repressors as actors of this mechanism.Furthermore, we found a multigenerational reduction of maternal behavior (F1-F3) induced by a loss in hypothalamic dopaminergic signaling.Using a cross-fostering paradigm, we identified that the reduction in maternal phenotype was normalized in EDC-exposed pups raised by unexposed dams, but no reversal of the pubertal phenotype was achieved.DISCUSSION: Rats developmentally exposed to an EDC mixture exhibited multi-and transgenerational disruption of sexual maturation and maternal care via hypothalamic epigenetic reprogramming.These results raise concerns about the impact of EDC mixtures on future generations.
Surprise Billing in Health Care
Authors: Join Y. Luh, Eric R. Hansen, Robert A. Bitonte
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
P-200 A phase II study of dose reductive XELOX plus bevacizumab in elderly or vulnerable patients with metastatic colorectal cancer: MCSGO-1202
Authors: K. Nakata, D. Sakai, J. Hasegawa, T. Kato, K. Murata, M. Ikenaga, T. Kudo, M. Uemura, T. Satoh, T. Mizushima, Y. Doki, H. Eguchi
Journal: Annals of Oncology (2021)
Association between race and maladaptive concentric left ventricular hypertrophy in American-style football athletes
Authors: Jason V Tso, Casey G Turner, Chang Liu, Angelo Galante, Carla R Gilson, Craig Clark, Herman A Taylor, Arshed A Quyyumi, Aaron L Baggish, Jonathan H Kim
Journal: British Journal of Sports Medicine (2021)

American-style football (ASF) athletes are at risk for the development of concentric left ventricular hypertrophy (C-LVH), an established cardiovascular risk factor in the general population. We sought to address whether black race is associated with acquired C-LVH in collegiate ASF athletes.Collegiate ASF athletes from two National Collegiate Athletic Association Division-I programmes were recruited as freshmen between 2014 and 2019 and analysed over 3 years. Demographics (neighbourhood family income) and repeated clinical characteristics and echocardiography were recorded longitudinally at multiple timepoints. A mixed-modelling approach was performed to evaluate acquired C-LVH in black versus white athletes controlling for playing position (linemen (LM) and non-linemen (NLM)), family income, body weight and blood pressure.At baseline, black athletes (N=124) were more often NLM (72% vs 54%, p=0.005) and had lower median neighbourhood family income ($54 119 vs $63 146, p=0.006) compared with white athletes (N=125). While both black and white LM demonstrated similar increases in C-LVH over time, among NLM acquired C-LVH was more common in black versus white athletes (postseason year-1: N=14/89 (16%) vs N=2/68 (3%); postseason year-2: N=9/50 (18%) vs N=2/32 (6%); postseason year-3: N=8/33 (24%) vs N=1/13 (8%), p=0.005 change over time). In stratified models, black race was associated with acquired C-LVH in NLM (OR: 3.70, 95% CI 1.12 to 12.21, p=0.03) and LM was associated with acquired C-LVH in white athletes (OR: 3.40, 95% CI 1.03 to 11.27, p=0.048).Independent of family income and changes in weight and blood pressure, black race was associated with acquired C-LVH among collegiate ASF NLM and LM was associated with acquired C-LVH in white athletes.
28561 The impact of telemedicine on the delivery of dermatologic care during the COVID-19 pandemic
Authors: Vartan Pahalyants, William Murphy, Nicole Gunasekera, Daniela Kroshinsky
Journal: Journal of the American Academy of Dermatology (2021)

Introduction: The COVID-19 pandemic has expanded the use of teledermatology. We report on the impact of teledermatology on care delivery at two urban high-volume academic practices. Methods: We reviewed all appointments for patients over 18 at Mass General Brigham between 1/1/20 and 7/31/20 for patient characteristics, appointment status and diagnosis. Results: 51,799 appointments were scheduled over the seven-month period. Patient volume dropped by more than half during office closures from March to May, but it has since returned to pre-pandemic levels. Teledermatology utilization decreased after office reopening (5,961 (80.4%) vs 4,803 (25.0%) P ˂ .001). Attendance rates were higher for virtual (85.8%) than in-person visits during the pandemic (76.8%) or before the pandemic (81.3%) (P ˂ .001). Compared with in-person appointments, the patients seen virtually were younger (50.4 vs 55.7 years, P ˂ .001), more likely to be female (67.9% vs 60.5%, P ˂ .001), nonwhite (24.0% vs 19.7%), and privately insured (69.3% vs 65.8%, P ˂ .001). Non-English speakers were not negatively impacted by the pandemic. Acne, medication management, eczema, and psoriasis appointments were more commonly seen virtually, while nevus and skin lesion evaluations were less common. Discussion: The pandemic has shown the promising future of teledermatology. Although some groups enjoyed greater access to care, further research is needed to determine the reasons for the differences in the demographics of patients seen virtually to ensure equitable access to dermatologic care, particularly among older and male patients. Our data also suggest that certain appointments may be more conducive to virtual visits and should be extended beyond the pandemic period.
Anxa1 in smooth muscle cells protects against acute aortic dissection
Authors: Changping Zhou, Zhiyong Lin, Huanhuan Cao, Yue Chen, Jingxuan Li, Xiaofeng Zhuang, Dong Ma, Liang Ji, Wei Li, Suowen Xu, Bing Pan, Lemin Zheng
Journal: Cardiovascular Research (2021)

Acute aortic dissection (AAD) is a life-threatening disease with high morbidity and mortality. Previous studies have showed that vascular smooth muscle cell (VSMC) phenotype switching modulates vascular function and AAD progression. However, whether an endogenous signalling system that protects AAD progression exists remains unknown. Our aim is to investigate the role of Anxa1 in VSMC phenotype switching and the pathogenesis of AAD.We first assessed Anxa1 expression levels by immunohistochemical staining in control aorta and AAD tissue from mice. A strong increase of Anxa1 expression was seen in the mouse AAD tissues. In line with these findings, micro-CT scan results indicated that Anxa1 plays a role in the development of AAD in our murine model, with systemic deficiency of Anxa1 markedly progressing AAD. Conversely, administration of Anxa1 mimetic peptide, Ac2-26, rescued the AAD phenotype in Anxa1-/- mice. Transcriptomic studies revealed a novel role for Anxa1 in VSMC phenotype switching, with Anxa1 deficiency triggering the synthetic phenotype of VSMCs via down-regulation of the JunB/MYL9 pathway. The resultant VSMC synthetic phenotype rendered elevated inflammation and enhanced matrix metalloproteinases (MMPs) production, leading to augmented elastin degradation. VSMC-restricted deficiency of Anxa1 in mice phenocopied VSMC phenotype switching and the consequent exacerbation of AAD. Finally, our studies in human AAD aortic specimens recapitulated key findings in murine AAD, specifically that the decrease of Anxa1 is associated with VSMC phenotype switch, heightened inflammation, and enhanced MMP production in human aortas.Our findings demonstrated that Anxa1 is a novel endogenous defender that prevents AAD by inhibiting VSMC phenotype switching, suggesting that Anxa1 signalling may be a potential target for AAD pharmacological therapy.
Recovery and outcomes of patients denied early liver transplantation for severe alcohol‐associated hepatitis
Authors: Jessica Musto, Dylan Stanfield, Dana Ley, Michael R. Lucey, Jens Eickhoff, John P. Rice
Journal: Hepatology (2021)

Liver transplantation (LT) in alcohol-associated hepatitis (AH) remains controversial, in part because spontaneous recovery (SR) can occur. There is a paucity of data on SR in patients with severe AH who undergo LT evaluation. The purpose of this study was to determine factors associated with SR and survival in patients with severe AH who undergo LT evaluation.This is a retrospective study of ALD patients with Model for End-Stage Liver Disease (MELD) >25 and <90 days abstinence who underwent LT evaluation at a single center between 2012 and 2018. One hundred forty-four patients (median age, 45.5 years; 68.1% male) were included. Forty-nine (34%) underwent LT and 95 (66%) patients did not undergo LT, and of those, 34 (23.6%) experienced SR. Factors associated with recovery were younger age (OR, 0.92; p = 0.004), lower index international normalized ratio (INR; 0.31; p = 0.03), and lower peak MELD (OR, 0.83; p = 0.02). Only 7 patients (20.6%) achieved a compensated state with a MELD <15 and absence of therapy for ascites or HE. Survival was improved in patients who underwent early LT when compared to SR. Survival was impaired in SR following relapse to alcohol use when compared to SR patients who abstained and LT recipients. Among all 6-month survivors of AH, alcohol use trended toward an association with mortality (HR, 2.05; p = 0.17), but only LT was associated with decreased mortality risk (HR, 0.20; p = 0.005).SR from AH after LT evaluation is associated with age, index INR, and lower peak MELD. Most recovered patients continue to experience end-stage complications. LT is the only factor associated with lower mortality.
Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers
Authors: Marie Zufferey, Yuanlong Liu, Daniele Tavernari, Marco Mina, Giovanni Ciriello
Journal: Genome biology (2021)

Spatial interactions and insulation of chromatin regions are associated with transcriptional regulation. Domains of frequent chromatin contacts are proposed as functional units, favoring and delimiting gene regulatory interactions. However, contrasting evidence supports the association between chromatin domains and transcription.
Medicine in defense against biological warfare
Authors: D. L. Huxsoll
Journal: JAMA (1989)

IT IS fitting in this issue ofThe Journalthat we turn our attention to another means of mass destruction—biological warfare. This method of warfare, first used in the sixth century BC, 1 is widely available, easily obtained, silent, and invisible. Whether it be a fraction of a microgram of lethal toxin inhaled by one person or a drifting cloud that can kill or incapacitate tens of thousands, the potential threat of biological warfare is clear. In this commentary, we explain why research in medical defenses against this threat is needed as we answer yes to Orient's 2 question, Should medical defenses against biological warfare be researched?  We define biological warfare as the use of microorganisms or toxins derived from living organisms to produce death or disease in humans, animals, or plants. This definition is compatible with the National Security Decisions signed in 1969 and 1970, in which the United
Should covid vaccination be mandatory for health and care staff?
Authors: Michael Parker, Helen Bedford, Michael Ussher, Martine Stead
Journal: BMJ (2021)

New English law will make vaccination a condition of employment for eligible care home workers, following similar moves in Italy, France, and Greece for healthcare staff. This is reasonable, argues <b>Michael Parker</b>, because care institutions have a duty to protect patients; but <b>Helen Bedford</b>, <b>Michael Ussher</b>, and <b>Martine Stead</b> worry that such a blunt approach is unnecessary and could be counterproductive
Usefulness of artificial intelligence for predicting recurrence following surgery for pancreatic cancer: Retrospective cohort study
Authors: Kwang-Sig Lee, Jin-Young Jang, Young-Dong Yu, Jin Seok Heo, Ho-Seong Han, Yoo-Seok Yoon, Chang Moo Kang, Ho Kyoung Hwang, Sunghwa Kang
Journal: International Journal of Surgery (2021)
Endothelial cells
Authors: Barbara J. Bain
Journal: American Journal of Hematology (2013)

In interpreting peripheral blood films it is necessary to recognise extraneous cells that are occasionally present.These can include epithelial cells (either nucleated or not), endothelial cells and even subcutaneous fat cells 1 .Noting the presence and recognising the nature of such cells is important, both because they may otherwise be misinterpreted as cells of pathological significance and because, in the case of fat cells, they may be sufficiently numerous to interfere with an automated count 2 .These images show endothelial cells at low power (top) and high power (bottom).These cells tend to occur in loose sheets and are pleomorphic with round to oval nuclei and variably condensed chromatin.Nuclei may be irregular or grooved and some cells appear to be multinucleated.
Small Airway Reduction and Fibrosis Is an Early Pathologic Feature of Idiopathic Pulmonary Fibrosis
Authors: Kohei Ikezoe, Tillie-Louise Hackett, Samuel Peterson, Dante Prins, Cameron J. Hague, Darra Murphy, Stacey LeDoux, Fanny Chu, Feng Xu, Joel D. Cooper, Naoya Tanabe, Christopher J. Ryerson, Peter D. Paré, Harvey O. Coxson, Thomas V. Colby, James C. Hogg, Dragoş M. Vasilescu
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: To improve disease outcomes in idiopathic pulmonary fibrosis (IPF), it is essential to understand its early pathophysiology so that it can be targeted therapeutically. Objectives: Perform three-dimensional assessment of the IPF lung microstructure using stereology and multiresolution computed tomography (CT) imaging. Methods: Explanted lungs from patients with IPF (n = 8) and donor control subjects (n = 8) were inflated with air and frozen. CT scans were used to assess large airways. Unbiased, systematic uniform random samples (n = 8/lung) were scanned with microCT for stereological assessment of small airways (count number, and measure airway wall and lumen area) and parenchymal fibrosis (volume fraction of tissue, alveolar surface area, and septal wall thickness). Measurements and Main Results: The total number of airways on clinical CT was greater in IPF lungs than control lungs (P < 0.01), owing to an increase in the wall (P < 0.05) and lumen area (P < 0.05) resulting in more visible airways with a lumen larger than 2 mm. In IPF tissue samples without microscopic fibrosis, assessed by the volume fraction of tissue using microCT, there was a reduction in the number of the terminal (P < 0.01) and transitional (P < 0.001) bronchioles, and an increase in terminal bronchiole wall area (P < 0.001) compared with control lungs. In IPF tissue samples with microscopic parenchymal fibrosis, terminal bronchioles had increased airway wall thickness (P < 0.05) and dilated airway lumens (P < 0.001) leading to honeycomb cyst formations. Conclusions: This study has important implications for the current thinking on how the lung tissue is remodeled in IPF and highlights small airways as a potential target to modify IPF outcomes.
Early Use of High-Dose Glucocorticoid for the Management of irAE Is Associated with Poorer Survival in Patients with Advanced Melanoma Treated with Anti–PD-1 Monotherapy
Authors: Xue Bai, Jiani Hu, Allison Betof Warner, Henry T. Quach, Christopher G. Cann, Michael Z. Zhang, Lu Si, Bixia Tang, Chuanliang Cui, Xiaoling Yang, Xiaoting Wei, Lalit Pallan, Catriona Harvey, Michael P. Manos, Olivia Ouyang, Michelle S. Kim, Gyulnara Kasumova, Justine V. Cohen, Donald P. Lawrence, Christine Freedman, Riley M. Fadden, Krista M. Rubin, Tatyana Sharova, Dennie T. Frederick, Keith T. Flaherty, Osama E. Rahma, Georgina V. Long, Alexander M. Menzies, Jun Guo, Alexander N. Shoushtari, Douglas B. Johnson, Ryan J. Sullivan, Genevieve M. Boland
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Programmed cell death receptor-1 (PD-1) inhibitors are frontline therapy in advanced melanoma. Severe immune-related adverse effects (irAEs) often require immunosuppressive treatment with glucocorticoids (GCCs), but GCC use and its correlation with patient survival outcomes during anti–PD-1 monotherapy remains unclear. Experimental Design: In this multicenter retrospective analysis, patients treated with anti–PD-1 monotherapy between 2009 and 2019 and detailed GCC use, data were identified from five independent cohorts, with median follow-up time of 206 weeks. IrAEs were tracked from the initiation of anti–PD-1 until disease progression, initiation of a new therapy, or last follow-up. Correlations between irAEs, GCC use, and survival outcomes were analyzed. Results: Of the entire cohort of 947 patients, 509 (54%) developed irAEs. In the MGH cohort [irAE(+) n = 90], early-onset irAE (within 8 weeks of anti–PD-1 initiation) with high-dose GCC use (≥60-mg prednisone equivalent once a day) was independently associated with poorer post-irAE PFS/OS (progression-free survival/overall survival) [post-irAE PFS: HR, 5.37; 95% confidence interval (CI), 2.10–13.70; P &amp;lt; 0.001; post-irAE OS: HR, 5.95; 95% CI, 2.20–16.09; P &amp;lt; 0.001] compared with irAEs without early high-dose GCC use. These findings were validated in the combined validation cohort [irAE(+) n = 419, post-irAE PFS: HR, 1.69; 95% CI, 1.04–2.76; P = 0.04; post-irAE OS: HR, 1.97; 95% CI, 1.15–3.39; P = 0.01]. Similar findings were also observed in the 26-week landmark analysis for post–irAE-PFS but not for post–irAE-OS. A sensitivity analysis using accumulated GCC exposure as the measurement achieved similar results. Conclusions: Early high-dose GCC use was associated with poorer PFS and OS after irAE onset. Judicious use of GCC early during anti–PD-1 monotherapy should be considered. Further prospective randomized control clinical trials designed to explore alternative irAE management options are warranted.
Covid-19：在第一次剂量后，辉瑞疫苗疗效为52％，纸张显示第二剂后95％
Authors: 伊丽莎白 Mahase.
Journal: BMJ (2020)

辉瑞和Biontech Covid-19疫苗可以提供一些早期的保护，从第一次给药后12天开始，同行审查的结果发现了一项审判。

这项研究，发表在新英格兰医学杂志 ,1发现第一和第二剂量之间的疫苗疗效为52％（95％可信间隔29.5％至68.4％），疫苗组中的39例Covid-19和安慰剂组中的82例。

第二剂后七天或更长时间，疫苗疗效然后上升至95％（90.3％至97.6％），疫苗组报告八个Covid-19例，安慰剂组162例。

The vaccine has so far been approved in Canada …
Serological markers of SARS-CoV-2 infection; anti-nucleocapsid antibody positivity may not be the ideal marker of natural infection in vaccinated individuals
Authors: Niamh Allen, Melissa Brady, Antonio Isidro Carrion Martin, Lisa Domegan, Cathal Walsh, Lorraine Doherty, Una Ni Riain, Colm Bergin, Catherine Fleming, Niall Conlon
Journal: Journal of Infection (2021)