tbuckley/cabot-search huggingface dataset:
Abstract 15221: Pulmonary Artery Banding Induces NF-κB activated Inflammation and Deteriorates RV Function
Authors: Keimei Yoshida, Kohtaro Abe, Mariko Tanaka, Masako Shinoda, Yukimitsu Kuwabara, Keita Saku, Yoshitaka Hirooka, Masahiko Oka, Kenji Sunagawa
Journal: Circulation (2015)

Background: Right ventricular (RV) dysfunction contributes to poor prognosis in patients with pulmonary hypertension. Although pulmonary artery banding (PAB) induces RV inflammation, its mechanisms are poorly understood. Hypothesis: We assessed the hypothesis that RV pressure overload induced by PAB leads to RV dysfunction through NF-κB-mediated inflammation and fibrosis. Methods and Results: We banded the main PA using an 18-gauge needle in adult Sprague-Dawley rats (BW: 180-220g). We measured hemodynamics and analyzed immunohistochemistry of RV at Day 1, 3, 7 and 14 after PAB (n=4-6, each group). PAB time-dependently increased RV systolic pressure (sham: 31.1±5.7 vs. Day14: 73.2±11.8mmHg, p&lt;0.01), RV end-diastolic pressure (RVEDP) (sham: 1.5±0.9 vs. Day14: 5.8±2.1mmHg, p&lt;0.05) and RV hypertrophy (ratio of RV/LV+septum weight) (sham: 0.29±0.04 vs. Day14: 0.68±0.08, p&lt;0.01) with high expression of activated p65 (NF-κB). PAB increased inflammatory cells, mainly CD68 positive macrophages (sham: 5.6±1.6 vs. Day1: 46.4±9.7 cell/mm2, p&lt;0.01), and fibrosis areas (Masson trichrome staining) time-dependently (sham: 0.7±0.2 vs. Day14: 7.6±0.8%, p&lt;0.01). Chronic administration of NF-κB inhibitor, pyrrolydine-dithiocarbamate (PDTC, 200mg/kg/day, orally, from Day 0 to 28), in PAB rats (n=4-7, each group) markedly decreased RVEDP (vehicle: 9.0±0.7 vs. PDTC: 3.4±1.3mmHg, p&lt;0.01), attenuated the expression of activated p65 and infiltration of CD68 positive macrophages (vehicle: 24.1±10.4 vs. PDTC: 5.6±2.0 cell/mm2, p&lt;0.01), and reduced fibrosis (vehicle: 8.7±1.1 vs. PDCT: 2.4±0.8%, p&lt;0.01) (Figure). Conclusions: These findings indicate that PAB immediately activates NF-κB and increases macrophage infiltration. Second, chronic treatment with PDTC attenuates NF-κB activation and macrophage infiltration in RV, leading to reduced fibrosis as well as RVEDP. NF-κB inhibition may be a therapeutic target for the RV dysfunction.
Update: Influenza Activity in the United States During the 2016–17 Season and Composition of the 2017–18 Influenza Vaccine
Authors: Lenee Blanton, Noreen Alabi, Desiree Mustaquim, Calli Taylor, Krista Kniss, Natalie Kramer, Alicia Budd, Shikha Garg, Charisse N. Cummings, Jessie Chung, Brendan Flannery, Alicia M. Fry, Wendy Sessions, Rebecca Garten, Xiyan Xu, Anwar Isa Abd Elal, Larisa Gubareva, John Barnes, Vivien Dugan, David E. Wentworth, Erin Burns, Jacqueline Katz, Daniel Jernigan, Lynnette Brammer
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

During the 2016-17 influenza season (October 2, 2016-May 20, 2017) in the United States, influenza activity* was moderate. Activity remained low through November, increased during December, and peaked in February nationally, although there were regional differences in the timing of influenza activity. Influenza A(H3N2) viruses predominated through mid-March and were predominant overall for the season, but influenza B viruses were most commonly reported from late March through May. This report summarizes influenza activity in the United States during October 2, 2016-May 20, 2017† and updates the previous summary (1).
Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer
Authors: James L. Gulley, Michael Borre, Nicholas J. Vogelzang, Siobhan Ng, Neeraj Agarwal, Chris C. Parker, David W. Pook, Per Rathenborg, Thomas W. Flaig, Joan Carles, Fred Saad, Neal D. Shore, Liddy Chen, Christopher R. Heery, Winald R. Gerritsen, Frank Priou, Niels C. Langkilde, Andrey Novikov, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2019)

PROSTVAC, a viral vector-based immunotherapy, prolonged median overall survival (OS) by 8.5 months versus placebo in metastatic castration-resistant prostate cancer in a phase II study. This phase III study further investigated those findings.Patients were randomly assigned to PROSTVAC (Arm V; n = 432), PROSTVAC plus granulocyte-macrophage colony-stimulating factor (Arm VG; n = 432), or placebo (Arm P; n = 433), stratified by prostate-specific antigen (less than 50 ng/mL v 50 ng/mL or more) and lactate dehydrogenase (less than 200 v 200 U/L or more). Primary end point was OS. Secondary end points were patients alive without events (AWE)-namely, radiographic progression, pain progression, chemotherapy initiation, or death-at 6 months and safety. The study design was a superiority trial of PROSTVAC (Arm V or Arm VG) versus Arm P. Three interim analyses were planned.At the third interim analysis, criteria for futility were met and the trial was stopped early. Neither active treatment had an effect on median OS (Arm V, 34.4 months; hazard ratio, 1.01; 95% CI, 0.84 to 1.20; P = .47; Arm VG, 33.2 months; hazard ratio, 1.02; 95% CI, 0.86 to 1.22; P = .59; Arm P, 34.3 months). Likewise, AWE at 6 months was similar (Arm V, 29.4%; odds ratio, 0.96; 95% CI, 0.71 to 1.29; Arm VG, 28.0%; odds ratio, 0.89; 95% CI, 0.66 to 1.20; placebo, 30.3%). Adverse events were similar for the treatment and placebo groups, with the most common being injection site reactions (62% to 72%) and fatigue (21% to 24%). Arrhythmias were the most common cardiac-related events (1.4% to 3.5%). There were no reports of either myocarditis or pericarditis. Serious treatment-related events occurred in less than 1% of all patients.Whereas PROSTVAC was safe and well tolerated, it had no effect on OS or AWE in metastatic castration-resistant prostate cancer. Combination therapy is currently being explored in clinical trials.
Policy Strategies for the “New Normal” in Healthcare to Ensure Access to High-Quality Cancer Care
Authors: Alyssa A. Schatz, Katy Winckworth Prejsnar, James McCanney, Meghan Gutierrez, Stefanie Joho, Joseph Alvarnas, Robert W. Carlson
Journal: Journal of the National Comprehensive Cancer Network (2019)

In recent years, oncology has seen a rapid increase in the introduction of high-cost innovative therapies while scrutiny around drug pricing has simultaneously amplified. Significant policy shifts impacting health coverage and benefit design are also being implemented, including narrow network health plans, uncertainty around the Affordable Care Act insurance exchanges, and threats to preexisting condition protections. Shifting health coverage policy combined with high drug prices and outdated reimbursement systems may create barriers to patient access to innovation and high-quality cancer care. To understand how trends in health policy are impacting the oncology ecosystem, NCCN convened the NCCN Policy Summit: Policy Strategies for the “New Normal” in Healthcare to Ensure Access to High-Quality Cancer Care on June 25, 2018. The summit included discussion of how innovation is changing cancer treatment, care delivery, and ways health systems are responding; the impact of narrow networks on access to academic cancer centers; and how the evolving health policy landscape is affecting access to high-quality cancer care for patients.
Oral Vitamin C Supplementation to Azacitidine in Patients with Myeloid Cancer: Normalization of Plasma Vitamin C Induces Epigenetic Changes
Authors: Linn Gillberg, Andreas Due Ørskov, Ammar Nasif, Hitoshi Otani, Zachary Madaj, Jakob Werner Hansen, Johanne Bay Mogensen, Minmin Liu, Inge Høgh Dufva, Lykkesfeldt Jens, Petra Hajkova, Peter A. Jones, Kirsten Grønbæk
Journal: Blood (2018)
An Isolated Osseous Rosai-Dorfman Disease Shown on FDG PET/CT
Authors: Mahdi Zirakchian Zadeh, Zhe Wen, Lisa J. States, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2019)

Abstract Rosai-Dorfman disease is typically presented as lymphadenopathy, especially in the neck. Extranodal diseases also frequently occur but are generally concurrent with nodal disease. We report FDG PET/CT findings of solitary femoral Rosai-Dorfman disease without any lymphadenopathy in a pediatric patient.
Early Awareness of Alzheimer Disease
Authors: Daniel M. Gibbs
Journal: JAMA Neurology (2019)

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 Neurology 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 Neurology journal
P141 Differential DNA methylation in peripheral naÏve CD4+T-cells in early rheumatoid arthritis patients
Authors: R Pitaksalee, AN Burska, I McInnes, P Emery, R Hodgett, F Ponchel
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Alterations in DNA methylation patterns (epimutations) have been related to several diseases, including Rheumatoid Arthritis (RA). We hypothesise that such epimutations occur early in the RA disease process. T-cells are important cells in early pathogenesis, therefore we choose to analyse patterns of differential methylation (DM) of the DNA of CD4+ T cells. <h3>Objectives</h3> To identify changes in DNA methylation pattern of naïve CD4 +T cells in early, drug naïve RA patients, towards understanding early events in disease pathogenesis. <h3>Methods</h3> DNA methylation of 480,000 CpGs (Illumina methylation genome-wide array) were analysed in cell sorted, naïve CD4+ T cell from 6 healthy control (HC) and 10 RA patients. To priorities DM gene, we designed a scoring system.<sup>1</sup> We examined potential interactions between DM genes using the STRING-database of protein-protein network analysis. Flow cytometry was used to characterise subpopulations of naïve CD4+ T cells in early RA for 4 DM genes, coding for cell surface molecules. <h3>Results</h3> We observed 648 DM-genes in naïve T-cells in early RA (354 hypo and 294 hyper-methylated). STRING analysis of these 648 genes/proteins revealed central of JAK1/STATs signalling, associated with an IL6/IL6R/STAT3 signalling node, a 2nd node for STAT2 linked to downstream interferon signalling, a 3rd node centred on IL2/IL15/STAT5, and many other associations notably related to TNF-alpha and TGF-beta signalling as well as a Th17 cell differentiation axis. Several genes were coding for cell surface proteins, notable CD4, IL2R, IL6R and CD62L. Analysis of CD4 and IL2R confirmed significant increased expression between RA and HC. CD62L identified 2 subpopulations of naïve T-cell in RA the classical naive CD62L+ cells and CD62L- naïve T-cells as previously reported<sup>2</sup>. IL6R expression was reduced in CD62L- naïve CD4+ T cell compared to CD62L+ cells. <h3>Conclusions</h3> DNA methylation pattern in naïve CD4+ T cell point to a central role for JAK1/STAT3/IL6 signalling in very early RA pathogenesis, with a pivotal role in diversification towards other pathways (notably TNF, Th17, Th1), which may already contribute to patient heterogeneity at this stage. Our data provides more understanding of early RA pathogenesis and should facilitate novel therapeutic strategies by targeting the right pathways. <h3>References</h3> Pitaksalee R, <i>et al</i>. P128 Analysis of DNA methylation patterns in rheumatoid arthritis patient: a system for prioritising meaningful difference. <i>ARD</i> 2018;77:A69. Ponchel F, <i>et al</i>. Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. <i>Blood</i> 2002;100:4550–4556. <h3>Disclosure of Interest</h3> None declared.
Clinical Features and Outcomes of Childhood Hypertrophic Cardiomyopathy
Authors: Alan W. Nugent, Piers E.F. Daubeney, Patty Chondros, John B. Carlin, Steven D. Colan, Michael Cheung, Andrew M. Davis, C.W. Chow, Robert G. Weintraub
Journal: Circulation (2005)

Background— Population-based studies have provided insight into the natural history of adult hypertrophic cardiomyopathy, but comparable information for affected children is lacking. Methods and Results— All Australian children who presented with primary cardiomyopathy at 0 to 10 years of age between January 1, 1987, and December 31, 1996, were enrolled in a longitudinal cohort study. A single cardiologist reviewed serial cardiac investigations on each subject. A total of 80 subjects with hypertrophic cardiomyopathy were identified. An underlying syndromal, genetic, or metabolic condition was identified in 46 subjects (57.5%). There were no cases of sudden death at presentation. Left ventricular outflow tract obstruction was present in 32 subjects (40%); right ventricular outflow obstruction was present in 10 (12.5%). Freedom from death or transplantation was 83% (95% CI, 73 to 90) 5 years after presentation and 76% (95% CI, 62 to 86) 10 years after presentation. By proportional-hazards regression analysis, risk factors for death or transplantation included concentric left ventricular hypertrophy, age at presentation &lt;1 year, lower initial fractional shortening Z score, and increasing left ventricular posterior wall thickness relative to body surface area. At the latest follow-up, 54 of 65 surviving subjects had no symptoms, and 46 were receiving no regular medication. Conclusions— Syndromal, genetic, and metabolic causes predominate in children with hypertrophic cardiomyopathy. Ventricular outflow tract obstruction is common. The clinical status of long-term survivors is good. This population-based study identifies children with hypertrophic cardiomyopathy who are at risk of adverse events.
Spermatogonial stem cells: updates from specification to clinical relevance
Authors: Swati Sharma, Joachim Wistuba, Tim Pock, Stefan Schlatt, Nina Neuhaus
Journal: Human Reproduction Update (2019)

Human spermatogonia are target for exploration of adult stem cell characteristics and potential source for the development of therapeutic applications. Almost 50 years ago, Yves Clermont stated with regard to the nature of the true stem cells: 'there is the possibility that other classes of spermatogonia exist beside the three classes (Adark, Apale and type B)…; …we still know too little about the human spermatogonial stem cells'… This review seeks to provide current knowledge, focusing on different aspects of human spermatogonia, and novel information based on species comparisons with regard to the adaptation of their proliferative potential. Moreover, the objective is to provide an update on the state of the art concerning the potential use of human spermatogonia for clinical applications. Germ cell specification mechanisms and epigenetic as well as transcriptional features of primordial germ cells (PGC) and adult spermatogonia at the single-cell level are reviewed. Studies on single-cell analyses have been included as they provide hitherto unequaled resolution of the transcriptional profiles of unselected human testicular cells and, thereby, new insights into the molecular aspects of germ cell differentiation. Datasets on models of spermatogonial expansion were identified and spermatogonial turnover and lifetime sperm production rates in various species were calculated, based exclusively on studies employing the optical dissector approach. Finally, the state of the art concerning causes of impaired spermatogonial function and fertility preservation were comprehensively reviewed. RNA sequencing data from PGC and spermatogonia indicate that transcriptional heterogeneity is a feature of germ cells prior to differentiation. Based on these data as well as lineage-tracing studies it is now debated whether spermatogonia are a rather plastic population of undifferentiated germ cells with the stem cell niche being the regulatory unit for cell fate decisions. Based on our novel calculations we suggest that spermatogonia are adapted to the individual reproductive lifespan and that the life-long sperm output from a spermatogonium is balanced against the duration of a generation. Thereby, the risk of jeopardizing genome integrity is balanced against a maximized sperm output. With reference to Yves Clermont's statement, and based on recent datasets, we suggest that the question that needs to be answered is: 'Is there a true stem cell?' or better 'Is there a population of various cells with distinct features serving as a stem cell pool?'. This review provides an update including novel views on various aspects of spermatogonial biology (from embryonic to adult stages). We consider this review relevant for all research scientists and clinicians dealing with fertility, spermatogenesis and fertility preservation.
Paired acute‐baseline serum tryptase levels in perioperative anaphylaxis: An observational study
Authors: Joana Vitte, Laurent Amadei, Marion Gouitaa, Soraya Mezouar, Laurent Zieleskiewicz, Jacques Albanese, Nicolas Bruder, David Lagier, Paul M. Mertès, Jean‐Louis Mège, Lawrence B. Schwartz, Marc Leone
Journal: Allergy (2019)

Anaphylaxis is recognized mainly through clinical criteria, which may lack specificity or relevance in the perioperative setting. The transient increase in serum tryptase has been proposed since 1989 as a diagnostic tool. Sampling for well-defined acute and baseline determinations has been recommended. We assessed the performance of four proposed algorithms with tightly controlled time frames for tryptase sampling, their robustness with inadequate sampling times, and the possible use of mature tryptase determination.A retrospective study was performed on 102 adult patients from the Aix-Marseille University Hospitals who had experienced a perioperative hypersensitivity reaction clinically suggesting anaphylaxis. EAACI and ICON criteria were used to diagnose anaphylaxis. Mature and total serum tryptase levels were measured.Based on EAACI guidelines, clinical diagnostic criteria for anaphylaxis were found in 76 patients and lacking in 26. The most effective algorithm was the international consensus recommendation of 2012 that acute total tryptase levels should be greater than ([1.2×baseline tryptase] + 2] μg/L to be considered a clinically significant rise. In our cohort, this algorithm achieved 94% positive predictive value (PPV), 53% negative predictive value (NPV), 75% sensitivity, 86% specificity, and a Youden's index value of 0.61. A detectable acute mature tryptase level showed lower sensitivity, particularly in patients with acute total tryptase levels lower than 16 μg/L. Acute tryptase levels varied as a function of the clinical severity of anaphylaxis.Total tryptase levels in serum discriminated between nonanaphylactic and anaphylactic events in a perioperative setting when acute and baseline levels were collected and analyzed by the consensus algorithm.
Structural Iatrogenesis — A 43-Year-Old Man with “Opioid Misuse”
Authors: Scott Stonington, Diana Coffa
Journal: New England Journal of Medicine (2019)

Interview with Dr. Scott Stonington on structures within medicine that may systematically harm patients. (09:27)Download When he gets tangled in new restrictive policies on opioid prescribing, a factory worker with severe rheumatoid arthritis, whose pain must be managed for him to perform his job, ends up buying oxycodone from a friend.
Summary of Notifiable Infectious Diseases and Conditions — United States, 2013
Authors: Deborah Adams, Kathleen Fullerton, Ruth Jajosky, Pearl Sharp, Diana Onweh, Alan Schley, Willie Anderson, Amanda Faulkner, Kiersten Kugeler
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

The Summary of Notifiable Infectious Diseases and Condition-United States, 2013 (hereafter referred to as the summary) contains the official statistics, in tabular and graphic form, for the reported occurrence of nationally notifiable infectious diseases and conditions in the United States for 2013. Unless otherwise noted, data are final totals for 2013 reported as of June 30, 2014. These statistics are collected and compiled from reports sent by U.S. state and territory, New York City, and District of Columbia health departments to the National Notifiable Diseases Surveillance System (NNDSS), which is operated by CDC in collaboration with the Council of State and Territorial Epidemiologists (CSTE). This summary is available at http://www.cdc.gov/mmwr/mmwr_nd/index.html. This site also includes summary publications from previous years.
Health-related quality of life in the ENDEAVOR study: carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed/refractory multiple myeloma
Authors: Heinz Ludwig, Philippe Moreau, Meletios A. Dimopoulos, Maria-Victoria Mateos, Martin Kaiser, Roman Hajek, Shibao Feng, Kim Cocks, Jaqueline Buchanan, Katja Weisel
Journal: Blood Cancer Journal (2019)

Abstract We examined effects of carfilzomib-dexamethasone (Kd56) versus bortezomib-dexamethasone (Vd) on health-related quality of life (HR-QoL) in relapsed/refractory multiple myeloma (MM) patients from the ENDEAVOR study. HR-QoL was assessed by the European Organisation for Research and Treatment of Cancer QoL Questionnaire (QLQ-C30), MM-specific module (QLQ-MY20), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-Ntx) “Additional Concerns” neurotoxicity subscale. The QLQ-C30 Global Health Status (GHS)/QoL scale and seven prespecified subscales were compared between groups using mixed model for repeated measures. Of 929 randomized patients, 911 with ≥1 post-baseline assessment were included. Kd56 was associated with statistically significant improvements in GHS/QoL, fatigue, pain, side effects, and FACT/GOG-Ntx scores versus Vd, although mean differences did not meet thresholds for clinical significance. The Kd56 group had longer time to deterioration (TTD) in GHS/QoL (median 3.7 versus 2.8 months, p = 0.0046), physical function (5.6 versus 3.7 months, p = 0.0390), nausea/vomiting (17.6 versus 8.2 months, p = 0.0358), side effects (6.4 versus 3.7 months p &lt; 0.0001), and FACT/GOG-Ntx (11.1 versus 5.5 months , p = 0.0004). Overall, Kd56 resulted in statistically but not clinically significant improvements in mean GHS/QoL scores versus Vd. Treatment with Kd56 versus Vd also significantly prolonged TTD in GHS/QoL, physical function, nausea/vomiting, side effects, and FACT/GOG-Ntx.