tbuckley/cabot-search huggingface dataset:
Soluble PD-L1 is a potential biomarker of cutaneous melanoma aggressiveness and metastasis in obstructive sleep apnoea patients
Authors: Carolina Cubillos-Zapata, Miguel Ángel Martínez-García, Francisco Campos-Rodríguez, Manuel Sánchez de la Torre, Eduardo Nagore, Antonio Martorell-Calatayud, Luis Hernández Blasco, Eusebi Chiner Vives, Jorge Abad-Capa, Josep María Montserrat, Valentín Cabriada-Nuño, Irene Cano-Pumarega, Jaime Corral-Peñafiel, Trinidad Diaz-Cambriles, Olga Mediano, María Somoza-González, Joan Dalmau-Arias, Isaac Almendros, Ramón Farré, Eduardo López-Collazo, David Gozal, Francisco García-Río
Journal: European Respiratory Journal (2018)

Obstructive sleep apnoea (OSA) upregulates the programmed cell death-1 receptor and its ligand (PD-L1) pathway, potentially compromising immunosurveillance. We compared circulating levels of soluble PD-L1 (sPD-L1) in patients with cutaneous melanoma according to the presence and severity of OSA, and evaluated relationships with tumour aggressiveness and invasiveness.In a multicentre observational study, 360 patients with cutaneous melanoma underwent sleep studies, and serum sPD-L1 levels were assayed using ELISA. Cutaneous melanoma aggressiveness indices included mitotic rate, Breslow index, tumour ulceration, Clark level and tumour stage, and sentinel lymph node (SLN) metastasis was recorded as a marker of invasiveness.sPD-L1 levels were higher in severe OSA compared to mild OSA or non-OSA patients. In OSA patients, sPD-L1 levels correlated with Breslow index and were higher in patients with tumour ulceration, advanced primary tumour stages or with locoregional disease. The incorporation of sPD-L1 to the classic risk factors to SLN metastasis led to net improvements in the classification of 27.3%.Thus, sPD-L1 levels are increased in melanoma patients with severe OSA, and, in addition, might serve as a potential biomarker of cutaneous melanoma aggressiveness and invasiveness in this group of subjects.
Health Disparities Among American Indians/Alaska Natives — Arizona, 2017
Authors: Monique Adakai, Michelle Sandoval-Rosario, Fang Xu, Teresa Aseret-Manygoats, Michael Allison, Kurt J. Greenlund, Kamil E. Barbour
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Compared with other racial/ethnic groups, American Indians/Alaska Natives (AI/AN) have a lower life expectancy, lower quality of life, and are disproportionately affected by many chronic conditions (1,2). Arizona has the third largest population of AI/AN in the United States (approximately 266,000 in 2017), and is home to 22 federally recognized American Indian tribal nations.* The small AI/AN sample size in previous Behavioral Risk Factor Surveillance System (BRFSS) surveys has presented analytic challenges in making statistical inferences about this population. To identify health disparities among AI/AN living in Arizona, the Arizona Department of Health Services (ADHS) and CDC analyzed data from the 2017 BRFSS survey, for which AI/AN were oversampled. Compared with whites, AI/AN had significantly higher prevalences of sugar-sweetened beverage consumption (33.0% versus 26.8%), being overweight or having obesity (76.7% versus 63.2%), diabetes (21.4% versus 8.0%), high blood pressure (32.9% versus 27.6%), report of fair or poor health status (28.7% versus 16.3%), and leisure-time physical inactivity during the past month (31.1% versus 23.0%). AI/AN also reported a lower prevalence of having a personal doctor or health care provider (63.1%) than did whites (72.8%). This report highlights the need to enhance surveillance measures at the local, state, and national levels and can inform interventions centered on confronting social inequities, developing culturally competent prevention strategies, and facilitating access to care to improve population health and work toward health equity.
Electrocardiographic Harbingers of Ventricular Tachycardia Arrest—A Moment of Pause
Authors: Colette DeJong, Arvind Nishtala, Nora Goldschlager
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
Abstract 18119: Mechanical Active Compression-Decompression With LUCAS2AD Provide Equivocal pEtCO2 Values to the Standard LUCAS2 During Out-of-Hospital Cardiopulmonary Resuscitation
Authors: Per-Olav Berve, Tore Skålhegg, Bjarne Madsen Hardig, Jonas Carlson, Jo Kramer-Johansen, Lars Wik
Journal: Circulation (2017)

Introduction: Studies comparing manual active compression-decompression CPR (ACD-CPR) to manual CPR have shown similar survival rates. Recently a new mechanical ACD-CPR device (LUCAS2AD, Jolife AB/...
Withdrawn as Duplicate: The many nuanced evolutionary consequences of duplicated genes
Authors: Ashley I Teufel, Mackenzie M Johnson, Jon M Laurent, Aashiq H Kachroo, Edward M Marcotte, Claus O Wilke
Journal: Molecular Biology and Evolution (2018)

Gene duplication is seen as a major source of structural and functional divergence in genome evolution. Under the conventional models of sub or neofunctionalization, functional changes arise in one of the duplicates after duplication. However, we suggest here that the presence of a duplicated gene can result in functional changes to its interacting partners. We explore this hypothesis by in silico evolution of a heterodimer when one member of the interacting pair is duplicated. We examine how a range of selection pressures and protein structures leads to differential patterns of evolutionary divergence. We find that a surprising number of distinct evolutionary trajectories can be observed even in a simple three member system. Further, we observe that selection to correct dosage imbalance can affect the evolution of the initial function in several unexpected ways. For example, if a duplicate is under selective pressure to avoid binding its original binding partner, this can lead to changes in the binding interface of a nonduplicated interacting partner to exclude the duplicate. Hence, independent of the fate of the duplicate, its presence can impact how the original function operates. Additionally, we introduce a conceptual framework to describe how interacting partners cope with dosage imbalance after duplication. Contextualizing our results within this framework reveals that the evolutionary path taken by a duplicate’s interacting partners is highly stochastic in nature. Consequently, the fate of duplicate genes may not only be controlled by their own ability to accumulate mutations but also by how interacting partners cope with them.
TET2 Deficiency Sets the Stage for B-cell Lymphoma
Authors: Jennifer R. Shingleton, Sandeep S. Dave
Journal: Cancer Discovery (2018)

Abstract Summary: TET2 is a well-established tumor suppressor in the context of myeloid malignancies, but its role in lymphoma development has been less clear. In this issue of Cancer Discovery, Dominguez and colleagues report that TET2 function is critical for germinal center exit and plasma cell differentiation, and its deficiency can lead to B-cell lymphoma phenotypes. See related article by Dominguez et al., p. 1632.
Fever, Rash, and Abnormal Liver Function Test Results
Authors: Mitsuru Mukaigawara, Shuichi Sugita
Journal: JAMA (2018)

A man in his 30s had a 5-day history of fever, rhinorrhea, nonproductive cough, fever, and a maculopapular rash on his neck and trunk that spread to the extremities. He had leukopenia, and liver enzyme levels were elevated. What would you do next?
Subcutaneous Daratumumab in Patients with Relapsed or Refractory Multiple Myeloma: Part 2 Safety and Efficacy Update of the Open-Label, Multicenter, Phase 1b Study (PAVO)
Authors: Ajai Chari, Maria-Victoria Mateos, Niels WCJ van de Donk, Jonathan L Kaufman, Philippe Moreau, Albert Oriol, Torben Plesner, Lotfi Benboubker, Hareth Nahi, Jie Tang, Peter Hellemans, Brenda Tromp, Pamela L Clemens, Andrew Farnsworth, Jesus F San-Miguel, Saad Z. Usmani
Journal: Blood (2018)
Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial
Authors: Giuseppe Lombardi, Gian Luca De Salvo, Alba Ariela Brandes, Marica Eoli, Roberta Rudà, Marina Faedi, Ivan Lolli, Andrea Pace, Bruno Daniele, Francesco Pasqualetti, Simona Rizzato, Luisa Bellu, Ardi Pambuku, Miriam Farina, Giovanna Magni, Stefano Indraccolo, Marina Paola Gardiman, Riccardo Soffietti, Vittorina Zagonel
Journal: The Lancet Oncology (2018)
Temporal trends in use of tests in UK primary care, 2000-15: retrospective analysis of 250 million tests
Authors: Jack W O’Sullivan, Sarah Stevens, F D Richard Hobbs, Chris Salisbury, Paul Little, Ben Goldacre, Clare Bankhead, Jeffrey K Aronson, Rafael Perera, Carl Heneghan
Journal: BMJ (2018)

To assess the temporal change in test use in UK primary care and to identify tests with the greatest increase in use.Retrospective cohort study.UK primary care.All patients registered to UK General Practices in the Clinical Practice Research Datalink, 2000/1 to 2015/16.Temporal trends in test use, and crude and age and sex standardised rates of total test use and of 44 specific tests.262 974 099 tests were analysed over 71 436 331 person years. Age and sex adjusted use increased by 8.5% annually (95% confidence interval 7.6% to 9.4%); from 14 869 tests per 10 000 person years in 2000/1 to 49 267 in 2015/16, a 3.3-fold increase. Patients in 2015/16 had on average five tests per year, compared with 1.5 in 2000/1. Test use also increased statistically significantly across all age groups, in both sexes, across all test types (laboratory, imaging, and miscellaneous), and 40 of the 44 tests that were studied specifically.Total test use has increased markedly over time, in both sexes, and across all age groups, test types (laboratory, imaging, and miscellaneous) and for 40 of 44 tests specifically studied. Of the patients who underwent at least one test annually, the proportion who had more than one test increased significantly over time.
Clinical research and the AMSSM Collaborative Research Network
Authors: Stephanie A Kliethermes, Anthony I Beutler
Journal: British Journal of Sports Medicine (2018)

> In order for any discipline to be legitimate, it has to create its own body of knowledge.
> 
> Dr Jim Puffer, American Medical Society for Sports Medicine (founding member and past president)The value of rigorous clinical research to the field of sports medicine is indisputable. In our data-dominated society, insurers, oversight watchdogs and increasingly even consumers demand much more than ‘we’ve always done it this way’. The recent string of randomised trials showing conservative care to be non-inferior to arthroscopy for degenerative meniscus tears underscores the power of data in shaping medical practice, perception, reimbursement and most importantly, quality of patient care. As we pursue our vision of being a worldwide leader in sports medicine, the American Medical Society for Sports Medicine (AMSSM) champions high quality sports medicine research through research support, collaboration, education and strategic partnerships.

Since its founding in 1991, AMSSM has fostered and showcased excellent research, particularly that involving musculoskeletal care. After many years devoted to building the AMSSM research infrastructure, the AMSSM Collaborative Research Network (CRN) was established in 2016 to enhance clinical …
AB0025 Mtor pathway activation in large vessel vasculitis
Authors: C. Comarmond, A. Maciejewski-Duval, A. Leroyer, M. Zaidan, A. Le Joncour, P. Cacoub, D. Sadoun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Mammalian target of rapamycin complex 1 (mTORC 1) drives the proinflammatory expansion of T helper (TH) type 1, TH17 cells and controls fibroblast proliferation, typical features of large vessel vasculitis (LVV) pathogenesis. Molecular pathways involved in arterial lesions of LVV are unknown. <h3>Objectives</h3> To analyse mTOR pathway activation in LVV (giant cell arteritis and Takayasu arteritis). <h3>Methods</h3> We evaluate pathway activation in the mTORC and the nature of cell proliferation in blood and vessels of patients with LVV compared non-inflammatory aorta by using double immunostaining, western blot and flow cytometry. Finally, using flow cytometry, we study the effect of rapamycin on T cells homeostasis in LVV compared to HD. <h3>Results</h3> Proliferation of both endothelial cells and vascular smooth-muscle cells was shown in vascular lesions in LVV. The vascular endothelium of proliferating aorta vessels from patients with LVV showed indications of activation of the mTORC1 pathway en endothelial cells (S6RP phosphorylation) compared to non-inflammatory aorta (45%<sup>24;48</sup> versus 10.4% [9.7;14.9] positive S6RP endothelial cells, p=0.03). In cultured vascular endothelial cells, sera from patients with LVV stimulated mTORC1 through the phosphorylation of S6RP. Activation of mTORC1 was also found in Th1 and Th17 cells both systemically and in the blood vessels. Patients with LVV exhibited a diminished S6RP phosphorylation in Tregs. Inhibition of mTORC1 pathway with rapamycin, increase Tregs and decrease effector CD4<sup>+</sup>IFNγ<sup>+</sup>, CD4<sup>+</sup>IL17<sup>+</sup> and CD4<sup>+</sup>IL21<sup>+</sup> T cells in patients with LVV. <h3>Conclusions</h3> Our results suggest that the mTORC1 pathway is involved in the vascular lesions of LVV. Targeting mTORC pathway may represent a new therapeutic option in patients with LVV. <h3>Disclosure of Interest</h3> None declared
Caffeine Protects Skin from Oxidative Stress-Induced Senescence through the Activation of Autophagy
Authors: Yi-Fang Li, Shu-Hua Ouyang, Long-Fang Tu, Xi Wang, Wei-Lin Yuan, Guo-En Wang, Yan-Ping Wu, Wen-Jun Duan, Hong-Min Yu, Zhong-Ze Fang, Hiroshi Kurihara, Youwei Zhang, Rong-Rong He
Journal: Theranostics (2018)

Skin cells are vulnerable to oxidative stress-induced senescence, which may lead to abnormal aging or aging-related disorders. Therefore, strategies that can ameliorate oxidative stress-induced senescence are expected to protect skin from damage, holding the promise of treating skin diseases in the clinic. This study aims to investigate whether caffeine, a well-known purine alkaloid, is able to prevent skin from oxidative stress-induced senescence, and to explore the underlying molecular mechanisms. Methods: A free radical inducer 2,2'-Azobis (2-amidinopropane) dihydrochloride (AAPH) was used to induce oxidative stress and cellular senescence in both transformed skin cells and in normal human epidermal keratinocytes (NHEKs). Ultraviolet (UV) irradiation was established as the in vivo oxidative stress model in mouse skin tissues. Cellular senescence was determined by SA β-galactosidase staining, immunofluorescence and western blotting. Activation of autophagy was confirmed by western blotting, immunofluorescence, and transmission electron microscopy. Reactive oxygen species (ROS) detection by commercial kits, gene knockdown by RNA interference (RNAi) and receptor activation/inactivation by agonist/antagonist treatment were applied in mechanistic experiments. Results: We report that AAPH induced senescence in both transformed skin cells and in NHEKs. Similarly, UV irradiation induced senescence in mouse skin tissues. Remarkably, low dose of caffeine (<10 μM) suppressed cellular senescence and skin damage induced by AAPH or UV. Mechanistically, caffeine facilitated the elimination of ROS by activating autophagy. Using a combination of RNAi and chemical treatment, we demonstrate that caffeine activates autophagy through a series of sequential events, starting from the inhibition of its primary cellular target adenosine A2a receptor (A2AR) to an increase in the protein level of Sirtuin 3 (SIRT3) and to the activation of 5' adenosine monophosphate-activated protein kinase (AMPK). Oral administration of caffeine increased the protein level of SIRT3, induced autophagy, and reduced senescence and tissue damage in UV-irradiated mouse skin. On the other hand, co-administration with autophagy inhibitors attenuated the protective effect of caffeine on UV-induced skin damage in mice. Conclusion: The results reveal that caffeine protects skin from oxidative stress-induced senescence through activating the A2AR/SIRT3/AMPK-mediated autophagy. Our study not only demonstrated the beneficial effect of caffeine using both in vitro and in vivo models, but also systematically investigated the underlying molecular mechanisms. These discoveries implicate the potential of caffeine in the protection of skin disease.
Abstract 20846: The Impact of a Palliative Care Intervention on Polypharmacy in Advanced HF: Results From Pal-HF
Authors: Bradi B Granger, Hongqiu Yang, Robert J Mentz, Daniel B Mark, Donald H Taylor, Karen E Steinhauser, Gwen C Dodson, Mona Fiuzat, Christopher M O'Connor, Kevin Anstrom, Robert Clare, Chet B Patel, James A Tulsky, Joseph G Rogers
Journal: Circulation (2017)

Introduction: Palliative care (PC) aims to improve symptoms and QOL in advanced HF, in part through medication management. However, the impact of PC on polypharmacy (≥5 medications) in advanced HF ...
Randomised, double-blind, placebo-controlled pilot trial of omeprazole in idiopathic pulmonary fibrosis
Authors: Prosenjit Dutta, Wendy Funston, Helen Mossop, Vicky Ryan, Rhys Jones, Rebecca Forbes, Shilpi Sen, Jeffrey Pearson, S Michael Griffin, Jaclyn A Smith, Christopher Ward, Ian A Forrest, A John Simpson
Journal: Thorax (2019)

Cough is a common, disabling symptom of idiopathic pulmonary fibrosis (IPF), which may be exacerbated by acid reflux. Inhibiting gastric acid secretion could potentially reduce cough. This study aimed to determine the feasibility of a larger, multicentre trial of omeprazole for cough in IPF, to assess safety and to quantify cough.Single-centre, double-blind, randomised, placebo-controlled pilot trial of the proton pump inhibitor (PPI) omeprazole (20 mg twice daily for 3 months) in patients with IPF. Primary objectives were to assess feasibility and acceptability of trial procedures. The primary clinical outcome was cough frequency.Forty-five participants were randomised (23 to omeprazole, 22 to placebo), with 40 (20 in each group) having cough monitoring before and after treatment. 280 patients were screened to yield these numbers, with barriers to discontinuing antacids the single biggest reason for non-recruitment. Recruitment averaged 1.5 participants per month. Geometric mean cough frequency at the end of treatment, adjusted for baseline, was 39.1% lower (95% CI 66.0% lower to 9.3% higher) in the omeprazole group compared with placebo. Omeprazole was well tolerated and adverse event profiles were similar in both groups, although there was a small excess of lower respiratory tract infection and a small fall in forced expiratory volume and forced vital capacity associated with omeprazole.A large randomised controlled trial of PPIs for cough in IPF appears feasible and justified but should address barriers to randomisation and incorporate safety assessments in relation to respiratory infection and changes in lung function.
Living with alopecia areata: an online qualitative survey study
Authors: L. Davey, V. Clarke, E. Jenkinson
Journal: British Journal of Dermatology (2018)

Living with alopecia areata (AA) totalis and universalis (collectively referred to here as AA) involves unpredictable, sometimes rapid hair loss. There is currently no effective treatment and patients describe feelings of shock, loss, trauma and disrupted identity. Cultural meanings attached to hair and hair loss, including associations between hair and femininity, and hair loss and cancer may exacerbate distress. Consequently, wigs and make-up are frequently used as camouflage, but this can produce feelings of inauthenticity, shame and anxiety.This article explores how meanings associated with hair and hair loss influence experiences of living with AA. We also aim to identify how this understanding might inform practice by healthcare professionals to best support patients to cope with the condition.A total of 95 participants with AA completed an online qualitative survey about their experiences of living with the condition. Data were subjected to thematic analysis within a critical realist theoretical framework.The following four themes were identified: (i) It's (not) only hair; (ii) A restricted life; (iii) Abandon hope all ye who lose their hair and (iv) Seeking support in 'a highly personal journey'.Findings suggest that negative cultural meanings of hair and hair loss are pervasive and may drive social avoidance and camouflage behaviours in people with AA. Normalizing social interactions with healthcare practitioners, significant others and peers were cited as pivotal to positive adjustment. Support groups and online forums were highly valued particularly as few had been offered specialist psychological support. Future research should develop and evaluate psychological support in order to address the specific challenges of living with AA.
Der p 1‐specific regulatory T‐cell response during house dust mite allergen immunotherapy
Authors: Tadech Boonpiyathad, Milena Sokolowska, Hideaki Morita, Beate Rückert, Jeannette I. Kast, Marcin Wawrzyniak, Atik Sangasapaviliya, Panitan Pradubpongsa, Rattanaporn Fuengthong, Pattarawat Thantiworasit, Sunee Sirivichayakul, William W. Kwok, Kiat Ruxrungtham, Mübeccel Akdis, Cezmi A. Akdis
Journal: Allergy (2018)

Allergen-specific immunotherapy (AIT) is the only available treatment for allergic diseases that can induce specific immune tolerance to allergens. The key mechanisms involved in this process include changes in allergen-specific regulatory T (Treg) cells.We studied 25 allergic rhinitis patients undergoing subcutaneous house dust mite-specific immunotherapy. Peripheral blood mononuclear cells were studied before and after 10, 30 weeks, and 3 years of AIT. Der p 1-specific T regulatory cell responses were investigated by characterization of Der p 1-MHC class II tetramer-positive cells and correlated with nasal symptom score.Twelve of 25 AIT patients matched with their MHC class II expression to the Der p 1 peptide-MHC class II tetramers. A significant increase in the numbers of Der p 1-specific FOXP3+ Helios+ CD25+ CD127- Treg cells after 30 weeks was observed, which slightly decreased after 3 years of AIT. In contrast, Der p 1-specific immunoglobulin-like transcript 3 (ILT3)+ CD25+ Treg cells decreased substantially from baseline after 3 years of AIT. ILT3+ Treg cells displayed compromised suppressive function and low FOXP3 expression. In addition, Der p 1-specific IL-10 and IL-22 responses have increased after 30 weeks, but only IL-10+ Der p 1-specific Treg cells remained present at high frequency after 3 years of AIT. Increased number of FOXP3+ Helios+ and IL-10+ and decreased ILT3+ Treg cell responses correlated with improved allergic symptoms.The results indicate that AIT involves upregulation of the activated allergen-specific Treg cells and downregulation of dysfunctional allergen-specific Treg cell subset. Correction of dysregulated Treg cells responses during AIT is associated with improved clinical response.