tbuckley/cabot-search huggingface dataset:
Killer cell immunoglobulin–like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1
Authors: Maureen P. Martin, Vivek Naranbhai, Patrick R. Shea, Ying Qi, Veron Ramsuran, Nicolas Vince, Xiaojiang Gao, Rasmi Thomas, Zabrina L. Brumme, Jonathan M. Carlson, Steven M. Wolinsky, James J. Goedert, Bruce D. Walker, Florencia P. Segal, Steven G. Deeks, David W. Haas, Stephen A. Migueles, Mark Connors, Nelson Michael, Jacques Fellay, Emma Gostick, Sian Llewellyn-Lacey, David A. Price, Bernard A. Lafont, Phillip Pymm, Philippa M. Saunders, Jacqueline Widjaja, Shu Cheng Wong, Julian P. Vivian, Jamie Rossjohn, Andrew G. Brooks, Mary Carrington
Journal: Journal of Clinical Investigation (2018)

HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected cells, but extensive heterogeneity exists in the level of HIV control among B*57+ individuals. Using whole-genome sequencing of untreated B*57+ HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only significant modifier of B*57 protection. The association was replicated in an independent cohort and across multiple outcomes. The modifying effect of I47V was confined to B*57:01 and was not observed for the closely related B*57:03. Positions 2, 47, and 54 tracked one another nearly perfectly, and 2 KIR3DL1 allotypes differing only at these 3 positions showed significant differences in binding B*57:01 tetramers, whereas the protective allotype showed lower binding. Thus, variation in an immune NK cell receptor that binds B*57:01 modifies its protection. These data highlight the exquisite specificity of KIR-HLA interactions in human health and disease.
Perspectives from a Pathologist: My Journey on the Path to Women's Health Research, Sex and Gender Policy, and Practice Implications
Authors: Vivian W. Pinn
Journal: Annual Review of Pathology Mechanisms of Disease (2018)

These words reflect my recollections of major transition points in my life and career: as I first became dedicated to becoming a physician, being introduced to the field of pathology and research, and then transitioning to a somewhat different career focus by becoming the first director of the National Institutes of Health Office of Research on Women's Health. Many of the experiences that I gained during my years in pathology served me well as I made efforts to establish women's health research and sex and gender based studies as scientific endeavors. Participating in research and teaching as an academic pathologist, setting funding priorities, and supporting and encouraging research careers through governmental office programs have been the essence of my more than 50 years as a pathologist and physician.
Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial
Authors: Sibylle Loibl, Joyce O'Shaughnessy, Michael Untch, William M Sikov, Hope S Rugo, Mark D McKee, Jens Huober, Mehra Golshan, Gunter von Minckwitz, David Maag, Danielle Sullivan, Norman Wolmark, Kristi McIntyre, Jose J Ponce Lorenzo, Otto Metzger Filho, Priya Rastogi, W Fraser Symmans, Xuan Liu, Charles E Geyer
Journal: The Lancet Oncology (2018)
Structural Plasticity in Adulthood with Motor Learning and Stroke Rehabilitation
Authors: Cassandra Sampaio-Baptista, Zeena-Britt Sanders, Heidi Johansen-Berg
Journal: Annual Review of Neuroscience (2018)

The development of advanced noninvasive techniques to image the human brain has enabled the demonstration of structural plasticity during adulthood in response to motor learning. Understanding the basic mechanisms of structural plasticity in the context of motor learning is essential to improve motor rehabilitation in stroke patients. Here, we review and discuss the emerging evidence for motor-learning-related structural plasticity and the implications for stroke rehabilitation. In the clinical context, a few studies have started to assess the effects of rehabilitation on structural measures to understand recovery poststroke and additionally to predict intervention outcomes. Structural imaging will likely have a role in the future in providing measures that inform patient stratification for optimal outcomes.
Brain Feeding Circuits after Roux-en-Y Gastric Bypass
Authors: Mohammed K. Hankir, Florian Seyfried, Alexander D. Miras, Michael A. Cowley
Journal: Trends in Endocrinology and Metabolism (2018)

HighlightsWeight loss after RYGB is attributable to multifaceted changes in feeding behavior in humans and animal models.Several feeding-regulatory neurotransmitter/neuromodulator systems have consistently been shown to be targeted by RYGB surgery in humans and animal models.The melanocortin 4 receptor (MC4R) and 5-hydroxytryptamine 2A (5-HT2A) receptor both positively modulate postoperative weight loss, indicating that appetite-suppressing, hypothalamic proopiomelanocortin (POMC) and dorsal raphe serotonergic pathways, respectively, are enhanced.Striatal function and brain μ-opioid receptor (MOR) signaling are lowered postoperatively, indicating that mesolimbic dopaminergic and brain opioidergic pathways, which promote palatable food intake, are suppressed.Gut hormones, microbiota products, and leptin likely generate this post-RYGB brain state.AbstractMetabolic surgical procedures, such as Roux-en-Y gastric bypass (RYGB), uniquely reprogram feeding behavior and body weight in obese subjects. Clinical neuroimaging and animal studies are only now beginning to shed light on some of the underlying central mechanisms. We present here the roles of key brain neurotransmitter/neuromodulator systems in food choice, value, and intake at various stages after RYGB. In doing so, we elaborate on how known signals emanating from the reorganized gut, including peptide hormones and microbiota products, impinge on newly mapped homeostatic and hedonic brain feeding circuits. Continued progress in the rapidly evolving field of metabolic surgery will inform the design of more effective weight-loss compounds.
Screening for Ovarian Cancer
Authors: Jill Jin
Journal: JAMA (2018)

US Preventive Services Task Force; David C. Grossman, MD, MPH; Susan J. Curry, PhD; Douglas K. Owens, MD, MS; Michael J. Barry, MD; Karina W. Davidson, PhD, MASc; Chyke A. Doubeni, MD, MPH; John W. Epling Jr, MD, MSEd; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Ann E. Kurth, PhD, RN, MSN, MPH; C. Seth Landefeld, MD; Carol M. Mangione, MD, MSPH; Maureen G. Phipps, MD, MPH; Michael Silverstein, MD, MPH; Melissa A. Simon, MD, MPH; Chien-Wen Tseng, MD, MPH, MSEE
Qualité, tolérance et acceptabilité de la gastroscopie. Etude prospective
Authors: I Tahri, W Khannoussi, G Kharrasse, I Zahi, A El Mekkaoui
Journal: Endoscopy (2018)

La fibroscopie oesogastroduodénale est l'examen le plus performant en matière d'exploration du tractus digestif haut. Toutefois, cet examen peut être anxiogène et source d'inconfort pour le patient, pouvant ainsi pénaliser la qualité de la procédure. Le but de cette étude est de rapporter le vécu de la FOGD par les patients et d'apprécier la tolérance du geste.
Abstract 15897: Identification of Candidates for Novel Interatrial Shunt Devices Through Non-invasive Testing in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Ajay Yadlapati, Debra Dixon, Lauren Beussink-Nelson, Mark Gajjar, Sumeet S Mitter, Sanjiv J Sanjiv
Journal: Circulation (2015)

Introduction: Interatrial shunt devices (IASD) are a novel therapeutic option for heart failure and preserved ejection fraction (HFpEF). IASDs work by decompressing the overloaded left atrium (LA) via shunting of blood to the right atrium (RA). Thus, optimal candidates for the IASD intervention will have an elevated pressure gradient between the LA and RA. We hypothesized that increased LA-RA gradient could be diagnosed non-invasively by echo. Methods: A total of 293 consecutive patients with HFpEF who also underwent invasive hemodynamic testing were were identified. All patients underwent comprehensive echo, including tissue Doppler. Patients were categorized into 2 groups based on the LA-RA pressure gradient (PCWP-RA pressure) at time of invasive hemodynamic testing (PCWP-RAP &gt; 10 mmHg [large pressure gradient] vs. PCWP 0-5 mmHg [low pressure gradient]), and clinical, laboratory, and echocardiography parameters were compared between groups. Results: Mean age was 64±12 years, 59% were female, 36% were African American, and comorbidities were common. Of the 293 patients, n=58 had PCWP-RAP gradient of 0-5 mmHg and n=114 had PCWP-RAP &gt; 10 mmHg, with the rest of the patients (n=56) in the PCWP-RAP 5-10 mmHg range. Patients with an elevated PCWP-RAP gradient were more often female and obese and less likely to have a history of atrial fibrillation (Table). On echocardiography, the 2 parameters that were most different between groups were TAPSE and lateral e’ velocity such that an elevated ratio of TAPSE to lateral e’ velocity identified patients with HFpEF who were most likely to have an elevated PCWP-RAP gradient &gt; 10 mmHg (area under the ROC curve = 0.69 [95% CI 0.60-0.78]; P=0.001). Conclusions: An elevated TAPSE/lateral e’ velocity ratio on echo in HFpEF is associated with invasive PCWP-RAP gradient &gt; 10 mmHg at rest and may aid in the identifying suitable HFpEF candidates who would benefit from an IASD.
P084 Poroinflammatory environment in RA and OA strongly influences adipose tissue activity
Authors: M Plebanczyk, A Radzikowska, U Musialowicz, I Janicka, A Kornatka, W Maslinski, E Kontny
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Rheumatoid arthritis (RA) and osteoarthritis (OA) are inflammatory diseases leading to joint destruction and disability. Apart from joint inflammation they are characterised by high-grade (RA) or low-grade (OA) systemic inflammation. Thus, it is possible that proinflammatory environment affect not only articular (AAT), but also subcutaneous adipose tissue (ScAT) activity. <h3>Objectives</h3> The aim of present work was to compare reactivity of AAT and ScAT from RA and OA patients to proinflammatory stimulus. <h3>Methods</h3> AAT and ScAT explants, obtained from OA (n=44) and RA (n=43) patients during knee joint replacement surgery, were cultured (100 mg/ml) for 24 hours in medium (DMEM) alone or in the presence of proinflammatory IL-1β (1 ng/ml), known to be overproduced in inflamed joint. Concentrations of cytokines (proinflammatory IL-6 and TNF, anti-inflammatory IL-1Ra, IL-10, TGFβ), chemokines (CCL2, CCL5) and metalloproteinase MMP-3 were measured in culture supernatants by ELISA. OA patients were treated with non-steroidal anti-inflammatory drugs while RA patients were given disease modifying drugs and/or glucocorticosteroids. Data were analysed as stimulation to control ratio (IS, index of stimulation) using Mann-Whitney U test and are expressed as median. <h3>Results</h3> In OA the levels of secreted factors were usually significantly higher in AAT, but ScAT was characterised by significantly higher increase of IL-6 (IS=16.4), TGFβ (IS=2.0), CCL2 (IS=1.8), and MMP-3 (IS=9.9) production than AAT (IS=70.3; 1.3; 1.3; 2.4 respectively). The up-regulation of other cytokines was similar in both tissues. By contrast, in AAT and ScAT from RA patients IL-1b-triggered increase of all tested factors secretion was similar. Moreover, upon IL-1b treatment the up-regulation of IL-6 (IS=13188) and MMP-3 (IS=9,1) in AAT of RA patients as well as of CCL2 from rheumatoid AAT (IS=3.2) and ScAT (IS=3.7) was significantly higher than in OA tissues (IS=70.3; 2.4; 1.3; 1.8 respectively). <h3>References</h3> We report that in OA ScAT, exposed <i>in vivo</i> to low-grade inflammation, retains higher reactivity to proinflammatory stimulus than AAT located in chronic high-grade inflammation. In RA, however, reactivity of both adipose tissue is rather similar but in the case of secretion of some factors (CCL2 and/or IL-6, MMP-3) higher than in OA, reflecting more destructive character of this disease. <h3>Acknowledgements</h3> This work was funded by the National Science Centre (grant number 2012/N/NZ5/00074). <h3>Disclosure of interest</h3> None declared
False Information About Breast Cancer Screening
Authors: Daniel B. Kopans
Journal: JAMA Internal Medicine (2018)

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Traitement endoscopique des diverticules de Zenker: techniques alternatives à la diverticulotomie assistée par diverticuloscope
Authors: B Brieau, M Barret, S Leblanc, B Bordacahar, S Ribière, C Leandri, MA Guillaumot, R Coriat, F Prat, S Chaussade
Journal: Endoscopy (2018)

Le diverticule de Zenker est une pathologie rare, prédominant chez les sujets âgés, concernant moins de 0,5% de la population, et se manifestant par une dysphagie. Actuellement, la diverticulotomie assistée par un diverticuloscope est la procédure standard, permettant l'exposition du «septum diverticulaire» entre le diverticule et l'oesophage. Le risque principal de ce traitement est la perforation avec son risque de médiastinite, rapportée chez environ 6,5% des patients et une section incomplète du septum source de récidive. Enfin, le positionnement du diverticuloscope est dans certains cas difficile, voire impossible. Outre les techniques chirurgicales ou par endoscopie rigide, il existe des procédures alternatives avec les endoscopes flexibles, telles que la nouvelle technique de dissection du septum par tunnelisation endoscopique (1) ou la dissection au capuchon (2).
Un tableau unique mixant les critères diagnostics validés est efficace pour améliorer la caractérisation et le choix thérapeutique chez les internes de gastroentérologie français: la classification CONECCT
Authors: M Pioche, J Jacques, J Rivory, M Fabritius, X Dray, L Brenet-Defour, E Coron, J Branche, JM Gonzalez, C Lepage, L Poincloux, JC Saurin, V Lepilliez, T Ponchon
Journal: Endoscopy (2018)

La caractérisation endoscopique des lésions néoplasiques colorectales est un élément clef pour choisir en cours de coloscopie la meilleure thérapeutique pour le patient. Cette caractérisation repose sur 5 classifications actuellement, difficiles à combiner pour les non-experts. Nous avons donc mixé les critères validés dans une classification unique (CONECCT) pour simplifier la prédiction histologique et le choix thérapeutique. Cette étude visait à mesurer le bénéfice de cette classification pour la caractérisation.
Endoscopies digestives à KInshasa (RDC): Pratique de l'endoscopie digestive interventionnelle. Etude multicentrique retrospective
Authors: A Tshimpi, P Phaka, T Ndarabu, A Nkodila, JR Makulo, H Situakibanza, JM Kayembe, R Matanda, S Mbendi
Journal: Endoscopy (2018)

Une étude menée en 2013 montrait que l'endoscopie digestive était peu pratiquée en RDC (1). La pratique de l'endoscopie interventionnelle semble encore plus exceptionnelle. Le but de cette étude multicentrique était de déterminer le nombre d'endoscopies digestives réalisées dans la ville province de Kinshasa et la proportion de l'endoscopie digestive interventionnelle.
Potentially Functional Variants of ATG16L2 Predict Radiation Pneumonitis and Outcomes in Patients with Non–Small Cell Lung Cancer after Definitive Radiotherapy
Authors: Juyi Wen, Hongliang Liu, Lili Wang, Xiaomeng Wang, Ning Gu, Zhensheng Liu, Ting Xu, Daniel R. Gomez, Ritsuko Komaki, Zhongxing Liao, Qingyi Wei
Journal: Journal of Thoracic Oncology (2018)
Afterload Hypersensitivity in Patients With Left Bundle Branch Block
Authors: John Aalen, Petter Storsten, Espen W Remme, Per A Sirnes, Ola Gjesdal, Camilla K Larsen, Erik Kongsgaard, Espen Boe, Helge Skulstad, Jonny Hisdal, Otto A Smiseth
Journal: JACC. Cardiovascular imaging (2018)
CCL2/CCL5 secreted by the stroma induce IL-6/PYK2 dependent chemoresistance in ovarian cancer
Authors: Jennifer Pasquier, Marie Gosset, Caroline Geyl, Jessica Hoarau-Véchot, Audrey Chevrot, Marc Pocard, Massoud Mirshahi, Raphael Lis, Arash Rafii, Cyril Touboul
Journal: Molecular Cancer (2018)

Minimal residual disease is the main issue of advanced ovarian cancer treatment. According to the literature and previous results, we hypothesized that Mesenchymal Stromal Cells (MSC) could support this minimal residual disease by protecting ovarian cancer cells (OCC) from chemotherapy. In vitro study confirmed that MSC could induce OCC chemoresistance without contact using transwell setting. Further experiments showed that this induced chemoresistance was dependent on IL-6 OCC stimulation. We combined meticulous in vitro profiling and tumor xenograft models to study the role of IL-6 in MSC/OCC intereactions. We demonstrated that Tocilizumab® (anti-IL-6R therapy) in association with chemotherapy significantly reduced the peritoneal carcinosis index (PCI) than chemotherapy alone in mice xenografted with OCCs+MSCs. Further experiments showed that CCL2 and CCL5 are released by MSC in transwell co-culture and induce OCCs IL-6 secretion and chemoresistance. Finally, we found that IL-6 induced chemoresistance was dependent on PYK2 phosphorylation. These findings highlight the potential key role of the stroma in protecting minimal residual disease from chemotherapy, thus favoring recurrences. Future clinical trials targeting stroma could use anti-IL-6 therapy in association with chemotherapy.
Abstract P062: Cardiovascular Health Awareness Among School Children in the Rural District of Midnapore, India: A School-Based Survey
Authors: Madhab Ray
Journal: Circulation (2015)

Introduction: India is the second most populous country in the world with two thirds of the population in their youth. With economic development and adoption of a western lifestyle, a large number of people in India will be affected by cardiovascular disease (CVD). As atherosclerosis starts in the second decade of life and many of the risk factors are better controlled if addressed early, health awareness among the school children assumes a central role for primary prevention. Currently, there is no established school health program for health education about CVD in India. This survey was conducted to assess the present level of health awareness about CVD in the adolescent school children with a goal to establish school-based health education, early detection of different risk factors and development of heart healthy lifestyle. Methods: A school-based survey was conducted between 15 th of June and 15 th of July, 2014 as a joint venture of Tufts University, USA and Kolkata Medical College, India in the rural district of Midnapore, India with approval from the IRB of Tufts University and the local ethics committee. This involved a pre-test with 20 questions each having 5 statements, a power point presentation by a physician of the study team, and a post-test using the same questions. The data were analyzed by the cluster sampling design method. Results: Nine hundred and fifty nine students (32 %) participated in the survey out of a target population of 3003 from 11 schools with a mean age 14.5 years, 58% male, 59% grade IX and 41% grade X. Prevalence of known CAD among the parents (as reported by the students) was 3% and current history of smoking (26%) was the predominant risk factor, while other identified risk factors were less common (hypertension 5%, diabetes mellitus 4%, and hyperlipidemia 3%). In the pretest evaluation, the mean score was 41/100 (IQR 33-48 and SD ± 10.5) with an improvement by 7% in the post test results (IQR 36-59, SD ± 16.9). This improvement was highly significant by Wilcoxon signed rank test with continuity correction (p &lt;0.001). A multivariable regression analysis showed family history of hypertension (p = 0.01) and higher parental education (p = 0.02) were the main determinants for an improved score. Conclusions: Cardiovascular health awareness was modest among the adolescent school children in the population under study. A school-based educational program may help improve awareness and reduce disease burden in this community.
Characterizing the Geographic Distribution of the Alpha-gal Syndrome: Relevance to Lone Star Ticks ( Amblyomma americanum ) and Rickettsia
Authors: Thomas A.E. Platts-Mills, Alexander J. Schuyler, Scott P. Commins, Tina K. Merritt, Erin E. McGintee, Hayley James, Lisa J. Workman, Jeffrey M. Wilson
Journal: Journal of Allergy and Clinical Immunology (2018)
DSM contre RME dans les tumeurs duodénales superficielles non ampullaires: revue systématique et méta-analyse incluant une expérience locale
Authors: E Perez-Cuadrado-Robles, L Quénéhervé, W Margos, TG Moreels, H Piessevaux, E Coron, A Jouret-Mourin, P Deprez
Journal: Endoscopy (2018)

La dissection sous-muqueuse endoscopique (DSM) a été développée comme une option pour le traitement des lésions oesophagiennes, gastriques et colorectales. Cependant, il n'y a pas de consensus sur le rôle de la DSM dans les tumeurs duodénales.
ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors)
Authors: M. Reinwald, J.T. Silva, N.J. Mueller, J. Fortún, C. Garzoni, J.W. de Fijter, M. Fernández-Ruiz, P. Grossi, J.M. Aguado
Journal: Clinical Microbiology and Infection (2018)
Correlation between Topographic Distribution of Aortic Valve Calcium and Hemodynamic Repercussion in Aortic Stenosis
Authors: Antonio S. de Santis, Flavio Tarasoutchi, Guilherme Spina, Vitor Rosa, Tarso Accorsi, Joao Fernandes, Cesar Nomura, Marcelo Vieira, Roney Sampaio, Max Grinberg
Journal: Circulation (2013)
Proteomic Profiling Reveals Targetable Pathways in MGUS (SLAMF6, TNFRSF8, TIMP1, TRL2) That May Contribute to Disease Progression
Authors: Tineke Casneuf, Volha Tryputsen, Homer Adams, Andrew Lysaght, A. Kate Sasser, Robert A Kyle, S. Vincent Rajkumar, Shaji K Kumar
Journal: Blood (2017)
Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children
Authors: Massimo Pifferi, Andrew Bush, Michele Rizzo, Alessandro Tonacci, Maria Di Cicco, Martina Piras, Fabrizio Maggi, Giulia Paiola, Angela Michelucci, Angela Cangiotti, Diego Peroni, Davide Caramella, Attilio L Boner
Journal: Thorax (2018)

Cilia have multiple functions including olfaction. We hypothesised that olfactory function could be impaired in primary ciliary dyskinesia (PCD). Olfaction, nasal nitric oxide (nNO) and sinus CT were assessed in patients with PCD and non-PCD sinus disease, and healthy controls (no CT scan). PCD and non-PCD patients had similar severity of sinus disease. Despite this, defective olfaction was more common in patients with PCD (P&lt;0.0001) and more severe in patients with PCD with major Transmission Electron Microscopy (TEM) abnormalities. Only in classical PCD did olfaction inversely correlate with sinusitis and nNO. We speculate that defective olfaction in PCD is primary in nature.