tbuckley/cabot-search huggingface dataset:
Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma
Authors: Mitchell J. Machiela, Jonathan N. Hofmann, Robert Carreras-Torres, Kevin M. Brown, Mattias Johansson, Zhaoming Wang, Matthieu Foll, Peng Li, Nathaniel Rothman, Sharon A. Savage, Valerie Gaborieau, James D. McKay, Yuanqing Ye, Marc Henrion, Fiona Bruinsma, Susan Jordan, Gianluca Severi, Kristian Hveem, Lars J. Vatten, Tony Fletcher, Kvetoslava Koppova, Susanna C. Larsson, Alicja Wolk, Rosamonde E. Banks, Peter J. Selby, Douglas F. Easton, Paul Pharoah, Gabriella Andreotti, Laura E. Beane Freeman, Stella Koutros, Demetrius Albanes, Satu Mannisto, Stephanie Weinstein, Peter E. Clark, Todd E. Edwards, Loren Lipworth, Susan M. Gapstur, Victoria L. Stevens, Hallie Carol, Matthew L. Freedman, Mark M. Pomerantz, Eunyoung Cho, Peter Kraft, Mark A. Preston, Kathryn M. Wilson, J. Michael Gaziano, Howard S. Sesso, Amanda Black, Neal D. Freedman, Wen-Yi Huang, John G. Anema, Richard J. Kahnoski, Brian R. Lane, Sabrina L. Noyes, David Petillo, Leandro M. Colli, Joshua N. Sampson, Celine Besse, Helene Blanche, Anne Boland, Laurie Burdette, Egor Prokhortchouk, Konstantin G. Skryabin, Meredith Yeager, Mirjana Mijuskovic, Miodrag Ognjanovic, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, Cezary Cybulski, Eleonora Fabianova, Viorel Jinga, Jolanta Lissowska, Jan Lubinski, Marie Navratilova, Peter Rudnai, Neonila Szeszenia-Dabrowska, Simone Benhamou, Geraldine Cancel-Tassin, Olivier Cussenot, H. Bas Bueno-de-Mesquita, Federico Canzian, Eric J. Duell, Börje Ljungberg, Raviprakash T. Sitaram, Ulrike Peters, Emily White, Garnet L. Anderson, Lisa Johnson, Juhua Luo, Julie Buring, I-Min Lee, Wong-Ho Chow, Lee E. Moore, Christopher Wood, Timothy Eisen, James Larkin, Toni K. Choueiri, G. Mark Lathrop, Bin Tean Teh, Jean-Francois Deleuze, Xifeng Wu, Richard S. Houlston, Paul Brennan, Stephen J. Chanock, Ghislaine Scelo, Mark P. Purdue
Journal: European Urology (2017)
How much should we spend on healthcare?
Authors: Fiona Godlee
Journal: BMJ (2017)

What's the right amount of spending on healthcare?And how does the UK's spending compare with that of its European neighbours?For a long time the view was that the UK spent less than the European average.But new estimates that are based on new accounting methods give a different picture.As John Appleby and Ben Gershlick explain (doi:10.1136/bmj.j3568),the new figure is 9.8% of GDP, which puts the UK ninth in the European Union league table and is pretty much bang on the EU average (though at the bottom end of the weighted average, if you're into the detail).
Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study
Authors: Martin J van den Bent, Brigitta Baumert, Sara C Erridge, Michael A Vogelbaum, Anna K Nowak, Marc Sanson, Alba Ariela Brandes, Paul M Clement, Jean Francais Baurain, Warren P Mason, Helen Wheeler, Olivier L Chinot, Sanjeev Gill, Matthew Griffin, David G Brachman, Walter Taal, Roberta Rudà, Michael Weller, Catherine McBain, Jaap Reijneveld, Roelien H Enting, Damien C Weber, Thierry Lesimple, Susan Clenton, Anja Gijtenbeek, Sarah Pascoe, Ulrich Herrlinger, Peter Hau, Frederic Dhermain, Irene van Heuvel, Roger Stupp, Ken Aldape, Robert B Jenkins, Hendrikus Jan Dubbink, Winand N M Dinjens, Pieter Wesseling, Sarah Nuyens, Vassilis Golfinopoulos, Thierry Gorlia, Wolfgang Wick, Johan M Kros
Journal: The Lancet (2017)
07.10 Psychological comorbidities associated with subclinical atherosclerosis in primary sjögren’s syndrome
Authors: Theofanis Karageorgas, Dimitrios Ioakeimidis, Clio P Mavragani
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Impaired sleep and psychological disorders are increasingly recognised as prevalent comorbidities in patients with primary Sjogren’s syndrome (pSS), as well as important contributors of atherosclerosis in the general population. In the current study we sought to explore a potential role of psychological comorbidities in the pronounced atherosclerotic risk of pSS patients. <h3>Methods</h3> 59 pSS patients fulfilling the ACR/EULAR criteria completed specific validated questionnaires assessing fatigue, depression, anxiety and sleep disturbances. Clinical, laboratory and histopathological characteristics together with traditional risk factors for atherosclerosis were documented in all enrolled patients. Subclinical atherosclerosis defined either as carotid and/or femoral plaque formation or increased Intima Media Thickness (IMT) levels were assessed by Doppler ultrasound. Univariate and multivariate analysis were performed. <h3>Results</h3> Plaque formation and high IMT levels were detected by ultrasound in 41 (69.5%) out of the 59 pSS patients. In univariate analysis, age and higher triglyceride serum levels were associated with both plaque formation and high IMT levels. Hypertension was associated only with high IMT levels. While increased rates of both state anxiety and impaired sleep were detected in pSS patients with plaque formation in a univariate model, only impaired sleep proved to be independently associated with plaque formation among pSS patients (OR=4.2, 95% CI=1.1–15.6, p=0.03). <h3>Conclusion</h3> This is the first study showing impaired sleep to confer a significantly higher risk of subclinical atherosclerosis in patients with pSS. Clinicians should take psychological disturbances into account when trying to assess and manage the cardiovascular disease risk of pSS patients. <h3>Grants/acknowledgements</h3> Dr. T. Karageorgas’ work was supported by a State Scholarship Foundation (IKY) Fellowship of Excellence for Postgraduate Studies in Greece-Siemens Programme.
THE INCIDENCE AND RISK FACTORS OF SHOULDER PAIN IN JUNIOR COMPETITIVE SWIMMERS
Authors: Yuta Suzuki, Yukio Urabe, Maeda Noriaki, Miho Morita, Toshiya Shima, Taizan Shirakawa
Journal: British Journal of Sports Medicine (2017)

Background The relationship between shoulder pain and shoulder flexibility has not been clarified because of different views regarding differences in age or competition level among research-targeted swimmers. Studies to date have hardly examined junior (aged 12 to 17) competitive swimmers. Objective To determine the risk factors related to shoulder pain and its prevention in junior competitive swimmers. Design A cross-sectional study. Setting Four swimming clubs belonging to the Hiroshima Prefecture Swimming Federation. Participants Eighty-one competitive swimmers (45 male and 36 female). Assessment of Risk Factors A self-administered questionnaire was used to investigate injury history with or without shoulder pain, years of swimming experience, and stroke specialty. To assess the effect of flexibility on shoulder pain, shoulder rotation width, latissimus dorsi flexibility, and internal rotation (IR) and external rotation (ER) angles in the second position were measured. Main Outcome Measurements Preliminary bivariate logistic regression analyses identified the aforementioned variables associated with shoulder pain, and variables with p values&lt;0.15 were retained for the multivariate analyses. The independent predictors of shoulder pain as well as odds ratios and 95% confidence intervals were calculated from the final logistic regression model. Results Of the 81 participants, 57 (70.4%) had competitive swimming–related pain. Among them, 28 (49.1%) had shoulder pain, the most prevalent pain type. Male swimmers with low IR angles and fewer years of swimming experience were at 1.06 and 1.42 times greater risk of shoulder pain, while female swimmers with low IR and wider shoulder rotation widths were at 1.02 and 1.07 times greater risk of shoulder pain, respectively. Conclusions This study showed that low shoulder flexibility were significantly associated with shoulder pain. To apply these findings practically to identify swimmers who may be at increased risk of developing shoulder pain and the use of proper preventive programs may prevent shoulder pain.
第2近赤外窓における強い吸収を有するPEG化Cu_3BiS_3三元半導体ナノロッドに基づく相乗的温熱放射線療法【Powered by NICT】
Authors: Li Ang, Li Xiang, Yu Xujiang, Li Wei, Zhao Ruyi, An Xiao, Cui Daxiang, Chen Xiaoyuan, Li Wanwan
Journal: Biomaterials (2017)
À long terme d’une série prospective de 46 patients porteurs d’un endo-brachyoesophage éradiqué par électrocoagulation par plasma d’argon et oméprazole
Authors: J Boyer, B Vielle, P Burtin, N Oberti, A de La Roche
Journal: Endoscopy (2004)

But: 1) Evaluer l’efficacité à long terme de l’éradication de l’endo-brachyoesophage (EBO) par électrocoagulation par plasma d’argon (APC) et oméprazole (OME) sur la prévention de la dysplasie et de l’adénocarcinome. 2) Apprécier les facteurs prédictifs de récidive de l’EBO après éradication. Patients et Méthodes: De mai 1995 à octobre 2000, 50 patients porteurs d’un EBO ont été inclus après information et consentement éclairé dans un protocole d’éradication par APC et OME puis de suivi à long terme après éradication complète endoscopique et histologique de l’EBO; 4 patients ont été exclus du protocole après échec d’éradication complète après 9 séances d’APC (n = 2) et décès survenus avant le premier contrôle endoscopique (n = 2). Parmi les 46 patients inclus (44 H, 2 F; âge moyen: 58,3 ± 11,9 ans), 5 patients avaient initialement une dysplasie de bas grade (DBG) et 14 une dysplasie de haut grade (DHG). Après éradication complète de l’EBO confirmée par endoscopie et biopsies, tous les patients recevaient un traitement d’OME 20 mg matin et soir; 13 patients étaient traités au cours du suivi par chirurgie anti reflux; en cas de récidive du RGO après chirurgie, l’OME était repris. Une surveillance endoscopique et histologique était effectuée tous les 6 mois; 4 biopsies étaient faites sur la ligne Z à chaque quadrant et sur d’éventuels ilôts ou languettes d’EBO, et 4 à 6 biopsies sur le bas ésophage dans les zones ré-épithélialisées; les récidives n’étaient pas éradiquées sauf en cas de DHG. Résultats: La moyenne de suivi était de 63,0 ± 18,4 mois; 17 patients ont présenté une récidive d’EBO ( 36,9%) dont 16 dans la première année de suivi; la hauteur maximale était de 10 mm et est restée stable tout au long du suivi; une métaplasie intestinale (MI) de la jonction oeso-gastrique était retrouvée chez 24 patients; une DBG était notée chez 4 d’entre eux ; des glandes en MI étaient retrouvées chez 4 patients dans le chorion du bas ésophage en zone ré-épithélialisée; aucune DHG ou adénocarcinome n’était retrouvée. En analyse univariée, une hernie hiatale (HH) > 3 cm, la non observance du traitement par OME, la persistance de signes cliniques de RGO, la survenue d’une oesophagite, la chirurgie anti-reflux, le score pH-métrique nocturne étaient significativement des signes prédictifs de récidives. En analyse multivariée, seules la HH > 3 cm et la non observance des IPP restaient significatives. En pH-métrie, le score pH-métrique nocturne était de 0,04 ± 0,14 en cas de non récidive et de 3,0 ± 4,1 en cas de récidive (p = 0,0001). Conclusion: L’éradication complète des EBO en DBG ou DHG par APC et OME suivie d’un traitement intensif du RGO est un traitement efficace dans la prévention de la DHG et adénocarcinome. Toutefois, ce traitement très astreignant ne peut être proposé qu’à des patients à haut risque de cancer, informés et motivés.
SP0027 Emerging therapies for osteoporosis
Authors: P Geusens
Journal: Annals of the Rheumatic Diseases (2017)

Currently, anti-resorptive drug therapy is the cornerstone of fracture prevention. Anti-resorptive drugs decrease bone remodelling, allowing the remaining bone to increase secondary mineralisation, and, with denosumab, also allowing periosteal bone modelling. Teriparatide is currently the only available bone-forming drug, which increases bone formation more than bone resorption, and has been shown to reduce the risk of vertebral and non-vertebral fractures. Recently, two randomized clinical trials have been published on the effect of new bone forming agents on the risk of fracture. Abaloparatide is a 1–34 fragment of PTHrP, with different pharmacokinetics and potential different signalling mechanisms compared to teriparatide. It increases bone formation more than bone resorption, both to a lesser degree than teriparatide. In the double blind, randomised placebo-controlled 18-month ACTIVE study, abaloparatide significantly reduced the risk of vertebral (-86%), clinical (-43%), non-vertebral (-43%) and major fractures (-70%). In a parallel randomised exploratory open-label comparison with teriparatide, bone density increased significantly more with abaloparatide, but the anti-fracture effect was similar, except for a significantly better result on prevention of major fractures. Romosozumab is a monoclonal antibody that binds sclerostin, which is an inhibitor of bone formation. In contrast to other bone forming agents, it disconnects the increase in bone formation from a decrease in bone resorption. In the double-blind placebo-controlled FRAME study, romosozumab significantly reduced the risk of vertebral (-63%) and clinical fractures (-36%) during the first year, an effect that was maintained by transitioning to one-year denosumab treatment. The effect on non-vertebral fractures was not significant, but geographic interaction was found. When excluding patients from South America, in whom fracture risk was low, one-year treatment with romosozumab significantly decreased the risk of non-vertebral fractures by 42%. Abaloparatide and romosozumab are new bone forming agents, with different effects on bone remodelling and remodelling and early effects on clinical fractures. This opens new perspectives in individualised treatment of patients with high fracture risk and for fracture prevention in patients with low bone turnover, multiple vertebral fractures, very low BMD and fractures or bone loss during anti-resorptive treatment. <h3>Disclosure of Interest</h3> P. Geusens Grant/research support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Roche, UCB, BMS, Novartis, Consultant for: Amgen
Valeur de l’échoendoscopie comme facteur pronostique de survie dans le cancer de l’oesophage
Authors: C Mariette, V Maunoury, G Taillier, JM Balon, JP Triboulet
Journal: Endoscopy (2004)

But: L’échoendoscopie (EE) est considérée comme le meilleur examen permettant l’évaluation de l’extension loco régionale du cancer de l’ésophage. Cette étude a cherché à évaluer la relation entre les données préopératoires de l’EE, la radicalité de l’exérèse chirurgicale et la survie. Patients et Méthodes: De janvier 1995 à juillet 2002, les données de 150 patients ayant bénéficié d’une EE dans le bilan pré-opératoire d’une tumeur de l’ésophage ont été analysées de façon prospective. Tous les patients ont bénéficié d’une chirurgie d’exérèse ésophagienne à visée curative, sans traitement néo-adjuvant. Aucun patient n’a été perdu de vue. Résultats: La survie des patients était significativement associée à l’envahissement tumoral (EE T, p = 0,003), ganglionnaire (EE N, p = 0,009), au stade tumoral (EE UICC, p = 0,004) et à la présence d’une sténose tumorale (p = 0,004), évalués en écho-endoscopie. Le stade EE T était un facteur de mauvais pronostique en analyse multivariée (risque relatif = 1,7 ; intervalle de confiance à 95% = 1,1–3,0; p = 0,046). Le caractère complet de la résection chirurgicale (R0) était significativement associé au stade EE T, EE N et EE UICC (p < 0,001). Le stade EE UICC était un facteur prédictif de résection R0 en analyse multivariée (risque relatif = 2,6; intervalle de confiance à 95% = 1,4–4,8; p = 0,003). Conclusion: La résection R0 et la survie des patients porteurs d’une tumeur ésophagienne étaient fortement liées aux données écho-endoscopiques. Ces résultats suggèrent que l’EE devrait être réalisée chez tous les patients atteints d’un cancer de l’ésophage, non seulement dans le cadre de l’évaluation de l’extension loco-régionale pré-opératoire mais également afin d’évaluer le pronostic.
Developmental origin and maintenance of distinct testicular macrophage populations
Authors: Noushin Mossadegh-Keller, Rebecca Gentek, Gregory Gimenez, Sylvain Bigot, Sebastien Mailfert, Michael H. Sieweke
Journal: The Journal of Experimental Medicine (2017)

Testicular macrophages (tMφ) are the principal immune cells of the mammalian testis. Beyond classical immune functions, they have been shown to be important for organogenesis, spermatogenesis, and male hormone production. In the adult testis, two different macrophage populations have been identified based on their distinct tissue localization and morphology, but their developmental origin and mode of homeostatic maintenance are unknown. In this study, we use genetic lineage–tracing models and adoptive transfer protocols to address this question. We show that embryonic progenitors give rise to the interstitial macrophage population, whereas peritubular macrophages are exclusively seeded postnatally in the prepuberty period from bone marrow (BM)–derived progenitors. As the proliferative capacity of interstitial macrophages declines, BM progenitors also contribute to this population. Once established, both the peritubular and interstitial macrophage populations exhibit a long life span and a low turnover in the steady state. Our observations identify distinct developmental pathways for two different tMφ populations that have important implications for the further dissection of their distinct roles in organ homeostasis and testicular function.
Retinoic acid and arsenic trioxide sensitize acute promyelocytic leukemia cells to ER stress
Authors: S Masciarelli, E Capuano, T Ottone, M Divona, S De Panfilis, C Banella, N I Noguera, A Picardi, G Fontemaggi, G Blandino, F Lo-Coco, F Fazi
Journal: Leukemia (2017)

Retinoic acid (RA) in association with chemotherapy or with arsenic trioxide (ATO) results in high cure rates of acute promyelocytic leukemia (APL). We show that RA-induced differentiation of human leukemic cell lines and primary blasts dramatically increases their sensitivity to endoplasmic reticulum (ER) stress-inducing drugs at doses that are not toxic in the absence of RA. In addition, we demonstrate that the PERK pathway, triggered in response to ER stress, has a major protective role. Moreover, low amounts of pharmacologically induced ER stress are sufficient to strongly increase ATO toxicity. Indeed, in the presence of ER stress, ATO efficiently induced apoptosis in RA-sensitive and RA-resistant APL cell lines, at doses ineffective in the absence of ER stress. Our findings identify the ER stress-related pathways as potential targets in the search for novel therapeutic strategies in AML.
Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis<i>ex vivo</i>
Authors: Mareike Lehmann, Martina Korfei, Kathrin Mutze, Stephan Klee, Wioletta Skronska-Wasek, Hani N. Alsafadi, Chiharu Ota, Rita Costa, Herbert B. Schiller, Michael Lindner, Darcy E. Wagner, Andreas Günther, Melanie Königshoff
Journal: European Respiratory Journal (2017)

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases with age, and ageing-related mechanisms such as cellular senescence have been proposed as pathogenic drivers. The lung alveolar epithelium represents a major site of tissue injury in IPF and senescence of this cell population is probably detrimental to lung repair. However, the potential pathomechanisms of alveolar epithelial cell senescence and the impact of senolytic drugs on senescent lung cells and fibrosis remain unknown. Here we demonstrate that lung epithelial cells exhibit increased P16 and P21 expression as well as senescence-associated β-galactosidase activity in experimental and human lung fibrosis tissue and primary cells. Primary fibrotic mouse alveolar epithelial type (AT)II cells secreted increased amounts of senescence-associated secretory phenotype (SASP) factors in vitro , as analysed using quantitative PCR, mass spectrometry and ELISA. Importantly, pharmacological clearance of senescent cells by induction of apoptosis in fibrotic ATII cells or ex vivo three-dimensional lung tissue cultures reduced SASP factors and extracellular matrix markers, while increasing alveolar epithelial markers . These data indicate that alveolar epithelial cell senescence contributes to lung fibrosis development and that senolytic drugs may be a viable therapeutic option for IPF.
Kidney Disease in HIV: Moving beyond HIV-Associated Nephropathy
Authors: Vasantha Jotwani, Mohamed G. Atta, Michelle M. Estrella
Journal: Journal of the American Society of Nephrology (2017)

In developed countries, remarkable advances in antiretroviral therapy have transformed HIV infection into a chronic condition. As a result, HIV-associated nephropathy, the classic HIV-driven kidney lesion among individuals of African descent, has largely disappeared in these regions. However, HIV-positive blacks continue to have much higher rates of ESRD than HIV-positive whites, which could be attributed to the APOL1 renal risk variants. Additionally, HIV-positive individuals face adverse consequences beyond HIV itself, including traditional risk factors for CKD and nephrotoxic effects of antiretroviral therapy. Concerns for nephrotoxicity also extend to HIV-negative individuals using tenofovir disoproxil fumarate–based pre-exposure prophylaxis for the prevention of HIV infection. Therefore, CKD remains an important comorbid condition in the HIV-positive population and an emerging concern among HIV-negative persons receiving pre-exposure prophylaxis. With the improved longevity of HIV-positive individuals, a kidney transplant has become a viable option for many who have progressed to ESRD. Herein, we review the growing knowledge regarding the APOL1 renal risk variants in the context of HIV infection, antiretroviral therapy–related nephrotoxicity, and developments in kidney transplantation among HIV-positive individuals.
Plasma asymmetrical-dimethyl-arginine (ADMA) as a regulator of vascular redox and nitric oxide bioavailability in human vessels
Authors: C Antoniades, C Shirodaria, P Leeson, D Tousoulis, R Pillai, C Ratnatunga, A Antonopoulos, T Van-Assche, C Stefanadis, K M Channon
Journal: Circulation (2007)