tbuckley/cabot-search huggingface dataset:
The end of family therapy for self-harm, or a new beginning?
Authors: Dennis Ougrin, Joan R Asarnow
Journal: The Lancet Psychiatry (2018)

Another randomised trial, the Self-Harm Intervention: Family Therapy (SHIFT) trial,1 has shown no benefit for another psychological therapy versus treatment as usual in adolescents who have self-harmed. Furthermore, in the study by David Cottrell and colleagues1 in The Lancet Psychiatry, rates of self-harm repetition were high across the family therapy and treatment as usual groups. These disappointing results have notable implications for future research in the field of adolescent self-harm.
Abstract 12243: A Contemporary Analysis of Predictors of Mortality in Patients With Heart Failure and Preserved Ejection Fraction From the National Inpatient Sample 2014 Database
Authors: Chayakrit Krittanawong, Bing Yue, Hafeez Ul Hassan Virk, HongJu J Zhang, Syed W Haider, Takeshi Kitai, W.H. Wilson Tang
Journal: Circulation (2017)

Introduction: There are limited data regarding the predictors of mortality in patients with heart failure and preserved ejection fraction (HFpEF). Hypothesis: We aim to study the impact of predicto...
Simultaneous sequencing of 37 genes identified causative mutations in the majority of children with renal tubulopathies
Authors: Emma J. Ashton, Anne Legrand, Valerie Benoit, Isabelle Roncelin, Annabelle Venisse, Maria-Christina Zennaro, Xavier Jeunemaitre, Daniela Iancu, William G. van’t Hoff, Stephen B. Walsh, Nathalie Godefroid, Annelies Rotthier, Jurgen Del Favero, Olivier Devuyst, Franz Schaefer, Lucy A. Jenkins, Robert Kleta, Karin Dahan, Rosa Vargas-Poussou, Detlef Bockenhauer
Journal: Kidney International (2018)
Cell‐mediated immunity assessed by skin testing (Multitest®)
Authors: F. Moesgaard, M. Lykkegaard Nielsen, P. Nørgaard Larsen, S. Christophersen, H. Mosbech
Journal: Allergy (1988)

In 60 healthy adult volunteers and 58 patients with gastrointestinal disease a test system (Multitest®) consisting of a plastic disposable multiple‐puncture device capable of simultaneously applying seven delayed‐type hypersensitivity antigens and a glycerin/saline diluent (negative control) was assessed. The Multitest device was applied on both the inner side of the forearm and on the back for assessment of cell‐mediated immunity (CMI). The antigens used were two toxoids, tetanus and diphtheria, three bacterial antigens. Streptococcus, tuberculin and Proteus and two fungal antigens, Candida and Trichophyton. A scoring system based on both number and size of positive response revealed a median “score” on arm and back of 19 mm and 14 mm respectively, in the healthy volunteers and a median “score” of 12 mm and 8 mm respectively in patients with gastrointestinal disease. In both groups a significant difference was found between back and arm (P &lt; 0.01). The coefficient of determination (r 2 ) shows that only 64% of the variability in scores on the back is explained by the regression line. Therefore, scores obtained from tests on the back cannot be interpreted with reference to normal values originating from tests applied to the inner side of the forearm
Principles for a Framework for Alternative Payment Models
Authors: Sam Nussbaum, Mark McClellan, Grischa Metlay
Journal: JAMA (2018)

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Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study
Authors: Jeanne Tie, Joshua D Cohen, Yuxuan Wang, Lu Li, Michael Christie, Koen Simons, Hany Elsaleh, Suzanne Kosmider, Rachel Wong, Desmond Yip, Margaret Lee, Ben Tran, David Rangiah, Matthew Burge, David Goldstein, Madhu Singh, Iain Skinner, Ian Faragher, Matthew Croxford, Carolyn Bampton, Andrew Haydon, Ian T Jones, Christos S Karapetis, Timothy Price, Mary J Schaefer, Jeanne Ptak, Lisa Dobbyn, Natallie Silliman, Isaac Kinde, Cristian Tomasetti, Nickolas Papadopoulos, Kenneth Kinzler, Bert Volgestein, Peter Gibbs
Journal: Gut (2018)

For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC.We enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4-10 weeks after surgery. Somatic mutations in individual patient's tumour were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. We then designed personalised assays to quantify ctDNA in plasma samples. Patients received adjuvant therapy at clinician discretion, blinded to the ctDNA results.We analysed 462 serial plasma samples from 159 patients. ctDNA was detectable in 77%, 8.3% and 12% of pretreatment, postchemoradiotherapy and postsurgery plasma samples. Significantly worse recurrence-free survival was seen if ctDNA was detectable after chemoradiotherapy (HR 6.6; P<0.001) or after surgery (HR 13.0; P<0.001). The estimated 3-year recurrence-free survival was 33% for the postoperative ctDNA-positive patients and 87% for the postoperative ctDNA-negative patients. Postoperative ctDNA detection was predictive of recurrence irrespective of adjuvant chemotherapy use (chemotherapy: HR 10.0; P<0.001; without chemotherapy: HR 22.0; P<0.001). Postoperative ctDNA status remained an independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors (HR 6.0; P<0.001).Postoperative ctDNA analysis stratifies patients with LARC into subsets that are either at very high or at low risk of recurrence, independent of conventional clinicopathological risk factors. ctDNA analysis could potentially be used to guide patient selection for adjuvant chemotherapy.
JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental study
Authors: Javier Milara, Beatriz Ballester, Anselm Morell, José L Ortiz, Juan Escrivá, Estrella Fernández, Francisco Perez-Vizcaino, Angel Cogolludo, Enrique Pastor, Enrique Artigues, Esteban Morcillo, Julio Cortijo
Journal: Thorax (2018)

Background Pulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends a poor prognosis. Recent studies using vasodilators approved for PH have failed in improving IPF mainly due to ventilation ( V )/perfusion ( Q ) mismatching and oxygen desaturation. Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown. Objective The study of JAK2 as potential target to treat PH in IPF. Methods and results JAK2 expression was increased in pulmonary arteries (PAs) from IPF (n=10; 1.93-fold; P=0.0011) and IPF+PH (n=9; 2.65-fold; P&lt;0.0001) compared with PA from control subjects (n=10). PA remodelling was evaluated in human pulmonary artery endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells (HPASMCs) from patients with IPF in vitro treated with the JAK2 inhibitor JSI-124 or siRNA-JAK2 and stimulated with transforming growth factor beta. Both JSI-124 and siRNA-JAK2 inhibited the HPAEC to mesenchymal transition and the HPASMCs to myofibroblast transition and proliferation. JAK2 inhibition induced small PA relaxation in precision-cut lung slice experiments. PA relaxation was dependent of the large conductance calcium-activated potassium channel (BK Ca ). JAK2 inhibition activated BK Ca channels and reduced intracellular Ca 2+ . JSI-124 1 mg/kg/day, reduced bleomycin-induced lung fibrosis, PA remodelling, right ventricular hypertrophy, PA hypertension and V / Q mismatching in rats. The animal studies followed the ARRIVE guidelines. Conclusions JAK2 participates in PA remodelling and tension and may be an attractive target to treat IPF associated to PH.
Erratum to: Corrigendum to “Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma”
Authors: Wei-Tien Tai, Ann-Lii Cheng, Chung-Wai Shiau, Hsiang-Po Huang, Jui-Wen Huang, Pei-Jer Chen, Kuen-Feng Chen
Journal: Journal of Hepatology (2017)
A Novel Method for Highly Sensitive Detection and Isolation of Chimeric Antigen Receptor and Cancer Associated Antigen-Expressing Cells
Authors: Ramakrishnan Gopalakrishnan, Hittu Matta, Sunju Choi, Venkatesh Natarajan, Ruben Prins, Songjie Gong, Arta Zenunovic, Nell Narasappa, Fatima Patel, Rekha Prakash, Varun Sikri, Saurabh Deepak Chitnis, Dan Wang, Vishan Chaudhary, Magdalena Falat, Michael Kahn, Naman Sharma, Jyotirmayee Lenka, Tomas Meza Stieben, Gabrielle Tulabot, Jason Braun, Pushti Bhagat, Ankita Batra, Katelyn Purvis, Johnny Lee, Kenta Ito, Preet M. Chaudhary
Journal: Blood (2017)
‘Reversing type 2 diabetes starts with ignoring the guidelines’: education from Dr Sarah Hallberg’s TEDx talk
Authors: Sarah Hallberg
Journal: British Journal of Sports Medicine (2018)

When I was preparing this talk for TEDx Purdue in 2015, I had no idea it would be viewed over 2.8 million times . I firmly believe the reaction to this talk is an expression of people being fed up . Fed up with the status quo . Fed up with listening to the advice they were given only to get worse . Fed up with yet another prescription bringing another side effect and more costs . Fed up and looking for advice that is not only evidence-based ,1–11 but also doable. Fed up and searching for a way to escape the progressive cycle of type 2 diabetes . Here it is . A solution that goes back to the basics and remembers that we can and should use Food as Medicine .

I have the best job in the world. I’m a doctor… believe me that’s not why. I am an obesity doctor. I have the honour to work with a group of people subject to the last accepted prejudice…being fat. These patients have suffered a lot by the time they come to see me - shame, guilt, blame and outright discrimination. The attitude most people take, including those in healthcare, is that these people are to blame for their situation. If they could just control themselves they would not be overweight. They are not motivated to change. Please let me tell you; that is not the case. The real blame, if we need to assign some, has been our advice and it’s time to change that. 

Obesity is a disease, not something created by lack of character. It is a hormonal disease. There are many hormones involved, and one of the main ones is a hormone called insulin. The vast majority of obese individuals are resistant to insulin and …
Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis
Authors: Jennifer L McQuade, Carrie R Daniel, Kenneth R Hess, Carmen Mak, Daniel Y Wang, Rajat R Rai, John J Park, Lauren E Haydu, Christine Spencer, Matthew Wongchenko, Stephen Lane, Dung-Yang Lee, Mathilde Kaper, Meredith McKean, Kathryn E Beckermann, Samuel M Rubinstein, Isabelle Rooney, Luna Musib, Nageshwar Budha, Jessie Hsu, Theodore S Nowicki, Alexandre Avila, Tomas Haas, Maneka Puligandla, Sandra Lee, Shenying Fang, Jennifer A Wargo, Jeffrey E Gershenwald, Jeffrey E Lee, Patrick Hwu, Paul B Chapman, Jeffrey A Sosman, Dirk Schadendorf, Jean-Jacques Grob, Keith T Flaherty, Dana Walker, Yibing Yan, Edward McKenna, Jeffrey J Legos, Matteo S Carlino, Antoni Ribas, John M Kirkwood, Georgina V Long, Douglas B Johnson, Alexander M Menzies, Michael A Davies
Journal: The Lancet Oncology (2018)
Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves' orbitopathy (MINGO): a randomised, observer-masked, multicentre trial
Authors: George J Kahaly, Michaela Riedl, Jochem König, Susanne Pitz, Katharina Ponto, Tanja Diana, Elena Kampmann, Elisa Kolbe, Anja Eckstein, Lars C Moeller, Dagmar Führer, Mario Salvi, Nicola Curro, Irene Campi, Danila Covelli, Marenza Leo, Michele Marinò, Francesca Menconi, Claudio Marcocci, Luigi Bartalena, Petros Perros, Wilmar M Wiersinga, Göksun Ayvaz, Lelio Baldeschi, Kostas Boborides, Antonella Boschi, Thomas H Brix, Lucy Clarke, Colin Dayan, Chantal Daumerie, A Jane Dickinson, Nicole Fichter, Laszlo Hegedüs, Onur Konuk, Gerassimos E Krassas, Carol Lane, John Lazarus, Dan S Morris, Maarten. Mourits, Marco Nardi, Chris Neoh, Jacques Orgiazzi, Simon H S Pearce, Georg von Arx, Milos Zarkovic
Journal: The Lancet Diabetes & Endocrinology (2018)
Usefulness of Clinical Scores for Patient Risk Stratification in Non-ST Elevation Acute Coronary Syndrome: Any Role for Serum Markers of Inflammation?
Authors: D Fernandez-Berges, FJ Felix Redondo, L Consuegra Sanchez, L Lozano Mera, Tejero Calderon, FJ Carrasco Sanchez, JM Cruz Fernandez
Journal: Circulation (2010)
A novel variant in <i>GLIS3</i> is associated with osteoarthritis
Authors: Elisabetta Casalone, Ioanna Tachmazidou, Eleni Zengini, Konstantinos Hatzikotoulas, Sophie Hackinger, Daniel Suveges, Julia Steinberg, Nigel William Rayner, Jeremy Mark Wilkinson, Kalliope Panoutsopoulou, Eleftheria Zeggini
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Osteoarthritis (OA) is a complex disease, but its genetic aetiology remains poorly characterised. To identify novel susceptibility loci for OA, we carried out a genome-wide association study (GWAS) in individuals from the largest UK-based OA collections to date. Methods We carried out a discovery GWAS in 5414 OA individuals with knee and/or hip total joint replacement (TJR) and 9939 population-based controls. We followed-up prioritised variants in OA subjects from the interim release of the UK Biobank resource (up to 12 658 cases and 50 898 controls) and our lead finding in operated OA subjects from the full release of UK Biobank (17 894 cases and 89 470 controls). We investigated its functional implications in methylation, gene expression and proteomics data in primary chondrocytes from 12 pairs of intact and degraded cartilage samples from patients undergoing TJR. Results We detect a genome-wide significant association at rs10116772 with TJR (P=3.7×10 −8 ; for allele A: OR (95% CI) 0.97 (0.96 to 0.98)), an intronic variant in GLIS3 , which is expressed in cartilage. Variants in strong correlation with rs10116772 have been associated with elevated plasma glucose levels and diabetes. Conclusions We identify a novel susceptibility locus for OA that has been previously implicated in diabetes and glycaemic traits.
Non-genomic effects of nuclear receptors: insights from the anucleate platelet
Authors: Amanda J Unsworth, Gagan D Flora, Jonathan M Gibbins
Journal: Cardiovascular Research (2018)

Nuclear receptors (NRs) have the ability to elicit two different kinds of responses, genomic and non-genomic. Although genomic responses control gene expression by influencing the rate of transcription, non-genomic effects occur rapidly and independently of transcriptional regulation. Due to their anucleate nature and mechanistically well-characterized and rapid responses, platelets provide a model system for the study of any non-genomic effects of the NRs. Several NRs have been found to be present in human platelets, and multiple NR agonists have been shown to elicit anti-platelet effects by a variety of mechanisms. The non-genomic functions of NRs vary, including the regulation of kinase and phosphatase activity, ion channel function, intracellular calcium levels, and production of second messengers. Recently, the characterization of mechanisms and identification of novel binding partners of NRs have further strengthened the prospects of developing their ligands into potential therapeutics that offer cardio-protective properties in addition to their other defined genomic effects.
CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T-cell responses
Authors: Hung-Wei Cheng, Lucas Onder, Jovana Cupovic, Maximilian Boesch, Mario Novkovic, Natalia Pikor, Ignazio Tarantino, Regulo Rodriguez, Tino Schneider, Wolfram Jochum, Martin Brutsche, Burkhard Ludewig
Journal: Journal of Allergy and Clinical Immunology (2018)

A particular characteristic of non-small cell lung cancer is the composition of the tumor microenvironment with a very high proportion of fibroblastic stromal cells (FSCs).Lapses in our basic knowledge of fibroblast phenotype and function in the tumor microenvironment make it difficult to define whether FSC subsets exist that exhibit either tumor-promoting or tumor-suppressive properties.We used gene expression profiling of lung versus tumor FSCs from patients with non-small cell lung cancer. Moreover, CCL19-expressing FSCs were studied in transgenic mouse models by using a lung cancer metastasis model.CCL19 mRNA expression in human tumor FSCs correlates with immune cell infiltration and intratumoral accumulation of CD8+ T cells. Mechanistic dissection in murine lung carcinoma models revealed that CCL19-expressing FSCs form perivascular niches to promote accumulation of CD8+ T cells in the tumor. Targeted ablation of CCL19-expressing tumor FSCs reduced immune cell recruitment and resulted in unleashed tumor growth.These data suggest that a distinct population of CCL19-producing FSCs fosters the development of an immune-stimulating intratumoral niche for immune cells to control cancer growth.
Single Fluid-Filled Intragastric Balloon Safe and Effective for Inducing Weight Loss in a Real-World Population
Authors: Eric J. Vargas, Carl M. Pesta, Ahmad Bali, Eric Ibegbu, Fateh Bazerbachi, Rachel L. Moore, Vivek Kumbhari, Reem Z. Sharaiha, Trace W. Curry, Gina DosSantos, Ramsey Schmitz, Abhishek Agnihotri, Aleksey A. Novikov, Tracy Pitt, Margo K. Dunlap, Andrea Herr, Louis Aronne, Erin Ledonne, Hoda C. Kadouh, Lawrence J. Cheskin, Manpreet S. Mundi, Andres Acosta, Christopher J. Gostout, Barham K. Abu Dayyeh
Journal: Clinical Gastroenterology and Hepatology (2018)
Similarities and differences in child development from birth to age 3 years by sex and across four countries: a cross-sectional, observational study
Authors: Ilgi Ozturk Ertem, Vibha Krishnamurthy, Mphelekedzeni C Mulaudzi, Yanina Sguassero, Hakan Balta, Ozlem Gulumser, Burcu Bilik, Roopa Srinivasan, Benjamin Johnson, Geliang Gan, Lisa Calvocoressi, Veronika Shabanova, Brian W C Forsyth
Journal: The Lancet Global Health (2018)

BackgroundKnowledge about typical development is of fundamental importance for understanding and promoting child health and development. We aimed to ascertain when healthy children in four culturally and linguistically different countries attain developmental milestones and to identify similarities and differences across sexes and countries.MethodsIn this cross-sectional, observational study, we recruited children aged 0–42 months and their caregivers between March 3, 2011, and May 18, 2015, at 22 health clinics in Argentina, India, South Africa, and Turkey. We obtained a healthy subsample, which excluded children with a low birthweight, perinatal complications, chronic illness, undernutrition, or anaemia, and children with missing health data. Using the Guide for Monitoring Child Development, caregivers described their child's development in seven domains: expressive and receptive language, gross and fine motor, play, relating, and self-help. Clinicians examining the children also completed a checklist about the child's health status. We used logit and probit regression models based on the lowest deviance information criterion to generate Bayesian point estimates and 95% credible intervals for the 50th percentile ages of attainment of 106 milestones. We assessed the significance of differences between sexes and countries using predefined criteria and regions of practical equivalence.FindingsOf 10 246 children recruited, 4949 children (48·3%) were included in the healthy subsample. For the 106 milestones assessed, the median age of attainment was equivalent for 102 (96%) milestones across sexes and 81 (76%) milestones across the four countries. Across countries, median ages of attainment were equivalent for all play milestones, 20 (77%) of 26 expressive language milestones, ten (67%) of 15 receptive language milestones, nine (82%) of 11 fine motor milestones, 14 (88%) of 16 gross motor milestones, and eight (73%) of 11 relating milestones. However, across the four countries the median age of attainment was equivalent for only two (22%) of nine milestones in the self-help domain.InterpretationThe ages of attainment of developmental milestones in healthy children, and the similarities and differences across sexes and country samples might aid the development of international tools to guide policy, service delivery, and intervention research, particularly in low-income and middle-income countries.FundingEunice Kennedy Shriver National Institute of Child Health and Human Development.