tbuckley/cabot-search huggingface dataset:
Imaging Advances in Chronic Obstructive Pulmonary Disease. Insights from the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) Study
Authors: Surya P. Bhatt, George R. Washko, Eric A. Hoffman, John D. Newell, Sandeep Bodduluri, Alejandro A. Diaz, Craig J. Galban, Edwin K. Silverman, Raúl San José Estépar, David A. Lynch
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study, which began in 2007, is an ongoing multicenter observational cohort study of more than 10,000 current and former smokers. The study is aimed at understanding the etiology, progression, and heterogeneity of chronic obstructive pulmonary disease (COPD). In addition to genetic analysis, the participants have been extensively characterized by clinical questionnaires, spirometry, volumetric inspiratory and expiratory computed tomography, and longitudinal follow-up, including follow-up computed tomography at 5 years after enrollment. The purpose of this state-of-the-art review is to summarize the major advances in our understanding of COPD resulting from the imaging findings in the COPDGene study. Imaging features that are associated with adverse clinical outcomes include early interstitial lung abnormalities, visual presence and pattern of emphysema, the ratio of pulmonary artery to ascending aortic diameter, quantitative evaluation of emphysema, airway wall thickness, and expiratory gas trapping. COPD is characterized by the early involvement of the small conducting airways, and the addition of expiratory scans has enabled measurement of small airway disease. Computational advances have enabled indirect measurement of nonemphysematous gas trapping. These metrics have provided insights into the pathogenesis and prognosis of COPD and have aided early identification of disease. Important quantifiable extrapulmonary findings include coronary artery calcification, cardiac morphology, intrathoracic and extrathoracic fat, and osteoporosis. Current active research includes identification of novel quantitative measures for emphysema and airway disease, evaluation of dose reduction techniques, and use of deep learning for phenotyping COPD.
Global Public Attitudes About Clinical Research and Patient Experiences With Clinical Trials
Authors: Annick Anderson, Deborah Borfitz, Kenneth Getz
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Effective, continuous improvement in patient engagement depends on an intimate understanding of public and patient perceptions and experiences in clinical research. <h3>Objectives</h3> To identify the views of clinical trial participants and nonparticipants and characterize trends in these views over time. <h3>Design, Setting, and Participants</h3> In this survey study, a questionnaire was administered online from May 8 to July 24, 2017, by the Center for Information and Study on Clinical Research Participation (CISCRP), and findings were compared with previous studies conducted in 2013 and 2015. The 2017 sample included responses from 12 427 individuals from 68 countries and represents a 10% participation rate. Similar to international assessments conducted by the CISCRP and other organizations, this study drew responses from a convenience sample; any adult older than 18 years who received an email or had online access was eligible to participate. <h3>Main Outcomes and Measures</h3> Significant changes were observed in the perceptions and clinical trial experiences of the public and study volunteers compared with past CISCRP studies. <h3>Results</h3> A total of 12 427 individuals (mean [SD] age, 55 [15] years; 7355 [59.2%] female; 10 085 [81.2%] white), 2194 (17.7%) of whom had participated in previous clinical research studies, responded to the survey in 2017. Findings indicated a belief in the importance of clinical research, but limited understanding of the research process persists. In 2017, a total of 10 506 individuals (84.5%) perceived clinical research to be very important to the discovery and development of new medicines; however, 4079 of 6919 respondents (59.0%) were unable to name a place where studies were conducted. A total of 11 182 respondents (90.0%) believed that clinical research is generally safe; however, 5578 of 12 427 individuals (44.9%) reported that clinical trials are rarely considered as an option when discussing treatments or medications with their physician. Clinical trial participation was perceived as inconvenient and burdensome; in the latest survey, 1075 respondents (49.0%) expressed that their clinical trial participation disrupted their daily routine. <h3>Conclusions and Relevance</h3> The results of this study may provide a foundation from which to build meaningful and effective engagement with the public and patients and revealed roadblocks, including knowledge gaps among the public, limited physician involvement in discussing clinical trials as treatment options, and the inconveniences that patients encounter after they volunteer to participate. These findings may inform patient engagement strategies and tactics and ultimately help accelerate the drug-development process.
Abstract IA03: Subgroup-specific enhancer hijacking in medulloblastoma
Authors: Paul A. Northcott
Journal: Cancer Research (2018)

Abstract In recent years, next-generation sequencing has uncovered the spectrum of driver genes and molecular processes contributing to most cancer entities, including pediatric cancer. This holds true for medulloblastoma (MB), the most common malignant childhood brain tumor. A multitude of genomic studies conducted on large patient cohorts have culminated in the recognition of at least four molecular and clinically distinct MB subgroups: WNT, SHH, Group 3, and Group 4. Moreover, comprehensive sequencing efforts have reported the prevalence and subgroup distribution of somatically altered genes in MB, informing tumor biology and suggesting rational candidates for molecularly targeted therapy. In contrast to WNT and SHH subgroup MB, which are typically characterized by mutations/copy-number alterations leading to aberrant signaling of the WNT and SHH pathways, respectively, Groups 3 and 4 harbor a paucity of recurrently mutated genes and exhibit remarkable heterogeneity in their molecular landscapes. Looking beyond somatic gene-level mutations and focusing our analyses on recurrent structural variants (SVs) in Group 3 and Group 4, we recently discovered a series of atypical SVs converging on chr9q34 that coincided with aberrant induction of GFI1B expression, a transcription factor normally active in the hematopoietic system. Meticulous mapping of SV breakpoints and subsequent integration with DNA methylation and histone ChIP-seq datasets implicated misappropriation of highly active enhancers secondary to the observed SV, a mechanism we termed “enhancer hijacking.” In light of this surprising discovery, we have now extended our analyses, including the development of new computational pipelines, to systematically explore the extent of enhancer hijacking in MB and other pediatric brain tumors. Emerging results from these efforts will be presented, including strategies being employed to validate aberrant enhancer-promoter interactions in MBs with presumed enhancer hijacking, as well as functional approaches we are using to engineer these alterations in relevant cellular systems. Citation Format: Paul A. Northcott. Subgroup-specific enhancer hijacking in medulloblastoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr IA03.
Flour to be fortified with folic acid within weeks, say reports
Authors: Matthew Limb
Journal: BMJ (2018)

Health experts have welcomed reports that the UK is poised to start fortifying flour with folic acid to help prevent birth defects such as spina bifida and anencephaly.

Nicholas Wald, of the Wolfson Institute of Preventive Medicine at Queen Mary University of London, said, “If this is officially confirmed, the UK is taking an important step in preventive medicine and helping to avoid disability or termination of pregnancy.”

The Royal College of Obstetricians and Gynaecologists said that such a move would see a “significant reduction in the incidence of neural tube defects, for the benefit of women and their babies and families.”

Leading medical organisations and charities have long been …
Interventions to reduce unnecessary caesarean sections in healthy women and babies
Authors: Ana Pilar Betrán, Marleen Temmerman, Carol Kingdon, Abdu Mohiddin, Newton Opiyo, Maria Regina Torloni, Jun Zhang, Othiniel Musana, Sikolia Z Wanyonyi, Ahmet Metin Gülmezoglu, Soo Downe
Journal: The Lancet (2018)
Abstract 15437: A Phase 3 Single-Blind Study of Eleclazine in Subjects With Type 3 Long QT Syndrome
Authors: Silvia Priori, Isabelle Denjoy, Christiana Blair, Jennifer Hellawell, Carol A Satler, Michael J Ackerman
Journal: Circulation (2017)

Introduction: This was a Phase 3 clinical trial designed to determine the efficacy, safety, and tolerability of the late sodium current inhibitor eleclazine in shortening the corrected QT (QTcF) in...
An open-label phase 1 trial of lenvatinib plus pembrolizumab in patients with advanced selected solid tumors
Authors: Shigehisa Kitano, Yutaka Fujiwara, Toshio Shimizu, Satoru Iwasa, Kan Yonemori, Shunsuke Kondo, Akihiko Shimomura, Takafumi Koyama, Takahiro Ebata, Sakura Iizumi, Hiroki Ikezawa, Masayuki Namiki, Tomoki Kubota, Takuma Miura, Noboru Yamamoto
Journal: Annals of Oncology (2018)
Glucose responses to acute and chronic exercise during pregnancy: a systematic review and meta-analysis
Authors: Margie H Davenport, Frances Sobierajski, Michelle F Mottola, Rachel J Skow, Victoria L Meah, Veronica J Poitras, Casey E Gray, Alejandra Jaramillo Garcia, Nick Barrowman, Laurel Riske, Marina James, Taniya S Nagpal, Andree-Anne Marchand, Linda G Slater, Kristi B Adamo, Gregory A Davies, Ruben Barakat, Stephanie-May Ruchat
Journal: British Journal of Sports Medicine (2018)

To perform a systematic review and meta-analysis to explore the relationship between prenatal exercise and glycaemic control.Systematic review with random-effects meta-analysis and meta-regression.Online databases were searched up to 6 January 2017.Studies of all designs were included (except case studies and reviews) if they were published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of acute or chronic exercise, alone ('exercise-only') or in combination with other intervention components (eg, dietary; 'exercise+cointervention') at any stage of pregnancy), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcome (glycaemic control).A total of 58 studies (n=8699) were included. There was 'very low' quality evidence showing that an acute bout of exercise was associated with a decrease in maternal blood glucose from before to during exercise (6 studies, n=123; mean difference (MD) -0.94 mmol/L, 95% CI -1.18 to -0.70, I2=41%) and following exercise (n=333; MD -0.57 mmol/L, 95% CI -0.72 to -0.41, I2=72%). Subgroup analysis showed that there were larger decreases in blood glucose following acute exercise in women with diabetes (n=26; MD -1.42, 95% CI -1.69 to -1.16, I2=8%) compared with those without diabetes (n=285; MD -0.46, 95% CI -0.60 to -0.32, I2=62%). Finally, chronic exercise-only interventions reduced fasting blood glucose compared with no exercise postintervention in women with diabetes (2 studies, n=70; MD -2.76, 95% CI -3.18 to -2.34, I2=52%; 'low' quality of evidence), but not in those without diabetes (9 studies, n=2174; MD -0.05, 95% CI -0.16 to 0.05, I2=79%).Acute and chronic prenatal exercise reduced maternal circulating blood glucose concentrations, with a larger effect in women with diabetes.
GW29-e1002 The current status of cardiac rehabilitation guidance before discharge for patients with acute coronary syndrome in China: Findings from CCC - ACS Project
Authors: Guoliang Hu, Jun Liu, Na Yang, Jing Liu, Yaling Han, Yong Huo, Gregg C. Fonarow, Junbo Ge, Kathryn A. Taubert, Louise Morgan, Changsheng Ma, Sidney C. Smith, Dong Zhao
Journal: Journal of the American College of Cardiology (2018)
Using High‐Resolution Computed Tomography to Detect Interstitial Lung Disease in Patients With Systemic Sclerosis: Comment on the Concise Communication by Bernstein et al
Authors: Ann E. Warner, Kent K. Huston
Journal: Arthritis & Rheumatology (2018)

To the Editor: We read with interest the concise communication by Bernstein et al 1 regarding practice patterns among rheumatologists when screening for interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). Referencing the study by Suliman et al 2, the authors state that pulmonary function tests (PFTs) are not sensitive or specific for detecting ILD in this population. The primary message in that study 2 is that PFTs yield a false-negative rate of 62.5% for early detection of ILD in SSc when high-resolution computed tomography (HRCT) is used as the gold standard. It is important to note, however, that the primary measurement used to define baseline abnormality in the study by Suliman and colleagues was forced vital capacity (FVC) <80% of predicted. As already pointed out by Degano et al 3, the incorporation of other measures, including diffusing capacity for carbon monoxide (DLco) and possibly functional residual capacity, improves sensitivity. This was documented by Suliman and colleagues, who found that incorporating other measures of pulmonary function, including DLco <70% of predicted, increased sensitivity for detecting ILD to 72%. Although the presence and extent of baseline fibrosis on HRCT has been shown to be prognostically valuable in SSc 4, a 1992 study by Steen and colleagues also showed that among patients with SSc who had normal DLco (defined as ≥80% of predicted, rather than ≥70% of predicted per the study by Suliman et al) at baseline, only 2 of 218 (<0.01%) developed clinically significant pulmonary disease after 7.2 years of follow-up 5. This suggests that baseline DLco may be a sensitive indicator of pulmonary disease requiring treatment in SSc, although lacking in specificity. Based on these considerations, we believe it may be premature to dismiss PFTs as a screening tool for clinically significant scleroderma lung disease. The significance of HRCT abnormalities suggestive of ILD in the absence of alterations in lung volumes or gas exchange remains unclear, as is reflected in the inconsistent use of this tool by rheumatologists, as described by Bernstein and colleagues.
Coeliac disease in children
Authors: Philippa C Thomas, Mark P Tighe, R Mark Beattie
Journal: BMJ (2018)

### What you need to know

A 3 year old boy is brought to his general practitioner by his mother. She is worried he is waking at night complaining of abdominal pain. He has smelly stools that float in the toilet, and has a cousin with coeliac disease. His growth has fallen from the 25th to the second centile for height and weight. On examination he has a distended, mildly tender abdomen with wasted buttocks. Laboratory results are strongly positive for coeliac disease with an IgA anti-tissue transglutaminase (anti-tTG) concentration of 134 IU/mL (normal range 0-2.9).

### Sources and selection criteria

In creating this article, we initially reviewed the BSPGHAN and ESPGHAN guidance, which formed the basis of the article.

We reviewed articles referred to within the guidance and conducted a PubMed search of papers published after 2000 using the search terms “celiac disease” and “children.” We also reviewed relevant additional references from papers obtained. We then added our personal archives of references to obtain a generalised overview of coeliac disease and issues specific to children. For more specific elements—such as the association of coeliac disease with menses and fertility—we performed specific PubMed searches in order to obtain more recent references.

The article was formatted as per the BMJ guidance, and clinical experience plus evidence collected were used to ensure that common issues which arise within paediatric coeliac disease were addressed.

Coeliac disease is a systemic, immune-mediated disorder elicited by gluten …
Natural Killer Cell–Derived Interferon‐Gamma Promotes Hepatocellular Carcinoma Through the Epithelial Cell Adhesion Molecule–Epithelial‐to‐Mesenchymal Transition Axis in Hepatitis B Virus Transgenic Mice
Authors: Yongyan Chen, Xiaolei Hao, Rui Sun, Haiming Wei, Zhigang Tian
Journal: Hepatology (2018)

Hepatitis B virus (HBV) is a major risk factor for development of hepatocellular carcinoma (HCC), at least partially due to dysfunctional anti-HBV adaptive immunity; however, the role of innate immune response to HBV in this process is not well understood. In this study, low-dose polyinosinic:polycytidylic acid (poly [I:C]), a natural killer (NK) cell activator (3 μg/g body weight, twice/week for 8 weeks), induced HCC in HBV transgenic (HBs-Tg) mice, with an incidence of 100% after 6 months, while HBs-Tg mice without treatment only had HCC with an incidence of 16.7%. In HBs-Tg mice, poly (I:C) induced liver inflammation with markedly increased infiltrating lymphocytes, along with the concurrently increased apoptosis and proliferation of hepatocytes, leading to the accelerated epithelial-to-mesenchymal transition (EMT) of hepatocytes shown by increased expression of the typical transcriptional factors (Slug, Twist, and mothers against decapentaplegic-interacting protein 1) and phenotypic proteins (vimentin and chemokine [C-X-C motif] receptor 4). The EMT and tumorigenesis in this model depended on the presence of NK cells because depletion of these cells significantly reduced the HCC rate to 28.6%. Further, intrahepatic NK cells highly expressed interferon-gamma (IFN-γ), anti-IFN-γ neutralizing monoclonal antibody might obviously alleviate the hepatitis, and hepatocyte-specific IFN-γ overexpression promoted HCC. Moreover, IFN-γ deficiency in HBs-Tg mice prevented HCC occurring, though hepatic NK cells existed and could be activated, suggesting the critical role of IFN-γ in NK cell-mediated tumorigenesis. In an in vitro experiment, IFN-γ up-regulated epithelial cell adhesion molecule (EpCAM) expression through phosphorylated signal transducer and activator of transcription (p-STAT1) pathway, which was followed by EMT, and p-STAT1 inhibitor might absolutely abolish the expression of EpCAM and EMT in HBV surface antigen-positive hepatocytes. Conclusion: This work demonstrates that NK cell-derived IFN-γ promotes HCC through the EpCAM-EMT axis in HBs-Tg mice, revealing the importance of innate immunity in pathogenesis of HBV-associated HCC.
Book: Staying Alive: A Family Memoir
Authors: Audrey Ardern-Jones
Journal: BMJ (2003)

This is a very brave book, and a good read for professionals caring for families with a high risk of breast cancer. This intimate family story explores the dynamics of a cancer (or precancer) diagnosis in not just one beloved relative but five women in a family: the author—who was found to have many individual primary sites of carcinoma in situ after prophylactic surgery—her mother, two aunts, and a cousin.​cousin.
The prognostic value of inositol polyphosphate 5-phosphatase in cutaneous squamous cell carcinoma
Authors: Helen J.L. Cumsky, Collin M. Costello, Nan Zhang, Richard Butterfield, Matthew R. Buras, Jessica E. Schmidt, Kevin Drenner, Steven A. Nelson, Shari A. Ochoa, Christian L. Baum, Mark R. Pittelkow, David J. DiCaudo, Aleksandar Sekulic, Aaron R. Mangold
Journal: Journal of the American Academy of Dermatology (2018)
Heat shock protein 90 (HSP90) inhibitor as a candidate treatment option for gastrointestinal stromal tumor with acquired resistance for conventional receptor tyrosine kinase inhibitors
Authors: M. Yamamura, A. Yamauchi, N. Katase, Y. Katata, H. Tanioka, M. Okawaki, T. Nagasaka, Y. Yamaguchi
Journal: Annals of Oncology (2018)
Caregivers of Patients Considering a Destination Therapy Left Ventricular Assist Device and a Shared Decision-Making Intervention
Authors: Colleen K. McIlvennan, Daniel D. Matlock, Jocelyn S. Thompson, Shannon M. Dunlay, Laura Blue, Shane J. LaRue, Eldrin F. Lewis, Chetan B. Patel, Diane L. Fairclough, Erin C. Leister, Keith M. Swetz, Vicie Baldridge, Mary Norine Walsh, Larry A. Allen
Journal: JACC Heart Failure (2018)
Subcutaneous fat necrosis in a newborn
Authors: Laura Adams, Tanya N Basu, Elizabeth Orrin
Journal: BMJ (2018)

A well, 13 day old boy presented with indurated, violaceous nodules on the back (fig 1) and raised corrected calcium of 2.97 mmol/L (2.15-2.60 mmol/L). The rash was initially treated as cellulitis, and he required …
Fractional polynomial network meta-analysis: A different approach to indirectly assess the comparative efficacy of 2L+ cancer immunotherapy (CIT) treatments for metastatic NSCLC
Authors: C. Schulz, P. Chu, C.G. Berardo, B. Karthuria, J. Foo, C. Morel, C. Watkins, M. Ballinger, D.R. Gandara
Journal: Annals of Oncology (2018)
Bright spots, physical activity investments that work—Gators in Motion: a holistic approach to sport-based youth development
Authors: Trevor Bopp, E Paul Roetert
Journal: British Journal of Sports Medicine (2018)

### Programme card

Across the USA, disparities closely linked with race and socioeconomic status (SES) exist such that physical, health and educational outcomes associated with youth development are negatively impacted for children and adolescents from underserved, marginalised communities. For instance, regular physical activity has been found to increase physical …
Survivorship, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology
Authors: Crystal S. Denlinger, Tara Sanft, K. Scott Baker, Gregory Broderick, Wendy Demark-Wahnefried, Debra L. Friedman, Mindy Goldman, Melissa Hudson, Nazanin Khakpour, Allison King, Divya Koura, Robin M. Lally, Terry S. Langbaum, Allison L. McDonough, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Javid J. Moslehi, Tracey O'Connor, Linda Overholser, Electra D. Paskett, Jeffrey Peppercorn, William Pirl, M. Alma Rodriguez, Kathryn J. Ruddy, Paula Silverman, Sophia Smith, Karen L. Syrjala, Amye Tevaarwerk, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole R. McMillian, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2018)

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period. This portion of the guidelines describes recommendations regarding the management of anthracycline-induced cardiotoxicity and lymphedema. In addition, recommendations regarding immunizations and the prevention of infections in cancer survivors are included.