tbuckley/cabot-search huggingface dataset:
Role of obesity in smoking behaviour: Mendelian randomisation study in UK Biobank
Authors: Robert Carreras-Torres, Mattias Johansson, Philip C Haycock, Caroline L Relton, George Davey Smith, Paul Brennan, Richard M Martin
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To determine whether body mass index, body fat percentage, and waist circumference influence smoking status and intensity. <h3>Design</h3> Mendelian randomisation study. <h3>Setting</h3> UK Biobank, with replication of results from the Tobacco and Genetics (TAG) consortium. <h3>Participants</h3> European descent participants from the UK Biobank cohort (n=372 791) and the TAG consortium (n=74 035). <h3>Main outcome measures</h3> Risk of current and past smoking, number of cigarettes smoked per day, age of smoking initiation. <h3>Results</h3> The Mendelian randomisation analysis indicated that each standard deviation increment in body mass index (4.6) increased the risk of being a smoker (odds ratio 1.18 (95% confidence interval 1.13 to 1.23), P&lt;0.001). This association was replicated in the TAG consortium data (1.19 (1.06 to 1.33), P=0.003). Furthermore, each standard deviation increment in body mass index was estimated to increase smoking intensity by 0.88 cigarettes per day (95% confidence interval 0.50 to 1.26, P&lt;0.001) in UK Biobank and 1.27 cigarettes per day in the TAG consortium (0.46 to 2.07, P=0.002). Similar results were also seen for body fat percentage and waist circumference in both UK Biobank and the TAG consortium data. <h3>Conclusions</h3> These results strongly suggest that higher adiposity influences smoking behaviour and could have implications for the implementation of public health interventions aiming to reduce the prevalence of these important risk factors.
On the Origin of Our Family
Authors: Jason M. Nagata
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Severe and predominantly active atopic eczema in adulthood and long term risk of cardiovascular disease: population based cohort study
Authors: Richard J Silverwood, Harriet J Forbes, Katrina Abuabara, Anna Ascott, Morten Schmidt, Sigrún A J Schmidt, Liam Smeeth, Sinéad M Langan
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To investigate whether adults with atopic eczema are at an increased risk of cardiovascular disease and whether the risk varies by atopic eczema severity and condition activity over time. <h3>Design</h3> Population based matched cohort study. <h3>Setting</h3> UK electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics, and data from the Office for National Statistics, 1998–2015. <h3>Participants</h3> Adults with a diagnosis of atopic eczema, matched (on age, sex, general practice, and calendar time) to up to five patients without atopic eczema. <h3>Main outcome measures</h3> Cardiovascular outcomes (myocardial infarction, unstable angina, heart failure, atrial fibrillation, stroke, and cardiovascular death). <h3>Results</h3> 387 439 patients with atopic eczema were matched to 1 528 477 patients without atopic eczema. The median age was 43 at cohort entry and 66% were female. Median follow-up was 5.1 years. Evidence of a 10% to 20% increased hazard for the non-fatal primary outcomes for patients with atopic eczema was found by using Cox regression stratified by matched set. There was a strong dose-response relation with severity of atopic eczema. Patients with severe atopic eczema had a 20% increase in the risk of stroke (hazard ratio 1.22, 99% confidence interval 1.01 to 1.48), 40% to 50% increase in the risk of myocardial infarction, unstable angina, atrial fibrillation, and cardiovascular death, and 70% increase in the risk of heart failure (hazard ratio 1.69, 99% confidence interval 1.38 to 2.06). Patients with the most active atopic eczema (active &gt;50% of follow-up) were also at a greater risk of cardiovascular outcomes. Additional adjustment for cardiovascular risk factors as potential mediators partially attenuated the point estimates, though associations persisted for severe atopic eczema. <h3>Conclusions</h3> Severe and predominantly active atopic eczema are associated with an increased risk of cardiovascular outcomes. Targeting cardiovascular disease prevention strategies among these patients should be considered.
BRAFV600E Mutation Does Not Significantly Affect the Efficacy of Radioiodine Therapy in Patients With Papillary Thyroid Carcinoma Without Known Distant Metastases
Authors: Guohua Shen, Ying Kou, Bin Liu, Rui Huang, Anren Kuang
Journal: Clinical Nuclear Medicine (2018)

The BRAF mutation is the most common and specific oncogenic event in papillary thyroid carcinoma (PTC). However, its role in radioiodine therapy decision making has yet to be established. This study aimed to evaluate the impact of the BRAF mutation on the clinical response to radioiodine therapy.This retrospective study included PTC patients who received total thyroidectomy with lymph node dissection, radioiodine therapy, and thyroid-stimulating hormone suppression between January 2012 and March 2016. Included patients were divided into 2 groups based on the BRAF mutation status. The association between the clinicopathological characteristics and the BRAF mutation was evaluated. After a median follow-up of 37 months, the clinical outcome between these 2 groups was also compared based on the ongoing risk stratification.A total of 512 PTC patients without distant metastases were included, with a positive BRAF mutation in 338 patients. No significant association was observed between the BRAF mutation and clinicopathological characteristics, except for sex, tumor size, and extrathyroidal extension. The initial risk stratification between the positive and negative mutation groups revealed no significant difference (P = 0.845). At the end of follow-up, no significant difference regarding the clinical response to radioiodine therapy was demonstrated between these 2 groups for all patients or patients with high recurrence risk (P = 0.586 and P = 0.680, respectively).The BRAF mutation status may not impact the clinical response to radioiodine therapy for PTC patients without distant metastases.
Response to Comment on Buckley et al. Intensive Versus Standard Blood Pressure Control in SPRINT-Eligible Participants of ACCORD-BP. Diabetes Care 2017;40:1733–1738
Authors: Leo F. Buckley, Dave L. Dixon, George F. Wohlford, Dayanjan S. Wijesinghe, William L. Baker, Benjamin W. Van Tassell
Journal: Diabetes Care (2018)

Drs. Mi and Mukamal (1) have recently proposed an additional interpretation of the discrepant results of the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) trial. Although we continue to support our conclusions that SPRINT-eligible ACCORD-BP participants benefited from intensive blood pressure lowering, we recognize that our results do not exclude the important contributions from other factors as explanations for the discrepant results of ACCORD-BP and SPRINT (2). Indeed, several alternative hypotheses have been proposed in an attempt to explain the discordant results of SPRINT and ACCORD-BP (3,4). We therefore welcome the contributions by Mi …
Norms, not moral norms: The boundaries of morality do not matter
Authors: Taylor Davis, Daniel Kelly
Journal: Behavioral and Brain Sciences (2018)

Abstract We endorse Stanford's project, which calls attention to features of human psychology that exhibit a “puzzling combination of objective and subjective elements,” and that are central to cooperation. However, we disagree with his delineation of the explanatory target. What he calls “externalization or objectification” conflates two separate properties, neither of which can serve as the mark of the moral.
PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project
Authors: Ming Sound Tsao, Keith M. Kerr, Mark Kockx, Mary-Beth Beasley, Alain C. Borczuk, Johan Botling, Lukas Bubendorf, Lucian Chirieac, Gang Chen, Teh-Ying Chou, Jin-Haeng Chung, Sanja Dacic, Sylvie Lantuejoul, Mari Mino-Kenudson, Andre L. Moreira, Andrew G. Nicholson, Masayuki Noguchi, Giuseppe Pelosi, Claudia Poleri, Prudence A. Russell, Jennifer Sauter, Erik Thunnissen, Ignacio Wistuba, Hui Yu, Murry W. Wynes, Melania Pintilie, Yasushi Yatabe, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2018)
The proto-oncogene Mer tyrosine kinase is a novel therapeutic target in mantle cell lymphoma
Authors: Cunzhen Shi, Xiangqun Li, Xiaogan Wang, Ning Ding, Lingyan Ping, Yunfei Shi, Lan Mi, Yumei Lai, Yuqin Song, Jun Zhu
Journal: Journal of Hematology & Oncology (2018)

Mantle cell lymphoma (MCL) is an incurable B cell-derived malignant tumor with a median overall survival of 4–5 years. Mer tyrosine kinase (MerTK) has been reported to be aberrantly expressed in leukemia, melanoma, and gastric cancer, and plays a pivotal role in the process of oncogenesis. This study assessed the role of MerTK in MCL for the first time. Immunohistochemistry and western blot were performed to figure out expression of MerTK in MCL. MerTK inhibition by either shRNA or treatment with UNC2250 (a MerTK-selective small molecular inhibitor) was conducted in MCL cell lines. MCL-cell-derived xenograft models were established to evaluate the anti-tumor effects of UNC2250 in vivo. MerTK was ectopically expressed in four of six MCL cell lines. Sixty-five of 132 (48.9%) MCL patients showed positive expression of MerTK. MerTK inhibition by either shRNA or treatment with UNC2250 decreased activation of downstream AKT and p38, inhibited proliferation and invasion in MCL cells, and sensitized MCL cells to treatment with vincristine in vitro and doxorubicin in vitro and in vivo. UNC2250 induced G2/M phase arrest and prompted apoptosis in MCL cells, accompanied by increased expression of Bax, cleaved caspase 3 and poly (ADP-ribose) polymerase, and decreased expression of Bcl-2, Mcl-1 and Bcl-xL. Moreover, UNC2250 delayed disease progression in MCL-cell-derived xenograft models. Our data prove that ectopic MerTK may be a novel therapeutic target in MCL, and further pre-clinical or even clinical studies of UNC2250 or new MerTK inhibitors are essential and of great significance.
Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition
Authors: Gabrielle S. Wong, Jin Zhou, Jie Bin Liu, Zhong Wu, Xinsen Xu, Tianxia Li, David Xu, Steven E. Schumacher, Jens Puschhof, James McFarland, Charles Zou, Austin Dulak, Les Henderson, Peng Xu, Emily O’Day, Rachel Rendak, Wei-li Liao, Fabiola Cecchi, Todd Hembrough, Sarit Schwartz, Christopher Szeto, Anil K. Rustgi, Kwok-Kin Wong, J. Alan Diehl, Karin Jensen, Francesco Graziano, Annamaria Ruzzo, Shaunt Fereshetian, Philipp Mertins, Steven A. Carr, Rameen Beroukhim, Kenichi Nakamura, Eiji Oki, Masayuki Watanabe, Hideo Baba, Yu Imamura, Daniel Catenacci, Adam J. Bass
Journal: Nature Medicine (2018)
Antibiotic‐Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant
Authors: Benjamin H. Mullish, Julie A.K. McDonald, Mark R. Thursz, Julian R. Marchesi
Journal: Hepatology (2018)

To the Editor: The study from Bajaj and colleagues, evaluating gut microbiome–metabonome changes in patients with cirrhosis receiving fecal microbiota transplant (FMT),(1) merits further discussion of its conclusions. In this study, patients with cirrhosis and hepatic encephalopathy (HE) taking standard of care therapy were randomized to either continue with standard of care alone or to also receive 5 days of gut antibiotics prior to a single FMT enema. The investigators demonstrate partial recovery of microbiota, bile acid, and short‐chain fatty acid profiles for patients in the FMT arm and conclude that FMT directly restores gut microbiome–metabonome interactions in antibiotic‐treated patients with cirrhosis.(1) However, there was no arm in this study where patients received antibiotics but no FMT; therefore, it is impossible to distinguish whether any changes observed were directly caused by FMT as claimed or at least partly represent purely gut microbiota recovery after completion of antibiotics. There are certainly grounds for questioning the efficacy of the FMT. Specifically, despite selecting a stool donor with high relative abundance of Lachnospiraceae and Ruminococcaceae, FMT recipients actually demonstrate a significantly reduced relative abundance of these bacterial families in stool post‐FMT (day 20) compared to baseline values (day 0) (see Bajaj et al., fig. 2B(1)). Furthermore, it is well established that human gut microbiota structure recovers to a profile comparable to that found pre‐antibiotics within a short period following completion of an antibiotic course.(2) Additionally, while poorly explored in cirrhosis, short‐chain fatty acid(3) and bile acid profiles(4) reconstitute over a time course of days to weeks after antibiotic cessation in healthy rodents without any specific intervention. If FMT directly treated HE through modulation of gut microbiota–metabonome interactions, then it would be expected that at least some of these variables would exceed baseline values post‐FMT, rather than only match baseline levels at best, as shown. Adverse events associated with FMT are uncommon, but serious adverse events are described—including bacteraemia—in the population without cirrhosis(5); such concerns are clearly amplified in patients with decompensated cirrhosis, given this group's propensity to and outcomes from sepsis. Until the safety profile of FMT in patients with cirrhosis has been further evaluated—and a potential mechanistic link between FMT and improvement in HE defined—FMT will remain at too early a stage to consider more widely as treatment for HE. 1 Potential conflict of interest Nothing to report.
Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial
Authors: Drew J Winston, Kathleen M Mullane, Oliver A Cornely, Michael J Boeckh, Janice Wes Brown, Steven A Pergam, Igoris Trociukas, Pavel Žák, Michael D Craig, Genovefa A Papanicolaou, Juan D Velez, Jens Panse, Kimberly Hurtado, Doreen A Fernsler, Jon E Stek, Lei Pang, Shu-Chih Su, Yanli Zhao, Ivan S F Chan, Susan S Kaplan, Janie Parrino, Ingi Lee, Zoran Popmihajlov, Paula W Annunziato, Ann Arvin, AC Basso, P Bonvehi, S Cerana, MO Dictar, P Campbell, G Playford, J Sasadeusz, J Maertens, X Poire, D Sellesag, R Schots, K Theunissen, E Willems, RS Alves, JFC Camargo, NS Castro, L Maria Fogliatto, O Rodrigo, F Courture, A McGeer, M Miller, JF Combariza, CL Sossa, JD Velez, D Nemet, S Ostojic Kolonic, L Jebavy, J Mayer, J Novak, D Pohlreich, B Maldonado, T Gastinne, L Karlin, O Launay, OA Cornely, HA Duerk, M Haenel, W Heinz, M Kaufmann, J Panse, D Teschner, M Verbeek, G Wulf, F Aviv, S Grisariu, A Nagler, M Yeshurun, A Bosi, P Corradini, G Martinelli, F Onida, A Rambaldi, A Velardi, I Trociukas, AD Gomez, MJ Wondergem, PF Ypma, E Fanilla, MDC Moreno Larrea, MM Abecasis, RB Ferreira, C Geraldes, J Castro, BV Afanasyev, IV Kruchkova, AY Zaritskiy, JW Cheong, SJ Kim, DG Lee, SS Yoon, B Aguado Bueno, I Jarque Ramos, C Solano Vercet, H Cherif, P Ljungman, K Vaht, G Cook, E Kanfer, DW Milligan, A Parker, L Akard, C Bachier, ED Ball, FR Betts, I Braunschweig, JM Brown, MP Carroll, PH Chandrasekar, R Collins, B Cooper, M Craig, N D'Cunha, ML Donato, J Essell, P Flomenberg, A Freifeld, C Freytes, MJ Guarino, MC Hall, JW Heimenz, KP High, LM Isola, L Kaminer, LM Klein, N Janakiraman, K Kane, K Komanduri, OI Krijanovski, SJ Lawrence, JF Leis, M Lill, WL Longo, JP Lynch, BI Mattar, J Mehta, KM Mullane, S Nathan, GA Papanicolaou, SA Pergam, V Roy, W Rybka, H Safah, D Saltzman, GM Segal, GB Selby, MW Schuster, S Shoham, JM Sloan, LM Strasfeld, M Styler, K Sullivan, W Tse, EA Vance, DJ Winston, S Yanovich
Journal: The Lancet (2018)
Deregulation of methylation of transcribed-ultra conserved regions in colorectal cancer and their diagnostic and prognostic value.
Authors: Anastasia E Kottorou, Anna G Antonacopoulou, Fotinos-Ioannis D. Dimtrakopoulos, Melpomeni Kalofonou, Georgia Diamantopoulou, Theodoros Theodorakopoulos, Chrysa Oikonomou, Evangelos Katsakoulis, Nikos Dimopoulos, Georgia Stephanou, Thomas Makatsoris, Michalis Stavropoulos, Konstantinos Thomopoulos, Haralabos Kalofonos
Journal: Journal of Clinical Oncology (2017)

e15130 Background: Expression of Transcribed Ultra Conserved Regions (T-UCRs) is often deregulated in cancer. We investigated the role of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal adenocarcinomas and their prognostic and diagnostic value. Methods: Expression and methylation levels of the T-UCRs were assessed in neoplastic and paired non-malignant fresh frozen (FF) tissue specimens from 64 colorectal cancer (CRC) patients, as well as in 6 FF adenoma tissue specimens. In addition, T-UCR methylation levels were assessed in FFPE tumor tissues from 80 CRC patients and in plasma from 161 patients (50 CRC, 59 adenoma patients, 40 healthy subjects and 12 patients with colon inflammation or diverticulosis). Results: Expression levels of all three T-UCRs were lower in neoplastic, compared to non-malignant tissues, although at a statistically significant level only for Uc160 ( p&lt; 0.001). Also, methylation levels of Uc160, Uc283 and Uc346 were higher in tumors compared to non-malignant tissues ( p&lt; 0.001, p= 0.001 and p= 0.004 respectively). Tissue methylation levels of Uc160 were associated with TTP ( p= 0.017). The combination of Uc283 and Uc346 methylation levels was related to OS, however without reaching statistical significance ( p= 0.066). Methylation status of Uc160 and Uc346 in plasma differed significantly among the four patient groups with CRC patients exhibiting the higher levels. Moreover, a strong correlation was found between Uc160 plasma methylation levels and adenoma or adenocarcinoma size and lymph node infiltration ( p&lt; 0.001 and p= 0.024 respectively). When methylation status was used to predict if a subject has CRC, sensitivity and specificity were 35% and 89% respectively, while the values changed to 45% and 74.3% respectively when we combined the sum of the three T-UCR plasma methylation levels. For adenomas, the combination of Uc160 and Uc346 plasma methylation displayed 30.2% (sensitivity) and 80.7% (specificity). Conclusions: T-UCR expression and methylation is deregulated in CRC while their methylation has prognostic value and appears a promising non-invasive screening test for CRC and adenomas, provided that the sensitivity of the assay is improved.
Abstract 2263: Preoperative Regurgitant Volume Can Predict “Unexpected” Left Ventricular Dysfunction After Mitral Valve Repair for Chronic Mitral Regurgitation
Authors: Tetsuhiro Yamano, A. M Gillinov, Nozomi Wada, Yoshiki Matsumura, Manatomo Toyono, James D Thomas, Takahiro Shiota
Journal: Circulation (2007)

Background:  Left ventricular (LV) dysfunction after mitral valve (MV) repair in patients with chronic mitral regurgitation (MR) carries a poor prognosis. It has been previously described that LV dysfunction could be predicted using preoperative echocardiographic parameters such as LV size and ejection fraction (EF). However, we encounter MR patients who have unexpected postoperative LV dysfunction despite preoperatively normal LV size and function.   Methods:  We retrospectively investigated pre- and post-operative (median 4th postoperative day) echocardiograms of 248 consecutive patients who underwent MV repair from June through December 2005 for degenerative MR without other heart complications except tricuspid regurgitation. Among these patients, 48 patients were excluded because of inadequate echo quality for regurgitant volume (RVol) quantitation. Our study consisted of the remaining 200 patients (mean age 57±13 years, 140 male) in whom we could clearly determine the preoperative RVol from either quantitative Doppler and/or proximal isovelocity surface area method.   Results:  After MV repair, the median (interquartile range) EF was significantly decreased from 68 (61–75) to 54 (41–63) % ( P  P  60% and LVDs  P  P  P  P    Conclusion:  A very large regurgitant volume was a significant predictor of postoperative LV dysfunction after MV repair despite preoperatively normal LV size and function. Quantification of MR volume is strongly recommended for earlier indication of MV repair in patients with severe MR.
Association between plasma ceramides and inducible myocardial ischemia in patients with established or suspected coronary artery disease undergoing myocardial perfusion scintigraphy
Authors: Alessandro Mantovani, Stefano Bonapace, Gianluigi Lunardi, Matteo Salgarello, Clementina Dugo, Guido Canali, Christopher D. Byrne, Stefania Gori, Enrico Barbieri, Giovanni Targher
Journal: Metabolism (2018)
The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase
Authors: Phillip J. White, Robert W. McGarrah, Paul A. Grimsrud, Shih-Chia Tso, Wen-Hsuan Yang, Jonathan M. Haldeman, Thomas Grenier-Larouche, Jie An, Amanda L. Lapworth, Inna Astapova, Sarah A. Hannou, Tabitha George, Michelle Arlotto, Lyra B. Olson, Michelle Lai, Guo-Fang Zhang, Olga Ilkayeva, Mark A. Herman, R. Max Wynn, David T. Chuang, Christopher B. Newgard
Journal: Cell Metabolism (2018)