tbuckley/cabot-search huggingface dataset:
Depression increases the risk of inflammatory bowel disease, which may be mitigated by the use of antidepressants in the treatment of depression
Authors: Alexandra D Frolkis, Isabelle A Vallerand, Abdel-Aziz Shaheen, Mark W Lowerison, Mark G Swain, Cheryl Barnabe, Scott B Patten, Gilaad G Kaplan
Journal: Gut (2018)

Objective Depression is associated with IBD, but the effect of antidepressants on IBD has been sparsely studied. We assessed the impact of depression and antidepressant therapies on the development of IBD. Design The Health Improvement Network (THIN) was used to identify a cohort of patients with new-onset depression from 1986 to 2012. THIN patients who did not meet the defining criteria for depression were part of the referent group. The outcome was incident Crohn’s disease (CD) or ulcerative colitis (UC). Cox proportional hazards modelling was performed to evaluate the rate of Crohn’s disease or UC development among patients with an exposure of depression after controlling for age, sex, socioeconomic status, comorbid conditions, smoking, anxiety and antidepressant use including atypical antidepressants, mirtazapine, monoamine oxidase inhibitors (MAOI), serotonin norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), serotonin modulators; and tricyclic antidepressants (TCA). Results We identified 403 665 (7.05%) patients with incident depression. Individuals with depression had a significantly greater risk of developing CD (adjusted HR=2.11, 95% CI 1.65 to 2.70) and UC (adjusted HR=2.23, 95% CI 1.92 to 2.60) after controlling for demographic and clinical covariates. SSRI and TCA were protective against CD, whereas mirtazapine, SNRI, SSRI, serotonin modulators and TCA were protective for UC. Conclusion Patients with a history of depression were more likely to be diagnosed with IBD. In contrast, antidepressant treatments were selectively protective for Crohn’s disease and UC. These results may impact counselling and management of depression and IBD.
Intensive Imaging-based Follow-up of Surgically Treated Localised Renal Cell Carcinoma Does Not Improve Post-recurrence Survival: Results from a European Multicentre Database (RECUR)
Authors: Saeed Dabestani, Christian Beisland, Grant D. Stewart, Karim Bensalah, Eirikur Gudmundsson, Thomas B. Lam, William Gietzmann, Paimaun Zakikhani, Lorenzo Marconi, Sergio Fernandéz-Pello, Serenella Monagas, Samuel Paul Williams, Christian Torbrand, Thomas Powles, Erik Van Werkhoven, Richard Meijer, Alessandro Volpe, Michael Staehler, Börje Ljungberg, Axel Bex
Journal: European Urology (2018)
Current situation,issues and prospects of "AYA get-together": a get-together for adolescents and young adults with cancer
Authors: Takatoshi Hirayama, Rebekah Kojima, Mariko Kobayashi, Ryoko Udagawa, Ayumi Makita, Yuko Yanai, Akie Shindo, Chiyuki Sasaki, Hiroto Ishiki, Ken Shimizu, Eriko Satomi
Journal: Annals of Oncology (2018)
Metabolic Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes by Inhibition of HIF1α and LDHA
Authors: Dongjian Hu, Annet Linders, Abir Yamak, Cláudia Correia, Jan David Kijlstra, Arman Garakani, Ling Xiao, David J. Milan, Peter van der Meer, Margarida Serra, Paula M. Alves, Ibrahim J. Domian
Journal: Circulation Research (2018)

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are a readily available, robustly reproducible, and physiologically appropriate human cell source for cardiac disease modeling, drug discovery, and toxicity screenings in vitro. However, unlike adult myocardial cells in vivo, hPSC-CMs cultured in vitro maintain an immature metabolic phenotype, where majority of ATP is produced through aerobic glycolysis instead of oxidative phosphorylation in the mitochondria. Little is known about the underlying signaling pathways controlling hPSC-CMs' metabolic and functional maturation.To define the molecular pathways controlling cardiomyocytes' metabolic pathway selections and improve cardiomyocyte metabolic and functional maturation.We cultured hPSC-CMs in different media compositions including glucose-containing media, glucose-containing media supplemented with fatty acids, and glucose-free media with fatty acids as the primary carbon source. We found that cardiomyocytes cultured in the presence of glucose used primarily aerobic glycolysis and aberrantly upregulated HIF1α (hypoxia-inducible factor 1α) and its downstream target lactate dehydrogenase A. Conversely, glucose deprivation promoted oxidative phosphorylation and repressed HIF1α. Small molecule inhibition of HIF1α or lactate dehydrogenase A resulted in a switch from aerobic glycolysis to oxidative phosphorylation. Likewise, siRNA inhibition of HIF1α stimulated oxidative phosphorylation while inhibiting aerobic glycolysis. This metabolic shift was accompanied by an increase in mitochondrial content and cellular ATP levels. Furthermore, functional gene expressions, sarcomere length, and contractility were improved by HIF1α/lactate dehydrogenase A inhibition.We show that under standard culture conditions, the HIF1α-lactate dehydrogenase A axis is aberrantly upregulated in hPSC-CMs, preventing their metabolic maturation. Chemical or siRNA inhibition of this pathway results in an appropriate metabolic shift from aerobic glycolysis to oxidative phosphorylation. This in turn improves metabolic and functional maturation of hPSC-CMs. These findings provide key insight into molecular control of hPSC-CMs' metabolism and may be used to generate more physiologically mature cardiomyocytes for drug screening, disease modeling, and therapeutic purposes.
Therapeutic Approach to Young Patients With Low-Risk Essential Thrombocythemia: Primum Non Nocere
Authors: Lucia Masarova, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2018)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 51-year-old woman was diagnosed with essential thrombocythemia (ET) the previous year (April 2016) when she was incidentally found to have increased platelets (747 × 10
The combi-targeting concept: a new cell signaling-based model for the selective targeting of the epidermal growth factor receptor (EGFR)- and Her2-expressing solid tumor cells by the complex combi-molecule RB24 (NSC 741279)
Authors: Ranjita Banerjee, James McNamee, Bertrand Jean-Claude
Journal: Cancer Research (2007)

4175  Within the context of the “Combi-Targeting” concept, we designed RB24 to inhibit EGFR or Her2 phosphorylation and to further degrade upon hydrolysis to RB10 (another EGFR/Her2 inhibitor) + a DNA methylating species. In vitro analyses using fluorescence microscopy, comet and Annexin-V binding assays showed that RB24 released RB10 in the perinuclear region, damaged DNA and induced apoptosis in the human MDA-MB-435 breast cancer cells. Transfection of the latter cells with ErbB1 or ErbB2 correlated with 2-3 fold higher levels of DNA damage, enhanced cell death by apoptosis and increased intensity of fluorescence associated with RB10 in the perinuclear region. The selective enhancement of DNA lesions in the transfected cells was abolished by co-incubation with exogenous RB10, suggesting that intact RB24 bound to its cognate perinuclear sites prior to releasing the alkylating species. Analysis of key signaling proteins in the cells demonstrated a DNA-damage dependent activation of JNK and down-regulation of Bad through inhibition of EGFR or Her2 phosphorylation by RB24. This translated in to a 10-20-fold stronger cytocidal activity by RB24 when compared with its clinical counterpart Temodal®.The results suggest a targeting model based on a by-stander effect that increases the levels of DNA damage in the transfectants and a cooperative enhancement of apoptosis through JNK activation and down regulation of Bad. This convergent mechanism may account for the remarkable potency of RB24 against the oncogenic expressing transfectants. The results in toto indicate that the Combi-Targeting concept may well represent a novel strategy to enhance the potency of alkylators in EGFR- and Her2-expressing cells.
A multicenter, open-label, uncontrolled study of ONO-7643/anamorelin in cachexia patients with gastrointestinal cancer
Authors: Junji Furuse, Satoru Hamauchi, Toshimi Takano, Yoshinori Munemoto, Ken Furuya, Hideo Baba, Manabu Takeuchi, Yasuhiro Choda, Takashi Higashiguchi, Tateaki Naito, Kei Muro, Koichi Takayama, Kazuo Tamura
Journal: Annals of Oncology (2018)
Law on gross negligence manslaughter is flawed, says leading medical lawyer
Authors: Clare Dyer
Journal: BMJ (2018)

The law on gross negligence manslaughter (GNM) is flawed because, unlike other areas of law, it asks a jury to decide what is or is not a criminal offence, the leading medical lawyer Robert Francis told members of parliament.

Francis, who chaired the inquiry into poor care at Mid Staffordshire NHS Foundation Trust, was giving evidence to the Commons Health and Social Care Committee, which is looking at the law on GNM in the wake of the case of the trainee paediatrician Hadiza Bawa-Garba.

She was convicted of manslaughter after the death of six year old Jack Adcock from sepsis. A medical practitioners’ tribunal suspended her from the medical register for 12 months, but the General Medical Council appealed to the …
Breastfeeding Report Card
Authors: Bridget Kuehn
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Abstract 13228: SUMO2 Induces Cardiac Hypertrophy in Vivo and in Vitro, Independent of Sumoylation
Authors: Alexander Bernt, Ashraf Y Rangrez, Matthias Eden, Claudia Rohr, Sylvia Katz, Andreas Jungmann, Tatjana Williams, Oliver Ritter, Oliver J Müller, Hugo A Katus, Derk Frank, Norbert Frey
Journal: Circulation (2016)

Introduction: The calcineurin (Cn)-NFAT signaling axis is a pivotal pathway in cardiac physiology and pathophysiology including remodeling and pathological hypertrophy. Methods and results: We have...
18F-Choline and 18F-FDG PET/CT in a Patient With Diffuse Large B-Cell Lymphoma and Recurrent Prostate Cancer
Authors: Nicolas De Leiris, Laurent Riou, Julien Leenhardt, Jean-Philippe Vuillez, Loïc Djaileb
Journal: Clinical Nuclear Medicine (2018)

We report herein the case of an 80-year-old man who was referred for a biochemical recurrence of a high-risk prostate cancer. In addition to prostate cancer recurrence, F-choline allowed partial initial staging of an incidental diffuse large B-cell lymphoma which was further confirmed and staged using F-FDG and a biopsy. Two types of metabolic behavior were therefore identified using F-choline and F-FDG which corresponded to 2 different uptake patterns, that is, those of the prostate and lymphoma tumoral cell contingents.
ERV1/ChemR23 Signaling Protects Against Atherosclerosis by Modifying Oxidized Low-Density Lipoprotein Uptake and Phagocytosis in Macrophages
Authors: Andres Laguna-Fernandez, Antonio Checa, Miguel Carracedo, Gonzalo Artiach, Marcelo H. Petri, Roland Baumgartner, Maria J. Forteza, Xintong Jiang, Teodora Andonova, Mary E. Walker, Jesmond Dalli, Hildur Arnardottir, Anton Gisterå, Silke Thul, Craig E. Wheelock, Gabrielle Paulsson-Berne, Daniel F.J. Ketelhuth, Göran K. Hansson, Magnus Bäck
Journal: Circulation (2018)

In addition to enhanced proinflammatory signaling, impaired resolution of vascular inflammation plays a key role in atherosclerosis. Proresolving lipid mediators formed through the 12/15 lipoxygenase pathways exert protective effects against murine atherosclerosis. n-3 Polyunsaturated fatty acids, including eicosapentaenoic acid (EPA), serve as the substrate for the formation of lipid mediators, which transduce potent anti-inflammatory and proresolving actions through their cognate G-protein-coupled receptors. The aim of this study was to identify signaling pathways associated with EPA supplementation and lipid mediator formation that mediate atherosclerotic disease progression.Lipidomic plasma analysis were performed after EPA supplementation in Apoe-/- mice. Erv1/Chemr23-/- xApoe-/- mice were generated for the evaluation of atherosclerosis, phagocytosis, and oxidized low-density lipoprotein uptake. Histological and mRNA analyses were done on human atherosclerotic lesions.Here, we show that EPA supplementation significantly attenuated atherosclerotic lesion growth induced by Western diet in Apoe-/- mice and was associated with local cardiovascular n-3 enrichment and altered lipoprotein metabolism. Our systematic plasma lipidomic analysis identified the resolvin E1 precursor 18-monohydroxy EPA as a central molecule formed during EPA supplementation. Targeted deletion of the resolvin E1 receptor Erv1/Chemr23 in 2 independent hyperlipidemic murine models was associated with proatherogenic signaling in macrophages, increased oxidized low-density lipoprotein uptake, reduced phagocytosis, and increased atherosclerotic plaque size and necrotic core formation. We also demonstrate that in macrophages the resolvin E1-mediated effects in oxidized low-density lipoprotein uptake and phagocytosis were dependent on Erv1/Chemr23. When analyzing human atherosclerotic specimens, we identified ERV1/ChemR23 expression in a population of macrophages located in the proximity of the necrotic core and demonstrated augmented ERV1/ChemR23 mRNA levels in plaques derived from statin users.This study identifies 18-monohydroxy EPA as a major plasma marker after EPA supplementation and demonstrates that the ERV1/ChemR23 receptor for its downstream mediator resolvin E1 transduces protective effects in atherosclerosis. ERV1/ChemR23 signaling may represent a previously unrecognized therapeutic pathway to reduce atherosclerotic cardiovascular disease.
Treatment of Varicocele in Children and Adolescents: A Systematic Review and Meta-analysis from the European Association of Urology/European Society for Paediatric Urology Guidelines Panel
Authors: Mesrur Selcuk Silay, Lisette Hoen, Josine Quadackaers, Shabnam Undre, Guy Bogaert, Hasan Serkan Dogan, Radim Kocvara, Rien J.M. Nijman, Christian Radmayr, Serdar Tekgul, Raimund Stein
Journal: European Urology (2018)
Clinical benefit of whole genome and transcriptome analysis (WGTA) in metastatic colorectal cancer (MCRC): Results from the personalized oncogenomics program (POG)
Authors: S.L. Liu, J. Loree, D. Renouf, M. Jones, S. Yip, M. Marra, S. Jones, J. Nelson, J. Laskin, H. Lim, S. Gill
Journal: Annals of Oncology (2018)
Real-world effectiveness of pazopanib in patients with intermediate prognostic risk advanced renal cell carcinoma (PRINCIPAL study)
Authors: G. Procopio, A. Bamias, M. Schmidinger, R. Hawkins, A. Rodriguez Sanchez, S. Vazquez, N. Srihari, H. Kalofonos, P. Bono, C. Pisal, Y. Hirschberg, L. Dezzani, Q. Ahmad, C. Suarez Rodriguez, E. Jonasch
Journal: Annals of Oncology (2018)
Selection of Reference Regions to Model Neurodegeneration in Huntington Disease by 18F-FDG PET/CT Using Imaging and Clinical Parameters
Authors: Diego Alfonso López Mora, Frederic Sampedro, Valle Camacho, Alejandro Fernández, Francisco Fuentes, Joan Duch, Jesús Pérez-Perez, Saül Martínez-Horta, Juan Marín-Lahoz, Anna Domènech, Albert Flotats, Montserrat Estorch, Jaime Kulisevsky, Ignasi Carrió
Journal: Clinical Nuclear Medicine (2018)

Normalization to an appropriate reference region in F-FDG PET imaging may enhance diagnostic performance in Huntington disease (HD). We aimed to identify stable brain areas that could be used to model neurometabolic degeneration in HD correlating imaging (SUVrvalues at the basal ganglia [BBGG]) and clinical parameters (disease burden score [DBS]).We performed brain F-FDG PET/CT in 38 manifest HD patients (meanage ± SD, 54 ± 14.3 years; CAGrepeats ± SD, 44.2 ± 3.1), 20 premanifest HD patients (meanage ± SD, 42.7 ± 11.7 years; CAGrepeats ± SD, 40 ± 3.8), and 18 healthy controls (NC; meanage ± SD, 45 ± 13.2 years). For quantitative analysis, we selected (a) defined reference regions from the Montreal Neurological Institute space atlas (pons, whole cerebellum, cerebral white matter, thalamus, and a pons-cerebellar vermis region of interest), and (b) reference clusters obtained by voxelwise statistical comparison across groups (P < 0.05 FWE; extent voxel threshold k = 200). Each candidate reference region and reference cluster was quantitatively assessed using imaging and clinical parameters.Comparing HD and NC groups, we obtained a reference cluster in the cerebellum, and in temporal and frontal lobes. Comparing manifest HD and premanifest HD patients, we observed reference clusters in the cerebellum, pons, thalamus, parietal lobe, and cuneus. The set of reference regions showed a significant correlation between SUVrvalues at the BBGG and DBS in all HD patients. In premanifest HD patients, the correlation between SUVrvalues at the BBGG and DBS was significant using the pons-cerebellar vermis region of interest, the thalamus as defined reference regions, and the pons and thalamus as reference clusters. In manifest HD patients, the correlation was significant using the temporal and white matter frontal lobe clusters. Variance between SUVrvalues in the set of reference regions and reference clusters was minimal within NC.The pons may be a stable and reliable region to calculate SUVrvalues to model the neurometabolic degeneration in quantitative F-FDG PET imaging in HD.
GW29-e0514 Impact of Baseline Smoking Status on Long-term Prognosis of Patients with Coronary Artery Disease Underwent Percutaneous Coronary Intervention: A Large Single-center Data
Authors: Ru LIU, Zhan Gao, Huanhuan Wang, Xiaofang Tang, Ying Song, Jingjing Xu, Jue Chen, Shubin Qiao, Yuejin Yang, Runlin Gao, Bo Xu, Jinqing Yuan
Journal: Journal of the American College of Cardiology (2018)
Abstract 12310: Benefits of Early Co-administration of Beta-blockers and Ivabradine in Patients Hospitalized Due to Worsening Heart Failure: Insights From a Prospective Pragmatic Study Within the Optimize Heart Failure Care Program
Authors: Yury Lopatin, Anna Grebennikova, Hamayak Sisakian, Hamlet Hayrapetyan, Zurab Pagava, Maria Glezer, Anna Chesnikova, Timur Abdullaev, Gulnaz Dadashova, Ekaterina Tarlovskaya, Alena Kurlianskaya, Natalia Koziolova, Salim Berkinbaev, Amina Rakisheva, Leonid Voronkov, Vera Tseluyko, Zviad Kipiani
Journal: Circulation (2017)

Introduction: Few trials have demonstrated an improvement in systolic function in patients hospitalized with heart failure (HF) after early co-administration of beta-blockers (BBs) and ivabradine. ...
Response to: ‘Effectiveness and safety of tocilizumab for the treatment of refractory systemic sclerosis associated interstitial lung disease: a case series’ by Narváez
Authors: Dinesh Khanna, Angelika Jahreis, Celia J F Lin
Journal: Annals of the Rheumatic Diseases (2018)

We read the intriguing findings by Narvaez1 about the effect of tocilizumab (TCZ) in patients with established systemic sclerosis-associated interstitial lung disease (SSc-ILD) with great interest. In the double-blind, randomised, placebo-controlled faSScinate study2 and open-label extension,3 we assessed the efficacy and safety of TCZ in patients with systemic sclerosis. There were important differences between our trial and the data presented by Narvaez1. In the faSScinate study, the patient population shown to benefit from TCZ had shorter duration of disease (mean disease duration of 1.6 years in faSScinate vs 6.9 years in Narvaez), increased serum acute phase reactants, …
Circulating tumour DNA (ctDNA) as a tool to assess response and guide therapy adaptation in rectal cancer
Authors: S. Khakoo, P. Carter, N. Valeri, R. Shaikh, T. Jones, R. Begum, I. Rana, S. Picchia, M. Bali, G. Brown, A. Wotherspoon, M. Terlizzo, K. von Loga, I. Ahmed, D. Watkins, I. Chau, N. Starling, D. Tait, M. Hubank, D. Cunningham
Journal: Annals of Oncology (2018)
Assessment of Attitudes Toward Deprescribing in Older Medicare Beneficiaries in the United States
Authors: Emily Reeve, Jennifer L. Wolff, Maureen Skehan, Elizabeth A. Bayliss, Sarah N. Hilmer, Cynthia M. Boyd
Journal: JAMA Internal Medicine (2018)

Use of harmful and/or unnecessary medications in older adults is prevalent. This can lead to avoidable harms such as adverse drug reactions, falls, hospitalization, and mortality. Primary care physicians report that patient resistance to discontinuing medication use is a significant barrier to deprescribing.To describe the attitudes of older adults toward deprescribing and to determine whether individual characteristics are associated with these attitudes.For this population-based survey study of US Medicare beneficiaries 65 years and older, data were obtained from the Medication Attitudes module fielded through in-person interviews in round 6 of the National Health and Aging Trends Study (weighted response rate of round 6 was 88.5%). The questions in this module were drawn from the Patients' Attitudes Towards Deprescribing questionnaire and its revised version. The Medication Attitudes module was fielded to a random one-third (n = 2124) of the National Health and Aging Trends Study participants (weighted response rate of this module was 94.8%).Responses to 2 statements ("If my doctor said it was possible, I would be willing to stop one or more of my regular medicines" and "I would like to reduce the number of medicines I am taking") were the main outcomes of interest.Of the 1981 Medicare beneficiaries included in the study, 1149 (55.2%, weighted) were women, and the majority (n = 715 [54.6%, weighted]) were 65 to 74 years old. A total of 1752 (92.0%, weighted) older adults reported being willing to stop taking 1 or more of their medicines if their physician said it was possible, and 1241 (66.6%, weighted) older adults wanted to reduce the number of medicines that they were taking. Older adults taking 6 or more medications had greater odds than those taking fewer than 6 medications of being willing to stop taking 1 or more of their medicines (adjusted odds ratio, 2.90; 95% CI, 1.74-4.82) and wanting to reduce the number of medicines that they were taking (adjusted odds ratio, 2.31; 95% CI, 1.71-3.13).Physicians considering deprescribing as part of comprehensive, patient-centered care should be reassured that a majority of older Americans are open to having 1 or more of their medicines deprescribed if their physician says it is possible, and more than two-thirds want to reduce the number of medicines that they are taking.