tbuckley/cabot-search huggingface dataset:
Association of methylation of genes in the taurine/hypotaurine pathway with worse prognosis in renal cell carcinoma.
Authors: Andrew Gross, Michel Choueiri, John P. Shen, James Michael Randall, Trey Ideker, Matan Hofree
Journal: Journal of Clinical Oncology (2013)

e15562 Background: Epigenetic silencing of genes associated with the taurine/hypotaurine pathway has been associated with worse outcome in several tumors such as CDO1 in breast cancer, and GAD1 in prostate cancer. Our objective was to assess the prognostic value of methylation status of genes in the taurine/hypotaurine pathway in patients with renal cell carcinoma (RCC). Methods: We performed an analysis of 283 RCC samples using data from The Cancer Genome Atlas (TCGA). Ten genes belonging to the taurine/hypotaurine metabolic were analyzed using principal component analysis to determine a composite methylation profile of the pathway. A Cox proportional-hazards regression model was then used to determine the association of the composite methylation profile with patient survival. Results: CDO1, GAD2, and GAD1 influenced the outcome of the composite gene the most. Increasing degree of methylation correlated with more advanced tumor stage, and was an independent predictor of overall patient survival. Among patients with localized and locally advanced disease (stages 1-3), high levels of methylation correlated with significantly worse OS (Table). No difference in outcome was noted in patients with metastatic disease. Conclusions: Silencing of genes in the taurine/hypotaurine pathway through methylation is predictive of poorer outcomes in patients with localized RCC. Increasing degree of methylation correlates with tumor stage. Among patients with localized disease and belonging to the same stage, higher degree of methylation correlated with with worse prognosis. Interestingly, this effect is not observed in patients with metastatic disease, indicating the possible activation of other pathways that override the role of the taurine/hypotaurine pathway. [Table: see text]
Combination Therapy to Target Reperfusion Injury After ST-Segment–Elevation Myocardial Infarction
Authors: Derek J. Hausenloy, Derek M. Yellon
Journal: Circulation (2017)

Article, see p 894 T imely reperfusion therapy by primary percutaneous coronary intervention (PPCI) combined with effective secondary preventive therapy has contributed to a decline in mortality rates after ST-segment-elevation myocardial infarction (STEMI) over the last few years.However, the incidence and severity of heart failure after STEMI are rising.Therefore, novel cardioprotective therapies are required to reduce myocardial infarct (MI) size and preserve left ventricular (LV) systolic function to prevent heart failure and improve clinical outcomes after PPCI. 1,2ver recent years, a large number of cardioprotective therapies, which have been demonstrated to be effective at reducing MI size in the laboratory setting, have been unable either to reduce MI size or to improve clinical outcomes after STEMI.][3] Another major reason for the failure to translate cardioprotection may have been the adoption of a single-targeted monotherapy approach, a strategy that may be inadequate to address the multifaceted components of myocardial reperfusion injury, including endothelial dysfunction, microvascular obstruction, oxidative stress, calcium overload, mitochondrial dysfunction, and inflammation. 2,46][7] The adoption of combination therapy as a multitargeted cardioprotective strategy may be mediated as follows: (1) using ≥2 therapies to target different cardioprotective intracellular signaling pathways within the cardiomyocyte 5,7 ; (2) using ≥2 therapies to target cardioprotection in different cell components within the heart such as endothelial cells, platelets, cardiomyocytes, and inflammatory cells; and (3) using 1 therapy with capabilities of reducing MI size through ≥2 cardioprotective targets such as inflammatory cells and cardiomyocytes.In this regard, the NACIAM study (NAC in Acute Myocardial Infarction) by Pasupathy et al 8 in this issue of Circulation investigated the MI-limiting effects of combining 2 "old" cardioprotective therapies, N-acetylcysteine (NAC; an antioxidant) and nitroglycerin (a nitric oxide donor), 9 in patients with STEMI treated by PPCI.In a multicenter study of 112 patients with STEMI, they found that the administration of a 48-hour intravenous infusion of NAC, initiated before PPCI, on a background of a low-dose 48-hour intravenous nitroglycerin infusion reduced acute MI size by >30% in a subset of 75 patients (quantified by late-gadolinium-enhancement cardiovascular magnetic resonance [CMR]).The MI-limiting effect of NAC was still present at Combination Therapy to Target Reperfusion Injury After ST-Segment-Elevation Myocardial InfarctionA More Effective Approach to Cardioprotection
Effective Teaching
Authors: A. Donald
Journal: BMJ (1998)

Good teaching sessions are a bit like parties. It is good to strike a balance between soundly preparing for who's coming and what people should learn, while allowing people enough time and freedom to ask questions and to take in new knowledge. Basic planning is also essential for timekeeping.

Providing the logistical information necessary to complete the session or course saves everyone time and frustration. It is helpful to provide a handout that includes the course outline, dates and times of teaching sessions, due dates for exams and assignments, how you can be contacted and any dates you will be away, office hours, reading lists, useful websites, and where reading materials can be found. People usually do not mind buying books that will be used often, and appreciate details of their cost and availability. Local booksellers are usually happy to supply enough books for the class. Packaging other printed materials into a reading pack also saves students a great deal of time. A librarian can help to obtain copyright permission from the relevant body.

### Summary points

Almost everyone has someone who took an interest in their welfare and development. You may not have thought of that person as a mentor, but you know that it was an important relationship and a valuable influence

Which problem(s) would you like learners to be able to solve after each session? Disordered concepts are extremely difficult to learn, so it is a good idea to …
Early Stage Follicular Lymphoma. Predictive Role of Minimal Residual Disease (MRD) and Impact of MRD-Driven Treatment with Radiotherapy and Rituximab on Clinical Outcome
Authors: Alessandro Pulsoni, Irene Della Starza, Maria Elena Tosti, Luca Vincenzo Cappelli, Giorgia Annechini, Marzia Cavalli, Lucia Anna De Novi, Gianna Maria D'Elia, Lavinia Grapulin, Anna Guarini, Ilaria Del Giudice, Robin Foa
Journal: Blood (2016)
Abstract 154: Allogeneic Cardiosphere-derived Cells From an Aged Donor Elicit Long-term Improvements in Left Ventricular Function and Myocyte Proliferation in a Mini-swine Model of Chronic Myocardial Ischemia
Authors: Brian R Weil, Gen Suzuki, Merced M Leiker, Andrew Goelz, John M Canty
Journal: Circulation Research (2015)

Objective: Virtually all large animal studies of cell-based therapy have employed young donor-recipient pairs. Since aging may impact the reparative ability of allogeneic cardiosphere-derived cells (CDCs), we tested whether CDCs from an aged donor promote functional repair of ischemic myocardium using a mini-swine model that enabled serial assessment of left ventricular (LV) function over an extended follow-up period. Methods: Immunosuppressed mini-swine (cyclosporine 100 mg/day) with a chronic (4-months) LAD stenosis were untreated (n=8) or received 20 million allogeneic aged CDCs (n=10). Cells were cultivated from a 9-year old mini-pig and infused into the 3 major coronary arteries under continuous flow (1 million cells/min). LV function was assessed by echocardiography at baseline and over a 3-month follow-up period, at which time histological assessment of myocyte morphometry, proliferation (Ki67), and cell retention (Y-FISH) was performed. Results: Wall thickening (WT) of the ischemic LAD region was impaired at baseline (LAD: 42.7 ± 2.1% vs. Remote: 81.4 ± 4.8%, p&lt;0.01) and not different between treatment groups. One month later, LAD WT improved in aged CDC-treated animals (from 41.0 ± 3.1 to 53.0 ± 1.7%, p=0.01) but remained depressed in untreated animals (from 45.1 ± 2.8% to 44.9 ± 2.6%, p=0.97). Extended follow-up revealed that LAD WT continued to improve, reaching 60.2 ± 1.6% (p=0.01) 3-months after CDC treatment. Histological analyses demonstrated morphometric changes consistent with myocyte regeneration, including an increase in myocyte nuclear density (1231 ± 34 vs. 1094 ± 34 nuclei/mm 2 , p=0.02) and reduction in myocyte diameter (13.9 ± 0.2 vs. 14.5 ± 0.3 μm, p=0.05). Increases in Ki67 + myocytes (468 ± 92 vs. 199 ± 32 nuclei/10 6 myocyte nuclei, p=0.02) and rare Y + cells in sex-mismatched recipients (0.5 ± 0.2 cells/cm 2 ) supported endogenous myocyte proliferation as the primary source of new myocytes. Conclusion: CDCs from an aged donor retain their reparative capacity to promote functional improvement and increase myocyte number following global intracoronary infusion. The progressive improvement in LV function 3-months after treatment with ongoing myocyte proliferation supports a long-lasting benefit after a single infusion.
Influence of muscle mass in the assessment of lower limb strength in COPD: validation of the prediction equation
Authors: Ruth Trethewey, Dale Esliger, Emily Petherick, Rachael Evans, Neil Greening, Benjamin James, Andrew Kingsnorth, Mike Morgan, Mark Orme, Lauren Sherar, Sally Singh, Nicole Toms, Michael Steiner
Journal: Thorax (2017)

Absence of established reference values limits application of quadriceps maximal voluntary contraction (QMVC) measurement. The impact of muscle mass inclusion in predictions is unclear. Prediction equations encompassing gender, age and size with (FFM+) and without (FFM−), derived in healthy adults (n=175), are presented and compared in two COPD cohorts recruited from primary care (COPD-PC, n=112) and a complex care COPD clinic (COPD-CC, n=189). Explained variance was comparable between the prediction models (R2: FFM+: 0.59, FFM−: 0.60) as were per cent predictions in COPD-PC (88.8%, 88.3%). However, fat-free mass inclusion reduced the prevalence of weakness in COPD, particularly in COPD-CC where 11.9% fewer were deemed weak.
New class of precision antimicrobials redefines role of <i>Clostridium difficile</i> S-layer in virulence and viability
Authors: Joseph A. Kirk, Dana Gebhart, Anthony M. Buckley, Stephen Lok, Dean Scholl, Gillian R. Douce, Gregory R. Govoni, Robert P. Fagan
Journal: Science Translational Medicine (2017)

Rare Clostridium difficile mutants lacking surface-layer protein A escape killing by Avidocin-CDs and display severe phenotypic defects that compromise virulence in animals.
Enhanced surveillance of initial cases of pandemic H1N1 2009 influenza in Ireland, April - July 2009
Authors: J Martin, J O’Donnell, D Igoe, A O’Hora, L Thornton, N Murphy, G Cullen, M Fitzgerald, S Cotter, P McKeown, D O’Flanagan, Collective in conjunction with the National Pu
Journal: Eurosurveillance (2009)

From 28 April to 18 July 2009 there were 156 cases of pandemic H1N1 2009 influenza confirmed in Ireland. During this time, Ireland was in containment phase, and detailed case-based epidemiological information was gathered on all cases presenting in the community and acute health care setting. Active case finding was performed among contacts of cases. Eighty percent of cases were in people under the age of 35 years, and 86% were imported. The most frequent symptoms were fever, sore throat, myalgia and dry cough. Nine people were hospitalised, no fatalities occurred.
Managing Conflicts of Interest in Practice Guidelines Panels—Reply
Authors: Harold C. Sox
Journal: JAMA (2017)

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
12‐OH‐17,18‐Epoxyeicosatetraenoic acid alleviates eosinophilic airway inflammation in murine lungs
Authors: T. Mochimaru, K. Fukunaga, J. Miyata, M. Matsusaka, K. Masaki, H. Kabata, S. Ueda, Y. Suzuki, T. Goto, D. Urabe, M. Inoue, Y. Isobe, M. Arita, T. Betsuyaku
Journal: Allergy (2017)

Abstract Background Asthma is characterized by airway inflammation and obstruction with eosinophil infiltration into the airway. Arachidonic acid, an omega‐6 fatty acid, is metabolized into cysteinyl leukotriene with pro‐inflammatory properties for allergic inflammation, whereas the omega‐3 fatty acid eicosapentaenoic acid (EPA) and its downstream metabolites are known to have anti‐inflammatory effects. In this study, we investigated the mechanism underlying the counter‐regulatory roles of EPA in inflamed lungs. Methods Male C57BL6 mice were sensitized and challenged by ovalbumin (OVA). After EPA treatment, we evaluated the cell count of Bronchoalveolar lavage fluid (BALF), mRNA expressions in the lungs by q‐PCR, and the amounts of lipid mediators by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS)‐based lipidomics. We investigated the effect of the metabolite of EPA by in vivo and in vitro studies. Results Eicosapentaenoic acid treatment reduced the accumulation of eosinophils in the airway and decreased mRNA expression of selected inflammatory mediators in the lung. Lipidomics clarified the metabolomic profile in the lungs. Among EPA‐derived metabolites, 12‐hydroxy‐17,18‐epoxyeicosatetraenoic acid (12‐OH‐17,18‐EpETE) was identified as one of the major biosynthesized molecules; the production of this molecule was amplified by EPA administration and allergic inflammation. Intravenous administration of 12‐OH‐17,18‐EpETE attenuated airway eosinophilic inflammation through downregulation of C‐C chemokine motif 11 ( CCL11 ) mRNA expression in the lungs. In vitro, this molecule also inhibited the release of CCL11 from human airway epithelial cells stimulated with interleukin‐4. Conclusion These results demonstrated that EPA alleviated airway eosinophilic inflammation through its conversion into bioactive metabolites. Additionally, our results suggest that 12‐OH‐17,18‐EpETE is a potential therapeutic target for the management of asthma.
The oncogenic role of the In1-ghrelin splicing variant in prostate cancer aggressiveness
Authors: Daniel Hormaechea-Agulla, Manuel D. Gahete, Juan M. Jiménez-Vacas, Enrique Gómez-Gómez, Alejandro Ibáñez-Costa, Fernando L-López, Esther Rivero-Cortés, André Sarmento-Cabral, José Valero-Rosa, Julia Carrasco-Valiente, Rafael Sánchez-Sánchez, Rosa Ortega-Salas, María M. Moreno, Natia Tsomaia, Steve M. Swanson, Michael D. Culler, María J. Requena, Justo P. Castaño, Raúl M. Luque
Journal: Molecular Cancer (2017)

The Ghrelin-system is a complex, pleiotropic family composed of several peptides, including native-ghrelin and its In1-ghrelin splicing variant, and receptors (GHSR 1a/b), which are dysregulated in various endocrine-related tumors, where they associate to pathophysiological features, but the presence, functional role, and mechanisms of actions of In1-ghrelin splicing variant in prostate-cancer (PCa), is completely unexplored. Herein, we aimed to determine the presence of key ghrelin-system components (native-ghrelin, In1-ghrelin, GHSR1a/1b) and their potential pathophysiological role in prostate cancer (PCa).In1-ghrelin and native-ghrelin expression was evaluated by qPCR in prostate tissues from patients with high PCa-risk (n = 52; fresh-tumoral biopsies), and healthy-prostates (n = 12; from cystoprostatectomies) and correlated with clinical parameters using Spearman-test. In addition, In1-ghrelin and native-ghrelin was measured in plasma from an additional cohort of PCa-patients with different risk levels (n = 30) and control-healthy patients (n = 20). In vivo functional (proliferation/migration) and mechanistic (gene expression/signaling-pathways) assays were performed in PCa-cell lines in response to In1-ghrelin and native-ghrelin treatment, overexpression and/or silencing. Finally, tumor progression was monitored in nude-mice injected with PCa-cells overexpressing In1-ghrelin, native-ghrelin and empty vector (control).In1-ghrelin, but not native-ghrelin, was overexpressed in high-risk PCa-samples compared to normal-prostate (NP), and this expression correlated with that of PSA. Conversely, GHSR1a/1b expression was virtually absent. Remarkably, plasmatic In1-ghrelin, but not native-ghrelin, levels were also higher in PCa-patients compared to healthy-controls. Furthermore, In1-ghrelin treatment/overexpression, and to a much lesser extent native-ghrelin, increased aggressiveness features (cell-proliferation, migration and PSA secretion) of NP and PCa cells. Consistently, nude-mice injected with PC-3-cells stably-transfected with In1-ghrelin, but not native-ghrelin, presented larger tumors. These effects were likely mediated by ERK1/2-signaling activation and involved altered expression of key oncogenes/tumor suppressor genes. Finally, In1-ghrelin silencing reduced cell-proliferation and PSA secretion from PCa cells.Altogether, our results indicate that In1-ghrelin levels (in tissue) and circulating levels (in plasma) are increased in PCa where it can regulate key pathophysiological processes, thus suggesting that In1-ghrelin may represent a novel biomarker and a new therapeutic target in PCa.
Survivorship Care Planning: Why Is It Taking So Long?
Authors: Sarah A. Birken, Deborah K. Mayer
Journal: Journal of the National Comprehensive Cancer Network (2017)

Survivorship care planning is a process that focuses on the transition from active cancer treatment to a coordinated and comprehensive care system to address patients' unique needs. Survivorship care plans (SCPs) are increasingly viewed as a key component of survivorship care planning. SCPs have been recommended for >10 years to promote care coordination, communication, and record-keeping efficiency; however, SCP implementation has been challenging. We elaborate on the challenges of SCP implementation, summarize evidence regarding potential methods of promoting SCP implementation, and describe a research agenda for generating more definitive evidence to support SCP implementation in practice.
Densification of Type I Collagen Matrices as a Model for Cardiac Fibrosis
Authors: Logan J. Worke, Jeanne E. Barthold, Benjamin Seelbinder, Tyler Novak, Russell P. Main, Sherry L. Harbin, Corey P. Neu
Journal: Advanced Healthcare Materials (2017)

Cardiac fibrosis is a disease state characterized by excessive collagenous matrix accumulation within the myocardium that can lead to ventricular dilation and systolic failure. Current treatment options are severely lacking due in part to the poor understanding of the complexity of molecular pathways involved in cardiac fibrosis. To close this gap, in vitro model systems that recapitulate the defining features of the fibrotic cellular environment are in need. Type I collagen, a major cardiac extracellular matrix protein and the defining component of fibrotic depositions, is an attractive choice for a fibrosis model, but demonstrates poor mechanical strength due to solubility limits. However, plastic compression of collagen matrices is shown to significantly increase its mechanical properties. Here, confined compression of oligomeric, type I collagen matrices is utilized to resemble defining hallmarks seen in fibrotic tissue such as increased collagen content, fibril thickness, and bulk compressive modulus. Cardiomyocytes seeded on compressed matrices show a strong beating abrogation as observed in cardiac fibrosis. Gene expression analysis of selected fibrosis markers indicates fibrotic activation and cardiomyocyte maturation with regard to the existing literature. With these results, a promising first step toward a facile heart-on-chip model is presented to study cardiac fibrosis.
Editorial: Response to the American College of Physicians Osteoporosis Guideline, 2017 Update
Authors: Liron Caplan, Karen E. Hansen, Kenneth G. Saag
Journal: Arthritis & Rheumatology (2017)

The American College of Physicians (ACP) recently updated their clinical practice guidelines for the treatment of low bone density and osteoporosis. These guidelines, aimed at generalists, importantly emphasize the critical nature of osteoporosis and provide a basic framework to guide its management. We support the ACP's effort to improve awareness and treatment of osteoporosis. However, we would like to address some important limitations encompassed by the six ACP recommendations that are particularly relevant to specialists, such as rheumatologists.

This article is protected by copyright. All rights reserved.
SP0095 Eular recommendations for the use of imaging in the diagnosis and management of large vessel vasculitis in clinical practice
Authors: C Dejaco
Journal: Annals of the Rheumatic Diseases (2017)

Large vessel vasculitis (LVV) is the most common form of primary vasculitis comprising giant cell arteritis (GCA) and Takayasu arteritis (TA). Although temporal artery biopsy and conventional angiography are still the golden standard diagnostic tests for GCA and TA, respectively, modern imaging methods including ultrasound, magnetic resonance imaging, computed tomography (CT) and <sup>18</sup>F-FDG positron emission tomography - CT are increasingly used. In clinical practice however, these methods are inconsistently applied and rheumatologists and other specialists are still uncertain about the specific value of these modalities. This project has been conducted with the aim to provide user-friendly, evidence-based recommendations for the use of modern imaging methods for diagnosis, monitoring and outcome prediction of primary LVV. Specifically, we give advice on 1) when to use these imaging techniques, 2) what specialists might conclude from imaging results and 3) what technical standards are required to achieve high quality imaging results. These recommendations aim at an early and specific diagnosis as well as an improved assessment of LVV, thus ultimately leading to better outcomes of patients with LVV. <h3>Disclosure of Interest</h3> C. Dejaco Grant/research support from: Pfizer, MSD, Esaote, Speakers bureau: Pfizer, MSD, AbVie, Celgene, UCB, Roche, BMS, GSK, Novartis, Sandoz
Better sleep may reduce mental illness symptoms, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Improving sleep with online digital cognitive behavioural therapy (CBT) is associated with significant reductions in paranoia and hallucinations, a randomised trial in UK university students with insomnia has found.1

The researchers, led by Daniel Freeman, from the University of Oxford’s Warneford Hospital, said, “This trial indicates the importance of sleep difficulties for mental health in the general population and the need for a reconsideration in clinical services of the priority given to improving sleep.

“It …