tbuckley/cabot-search huggingface dataset:
Incidence trends of gastroenteropancreatic neuroendocrine tumors in the United States from 1975 to 2012.
Authors: Mi Ri Lee, Cynthia Harris, Kiwoon Joshua Baeg, Juan P. Wisnivesky, Michelle Kang Kim
Journal: Journal of Clinical Oncology (2018)

231 Background: Although multiple studies document a rise in gastroenteropancreatic neuroendocrine tumor (GEP-NET) incidence over the past several decades, there are limited national data regarding recent trends. Using a population-based registry, we evaluated GEP-NET incidence trends in the US population from 1975-2012 by age and calendar year at diagnosis and year of birth. Methods: GEP-NET cases between 1975-2012 were identified from the most recent version of the Surveillance, Epidemiology, and End Results (SEER) registry based on histologic and site codes. We calculated overall annual incidence, age-adjusted incidence (number of cases per 100,000), annual percent change (APC), and average APC by 5 year age intervals. We also evaluated the incidence rates by age, period, and birth year cohorts. Results: We identified 22,744 patients with GEP-NETs. In adults age 25-39 years, GEP-NET incidence rates declined from the mid 1970s to early 1980s, then increased until 2012 (Table 1). In adults age 40 and older and between ages 15-24 years, incidence rates generally increased continuously from 1975 to 2012. Adults age 40-69 years demonstrated the most rapid increases in average APC, approximately 4-6% per year. Overall incidence rates were highest in adults age 70-84 years. Since the late 1880s, GEP-NET incidence has increased in consecutive birth cohorts. Conclusions: Our study demonstrates that more recent generations have had higher incidence rates than more distant generations. In addition, GEP-NETs are more common among older adults and the number of GEP NETs has increased in past decades. [Table: see text]
Alport syndrome: a unified classification of genetic disorders of collagen IV α345: a position paper of the Alport Syndrome Classification Working Group
Authors: Clifford E. Kashtan, Jie Ding, Guido Garosi, Laurence Heidet, Laura Massella, Koichi Nakanishi, Kandai Nozu, Alessandra Renieri, Michelle Rheault, Fang Wang, Oliver Gross
Journal: Kidney International (2018)
Blocking fatty acid–fueled mROS production within macrophages alleviates acute gouty inflammation
Authors: Christopher J. Hall, Leslie E. Sanderson, Lisa M. Lawrence, Bregina Pool, Maarten van der Kroef, Elina Ashimbayeva, Denver Britto, Jacquie L. Harper, Graham J. Lieschke, Jonathan W. Astin, Kathryn E. Crosier, Nicola Dalbeth, Philip S. Crosier
Journal: Journal of Clinical Investigation (2018)

Gout is the most common inflammatory arthritis affecting men. Acute gouty inflammation is triggered by monosodium urate (MSU) crystal deposition in and around joints that activates macrophages into a proinflammatory state, resulting in neutrophil recruitment. A complete understanding of how MSU crystals activate macrophages in vivo has been difficult because of limitations of live imaging this process in traditional animal models. By live imaging the macrophage and neutrophil response to MSU crystals within an intact host (larval zebrafish), we reveal that macrophage activation requires mitochondrial ROS (mROS) generated through fatty acid oxidation. This mitochondrial source of ROS contributes to NF-κB–driven production of IL-1β and TNF-α, which promote neutrophil recruitment. We demonstrate the therapeutic utility of this discovery by showing that this mechanism is conserved in human macrophages and, via pharmacologic blockade, that it contributes to neutrophil recruitment in a mouse model of acute gouty inflammation. To our knowledge, this study is the first to uncover an immunometabolic mechanism of macrophage activation that operates during acute gouty inflammation. Targeting this pathway holds promise in the management of gout and, potentially, other macrophage-driven diseases.
Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis
Authors: Stella Cosenza, Karine Toupet, Marie Maumus, Patricia Luz-Crawford, Olivier Blanc-Brude, Christian Jorgensen, Danièle Noël
Journal: Theranostics (2018)

Objectives: Mesenchymal stem cells (MSCs) release extracellular vesicles (EVs) that display a therapeutic effect in inflammatory disease models. Although MSCs can prevent arthritis, the role of MSCs-derived EVs has never been reported in rheumatoid arthritis. This prompted us to compare the function of exosomes (Exos) and microparticles (MPs) isolated from MSCs and investigate their immunomodulatory function in arthritis. Methods: MSCs-derived Exos and MPs were isolated by differential ultracentrifugation. Immunosuppressive effects of MPs or Exos were investigated on T and B lymphocytes in vitro and in the Delayed-Type Hypersensitivity (DTH) and Collagen-Induced Arthritis (CIA) models. Results: Exos and MPs from MSCs inhibited T lymphocyte proliferation in a dose-dependent manner and decreased the percentage of CD4+ and CD8+ T cell subsets. Interestingly, Exos increased Treg cell populations while parental MSCs did not. Conversely, plasmablast differentiation was reduced to a similar extent by MSCs, Exos or MPs. IFN-γ priming of MSCs before vesicles isolation did not influence the immunomodulatory function of isolated Exos or MPs. In DTH, we observed a dose-dependent anti-inflammatory effect of MPs and Exos, while in the CIA model, Exos efficiently decreased clinical signs of inflammation. The beneficial effect of Exos was associated with fewer plasmablasts and more Breg-like cells in lymph nodes. Conclusions: Both MSCs-derived MPs and Exos exerted an anti-inflammatory role on T and B lymphocytes independently of MSCs priming. However, Exos were more efficient in suppressing inflammation in vivo. Our work is the first demonstration of the therapeutic potential of MSCs-derived EVs in inflammatory arthritis.
Master of Philosophy (MPhil) in Epidemiology
Authors: Peter Aquino
Journal: BMJ (2007)

FURTHER INFORMATION 

Postgraduate secretary, Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge Forvie Site, Robinson Way, Cambridge CB2 2SR. Tel 01223 330328, www.phpc.cam.ac.uk/mphil.

Yes, I did the course at Cambridge University. The full time course lasted one year and consisted of a taught component (mostly in the first two terms) and a research component (third term).

The course is aimed at graduate students (including doctors) who wish …
6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial
Authors: Joo-Yong Hahn, Young Bin Song, Ju-Hyeon Oh, Deok-Kyu Cho, Jin Bae Lee, Joon-Hyung Doh, Sang-Hyun Kim, Jin-Ok Jeong, Jang-Ho Bae, Byung-Ok Kim, Jang Hyun Cho, Il-Woo Suh, Doo-il Kim, Hoon-Ki Park, Jong-Seon Park, Woong Gil Choi, Wang Soo Lee, Jihoon Kim, Ki Hong Choi, Taek Kyu Park, Joo Myung Lee, Jeong Hoon Yang, Jin-Ho Choi, Seung-Hyuk Choi, Hyeon-Cheol Gwon, Hyeon-Cheol Gwon, Joo-Yong Hahn, Young Bin Song, Taek Kyu Park, Joo Myung Lee, Jeong Hoon Yang, Jin-Ho Choi, Seung-Hyuk Choi, Jong-Young Lee, Woong Gil Choi, Jang-Ho Bae, Hun Sik Park, Jin-Yong Hwang, Seung-Ho Hur, Seung-Woon Rha, Deok-Kyu Cho, Sang Cheol Cho, Won You Kang, Seong-Hoon Lim, Jin Bae Lee, Moo Hyun Kim, Kwang Soo Cha, Rak Kyung Choi, In-Ho Chae, Ju-Hyeon Oh, Woo Jin Jang, Yong Hawn Park, Woo Jung Chun, Sang-Hyun Kim, Jang Hyun Cho, Il-Woo Suh, Jong-Seon Park, Jae Woong Choi, Byung-Ok Kim, Joon-Hyung Doh, Doo-il Kim, Myung Ho Jeong, Seung Ho Kang, Wang Soo Lee, Hoon-Ki Park, Jin-Ok Jeong, Kyung-Ju Ahn
Journal: The Lancet (2018)
EXOSOMES FROM INDUCED PLURIPOTENT STEM CELL-DERIVED CARDIOMYOCYTES SALVAGE THE INJURED MYOCARDIUM BY MODULATION OF AUTOPHAGY
Authors: Michelle Santoso, Hiromi Sano, Yuko Tada, Raymond Sierra, Andrew Goldstone, Daniel von Bornstaedt, Cornelius Gati, Y. Woo, Phillip Yang
Journal: Journal of the American College of Cardiology (2018)
NHS cutbacks are eroding postgraduate training standards, warns BMA
Authors: Caroline White
Journal: BMJ (2012)

The financial squeeze on the NHS is already taking its toll on the quality of postgraduate medical training, warns the newly elected chairman of the BMA’s Junior Doctors Committee.

Ben Molyneux, a general practitioner trainee in London who took up the post on 29 September, described the combination of the current financial pressures and the structural reorganisation of the NHS as “a perfect storm for the potential erosion of high quality medical training.”

He said that safeguarding the quality of training would be …
Breaking down professional barriers
Authors: Bruno Rushforth
Journal: BMJ (2004)

In healthcare, interprofessional education isn't just about having nursing and medical students taught side-by-side in the lecture hall, it's more about allowing different professions to come together so that they can learn from and about each other, with the aim of improving collaboration and ultimately the quality of patient care. For example, participants from different health and social care professions might as a team work through a complex ethical dilemma or ‘near-miss‘ incident to generate possible solutions that incorporate a variety of professional perspectives.

Interprofessional education is said to be most effective when it occurs in small groups or interactive settings where participants can draw upon their different experiences and knowledge, and where they value the contributions of other professionals or students (see box 1). In a sense, this takes place informally on a daily basis in most hospitals and primary care settings, but there are moves to …
FATAL ARRHYTHMIA AND SUDDEN UNEXPECTED DEATH IN PATIENTS WITH AN IMPLANTED CARDIAC DEFIBRILLATOR AND POST-MORTEM INTERROGATION IN MADIT-CRT
Authors: Robert E. Goldstein, Margaret L. McCarthy, Ronald J. Krone, Mark C. Haigney, Wojciech Zareba, Arthur J. Moss
Journal: Journal of the American College of Cardiology (2018)
Association Between <i>HLA-B*1301</i> and Dapsone-Induced Cutaneous Adverse Drug Reactions
Authors: Wimonchat Tangamornsuksan, Manupat Lohitnavy
Journal: JAMA Dermatology (2018)

Dapsone-induced hypersensitivity syndrome (DHS) is a life-threatening adverse drug reaction. Based on available epidemiologic studies, HLA genotypes may play an important role in DHS.
Abstract P1-01-15: Investigation of phosphoserine aminotransferase 1 and its role in breast cancer progression
Authors: S Metcalf, T Kruer, C Klinge, B Clem
Journal: Cancer Research (2018)

Abstract Metastasis and endocrine resistance are two factors that complicate therapeutic intervention in breast cancer patients and lead to poorer overall survival. Metastasis is known to be responsible for 90% of cancer related deaths, and is especially prevalent in triple negative breast cancer (TNBC); while endocrine resistance can affect up to 50% of patients diagnosed with estrogen receptor positive breast cancer (ER+BC). Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second step within de novo serine biosynthesis and increased expression of enzymes in this pathway have been linked to progression of breast cancer and poor clinical outcomes. Within our preliminary retrospective analysis of human breast cancer patients, we identified an inverse association with elevated transcript levels and poorer distant metastasis free survival, which, coupled to a previously reported correlation of PSAT1 with response to endocrine therapy in patients with ER+BC, we postulate that PSAT1 contributes to breast cancer progression through promotion of metastasis and/or endocrine resistance. To initially determine relevance for PSAT1, immunohistochemistry was performed to determine PSAT1 expression in human breast cancer patients. We found that PSAT1 expression is increased through breast cancer progression, with highest levels observed within metastatic conditions. To investigate the metastatic contribution of PSAT1, we silenced PSAT1 expression within the triple negative breast cancer cell line (TNBC), MDA-MB-231. While suppression of PSAT1 had no effect on proliferation, there was a significant decrease in the motility and invasion of these cells. In addition, decreased PSAT1 substantially inhibited lung metastasis following tail-vein injections of MDA-MB-231 cells in vivo. To investigate PSAT1's role in endocrine resistance, we used parental MCF-7 cells and an endocrine-resistant derivative cell line (LY2) and found that LY2-resistant cells exhibited higher PSAT1 expression compared to parental MCF-7 cells. Lastly, suppression of PSAT1 was able to sensitize the LY2 cells to 4-hydroxytamoxifen treatment. Taken together, these data indicate that PSAT1 may contribute to the progression of human breast cancer via either metastasis or endocrine resistance or both and could potentially serve as a viable target for new therapies. Citation Format: Metcalf S, Kruer T, Klinge C, Clem B. Investigation of phosphoserine aminotransferase 1 and its role in breast cancer progression [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-01-15.
Response to Comment on Ohkuma et al. Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial. Diabetes Care 2017;40:1203–1209
Authors: Toshiaki Ohkuma, Mark Woodward, John Chalmers
Journal: Diabetes Care (2018)

We would like to thank Dr. Kawada for the comments (1) on our paper (2).

First, we agree that the use of biomarkers is beneficial for early detection of heart failure and prevention of subsequent other cardiovascular diseases.

Second, we agree with the need for careful monitoring of the incidence of cardiovascular diseases other than heart failure, as heart failure is the second most common initial presentation of cardiovascular disease in patients with type 2 diabetes after peripheral arterial disease …
I am a registrar from Pakistan and I have passed the fellowship exam in obstetrics and gynaecology in Pakistan. I now want to take the MRCOG part 2 exam, but I know many candidates who have failed part 2 even after passing the local exam, perhaps because they have not worked in the United Kingdom. Should I try for a job in the United Kingdom or go for the exam?
Authors: Philip Owen
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>
The value of cross specialty training
Authors: Babar Vaqas, Charlie Giddings
Journal: BMJ (2008)

“Why ENT—I have always wanted to be a neurosurgeon?” Recent reforms of training have formalised exposure to allied specialties. Many trainees were arranging this independently before but also spending five years in the senior house officer grade. But when I attained my specialty training year 2 run-through for neurosurgery I found unexpectedly that I was to have six months of training in ear, nose, and throat surgery (ENT), something I may well not have considered if independently arranging stand alone posts. However, as I have progressed through training I have realised it is just one of many allied specialties (box 1).

#### Box 1: Specialties relevant to neurosurgery trainees

Sharing ideas between ENT and neurosurgery is not new. In 1906 the Austrian otolaryngologist Herman Schloffer …
Unstable Inflation Causing Injury. Insight from Prone Position and Paired Computed Tomography Scans
Authors: Yi Xin, Maurizio Cereda, Hooman Hamedani, Mehrdad Pourfathi, Sarmad Siddiqui, Natalie Meeder, Stephen Kadlecek, Ian Duncan, Harrilla Profka, Jennia Rajaei, Nicholas J. Tustison, James C. Gee, Brian P. Kavanagh, Rahim R. Rizi
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

It remains unclear how prone positioning improves survival in acute respiratory distress syndrome. Using serial computed tomography (CT), we previously reported that "unstable" inflation (i.e., partial aeration with large tidal density swings, indicating increased local strain) is associated with injury progression.
HIGH-DOSE BETA-BLOCKERS (BB) AND OUTCOMES IN PATIENTS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION (HFPEF) AND HEART RATE ≥70 BEATS PER MINUTE (BPM)
Authors: Phillip Hong Lam, Daniel Dooley, Apostolos Tsimploulis, Helen Sheriff, Charles Faselis, Prakash Deedwania, Gregg C. Fonarow, Ali Ahmed
Journal: Journal of the American College of Cardiology (2018)
Tanning addiction: conceptualization, assessment and correlates
Authors: C.S. Andreassen, S. Pallesen, T. Torsheim, Z. Demetrovics, M.D. Griffiths
Journal: British Journal of Dermatology (2018)

Research into problematic tanning (or 'tanning addiction') has markedly increased over the past few years. Although several instruments exist to measure excessive tanning, most of these are psychometrically poor, are not theoretically anchored, and have been used mainly on small samples.To develop a new tanning addiction scale based on a specific theoretical approach utilizing core addiction criteria.A scale comprising seven items (salience/craving, tolerance, mood modification, relapse/loss of control, withdrawal, conflict and problems) was administered online to a cross-sectional convenience sample of 23 537 adults (mean ± SD age 35·8 ± 13·3 years). There was also assessment of demographic factors, the five-factor model of personality, and symptoms of obsessive-compulsive disorder, anxiety and depression.A confirmatory factor analysis showed that a one-factor model gave an optimal fit with the data collected [root mean square error of approximation = 0·050, 90% confidence interval (CI) 0·047-0·053; comparative fit index = 0·99; Tucker-Lewis index = 0·99]. High factor loadings (0·78-0·91, all P < 0·001) and coefficient omega indicator of reliability (ω = 0·94, 95% CI 0·94-0·94) were also found using the new scale. In a multiple linear regression analysis, tanning addiction was positively associated with being female, not being in a relationship, extraversion, neuroticism, anxiety and obsessive-compulsiveness. It was also found that educational level, intellect/openness and depression were inversely associated with tanning addiction.The new scale, the Bergen Tanning Addiction Scale (BTAS), showed good psychometric properties, and is the first scale to conceptualize tanning addiciton fully within a contemporary addiction framework. Given this, the BTAS may potentially assist future clinical practice in providing appropriate patient care, prevention and disease management.
Changing with NLP
Authors: Tina Ambury
Journal: BMJ (2004)

H aving been aware of neurolinguistic programming (NLP) for a while and having been officially employed as a “change agent” (cue Bond theme) for several years, I was keen to explore this book.

The bold assertion in the foreword that readers could “immediately use” some of the techniques in the book had me hooked, and I eagerly started reading in anticipation of learning a useful skill.

Alas, this was not to be. This is one of the most difficult books I've read. Not because it is boring, but because there is so much …
Nuclear factor-kappa B p65 evaluation on the Canadian Prostate Cancer Biomarker Network (CPCBN) TMA-series for biomarker validation.
Authors: Fred Saad, Veronique Ouellet, Andree-Anne Grosset, Christine Caron, Veronique Barres, Mathieu Latour, Dominique Trudel, Armen G. Aprikian, Alain Bergeron, Fadi Brimo, Simone Chevalier, Darrel Drachenberg, Ladan Fazli, Neil Eric Fleshner, Martin Gleave, Pierre I. Karakiewicz, Louis Lacombe, Jean-Baptiste Lattouf, Theodorus van der Kwast, Anne-Marie Mes-Masson
Journal: Journal of Clinical Oncology (2018)

80 Background: The CPCBN has assembled a TMA-based resource comprising the specimens of 1512 prostate cancer patients treated by radical prostatectomy. This richly annotated and multi-institutional resource is available to researchers who wish to access a large cohort to validate prognostic biomarkers (http://www.tfri.ca/en/research/translational-research/cpcbn.aspx). Over the last decade, our laboratory demonstrated with an independent cohort (Gannon PO, et al. Eur J Cancer. 2013 Jul;49(10):2441-8, Labouba I, et al. PLoS One. 2015 Jul 17;10(7):e0131024), the reproducible association of nuclear factor-kappa B (NF-kB) p65 with patient’s risk of biochemical recurrence. Here, we evaluated the CPCBN TMA-series for p65 expression. Methods: Two independent observers scored the frequency of p65 nuclear localisation on digital images obtained after automated immunohistochemistry analysis of p65. Over the available minimum 3 cores of tumour tissue per patient, an average percentage of positive nucleus frequency was used. Statistical analyses were performed using SPSS software. Results: High nuclear frequency of NF-kB p65 (cut-off at 3%) was associated with an increased risk for patients to experience a biochemical relapse (p &lt; 0.001; Exp(B) = 1.599; 95%CI = 1.321-1.937), develop bone metastasis (p = 0.007; Exp(B) = 2.126; 95%CI = 1.234-3.663)and die from their disease (p = 0.001; Exp(B) = 3.117; 95%CI = 1.55-6.266). In multivariate analyses, p65 also remained independent from clinical parameters (PSA, Gleason score and pTNM): biochemical relapse (p = 0.005; Exp(B) = 1.331; 95%CI = 1.092-1.623), bone metastasis (p = 0.033; Exp(B) = 1.82; 95%CI = 1.04- 3.158), mortality (p = 0.007; Exp(B) = 2.626; 95%CI = 1.298-5.312) Conclusions: Using a large cohort of Canadian men, our study reiterates the previous study linking NF-kB p65 with prostate cancer progression and highlights the suitability of CPCBN TMAs for biomarker validation. Our results also reveal the role of p65 as a predictor of bone metastasis development and prostate cancer-specific mortality.