tbuckley/cabot-search huggingface dataset:
COMPARISON OF NEOINTIMAL CHARACTERISTICS BETWEEN EVEROLIMUS-ELUTING STENT AND BARE-METAL STENT AT MORE THAN 3 YEARS AFTER IMPLANTATION
Authors: Hiroaki Ohya, Taishi Yonetsu, Yoshihisa Kanaji, Eisuke Usui, Masahiro Hoshino, Yohei Sumino, Masahiro Hada, Tadashi Fukuda, Rikuta Hamaya, Yoshinori Kanno, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2018)
OUTCOMES OF CARDIAC CATH/PCI IN PATIENTS WITH AF: INSIGHTS FROM THE ORBIT II REGISTRY
Authors: Matthew William Sherwood, Jonathan Piccini, DaJuanicia Holmes, Karen Pieper, Gregg C. Fonarow, Peter Kowey, Bernard Gersh, Kenneth Mahaffey, Eric D. Peterson, Sunil V. Rao
Journal: Journal of the American College of Cardiology (2018)
Operations could be cancelled if anaesthesia training posts are diverted to general practice, anaesthetists warn
Authors: Abi Rimmer
Journal: BMJ (2014)

Plans to divert specialty training posts from anaesthesia to general practice could lead to around 300 operations being cancelled at Leeds Teaching Hospitals NHS Trust, anaesthetists have warned.

The Association of Anaesthetists of Great Britain and Ireland has written to Health Education England about the issue.1 The letter warned that changes made by Yorkshire and Humber Local Education Training Board posed a major threat to patient safety, the delivery of an effective clinical service, and doctors’ wellbeing.

The letter said, “The AAGBI [Association of Anaesthetists of Great Britain and Ireland] has been informed that the Yorkshire and the Humber LETB has diverted specialty training posts from anaesthesia to general practice without appropriate consultation and consideration of the …
I am a medical graduate from India and I want to join a GPVTS. Are there any exams to enter this training and, if so, when are these exams conducted? Do any institutions provide training or coaching for these exams?
Authors: Rodger Charlton
Journal: BMJ (2005)

<b>www.bmjcareers.com/advicezone</b> Have 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 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.
GMC proposes limiting provisional registration to three years
Authors: Helen Jaques
Journal: BMJ (2012)

The General Medical Council is seeking views on proposals to limit the amount of time a doctor can hold provisional registration to three years.

Limiting the duration of provisional registration will reinforce the message that its sole purpose is to allow a doctor to complete a training programme leading to full registration with a licence to practise, the regulator says.

Most doctors who hold provisional registration are in foundation year one and are granted full registration on successful completion …
Survival outcomes for de novo versus relapsed stage IV gastric and gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Bryan Anthony Chan, Hao-Wen Sim, Akina Natori, Stephanie Moignard, Daniel Yokom, Charles Henry Lim, Di Maria Jiang, Eric Xueyu Chen, Jennifer J. Knox, Geoffrey Liu, Gail Elizabeth Darling, Carol Jane Swallow, Savtaj Singh Brar, James D. Brierley, Jolie Ringash, Rebecca Wong, John Kim, Sara Hafezi-Bakhtiari, Elena Elimova, Raymond Woo-Jun Jang
Journal: Journal of Clinical Oncology (2018)

148 Background: In gastric/GEJ cancer, 40% of patients (pts) are metastatic at diagnosis ( de novo stage IV) and up to 70% with locoregional disease recur (relapsed stage IV). We compared survival outcomes between de novo vs relapsed stage IV. Methods: A retrospective observational study of stage IV gastric/GEJ pts was conducted (2012-2015). Overall survival (OS) was from date of stage IV diagnosis. PFS1 defined the period from stage IV diagnosis to first progression. PFS2 was from first to second progression. For relapsed stage IV pts, disease-free interval (DFI) was the period from initial diagnosis to metastatic relapse. Cox proportional hazards models compared OS, PFS1 and PFS2 between de novo vs relapsed stage IV pts, stratified by DFI [ &lt; 6, 6-12 and &gt; 12 months (mo)] and controlled for baseline patient characteristics. Results: Of 198 pts, 62% were male and median age was 64 years (26-93), with 64% gastric and 36% GEJ adenocarcinomas. Primary therapy for locoregional pts included surgery (75%), perioperative chemotherapy (42%) and radiotherapy (42%). De novo and relapsed stage IV pts represented 68% and 32% of the cohort respectively. Median follow-up was 13 mo. Controlled for age, performance status and Charlson comorbidity index, there were no significant differences in OS (median OS 12.5 ( de novo) vs 12.2 mo (relapsed); HR 1.22, 95% CI 0.83-1.77, p = 0.31), PFS1 (6.8 vs 7.4 mo; HR 1.00, 95% CI 0.65-1.56, p = 0.98) or PFS2 (3.8 vs 3.0 mo; HR 1.03, 95% CI 0.44-2.41, p = 0.95). Median OS for relapsed stage IV patients were different by DFI groups (log-rank p = 0.02): 22.9 mo (for DFI &gt; 12mo; n = 31), 11.2 mo (DFI 6-12; n = 19) and 7.5 mo (DFI &lt; 6; n = 14). Additionally, OS was significantly better if the DFI was greater than 12 mo, compared with de novo stage IV (HR 0.50, 95% CI 0.28-0.88, p = 0.02). Conclusions: There was no observed difference in the natural history of de novo vs relapsed stage IV gastric/GEJ pts. DFI was strongly prognostic with median OS (from date of relapse) approaching 2 years for relapsed pts with DFI &gt; 12 mo. In addition to implications for treatment strategy, tumor biology within subgroups should be examined to identify novel biomarkers and potential therapeutic targets.
Assessment of immunohistochemical testing for androgen receptor splice variant 7 as a biomarker to predict resistance to androgen receptor signaling inhibitors in metastatic prostate cancer.
Authors: Ojas Harihar Vyas, Matthew James Butler, Elizabeth Ann Bowhay-Carnes, Muhammad Pathan, Paromita Datta
Journal: Journal of Clinical Oncology (2018)

308 Background: Androgen receptor splice variant 7 (AR-V7) has been shown to confer resistance to androgen receptor signaling inhibitors (ARS-I) such as enzalutamide (enza) and abiraterone (abi). Resistance can be observed at the time of initial treatment, or may be acquired later in the disease course. Prior research has primarily focused on AR-V7 expression in circulating tumor cells (CTCs) but the utility of more affordable immunohistochemical (IHC) testing to predict for primary resistance to ARS-I remains unknown, which is of particular relevance as ARS-I gain use as initial therapy. Methods: We identified patients in the South Texas Veterans Health Administration Tumor Registry with metastatic, castrate-resistant prostate cancer who received ARS-I since 2011. IHC for AR-V7 staining was validated on controls and performed on tissue from the most recent tissue specimen (diagnostic biopsy, prostatectomy, or biopsy of a metastatic site) on all identified patients with adequate tissue available. Results: 25 of 42 (60%) patients receiving abi had PSA response with median duration of response (DOR) of 231 days. 14 of 26 (54%) of patients receiving enza experienced PSA response with a median DOR of 165 days. IHC is currently being interpreted on stored tissue specimens to assess predictive efficacy of AR-V7 staining. The de-novo rate of AR-V7 expression and correlation with response to ARS-I in the veteran population will be reported with final results. Conclusions: IHC testing for AR-V7 may provide a cost-effective biomarker to identify patients resistant to ARS-I, thus avoiding thus avoiding time-consuming and costly treatment with ineffective therapy. Further study is warranted to assess cost-effectiveness and reduction in unnecessary toxicity by the use of IHC testing for AR-V7 in the front-line setting to predict primary resistance for patients that would otherwise qualify for ARS-I.
PRIOR BARIATRIC SURGERY CORRELATES WITH IMPROVED IN-HOSPITAL MORTALITY AND DECREASED HOSPITALIZATION COST AND LENGTH OF STAY COMPARED TO MORBIDLY OBESE PATIENTS WITH ACUTE MYOCARDIUM INFARCTION: A NATIONWIDE ANALYSIS FROM 2006 TO 2014
Authors: Xin Wei, Hedong Han, Kevin Gu, Chayakrit Krittanawong, Bing Yue, Basera Sabharwal, Ahmadreza Moradi, Mario Rodriguez, Karan Sud, Mariam Khandaker, Shuyang Fang, Eyal Herzog
Journal: Journal of the American College of Cardiology (2018)
Junior doctors benefit from working in emergency departments, study finds
Authors: Matthew Limb
Journal: BMJ (2015)

Junior doctors benefit significantly from working in hospital emergency departments despite reporting reduced job satisfaction, a study has found.

The researchers behind the study said that, although some elements of wellbeing worsened, juniors felt more confident and competent, “with no significant adverse impact on anxiety levels.” They said that their findings gave “a more positive picture” of junior doctors’ wellbeing than previous studies, which showed high levels of psychological distress, depression, and burnout.

The research was led by Sheffield University’s School of Health and Related Research and published in the Emergency Medicine Journal .1 The longitudinal study examined wellbeing, confidence, and …
Dennis James Stoker
Authors: Mark Davies
Journal: BMJ (2018)

A son of a general practitioner, Dennis James Stoker was educated at Oundle before going on to study medicine at Guy’s Hospital, London. He spent a substantial part of his early career as a physician in the medical branch of the Royal Air Force, including in Cyprus and Aden; he retired after 16 years with the rank of wing commander. The overseas postings are evidenced by publications in The BMJ on bacillary dysentery and histoplasmosis. He then retrained as a radiologist and was appointed a consultant jointly at St George’s Hospital and the Royal National Orthopaedic Hospital in 1972 and later to full …
Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans
Authors: Paul Tuijnenburg, Hana Lango Allen, Siobhan O. Burns, Daniel Greene, Machiel H. Jansen, Emily Staples, Jonathan Stephens, Keren J. Carss, Daniele Biasci, Helen Baxendale, Moira Thomas, Anita Chandra, Sorena Kiani-Alikhan, Hilary J. Longhurst, Suranjith L. Seneviratne, Eric Oksenhendler, Ilenia Simeoni, Godelieve J. de Bree, Anton T.J. Tool, Ester M.M. van Leeuwen, Eduard H.T.M. Ebberink, Alexander B. Meijer, Salih Tuna, Deborah Whitehorn, Matthew Brown, Ernest Turro, Adrian J. Thrasher, Kenneth G.C. Smith, James E. Thaventhiran, Taco W. Kuijpers, Zoe Adhya, Hana Alachkar, Ariharan Anantharachagan, Richard Antrobus, Gururaj Arumugakani, Chiara Bacchelli, Helen Baxendale, Claire Bethune, Shahnaz Bibi, Barbara Boardman, Claire Booth, Michael Browning, Mary Brownlie, Siobhan Burns, Anita Chandra, Hayley Clifford, Nichola Cooper, Sophie Davies, John Dempster, Lisa Devlin, Rainer Doffinger, Elizabeth Drewe, David Edgar, William Egner, Tariq El-Shanawany, Bobby Gaspar, Rohit Ghurye, Kimberley Gilmour, Sarah Goddard, Pavel Gordins, Sofia Grigoriadou, Scott Hackett, Rosie Hague, Lorraine Harper, Grant Hayman, Archana Herwadkar, Stephen Hughes, Aarnoud Huissoon, Stephen Jolles, Julie Jones, Peter Kelleher, Nigel Klein, Taco Kuijpers, Dinakantha Kumararatne, James Laffan, Hana Lango Allen, Sara Lear, Hilary Longhurst, Lorena Lorenzo, Jesmeen Maimaris, Ania Manson, Elizabeth McDermott, Hazel Millar, Anoop Mistry, Valerie Morrisson, Sai Murng, Iman Nasir, Sergey Nejentsev, Sadia Noorani, Eric Oksenhendler, Mark Ponsford, Waseem Qasim, Ellen Quinn, Isabella Quinti, Alex Richter, Crina Samarghitean, Ravishankar Sargur, Sinisa Savic, Suranjith Seneviratne, Carrock Sewall, Fiona Shackley, Ilenia Simeoni, Kenneth G.C. Smith, Emily Staples, Hans Stauss, Cathal Steele, James Thaventhiran, Moira Thomas, Adrian Thrasher, Steve Welch, Lisa Willcocks, Sarita Workman, Austen Worth, Nigel Yeatman, Patrick Yong, Sofie Ashford, John Bradley, Debra Fletcher, Tracey Hammerton, Roger James, Nathalie Kingston, Willem Ouwehand, Christopher Penkett, F Lucy Raymond, Kathleen Stirrups, Marijke Veltman, Tim Young, Sofie Ashford, Matthew Brown, Naomi Clements-Brod, John Davis, Eleanor Dewhurst, Marie Erwood, Amy Frary, Rachel Linger, Jennifer Martin, Sofia Papadia, Karola Rehnstrom, William Astle, Antony Attwood, Marta Bleda, Keren Carss, Louise Daugherty, Sri Deevi, Stefan Graf, Daniel Greene, Csaba Halmagyi, Matthias Haimel, Fengyuan Hu, Roger James, Hana Lango Allen, Vera Matser, Stuart Meacham, Karyn Megy, Christopher Penkett, Olga Shamardina, Kathleen Stirrups, Catherine Titterton, Salih Tuna, Ernest Turro, Ping Yu, Julie von Ziegenweldt, Abigail Furnell, Rutendo Mapeta, Ilenia Simeoni, Simon Staines, Jonathan Stephens, Kathleen Stirrups, Deborah Whitehorn, Paula Rayner-Matthews, Christopher Watt
Journal: Journal of Allergy and Clinical Immunology (2018)
I am a surgical SHO interested in a career in clinical radiology. I am interested in applying for one year deferred entry to a specialist registrar post, in order to travel. Is this feasible and if so, how do I go about it?
Authors: Alan Denison
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>
Single-Cell Sequencing of the Healthy and Diseased Heart Reveals Cytoskeleton-Associated Protein 4 as a New Modulator of Fibroblasts Activation
Authors: Monika M. Gladka, Bas Molenaar, Hesther de Ruiter, Stefan van der Elst, Hoyee Tsui, Danielle Versteeg, Grègory P.A. Lacraz, Manon M.H. Huibers, Alexander van Oudenaarden, Eva van Rooij
Journal: Circulation (2018)

Background: Genome-wide transcriptome analysis has greatly advanced our understanding of the regulatory networks underlying basic cardiac biology and mechanisms driving disease. However, so far, the resolution of studying gene expression patterns in the adult heart has been limited to the level of extracts from whole tissues. The use of tissue homogenates inherently causes the loss of any information on cellular origin or cell type-specific changes in gene expression. Recent developments in RNA amplification strategies provide a unique opportunity to use small amounts of input RNA for genome-wide sequencing of single cells. Methods: Here, we present a method to obtain high-quality RNA from digested cardiac tissue from adult mice for automated single-cell sequencing of both the healthy and diseased heart. Results: After optimization, we were able to perform single-cell sequencing on adult cardiac tissue under both homeostatic conditions and after ischemic injury. Clustering analysis based on differential gene expression unveiled known and novel markers of all main cardiac cell types. Based on differential gene expression, we could identify multiple subpopulations within a certain cell type. Furthermore, applying single-cell sequencing on both the healthy and injured heart indicated the presence of disease-specific cell subpopulations. As such, we identified cytoskeleton-associated protein 4 as a novel marker for activated fibroblasts that positively correlates with known myofibroblast markers in both mouse and human cardiac tissue. Cytoskeleton-associated protein 4 inhibition in activated fibroblasts treated with transforming growth factor β triggered a greater increase in the expression of genes related to activated fibroblasts compared with control, suggesting a role of cytoskeleton-associated protein 4 in modulating fibroblast activation in the injured heart. Conclusions: Single-cell sequencing on both the healthy and diseased adult heart allows us to study transcriptomic differences between cardiac cells, as well as cell type-specific changes in gene expression during cardiac disease. This new approach provides a wealth of novel insights into molecular changes that underlie the cellular processes relevant for cardiac biology and pathophysiology. Applying this technology could lead to the discovery of new therapeutic targets relevant for heart disease.
Antitumor Efficacy of Dual Blockade of EGFR Signaling by Osimertinib in Combination With Selumetinib or Cetuximab in Activated EGFR Human NCLC Tumor Models
Authors: Carminia Maria Della Corte, Vincenza Ciaramella, Claudia Cardone, Silvia La Monica, Roberta Alfieri, Pier Giorgio Petronini, Umberto Malapelle, Elena Vigliar, Francesco Pepe, Giancarlo Troncone, Maria Domenica Castellone, Teresa Troiani, Erika Martinelli, Fortunato Ciardiello, Floriana Morgillo
Journal: Journal of Thoracic Oncology (2018)
What's the scope for a GP with a special interest in obstetrics and gynaecology?
Authors: Philip Owen
Journal: BMJ (2005)

Have 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 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. <b>www.bmjcareers.com/advicezone</b>
Epigenetic inactivation of arginine biosynthesis genes in paediatric intracranial ependymoma
Authors: Katherine Karakoula, Nelofer Syed, Thomas Jacques, Kim Phipps, Dominic Thompson, John Darling, Tracy Warr
Journal: Neuro-Oncology (2018)

Aberrant cellular metabolism is recognized as a major event in the growth and development of many cancers and the targetting of metabolic defects in tumour cells represents a new therapeutic opportunity. For example, cells that do not express sufficient levels of argininosuccinate synthetase-1 (ASS1) or argininosuccinate lyase (ASL) become auxotrophic for arginine and require exogenous supply. Arginine deprivation using arginine deiminase (ADI-PEG20) is currently under evaluation in clinical trials for adult GBM. In this study, we investigated the arginine biosynthesis pathway in paediatric intracranial ependymoma, comprising 24 fresh frozen biopsies and 17 short-term cell cultures of low passage (<10). The methylation status of ASS1 and ASL was assessed by methylation-specific PCR and gene expression levels were measured using real-time Q-PCR analysis. The response of ependymoma cell cultures in vitro to ADI-PEG20 was determined at various time points using the sulphorodamine B (SRB) assay. Promoter hypermethylation of ASS1 was present in 41.5% ependymoma (17/41 samples) and methylation correlated with down-regulation of ASS1 expression (p<0.0001, Fisher’s exact test). Importantly, methylation and expression status was maintained in 6 patient-derived cell cultures for which paired biopsies were available. Conversely, methylation of ASL was not detected in any samples. Treatment with ADI-PEG20 inhibited proliferation of ependymoma cells only in those cultures with methylation-dependent silencing of ASS1. Our findings suggest that argininine depletion therapy may benefit a significant proportion of paediatric patients with intracranial ependymoma.
Association of Vegetation Size With Embolic Risk in Patients With Infective Endocarditis
Authors: Divyanshu Mohananey, Ashley Mohadjer, Gosta Pettersson, Jose Navia, Steven Gordon, Nabin Shrestha, Richard A. Grimm, L. Leonardo Rodriguez, Brian P. Griffin, Milind Y. Desai
Journal: JAMA Internal Medicine (2018)

<h3>Importance</h3> Infective endocarditis is a life-threating condition with annual mortality of as much as 40% and is associated with embolic events in as many as 80% of cases. These embolic events have notable prognostic implications and have been linked to increased length of stay in intensive care units and mortality. A vegetation size greater than 10 mm has often been suggested as an optimal cutoff to estimate the risk of embolism, but the evidence is based largely on small observational studies. <h3>Objective</h3> To study the association of vegetation size greater than 10 mm with embolic events using meta-analytic techniques. <h3>Data Sources</h3> A computerized literature search of all publications in the PubMed and EMBASE databases from inception to May 1, 2017, was performed with search terms including varying combinations of<i>infective endocarditis</i>,<i>emboli</i>,<i>vegetation size</i>,<i>pulmonary infarct</i>,<i>stroke</i>,<i>splenic emboli</i>,<i>renal emboli</i>,<i>retinal emboli</i>, and<i>mesenteric emboli</i>. This search was last assessed as being up to date on May 1, 2017. <h3>Study Selection</h3> Observational studies or randomized clinical trials that evaluated the association of vegetation size greater than 10 mm with embolic events in adult patients with infective endocarditis were included. Conference abstracts and non–English language literature were excluded. The search was conducted by 2 independent reviewers blinded to the other’s work. <h3>Data Extraction and Synthesis</h3> Following PRISMA guidelines, the 2 reviewers independently extracted data; disputes were resolved with consensus or by a third investigator. Categorical dichotomous data were summarized across treatment arms using Mantel-Haenszel odds ratios (ORs) with 95% CIs. Heterogeneity of effects was evaluated using the Higgins<i>I</i><sup>2</sup>statistic. <h3>Results</h3> The search yielded 21 unique studies published from 1983 to 2016 with a total of 6646 unique patients with infective endocarditis and 5116 vegetations with available dimensions. Patients with a vegetation size greater than 10 mm had increased odds of embolic events (OR, 2.28; 95% CI, 1.71-3.05;<i>P</i> &lt; .001) and mortality (OR, 1.63; 95% CI, 1.13-2.35;<i>P</i> = .009) compared with those with a vegetation size less than 10 mm. <h3>Conclusions and Relevance</h3> In this meta-analysis of 21 studies, patients with vegetation size greater than 10 mm had significantly increased odds of embolism and mortality. Understanding the risk of embolization will allow clinicians to adequately risk stratify patients and will also help facilitate discussions regarding surgery in patients with a vegetation size greater than 10 mm.