tbuckley/cabot-search huggingface dataset:
Candidate biomarkers for the diagnosis and prognosis of drug‐induced liver injury: An international collaborative effort
Authors: Rachel J. Church, Gerd A. Kullak‐Ublick, Jiri Aubrecht, Herbert L. Bonkovsky, Naga Chalasani, Robert J. Fontana, Jens C. Goepfert, Frances Hackman, Nicholas M. P. King, Simon Kirby, Patrick Kirby, John Marcinak, Sif Ormarsdottir, Shelli J. Schomaker, Ina Schuppe‐Koistinen, Francis Wolenski, Nadir Arber, Michael Merz, John‐Michael Sauer, Raul J. Andrade, Florian van Bömmel, Thierry Poynard, Paul B. Watkins
Journal: Hepatology (2018)

Current blood biomarkers are suboptimal in detecting drug‐induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of 14 promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n = 192 and n = 81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n = 55 and n = 92) and DILI patients (n = 98, n = 28, and n = 143) were assayed for microRNA‐122 (miR‐122), glutamate dehydrogenase (GLDH), total cytokeratin 18 (K18), caspase cleaved K18, glutathione S ‐transferase α, alpha‐fetoprotein, arginase‐1, osteopontin (OPN), sorbitol dehydrogenase, fatty acid binding protein, cadherin‐5, macrophage colony‐stimulating factor receptor (MCSFR), paraoxonase 1 (normalized to prothrombin protein), and leukocyte cell‐derived chemotaxin‐2. Most candidate biomarkers were significantly altered in DILI cases compared with healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase than miR‐122, and there was a surprisingly wide inter‐ and intra‐individual variability of miR‐122 levels among healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver‐related death or transplantation within 6 months of DILI onset. Prediction of prognosis among DILI patients using the Model for End‐Stage Liver Disease was improved by incorporation of K18 and MCSFR levels. Conclusion : GLDH appears to be more useful than miR‐122 in identifying DILI patients, and K18, OPN, and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management.
Epigenome-wide SRC-1–Mediated Gene Silencing Represses Cellular Differentiation in Advanced Breast Cancer
Authors: Elspeth Ward, Damir Varešlija, Sara Charmsaz, Ailis Fagan, Alacoque L. Browne, Nicola Cosgrove, Sinéad Cocchiglia, Siobhan P. Purcell, Lance Hudson, Sudipto Das, Darran O'Connor, Philip J. O'Halloran, Andrew H. Sims, Arnold D. Hill, Leonie S. Young
Journal: Clinical Cancer Research (2018)

Purpose: Despite the clinical utility of endocrine therapies for estrogen receptor-positive (ER) breast cancer, up to 40% of patients eventually develop resistance, leading to disease progression. The molecular determinants that drive this adaptation to treatment remain poorly understood. Methylome aberrations drive cancer growth yet the functional role and mechanism of these epimutations in drug resistance are poorly elucidated.Experimental Design: Genome-wide multi-omics sequencing approach identified a differentially methylated hub of prodifferentiation genes in endocrine resistant breast cancer patients and cell models. Clinical relevance of the functionally validated methyl-targets was assessed in a cohort of endocrine-treated human breast cancers and patient-derived ex vivo metastatic tumors.Results: Enhanced global hypermethylation was observed in endocrine treatment resistant cells and patient metastasis relative to sensitive parent cells and matched primary breast tumor, respectively. Using paired methylation and transcriptional profiles, we found that SRC-1-dependent alterations in endocrine resistance lead to aberrant hypermethylation that resulted in reduced expression of a set of differentiation genes. Analysis of ER-positive endocrine-treated human breast tumors (n = 669) demonstrated that low expression of this prodifferentiation gene set significantly associated with poor clinical outcome (P = 0.00009). We demonstrate that the reactivation of these genes in vitro and ex vivo reverses the aggressive phenotype.Conclusions: Our work demonstrates that SRC-1-dependent epigenetic remodeling is a 'high level' regulator of the poorly differentiated state in ER-positive breast cancer. Collectively these data revealed an epigenetic reprograming pathway, whereby concerted differential DNA methylation is potentiated by SRC-1 in the endocrine resistant setting. Clin Cancer Res; 24(15); 3692-703. ©2018 AACR.
EFFECT OF MAINTENANCE OF SINUS RHYTHM AFTER CATHETER ABLATION ON BODY WEIGHT IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Bipin Sunkara, Yumeng Li, Konstantinos Siontis, Miki Yokokawa, Rakesh Latchamsetty, Hamid Ghanbari, Thomas C. Crawford, Krit Jongnarangsin, Frank Pelosi, Aman Chugh, Fred Morady, Hakan Oral
Journal: Journal of the American College of Cardiology (2018)
I have recently been appointed as a first year specialist registrar. I was on the maximum pay scale for senior house officer level. Now my basic pay has been reduced by nearly £8000. Is this fair? My understanding was that my basic pay cannot be reduced as I have put in a number of years of service with the NHS.
Authors: Rachel L Hooke
Journal: BMJ (2007)

Have a career related problem that needs answering? Can9t find the 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>
Global health short course
Authors: Sabina Ikram
Journal: BMJ (2012)

The global health short course held at Imperial College London has been running once a year for the past few years. It takes place over five days and offers an introduction to global health, covering a wide range of related topics. The course directors are Alan Fenwick, professor of tropical parasitology at the college, and Helen Ward, director of education at the college’s School of Public Health.

The course is for anyone with an interest or career aspirations in the field of global health. Participants on this year’s course came from across the world and from a variety of backgrounds—for example, medical students, doctors, a nursing student, a midwife, and nutritionists.

I did the course during the second year of my foundation training, but the course would be suitable for students and doctors at any stage of training. 

I hope to pursue a career in infectious diseases medicine and would like to work abroad at some point to gain further experience …
P042 Targeting NF-Κb signalling in B cells: a potential new treatment modality for antibody mediated autoimmune diseases
Authors: JP Van Hamburg, P Tuijnenburg, B Helder, L van Keep, K Wesenhagen, P Kucharzewka, MH Jansen, A Al-Soudi, PL Klarenbeek, H Olsson, N de Vries, T Kuijpers, SW Tas
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The pivotal role of B cells in the pathogenesis autoimmune diseases such as ANCA-associated vasculitis (AAV) is well-established and further substantiated by beneficial therapeutic effects of rituximab (anti-CD20 B cell targeted therapy). However, this results in prolonged B cell depletion while long-lived plasma cells are not targeted. Thus there is a need for novel therapeutics targeting cells in the B-cell lineage in AAV. Novel targets might be encountered in the NF-κB signalling pathway, which acts downstream of various B cell surface receptors, including the B cell antigen receptor, CD40, BAFFR and TLRs, and is crucially involved in B cell responses. <h3>Objectives</h3> To identify whether inhibition of NF-κB signalling by novel pharmacological inhibitors is effective in targeting B cell responses in general and more specifically blocks (auto)antibody production and plasmablast differentiation in B cells from AAV patients. <h3>Methods</h3> PBMC and sorted B cells from AAV patients and healthy donors were cultured with T cell-dependent (anti-IgM +anti CD40+IL-21) and T cell-independent (CpG +IL-2) stimuli. NF-κB signalling was targeted in these cultures by small molecule inhibitors of NF-κB inducing kinase (NIK, non-canonical NF-κB signalling) and IKKβ (canonical NF-κB signalling). Downstream NF-κB signalling and nuclear NF-κB translocation was determined by Western blot and confocal imaging. Effects on B cell proliferation and differentiation were determined by CFSE dilution assays and flow cytometric analysis of B cell markers. (Auto)antibody production was measured by ELISA. <h3>Results</h3> In B cells, targeting of NIK and IKKβ effectively inhibited non-canonical or canonical NF-κB signalling, respectively. In a B cell stimulation assay, NIK and IKKβ inhibition significantly reduced T cell-dependent (anti-IgM +anti CD40+IL-21) and T cell-independent (CpG +IL-2) B cell proliferation, plasmablast differentiation (CD27++/CD38+), and antibody production. The effects of NIK inhibition appeared to be B cell-specific as T cell proliferation was largely unaffected. Currently, studies are ongoing to investigate the effect of IKKβ inhibition on B cell responses and to explore the effects of targeting NF-κB signalling in AAV B cells. <h3>Conclusions</h3> These data demonstrate that inhibition of NF-κB signalling in B cells results in the modulation of various B cell responses. Ongoing studies will indicate whether targeting of NF-κB signalling in B cells may be an effective novel treatment modality for AAV. <h3>Disclosure of interest</h3> None declared
Improved JAK Inhibition in Myelofibrosis—The Long Road Ahead
Authors: Maximilian Stahl, Amer M. Zeidan
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Oncology journal
A third of clinical trials publishing interim findings fail to report final results, review finds
Authors: Susan Mayor
Journal: BMJ (2018)

More than one third of clinical trials publishing interim findings fail to report final results and one in five change their conclusions in final publications, a review of randomised trials has found.1

Researchers searched PubMed for all randomised trials published between 1 January 2006 and 31 December 2015 reporting interim results, excluding pilot studies, protocols, and cancer trials reporting final primary results but interim secondary outcomes. They then searched for final publications and compared the findings, or contacted the authors if no final publication could be found.

Results, reported in JAMA , showed that final results were published for only 61% of …
Clinical Outcome and Characteristics of Patients with Primary Central Nervous System Lymphomas (PCNSL) in a Brazilian Population
Authors: Diego Reis, Tatiane Ishida, Luis A. P. C. Lage, Hebert F. Culler, Renata O. Costa, Maria C. Zerbini, Debora Levy, Vanderson Rocha, Juliana Pereira
Journal: Blood (2017)
Quality of Health Care for Children
Authors: David C. Grossman
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Inhibiting intimal hyperplasia in prosthetic vascular grafts via immobilized all-trans retinoic acid
Authors: Elaine K. Gregory, Antonio Webb, Janet M. Vercammen, Megan E. Kelly, Banu Akar, Robert van Lith, Edward M. Bahnson, Wulin Jiang, Guillermo A. Ameer, Melina R. Kibbe
Journal: Journal of Controlled Release (2018)
Relaxing boundary rules could affect GPs’ ability to care for patients
Authors: Ingrid Torjesen
Journal: BMJ (2012)

Government proposals to allow patients to register with a general practice remote from their home could affect the practice’s accountability for its patients and its ability to provide continuity of care, a medical defence organisation has warned.

The government is looking at relaxing rules on general practice boundaries to enable patients to see a GP at a practice further away from where they live, because for many it would be more convenient to have a consultation near their place of work or where their children are at school. A year long pilot scheme to test the feasibility of the plan is due to start …
Insight from mitochondrial functions and proteomics to understand cardiometabolic disorders in survivors of acute lymphoblastic leukemia
Authors: Jade Leahy, Schohraya Spahis, Eric Bonneil, Carole Garofalo, Guy Grimard, Sophia Morel, Caroline Laverdière, Maja Krajinovic, Simon Drouin, Edgard Delvin, Daniel Sinnett, Valérie Marcil, Emile Levy
Journal: Metabolism (2018)
How should I train for a career in A&amp;E? I did my foundation year 2 with only four months of A&amp;E—will I be able to take any exams with that? Which college should I contact for details?
Authors: Simon Eccles
Journal: BMJ (2007)

Have a career related problem that needs answering? Can9t find the 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>
We need to talk about manels: the problem of implicit gender bias in sport and exercise medicine
Authors: Sheree Bekker, Osman H Ahmed, Ummukulthoum Bakare, Tracy A Blake, Alison M Brooks, Todd E Davenport, Luciana De Michelis Mendonça, Lauren V Fortington, Michael Himawan, Joanne L Kemp, Karen Litzy, Roland F Loh, James MacDonald, Carly D McKay, Andrea B Mosler, Margo Mountjoy, Ann Pederson, Melanie I Stefan, Emma Stokes, Amy J Vassallo, Jackie L Whittaker
Journal: British Journal of Sports Medicine (2018)

In 2015, a website (www.allmalepanels.tumblr.com/) began documenting instances of all-male panels (colloquially known as a ‘manel’). This, along with the Twitter hashtag #manel, has helped drive recognition of the persistent and pervasive gender bias in the composition of experts assembled to present at conferences and other events.

Recent social media discussions have similarly highlighted the prevalence of all-male panels in Sport and Exercise Medicine (SEM). While, to our knowledge, all-male panel trends in SEM have not yet formally been documented or published, one need look no further than SEM conference committees, keynote speaker lists, panels and other events to see that it exists in practice. Why, in 2018, is SEM and its related disciplines still failing to identify and acknowledge the role that implicit bias plays in the very structure of our own research, practice and education? SEM is, after all, a profession that contains experts, and serves populations, of all genders.

This editorial will introduce the definition, implications and manifestations of implicit gender bias and then explore how the SEM community can begin to address this issue, advance the discussion and develop a more equitable global community.

Social cognitive theory describes ‘implicit bias’ as the unconscious …
Outcomes and patterns of disease progression in metastatic renal cell carcinoma patients treated with nivolumab.
Authors: Haris Zahoor, Pedro C. Barata, Kimberly D Allman, Allison Martin, Moshe Chaim Ornstein, Petros Grivas, Timothy D. Gilligan, Jorge A. Garcia, Brian I. Rini
Journal: Journal of Clinical Oncology (2018)

654 Background: Nivolumab (nivo) has been approved for the treatment of refractory metastatic renal cell carcinoma (mRCC). Data regarding the characteristics and outcomes of patients (pts) who progress on nivo are lacking. Methods: A retrospective analysis of pts with clear cell mRCC who received nivo at Cleveland Clinic (2015-2017) was performed. Pts were divided into two groups; 1) PD group; pts with progressive disease (PD) per RECIST v1.1 or clinical PD, and 2) NPD group; pts with non-progressive disease on nivo. Results: Ninety pts (PD group n = 55, NPD group n = 35) with median age of 67 (33-83), 74% men, and 79% ECOG 0-1 were included. Pts had received 1 (44%), 2 (29%), or ≥ 3 (27%) prior systemic treatments, most commonly with sunitinib (71%), axitinib (39%) and pazopanib (33%). Pts in the PD group had a greater incidence of baseline liver metastases (PD, 40% vs. NPD, 14%; p = 0.01), with other baseline characteristics not significantly different. Median follow up was similar in both groups (PD group, 8.0 months (95% CI, 5.5-10.5) and NPD group, 7.1 months (95% CI, 4.9-9.3); p = 0.87). Median duration of treatment for PD group was 8.7 months (95% CI, 7.3-10.1) compared to 16.1 months (95% CI, 8.6-23.6) for NPD group (p = 0.02). In the PD group, 50 (91%) pts developed PD per RECIST v1.1 whereas 5 (9%) pts had clinical PD. New organ sites of metastases were found in 20/55 (36%) pts; brain (8/20; 40%), liver (4/20; 20%), soft tissue (4/20; 20%), and locoregional (4/20; 20%) were the most common new organ sites, whereas lungs, lymph nodes and pancreas were never involved at PD as new organ sites. Twelve pts received treatment beyond progression (TBP) with a median duration of TBP of 2.8 months (95% CI, 0.6-5.0) and 50% of pts had stable disease as their best response. Median overall survival (OS) and progression free survival (PFS) on nivo were 10.1 months (95% CI, 6.6-13.6) and 5.5 months (95% CI, 2.9-8.1), respectively. Conclusions: Pts with PD on nivo have a higher incidence of hepatic metastases at baseline, and one third of these pts develop new sites of metastases at PD, most commonly brain.
GMC publishes new version of<i>Good Medical Practice</i>
Authors: Helen Jaques
Journal: BMJ (2013)

The General Medical Council has published an updated version of its core guidance for doctors, Good Medical Practice , which emphasises doctors’ role in ensuring minimum standards of care and compassion.

The new version of the guidance has been pared down from the 2006 original, with much of the explanatory detail moved into eight pieces of accompanying guidance. The regulator has also published explanatory guidance on social media for the first time.

The guidance has been restructured so that it corresponds with the four domains in the Good Medical Practice Framework for Appraisal and Revalidation : knowledge, skills, and performance; safety and quality; communication, partnership, and team …
Appraisals should tackle bullying of part time doctors, says academy
Authors: Abi Rimmer
Journal: BMJ (2013)

The issue of bullying should be raised in doctors’ annual appraisals to help reduce undermining of doctors who work less than full time, the Academy of Medical Royal Colleges has said.

A survey on part time working carried out by the academy found that 24.5% of women and 25% of men had experienced bullying or undermining behaviour at some point in their career.1 …
Musculoskeletal ultrasound: postgraduate certificate in medical imaging (medical ultrasound)
Authors: Manoj Sivan, James Brown
Journal: BMJ (2011)

Professionals who work in the field of musculoskeletal (MSK) medicine—musculoskeletal physicians, sports physicians, rehabilitation physicians, rheumatologists, radiographers, physiotherapists, podiatrists, and general practitioners with a special interest in MSK medicine.

We did the course while training in musculoskeletal and sports medicine. We use portable ultrasound regularly in outpatient clinics for diagnosis and guiding interventions.

The use of portable ultrasound in outpatient clinics is gaining popularity among clinicians in this area. As ultrasound is highly dependent on the operator, a formal qualification is necessary to set standards comparable to those of radiologists and radiographers providing a similar service.

The use of portable equipment in clinics enables on the spot diagnosis and helps explain findings to the patient. Using ultrasound to guide the injection during procedures increases the confidence of the clinician and the patient. Having seen the images on the screen, patients understand their condition better and are more likely to comply with the treatment plan. The …