tbuckley/cabot-search huggingface dataset:
Visceral metastases on abiraterone vs. placebo: A post-hoc analysis of mode of radiographic progression in COU-AA-302.
Authors: Benjamin A. Teply, Fang Qiu, Emmanuel S. Antonarakis, Michael Anthony Carducci, Samuel R. Denmeade
Journal: Journal of Clinical Oncology (2018)

194 Background: Abiraterone prolongs survival in patients with prostate cancer due to its potent inhibition of androgen synthesis. We previously observed increased rates of visceral metastatic disease at the time of progression on abiraterone compared to baseline, a poor prognostic feature associated with non-AR dependent prostate cancer. We hypothesized that the rate of development of visceral disease was increased with abiraterone compared to other treatments without potent androgen signaling inhibition. In order to test this, we examined time to visceral disease among patients treated with abiraterone vs placebo on the COU-AA-302 trial. Methods: We performed a post-hoc analysis of radiographic progression data for the phase 3 study of abiraterone vs placebo, via a data sharing agreement through the Yale Open Data Access Project. Data were censored at end of study treatment. The distribution of cumulative incidence for visceral metastases was calculated by the Kaplan-Meier method and compared with log-rank testing. Multivariable cox regression analysis was performed to assess for independent association of study treatment (abiraterone vs placebo) with the development of visceral metastases. Results: Median follow-up was 12.5mo, and 84 of 1088 patients developed visceral metastases. Univariate log-rank testing showed no difference in time to visceral metastasis between groups (p = 0.97). 1- and 3-yr cumulative incidence of visceral metastases were estimated at 6.4% and 15.6% for abiraterone and 4.6% and 17.0% for placebo, respectively. Study treatment was not a significant predictor for the development of visceral metastasis (HR 0.76; 95% CI 0.47-1.21) after adjustment for baseline metastatic disease burden (soft tissue and bone) and LDH. Conclusions: Abiraterone was not associated with increased visceral metastases at progression compared to placebo. These data give more confidence to oncologists that abiraterone is not driving prostate cancer to an aggressive phenotype characterized by visceral metastases - a finding that is particularly important as abiraterone is increasingly used in early disease states.
Herpetiform pemphigus with characteristic transmission electron microscopic findings of various‐sized ballooning vacuoles in keratinocytes without acantholysis
Authors: N. Ishiura, M. Tamura‐Nakano, H. Okochi, C. Tateishi, M. Maki, Y. Shimoda, N. Ishii, T. Hashimoto, T. Tamaki
Journal: British Journal of Dermatology (2018)

We report a unique case of a Japanese woman with herpetiform pemphigus (HP) who had IgG autoantibodies reactive with nondesmosomal sites of keratinocytes and presented characteristic transmission electron microscopic (TEM) findings of various‐sized vacuoles in keratinocytes without acantholysis. The patient presented with pruritic annular oedematous erythemas with small blisters lining the margins on the trunk and extremities. Histopathological examinations showed intraepidermal blisters with prominent infiltrations of eosinophils. Direct and indirect immunofluorescence tests revealed the presence of in vivo bound and circulating IgG autoantibodies to the keratinocyte cell surfaces. However, enzyme‐linked immunosorbent assays for desmoglein (Dsg) 1, Dsg3 and desmocollins 1–3 showed negative results. Immunoblotting using the full‐length human Dsg1 recombinant protein showed a positive band. TEM examination showed various‐sized vacuoles squashing the nuclei in many keratinocytes, resulting in rupture of the cells. Immunoelectron microscopic examination revealed IgG deposition over the entire keratinocyte cell surfaces, which spared the desmosomes. IgG antibodies were also present on the inside walls of the vacuoles around the nuclei of keratinocytes and on the cell surfaces of infiltrating eosinophils. This patient also had marked eosinophilia and high levels of thymus and activation‐regulated chemokine and interleukin‐5 in the serum. These results indicated a novel autoantigen on the nondesmosomal keratinocyte cell surfaces and the pathogenesis of bullous spongiotic change with inflammation in HP.
PRDM8 exhibits antitumor activities toward hepatocellular carcinoma by targeting NAP1L1
Authors: Zhiqiang Chen, Wen Gao, Liyong Pu, Long Zhang, Guoyong Han, Xueliang Zuo, Yao Zhang, Xiangcheng Li, Hongbing Shen, Jindao Wu, Xuehao Wang
Journal: Hepatology (2018)

Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. PRDI‐BF1 and RIZ homology domain containing 8 (PRDM8) is a key regulator in neural development and testis steroidogenesis; however, its role in liver carcinogenesis remains to be investigated. In this study, PRDM8 was found to be down‐regulated in HCC, which was linked with shorter recurrence‐free survival. Lentiviral‐based overexpression and knockdown approaches showed that PRDM8 inhibited HCC cell proliferation, migration, and invasion. PRDM8 caused G1/S cell cycle arrest and induced apoptosis. An in vivo tumor model confirmed the antitumor role of PRDM8 in HCC growth and metastasis. Mechanistic study showed that PRDM8 suppressed the PI3K/AKT/mTOR signaling cascade through the regulation of nucleosome assembly protein 1‐like 1 (NAP1L1). Conclusion : PRDM8 as a functional tumor suppressor is frequently down‐regulated in HCC. Through regulating NAP1L1, PRDM8 inhibits PI3K/AKT/mTOR signaling in HCC. PRDM8 is a potential target for therapies of HCC. (H epatology 2018).
Eroding Access and Quality of Childbirth Care in Rural US Counties
Authors: Neel T. Shah
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
Hypoxia-activated evofosfamide for treatment of recurrent bevacizumab-refractory glioblastoma: a phase I surgical study
Authors: Andrew Brenner, Richard Zuniga, Jessica D Sun, John Floyd, Charles P Hart, Stew Kroll, Lisa Fichtel, David Cavazos, Laura Caflisch, Aleksandra Gruslova, Shiliang Huang, Yichu Liu, Alessia Lodi, Stefano Tiziani
Journal: Neuro-Oncology (2018)

Anti-angiogenic therapy is known to induce a greater degree of hypoxia, including in glioblastoma (GBM). Evofosfamide (Evo) is a hypoxia-activated prodrug which is reduced, leading to the release of the alkylating agent bromo-isophosphoramide mustard. We assessed the safety, tolerability, preliminary efficacy, and biomarkers of Evo plus bevacizumab (Bev) in Bev-refractory GBM.
Expedition medicine and field skills for diverse environments
Authors: Alice Mavrogordato
Journal: BMJ (2008)

Any health professional with an interest in expedition medicine and who is considering accompanying an expedition. Candidates consisted mainly of doctors and acute care nurses, some with previous experience of remote medicine. Knowledge of advanced trauma life support is assumed.

While I was a surgical senior house officer, after completing membership of the Royal College of Surgeons.

I wanted to learn more about expedition medicine, to meet people with first hand experience of expeditions, and to prepare myself for being an expedition medical officer.

There was no pre-course reading; lectures were comprehensive and reinforced by a good course booklet. Reasonable physical fitness is required and necessary for the basic overnight camp conditions. …
Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct Models
Authors: Addie E. Embry, Zhenan Liu, Joel M. Henderson, F. Jefferson Byfield, Liping Liu, Joonho Yoon, Zhenzhen Wu, Katrina Cruz, Sara Moradi, C. Barton Gillombardo, Rihanna Z. Hussain, Richard Doelger, Olaf Stuve, Audrey N. Chang, Paul A. Janmey, Leslie A. Bruggeman, R. Tyler Miller
Journal: Journal of the American Society of Nephrology (2018)

Background FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear.Methods Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury.Results Compared with wild-type glomeruli, Tg26 glomeruli became progressively more deformable with disease progression, despite increased collagen content. Tg26 podocytes had disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion; they failed to respond to mechanical signals and exerted minimal traction force in three-dimensional collagen gels. Protamine treatment had similar but milder effects on glomeruli and podocytes.Conclusions Reduced structural integrity of Tg26 podocytes causes increased deformability of glomerular capillaries and limits the ability of capillaries to counter hemodynamic force, possibly leading to further podocyte injury. Loss of normal podocyte mechanical integrity could injure neighboring podocytes due to the absence of normal biophysical signals required for podocyte maintenance. The severe defects in podocyte mechanical behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively, despite increased collagen deposition, and may be the basis for the rapid course of glomerular diseases associated with severe podocyte injury. In milder injury (protamine), similar processes occur but over a longer time.
The impact of the preoperative waiting period on the survival in patients with clinical stage II / III gastric cancer.
Authors: Furukawa Kenichiro, Rie Makuuchi, Keiichi Fujiya, Noriyuki Nishiwaki, Hayato Omori, Sanae Kaji, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Yusuke Koseki, Raito Asaoka, Kenichi Nakamura, Yuhei Waki, Tomoyuki Irino, Masanori Terashima
Journal: Journal of Clinical Oncology (2018)

27 Background: Although prolonged preoperative waiting period (PWP) for gastric cancer (GC) may influence the prognosis, the relationship between PWP and survival outcome has not been elucidated. The aim of this study is to identify the impact of PWP on survival in patients with clinical stage (cStage) II / III GC. Methods: A total of 483 patients who underwent surgery for cStage II / III GC according to Japanese classification of GC, 14th edition, between January 2002 and December 2012 were included. The patients who underwent endoscopic submucosal dissection or neoadjuvant chemotherapy, or who had multiple cancer, special histological types of tumor, or urgent symptoms were excluded. We defined PWP as the period from the date of endoscopy for initial diagnose to that of surgery. Patients were divided into two groups according to PWP; short waiting period group (SWPG, PWP ≤ 60 days, n = 357) and long waiting period group (LWPG, PWP &gt; 60 days, n = 126). Survival outcomes were compared between the groups and multivariate analysis for overall survival (OS) was conducted to identify independent prognostic factors. Results: The median PWP was 49 (21-323) days. In LWPG, patients were significantly older (P = 0.001) and had more comorbidities (P = 0.042) than those in SWPG. Preoperative lymph node status was significantly lower in LWPG (P = 0.031), although there were no differences in tumor depth and cStage between the groups. There was no difference in OS between the groups (5-year OS, SWPG: 61.0%, LWPG: 63.2%, P = 0.612). Multivariate analysis for OS identified age, BMI, histological type, and cStage as independent prognostic factors. Conclusions: Preoperative waiting period appears to have no influence on survival in patients with cStage II / III GC.
MSc in clinical microbiology
Authors: Joanne Malkin
Journal: BMJ (2007)

Credit: CDC



FURTHER INFORMATION 

Professor Ala'Aldeen at daa@nottingham.ac.uk

Postgraduates with a good honours degree in biological sciences, medical science, or a related subject and trainees in medical microbiology, infectious diseases, and public health medicine. Half of my intake were doctors (with varying backgrounds and nationalities) and half were postgraduates with a medical science degree. Other years also have a number of biomedical scientists working in the NHS or private microbiology laboratories. The fees for British or European Union citizens are £3085 (about €4700; $6000) full time (part time …
British Association of Dermatologists’ guidelines for the investigation and management of generalized pruritus in adults without an underlying dermatosis, 2018
Authors: G.W.M. Millington, A. Collins, C.R. Lovell, T.A. Leslie, A.S.W. Yong, J.D. Morgan, T. Ajithkumar, M.J. Andrews, S.M. Rushbook, R.R. Coelho, S.J. Catten, K.Y.C. Lee, A.M. Skellett, A.G. Affleck, L.S. Exton, M.F. Mohd Mustapa, N.J. Levell, P.M. McHenry, K. Gibbon, D.A. Buckley, T.A. Leslie, E.C. Mallon, S. Wakelin, S. Ungureanu, R.Y.P. Hunasehally, M. Cork, G.A. Johnston, N. Chiang, J. Natkunarajah, F.S. Worsnop, C.E. Duarte Williamson, J. Donnelly, K. Towers, C. Saunders, A. Adbi Salad, A.G. Brain
Journal: British Journal of Dermatology (2018)

Plain language summary available online
Assessment of Plasmablastic Lymphoma by F-18 FDG PET/CT
Authors: Thomas Cazaentre, Laurence Sanhes, Guillaume Laurent, Keltoum Costa, Xavier Vallantin, Dominique Pascal-Ortiz
Journal: Clinical Nuclear Medicine (2010)

We presented an initial localization of plasmablastic lymphoma mimicking solitary plasmacytoma with widespread lymph node metastases after radiotherapy: a 68-year-old man reported lumbar pain symptoms of 3 months duration, which allowed to reveal an sacral osteolytic mass. The first diagnosis made was solitary plasmacytoma and the patient received 46 Gy by external radiotherapy. Three months later, the patient reported renal failure with deep asthenia and weight loss. The abdominal ultrasonography performed in emergency room revealed a huge retroperitoneal mass involving the both ureter with bilateral hydronephrosis. This unexpected progressive disease after radiotherapy changed the diagnosis to plasmablastic lymphoma.
Malaria in pregnancy alters <scp>l</scp> -arginine bioavailability and placental vascular development
Authors: Chloe R. McDonald, Lindsay S. Cahill, Joel L. Gamble, Robyn Elphinstone, Lisa M. Gazdzinski, Kathleen J. Y. Zhong, Adrienne C. Philson, Mwayiwawo Madanitsa, Linda Kalilani-Phiri, Victor Mwapasa, Feiko O. ter Kuile, John G. Sled, Andrea L. Conroy, Kevin C. Kain
Journal: Science Translational Medicine (2018)

Malaria in pregnancy alters l -arginine biosynthesis in Malawian women, and l -arginine supplementation improves placental vasculature and birth outcomes in a preclinical model.
CATHETER ABLATION VERSUS OTHER STRATEGIES FOR TREATMENT OF ATRIAL FIBRILLATION IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION: A META-ANALYSIS ON CHANGE IN EJECTION FRACTION
Authors: Nirav Patel, Rajkumar Doshi, Rajat Kalra, Navkaranbir Bajaj, Garima Arora, Pankaj Arora
Journal: Journal of the American College of Cardiology (2018)
12-MONTH PROGRESSION TO SEVERITY IN NON-CLINICALLY SIGNIFICANT FUNCTIONAL MITRAL REGURGITATION [NSFMR] PATIENTS WITH AND WITHOUT ISCHEMIA IN MEDICARE FEE-FOR-SERVICE PATIENTS
Authors: David Patrick Cork, Emilie Kottenmeier, Patrick Verta, Sarah Mollenkopf, Teresa Green, Hirsch Mehta
Journal: Journal of the American College of Cardiology (2018)
Bullying of surgeons remains big problem in Australia, study finds
Authors: Matthew Limb
Journal: BMJ (2016)

High levels of workplace bullying remain a major problem in general surgery in Australia, with consultants the worst offenders, researchers have found.

The researchers found that some surgeons may view intimidation and harassment as “functional tools in surgical education.” Their study indicates that much bullying is not formally logged.

The researchers surveyed 370 trainees and consultant surgeons and found that nearly half (47%) reported having been bullied to some degree, implying a culture of bullying within organisations. Trainees (64%) and women (57%) experienced the most bullying, and consultants were the most common source of bullying of …
GMC language tests for doctors from EU are expected to be in place this summer
Authors: Abi Rimmer
Journal: BMJ (2014)

The Department of Health in England has confirmed that it will implement a UK-wide plan to allow the General Medical Council to test the English language competence of doctors from other European Union countries. The GMC said it expects the changes to be introduced in the summer of 2014.

The health department’s consultation on plans to change the Medical Act 1983 to give the GMC more power to test the language skills of doctors from the European Union closed on 2 December. The proposed amendments to the act will now be made as soon as possible, subject to parliamentary approval, the department has said.1

The changes will give the GMC the power to “require evidence of English language capability as part of the licensing process …
Royal college launches five year plan to increase applicants to psychiatry
Authors: Helen Jaques
Journal: BMJ (2012)

The Royal College of Psychiatrists has announced a five year plan to increase applications to core training in psychiatry by 50% and achieve a 95% fill rate for these posts.

Last year at the end of round two recruitment in England and Wales only 83% of the 478 vacancies for core psychiatry training had been filled, with fill rates particularly poor in Wales but good in London. 

The college aims to increase the number of unique applicants …
Trends in Obesity and Severe Obesity Prevalence in US Youth and Adults by Sex and Age, 2007-2008 to 2015-2016
Authors: Craig M. Hales, Cheryl D. Fryar, Margaret D. Carroll, David S. Freedman, Cynthia L. Ogden
Journal: JAMA (2018)

Cynthia L. Ogden, PhD; Cheryl D. Fryar, MSPH; Craig M. Hales, MD; Margaret D. Carroll, MSPH; Yutaka Aoki, PhD; David S. Freedman, PhD
Fundamentals of disaster management course (FDM)
Authors: Tiago Villanueva
Journal: BMJ (2007)

Credit: STEVE MAISEY/REX



FURTHER INFORMATION 

www.sccm.org/SCCM—American Society of Critical Care Medicine

The course is aimed at doctors working in primary care, emergency medicine, and critical care, as well as other healthcare professionals such as nurses, pre-hospital providers, and critical care transport professionals.

I did it because I went to a congress on disaster medicine last year, and gained a general awareness of the field. When I heard about the possibility of doing this course, it occurred to me that it would be the perfect follow up to the congress and …
Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer—The New Standard of Care?
Authors: Theodore S. Hong, David P. Ryan
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
Could you please tell me how I can do an MD in the United Kingdom?
Authors: Brian Angus
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>
Postpartum Depression and Its Long-term Impact on Children
Authors: Myrna M. Weissman
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal