tbuckley/cabot-search huggingface dataset:
A microRNA-based signature predicting immune-related toxicity (iRAEs) to pembrolizumab in prostate cancer patients.
Authors: Joanne B. Weidhaas, Kirk Wilenius, Aaron Wolfe Scheffler, Juliana Higa, Donatello Telesca, Mark C. Scholz
Journal: Journal of Clinical Oncology (2018)

269 Background: The need to predict immune-related adverse events (iRAEs) for patients receiving checkpoint inhibitors is a pressing issue, with up to 25-30% Grade 2 or higher toxicity with single agent therapy, regardless of cancer type. Our group is studying a novel class of inherited mutations that disrupt the normal regulatory process of microRNAs as they function to control the genome. We have previously applied a panel of these mutations to predict iRAEs in melanoma and NSCLC patients receiving anti-PD1/anti-PDL1 therapy. We hypothesize that our mutations will predict iRAEs across cancer types. Here we have investigated their ability to predict iRAEs in a cohort of recurrent or advanced prostate cancer patients receiving Pembrolizumab (Pembro). Methods: We previously trained several statistical classifiers on a set of 86 melanoma and NSCLC patients evaluated for iRAEs. Subjects were classified as experiencing high toxicity (grade 2 or more) versus low toxicity (less than 2). We next tested the performance of the identified biomarkers on a set of 40 prospectively-treated prostate cancer patients who had received at least three cycles of Pembro, 200mg every 3 weeks. Samples were collected via cheek swab and germ-line DNA was isolated for testing. Predictive models of high-grade toxicity were based on 49 common markers between training and test samples. Classifiers were built comparing: classification trees, LASSO-regularized logistic regression, and random forests. All models were tuned at training using leave-one-out cross validation. The final extrapolation test errors were estimated on the prostate cohort as validation data not used in training. Results: Within the melanoma and NSCLC training sample we estimate toxicity with 71% accuracy (85% sensitivity, 43% specificity). We found that our biomarker panel when applied to prostate cancer patients extrapolates quite well, where our biomarkers predict toxicity with 68% accuracy (82% sensitivity, 38% specificity). Conclusions: We have identified a panel of microRNA-based, germ-line biomarkers which predict the risk of iRAEs. This panel appears to predict iRAEs across cancer types, including prostate cancer.
IMPACT OF VESSEL SIZE ON STENT PATENCY FOLLOWING SELF-EXPANDING STENTS IMPLANTATION IN SUPERFICIAL FEMORAL ARTERY LESIONS
Authors: Kojiro Miki, Koji Yanaka, Nagataka Yoshihara, Kenji Kawai, Takahiro Imanaka, Hirokuni Akahori, Tohru Masuyama, Masaharu Ishihara
Journal: Journal of the American College of Cardiology (2018)
Vitamin therapy in critically ill patients: focus on thiamine, vitamin C, and vitamin D
Authors: Karin Amrein, Heleen M. Oudemans-van Straaten, Mette M. Berger
Journal: Intensive Care Medicine (2018)

Recent hypothesis-generating studies have sparked new interest in an old concept: adjuvant vitamin therapy in critical illness or “metabolic resuscitation”. In this mini-review, we report on the most promising players in this setting: thiamine (vitamin B1), vitamin C, and vitamin D. Their main characteristics are summarized in Table 1 (see also electronic supplementary material, ESM). 

Table 1

The characteristics of thiamine, vitamin C, and vitamin D and the symptoms and management of deficiency
I wish to do postgraduate studies in anaesthetics or paediatrics in either the United Kingdom or Australia. Please advise me on selecting one field, taking into consideration job opportunities, risk, salary, and other aspects
Authors: Patrick Strube
Journal: BMJ (2006)

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>
Prevention and Management of Heat-Related Illness Among Spectators and Staff During the Olympic Games—Atlanta, July 6-23, 1996
Journal: JAMA (1996)

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
I'm a general practitioner planning to work in a developing country for a while. How will this affect my appraisal and revalidation?
Authors: Brian Keighley
Journal: BMJ (2004)

Got a career or related problem that needs answering? Can't 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.
Italy’s New Advance Directive Law
Authors: Daniel P. Sulmasy
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Aurora Kinase A (AURKA) is an independent predictor of recurrence in breast ductal carcinoma in situ (DCIS)
Authors: I.M. Miligy, A. Gaber, M.S. Toss, A. Hamad, C. Nolan, M. Diez-Rodriguez, I.O. Ellis, A. Green, E. Rakha
Journal: Annals of Oncology (2018)
Bivalirudin or Heparin in Patients Undergoing Invasive Management of Acute Coronary Syndromes
Authors: Giuseppe Gargiulo, Greta Carrara, Enrico Frigoli, Pascal Vranckx, Sergio Leonardi, Nestor Ciociano, Gianluca Campo, Ferdinando Varbella, Paolo Calabrò, Stefano Garducci, Alessandro Iannone, Carlo Briguori, Giuseppe Andò, Gabriele Crimi, Ugo Limbruno, Roberto Garbo, Paolo Sganzerla, Filippo Russo, Alessandro Lupi, Bernardo Cortese, Arturo Ausiello, Salvatore Ierna, Giovanni Esposito, Dennis Zavalloni, Andrea Santarelli, Gennaro Sardella, Simone Tresoldi, Nicoletta de Cesare, Alessandro Sciahbasi, Antonio Zingarelli, Paolo Tosi, Arnoud van ’t Hof, Elmir Omerovic, Salvatore Brugaletta, Stephan Windecker, Marco Valgimigli
Journal: Journal of the American College of Cardiology (2018)
TEMPORAL CHANGES IN DIASTOLIC FUNCTION IN WOMEN WITH BREAST CANCER RECEIVING SEQUENTIAL THERAPY WITH ANTHRACYCLINE AND TRASTUZUMAB
Authors: Mark T. Nolan, Jennifer Meloche, Eitan Amir, Christine M. Brezden, Babitha Thampinathan, Maria Michalowska, Anna Woo, Bernd Wintersperger, Paaladinesh Thavendiranathan
Journal: Journal of the American College of Cardiology (2018)
Current Strategies for Brain Drug Delivery
Authors: Xiaowei Dong
Journal: Theranostics (2018)

The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery.The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB.Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted.The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years.It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain.After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles.Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake.Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.
Long-lasting Intense Bone Tracer Activity at the Sites of Collagen Injection
Authors: Ling Wang, Xiaona Jin, Fang Li
Journal: Clinical Nuclear Medicine (2018)

Collagen injection has been used as dermal filler in plastic and cosmetic surgery. A technetium Tc methylene diphosphonate bone scintigraphy was performed in a 47-year-old woman as part of the breast cancer evaluation. The images showed intense methylene diphosphonate activity on both sides of the frontal head, where she received collagen injection 1 year prior. The activity was visualized again in all 3 follow-up bone scans over the subsequent 3 years.
Reactivation of Mutant-EGFR Degradation through Clathrin Inhibition Overcomes Resistance to EGFR Tyrosine Kinase Inhibitors
Authors: Ludovic Ménard, Nicolas Floc'h, Matthew J. Martin, Darren A.E. Cross
Journal: Cancer Research (2018)

Tyrosine kinase inhibitors (TKI) targeting mutant EGFR in non-small cell lung cancer (NSCLC) have been successful to control cancer growth, but acquired resistance inevitably occurs, including mutations directly on EGFR, for example, T790M and C797S. Strategies to prevent such acquired mutations by reducing mutant-EGFR expression have met limited success. Here, we propose a new model of mutant-EGFR trafficking and demonstrate that clathrin inhibition induces rapid degradation across a large panel of endogenous mutant-EGFR (Ex19del, L858R, and Ex20Ins). This panel included mutant-EGFR (T790M) resistant to the first- and second-generation EGFR inhibitors and to the third-generation TKI osimertinib and occurs through both mutational (C797S) and nonmutational EGFR mechanisms. Clathrin-mediated endocytosis inhibition of mutant EGFR induced a macropinocytosis-dependent lysosomal pathway associated with a loss of mutant-EGFR-dependent signaling (pAKT, pERK). Moreover, induction of this macropinocytic pathway led to robust apoptosis-dependent death across all mutant-EGFR cell lines tested, including those resistant to TKIs. We, therefore, propose a novel strategy to target mutant-EGFR refractory to approved existing TKI treatments in NSCLC and where new treatment strategies remain a key area of unmet need.Significance: These findings extend our mechanistic understanding of NSCLC mutant EGFR trafficking biology, the role that trafficking may play in resistance of mutant EGFR to tyrosine kinase inhibitors, and provide new therapeutic and biological insights to tackle this fundamental issue and improve benefit to patients. Cancer Res; 78(12); 3267-79. ©2018 AACR.
Career Options in General Practice⇓
Authors: Judith Harvey
Journal: BMJ (2004)

A generation ago a book entitled Career Options in General Practice would have been unthinkable. General practitioners (GPs) spent their working lives in one practice, and leaving a partnership was as shameful as a divorce had been in Victorian times.

If a GP from the 1950s would have been surprised by the title, he or she would have been shocked by the first chapter: “How hard do you want to work?”; this wasn't a question doctors asked themselves. But in those days you could go home …
PERCUTANEOUS CLOSURE OF PATENT FORAMEN OVALE OR MEDICAL THERAPY FOR STROKE PREVENTION: A META-ANALYSIS OF RANDOMIZED TRIALS
Authors: Khagendra Dahal, Adil Yousuf, Magdy Hanna, Sharan Sharma, Jharendra Rijal, Hussam Watti, Nelson Telles Garcia, Augustine Njoku, Juyong Lee, Pavan Katikaneni, Enrique Jimenez, Kalgi Modi, Neeraj Tandon
Journal: Journal of the American College of Cardiology (2018)
Disseminated intravascular coagulation secondary to advanced prostate cancer: Clinical characteristics, management, and prognosis.
Authors: Benny Ni, Jue Wang
Journal: Journal of Clinical Oncology (2018)

355 Background: Although disseminated intravascular coagulation (DIC) is a recognized complication of prostate cancer, little is known about the clinical features and optimal management of these patients. Although anecdotal case studies indicating that the prognosis of prostate cancer associated with DIC might improve with chemotherapy, the clinical data from single case report are far from sufficient for establishment of a standardized treatment strategy. The main objective of this study was to determine the clinical features, treatment and prognosis clinical outcome of patients with prostate cancer complicated by DIC. Methods: We conducted a pooled analysis of 85 prostate cancer patients diagnosed with DIC, two treated in our institution and 83 patients from published literature between January 1976 and June 2017. Results: Eighty-five patients were included in final analysis. The median age was 68 years (range, 44 to 92 years). The majority of patients (98%) has adenocarcinoma. Two (2%) patients with small cell carcinoma. The median of PSA was 614 ng/ml (range: 0.8 – 8138). A Gleason score of 8 or higher was found in 67% of patients. Distant metastasis was reported in 98% of patients. At diagnosis of DIC, the median platelet count was 75 *10 9 /L (range: 3-205). Regarding the presenting symptoms of DIC, subcutaneous bleeding was reported in 64% of cases; hematuria in 27%. Invasive procedure including prostate biopsy might have been the provoking events of DIC in 25% of the cases. Seventy-one patients received cancer directed therapy including various androgen deprivation, chemotherapy, and novel androgen signaling inhibitor, whereas 13 patients received only best supportive care (BSC). The median overall survival (OS) of the entire cohort of patients was 10 months (95% confidence interval [CI], 5.3-14.7). Significantly prolonged OS was observed in the cancer therapy group, with a median survival of 12 months compared to 2 weeks in the BSC group (p &lt; 0.001, log-rank test). Conclusions: Our analysis showed that patients with prostate cancer complicated by DIC had very poor prognosis, and active cancer therapy might improve OS of these patients.
Racial and Ethnic Disparities in Sustained Viral Suppression and Transmission Risk Potential Among Persons Receiving HIV Care — United States, 2014
Authors: Nicole Crepaz, Xueyuan Dong, Xiao Wang, Angela L. Hernandez, H. Irene Hall
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Non-Hispanic blacks/African Americans (blacks) represent 12% of the U.S.* However, in 2014 an estimated 43% (471,500) of persons living with diagnosed and undiagnosed human immunodeficiency virus (HIV) infection were blacks (1). In 2016, blacks accounted for 44% of all new HIV diagnoses (2). Although antiretroviral therapy (ART) prescriptions among persons in HIV care increased overall from 89% in 2009 to 94% in 2013, fewer blacks than Hispanics or Latinos (Hispanics) and non-Hispanic whites (whites) were on ART and had a suppressed viral load (<200 HIV RNA copies/mL) in their most recent viral load test result (3). Blacks also might be less likely to have sustained viral suppression over time and to experience longer periods with viral loads >1,500 HIV RNA copies/mL, a level that increases the risk for transmitting HIV (4-7). National HIV Surveillance System (NHSS) data are among those used to monitor progress toward reaching the national goal of reducing health disparities. CDC analyzed NHSS data to describe sustained viral suppression and transmission risk potential by race/ethnicity. Among 651,811 persons with HIV infection diagnosed through 2013 and who were alive through 2014 in 38 jurisdictions with complete laboratory reporting, a lower percentage of blacks had sustained viral suppression (40.8%), than had Hispanics (50.1%) and whites (56.3%). Among persons who were in care (i.e., had at least one viral load test in 2014) and had not achieved sustained viral suppression in 2014, blacks experienced longer periods (52.1% of the 12-month period) with viral loads >1,500 copies/mL, than did Hispanics (47.2%) and white (40.8%). Blacks aged 13-24 years had the lowest prevalence of sustained viral suppression, a circumstance that might increase transmission risk potential. Strengthening interventions that improve access to ART, promote adherence, and address barriers to clinical care and supportive services for all persons with diagnosed HIV infection is important for achieving the national goal of reducing health disparities.
Phase 1/2 study of safety/efficacy using trabectedin, ipilimumab, and nivolumab as first-line treatment of advanced soft tissue sarcoma (STS).
Authors: Erlinda Maria Gordon, Victoria S. Chua-Alcala, Katherine Kim, William W. Tseng, Doris M Quon, Sant P Chawla
Journal: Journal of Clinical Oncology (2018)

TPS46 Background: Sarcoma cells are most immunogenic at the onset of cancer when the immune system can recognize and destroy them. Hence, immune checkpoint inhibitors would be most effective when given as first line therapy. Objectives: (1) To investigate the maximum tolerated dose of trabectedin, an alkylating agent, when given sequentially with ipilimumab, a CTLA4 inhibitor, and nivolumab, a PD-1 inhibitor, in advanced STS, (2) To investigate the objective response rate (ORR), progression free survival (PFS) and overall survival (OS) , and (3) To correlate PFS with PD-L1 and other biomarker expression in patients’ tumors. Methods: Forty patients ≥18 years of age with advanced STS will be enrolled. This is a phase 1/2 study using a defined dose of ipilimumab (1 mg/kg i.v. q 12 weeks), nivolumab (3 mg/kg i.v. q 2 weeks), and escalating doses of trabectedin (1.0, 1.3, 1.5 mg/m 2 i.v. q 3 weeks). I. Dose Escalation Phase 1 (previously treated patients): The study will employ the standard “cohort of three” design. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. II. Expansion Phase 2 (previously untreated patients): An additional 22-28 patients will receive trabectedin at the MTD and defined doses of ipilimumab and nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients may continue treatment until significant disease progression or unacceptable toxicity occurs. Statistical Considerations: NIH CTCAE v4.03 and RECIST v1.1 will be used. Categorical variables will be summarized by the n and percent in each category. Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. The analyses of all study objectives will be descriptive and hypothesis generating, for planning Phase 2/3 studies. Clinical trial information: NCT 03138161.
Femoroacetabular impingement surgery allows 74% of athletes to return to the same competitive level of sports participation but their level of performance remains unreported: a systematic review with meta-analysis
Authors: Michael P Reiman, Scott Peters, Jonathan Sylvain, Seth Hagymasi, Richard C Mather, Adam P Goode
Journal: British Journal of Sports Medicine (2018)

Background Femoroacetabular impingement (FAI) syndrome is one source of hip pain that can limit sport participation among athletes. Objective To summarise the return to sport (RTS) rate for athletes after surgery for FAI syndrome. Methods A computer-assisted search of MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and EMBASE databases was performed using keywords related to RTS and RTS at preinjury level (RTS PRE ) of competition for FAI syndrome. The risk of bias in the included studies was assessed using the Methodological Index for Non-Randomized Studies scale. Results 35 studies (1634 athletes/1828 hips) qualified for analysis. Based on evidence of limited to moderate strength (level 3b to 4 studies), athletes return to sport at preinjury level post surgery for FAI syndrome at a rate of only 74% (67%–81%). Only 37% of studies reported RTS PRE . The mean time from surgery to RTS was 7.0±2.6 months. The mean follow-up postsurgery was 28.1±15.5 months. Professional athletes returned to sport (p=0.0002) (although not the preinjury sport level; p=0.63) at a higher rate than collegiate athletes. Only 14% of studies reported on athletic presurgery and postsurgery athletic performance, which means it is impossible to comment on whether athletes return to their previous level of performance or not. No studies reported on the specific criteria used to permit players to return to sport. 20% of studies reported on career longevity, 51% reported surgical complications and 77% reported on surgical failures. Conclusion There was limited to moderate evidence that one in four athletes did not return to their previous level of sport participation after surgery for FAI syndrome. Only 37% of the included studies clearly distinguished RTS from RTS PRE . Poor outcome reporting on athletic performance postsurgery makes it difficult to determine to what level of performance these athletes actually perform. Thus, if a player asks a surgeon ‘Will I get back to my previous level of performance?’ there are presently little to no published data from which to base an answer. PROSPERO registration number CRD42017072762.
Masters in medical sciences in clinical psychiatry (M Med Sci in clinical psychiatry)
Authors: Arun Chopra
Journal: BMJ (2007)

FURTHER INFORMATION 

Denise Dobbs, M Med Sci course administrator, Duncan Macmillan House, Nottingham NG3 6AA denise.dobbs@nottingham.ac.uk

Currently, it's for doctors interested in psychiatry and those taking membership examinations. However, moves are under way to convert the degree to a masters in mental health studies in 2008, opening up entry to professionals from paramedical backgrounds. Some modules will remain compulsory for doctors.

As a senior house officer on the Nottingham psychiatry rotation.

To learn more about different aspects of mental health and illness and as an introduction to research …