tbuckley/cabot-search huggingface dataset:
The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers
Authors: Britta Weigelt, Rui Bi, Rahul Kumar, Pedro Blecua, Diana L Mandelker, Felipe C Geyer, Fresia Pareja, Paul A James, Fergus J Couch, Diana M Eccles, Fiona Blows, Paul Pharoah, Anqi Li, Pier Selenica, Raymond S Lim, Gowtham Jayakumaran, Nic Waddell, Ronglai Shen, Larry Norton, Hannah Y Wen, Simon N Powell, Nadeem Riaz, Mark E Robson, Jorge S Reis-Filho, Georgia Chenevix-Trench
Journal: JNCI Journal of the National Cancer Institute (2018)

Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.
THE INFLUENCE OF PATIENT RACE, SEX AND EDUCATION ON PROVIDER SPECIALTY ANTICOAGULATION PRESCRIPTION PATTERNS AND OUTCOMES IN ATRIAL FIBRILLATION
Authors: Wesley O’Neal, J’Neka Claxton, Pratik Sandesara, Richard MacLehose, Faye Norby, Lin Chen, Lindsay Bengtson, Alanna Chamberlain, Pamela Lutsey, Alvaro Alonso
Journal: Journal of the American College of Cardiology (2018)
Abstract 16444: Aging on Cardiovascular Functional and Structural Responses: Does the Presence of β3-Adrenergic Receptors Have a Role?
Authors: Che Ping Cheng, Michael F Callahan, Zhi Zhang, Tiankai Li, Xiaowei Zhang, Satoshi Masutani, Dalane Kitzman, Heng-Jie Cheng
Journal: Circulation (2017)

Background: Aging has a remarkable effect on the heart and arterial system. Although cardiovascular functional responses to aging have not been fully investigated, recent evidence suggests that car...
Just 23 GPs and 36 hospital specialists have had revalidation deferred owing to concerns, GMC figures show
Authors: Abi Rimmer
Journal: BMJ (2014)

Just 23 GPs and 36 hospital specialists in the UK have had their revalidation deferred because of local issues, such as being involved in a disciplinary process, figures published by the General Medical Council have shown.

Revalidation operational data reports published by the GMC give figures on numbers of doctors who were revalidated or were due to be revalidated from December 2012 to September 2013.1

The …
Targeting HSF1: A Prime Integrator of Proteotoxic Stress Response in Myeloma
Authors: Samir Parekh
Journal: Clinical Cancer Research (2018)

The HSF1 transcription factor is an integrator of the cellular stress response, and its expression has demonstrated poor prognosis in multiple myeloma. The novel anti-HSF1 small-molecule inhibitors CCT251236 and KRIB11 demonstrate in vitro and in vivo antimyeloma activity, representing a novel approach for targeting the heat shock response in myeloma. Clin Cancer Res; 24(10); 2237-8. ©2018 AACRSee related article by Fok et al., p. 2395.
Editor’s Choice: In the spotlight
Authors: Tom Moberly
Journal: BMJ (2016)

Doctors’ interactions with the media are examined from two different perspectives in this week’s BMJ Careers. Rachel Birch considers what doctors should do when they are approached by the media for comment on a story (http://careers.bmj.com/careers/advice/In\_the\_eye\_of\_the\_media\_storm), while Rachel Isba and Lucy Potter describe their experiences working in the media (http://careers.bmj.com/careers/advice/The\_art\_of\_communicating\_science).

Birch …
RAPID VENTRICULAR PACING DURING TRANSCATHETER VALVE PROCEDURES USING AN INTERNAL DEVICE AND PROGRAMMER: A DEMONSTRATION OF FEASIBILITY
Authors: Yash Jobanputra, Brandon Jones, Amar Krishnaswamy, Stephanie Mick, Mandeep Bhargava, Bruce Wilkoff, Samir Kapadia
Journal: Journal of the American College of Cardiology (2018)
PRACTICE MAKES PERFECT? THE CORRELATION BETWEEN HOSPITAL VOLUME OF TARGETED TEMPERATURE MANAGEMENT AND IN-HOSPITAL MORTALITY RATE: A NATIONWIDE ANALYSIS FROM 2010 TO 2014
Authors: Xin Wei, Kevin Gu, Ahmadreza Moradi, Bing Yue, Xiaochuan Yang, Chayakrit Krittanawong, Karan Sud, Mario Rodriguez, Mariam Khandaker, Basera Sabharwal, Eyal Herzog
Journal: Journal of the American College of Cardiology (2018)
Role of a clinical prediction score in a chronic thromboembolic pulmonary hypertension rule-out strategy
Authors: Remedios Otero, Laurent Bertoletti, Alfonso Muriel, Carmine Siniscalchi, Carmen Jimenez, Jose Luis Lobo, Dana Kigitovica, Roberto Quintavalla, Anna Rocci, Luis Jara-Palomares, Manuel Monreal
Journal: European Respiratory Journal (2018)

<b>The current predictive score, based on data during the index pulmonary embolism, is not sensitive enough in a chronic thromboembolic pulmonary hypertension (CTEPH) rule-out strategy</b>http://ow.ly/8fGy30iIjgN
Abstract 12322: Physical Symptoms and Depression Interact in Predicting Quality-of-Life in Heart Failure
Authors: Quin E Denfeld, James O Mudd, Shirin O Hiatt, Jill M Gelow, Christopher V Chien, Christopher S Lee
Journal: Circulation (2015)

Introduction: Quality-of-life (QOL) is an important patient-oriented outcome in heart failure (HF). The interaction effect of physical symptoms and depression in predicting QOL in HF, however, is not well understood. Hypothesis: There is a strong interaction effect between physical symptom and depression in predicting QOL among adults with moderate to advanced HF. Methods: This was a secondary analysis of combined data collected during two prospective cohort studies of symptoms among adults with moderate to advanced HF. Physical symptoms were measured with the Heart Failure Somatic Perception Scale subscale (HFSPS), and depression was measured with the Patient Health Questionnaire-9 (PHQ-9). QOL was measured with the visual analog scale (VAS) of the EQ-5D. Results: The average age of the sample (n=291) was 56.7±13.3 years, and most were male (61.9%). A majority of subjects were classified as New York Heart Association Class III HF (56.4%), and most had non-ischemic etiology (65.2%). Average VAS score on the EQ-5D was 54.27±22.54. Both HFSPS scores (β = -0.58 ± 0.12, p&lt;0.001) and PHQ9 scores (β = -1.77 ± 0.38, p&lt;0.001) were significantly related to VAS scores. There was a significant interaction effect of HFSPS scores and PHQ9 scores in predicting VAS scores (Figure 1; interaction effect: β = 0.02 ± 0.01, p&lt;0.05; model: R2 = 0.28, F(3,265) = 35.18, p&lt;0.001). Conclusions: Physical symptoms and depression have strong independent and interactive effects in predicting QOL in HF, indicating that both should be considered concurrently when managing QOL among adults with HF.
TRANSITIONING FROM CARDIAC SPECT TO PET MYOCARDIAL PERFUSION IMAGING RESULTED IN INCREASED ASCERTAINMENT OF INDIVIDUALS REQUIRING REVASCULARIZATION
Authors: David B. Min, Steve Mason, Stacey Knight, JD Ethington, Viet T. Le, Kent Meredith, Ritesh Dhar, Jeffrey Anderson, J. Muhlestein, Donald Lappe, Kirk Knowlton
Journal: Journal of the American College of Cardiology (2018)
Royal college calls for surgeon title to be protected
Authors: Helen Jaques
Journal: BMJ (2012)

The Royal College of Surgeons is seeking legal protection for the job title “surgeon” so that only people who have qualified as a medical doctor and undertaken postgraduate surgical training can use the title.

The college argues that patients can be confused by the different types of non-medical healthcare professionals who use the title “surgeon,” such as podiatric surgeons and aesthetic surgeons.

In some cases patients being treated in the NHS by a “surgeon” may wrongly assume that the person holds a medical degree and is a surgical specialist, it says, potentially undermining patients’ ability to give informed consent and …
Rising costs are putting junior consultants off private practice, accountant says
Authors: Abi Rimmer
Journal: BMJ (2015)

Junior consultants are choosing not to enter private practice because of rising costs, a specialist medical accountant has said.

Speaking at the BMA’s private practice conference in London on Thursday 30 April, Ray Stanbridge, director of Stanbridge Associates, said that younger consultants were choosing not to set up their own private practices. 

“Many junior consultants are electing not to go into …
LETTER OF THE MONTH While we are all so busy worrying about the patients... who is looking after the doctors?
Authors: Tafadzwa Makaya
Journal: BMJ (2007)

We welcome your rapid responses, whether in direct response to an article in Career Focus or as a way of sharing your own ideas. As long as it isn9t libellous or offensive, we9ll post it on our website. We print a selection of rapid reponses here and the writer of the best each month wins an <i>Oxford Handbook</i> of their choice. Letter of the month prize is donated by OUP.
I am an overseas doctor and I have passed my Professional and Linguistic Assessments Board (PLAB) test part 2. Can I apply for a senior house officer job in the armed forces in the United Kingdom?
Authors: Mel Temple
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>
RISK ASSOCIATED WITH MYOCARDIAL FIBROSIS IS MODULATED BY THE EXTENT OF LEFT VENTRICULAR REMODELING DUE TO NON-ISCHEMIC CARDIOMYOPATHY
Authors: Nishant Shah, Sharif Sabe, Nancy Obuchowski, Ahmed Bafadel, Karim Adurrehman, Scott Flamm, Wai Hong Tang, Brian Griffin, Deborah Kwon
Journal: Journal of the American College of Cardiology (2018)
68Ga-PSMA PET/CT Revealing Unusual Inguinal Canal and Distant Nodal Metastasis in a Case of Castration-Resistant Prostate Cancer
Authors: Shelvin Kumar Vadi, Rajender Kumar, Bhagwant Rai Mittal, Harmandeep Singh, Shrawan Kumar Singh
Journal: Clinical Nuclear Medicine (2018)

Gallium-prostate-specific membrane antigen (Ga-PSMA) is well established in the imaging of prostate cancer (PC). Here, we report a case of castration-resistant PC who underwent Ga-PSMA PET/CT for recurrence evaluation, which revealed metastatic lesions in distant lymph nodes and additionally an unusual metastatic deposit in the inguinal canal. The second Ga-PSMA PET/CT done after oral hormonal therapy yielded a favorable response. This pattern of distant metastatic spread is a rare presentation of PC, and PSMA PET/CT revealed the unusual metastasis in the inguinal canal with a timely therapy culminating in favorable disease response.
Why do SAS doctors fail to take up CPD opportunities?
Authors: Umesh Dashora, Subir Mukherjee
Journal: BMJ (2015)

In the first part of their investigation <b>Umesh Dashora </b>and<b> Subir Mukherjee</b> looked at the reasons why few SAS doctors take up training opportunities (http://careers.bmj.com/careers/advice/SAS_doctors_are_unaware_of_training_opportunities). Here they investigate further
Statin use and risk of renal cell carcinoma in three prospective cohort studies.
Authors: Kathryn M. Wilson, Alejandro Sanchez, Rebecca E. Graff, Sabina Signoretti, Toni K. Choueiri, David F. McDermott, Eunyoung Cho, Mark A Preston
Journal: Journal of Clinical Oncology (2018)

679 Background: Evidence on statin use and incidence of renal cell carcinoma (RCC) is mixed. Previous results from the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) found a suggestive protective effect in women but not in men (Liu et al, Cancer 2012). We conducted an updated analysis of statin use and risk of total and fatal RCC in the NHS, HPFS, and NHS 2 cohorts, with more than twice as many cases. Methods: We examined the associations between statin use and risk of RCC from 1990 to 2016 in HPFS (men), 1994 to 2016 in NHS (women), and 1999 to 2015 in NHS 2 (women). Information on statin use was collected every two years. We used Cox proportional hazards models, adjusting for known and suspected risk factors, to estimate hazard ratios (HR) and 95% confidence intervals (CI) for use of statins and risk of total and fatal RCC, RCC by stage at diagnosis, and clear cell RCC. We pooled results across cohorts using a random effects model. Results: We documented 661 cases of RCC (310 in HPFS, 255 in NHS, 96 in NHS 2), of which 132 (20%) were fatal. Of the 661 cases, 458 (69%) were clear cell. The pooled multivariable HR for total RCC was 1.01 (95% CI 0.84-1.21) for current statin use, updated over time. Current use was not associated with risk of fatal, advanced (stage T3 or higher), or localized (stage T1 or T2) disease. There were no associations between duration of statin use and risk of RCC; compared to never users, those with less than four years of total use had an HR of 0.91 (95% CI 0.71-1.18), and those with four or more years of use had an HR of 1.03 (95% CI 0.84-1.27). Among men, statin use was associated with increased risk of clear cell RCC (HR for current use: 1.48, 95% CI 1.04-2.11; HR for 4 or more years of use: 1.58, 95% CI 1.05-2.36). Statins were not associated with risk of clear cell RCC in women (HR for current use: 0.77, 95% CI 0.58-1.03; p-value for heterogeneity across cohorts = 0.02). Conclusions: Overall, statin use was not associated with risk of RCC in three large, prospective cohorts of US women and men. Statin use was associated with increased risk of clear cell RCC among men.
Should I send a covering letter when applying for a senior house officer post, and what should it contain?
Authors: John Adsett
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 (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.
The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing
Authors: Xiaoxing Kou, Xingtian Xu, Chider Chen, Maria Laura Sanmillan, Tao Cai, Yanheng Zhou, Claudio Giraudo, Anh Le, Songtao Shi
Journal: Science Translational Medicine (2018)

Mesenchymal stem cells use the Fas/Fap-1/Cav-1 axis to control vesicle and cytokine secretion to accelerate wound healing in mice.
18F-Fluoroestradiol PET/CT Correctly Diagnosed 18F-FDG–Avid Inflammatory Lymph Nodes in a Patient With Estrogen Receptor–Positive Breast Cancer
Authors: Tomohiko Yamane, Shigeto Ueda, Akira Seto, Ichiei Kuji
Journal: Clinical Nuclear Medicine (2018)

Abstract A 77-year-old woman with left breast cancer received 18 F-FDG PET/CT for initial staging, and 18 F-FDG–avid lymph nodes were observed in the bilateral axillae. As estrogen receptor (ER) status of primary lesion was positive, the patient also received 18 F-fluoroestradiol ( 18 F-FES) PET/CT. Unlike primary lesion, no remarkable 18 F-FES uptakes in the lymph nodes were observed. 18 F-FDG uptakes in the nodes were finally interpreted as inflammation. 18 F-FES PET that can noninvasively evaluate the ER status may have a potential to reveal the pathology of the false-positive lesion observed in 18 F-FDG PET for patients with ER-positive breast cancer.
MMC's National Director (England)
Authors: Peter Cross
Journal: BMJ (2006)

Professor Alan Crockard is a neurosurgeon specialising in spinal conditions. He has been involved in training for many years, culminating in his appointment as director of education at the Royal College of Surgeons England in 1997. Professor Crockard was appointed to the Modernising Medical Careers (MMC) team in April 2003 and shortly after became national director (England).
How competitive is the psychiatry training in United Kingdom?
Authors: Jim Bolton
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.
Taskforce will examine effects of European Working Time Directive
Authors: Caroline White
Journal: BMJ (2013)

The government has set up an independent taskforce to review the effects of the European Working Time Directive on doctors’ training and the continuity of care.1

The Royal College of Surgeons, a longstanding critic of the directive’s effect on the quality of surgical training,2 will lead the review. The taskforce includes representatives of the Academy of Medical Royal Colleges, the BMA, the NHS Confederation, Health Education England, and patients’ and trainee doctors’ groups. It …
Use of cancer immunotherapies in the real-world in the setting of microsatellite instability.
Authors: Vineeta Agarwala, Anala Gossai, Gaurav Singal, Claire O'Connell, Gerald Li, Ken Kao, David Bourque, Dana Feuchtbaum, Garrett Alpha Cobb, Allen Nunnally, Garrett Michael Frampton, Siraj Mahamed Ali, Amy Pickar Abernethy, Sarah Kramarz, Sally E. Trabucco
Journal: Journal of Clinical Oncology (2018)

30 Background: In May 2017, the FDA approved for the first time a cancer therapy (pembrolizumab) for use in patients based on the presence of a genomic marker (microsatellite instability, or MSI) rather than anatomical tumor type. Real-world data on the rates and clinical impact of MSI on treatment selection and response are scant, especially outside of colorectal cancer. Methods: We performed a retrospective study of all patients treated in the Flatiron Health network (&gt;265 oncology practices across the U.S.) between January 2011 and June 2017, and who underwent FoundationOne tumor sequencing as part of routine clinical care. Tumor type was determined by pathologist review of specimens submitted to Foundation Medicine. Data on therapy use was sourced from electronic health records (EHRs). Assessment of MSI was performed from DNA sequencing across the coding regions of &gt;300 genes. Results: Our overall cohort included n=16,020 patients. Among patients in whom MSI status could be assessed (n=12,411), 207 patients had MSI-high tumors. The observed rate of MSI-high was 1.7% across all tumor types combined; tumor-specific rates varied significantly, from 4.9% in colorectal adenocarcinoma to 0.3% in breast and non-small cell lung cancer. The rate of MSI-high was 2.4% in patients with an unknown primary based on specimen review. A total of 1,329 patients received common checkpoint inhibitors (nivolumab, pembrolizumab, atezolizumab). Among the checkpoint-inhibitor treated patients with known MSI status (n=1,175), 14 (1.2%) had MSI-high tumors, and the majority of these patients (n=8) had colorectal cancer. Conclusions: Evidence of MSI-high is rare in real world cancer care settings. Early identification of patients with this biomarker is important in order to efficiently match them to treatment. Further evaluation of the real-world effectiveness of immune checkpoint inhibitors in the MSI-high population is still needed. Because most patients receiving these therapies today do not have high MSI, exploration of additional biomarkers for immunotherapy response is also critical.
IMPAIRMENTS IN LIMB FUNCTION IN SUBCLINICAL LOWER EXTREMITY PERIPHERAL ARTERIAL DISEASE: RESULTS FROM THE CAMERON COUNTY HISPANIC COHORT
Authors: Maria Limas, Nelson Gonzalez, Miryoung Lee, Audrey Choh, Gordon Watt, Joseph McCormick, Marlene Garcia, Susan Fisher-Hoch, Anand Prasad
Journal: Journal of the American College of Cardiology (2018)
Nuclear Receptor LRH-1 Functions to Promote Castration-Resistant Growth of Prostate Cancer via Its Promotion of Intratumoral Androgen Biosynthesis
Authors: Lijia Xiao, Yuliang Wang, Kexin Xu, Hao Hu, Zhenyu Xu, Dinglan Wu, Zhu Wang, Wenxing You, Chi-Fai Ng, Shan Yu, Franky Leung Chan
Journal: Cancer Research (2018)

Targeting of steroidogenic enzymes (e.g., abiraterone acetate targeting CYP17A1) has been developed as a novel therapeutic strategy against metastatic castration-resistant prostate cancer (CRPC). However, resistance to steroidal inhibitors inevitably develops in patients, the mechanisms of which remain largely unknown. Liver receptor homolog-1 (LRH-1, NR5A2) is a nuclear receptor, originally characterized as an important regulator of some liver-specific metabolic genes. Here, we report that LRH-1, which exhibited an increased expression pattern in high-grade prostate cancer and CRPC xenograft models, functions to promote de novo androgen biosynthesis via its direct transactivation of several key steroidogenic enzyme genes, elevating intratumoral androgen levels and reactivating AR signaling in CRPC xenografts as well as abiraterone-treated CRPC tumors. Pharmacologic inhibition of LRH-1 activity attenuated LRH-1-mediated androgen deprivation and anti-androgen resistance of prostate cancer cells. Our findings not only demonstrate the significant role of LRH-1 in the promotion of intratumoral androgen biosynthesis in CRPC via its direct transcriptional control of steroidogenesis, but also suggest targeting LRH-1 could be a potential therapeutic strategy for CRPC management.Significance: These findings not only demonstrate the significant role of the nuclear receptor LRH-1 in the promotion of intratumoral androgen biosynthesis in CRPC via its direct transcriptional control of steroidogenesis, but also suggest targeting LRH-1 could be a potential therapeutic strategy for CRPC management. Cancer Res; 78(9); 2205-18. ©2018 AACR.
Tissue Tranglutaminase Regulates Interactions between Ovarian Cancer Stem Cells and the Tumor Niche
Authors: Salvatore Condello, Livia Sima, Cristina Ivan, Horacio Cardenas, Gary Schiltz, Rama K. Mishra, Daniela Matei
Journal: Cancer Research (2018)

Cancer progression and recurrence are linked to a rare population of cancer stem cells (CSC). Here, we hypothesized that interactions with the extracellular matrix drive CSC proliferation and tumor-initiating capacity and investigated the functions of scaffold protein tissue transglutaminase (TG2) in ovarian CSC. Complexes formed by TG2, fibronectin (FN), and integrin β1 were enriched in ovarian CSC and detectable in tumors. A function-inhibiting antibody against the TG2 FN-binding domain suppressed complex formation, CSC proliferation as spheroids, tumor-initiating capacity, and stemness-associated Wnt/β-catenin signaling. Disruption of the interaction between TG2 and FN also blocked spheroid formation and the response to Wnt ligands. TG2 and the Wnt receptor Frizzled 7 (Fzd7) form a complex in cancer cells and tumors, leading to Wnt pathway activation. Protein docking and peptide inhibition demonstrate that the interaction between TG2 and Fzd7 overlaps with the FN-binding domain of TG2. These results support a new function of TG2 in ovarian CSC, linked to spheroid proliferation and tumor-initiating capacity and mediated through direct interactions with Fzd7. We propose this complex as a new stem cell target.Significance: These findings reveal a new mechanism by which ovarian CSCs interact with the tumor microenvironment, promoting cell proliferation and tumor initiation. Cancer Res; 78(11); 2990-3001. ©2018 AACR.
PREDICTORS OF IN-STENT YELLOW PLAQUES AFTER 2ND-GENERATION DRUG-ELUTING STENT: THE MICASA STUDY
Authors: Kazuoki Dai, Hiroshi Matsuoka, Hideo Kawakami, Tetsuya Sato, Kouki Watanabe, Yasuharu Nakama, Masaharu Ishihara
Journal: Journal of the American College of Cardiology (2018)