tbuckley/cabot-search huggingface dataset:
Abstract P6-08-01: Race and recurrence by PAM50 intrinsic subtype and ROR-PT score: The Carolina breast cancer study
Authors: X Sun, KE Reeder-Hayes, EL Kirk, L Olsson, C-K Tse, MB Bell, HS Earp, LA Carey, CM Perou, AF Olshan, MA Troester
Journal: Cancer Research (2018)

Abstract Compared with white women, black women have higher breast cancer mortality. Racial differences have been reported in frequency of PAM50 intrinsic subtypes, and PAM50 intrinsic subtype is associated with prognosis. However, there is a paucity of data from large population-based studies with adequate representation of black women to evaluate its role in racial differences in breast cancer outcomes. We studied breast cancer recurrence in relation to PAM50 intrinsic subtype using data from the Carolina Breast Cancer Study Phase III (CBCS3), a large population-based prospective cohort study oversampled black women. The current analysis included 472 black and 463 white women with stage I-III tumor and available Nanostring gene expression data for PAM50 subtype and risk of recurrence score (ROR-PT, a score calculated based on subtype, proliferation level, and tumor size; categorized as low, medium, and high). Cox proportional hazard regression was used to estimate the association of recurrence with PAM50 intrinsic subtype and ROR-PT, overall and stratified by race, adjusted for tumor size, grade, and lymph node status. During a median follow-up of 5.78 years (range=0.39-8.22), 110 recurrent cases were identified (68 blacks and 42 whites). Consistently with previous data, basal-like tumors had the highest risk for recurrence (reference=luminal A, adjusted hazard ratio [HR]=2.85, 95% confidence interval [CI]=1.44-5.66), followed by luminal B (adjusted HR=2.35, 95%CI=1.18-4.69) and Her2-enriched (adjusted HR=2.19, 95%CI=1.01-4.74). High-ROR-PT score was also associated with increased risk in both black (adjusted HR=1.55, 95%CI=0.93-2.60) and white (adjusted HR=2.07, 95%CI=1.04-4.11). Recurrence rate for black women with medium/low ROR-PT scores was suggested higher than that for white women with similar scores (adjusted HR=1.54, 95%CI=0.69-3.42). Our results demonstrate that PAM50 subtype and ROR-PT score are associated with breast cancer recurrence in both black and white women. Given the higher relative frequency of poor prognosis subtypes in black women, these findings help explain prognosis disparities by race. Citation Format: Sun X, Reeder-Hayes KE, Kirk EL, Olsson L, Tse C-K, Bell MB, Earp HS, Carey LA, Perou CM, Olshan AF, Troester MA. Race and recurrence by PAM50 intrinsic subtype and ROR-PT score: The Carolina breast cancer study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-01.
Is there any higher education training in paediatric oncology that lasts between six to 12 months with a specific qualification? An MD or PhD will be too long in my present situation. Are there alternative paths to higher education?
Authors: Howard Clark
Journal: BMJ (2007)

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>
TRAP-seq identifies cystine/glutamate antiporter as a driver of recovery from liver injury
Authors: Amber W. Wang, Kirk J. Wangensteen, Yue J. Wang, Adam M. Zahm, Nicholas G. Moss, Noam Erez, Klaus H. Kaestner
Journal: Journal of Clinical Investigation (2018)

Understanding the molecular basis of the regenerative response following hepatic injury holds promise for improved treatment of liver diseases. Here, we report an innovative method to profile gene expression specifically in the hepatocytes that regenerate the liver following toxic injury. We used the Fah-/- mouse, a model of hereditary tyrosinemia, which conditionally undergoes severe liver injury unless fumarylacetoacetate hydrolase (FAH) expression is reconstituted ectopically. We used translating ribosome affinity purification followed by high-throughput RNA sequencing (TRAP-seq) to isolate mRNAs specific to repopulating hepatocytes. We uncovered upstream regulators and important signaling pathways that are highly enriched in genes changed in regenerating hepatocytes. Specifically, we found that glutathione metabolism, particularly the gene Slc7a11 encoding the cystine/glutamate antiporter (xCT), is massively upregulated during liver regeneration. Furthermore, we show that Slc7a11 overexpression in hepatocytes enhances, and its suppression inhibits, repopulation following toxic injury. TRAP-seq allows cell type-specific expression profiling in repopulating hepatocytes and identified xCT, a factor that supports antioxidant responses during liver regeneration. xCT has potential as a therapeutic target for enhancing liver regeneration in response to liver injury.
NOVEL 3D NONINVASIVE ULTRASOUND IMAGING LOCALIZES ACCESSORY PATHWAYS IN ADULTS AND ADOLESCENTS WITH WOLFF-PARKINSON-WHITE SYNDROME
Authors: Christopher Grubb, Lea Melki, Leonardo Liberman, Eric Silver, Carmine Sorbera, Daniel Y. Wang, Vivek Iyer, Rina Shah, Marc Waase, Hasan Garan, Elisa Konofagou, Elaine Wan
Journal: Journal of the American College of Cardiology (2018)
I'm working as a locum GP and I'd like to sit the MRCGP exam. How do I find a practice where I can do my video consultations for the exam?
Authors: Robbie Coull
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.
CARDIAC RESYNCHRONIZATION THERAPY IN 3D USING ELECTROMECHANICAL WAVE IMAGING: A NOVEL NON INVASIVE ULTRASOUND-BASED IMAGING TECHNIQUE
Authors: Christopher Grubb, Lea Melki, Daniel Y. Wang, James Peacock, Jose Dizon, Hasan Garan, Elisa Konofagou, Elaine Wan
Journal: Journal of the American College of Cardiology (2018)
PRIOR HEART FAILURE HOSPITALIZATION AMONG PATIENTS HOSPITALIZED FOR WORSENING CHRONIC HEART FAILURE: FROM THE ASCEND-HF TRIAL
Authors: Stephen Greene, Adrian Hernandez, Jie Sun, Javed Butler, Paul Armstrong, Justin Ezekowitz, Marco Metra, Adriaan Voors, Adrian Coles, Robert M. Califf, Christopher O’Connor, Robert Mentz
Journal: Journal of the American College of Cardiology (2018)
Are nights a good educational opportunity for medical students?
Authors: Sarah Cregan, Victoria Leyland, Trudi Rogers
Journal: BMJ (2008)

OBJECTIVE: To refine odor identification deficit (OID) as a biomarker for an amnestic disorder (Alzheimer’s disease (AD) and amnestic Mild Cognitive Impairment (aMCI)) by correlating it with global and tissue specific brain volume measures. BACKGROUND: OID has been associated with AD and aMCI with an ROC AUC of 0.82 for identifying an amnestic disorder. Volumetric correlation of OID in amnestic disorders has not been reported yet. METHODS: Cross-sectional study of normal controls (N=27) and amnestic disorder (AD(N=35) and aMCI (N=15)) was performed by measuring OID by the University of Pennsylvania Smell Identification Test (UPSIT) and normalized volumes of gray matter (GM), white matter, brain parenchyma, lateral ventricle and neocortex using T1-weighted MRI as determined by the SIENAX software algorithm. Smell identification measures included the total UPSIT; the top 10 smells by logistic regression and the previously proposed 10-item subset by Tabert. Smeller/non-smeller status was assigned with a cut off of 7 (less than or equal to 7,non-smeller; greater than 7,smeller) based on the top 10-item based on logistic regression. Volumes were compared between smellers and non-smellers within the groups with age and sex as covariates (ANCOVA). RESULTS: GM and neocortex volumes were lower among non-smellers as compared to smellers within each group. Specifically, in the amnestic group OID was associated with GM (p=0.033) and neocortex volume loss (p=0.017). In the AD group the relationship of neocortex volume loss and smell identification scores are consistent between all OID measures. CONCLUSION: Olfactory deficit is associated with lower neocortical and GM volumes suggesting that OID is an indicator of neurodegeneration. The consistent association of all OID measures with neocortical and GM volumes loss suggests the utility of the short version. Longitudinal studies are needed to delineate the relationship between decline in smell sensation, cognition and cerebral atrophy. Study Supported by: NIA/K23/AG036852 MH/NIMH/R25/MH071544 <b>Disclosure:</b> Dr. Rafique has nothing to disclose. Dr. Hagemeier has nothing to disclose. Dr. Woodward has nothing to disclose. Dr. Bergsland has nothing to disclose. Dr. Benedict has received personal compensation for activities with Actelion, Biogen Idec, Bayer, and Novartis as a consultant. Dr. Zivadinov has received personal compensation for activities with Teva Neuroscience, Biogen Idec, EMD Serono, Novartis, Claret Medical Inc., and Genzyme Corporation as a speaker and/or consultant. Dr. Szigeti has nothing to disclose.
Sonochemistry‐Assembled Stimuli‐Responsive Polymer Microcapsules for Drug Delivery
Authors: Zhanfeng Li, Zonghua Wang, Xiaoyu Du, Chao Shi, Xuejun Cui
Journal: Advanced Healthcare Materials (2018)

Abstract Stimuli‐responsive polymer microcapsules (PMs) fabricated by the sonochemical method have emerged for developing useful drug delivery systems, and the latest developments are mainly focusing on the synthetic strategies and properties such as structure, size, stability, loading capacity, drug delivery, and release. There, the primary attribution of sonochemistry is to offer a simple and practical approach for the preparation of PMs. Structure, size, stability, and properties of PMs are designed mainly according to synthetic materials, implementation schemes, or specific demands. Numerous functionalities of PMs based on different stimuli are demonstrated: targeting motion in a magnetic field or adhering to the living cells with sensitive sites through molecular recognition, and stimuli‐triggered release including enzymatic catalysis, chemical reaction as well as physical or mechanical process. The current review discusses the basic principles and mechanisms of stimuli effects, and describes the progress in the application such as targeted drug systems and controlled drug systems, and also gives an outlook on the future challenges and opportunities for drug delivery and theranostics.
MRC tackles barriers to career progression for female and ethnic minority medical researchers
Authors: Matthew Limb
Journal: BMJ (2015)

Barriers to career progression for female and ethnic minority medical researchers will be tackled as part of improved careers support being offered by the Medical Research Council (MRC).

The move comes after a review by the council identified issues around career progression and concerns about diversity. The review found that women were more likely than men to have found it difficult to pursue the research career path they wanted. In addition, researchers from non-white ethnic backgrounds were less likely than their white counterparts to think that they had received reward and recognition for their work. The MRC said that more needed to be done to allow research organisations to attract and retain the best and most diverse workforce.

John Savill, MRC chief executive, said that the council was refreshing its support and recognised that the speed of career progression can be “affected by factors unrelated to a person’s scientific potential.” He said …
Abstract P4-07-01: Assessment of the hereditary component in 94 cancer predisposition genes to triple negative breast cancer
Authors: RE Ellsworth, LA Lovejoy, CD Shriver
Journal: Cancer Research (2018)

Abstract Background: In women with triple negative breast cancer (TNBC) unselected for age or family history, 8-14% and 5% of patients harbor germline mutations in BRCA1 and BRCA2, respectively. Diagnosis of TNBC &amp;lt;60 years of age is one of the NCCN criterion for genetic testing of BRCA1 and BRCA2. The contribution of germline mutations in other cancer predisposition genes to TNBC, is, however, not well-studied. Methods: TNBC was classified as tumors with &amp;lt;1% positively staining cells for ER and PR and HER2 = 0+, 1+ or 2+/not amplified. Genomic DNA was isolated from blood samples and targeted sequencing was performed using the TruSight Cancer panel (Illumina). Pathogenic mutations were identified using VariantStudio and classified as pathogenic, uncertain significance (VUS) or benign using ClinVar. Results: 196 female patients diagnosed with TNBC 2001-2014 had genomic DNA available. Average age at diagnosis was 52.8 years (range 34.1-83.4 years). The majority of patients were of European (66%) or African (31%) American ancestry; 26% had a family history and 13% had died of disease with an average time to death of 2.81 years. Twenty-three (12%) of women with TNBC had pathogenic mutations in breast cancer genes BRCA1 (n=14), BRCA2 (n=5), PALB2 (n=1) and CHEK2 (n=3), two women had mutations in the colon cancer genes MUTYH, one had a mutation in the ovarian cancer gene BRIP1, and an additional three women had pathogenic mutations in cancer predisposition genes FANCD2, SDHB and XPC. An additional 42 women had VUS in 20 genes, including one in BRCA1 and 5 in BRCA2. Discussion: Although the majority of pathogenic mutations in this cohort of women with TNBC were in the BRCA1 and BRCA2 genes (10%), panel testing allowed for the detection of mutations in other breast (2%), colon (1%), ovarian (1%) and other cancer (2%) predisposition genes. Panel testing thus identifies genes other than BRCA1/2 associated with increased risk of TNBC and may incidentally identify women who would benefit from enhanced surveillance for other cancers. The opinions or assertions contained herein are the private ones of the author/speaker and are not to be construed as official or reflecting the views of the Department of Defense, the Uniformed Services University of the Health Sciences or any other agency of the U.S. Government. Citation Format: Ellsworth RE, Lovejoy LA, Shriver CD. Assessment of the hereditary component in 94 cancer predisposition genes to triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-07-01.
A multi-institutional predicting nomogram for BCLC stage C hepatocellular carcinoma after stereotactic body radiotherapy.
Authors: Wen-Yen Huang, Yu-Ju Lin, Jason C. Cheng, Jenny Que, Mei-Hsuan Lee, Chiao-Ling Tsai, Cheng-Hsiang Lo
Journal: Journal of Clinical Oncology (2018)

353 Background: The study aimed to develop a nomogram to predict overall survival (OS) among hepatocellular carcinoma (HCC) patients with BCLC stage C after stereotactic body radiotherapy (SBRT). Methods: Clinical data from the multicenter study consisted of 270 HCC patients with BCLC stage C. The patients underwent SBRT with a median dose of 40 Gy (range: 25-60 Gy) in 2-6 fractions. The model included age, gender, ECOG performance status, etiology (HBV, HCV, and non-B, non-C), number of tumor, tumor size, AFP level, presence of macrovascular invasion, Child-Pugh class, N stage, M stage, sorafinib use, and biologically effective dose. Cox’s proportional hazards models were utilized to estimate regression coefficients of death risk predictors and derive risk scores. The area under receiver operating curve (AUROC) was used to evaluate the performance of the risk models. Results: The median survival was 12.6 months, with 1-year and 2-year OS rates of 51.6% and 30.8%, respectively. Multiple regression showed age (with 5-year increase, HR = 0.89, p = 0.002), ECOG (1 vs. 0, HR = 1.72, p = 0.016; 2 vs. 0, HR = 2.64, p = 0.002), number and size of tumors ( &gt; 5 tumors or &gt; 8 cm vs. ≤5 tumors and ≤ 8 cm, HR = 1.83, p = 0.003; &gt; 5 tumors and &gt; 8cm vs. ≤5 tumors and ≤ 8 cm, HR = 2.04, p = 0.013), macrovascular invasion (yes vs. no, HR = 2.22, p &lt; 0.001), Child-Pugh class (B vs. A, HR = 2.83, p &lt; 0.001), and M stage (1 vs. 0, HR = 2.30, p = 0.001) are statistically significant predictors for OS. All of these significant predictors were included in the risk prediction model. The total risk score of the prediction model ranged from 0 to 48. Each score had its corresponding risk of OS. The AUROC for predicting 1-year OS was 0.820. Conclusions: The nomogram we generated among HCC patients undergoing SBRT had discrimination satisfactory predictability for OS. It can be used to stratify high-risk patients and select appropriate patients for future clinical trials.
Intradural spinal tumors - a review of post operative outcomes between intramedullary and extramedullary tumors from a single institution’s experience
Authors: Zhixu Ng, Sheryl Ng, Vincent Nga, Kejia Teo, Sein Lwin, Ning Chou, Tseng Tsai Yeo
Journal: Neuro-Oncology (2018)

Intradural spinal tumors are rare and can be classified into extra or intra-medullary. They commonly present with symptoms such as intractable back pain or neurological deficits. We retrospectively reviewed 91 cases of intradural spinal tumor operated in our institution from 2011 to 2016 and their clinical outcomes. Majority of intradural tumors were extra-medullary (89%) and the most common pathology being schwanommas (38.4%), followed by meningiomas (29.7%). Comparing extra vs. intra-medullary tumors, both groups experienced improvement in neurologic status post surgery (92.6% vs. 90%, P=0.77). We achieved total resection in majority of patients with both extra and intra-medullary tumors (65.4% vs. 70%, P=0.91). Patients of age less than 65 (OR 4.40 CI 0.72 - 26.9, P=0.11) and complete resection of tumor (OR 2.92 CI 0.61–14.0, P = 0.18) was associated with higher odds of improved clinical outcomes but our results were not statistically significant. The use of spinal nerve monitoring was not associated with improved neurological outcomes (OR 0.56 CI 0.10 – 3.05, P=0.50).
Changes to checks on EU doctors raise safety concerns, warns GMC
Authors: Abi Rimmer
Journal: BMJ (2015)

The General Medical Council says that it has patient safety concerns over plans to introduce a “passport to practise” for doctors from the European Union.

From January 2016 a European professional card will be introduced for nurses, pharmacists, and physiotherapists in the United Kingdom, and it is expected to apply to doctors from 2018. The card will be an electronic certificate issued by the professional’s country of departure, designed to provide automatic recognition of doctors’ professional qualifications in the host country.1

With its introduction, the GMC said that …
Effect of Ezetimibe Monotherapy on Plasma Lipoprotein(a) Concentrations in Patients with Primary Hypercholesterolemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Kamal Awad, Dimitri P. Mikhailidis, Niki Katsiki, Paul Muntner, Maciej Banach
Journal: Drugs (2018)
Gastric carcinoids: Does type of surgery or tumor affect survival?
Authors: Angelena Crown, Zaheer S. Kanji, Alexandra G Lopez-Aguiar, Mary Dillhoff, George A. Poultsides, Eleftherios Makris, Kamran Idrees, Paula Marincola Smith, Hari Nathan, Megan Beems, Sharon M. Weber, Alexander V Fisher, Ryan Fields, Jesse Davidson, Shishir Maithel, Flavio G. Rocha
Journal: Journal of Clinical Oncology (2018)

139 Background: Gastric carcinoids are rare neuroendocrine tumors of the GI tract. They are typically managed according to their etiology. However, there is little known about the impact of surgical strategy on the long-term outcomes of these patients. Methods: All patients who underwent resection of gastric carcinoids at 8 institutions from 2000-2016 were analyzed retrospectively. Tumors were stratified according to subtype (I, II, III, IV) and resection type (local resection LR or formal gastrectomy FG). Clinicopathological parameters, recurrence-free (RFS), and overall survival (OS) were compared between groups. Results: Of 79 patients identified with gastric carcinoids, 34 had type I lesions associated with atrophic gastritis, 4 had type II lesions associated with a gastrinoma, 37 had type III sporadic lesions, and 4 had type IV poorly-differentiated lesions. The mean age of presentation was 56 years in predominantly Caucasian (77%) and female (63%) patients. Mean tumor size was 2.4 cm and multifocal tumors were found in 24 (30%) of patients with the majority occurring in those with type I tumors. Lymph node positive tumors were seen in 15 (19%) patients and 7 (8%) had M1 disease; both most often in type IV followed by type III tumors. R0 resection was achieved in 56 (71%) patients while 15 (19%) had R1 resections and 6 (8%) had R2 resections. Patients with type I and III tumors were equally likely to have a LR (50% and 43% respectively) compared to FG while those with type II and IV all had FG with one exception. Type IV tumors had the poorest RFS and OS while Type II tumors had the most favorable RFS and OS (p &lt; 0.04 and p &lt; 0.0004, respectively). While there was no difference in RFS in those patients undergoing FG versus LR, OS was worse in the FG group (p &lt; 0.017). This trend persisted when type II and type IV groups were excluded (p &lt; 0.045). Conclusions: Gastric carcinoid treatment should be tailored to tumor type, as biologic behavior rather than resection technique is the more important factor contributing to long-term outcomes.
Problems of private practice may deter young doctors, consultants warn
Authors: Matthew Limb
Journal: BMJ (2015)

Senior consultants in private practice fear that the sector’s problems may deter younger doctors from entering it and that some will not be sufficiently skilled, a conference has heard.

Brian O’Connor, who chairs the specialist committee of the Independent Doctors Federation, warned of the effects of falling profit margins and increasing constraints on doctors’ private work. “We are concerned about younger doctors electing not to go into private practice,” he said. “There’s a fear among us of a slightly older generation that the newer guys are not necessarily being trained up to the calibre that is …