tbuckley/cabot-search huggingface dataset:
Comparison of different testing methods for detection of BRAF V600 mutation in metastatic melanoma
Authors: J. Hernandez-Losa, Y. Ruano, I. Trigo Sanchez, R. Somoza, B. Ferrer, F. Garcia Verdes-Montenegro, M. Urech, Y. Cajal, J.J. Rios Martin, J.L. Rodriguez-Peralto, S. Ramon
Journal: Annals of Oncology (2018)
Effect of aberrant expression of miR-421, miR-29b_1_5p and miR-27b_5p on gastric adenoma development.
Authors: Yu Jin Kim, Sang Woo Kim, Yong Chan Lee, Pumsoo Kim
Journal: Journal of Clinical Oncology (2018)

77 Background: Gastric cancer (GC) is the fourth leading cause of cancer-related death in the world. Some gastric adenomas may progress to adenocarcinoma in a short time. Several studies have examined adenomas the intermediate step of gastric carcinoma development. MicroRNAs have an important role in progression of gastric cancer but less is known about their role in premalignant adenomas. Changes in the expression pattern of miRNAs can be informative and highly significant in the gastric adenoma-carcinoma sequence progression as well. However, to date precancerous lesions (such as adenomas) have been investigated less frequently than cancers compared to healthy tissues. The aim of the present study was to perform a miRNA microarray analysis of normal, low-grade dysplasia, and high-grade dysplasia using fresh frozen tissues. Changes in miRNA expression patterns were also verified from samples obtained from the same patients using TaqMan MicroRNA Assays. Methods: Human tissue samples were obtained from nine patients who underwent endoscopic submucosal dissection (ESD) due to gastric adenoma or early gastric cancer at Severance Hospital of Yonsei University. Tumor and non-tumor mucosa tissue in each patient were taken just before ESD using biopsy forceps and frozen in the nitrogen tank. The miRNA expression profiles were analyzed by Affymetrix Gene-Chip miRNA 4.0 array (Homo sapiens). qRT-PCR was performed using TaqMan MicroRNA Assays (Applied Biosystems). Results: There were 28 (up-regulation) and 10 (down-regulation) miRNAs which showed significantly different expression between control group and low-/high-grade dysplasia group. miRNAs showing altered expression in normal and low-/high-grade dysplasia by microarrays were selected, and the expression tendencies were detected by real-time PCR validation. Three miRNAs (miR-421, miR-29b-1-5p, miR-27b-5p) were selected the continually upregulated from normal to low-/high-grade dysplasia based qRT-PCR in tissue samples. Conclusions: We identified new, less known miRNAs (miR-421, miR-29b-1-5p, miR-27b-5p), with altered expression in different grade dysplasia compare with normal samples.
Abstract 15015: Prognostic Value of Serial Changes of High-Sensitivity Cardiac Troponin I and T Using Reference Change Values Among Hemodialysis Patients
Authors: Yader Sandoval, Charles A Herzog, Sara A Love, Alan H Wu, Yan Hu, David T Gilbertson, Steven M Brunelli, Amy Young, Ranka Ler, Fred S Apple
Journal: Circulation (2015)

Introduction: Measurement of the biological variation of cardiac troponin (cTn) allows determination of reference change values (RCVs) to use for interpreting serial testing. Using plasma collected serially over 12-months from a stable outpatient hemodialysis (HD) population, our goals were two-fold. First, we calculated RCVs for hs-cTnI and hs-cTnT assays. Second, we determined outcomes based on hs-cTnI and hs-cTnT RCVs. Methods: hs-cTnI (Abbott) and hs-cTnT (Roche) were measured in 677 stable outpatient HD patients (enrolled May 2011-November 2012). Hazard ratios (HR), based on RCVs calculated for each hs-cTn assay, for ‘all-cause’, ‘sudden cardiac death (SCD)’ and ‘infectious’ mortality were determined with serial measurements obtained 3 months apart. Results: Patient demographics were: mean age 59±14y; mean dialysis duration 5.2±4.2y; 53% male; 59% African American and 50% diabetic ESRD. 18.6% of patients died during a 3-year follow-up. RCVs were: hs-cTnI, +37% and -30%; hs-cTnT, +25% and -20%. Patients with serial hs-cTnI and hs-cTnT changes &gt;RCV had all-cause mortality of 25.2% and 23.8% respectively, compared to 15.0% and 16.5% with ≤RCV (both p&lt;0.05). Outcomes and adjusted HRs are shown in Table. Patients with serial hs-cTnI and hs-cTnT changes &gt;RCV showed a greater risk of all-cause mortality compared to ≤RCV (HR: 1.9 (95% CI: 1.4, 2.8), p=0.0003; and HR: 1.7 (95% CI: 1.2, 2.4), p=0.0066; respectively). However, only hs-cTnI changes &gt;RCV were predictive of SCD (HR: 2.6 (95% CI: 1.3, 5.1), p=0.005). Conclusions: Our findings are unique in two ways. First we determined the biological variation of hs-cTnI and hs-cTnT in a large HD population. Second, based on the RCV for each hs-assay, serial changes in hs-cTnI and hs-cTnT &gt;RCV identify patients at greater risk of all-cause mortality, with hs-cTnI also predictive of SCD. These findings support the use of serial changes &gt;RCV for risk-stratification in HD patients.
How do you become a GP who also works part time in A&amp;E as a middle grade? Do you have to do the new A&amp;E exams?
Authors: Andy Lockey
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>
INCREASED MYOCARDIAL STIFFNESS ESTIMATED BY INTRINSIC VELOCITY PROPAGATION METHOD IS ASSOCIATED WITH ADVERSE CARDIAC EVENTS AT FOLLOW-UP IN PATIENTS WITH AMYLOIDOSIS
Authors: Cristina Pislaru, Filip Ionescu, Ioana Petrescu, Patricia Pellikka, Martha Grogan, Angela Dispenzieri, Sorin Pislaru
Journal: Journal of the American College of Cardiology (2018)
STPs: from sticky toffee puddings to just plain fudge
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Last week the great and the good from the NHS, local government, the voluntary sector, and beyond convened in Westminster to discuss the next steps for delivering NHS England’s sustainability and transformation partnerships (formerly plans), the ambitious vehicle for future proofing health and social care services by integrating care across 44 areas of the country.

STPs—nicknamed “sticky toffee puddings” by from some health service wags—and their offshoots the accountable care organisations have been a lightning rod for controversy over the past 18 months.1234567 The haste in which the plans were drawn up, the lack of …
A doctor's Christmas
Authors: Graham Easton
Journal: BMJ (2004)

Christmas means different things to different doctors—but many will recognise this week's festive themes. We have Christmas cards, alcohol, and even a busy understaffed clinic; though all is not quite what it seems.

The cards are not from grateful patients, but from doctors all over the world. We asked some friends of Career Focus to tell us what they'll be getting up to over the …
Doctors must be trained to work as part of team, say NHS Alliance
Authors: Abi Rimmer
Journal: BMJ (2014)

All doctors must be trained to work in partnership with other healthcare professionals, the NHS Alliance has said. In its report, Think Big, Act Now: Creating a Community of Care , the organisation that represents primary care providers focuses on the pressures facing the sector.1

It said that making better use of the current healthcare workforce, such as community pharmacists, could help to reduce the pressures on GPs. “Current pressure on primary care may be relieved in the short term by making better use of some of the practitioners already available …
Abstract P4-06-09: Addition of a remote genetic counselor to the breast specialist's team improves clinical decision-making
Authors: B Rosen, E O'Leary, Y Shan, W Pat, B Peter
Journal: Cancer Research (2018)

Abstract Background: There is a shortage of trained genetic counselors (GC) and often long wait times for appointments, resulting in other specialists frequently ordering genetic testing. However, non-genetic specialists, including breast surgeons, find it difficult to stay current in genetics due to rapid advances in gene discovery, expanded panel offerings, and frequent changes to professional guidelines. We tested a novel model for hereditary cancer risk assessment where breast surgeons had “on demand” access to a remote laboratory-based genetic counselor for peer to peer consultation. In this study we sought to determine the impact this model has on breast surgeons' routinely ordering genetic testing including test identification, ordering patterns, and medical management. Methods: An IRB approved multi-center prospective study involved 14 community-based breast cancer surgeons experienced with hereditary cancer risk assessment without a genetic counselor as part of their practice. Cases were all discussed with a remote Invitae GC to determine testing eligibility and selection. Physicians had the option to utilize remote GCs to discuss results or to refer to traditional genetic counseling services. Pre and post-test surveys were completed for each patient by the testing physician. To protect patient privacy, a unique case ID was used to link patient test data with identifying data. Results: A total of 192 patients were evaluated with median age of 52. Risk assessment via BRCAPRO and the Hughes Risk model were performed on 98% of patients by the physicians. 65% of patients met NCCN guidelines for testing. Pathogenic mutations were found in 14% of patients. Breast surgeons changed their test selection 21% of the time after discussion with a GC. They called to discuss results in 47% of cases and medical management changes were incorporated in 15% of these cases based on discussion with a remote GC. Conclusions: Remote GC provider support assisted physicians in facilitating customized test selection, aided in navigating challenging counseling cases, and impacted clinical management. This service may serve as a viable, effective model for 'on demand' genetic counseling support and may be a novel opportunity to expand genetic testing in a breast surgery setting. Citation Format: Rosen B, O'Leary E, Shan Y, Pat W, Peter B. Addition of a remote genetic counselor to the breast specialist's team improves clinical decision-making [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 P4-06-09.
Opinions on the role of brachytherapy boost in management of high-risk prostate cancer: A survey of North American genitourinary expert radiation oncologists.
Authors: Shearwood McClelland, Kiri A Sandler, Catherine Degnin, Yiyi Chen, Timur Mitin
Journal: Journal of Clinical Oncology (2018)

373 Background: Three randomized clinical trials have established brachytherapy (BT) boost in combination with external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) as superior to definitive EBRT and ADT alone in terms of biochemical control (but not overall survival) at the expense of increased toxicity in men with high-risk (HR) prostate cancer (PCa). The current view regarding these two treatment algorithms among North American genitourinary (GU) experts is not known. Methods: A survey was distributed to 88 practicing North American GU physicians serving on decision-making committees of cooperative group research organizations. Questions pertained to opinions regarding BT as monotherapy for low-risk (LR) PCa and BT boost for HR PCa. Responders were asked to self-identify as BT experts vs non-experts. Treatment recommendations were correlated with practice patterns using Fisher’s exact test. Results: Forty-two radiation oncologists completed the survey, of whom 23 (55%) recommend EBRT and ADT alone and 19 (45%) recommend addition of BT boost. Twenty-five participants (60%) identified themselves as BT experts. Nearly 90% of those recommending BT boost were BT experts versus approximately 10% of non-BT experts (p &lt; 0.001). Responders who recommended BT monotherapy as first-choice treatment for LR PCa were more likely to recommend BT boost for HR PCa (p &lt; 0.0001). Conclusions: There is a dramatic polarization in opinions regarding incorporation of BT boost into EBRT+ADT therapy for patients with HR PCa among North American GU radiation oncology experts, who serve on decision-making committees and influence the national treatment guidelines and future clinical trials. Those who identify themselves as BT experts are significantly more likely to recommend BT boost, which may serve as a self-fulfilling prophecy regarding the role of BT in North American clinical practice. These findings are likely to influence the national guidelines and implementation of BT boost in current and future North American PCa clinical studies.
Tumor-Repopulating Cells Induce PD-1 Expression in CD8+ T Cells by Transferring Kynurenine and AhR Activation
Authors: Yuying Liu, Xiaoyu Liang, Wenqian Dong, Yi Fang, Jiadi Lv, Tianzhen Zhang, Roland Fiskesund, Jing Xie, Jinyan Liu, Xiaonan Yin, Xun Jin, Degao Chen, Ke Tang, Jingwei Ma, Huafeng Zhang, Jing Yu, Jun Yan, Huaping Liang, Siqi Mo, Feiran Cheng, Yabo Zhou, Haizeng Zhang, Jing Wang, Jingnan Li, Yang Chen, Bing Cui, Zhuo-Wei Hu, Xuetao Cao, F. Xiao-Feng Qin, Bo Huang
Journal: Cancer Cell (2018)
Ultrasound targeted gene therapy in a mouse model of prostate cancer: Evaluation of immune response.
Authors: Flavia De Carlo, Litty Thomas, Rounak Nande, Olivia Boskovic, Gailen Marshall, Pier Paolo Claudio, Candace M Howard
Journal: Journal of Clinical Oncology (2018)

120 Background: Gene transfer to malignant sites using human adenoviruses (hAd) has been limited because of their immunogenicity. Murine cells often lack some of the receptors needed for hAd infection; therefore, are generally non-permissive for hAd infection and replication, which limits translational studies of adenoviral gene transfer techniques. We developed a gene transfer method, which uses a combination of lipid-encapsulated perfluorocarbon microbubbles (MBs) and ultrasound (US) to shield and deliver hAds to a specific tissue bypassing the requirement of the coxsackie and adenovirus receptor (CAR). Methods: Transduction efficiency and GFP protein expression of hAd.GFP was assessed by flow cytometry and fluorescence microscopy in murine TRAMP-C2 and human DU145 prostate cancer cells. Innate and acquired immunity response was determined by ELISA and CTL assay in C57BL/6 mice bearing TRAMP-C2 syngeneic tumor grafts following injections of MBs-Ad.GFP complexes in the presence or absence of ultrasound. Results: We observed that the murine prostate cancer cells TRAMP-C2 were transduced less efficiently by hAd.GFP than the human DU145 cells. We showed in vitro that the transduction rate was increased significantly in both TRAMP-C2 and DU145 prostate cancer cells when delivering the Ad particles by a combination of MBs and US. Moreover, we observed expression of the GFP transgene in both cell lines at 48 hours and 72 hours. Lack of activation of the innate and acquired immunity was observed in vivo by quantifying IL-6 and TNF-α cytokines, and by assaying neutralizing IgG antibodies and CTLs activity, following intratumoral or intravenous injections of MBs-Ad.GFP complexes in the presence or absence of ultrasound. Conclusions: This study demonstrates the feasibility of using the TRAMP-C2 murine model of prostate adenocarcinoma to translate our ultrasound-mediated MB-Ad delivery system from the bench to the clinic. Our data provides evidence that the TRAMP-C2 prostate cancer graft model is a suitable system to study in immune competent animals the capacity of lipid-encapsulated perfluorocarbon MBs and US, to shield and deliver hAds to a site-specific tissue bypassing the requirement of specific receptors.
Vitamin D–Binding Protein Enhances Epithelial Ovarian Cancer Progression by Regulating the Insulin-like Growth Factor-1/Akt Pathway and Vitamin D Receptor Transcription
Authors: Yu-Fang Huang, Yi-Hui Wu, Wen-Fang Cheng, Shu-Ling Peng, Wan-Lin Shen, Cheng-Yang Chou
Journal: Clinical Cancer Research (2018)

Purpose: Malignant ascites of epithelial ovarian cancer (EOC) helps identify prognostic biomarkers or mechanisms of tumor progression. Vitamin D-binding protein (DBP) was revealed to be upregulated in EOC ascites in our previous proteomic study. Here, we examined the role of DBP in EOC.Experimental Design: We analyzed ascites, serum, and tissue samples of patients with newly diagnosed EOC to determine the prognostic effects of DBP. We verified DBP function using orthotopic animal models and DBP regulation in ovarian cancer cell lines.Results: Elevated ascitic DBP was significantly associated with poor response to chemotherapy, short progression-free interval, increased cancer progression, and death. Ascitic DBP overexpression was an independent unfavorable biomarker for progression-free survival; DBP overexpression in cancerous tissue was significantly related to chemoresistance. In vivo and in vitro investigations demonstrated an important role for DBP in ovarian cancer progression. Orthotopic model mice inoculated with DBP knockdown ovarian cancer cells displayed a significant reduction in tumor formation, malignant cell number, ascitic DBP levels, invasiveness, and metastasis, and increased survival compared with controls. In presence of vitamin D receptor (VDR), DBP promoted cell aggression (invasion and doubling time) via activation of the insulin-like growth factor-1/insulin-like growth factor-binding protein-2/Akt axis, and induced suppression of vitamin D-responsive genes. A NF-κB p65-binding site in the VDR promoter was identified as a major determinant of DBP-dependent VDR promoter activation.Conclusions: This study highlights the importance of DBP in ovarian tumor progression and the potential application of DBP as a therapeutic target for EOC. Clin Cancer Res; 24(13); 3217-28. ©2018 AACR.
GMC asks doctors whether its processes are fair and objective
Authors: Matthew Limb
Journal: BMJ (2013)

Thousands of doctors are being involved in new research to look at whether the General Medical Council is operating fairly and objectively.

A survey of 7000 doctors from different backgrounds will gauge their views of the regulator and its processes. The GMC has commissioned the survey from the National Centre for Social Research, an independent, not for profit agency.

The …
Targeting few to help hundreds: JAK, MAPK and ROCK pathways as druggable targets in atypical chronic myeloid leukemia
Authors: Stefania Rocca, Giovanna Carrà, Pietro Poggio, Alessandro Morotti, Mara Brancaccio
Journal: Molecular Cancer (2018)

Atypical Chronic Myeloid Leukemia (aCML) is a myeloproliferative neoplasm characterized by neutrophilic leukocytosis and dysgranulopoiesis. From a genetic point of view, aCML shows a heterogeneous mutational landscape with mutations affecting signal transduction proteins but also broad genetic modifiers and chromatin remodelers, making difficult to understand the molecular mechanisms causing the onset of the disease. The JAK-STAT, MAPK and ROCK pathways are known to be responsible for myeloproliferation in physiological conditions and to be aberrantly activated in myeloproliferative diseases. Furthermore, experimental evidences suggest the efficacy of inhibitors targeting these pathways in repressing myeloproliferation, opening the way to deep clinical investigations. However, the activation status of these pathways is rarely analyzed when genetic mutations do not occur in a component of the signaling cascade. Given that mutations in functionally unrelated genes give rise to the same pathology, it is tempting to speculate that alteration in the few signaling pathways mentioned above might be a common feature of pathological myeloproliferation. If so, targeted therapy would be an option to be considered for aCML patients.
IMPACT OF NO-COST CORONARY CALCIUM SCORE TESTING IN PATIENTS AT RISK FOR CARDIOVASCULAR DISEASE ON PATIENT REPRESENTATION AND DIAGNOSTIC YIELD
Authors: Sadeer G. Al-Kindi, David Zidar, Matthew Wilson, Daniel Simon, Marco Costa, Robin Rowell, Les Ciancibello, Richard Josephson, Robert Gilkeson, Sanjay Rajagopalan
Journal: Journal of the American College of Cardiology (2018)
Aspartyl (Asparaginyl) β-Hydroxylase AABH as a serum biomarker for colorectal cancer.
Authors: Mahmood Moshiri, Kiarash Moshiri, Yasamin Farbod, Arsha Moshiri, Mohammad Hadi Sekhavati
Journal: Journal of Clinical Oncology (2018)

86 Background: Colorectal Cancer (CRC) is the third most common type of cancer diagnosed in the US and Canada. WHO, Canadian Cancer Society (CCS), the National Comprehensive Cancer Network (NCCN) and American Cancer Society (ACS) recommend that men and women begin CRC screening at age 50 or younger if at high risk. Recommended screening procedures: Annual occult fecal blood test (OFBT), a colonoscopy every 5 years, OFBT and colonoscopy every 5 years, or a colonoscopy every 10 years. According to The Surveillance, Epidemiology, and End Results (SEER) Program, only 39% of CRC are diagnosed in stage I, 36% are diagnosed in Stage II, 19% are diagnosed with metastasis. The corresponding 5-year survival rates are 89.8%, 67.7%, and 10.3%. Neither the CCS nor the ACS recommends a blood test be done as part of screening. This is due to the fact that, until now, there has not been a blood test with adequate sensitivity or specificity for screening. Methods: In this study we discovered that Aspartyl (Asparaginyl) β-Hydroxylase (AABH) measurement in serum can be used as an screening test for CRC. AABH has been detected by immunohistochemical staining (IHC) on the cell surface of different cancers including CRC. It has been detected by IHC in &gt; 97% of tumor specimens tested (n &gt; 200) but has not been found in tissue samples from normal individuals. Results: This observation and the observation that AABH is found in the serum of patients with cancer, but not in n0n cancer patients, led us to develop a Sandwich ELISA Assay to measure AABH in serum. In the current study we have quantified AABH levels in CRC patients and compared it with normal individual. Increased levels of AABH were found in the serum of 91.5% of patients with CRC in all different stages of Cancer (n = 60). In normal individuals, AABH was essentially undetectable in serum (n = 30). AABH was identified in serum from patients with CRC irrespective of cancer stage. All serum AABH levels for stages I, II, III and IV were more than 3.3 ng/mL. Conclusions: Thus, our data indicate that by measuring AABH in the serum, we should be able to detect CC at an earlier stage than it is currently detected, resulting to a much better 5-year survival for CC.
Abstract 14076: Mortality Risk Spectrum and Time-Varying Prognostication After Acute Type A Aortic Dissection Repair
Authors: Harleen K Sandhu, Akiko K Tanaka, Kristofer M Charlton-Ouw, Elizabeth Habrel, Charles C Miller, Hazim J Safi, Anthony L Estrera
Journal: Circulation (2016)

Introduction: Traditional mortality risk-assessments after acute type A dissection(AAAD) repair assume that predictors have a constant risk during the postoperative period. Such analysis can over/u...
I have done eight years of paediatrics in the United Kingdom. What are the criteria for becoming a specialist paediatric general practitioner?
Authors: Fiona Jewkes
Journal: BMJ (2004)

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.