tbuckley/cabot-search huggingface dataset:
Abstract P6-07-10: The ERβ4 variant induce transformation of the normal breast mammary epithelial cell line MCF-10A; the ERβ variants ERβ2, ERβ4 and ERβ5 increase aggressiveness of TNBC by regulation of hypoxic signaling
Authors: M Faria, S Karami, S Granados-Principal, P Dey, A Verma, DS Choi, O Elemento, T Bawa-Khalfe1, JC Chang, J-A Gustafsson, AM Strom
Journal: Cancer Research (2018)

Abstract Triple negative breast cancer (TNBC) still remains a challenge to treat in the clinic due to a lack of good targets for treatment. Although TNBC lacks expression of ERα, the expression of ERβ and its variants are detected quite frequently in this cancer type and can represent an avenue for treatment. We show that the variants of ERβ, namely ERβ1, ERβ2, ERβ4, and ERβ5, regulate aggressiveness of TNBC by regulating hypoxic signaling. RNA-seq of patient derived xenografts (PDX) from TNBC show expression of ERβ4 and ERβ5 variants in more than half of the samples. Furthermore, expression of ERβ4 in the immortalized, normal mammary epithelial cell line MCF-10A that is resistant to mammosphere formation caused transformation and development of mammospheres. By contrast, ERβ1, ERβ2 or ERβ5 were unable to support mammosphere formation. We have previously shown that all variants except ERβ1 stabilizes HIF-1α but only ERβ4 appear to have the ability to transform normal mammary epithelial cells, pointing towards a unique property of ERβ4. We propose that ERβ variants may be good diagnostic tools and also serve as novel targets for treatment of breast cancer. Citation Format: Faria M, Karami S, Granados-Principal S, Dey P, Verma A, Choi DS, Elemento O, Bawa-Khalfe1 T, Chang JC, Gustafsson J-A, Strom AM. The ERβ4 variant induce transformation of the normal breast mammary epithelial cell line MCF-10A; the ERβ variants ERβ2, ERβ4 and ERβ5 increase aggressiveness of TNBC by regulation of hypoxic signaling [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 P6-07-10.
Cambridge Intermediate Anastomosis Workshop
Authors: Muhammad E A Khan
Journal: BMJ (2010)

One of the most important attributes of a safe surgeon is the ability to achieve a good and safe anastomosis. Even more importantly, the surgeon must be able to recognise whether or not this has been achieved. It is for this reason that the Cambridge Anastomosis Workshop has been organised by Mr Clive Quick at Addenbrooke’s Postgraduate Medical Centre once a year, every summer, for the past 27 years.

This course is open to surgical trainees from specialty training year 2 through to consultants. Preference is given to surgical trainees who have completed their basic surgical training and are about to start in specialist registrar grades, which makes it an intermediate surgical skills course.

I took this course in June 2009.

The course was held in the department of pathology on the Downing Street site …
Non-B-Form DNA Is Enriched at Centromeres
Authors: Sivakanthan Kasinathan, Steven Henikoff
Journal: Molecular Biology and Evolution (2018)

Abstract Animal and plant centromeres are embedded in repetitive “satellite” DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in &lt;10-bp dyad symmetries predicted to adopt non-B-form conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequence-specific DNA-binding proteins with DNA-bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B-form DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically nonessential. We also detected dyad symmetries and predicted non-B-form DNA structures at neocentromeres, which form at ectopic loci. We propose that centromeres form at non-B-form DNA because of dyad symmetries or are strengthened by sequence-specific DNA binding proteins. This may resolve the CENP-B paradox and provide a general basis for centromere specification.
PREDICTIVE VALUE OF SEATTLE HEART FAILURE MODEL IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Everett Sinibaldi, Thammi Ramanan, Abhishek Sawant, Aishwarya Bhardwaj, Rosemary Hansen, Michael Pham, Charl Khalil, Ashutosh Sharma, Abhinav Kumar, Vijay Iyer
Journal: Journal of the American College of Cardiology (2018)
Diploma in clinical risk and claims management
Authors: Andrew R L Medford
Journal: BMJ (2008)

Identification, evaluation and management of disordered eating (DE) is complex. DE exists along the spectrum from optimised nutrition through to clinical eating disorders (EDs). Individual athletes can move back and forth along the spectrum of eating behaviour at any point in time over their career and within different stages of a training cycle. Athletes are more likely to present with DE than a clinical ED. Overall, there is a higher prevalence of DE and EDs in athletes compared with non-athletes. Additionally, athletes participating in aesthetic, gravitational and weight-class sports are at higher risk of DE and EDs than those in sports without these characteristics. The evaluation and management of DE requires a cohesive team of professional practitioners consisting of, at minimum, a doctor, a sports dietitian and a psychologist, termed within this statement as the core multidisciplinary team. The Australian Institute of Sport and the National Eating Disorders Collaboration have collaborated to provide this position statement, containing guidelines for athletes, coaches, support staff, clinicians and sporting organisations. The guidelines support the prevention and early identification of DE, and promote timely intervention to optimise nutrition for performance in a safe, supported, purposeful and individualised manner. This position statement is a call to action to all involved in sport to be aware of poor self-image and poor body image among athletes. The practical recommendations should guide the clinical management of DE in high performance sport.
MMC: NEW GAME, OLD RULES The bigger picture
Authors: Anna Popova
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.
The clinical trials landscape for glioblastoma: is it adequate to develop new treatments?
Authors: Alyssa M Vanderbeek, Rifaquat Rahman, Geoffrey Fell, Steffen Ventz, Tianqi Chen, Robert Redd, Giovanni Parmigiani, Timothy F Cloughesy, Patrick Y Wen, Lorenzo Trippa, Brian M Alexander
Journal: Neuro-Oncology (2018)

There have been few treatment advances for patients with glioblastoma (GBM) despite increasing scientific understanding of the disease. While factors such as intrinsic tumor biology and drug delivery are challenges to developing efficacious therapies, it is unclear whether the current clinical trial landscape is optimally evaluating new therapies and biomarkers. We queried ClinicalTrials.gov for interventional clinical trials for patients with GBM initiated between January 2005 and December 2016 and abstracted data regarding phase, status, start and end dates, testing locations, endpoints, experimental interventions, sample size, clinical presentation/indication, and design to better understand the clinical trials landscape. Only approximately 8%–11% of patients with newly diagnosed GBM enroll on clinical trials with a similar estimate for all patients with GBM. Trial duration was similar across phases with median time to completion between 3 and 4 years. While 93% of clinical trials were in phases I–II, 26% of the overall clinical trial patient population was enrolled on phase III studies. Of the 8 completed phase III trials, only 1 reported positive results. Although 58% of the phase III trials were supported by phase II data with a similar endpoint, only 25% of these phase II trials were randomized. The clinical trials landscape for GBM is characterized by long development times, inadequate dissemination of information, suboptimal go/no-go decision making, and low patient participation.
Combination checkpoint immunotherapy and cytotoxic chemotherapy: Further results from a phase Ib/II trial of pembrolizumab and docetaxel or gemcitabine in patients with advanced or metastatic urothelial cancer.
Authors: Mamta Parikh, Chong-xian Pan, Laurel Beckett, Yueju Li, Daniel Robles, Christina DeVisser, Primo Lara
Journal: Journal of Clinical Oncology (2018)

525 Background: We previously reported tolerability of pembrolizumab plus either docetaxel or gemcitabine in platinum-treated metastatic urothelial cancer patients (pts), given the hypothesis that chemotherapy might enhance tumoral neoantigen expression and modulate immunogenicity of tumor cells, potentially enhancing the response to anti-PD-1 therapy. Herein we report further results from an expansion cohort. Methods: Eligible pts had Zubrod PS 0-1, adequate end-organ function, and up to 2 prior lines of chemotherapy (at least one platinum based). Patients were treated with pembrolizumab 200 mg IV on D1 q3weeks plus either docetaxel 75 mg/m2 IV on D1 (Arm A) or gemcitabine 1000 mg/m2 IV on D1 &amp; D8 (Arm B). Primary endpoint was safety; secondary endpoints were overall response rate (RR) and progression free-survival (PFS). Results: A total of 20 pts have enrolled, 9 in Arm A, 11 in Arm B. Mean age was 66 (range 31-84). Most common AEs ≥ Grade 3 were hyponatremia (8/20), anemia (5/20), fatigue (5/20), neutropenia (4/20), leukopenia (4/20) acute kidney injury (3/20), hypophosphatemia (3/20). There were no treatment-related deaths; 13 died from tumor progression (PD). In total, 1 pt had complete response (CR), 5 pts had partial responses (PR), 3 pts had minor responses (MR), 4 had stable disease (SD), and 7 progressed (PD); overall RR was 45% and Disease Control Rate (DCR) was 65%. Arm A had overall RR of 44%, DCR 56%. Arm B had overall RR of 45%, DCR 73%. Median PFS (overall, Arm A &amp; Arm B) was 7, 13.3, and 5.9 months. Conclusions: The combination of pembrolizumab with either docetaxel or gemcitabine is tolerated with expected adverse effects, with evidence of efficacy. Expanded cohorts continue to enroll. Clinical trial information: NCT02437370.
Acute hepatitis B virus infection in humanized chimeric mice has multiphasic viral kinetics
Authors: Yuji Ishida, Tje Lin Chung, Michio Imamura, Nobuhiko Hiraga, Suranjana Sen, Hiroshi Yokomichi, Chise Tateno, Laetitia Canini, Alan S. Perelson, Susan L. Uprichard, Harel Dahari, Kazuaki Chayama
Journal: Hepatology (2018)

Chimeric urokinase type plasminogen activator (uPA)/severely severe combined immunodeficiency (SCID) mice reconstituted with humanized livers are useful for studying hepatitis B virus (HBV) infection in the absence of an adaptive immune response. However, the detailed characterization of HBV infection kinetics necessary to enable in-depth mechanistic studies in this in vivo HBV infection model is lacking. To characterize HBV kinetics post-inoculation (p.i.) to steady state, 42 mice were inoculated with HBV. Serum HBV DNA was frequently measured from 1 minute to 63 days p.i. Total intrahepatic HBV DNA, HBV covalently closed circular DNA (cccDNA), and HBV RNA was measured in a subset of mice at 2, 4, 6, 10, and 13 weeks p.i. HBV half-life (t1/2 ) was estimated using a linear mixed-effects model. During the first 6 hours p.i., serum HBV declined in repopulated uPA/SCID mice with a t1/2 = 62 minutes (95% confidence interval [CI] = 59-67). Thereafter, viral decline slowed followed by a 2-day lower plateau. Subsequent viral amplification was multiphasic with an initial mean doubling time of t2 = 8 ± 3 hours followed by an interim plateau before prolonged amplification (t2 = 2 ± 0.5 days) to a final HBV steady state of 9.3 ± 0.3 log copies (cps)/mL. Serum HBV and intrahepatic HBV DNA were positively correlated (R2 = 0.98).HBV infection in uPA/SCID chimeric mice is highly dynamic despite the absence of an adaptive immune response. Serum HBV t1/2 in humanized uPA/SCID mice was estimated to be ∼1 hour regardless of inoculum size. The HBV acute infection kinetics presented here is an important step in characterizing this experimental model system so that it can be effectively used to elucidate the dynamics of the HBV life cycle and thus possibly reveal effective antiviral drug targets. (Hepatology 2018).
Future of Neurologic Examination in Clinical Practice—Reply
Authors: Michael J. Aminoff
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
1000 EMQs for PLAB: based on current exams
Authors: Kuntal J Patel
Journal: BMJ (2005)

Sherif W Helmy

Radcliffe Publishing Ltd, 2004, £19.95, 200 pages

ISBN 1 85775 676 2

Rating: ⋆⋆⋆/5



An increasing number of doctors are now taking the Professional Linguistic Assessment Board (PLAB) examination. Since September 2004, single best answers (SBA) have been included, which make up to 30% of questions. Unfortunately, SBAs are not included in this book, as they are a recent change in the exam. …
More must be done to promote attractiveness of GP career, says Hunt
Authors: Abi Rimmer
Journal: BMJ (2015)

More needs to be done to promote general practice at every stage of a doctor’s career, Jeremy Hunt, the health secretary for England, has said.

During a speech at Nelson Medical Practice in London on Friday 19 June, the health secretary outlined his plans for a “new deal” for general practice.1 Hunt said that, to tackle GP recruitment problems, especially in under-doctored areas, general practice needed to be promoted as a career. “Quite simply, at every stage of a doctor’s career we must do more to promote the attractiveness of general practice,” he said.

Recent data from the General Practice National Recruitment Office has shown that 28% of GP training posts across the UK were unfilled this year …
Prevention and treatment of low back pain: evidence, challenges, and promising directions
Authors: Nadine E Foster, Johannes R Anema, Dan Cherkin, Roger Chou, Steven P Cohen, Douglas P Gross, Paulo H Ferreira, Julie M Fritz, Bart W Koes, Wilco Peul, Judith A Turner, Chris G Maher, Rachelle Buchbinder, Jan Hartvigsen, Dan Cherkin, Nadine E Foster, Chris G Maher, Martin Underwood, Maurits van Tulder, Johannes R Anema, Roger Chou, Stephen P Cohen, Lucíola Menezes Costa, Peter Croft, Manuela Ferreira, Paulo H Ferreira, Julie M Fritz, Stéphane Genevay, Douglas P Gross, Mark J Hancock, Damian Hoy, Jaro Karppinen, Bart W Koes, Alice Kongsted, Quinette Louw, Birgitta Öberg, Wilco C Peul, Glenn Pransky, Mark Schoene, Joachim Sieper, Rob J Smeets, Judith A Turner, Anthony Woolf
Journal: The Lancet (2018)
Wide QRS Complex Tachycardia
Authors: Alberto Vera, Alberto Cecconi, Maria Teresa Nogales-Romo, Francisco de la Cuerda, Jorge Salamanca, Luis Jesus Jimenez-Borreguero, Fernando Alfonso
Journal: Circulation (2018)

ECG CHALLENGEA 70-year-old man was admitted to the emergency department for several hours of palpitations, dizziness, and dyspnea.The patient had a history of hypertension, diabetes mellitus, dyslipidemia, chronic obstructive pulmonary disease, and paroxysmal atrial fibrillation.His medications included eprosartan, amlodipine, atorvastatin, sitagliptin, indacaterol, and acenocoumarol.On arrival, his heart rate was 170 bpm and blood pressure was 110/50 mm Hg.The following 12-lead ECG was obtained (Figure 1).Based on the ECG, what is the most likely diagnosis?Please turn the page to read the diagnosis.
LEFT ATRIAL FUNCTION IN HEART FAILURE WITH PRESERVED AND REDUCED EJECTION FRACTION
Authors: Julio A. Chirinos, Zeba Hashmath, Anila Hussain, Rushik Bhuva, Swapna Varakantam, Jonathan Lee, Vaibhav Satija, Harry Oldland, Khuzaima Javaid, Scott Akers
Journal: Journal of the American College of Cardiology (2018)
Abstract OT2-07-01: Phase 1/2 trial of the oncolytic virus, talimogene laherparpvec, in combination with neoadjuvant chemotherapy in stage II/III triple negative breast cancer
Authors: HH Soliman, D Hogue, H Han, C Lee, R Ismail-Khan, H Khong, B Niell, B Czerniecki
Journal: Cancer Research (2018)

Abstract Background: The host anti-tumor immune response plays an important role in determining natural history and therapy response for early stage breast cancer. Tumors with high levels of lymphocytic infiltration appear to have a superior prognosis and response rate to neoadjuvant chemotherapy. However, these tumors are in the minority so methods to enhance tumor lymphocyte infiltration should be identified. The oncolytic virus, talimogene laherparpvec (TVEC) is a genetically modified HSV1 virus which selectively replicates in transformed cells while sparing normal tissue. This leads to lysis of infected tumor cells along with co-expression of GM-CSF to elicit an enhanced anti-tumor immune response. Prior data has shown TVEC can be safely combined with chemotherapy in other indications, so we launched an investigator initiated study to determine the safety and efficacy of combining TVEC with neoadjuvant dose dense chemotherapy in stage II-III TNBC. Study design: The study is a phase 1 (2 dose levels of TVEC, 3+3 design) and phase 2 single arm Simon two stage combination trial. Primary endpoints of phase 1 is safety of intratumoral TVEC (DL1=106 PFU x 5 injections, DL2=106 PFU x 1 then 108 PFU x 4 injections) administered q2-3 weeks concurrently with weekly paclitaxel followed by standard dose dense AC x 4 and local therapy as indicated. Phase 2 primary endpoint is pCR rate of the study treatment, secondary endpoints include DFS, OS, immune correlates in resected tumor specimens. Eligibility criteria includes females &amp;gt;17 years old, newly diagnosed T2-3N0-3 TNBC, adequate organ function, primary tumor amenable to injection with TVEC, no immunosuppressive or autoimmune conditions, no inflammatory or bilateral/multifocal disease. Sample size is up to 49 patients (12 phase 1, 37 phase 2) with 80% power to detect increase in pCR rate from 30% to 50% with one sided p=.1 in phase 2. Study status: This novel Amgen supported investigator initiated study activated to accrual 3/2017 and first patient on study was on 5/2017. The study is currently open only at the Moffitt Cancer Center. Target study completion date 8/2021. (NCT02779855) Citation Format: Soliman HH, Hogue D, Han H, Lee C, Ismail-Khan R, Khong H, Niell B, Czerniecki B. Phase 1/2 trial of the oncolytic virus, talimogene laherparpvec, in combination with neoadjuvant chemotherapy in stage II/III 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 OT2-07-01.
EPICARDIAL ADIPOSE TISSUE IS RELATED TO ARTERIAL STIFFNESS IN PATIENTS WITH CARDIO-METABOLIC DISEASE
Authors: Shaween Al-Talabany, Faisel Khan, Graeme Houston, Helen Colhoun, Jonathan Weir-McCall, Daniel Leven, Fiona Dove, Deirdre Cassidy, Helen Looker, Chim Lang
Journal: Journal of the American College of Cardiology (2016)
Eczema’s Big Break in Hollywood
Authors: Amit Om
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Decision making in root‐coverage procedures for the esthetic outcome
Authors: Martina Stefanini, Matteo Marzadori, Sofia Aroca, Pietro Felice, Matteo Sangiorgi, Giovanni Zucchelli
Journal: Periodontology 2000 (2018)

Abstract The primary indication for treatment of gingival recessions is esthetics. In the last decades, patients have become increasingly more demanding in the esthetic outcome expected. In order to obtain a successful final result, periodontal plastic surgery should provide not only complete root coverage but also perfect blending in terms of color and texture. In the literature, many techniques have been demonstrated to be effective in obtaining complete root coverage, and the selection of one surgical technique over another depends on several factors related to the anatomic characteristics of the defect. The purpose of this paper was to suggest a decision‐making process which starts from the clinical observation of the defects and is structured in progressive nodes that will guide the clinician through the most suitable surgical technique to achieve the ideal esthetic outcome.