tbuckley/cabot-search huggingface dataset:
Evaluation of VTE-BLEED for predicting intracranial or fatal bleeding in stable anticoagulated patients with venous thromboembolism
Authors: Frederikus A. Klok, Stefano Barco, Stavros V. Konstantinides
Journal: European Respiratory Journal (2018)

Current international guidelines recommend discontinuing anticoagulant therapy for unprovoked acute pulmonary embolism or deep vein thrombosis after the first 3 months of treatment only in patients considered at high risk of bleeding [1, 2]. The rationale for this recommendation is that unprovoked venous thromboembolism (VTE) is associated with high rates of recurrence after anticoagulant therapy quantified as up to 50% in the first 10 years [3]. It remains, however, unknown how the assessment of the bleeding risk in the individual patient should be performed given the lack of sufficiently validated risk assessment models or scores, as well as outcome trials that successfully applied those tools [4, 5]. VTE-BLEED predicts fatal and/or intracranial bleeding in patients with venous thromboembolism treated with long-term anticoagulants <http://ow.ly/3hqg30iXK5a> We thank the steering committees of the Hokusai-VTE study and the RE-COVER trials for being allowed to use the data.
Survival in patients with spinocerebellar ataxia types 1, 2, 3, and 6 (EUROSCA): a longitudinal cohort study
Authors: Alhassane Diallo, Heike Jacobi, Arron Cook, Robyn Labrum, Alexandra Durr, Alexis Brice, Perrine Charles, Cecilia Marelli, Caterina Mariotti, Lorenzo Nanetti, Marta Panzeri, Maria Rakowicz, Anna Sobanska, Anna Sulek, Tanja Schmitz-Hübsch, Ludger Schöls, Holger Hengel, Bela Melegh, Alessandro Filla, Antonella Antenora, Jon Infante, José Berciano, Bart P van de Warrenburg, Dagmar Timmann, Sylvia Boesch, Massimo Pandolfo, Jörg B Schulz, Peter Bauer, Paola Giunti, Jun-Suk Kang, Thomas Klockgether, Sophie Tezenas du Montcel
Journal: The Lancet Neurology (2018)
Hybrid Materials: Flexible Modulation of CO‐Release Using Various Nuclearity of Metal Carbonyl Clusters on Graphene Oxide for Stroke Remediation (Adv. Healthcare Mater. 5/2018)
Authors: Mein Jin Tan, Han‐Chi Pan, Hui Ru Tan, Jian Wei Chai, Qi Feng Lim, Ten It Wong, Xiaodong Zhou, Zi‐Yao Hong, Lun‐De Liao, Kien Voon Kong
Journal: Advanced Healthcare Materials (2018)

A facile CO-release material for in-situ vasodilation as a treatment for stroke-related vascular diseases is developed by K.V. Kong, L.D. Liao and co-workers in article number 1701113. Utilizing the size dependent adsorption properties of ruthenium carbonyl clusters (Ru-CO) onto graphene oxide (GO), the rate and amount of formation of the CO release-active RuII(CO)2 species can be modulated by a simple mixing procedure. Further modulation of thermal and CO release properties can be achieved via a hybridization of medium- and high- nuclearity of Ru-CO clusters that can provide photo-thermal response for in-situ CO release in a cortical photo-thrombotic ischemia rat model.
Prognostic impact of percentage of squamous differentiation in patients with nonbilharzial squamous cell carcinoma and transitional cell carcinoma treated with radical cystectomy.
Authors: Marine Slim, Eva Comperat, Morgan Roupret, Jerome Parra, Jean-Marc Simon, David Khayat, Marc-Olivier Bitker, Jean-Philippe Spano, Gabriel G. Malouf
Journal: Journal of Clinical Oncology (2018)

498 Background: Squamous differentiation has been reported to occur in 10-22 % of transitional cell carcinoma. The prognostic impact of squamous differentiation is controversial. In addition, it remains unclear whether the percentage of squamous differentiation impact outcome of patients with nonbilharzial squamous cell carcinoma and transitional cell carcinoma treated with radical cystectomy Methods: We performed a retrospective study of patients with non-bilharzial squamous variants or squamous bladder carcinoma treated in two French institutions. The percentage of squamous differentiation was determined by an expert GU pathologist on radical cystectomy specimens. Progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed according to the percent of squamous differentiation. Survivals were estimated using the Kaplan-Meier method and compared using multivariate Cox proportional hazard regression analysis. Results: Forty patients were identified including 28 and 12 patients which tumors were classified as transitional cell carcinomas cases with squamous cell differentiation and pure non-bilharzial squamous bladder carcinoma, respectively. Patients with tumors harboring more than 50% of squamous differentiation had a PFS of 6.3 months as compared to 60.2 months for those with squamous differentiation present in less than 50% (p = 0.014). In multivariate analysis, the percentage of squamous differentiation was the only independent prognostic factor for PFS (HR = 2.63 (IC 95%: 1.22-5.67). First site of recurrence of patients with squamous differentiation ≥50% were more frequently the pelvis (72% versus 17 %; p = 0.049). No difference in CSS were observed between patients with tumors &lt; 50% or ≥50% squamous differentiation (16.3 months versus 62 months) (p = 0.2). Conclusions: Extensive squamous differentiation in bladder cancer is associated with poor PFS and pelvic progression, suggesting that those patients might benefit from adjuvant pelvic radiotherapy. Larger studies are needed to validate these findings.
CARDIO-PULMONARY EXERCISE TESTING (CPET) IN PATIENTS WITH REFRACTORY ANGINA PECTORIS UNDERGOING CORONARY SINUS REDUCER IMPLANTATION
Authors: Maayan Konigstein, Alessia Azzano, Shmuel Banai, Yan Topilsky, Stefan Verheye
Journal: Journal of the American College of Cardiology (2018)
Relationship between human epidermal growth factor receptor 2 (HER2) status and central nervous system metastases in gastroesophageal cancer.
Authors: Lucy Xiaolu Ma, Charles Henry Lim, Peiran Sun, Maria Jiang, Hao-Wen Sim, Akina Natori, Bryan Anthony Chan, Daniel Yokom, Stephanie Moignard, Lisa W Le, Eric Xueyu Chen, Geoffrey Liu, Carol Jane Swallow, Gail Elizabeth Darling, Paul N. Kongkham, David Shultz, Sara Hafezi-Bakhtiari, James Conner, Elena Elimova, Raymond Woo-Jun Jang
Journal: Journal of Clinical Oncology (2018)

145 Background: Central nervous system (CNS) metastases (mets) in gastroesophageal (GE) cancers are rare. There have only been limited studies examining the role of HER2 status in CNS mets in GE cancers. Methods: A retrospective analysis was performed for patients (pts) treated for GE cancers at the Princess Margaret Cancer Centre from 2011-2016. Quantitative and qualitative data were collected for all pts with CNS mets. Kaplan-Meier method was used to calculate overall survival (OS) and CNS progression free survival (PFS) for CNS mets pts. Results: Of 34 GE cancer pts diagnosed with CNS mets, 11 were HER2+, 11 HER2- and 12 had unknown HER2 status. Median time from initial cancer diagnosis to CNS mets was 10.3 months (13.4 in HER2+, 5.8 in HER2-, 11.7 in HER2 unknown). Characteristics at CNS mets diagnosis included: median age 63; 85% male; 74% had extracranial systemic mets; performance status ECOG 0-1 (64%), 2 (12%), 3-4 (24%). Treatment for CNS mets is shown in Table 1. Median OS from diagnosis of CNS mets was 6.1 months (95%CI 3.2-16.4) for all pts, 17.1 (95%CI 9.9-NA) in HER2+, 1.8 (95%CI 0.6-NA) in HER2-, 6.0 (95%CI 1.9-NA) in HER2 unknown, p=0.01. Median OS from initial cancer diagnosis was 18.5 months (95%CI 13.6-33.7) for all pts, 28.9 (95%CI 21.32-NA) in HER2+, 10.8 (95%CI 6.37-NA) in HER2-, 18.6 (95%CI 10-NA) in HER2 unknown, p=0.015. The 1 year CNS PFS rate was 35% (95%CI 22.1 – 55.5%) for all pts, 53% (95%CI 29.9 – 94%) in HER2+, 18.2% (95%CI 5.3 – 63.7%) in HER2-, 33% (95%CI 15 – 74.2%) in HER2 unknown, p=0.053. Conclusions: HER2+ pts tended to develop CNS mets later than HER2-. HER2+ pts were more likely to receive CNS-directed interventions, with more HER2+ pts having surgery for CNS mets while more HER2- had supportive care. This analysis is the first to suggest that in pts with CNS mets, HER2+ pts had longer survival than HER2-, both from initial diagnosis and after developing CNS metastases.[Table: see text]
RNAi‐mediated reduction of hepatic Tmprss6 diminishes anemia and secondary iron overload in a splenectomized mouse model of β‐thalassemia intermedia
Authors: Paul J. Schmidt, Kaifeng Liu, Gary Visner, Kevin Fitzgerald, Shannon Fishman, Tim Racie, Julia L. Hettinger, James S. Butler, Mark D. Fleming
Journal: American Journal of Hematology (2018)

Diminished β-globin synthesis in β-thalassemia is associated with ineffective erythropoiesis, leading to secondary iron overload caused by inappropriately low levels of hepcidin and to splenomegaly in the symptomatic thalassemias. Splenectomy is often employed in patients with β-thalassemia to reduce hemolysis. Expression of the iron regulatory peptide hormone hepcidin is repressed by the serine protease TMPRSS6. Hepcidin induction by RNAi-mediated inhibition of TMPRSS6 expression reduces iron overload and mitigates anemia in murine models of β-thalassemia intermedia. To interrogate the efficacy of RNAi-mediated reduction of Tmprss6 in splenectomized β-thalassemia, splenectomized β-thalassemic Hbbth3/+ animals were treated with a GalNAc-conjugated siRNA targeting Tmprss6 (GalNAc-Tmprss6) and their hematological and iron parameters monitored. We demonstrate that treatment with GalNAc-Tmprss6 significantly diminishes Tmprss6 expression and appropriately elevates hepcidin expression in splenectomized Hbbth3/+ animals. Similar to unsplenectomized animals, treated animals have markedly improved anemia due to diminished ineffective erythropoiesis and reduced iron loading in both serum and tissue. These results suggest that RNAi-mediated reduction of Tmprss6 may have positive outcomes even in splenectomized β-thalassemia patients.
I have finished medical university in Mongolia and have worked as a general practitioner for a year. I would like to work and live in the UK—what are my chances?
Authors: Kay Mohanna
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 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>
Redox regulation of Cdc25B by novel cell active quinolinediones
Authors: Marni Brisson, Theresa Nguyen, Peter Wipf, Beomjun Joo, Billy W. Day, John S. Skoko, Emanuel M. Schreiber, Pallavi Bansal, John S. Lazo
Journal: Cancer Research (2005)

660   Cdc25 dual specificity phosphatases are overexpressed in many human tumors and have oncogenic properties. Although several quinone inhibitors of Cdc25 phosphatase have been identified, their selectivity and cellular mechanisms of action have not been fully established. We synthesized and evaluated five novel quinolinedione congeners of a previously reported Cdc25 inhibitor, 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5,8-dione (DA3003-1 or NSC 663284). All five quinolinediones inhibited Cdc25A, B and C. The dehalogenated and minimal structure, JUN1111, was a more selective  in vitro  inhibitor of Cdc25 phosphatases compared with DA3003-1. Like DA3003-1, JUN1111 caused cell cycle arrest and directly inhibited etopically expressed Cdc25B activity in transfected cells.  In vitro  Cdc25B inhibition by these compounds was sensitive to dithiothreitol concentration, pH, and the presence of glutathione and catalase, suggesting that oxidation was a mechanism for irreversible Cdc25B inactivation. Mass spectrometric analysis showed that the catalytic cysteine of Cdc25B was indeed irreversibly oxidized to its sulfonic acid (SO 3 ) form upon treatment with DA3003-1. DA3003-1 and JUN1111 were also shown to rapidly generate reactive oxygen species in cells, further supporting enzyme inhibition by oxidation. We propose that these quinolinediones regulate the phosphatase activity of Cdc25 through selective and irreversible oxidation at the active site cysteine.
Characterization and application of size-sorted zonal chondrocytes for articular cartilage regeneration
Authors: Lu Yin, Yingnan Wu, Zheng Yang, Vinitha Denslin, Xiafei Ren, Ching Ann Tee, Zhangxing Lai, Chwee Teck Lim, Jongyoon Han, Eng Hin Lee
Journal: Biomaterials (2018)
Effect of High-Deductible Insurance on High-Acuity Outcomes in Diabetes: A Natural Experiment for Translation in Diabetes (NEXT-D) Study
Authors: J Frank Wharam, Fang Zhang, Emma M Eggleston, Christine Y Lu, Stephen B Soumerai, Dennis Ross-Degnan
Journal: Diabetes Care (2018)

High-deductible health plans (HDHPs) are now the predominant commercial health insurance benefit in the U.S. We sought to determine the effects of HDHPs on emergency department and hospital care, adverse outcomes, and total health care expenditures among patients with diabetes.
Photothermally Controlled MHC Class I Restricted CD8<sup>+</sup> T‐Cell Responses Elicited by Hyaluronic Acid Decorated Gold Nanoparticles as a Vaccine for Cancer Immunotherapy
Authors: Fengqiang Cao, Mengmeng Yan, Yijia Liu, Lanxia Liu, Guilei Ma
Journal: Advanced Healthcare Materials (2018)

Abstract Cancer vaccines aim to induce a strong major histocompatibility complex class I (MHC‐I)‐restricted CD8 + cytotoxic T‐cell response, which is an important prerequisite for successful cancer immunotherapy. Herein, a hyaluronic acid (HA) and antigen (ovalbumin, OVA)‐decorated gold nanoparticle (AuNPs)‐based (HA‐OVA‐AuNPs) vaccine is developed for photothermally controlled cytosolic antigen delivery using near‐infrared (NIR) irradiation and is found to induce antigen‐specific CD8 + T‐cell responses. Chemical binding of thiolated HA and OVA to AuNPs facilitates antigen uptake of dendritic cells via receptor‐mediated endocytosis. HA‐OVA‐AuNPs exhibit enhanced NIR absorption and thermal energy translation. Cytosolic antigen delivery is then permitted through the photothermally controlled process of local heat‐mediated endo/lysosome disruption by laser irradiation along with reactive oxygen species generation, which helps to augment proteasome activity and downstream MHC I antigen presentation. Consequently, the HA‐OVA‐AuNPs nanovaccine can effectively evoke a potent anticancer immune response in mice under laser irradiation. This NIR‐responsive nanovaccine is promising as a potent vaccination method for improving cancer vaccine efficacy.
Developing consensus on clinical assessment of acute lateral ankle sprain injuries: protocol for an international and multidisciplinary modified Delphi process
Authors: Daniela S Bossard, Alexandria Remus, Cailbhe Doherty, Phillip A Gribble, Eamonn Delahunt
Journal: British Journal of Sports Medicine (2018)

Within a year of first-time acute lateral ankle sprain injury, as many as 40% of individuals develop long-term injury-associated symptoms and chronic ankle instability.1 Chronic ankle instability is founded in a combination of mechanical and sensorimotor impairments, which manifest after the injury.2 

Before effective management protocols for lateral ankle sprain injuries can be developed and implemented, it is pertinent that a best practice, evidence-based approach to the clinical assessment of acute lateral ankle sprain injury is established. Second to diagnosis of the acute injury, clinical assessment should establish the presence or otherwise of mechanical and sensorimotor impairments that associate with chronic ankle instability. Developing structured, best practice, evidence-based recommendations for the clinical assessment of acute lateral ankle sprain injuries could be achieved by a …
miR-30a-5p as a tumor suppressor gene in gastric cancer.
Authors: Jimin Min, Tae-su Han, Boram Choi, Keun Hur, Kazuyoshi Yanagihara, V Narry Kim, Hyuk-Joon Lee, Han-Kwang Yang
Journal: Journal of Clinical Oncology (2018)

84 Background: Gastric cancer (GC) is the second leading cause of cancer-related death. MicroRNAs (miRNAs) are an abundant class of negative gene regulator and regulate multiple gene targets. miRNAs control a wide range of biological functions such as cellular proliferation, differentiation and apoptosis. Moreover, many miRNAs are highly conserved, and their deregulation is often associated with human malignancies. The aims of this study are to determine the miR-30a functions as a tumor suppressor gene and to evaluate whether the miR-30a-5p is able to use the diagnostic or prognostic marker in GC. Methods: To identify the gastric tumor-associated miRNAs, miRNA microarray was performed using the gastric cancer tissues. qRT-PCR was employed to confirm the microarray results. Also, to determine the miR-30a-5p biological functions in GC, miR-30a-5p mimic or inhibitor was treated in GC cell lines. Results: In miRNA microarray data, miR-30a-5p was down-regulated in GC tissues compared to normal mucosa. When we performed qRT-PCR to confirm miR-30a-5p expression, it was frequently down-regulated in our GC cohort, (n = 30, P &lt; 0.001). Furthermore, ectopic expression of miR-30a-5p decreased cell growth, migration capacity and colony formation in vitro. Conclusions: Taken together, the miR-30a-5p expression was frequently down-regulated in GC. In addition, the miR-30a-5p suppressed tumorigenesis. Therefore, we suggest that miR-30a-5p activation may be a useful strategy of GC patient therapy and it can serve as a diagnostic or prognostic marker for GC.
Prognostic interaction between bone marrow morphology and SF3B1 and ASXL1 mutations in myelodysplastic syndromes with ring sideroblasts
Authors: Abhishek A. Mangaonkar, Terra L. Lasho, Christy M. Finke, Naseema Gangat, Aref Al-Kali, Michelle A. Elliott, Kebede H. Begna, Hassan Alkhateeb, Alexandra P. Wolanskyj-Spinner, Curtis A. Hanson, Rhett P. Ketterling, William J. Hogan, Animesh Pardanani, Mark R. Litzow, Ayalew Tefferi, Mrinal M. Patnaik
Journal: Blood Cancer Journal (2018)
SOCIAL DETERMINANTS OF LIFESTYLE AND CARDIOVASCULAR HEALTH IN A MINORITY COMMUNITY STUDY FOR PROMOTION OF HEALTH
Authors: Rodrigo Fernandez-Jimenez, Jacqueline Latina, Ana Victoria Soto, Sameer Bansilal, Rajesh Vedanthan, Risa Jaslow, Maribel Santana, Raquel Diaz-Munoz, Valentina Regazzoni, Briana Cortez, Andrea Clarke-Littman, Elizabeth Hernandez, Monali Fatterpekar, Alexa Schulman, Chiara Giannarelli, Jason Kovacic, Andrew Kasarskis, Zahi Fayad, Roger Hajjar, Valentin Fuster
Journal: Journal of the American College of Cardiology (2018)
Masters degree in disaster relief health care
Authors: James Coulston
Journal: BMJ (2009)

The masters degree in disaster relief health care is for any member of a multidisciplinary team interested in disaster relief, especially disaster health care. I was the only surgeon in my entry year, but there was a good mix of military and non-military healthcare professionals, and healthcare logistic professionals.

The degree is a three year part time distance learning course, and I completed it during the first three years of my surgical registrar training. This approach worked well for me as there is a natural gap in postgraduate surgical exams at this point, leaving me a little more time to study.

I have always envisaged that …
The impact of facility case volume on overall survival in patients with metastatic renal cell carcinoma in the targeted therapy era.
Authors: Yu-Wei Chen, Katherine Tullio, Moshe Chaim Ornstein, Petros Grivas, Jorge A. Garcia, Brian I. Rini
Journal: Journal of Clinical Oncology (2018)

590 Background: Prognosis of metastatic renal cell carcinoma (mRCC) has significantly improved in the targeted therapy era. We aimed to investigate whether higher facility case volume (FCV) is associated with improved overall survival (OS) for mRCC. Methods: Patients diagnosed with mRCC from 2006-2012 were identified in the National Cancer Database. FCV was determined by the total cases of renal cell carcinoma (metastatic and non-metastatic) at each treating facility. Multivariable Cox regression model was used to investigate the association between FCV and OS. Covariates adjusted for were treatment modalities [targeted therapy, cytoreductive nephrectomy, and metastasectomy], tumor characteristics and patient sociodemographics. Results: There were 18,571 mRCC patients included in this study. The mean follow-up time was 13.2 months (median: 6; interquartile range: 2.3-17.9). After adjusting for baseline characteristics including treatment modalities (table), every increment of 100 FCV of the treating facility was associated with improved OS (AHR: 0.99, 95 CI: 0.98-0.99, p-value: 0.003). FCV was dichotomized at increasing percentiles (50 th , 80 th , 85 th , 90 th , and 95 th ). Improved OS was observed when high FCV was defined at 90 th percentile (47 cases/year; AHR: 0.96, 95% CI: 0.92-0.99, p-value: 0.02) and 95 th percentile (68 cases/year; AHR: 0.95, 95% CI: 0.91-0.98, p-value: 0.04) but not at 50 th (8 cases/year), 80 th (30 cases/year) or 85 th percentile (38 cases/year). Conclusions: Our results suggest that treatment at hospitals with higher renal cell carcinoma FCV is associated with improved OS for patients diagnosed with mRCC in the targeted therapy era. Model is also adjusted for age, race, sex, insurance status, Charlson comorbidity score, tumor stage, nodal status, histology type, year of diagnosis, and zip code-level socioeconomic data (income, education level and residence type). [Table: see text]
Intravascular Optical Molecular Imaging of a Macrophage Subset Within Intraplaque Hemorrhages
Authors: Jae Joong Lee, Min Woo Lee, Tae Shik Kim, Joon Woo Song, Hyeong Soo Nam, Dong Joo Oh, Wang-Yuhl Oh, Hongki Yoo, Kyeongsoon Park, Jin Won Kim
Journal: JACC. Cardiovascular imaging (2018)
Making Sense of Your Medical Career
Authors: Hamed Khan, Iqbal Khan
Journal: BMJ (2007)

Hodder Arnold, 2007, £17.99, pages

ISBN: 9780340887370

ISBN-10: 0340887370

Rating: \***|.5/5

This book provides a fast way of finding out all those things you need to assemble a portfolio of achievements to be in the running for competitive jobs. The author presents a cogent summary of areas often uncovered during discussions with peers over the years. His emphasis is on starting to build an impressive portfolio as a medical student rather than after qualification, …