tbuckley/cabot-search huggingface dataset:
Pharmacological Ascorbate Suppresses Growth of Gastric Cancer Cells with GLUT1 Overexpression and Enhances the Efficacy of Oxaliplatin Through Redox Modulation
Authors: Yun-Xin Lu, Qi-Nian Wu, Dong-Liang Chen, Le-Zong Chen, Zi-Xian Wang, Chao Ren, Hai-Yu Mo, Ya Chen, Hui Sheng, Ying-Nan Wang, Yun Wang, Jia-Huan Lu, De-Shen Wang, Zhao-Lei Zeng, Feng Wang, Feng-Hua Wang, Yu-Hong Li, Huai-Qiang Ju, Rui-Hua Xu
Journal: Theranostics (2018)

Rationale: The antitumor activity of high-dose ascorbate has been re-evaluated recently, but the mechanism underlying cell-specific sensitivity to ascorbate has not yet been clarified. Methods: The effects of high-dose ascorbate on gastric cancer were assessed using cancer cell lines with high and low expression of GLUT1 via flow cytometry and colony formation assays in vitro and patient-derived xenografts in vivo. Results: In this study, we demonstrated that gastric cancer cells with high GLUT1 expression were more sensitive to ascorbate treatment than cells with low GLUT1 expression. GLUT1 knockdown significantly reversed the therapeutic effects of pharmacological ascorbate, while enforced expression of GLUT1 enhanced the sensitivity to ascorbate treatment. The efficacy of pharmacological ascorbate administration in mice bearing cell line-based and patient-derived xenografts was influenced by GLUT1 protein levels. Mechanistically, ascorbate depleted intracellular glutathione, generated oxidative stress and induced DNA damage. The combination of pharmacological ascorbate with genotoxic agents, including oxaliplatin and irinotecan, synergistically inhibited gastric tumor growth in mouse models. Conclusions: The current study showed that GLUT1 expression was inversely correlated with sensitivity of gastric cancer cells to pharmacological ascorbate and suggested that GLUT1 expression in gastric cancer may serve as a marker for sensitivity to pharmacological ascorbate.
Can I work as a specialist registrar in the United Kingdom after completing MRCP (Ireland) in general medicine?
Authors: Brian Angus
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>
CLINICAL FEATURES AND OUTCOMES OF ATRIAL FIBRILLATION IN PATIENTS HOSPITALIZED WITH ACUTE PANCREATITIS
Authors: Jasmin Martinez Castellanos, Sandeep Dayanand, Abhinav Goyal, Kshitijee Chatterjee, Fnu Hafeez Hassan, Carissa Jeannette, Janani Rangaswami, Vincent Figueredo
Journal: Journal of the American College of Cardiology (2018)
Characteristics and Prognosis in Women and Men With Type 1 Diabetes Undergoing Coronary Angiography: A Nationwide Registry Report
Authors: Viveca Ritsinger, Christel Hero, Ann-Marie Svensson, Nawzad Saleh, Bo Lagerqvist, Katarina Eeg-Olofsson, Anna Norhammar
Journal: Diabetes Care (2018)

To describe sex aspects on extent of coronary artery disease (CAD) and prognosis in a contemporary population with type 1 diabetes.All patients undergoing coronary angiography, 2001-2013, included in the Swedish Coronary Angiography and Angioplasty Registry and the Swedish National Diabetes Register as type 1 diabetes were followed for mortality until 31 December 2013. The coronary angiogram was classified into normal, one-vessel disease, two-vessel disease, three-vessel disease, and left main stem disease.In all, 2,776 patients (42% women) with mean age 58 years (SD 11) were followed for 7.2 years (SD 2.2). Diabetes duration was longer in women (37 ± 14 vs. 34 ± 14 years in men; P < 0.001), who also had more retinopathy (68% vs. 65%; P = 0.050), whereas microalbuminuria was less common (41% vs. 51%; P < 0.001). Indications for coronary angiography did not substantially differ in women and men. The extent of CAD was somewhat less severe in women (normal angiogram 23.5% vs. 19.1%, three-vessel and left main stem disease 34.5% vs. 40.4%; P = 0.002), whereas mortality did not differ (adjusted hazard ratio 1.03 [95% CI 0.88-1.20]; P = 0.754). The standard mortality ratio for women the first year was 7.49 (5.73-9.62) and for men was 4.58 (3.60-5.74).In patients with type 1 diabetes admitted for coronary angiography, the extent of CAD was almost similar in women and men, and total long-term mortality did not differ. Type 1 diabetes was associated with higher mortality risk in women than in men when compared with the general population. These data support that type 1 diabetes attenuates the cardiovascular risk difference seen in men and women in the general population.
Seizure outcomes of supratentorial brain tumor resection in pediatric patients
Authors: Fadi S Saadeh, Edward F Melamed, Nolan D Rea, Mark D Krieger
Journal: Neuro-Oncology (2018)

This study aims to identify the prevalence of and risk factors for seizure development after supratentorial brain tumor resection in pediatric patients. This could be used to guide the postoperative management and usage of anti-epileptic drugs (AEDs).
Abstract P5-14-02: Effects of bazedoxifene and/or letrozole in the prevention of chemically-induced mammary cancers
Authors: BK Dunn, CJ Grubbs
Journal: Cancer Research (2018)

Abstract Bazedoxifene is described as a third-generation selective estrogen receptor modulator (SERM) that has been approved in Europe for the prevention and treatment of postmenopausal osteoporosis. The agent has also been shown to have therapeutic activity against estrogen receptor positive (ER+) breast cancer. Our laboratory has evaluated bazedoxifene for chemopreventive efficacy against mammary cancers when given alone or in combination with the aromatase inhibitor letrozole. Initially, the agents were evaluated alone to determine effective chemopreventive doses in the methylnitrosourea (MNU) ER+ mammary cancer model using female Sprague-Dawley rats. Bazedoxifene was mixed directly into a standard (Teklad, 4% fat) diet, while letrozole was gavaged 7x/week (vehicle was ethanol: PEG 400, 10:90, v/v). When evaluated alone in rats receiving MNU at 50 days of age, bazedoxifene (started one week after MNU) at doses of 100 and 30 mg/kg diet decreased mammary cancer multiplicity by 93 and 88%, respectively. In a similar protocol, letrozole at a dose of 0.1 mg/kg BW/day reduced cancer multiplicity by 89%, while a dose of 0.05 mg/kg BW/day reduced the number by 47%. In a separate study evaluating lower doses of bazedoxifene (5 mg/kg diet) and letrozole (0.04 mg/kg BW/day), mammary cancer multiplicity was decreased by 73% by both agents. When the agents were given in combination at these lower dose levels, cancer number was reduced by 91%. It is obvious that bazedoxifene is as effective as letrozole in the prevention of ER+ mammary cancers. Furthermore, administration of the agents in combination suggests an additive effect. The large increase in body weight gain generally noted in letrozole treated rats was not observed in rats receiving bazedoxifene; of interest, rats receiving the combination also had no increase in body weights. Several published invitro studies suggested that bazedoxifene might also be effective in preventing ER- mammary cancers; e.g., the agent is a novel inhibitor of IL-6/GP130 protein-protein interactions using multiple ligand simultaneous docking and drug repositioning approaches that result in apoptosis. In an initial study using MMTV/Neu mice (N=21/group) that received dimethylbenzanthracene (DMBA), we showed that administering bazedoxifene (15 mg/kg diet) would reduce the mammary tumor multiplicity from 5.4/mouse in controls to 1.1/mouse (an 80% decrease). These studies suggested that bazedozxifene is superior to other similar agents in that both ER+ and ER- mammary cancers are prevented at non-toxic doses. Supported by NCI contract HHSN261201200021I, Task Order HHSN26100007. Citation Format: Dunn BK, Grubbs CJ. Effects of bazedoxifene and/or letrozole in the prevention of chemically-induced mammary cancers [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 P5-14-02.
Periurethral Mass Mimicking Neoplasm After Injection of Macroplastique for Postprostatectomy Stress Incontinence
Authors: Capucine Richard, Sébastien Dejust, Abdenasser Moubtakir, Claire Bruna-Muraille, David Morland
Journal: Clinical Nuclear Medicine (2018)

Abstract A 64-year-old man underwent initial 18 F-FDG PET/CT staging for gastric cardia adenocarcinoma, which showed the primary gastric tumor, several bone metastases, and high uptake in a periurethral mass mimicking pelvic neoplasm developed after injection of polydimethylsiloxane (Macroplastique) urethral bulking agent 6 years ago for postprostatectomy stress urinary incontinence. This case showed a very rare complication of silicon particle injection therapy, and the intense uptake is likely due to granulomatous reaction around the implant.
Updated overall survival and safety profile of durvalumab monotherapy in advanced NSCLC.
Authors: Matthew D. Hellmann, Scott Joseph Antonia, Ani Sarkis Balmanoukian, Julie R. Brahmer, Sai-Hong Ignatius Ou, Sang-We Kim, Myung-Ju Ahn, Dong-Wan Kim, Martin Gutierrez, Stephen V. Liu, Patrick Schoffski, Dirk Jaeger, Rahima Jamal, Joseph W. Leach, Guy Heinrich Maria Jerusalem, Jose Lutzky, John J. Nemunaitis, Yu Gu, Shaad Essa Abdullah, Neil Howard Segal
Journal: Journal of Clinical Oncology (2018)

169 Background: Single-agent durvalumab is being evaluated in patients with advanced squamous and non-squamous NSCLC in an ongoing Phase 1/2 study (NCT01693562). Here we present updated survival and safety data in NSCLC patients. Methods: Treatment-naïve (1L) and previously treated (2L or 3L+) stage IIIB/IV NSCLC patients received durvalumab 10 mg/kg Q2W for up to 12 months. Patients were stratified by tumor PD-L1 expression (Ventana PD-L1 [SP263] Assay [PD-L1 high: ≥25% of tumor cells with membrane staining]), treatment line, and histology. Results: As of 05 September 2017, 304 NSCLC patients received durvalumab monotherapy. Median duration of follow-up was 35.6 (0.3–50.9) months. Investigator-assessed ORR ranged between 23.2% and 30.0% among PD-L1 high patients, and between 3.6% and 8.3% among PD-L1 low/negative patients. Median PFS and median OS were longer in PD-L1 high vs PD-L1 low/negative patients (Table). Any-grade treatment-related AEs (TRAEs) were reported in 57.2% of pts (including fatigue, 17.4%, decreased appetite, 9.2%, diarrhea, 8.9%); in 10.2% of pts these were Grade 3 or 4. TRAEs resulting in treatment discontinuation were reported in 17 patients (5.6%); 1 patient had a Grade 5 TRAE (pneumonia). Conclusions: In this ongoing phase 1 study, OS and safety profile appear encouraging in treatment-naïve and previously treated NSCLC patients, particularly among PD-L1 high patients. Further investigation regarding PD-L1 expression for selection of patients who most likely benefit from durvalumab is needed. Clinical trial information: NCT01693562. [Table: see text]
Publisher Correction: Medial preoptic circuit induces hunting-like actions to target objects and prey
Authors: Sae-Geun Park, Yong-Cheol Jeong, Dae-Gun Kim, Min-Hyung Lee, Anna Shin, Geunhong Park, Jia Ryoo, Jiso Hong, Seohui Bae, Cheol-Hu Kim, Phill-Seung Lee, Daesoo Kim
Journal: Nature Neuroscience (2018)
Treatment of Osteoporosis
Authors: Kamala Gullapalli Cotts, Adam S. Cifu
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
MACHINE LEARNING IN PREDICTING CORONARY HEART DISEASE AND CARDIOVASCULAR DISEASE EVENTS: RESULTS FROM THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA)
Authors: Rine Nakanishi, Damini Dey, Frederic Commandeur, Piotr Slomka, Julian Betancur, Heidi Gransar, Christopher Dailing, Kazuhiro Osawa, Daniel Berman, Matthew Budoff
Journal: Journal of the American College of Cardiology (2018)
Fibroblast growth factor 21 in cardio-metabolic disorders: a systematic review and meta-analysis
Authors: Ishan Lakhani, Mengqi Gong, Wing Tak Wong, George Bazoukis, Konstantinos Lampropoulos, Sunny Hei Wong, William K.K. Wu, Martin C.S. Wong, Kwok-Leung Ong, Tong Liu, Gary Tse
Journal: Metabolism (2018)
Toward methylation-based classification of central nervous system tumors
Authors: Monika E Hegi, Paul Kleihues, Patrick Y Wen, Mario L Suvà
Journal: Neuro-Oncology (2018)

Precise classification of nervous system tumors into coherent clinicopathologic entities is the necessary first step for the appropriate management of patients. While this has been traditionally performed by histopathology only, recent accelerations in our understanding of the molecular features of nervous system tumors have led to the integration of molecular characteristics into diagnostic criteria. The updated WHO 2016 classification of tumors of the central nervous system (CNS)1 thus includes both histologic and molecular features—primarily mutational status of individual genes and copy number alterations—facilitating the precise diagnosis of CNS tumors. While this has led to increased objectivity and reproducibility, classification progress is still required, especially for rare and for poorly understood entities.
Efficacy and safety of intermittent intravenous outpatient administration of levosimendan in patients with advanced heart failure: the LION‐HEART multicentre randomised trial
Authors: Josep Comín‐Colet, Nicolás Manito, Javier Segovia‐Cubero, Juan Delgado, José Manuel García Pinilla, Luis Almenar, María G. Crespo‐Leiro, Alessandro Sionis, Teresa Blasco, Domingo Pascual‐Figal, Francisco Gonzalez‐Vilchez, José Luis Lambert‐Rodríguez, María Grau, Jordi Bruguera
Journal: European Journal of Heart Failure (2018)
[44Sc]Sc-PSMA-617 Biodistribution and Dosimetry in Patients With Metastatic Castration-Resistant Prostate Carcinoma
Authors: Ambreen Khawar, Elisabeth Eppard, Jean Phlippe Sinnes, Frank Roesch, Hojjat Ahmadzadehfar, Stefan Kürpig, Michael Meisenheimer, Florian C. Gaertner, Markus Essler, Ralph A. Bundschuh
Journal: Clinical Nuclear Medicine (2018)

[Sc]Sc-PSMA-617 with 3.9-hour half-life, in vitro and in vivo characteristics similar to [Lu]Lu-PSMA-617 and possibility of delayed imaging after 24 hours or later, implies it to be advantageous than [ Ga]Ga-PSMA-617 for pretherapeutic dosimetric assessment for [Lu]Lu-PSMA-617 in metastatic castration-resistant prostate carcinoma (mCRPC) patients. In this study, we investigated biodistribution and radiation exposure to normal organs with [Sc]Sc-PSMA-617 in mCRPC patients.Five mCRPC patients (mean age, 69 years) enrolled for [Lu]Lu-PSMA-617 therapy were injected with 40-62 MBq [Sc]Sc-PSMA-617 intravenously; Siemens Biograph 2 PET/CT system was used to acquire dynamic PET data (30 minutes) in list mode over the abdomen, followed by the collection of static PET/CT images (skull to mid-thigh) at 45 minutes, 2 and approximately 20 hours postinjection. Time-dependent changes in percentage activity in source organs (kidneys, bladder, salivary glands, small intestine, liver, spleen, and whole body) were determined. Bone marrow and urinary bladder contents residence time were also calculated. Source organs residence time, organ-absorbed doses, and effective doses were determined using OLINDA/EXM software.Physiological tracer uptake was seen in kidneys, liver, spleen, small intestine, urinary bladder, and salivary glands and in metastases. Kidneys with highest radiation absorbed dose of 3.19E-01 mSv/MBq were the critical organs, followed by urinary bladder wall (2.24E-01 mSv/MBq, spleen [1.85E-01], salivary glands [1.11E-01], and liver [1.07E-01] mSv/MBq). Red marrow dose was found to be 3.31E-02 mSv/MBq. The mean effective dose of 3.89E-02 mSv/MBq and effective dose of 1.95 mSv was estimated from 50 MBq (treatment planning dose) of [Sc]Sc-PSMA-617.[Sc]Sc-PSMA-617 is found to be a very promising radiopharmaceutical that can be used for pre [Lu]Lu-PSMA-617 therapeutic dosimetric assessment.
Higher Growth Rate of Branch Duct Intraductal Papillary Mucinous Neoplasms Associates With Worrisome Features
Authors: Jennifer M. Kolb, Pamela Argiriadi, Karen Lee, Xiaoyu Liu, Emilia Bagiella, Shivani Gupta, Aimee L. Lucas, Michelle Kang Kim, Nikhil A. Kumta, Satish Nagula, Umut Sarpel, Christopher J. DiMaio
Journal: Clinical Gastroenterology and Hepatology (2018)
MULTIMODALITY NON-INVASIVE ASSESSMENT OF TRICUSPID REGURGITATION: COMPARISON OF DIFFERENT IMAGING PARAMETERS
Authors: Menhel Kinno, Richard Matiasz, Sasan Raissi, Kristoff Olson, Laura Davidson, Vibhav Rangarajan, Mark Ricciardi, Charles Davidson, Patrick McCarthy, Jyothy Puthumana, James Thomas
Journal: Journal of the American College of Cardiology (2018)
STRONG CORRELATION BETWEEN AORTIC VALVE CALCIFICATION SCORE BY CARDIAC COMPUTED TOMOGRAPHY AND TOTAL VALVE CALCIUM IN PATIENTS WITH SEVERE AORTIC VALVE STENOSIS
Authors: Louise Linde, Rasmus Carter-Storch, Nikolaj L. Christensen, Jordi Dahl, Kristian A. Ovrehus, Axel Diederichsen, Pia S. Jensen, Lars M. Rasmussen, Jacob E. Moller
Journal: Journal of the American College of Cardiology (2018)
Prevalence of Major Behavioral Risk Factors for Type 2 Diabetes
Authors: Karen R. Siegel, Kai McKeever Bullard, Giuseppina Imperatore, Mohammed K. Ali, Ann Albright, Carla I. Mercado, Rui Li, Edward W. Gregg
Journal: Diabetes Care (2018)

OBJECTIVE We examined the proportion of American adults without type 2 diabetes that engages in lifestyle behaviors known to reduce type 2 diabetes risk. RESEARCH DESIGN AND METHODS We conducted a cross-sectional analysis of 3,679 nonpregnant, nonlactating individuals aged ≥20 years without diabetes (self-reported diagnosis or glycated hemoglobin ≥6.5% [8 mmol/mol] or fasting plasma glucose ≥126 mg/dL) and who provided 2 days of reliable dietary data in the 2007–2012 National Health and Nutrition Examination Surveys (NHANES). We used the average of 2 days of dietary recall and self-reported leisure-time physical activity to assess whether participants met type 2 diabetes risk reduction goals (meeting four or more MyPlate recommendations [adequate consumption of fruits, vegetables, dairy, grains, meat, beans, and eggs]; not exceeding three maximum allowances for alcoholic beverages, added sugars, fat, and cholesterol; and meeting physical activity recommendations [≥150 min/week]). RESULTS Approximately 21%, 29%, and 13% of individuals met fruit, vegetable, and dairy goals, respectively. Half (51.6%) met the goal for total grains, compared with 18% for whole grains, and 54.2% met the meat/beans goal and 40.6% met the oils goal. About one-third (37.8%) met the physical activity goal, and 58.6% met the weight loss/maintenance goal. Overall, 3.1% (95% CI 2.4–4.0) of individuals met the majority of type 2 diabetes risk reduction goals. Younger age and lower educational attainment were associated with lower probability of meeting goals. CONCLUSIONS A small proportion of U.S. adults engages in risk reduction behaviors. Research and interventions targeted at young and less-educated segments of the population may help close gaps in risk reduction behaviors.
Incidence and predictors of mortality following major urologic cancer surgery.
Authors: Matthew Mossanen, Ross Krasnow, Dimitar V. Zlatev, Steven Lee Chang
Journal: Journal of Clinical Oncology (2018)

435 Background: Mortality following major urologic cancer surgery is a significant outcome to patients and providers. We utilized a population based cohort to test the hypothesis that the nature and number of perioperative complications impact the probability of mortality in major urologic surgery. Methods: Using the Premier Hospital Database we identified patients that underwent major urologic cancer surgery: radical prostatectomy (RP), radical nephrectomy (RN), or radical cystectomy (RC). Ninety-day complications were captured using ICD9 codes and complications were categorized according to the Agency for Healthcare Research and Quality Clinical Classification categories. The primary outcome was predicted probability of perioperative morality. Adjusted regression models were used and analyses were survey weighted. Models were adjusted for patient, hospital, and surgery characteristics, and we examined the predicted probability of mortality in three scenarios (no complication, index complication, or readmission complication). Results: From 2005-2013 we identified 630 828 RP, 306 532 RN, and 57 533 RC patients. At 90 days, 14.2% of RP patients had a complication, compared to 39% of RN patients and 68.3% of RC patients. Readmission rates at 90 days for RP were 1.9%, 5.9% for RN, and 19.9% for RC. For RN and RC the presence of a complication resulting in readmission compared to an index complication nearly doubled the predicted probability of mortality (RN 1.7% to 3.6%, and RC 3.9% to 6.8%). The number of complications during the index stay and on readmission compounded the impact on mortality. For RN and RC, 1 complication vs. 4 complications resulted in a nearly 3-fold increase in predicted probability of mortality. The nature of complications varied by incidence however, the three most common complications that resulted in the greatest increase in predicted probability of mortality across all three operations included pulmonary, cardiac, and renal complications. Conclusions: The number and nature of complications after major urologic cancer surgery impact the predicted probability of perioperative mortality and such data may be used to counsel patients when providing urologic cancer care.