tbuckley/cabot-search huggingface dataset:
Abstract P4-05-24: A stroma-adjusted ZEB1 expression signature is associated with decreased immune cell infiltration and poor overall survival in breast cancer
Authors: C James Block, Guojun Wu
Journal: Cancer Research (2020)

Abstract The epithelial-to-mesenchymal transition (EMT) is a critical physiologic process which can be activated by cancer cells to enhance metastatic and chemoresistant properties in experimental models. Recent studies have identified positive associations between the expression of EMT-associated gene signatures with both the immune response and survival in multiple cancer types. Although these studies relied upon whole-tumor RNA sequencing data, which can be confounded by infiltrating immune and stromal cells, they failed to investigate this potential confounding effect. In this study, we comprehensively dissected the associations between the expression of multiple EMT transcription factors with stromal and immune cell tumor infiltration in breast cancer. We demonstrated that previously-reported associations between the expression of EMT marker genes and immune activity were confounded by stromal cell infiltration. Adjusting for this confounding effect eliminated these reported associations. Interestingly, we discovered that stroma-adjusted ZEB1 expression has a unique, inverse association with immune cell activity in multiple cancer types, most significantly in breast cancer. Further analysis revealed that ZEB1 is significantly correlated with reduced tumor infiltration of multiple immune cell types. By deriving a high-confidence stroma-adjusted ZEB1-activated gene signature, we confirmed that ZEB1 transcriptional activity has similar associations with both tumor immune activity and stromal content as ZEB1, thus identifying potential mechanisms underlying decreased immune cell infiltration. Finally, multivariate survival analysis reveals that the ZEB1 gene signature has significant associations with reduced overall survival in breast cancer patients. In conclusion, this study identifies a novel association between stroma-adjusted ZEB1 expression and tumor immune activity and addresses the critical issue of confounding between EMT-associated genes and tumor stromal content. Citation Format: C James Block, Guojun Wu. A stroma-adjusted ZEB1 expression signature is associated with decreased immune cell infiltration and poor overall survival in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-05-24.
Nrf2 and HIF1α converge to arsenic-induced metabolic reprogramming and the formation of the cancer stem-like cells
Authors: Zhuoyue Bi, Qian Zhang, Yao Fu, Priya Wadgaonkar, Wenxuan Zhang, Bandar Almutairy, Liping Xu, M'Kya Rice, Yiran Qiu, Chitra Thakur, Fei Chen
Journal: Theranostics (2020)

In this report, we demonstrated that inorganic arsenic (iAs) induces generation of the cancer stem-like cells (CSCs) through Nrf2-dependent HIF1α activation, and the subsequent metabolic reprogramming from mitochondrial oxidative phosphorylation to glycolysis in epithelial cells.Methods: Genome-wide ChIP-seq analysis was performed to investigate the global binding of Nrf2 and/or HIF1α on the genome in the cells treated with iAs.Both untargeted metabolomics and UDP-13 C-glucose flux were applied to determine metabolic reprogramming in the iAs-induced CSCs.The role of Nrf2 on iAs-induced HIF1α and other stemness gene expression was validated by lentiviral transfection of Nrf2 inhibitor Keap1 and CRISPR-Cas9-mediated Nrf2 gene knockout, respectively.Results: The CSCs induced by iAs exhibit a diminished mitochondrial oxidative phosphorylation and an enhanced glycolysis that is actively shunted to the hexosamine biosynthetic pathway (HBP) and serine/glycine pathway.ChIP-seq data revealed that treatment of the cells with iAs amplified Nrf2 enrichment peaks in intergenic region, promoter and gene body.In contrast, a shift of the HIF1α peaks from distal intergenic region to gene promoter and the first exon was noted.Both Nrf2 and HIF1α are responsible for the iAs-induced expression of the glycolytic genes and the genes important for the stemness of the CSCs.Intriguingly, we also discovered a mutual transcriptional regulation between Nrf2 and HIF1α.Inhibition of Nrf2 by lentiviral infection of Keap1, or knockout of Nrf2 by CRISPR-Cas9 gene editing, not only blocked iAs-induced HIF1α activation, but reduced the expression of the key stemness genes for the formation of CSCs also. Conclusion:We demonstrated that Nrf2 activation is an initiating signal for iAs-induced HIF1α activation, and Nrf2 and HIF1α played a concerted role on inducing metabolic reprogramming and the CSCs.
Loss of EGR-1 uncouples compensatory responses of pancreatic β cells
Authors: Sy-Ying Leu, Li-Hua Kuo, Wen-Tsan Weng, I-Chia Lien, Ching-Chun Yang, Tai-Tzu Hsieh, Yi-Ning Cheng, Po-Hsiu Chien, Li-Chun Ho, Shun-Hua Chen, Yan-Shen Shan, Yun-Wen Chen, Pei-Chun Chen, Pei-Jane Tsai, Junne-Ming Sung, Yau-Sheng Tsai
Journal: Theranostics (2020)

Rationale: Subjects unable to sustain β-cell compensation develop type 2 diabetes. Early growth response-1 protein (EGR-1), implicated in the regulation of cell differentiation, proliferation, and apoptosis, is induced by diverse metabolic challenges, such as glucose or other nutrients. Therefore, we hypothesized that deficiency of EGR-1 might influence β-cell compensation in response to metabolic overload. Methods: Mice deficient in EGR-1 (Egr1-/-) were used to investigate the in vivo roles of EGR-1 in regulation of glucose homeostasis and beta-cell compensatory responses. Results: In response to a high-fat diet, Egr1-/- mice failed to secrete sufficient insulin to clear glucose, which was associated with lower insulin content and attenuated hypertrophic response of islets. High-fat feeding caused a dramatic impairment in glucose-stimulated insulin secretion and downregulated the expression of genes encoding glucose sensing proteins. The cells co-expressing both insulin and glucagon were dramatically upregulated in islets of high-fat-fed Egr1-/- mice. EGR-1-deficient islets failed to maintain the transcriptional network for β-cell compensatory response. In human pancreatic tissues, EGR1 expression correlated with the expression of β-cell compensatory genes in the non-diabetic group, but not in the diabetic group. Conclusion: These results suggest that EGR-1 couples the transcriptional network to compensation for the loss of β-cell function and identity. Thus, our study highlights the early stress coupler EGR-1 as a critical factor in the development of pancreatic islet failure.
TCTAP A-102 Repeat Revascularization Following Percutaneous Coronary Intervention: Target Lesion Versus Non-target Lesion Revascularization
Authors: Sung Hun Park, Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Min Shim, Jun Hyuk Kang, Woo Hyeun Kim, Eun Jin Park, Jah Yeon Choi, Sunki Lee, Li Hu, Jin Oh Na, Cheolung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2017)
EXERCISE CAPACITY AND MORTALITY IN PATIENTS WITH ISCHEMIC LEFT VENTRICULAR DYSFUNCTION RANDOMIZED TO CORONARY ARTERY BYPASS SURGERY OR MEDICAL THERAPY: AN ANALYSIS FROM THE SURGICAL TREATMENT FOR ISCHEMIC HEART FAILURE TRIAL
Authors: Ralph Stewart, Dominika Szalewska, Lilin She, Mark Drazner, Kerry Lee, Barbara Lubiszewska, Dragana Kosevic, Permyos Ruengsakulrach, Jose Nicolau, Benoit Coutu, Shiv Choudhary, Daniel Mark, John Cleland, Ileana Pina, Eric Velazquez, Andrzej Rynkiewicz, Harvey White
Journal: Journal of the American College of Cardiology (2014)
All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide
Authors: Danni Ran, Jianfen Zhou, Zhilan Chai, Jinyang Li, Cao Xie, Jiani Mao, Linwei Lu, Yanyu Zhang, Sunyi Wu, Changyou Zhan, Weiyue Lu
Journal: Theranostics (2020)

Uncontrollable cell proliferation and irreversible neurological damage make glioma one of the most deadly diseases in clinic.Besides the multiple biological barriers, glioma stem cells (GSCs) that are responsible for the maintenance and recurrence of tumor tissues also hinder the therapeutic efficacy of chemotherapy.Therefore, all-stage precisional glioma targeted therapy regimens that could efficiently deliver drugs to glioma cells and GSCs after overcoming multiple barriers have received increasing scrutiny.Methods: A polymeric micelle-based drug delivery system was developed by modifying a "Yshaped" well-designed ligand of both GRP78 protein and quorum sensing receptor to achieve all-stage precisional glioma targeting, then we evaluated the targeting ability and barrier penetration ability both in vitro and in vivo.In order to achieve all-stage precisional therapy, we need kill both GSCs and glioma related cells.Parthenolide (PTL) has been investigated for its selective toxicity to glioma stem cells while Paclitaxel (PTX) and Temozolomide (TMZ) are widely used in experimental and clinical therapy of glioma respectively.So the in vivo anti-glioma effect of combination therapy was evaluated by Kaplan-Meier survival analysis and immunohistochemical (IHC) examination of tumor tissues. Results:The "Y-shaped" well-designed peptide, termed D WVAP, exhibited excellent glioma (and GSCs) homing and barrier penetration ability.When modified on micelle surface, D WVAP peptide significantly enhanced accumulation of micelles in brain and glioma.In addition, D WVAP micelles showed no immunogenicity and cytotoxicity, which could guarantee their safety when used in vivo.Treatment of glioma-bearing mice with PTL loaded D WVAP modified PEG-PLA micelles plus PTX loaded D WVAP modified PEG-PLA micelles or PTL loaded D WVAP modified PEG-PLA micelles plus TMZ showed improved anti-tumor efficacy in comparison to PTL and PTX loaded unmodified micelles or PTL loaded unmodified micelles plus TMZ. Conclusion:Combination of all-stage targeting strategy and concomitant use of chemotherapeutics and stem cell inhibitors could achieve precise targeted therapy for glioma
TCT-136 Cutoff Value and Long-Term Prediction of Clinical Events by FFR Measured Immediately After Implantation of a Drug-Eluting Stent in Patients With Coronary Artery Disease: 1- to 3-Year Results From the DKCRUSH VII Registry Study
Authors: Suiji Li, Shao-Liang Chen, Zhen Ge, Jing Kan, Junjie Zhang, Fei Ye, Tak Kwan, Teguh Santoso, Song Yang, Imad Sheiban, Xue-Song Qian, Nailiang Tian, Tanveer Rab, Ling Tao
Journal: Journal of the American College of Cardiology (2017)
TCT-583 Multi Center, Prospective, Randomized, Single Blind, Consecutive Enrollment Evaluation a Novolimus-Eluting Coronary Stent System with Bioabsorbable Polymer Compared to a Zotarolimus-Eluting Coronary Stent System: 12- Month Clinical and 6-Month Angiographic and IVUS Results: the EXCELLA BD Study
Authors: Alexandre Abizaid, Roberto Botelho, Joachim Schofer, Stefan Verheye, Ricardo Costa, Luiz Fernando Tanajura, Katsuhisa Waseda, lynn morrison, Sara Toyloy, Peter Fitzgerald
Journal: Journal of the American College of Cardiology (2012)
GALECTIN-3 IN HEART FAILURE WITH PRESERVED EJECTION FRACTION: A RELAX SUBSTUDY
Authors: Omar AbouEzzeddine, Philip Haines, Susanna Stevens, Monica Shah, Marc Semigran, Martin LeWinter, Jean Rouleau, David Bull, G. Michael Felker, Barry Borlaug, Horng Chen
Journal: Journal of the American College of Cardiology (2014)
Withdrawal of Neurohumoral Blockade After Cardiac Resynchronization Therapy
Authors: Petra Nijst, Pieter Martens, Jeroen Dauw, W.H. Wilson Tang, Philippe B. Bertrand, Joris Penders, Liesbeth Bruckers, Gabor Voros, Rik Willems, Pieter M. Vandervoort, Matthias Dupont, Wilfried Mullens
Journal: Journal of the American College of Cardiology (2020)
OUTCOMES FOLLOWING URGENT/EMERGENT TRANSCATHETER AORTIC VALVE REPLACEMENT: INSIGHTS FROM THE STS/ACC TVT REGISTRY
Authors: Dhaval Kolte, Sahil Khera, Sreekanth Vemulapalli, Dadi David Dai, Stephan Heo, Andrew Michael Goldsweig, Herbert D. Aronow, Ignacio Inglessis, Sammy Elmariah, Barry Sharaf, Paul Gordon, J. Abbott
Journal: Journal of the American College of Cardiology (2018)
2-Year Outcomes After Stenting of Lipid-Rich and Nonrich Coronary Plaques
Authors: Myong Hwa Yamamoto, Akiko Maehara, Gregg W. Stone, Annapoorna S. Kini, Emmanouil S. Brilakis, David G. Rizik, Kendrick Shunk, Eric R. Powers, Jonathan M. Tobis, Brijeshwar S. Maini, Simon R. Dixon, James A. Goldstein, John L. Petersen, Philippe Généreux, Priti R. Shah, Aaron Crowley, Stephen J. Nicholls, Gary S. Mintz, James E. Muller, Giora Weisz
Journal: Journal of the American College of Cardiology (2020)
COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives
Authors: Jiumeng Sun, Wan-Ting He, Lifang Wang, Alexander Lai, Xiang Ji, Xiaofeng Zhai, Gairu Li, Marc A. Suchard, Jin Tian, Jiyong Zhou, Michael Veit, Shuo Su
Journal: Trends in Molecular Medicine (2020)
Infection, Antibiotics, and Patient Outcomes in the Intensive Care Unit
Authors: Mo Yin, Paul Anantharajah Tambyah, Eli N. Perencevich
Journal: JAMA (2020)

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
Transcatheter Electrosurgery
Authors: Jaffar M Khan, Toby Rogers, Adam B Greenbaum, Vasilis C Babaliaros, Dursun Korel Yildirim, Christopher G Bruce, Daniel A Herzka, William H Schenke, Kanishka Ratnayaka, Robert J Lederman
Journal: Journal of the American College of Cardiology (2020)
Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW: A quantitative dose-escalation study
Authors: Floris Jan Voskuil, Steven Jakob de Jongh, Wouter Tjerk Rudolph Hooghiemstra, Matthijs David Linssen, Pieter Jan Steinkamp, Sebastiaan Antonius Hendrik J de Visscher, Kees-Pieter Schepman, Sjoerd Geert Elias, Gert-Jan Meersma, Pascal Klaas Christiaan Jonker, Jan Johannes Doff, Annelies Jorritsma-Smit, Wouter Bastiaan Nagengast, Bert van der Vegt, Dominic James Robinson, Gooitzen Michell van Dam, Max Johannes Hendrikus Witjes
Journal: Theranostics (2020)

Tumor-positive resection margins are present in up to 23% of head and neck cancer (HNC) surgeries, as intraoperative techniques for real-time evaluation of the resection margins are lacking.In this study, we investigated the safety and potential clinical value of fluorescence-guided imaging (FGI) for resection margin evaluation in HNC patients.We determined the optimal cetuximab-800CW dose by quantification of intrinsic fluorescence values using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy.Methods: Five cohorts of three HNC patients received cetuximab-800CW systemically: three single dose cohorts (10, 25, 50 mg) and two cohorts pre-dosed with 75 mg unlabeled cetuximab (15 or 25 mg).Fluorescence visualization and MDSFR/SFF spectroscopy quantification was performed and were correlated to histopathology.Results: There were no study-related adverse events higher than Common Terminology Criteria for Adverse Events grade-II.Quantification of intrinsic fluorescence values showed a dose-dependent increase in background fluorescence in the single dose cohorts (p<0.001,p<0.001), which remained consistently low in the pre-dosed cohorts (p=0.6808).Resection margin status was evaluated with a sensitivity of 100% (4/4 tumor-positive margins) and specificity of 91% (10/11 tumor-negative margins). Conclusion:A pre-dose of 75 mg unlabeled cetuximab followed by 15 mg cetuximab-800CW was considered the optimal dose based on safety, fluorescence visualization and quantification of intrinsic fluorescence values.We were able to use a lower dose cetuximab-800CW than previously described, while remaining a high sensitivity for tumor detection due to application of equipment optimized for IRDye800CW detection, which was validated by quantification of intrinsic fluorescence values.
Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts
Authors: Gert Jan Lammers, Claudio L.A. Bassetti, Leja Dolenc-Groselj, Poul J. Jennum, Ulf Kallweit, Ramin Khatami, Michel Lecendreux, Mauro Manconi, Geert Mayer, Markku Partinen, Giuseppe Plazzi, Paul J. Reading, Joan Santamaria, Karel Sonka, Yves Dauvilliers
Journal: Sleep Medicine Reviews (2020)

The aim of this European initiative is to facilitate a structured discussion to improve the next edition of the International Classification of Sleep Disorders (ICSD), particularly the chapter on central disorders of hypersomnolence. The ultimate goal for a sleep disorders classification is to be based on the underlying neurobiological causes of the disorders with clear implication for treatment or, ideally, prevention and or healing. The current ICSD classification, published in 2014, inevitably has important shortcomings, largely reflecting the lack of knowledge about the precise neurobiological mechanisms underlying the majority of sleep disorders we currently delineate. Despite a clear rationale for the present structure, there remain important limitations that make it difficult to apply in routine clinical practice. Moreover, there are indications that the current structure may even prevent us from gaining relevant new knowledge to better understand certain sleep disorders and their neurobiological causes. We suggest the creation of a new consistent, complaint driven, hierarchical classification for central disorders of hypersomnolence; containing levels of certainty, and giving diagnostic tests, particularly the MSLT, a weighting based on its specificity and sensitivity in the diagnostic context. We propose and define three diagnostic categories (with levels of certainty): 1/"Narcolepsy" 2/"Idiopathic hypersomnia", 3/"Idiopathic excessive sleepiness" (with subtypes).
Life as a doctor in the Royal Navy
Authors: Helen Jones
Journal: BMJ (2020)

Life as a doctor in the Royal Navy is incredibly varied and no two days are the same. You could be working on shore providing daily GP care to your colleagues or be the only doctor on board a ship searching for pirates in the Indian Ocean. You could be contributing humanitarian medical support in the Caribbean following a hurricane or dealing with casualties in a helicopter search and rescue operation.

All fully qualified doctors spend their first six months in the navy completing the new entry medical officer course, which provides specialist training in areas such as battlefield advanced trauma life support and pre-hospital care techniques—things that most civilian doctors don’t get to learn.

Doctors are then streamed into the three different branches of the Royal Navy—surface fleet, submarines, or the Royal Marines. Where any doctor ends up working will depend on preferences …
TCT-513 Discordance In Stenosis Classification by pressure-Only indices of stenosis severity is Related to Differences in coronary flow reserve: The RESOLVING DISCORD study
Authors: Christopher Cook, Allen Jeremias, Yousif Ahmad, Matthew Shun-Shin, Sukhjinder Nijjer, Guus de Waard, Sayan Sen, Tim van de Hoef, Mauro Echavarria Pinto, Martijn van Lavieren, Ricardo Petraco, Rasha Al-Lamee, Martijn Meuwissen, Ibrahim Danad, Paul Knaapen, Akiko Maehara, Bon-Kwon Koo, Gary Mintz, Javier Escaned, Gregg Stone, Jan Piek, Niels van Royen, Justin Davies
Journal: Journal of the American College of Cardiology (2016)
CLINICAL OUTCOMES AT 2 YEARS OF THE ABSORB BIORESORBABLE VASCULAR SCAFFOLD VERSUS THE XIENCE DRUG-ELUTING METALLIC STENT IN PATIENTS PRESENTING WITH ACUTE CORONARY SYNDROME VERSUS STABLE CORONARY DISEASE: AIDA TRIAL SUB-STUDY
Authors: Ruben Tijssen, Rene J. van der Schaaf, Robin Kraak, Laura S.M. Kerkmeijer, Sjoerd H. Hofma, Karin Arkenbout, Auke P.J.D. Weevers, Yoshinobu Onuma, Patrick Serruys, Marcel Beijk, Jan Baan, Maartje Vis, Karel T. Koch, Jan Piek, Jan Tijssen, José Henriques, Robbert de Winter, Joanna Wykrzykowska
Journal: Journal of the American College of Cardiology (2019)
ECONOMIC OUTCOMES OF BIORESORBABLE VASCULAR SCAFFOLDS VERSUS EVEROLIMUS-ELUTING STENTS IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY REVASCULARIZATION: ONE YEAR RESULTS FROM THE ABSORB III TRIAL
Authors: Suzanne Baron, Yang Lei, Katherine Vilain, Elizabeth Magnuson, Dean Kereiakes, Stephen Ellis, Gregg Stone, David Cohen
Journal: Journal of the American College of Cardiology (2016)