tbuckley/cabot-search huggingface dataset:
Abstract 16728: Cigarette Smoke Impairs the Anti-Oxidative Response by Reducing Heme Levels and Inducing Bach1
Authors: Mohamad M Almedawar, Melanie Brux, Coy Brunssen, Henning Morawietz
Journal: Circulation (2018)

Introduction: Cigarette smoke is a major risk factor of cardiovascular diseases. Heme regulates the activity of enzymes and transcription factors including Bach1. Bach1 competes with Nrf2 transcriptional activity and inhibits the expression of anti-oxidative enzymes. However, the molecular mechanism of Bach1 activation and its impact on the anti-oxidative response after exposure to cigarette smoke is not clear. Hypothesis: We aim to understand the mechanism through which cigarette smoke impairs the anti-oxidative response. Methods: Primary human umbilical vein endothelial cells (HUVEC) were exposed to a cigarette smoke extract (CSE) (3 mg/ml nicotine) under static and unidirectional shear stress conditions. Shear stress was induced using the ibidi pump system and cone-and-plate viscometer. Llevels of reduced glutathione (GSH) were measured using the fluorescent probe o-phthalaldehyde. Heme levels were measured after oxalic acid extraction. Gene and miR expression was quantified by RT-qPCR. Immunofluorescence imaging was performed on fixed HUVEC. MiR-125b overexpression was achieved by transfecting mimics. Inhibition of Bach1 was done using siRNA transfection. Apoptosis was assessed using the caspase 3/7 assay. Human umbilical veins as an ex vivo model were exposed to CSE under static conditions. Results: Exposure to CSE induced the expression of BACH1 (1.90±0.18; p&lt;0.05) and reduced total heme levels (0.30±0.04; p&lt;0.001) in HUVEC. It also reduced miR-125b expression in HUVEC (0.39±0.09; p&lt;0.001) and umbilical veins (0.72±0.12; p&lt;0.05), whereas the expression of miR-125b target AhR repressor ( AHRR ) increased (14.93±4.08; p&lt;0.05). Inhibiting BACH1 rescued miR-125b expression (1.02±0.45; p&gt;0.05) and reduced AHRR expression (0.66±0.12; P&lt;0.05). Acute exposure to CSE led to a high oxidative stress load. This observation was supported by a 2-fold reduction in glutathione levels, an increase in nuclear:cytosolic ratio of the upstream transcription factor Nrf2 (1.33±0.05; p&lt;0.01) and an increase in expression of anti-oxidative HMOX1 (18.18±1.8; p&lt;0.001) and NQO1 (16.12±1.99; p&lt;0.001). CSE-induced apoptosis (1.23±0.04; p&lt;0.001) was reversible by pre-conditioning with 1 mM N-acetyl cysteine (0.99±0.02; p&gt;0.05) or overexpression of miR-125b (0.99±0.07; p&gt;0.05). Conclusions: These results show that cigarette smoke-induced Bach1 impairs the anti-oxidative response through inhibiting miR-125b in the human endothelium. Reduced heme levels could be involved in the upregulation of Bach1 activity.
TCT-661 Angiographic Results of Everolimus-Eluting Stents for the Treatment of In-Stent Restenosis
Authors: Jens Wiebe, Himanshu Rai, Tobias Rheude, Roisin Colleran, Salvatore Cassese, Heribert Schunkert, Michael Joner, Adnan Kastrati, Robert Byrne
Journal: Journal of the American College of Cardiology (2019)
Ignoring Data Delays Our Reaction to Emerging Public Health Tragedies Like <i>13 Reasons Why</i>
Authors: Eric C. Leas, Mark Dredze, John W. Ayers
Journal: JAMA Psychiatry (2019)

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 Psychiatry 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 Psychiatry journal
TCT-505 Impact of Sex and Door-to-Balloon Times on Long-Term Mortality in Patients Presenting With ST-Segment Elevation Myocardial Infarction (STEMI)
Authors: Alexandra Murphy, Matias Yudi, Omar Farouque, Anoop Koshy, Diem Dinh, Stephen Duffy, Angela Brennan, Christopher Reid, Nick Andrianopoulos, Lorelle Martin, Misha Dagan, Melanie Freeman, David Blusztein, Andrew Ajani, David Clark
Journal: Journal of the American College of Cardiology (2019)
TCT-513 Endovascular Therapeutic Hypothermia Is Feasible as an Adjuvant Therapy in Acute ST-Segment Elevation Myocardial Infarction Patients Without Delay in Door-to-Balloon Time
Authors: Luis Dallan, Natali Giannetti, Michael Dae, Thatiane Polastri, Carlos Eduardo Rochitte, Cesar Higa Nomura, Ludhmila Abrahao Hajjar, Claudia Bernoche, Silvia Lage, Felipe Lima, Jose Carlos Nicolau, Mucio Tavares, Expedito Ribeiro, Roberto Kalil, Pedro A. Lemos, Sergio Timerman
Journal: Journal of the American College of Cardiology (2019)
Nelfinavir and Lenalidomide/Dexamethasone in Patients with Lenalidomide-Refractory Multiple Myeloma. A Phase I/II Trial — SAKK 39/10
Authors: Felicitas Hitz, Thomas Pabst, Dagmar Hess, Marianne Kraus, Lenka Besse, Urban Novak, Katja Seipel, Stephanie Rondeau, Silvia Stüdeli, Simona Berardi, Samaras Panagiotis, Ulrich Mey, Christoph Driessen
Journal: Blood (2017)
TCT-646 Markers of Frailty Predict Conservative Management in Very Elderly (&gt;85 Years) Patients Presenting with Non–ST-Segment Elevation Myocardial Infarction (NSTEMI)
Authors: Alexandra Murphy, Anoop Koshy, Georgina Meehan, Phelia Kunniardy, Jay Ramchand, Omar Farouque, David Clark, Matias Yudi
Journal: Journal of the American College of Cardiology (2019)
TCT-170 Endothelial Shear Stress and Vascular Remodeling in Bioresorbable Scaffold and Metallic Stent
Authors: Erhan Tenekecioglu, Yuki Katagiri, Kuniaki Takahashi, Pieter Kitslaar, Jouke Dijkstra, Johan Reiber, Christos Bourantas, Frank Gijsen, Yoshinobu Onuma, Kerem Pekkan, Robert-Jan Van Geuns, Ryo Torii, Patrick Serruys
Journal: Journal of the American College of Cardiology (2019)
Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial
Authors: Dora Buonfrate, Joaquin Salas-Coronas, José Muñoz, Begoña Trevino Maruri, Paola Rodari, Francesco Castelli, Lorenzo Zammarchi, Leila Bianchi, Federico Gobbi, Teresa Cabezas-Fernández, Ana Requena-Mendez, Gauri Godbole, Ronaldo Silva, Marilena Romero, Peter L Chiodini, Zeno Bisoffi
Journal: The Lancet Infectious Diseases (2019)
TCT-180 Neointimal Tissue Coverage and Characterization Assessment Using Optical Coherence Tomography Surveillance 6 Months After Implantation of Bioresorbable Scaffolds Versus Conventional Everolimus-Eluting Stents in ISAR-Absorb MI Trial
Authors: Himanshu Rai, Fernando Alfonso, Michael Maeng, Christian Bradaric, Jens Wiebe, Evald Christiansen, Fiona Harzer, Salvatore Cassese, Roisin Colleran, Simon Schneider, Karl-Ludwig Laugwitz, Adnan Kastrati, Robert Byrne
Journal: Journal of the American College of Cardiology (2019)
TCT-694 Prognostic Impact of Aortic Valve Calcification in Patients With Low Flow Low Gradient Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
Authors: Sebastian Ludwig, Alina Gossling, Lara Waldschmidt, Matthias Linder, Andreas Schäfer, Florian Deuschl, Johannes Schirmer, Hermann Reichenspurner, Stefan Blankenberg, Ulrich Schäfer, Moritz Seiffert, Dirk Westermann, Lenard Conradi, Niklas Schofer
Journal: Journal of the American College of Cardiology (2019)
The genomic landscape of metastatic breast cancer highlights changes in mutation and signature frequencies
Authors: Lindsay Angus, Marcel Smid, Saskia M. Wilting, Job van Riet, Arne Van Hoeck, Luan Nguyen, Serena Nik-Zainal, Tessa G. Steenbruggen, Vivianne C. G. Tjan-Heijnen, Mariette Labots, Johanna M. G. H. van Riel, Haiko J. Bloemendal, Neeltje Steeghs, Martijn P. Lolkema, Emile E. Voest, Harmen J. G. van de Werken, Agnes Jager, Edwin Cuppen, Stefan Sleijfer, John W. M. Martens
Journal: Nature Genetics (2019)
TCT-275 Results of Percutaneous Coronary Intervention With Second-Generation Drug-Coated Balloons in Diabetic Patients at Long-Term Follow-Up
Authors: Ignacio Sanchez-Perez, José Abellán-Huerta, María López-Lluva, Pedro Pérez-Díaz, Jesus Piqueras-Flores, Ramón Maseda Uriza, Juan Antonio Requena, Alfonso Jurado-Román, Fernando Lozano
Journal: Journal of the American College of Cardiology (2019)
A multicentre analysis of the long-term outcomes of patients with localized rectal cancer treated with chemotherapy and/or radiotherapy alone due to medical inoperability or patient refusal
Authors: L. Lim, M. Chao, J. Shapiro, J. Millar, D. Kipp, A. Rezo, A. Fong, I. Jones, S. McLaughlin, P. Gibbs
Journal: Journal of Clinical Oncology (2006)

3633 Background: The outcome for patients with localized rectal cancer treated with chemoradiotherapy (CMT) or radiotherapy alone (RT) and no planned subsequent surgery is unknown. Insights can be provided by study of patients that do not undergo surgery due to excessive operative risk (medically inoperable) as a result of advanced age and/or co-morbidities, or patient refusal. Methods: A retrospective analysis at 6 Australian centers. Patients with recurrent rectal cancer, metastatic disease or primary tumors that were considered unresectable were excluded from the study. Results: We identified 48 patients treated between August 1998 and June 2005 meeting our criteria. There were 13 females and 35 males with a median age of 76 years (range 49 - 94). 24 patients (50%) were deemed medically inoperable and 24 patients refused surgery (the most common reasons were the desire to avoid a stoma or fear of surgery). Treatment was with standard long course radiation plus 5-FU (either bolus or continuous infusion) in 36 patients (75%) and 12 (25%) received RT alone. A complete clinical response was documented in 23 patients (48%) and a partial clinical response was documented in 14 patients (30%). At a median follow-up of 49 months, 18 patients (37.5%) have documented disease progression including 10 of 24 in the medically inoperable group and 8 of 24 in the refused surgery group. The median progression-free survival for all patients was 30+ months. 7 had local progression only, 7 had distant progression only and 4 patients had both local and distant progression. Of the 23 deceased patients, 16 (70%) died from progressive disease and 7 (30%) from non-cancer causes, including 4 from the refused surgery group. The median survival for all patients was 35 + months. Conclusions: In patients who are not suitable candidates for surgical resection due to advanced age and/or comorbidity CRT or RT alone is a safe alternative that results in significant progression-free and overall survival times, with many patients succumbing to co-morbidities rather than progressive disease. Many of these patients refusing surgery will have long periods of disease control after treatment with CRT or RT. No significant financial relationships to disclose.
TCT-728 Low-Risk Transcatheter Versus Surgical Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials
Authors: Mahesh Anantha Narayanan, Vimalkumar Veerappan Kandasamy, Yogesh N.V. Reddy, Michael Megaly, Janani Baskaran, Ashish Pershad, Rakesh Suri, Santiago Garcia
Journal: Journal of the American College of Cardiology (2019)
TCT-581 Jailed Pressure Wire to Assess the Side Branch Result for Bifurcation Lesions Treated by Provisional Stenting Strategy: iFR as a New Index
Authors: Francisco Hidalgo, Soledad Ojeda, Adrián Lostalo, Javier Suarez De Lezo, Aurora Luque, Miguel Romero, José Segura, Manuel Pan
Journal: Journal of the American College of Cardiology (2019)
Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer
Authors: Peter T. Harrison, Simon Vyse, Paul H. Huang
Journal: Seminars in Cancer Biology (2019)

Epidermal growth factor receptor (EGFR) mutations are the second most common oncogenic driver event in non-small cell lung cancer (NSCLC). Classical activating mutations (exon 19 deletions and the L858R point mutation) comprise the vast majority of EGFR mutations and are well defined as strong predictors for good clinical response to EGFR tyrosine kinase inhibitors (EGFRi). However, low frequency mutations including point mutations, deletions, insertions and duplications occur within exons 18–25 of the EGFR gene in NSCLC and are associated with poorer responses to EGFRi. Despite an increased uptake of more sensitive detection methods to identify rare EGFR mutations in patients, our understanding of the biology of these rare EGFR mutations is poor compared to classical mutations. In particular, clinical data focused on these mutations is lacking due to their rarity and challenges in trial recruitment, resulting in an absence of effective treatment strategies for many low frequency EGFR mutations. In this review, we describe the structural and mechanistic features of rare EGFR mutations in NSCLC and discuss the preclinical and clinical evidence for EGFRi response for individual rare EGFR mutations. We also discuss EGFRi sensitivity for complex EGFR mutations, and conclude by offering a perspective on the outstanding questions and future steps required to make advances in the treatment of NSCLC patients that harbour rare EGFR mutations.
Quantifying and monitoring fibrosis in non-alcoholic fatty liver disease using dual-photon microscopy
Authors: Yan Wang, Grace Lai-Hung Wong, Fang-Ping He, Jian Sun, Anthony Wing-Hung Chan, Jinlian Yang, Sally She-Ting Shu, Xieer Liang, Yee Kit Tse, Xiao-Tang Fan, Jinlin Hou, Henry Lik-Yuen Chan, Vincent Wai-Sun Wong
Journal: Gut (2019)

Objective Fibrosis stage is strongly associated with liver-related outcomes and is a key surrogate endpoint in drug trials for non-alcoholic steatohepatitis. Dual-photon microscopy allows automated quantification of fibrosis-related parameters (q-FPs) and may facilitate large-scale histological studies. We aim to validate the performance of q-FPs in a large histological cohort. Design 344 patients with non-alcoholic fatty liver disease (NAFLD) underwent 428 liver biopsies (240 had paired transient elastography examination). Fibrosis stage was scored using the NASH Clinical Research Network system, and q-FPs were measured by dual-photon microscopy using unstained slides. Patients were randomly assigned to the training and validation cohorts to test the performance of individual q-FPs and derive optimal cut-offs. Results Over 25 q-FPs had area under the receiver-operating characteristics curves &gt;0.90 for different fibrosis stages. Among them, the perimeter of collagen fibres and number of long collagen fibres had the highest accuracy. At the best cut-offs, the two q-FPs had 88.3%–96.2% sensitivity and 78.1%–91.1% specificity for different fibrosis stages in the validation cohort. q-FPs and histological scoring had nearly identical correlations with liver stiffness measurement, suggesting that the accuracy of q-FPs approached that of histological assessment. Among patients with paired liver biopsies, changes in the same q-FPs were associated with changes in fibrosis stage. At a median follow-up of 5.6 years, baseline q-FPs predicted liver-related events. Conclusion q-FP is highly accurate in the assessment of fibrosis in NAFLD patients. This automated platform can be used in future studies as objective and reliable evaluation of histological fibrosis.
Discovering Causal Mechanistic Pathways in Sepsis-associated Acute Respiratory Distress Syndrome
Authors: Keith R. Walley
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

neutrophils and occlude the pulmonary vasculature in a caspase 1-and IL-1-dependent manner.These findings are intriguing because they shed new light on platelet-derived EVs in SCD and link platelet-derived EVs to previously described roles of platelet-neutrophil aggregates in ACS.The authors postulate that platelet EVs may potentiate the formation of heterotypic platelet-neutrophil aggregates, resulting in additional EV shedding in a positive feedback loop.These investigations also bring to light the potential that additional TLRs may contribute to activation of the inflammasome, platelet EV shedding, and the formation of platelet-neutrophil aggregates in SCD, an important area for further investigation.For example, TLR9 is known to bind free heme (generated during hemolysis, a prominent feature of SCD).Gram-positive bacteria and porins (components of encapsulated organism cell walls) are ligands for TLR2.Thus, additional TLRs could be targets for future investigations.In addition, the role of EVs derived from red blood cells and endothelial cells in driving vaso-occlusive crisis remains incompletely understood.Finally, these findings indicate that inhibiting the shedding of platelet EVs may be of therapeutic benefit in SCD, particularly with regard to prevention or treatment of ACS.Indeed, these novel data may function as a catalyst to employ pharmacologically available inhibitors of IL-1B (anakinra), TLR4 (eritoran), and caspase 1 (VX-765) in clinical trials of vaso-occlusive crisis in patients with SCD.
Gasdermins and their role in immunity and inflammation
Authors: Pontus Orning, Egil Lien, Katherine A. Fitzgerald
Journal: The Journal of Experimental Medicine (2019)

The gasdermins are a family of pore-forming proteins recently implicated in the immune response. One of these proteins, gasdermin D (GSDMD), has been identified as the executioner of pyroptosis, an inflammatory form of lytic cell death that is induced upon formation of caspase-1–activating inflammasomes. The related proteins GSDME and GSDMA have also been implicated in autoimmune diseases and certain cancers. Most gasdermin proteins are believed to have pore-forming capabilities. The best-studied member, GSDMD, controls the release of the proinflammatory cytokines IL-1ß and IL-18 and pyroptotic cell death. Because of its potential as a driver of inflammation in septic shock and autoimmune diseases, GSDMD represents an attractive drug target. In this review, we discuss the gasdermin proteins with particular emphasis on GSDMD and its mechanism of action and biological significance.
Self-generating oxygen enhanced mitochondrion-targeted photodynamic therapy for tumor treatment with hypoxia scavenging
Authors: Zhengyang Yang, Jiafeng Wang, Shichao Ai, Jianfei Sun, Xiaoli Mai, Wenxian Guan
Journal: Theranostics (2019)

Tumor hypoxia is an important reason for the limited therapeutic efficacy of photodynamic therapy (PDT) because of the oxygen requirement of the therapeutic process. PDT consumes tissue oxygen and destroys tumor vasculature, further hampering its own efficacy in promoting tumor deterioration. Therefore, overcoming the photodynamic exacerbation of tumor hypoxia is urgent. Methods: Herein, we report a photodynamic nanoparticle with sustainable hypoxia remission skills by both intratumoral H2O2 catalysis and targeted mitochondrial destruction. The Mn3O4@MSNs@IR780 nanoparticles are formed by absorbing a photosensitizer (IR780) into 90 nm mesoporous silica nanoparticles (MSNs) and capping the surface pores with 5 nm Mn3O4 nanoparticles. Results: These Mn3O4 nanoparticles can accumulate in tumors and respond to the H2O2-enriched tumor microenvironment by decomposing and catalyzing H2O2 into O2. Afterwards, IR780 is released and activated, spontaneously targeting the mitochondria due to its natural mitochondrial affinity. Under laser irradiation, this self-generated oxygen-enhanced PDT can destroy mitochondria and inhibit cell respiration, resulting in sustainable hypoxia remission in tumor tissues and consequently enhancing the therapeutic outcome. In vitro experiments suggest that Mn3O4@MSNs@IR780 exhibited highly mitochondrion-targeted properties and could sustainably inhibit tumor hypoxia. Additionally, the highest photoacoustic signal of HbO2 with the lowest Hb was observed in tumors from mice after PDT, indicating that these nanoparticles can also prevent tumor hypoxia in vivo. Conclusion: Taken together, our study indicated a new approach for overcoming the sustainable hypoxia limitation in traditional PDT by targeted oxygen supplementation and mitochondria destruction.
TCT-5 Is Surgical Aortic Valve Replacement Still an Option for Radiation-Induced Aortic Stenosis in the Transcatheter Aortic Valve Replacement Era?
Authors: Farhang Yazdchi, Sameer Hirji, Anju Nohria, Isidore Dinga Madou, Edward Percy, Julius Ejiofor, Siobhan McGurk, Marc Pelletier, Pinak Shah, Tsuyoshi Kaneko
Journal: Journal of the American College of Cardiology (2019)
TCT-454 Characteristics and Outcomes of Patients Who Are Denied From a Percutaneous Edge-to-Edge Mitral Valve Repair After Being Referred to a Transcatheter Mitral Valve Program: Impact of a Dedicated Multidisciplinary Mitral Heart Team Approach
Authors: Frederic Beaupre, Anthony Poulin, Caroline Gravel, Sandra Hadjadj, Mathieu Bernier, Jonathan Beaudoin, Kim O'Connor, Alfredo Nunes Ferreira Neto, Lluis Asmarats, François Dagenais, Josep Rodés-Cabau, Jean-Michel Paradis
Journal: Journal of the American College of Cardiology (2019)
Statistics chief asks for clarity on source of “new” NHS money
Authors: Nigel Hawkes
Journal: BMJ (2019)

The UK Statistics Authority has written to the Department of Health and Social Care asking how it justified its recent claims about £1.8bn of new funding for the NHS in England.

When the prime minister announced the spending on 5 August,1 he referred to it as “a new £1.8bn cash injection.” The Department of Health and Social Care explained in a press release that this “new” money consisted of £850m for 20 hospitals to upgrade facilities and equipment and a £1bn boost to NHS capital spending.

Outsiders immediately began raising questions about how new this money really was. Sally Gainsbury, an expert on …