tbuckley/cabot-search huggingface dataset:
Acute Myocardial Infarction
Authors: Etienne Puymirat, Tabassome Simon, Guillaume Cayla, Yves Cottin, Meyer Elbaz, Pierre Coste, Gilles Lemesle, Pascal Motreff, Batric Popovic, Khalife Khalife, Jean-Noel Labèque, Thibaut Perret, Christophe Le Ray, Laurent Orion, Bernard Jouve, Didier Blanchard, Patrick Peycher, Johanne Silvain, Philippe Gabriel Steg, Patrick Goldstein, Pascal Guéret, Loic Belle, Nadia Aissaoui, Jean Ferrières, François Schiele, Nicolas Danchin
Journal: Circulation (2017)

Background: ST-segment–elevation myocardial infarction (STEMI) and non–ST-segment–elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. Methods: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14 423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. Results: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ≤72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. Conclusions: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.
Constitutive Signaling from an Engineered IL7 Receptor Promotes Durable Tumor Elimination by Tumor-Redirected T Cells
Authors: Thomas Shum, Bilal Omer, Haruko Tashiro, Robert L. Kruse, Dimitrios L. Wagner, Kathan Parikh, Zhongzhen Yi, Tim Sauer, Daofeng Liu, Robin Parihar, Paul Castillo, Hao Liu, Malcolm K. Brenner, Leonid S. Metelitsa, Stephen Gottschalk, Cliona M. Rooney
Journal: Cancer Discovery (2017)

Successful adoptive T-cell immunotherapy of solid tumors will require improved expansion and cytotoxicity of tumor-directed T cells within tumors. Providing recombinant or transgenic cytokines may produce the desired benefits but is associated with significant toxicities, constraining clinical use. To circumvent this limitation, we constructed a constitutively signaling cytokine receptor, C7R, which potently triggers the IL7 signaling axis but is unresponsive to extracellular cytokine. This strategy augments modified T-cell function following antigen exposure, but avoids stimulating bystander lymphocytes. Coexpressing the C7R with a tumor-directed chimeric antigen receptor (CAR) increased T-cell proliferation, survival, and antitumor activity during repeated exposure to tumor cells, without T-cell dysfunction or autonomous T-cell growth. Furthermore, C7R-coexpressing CAR T cells were active against metastatic neuroblastoma and orthotopic glioblastoma xenograft models even at cell doses that had been ineffective without C7R support. C7R may thus be able to enhance antigen-specific T-cell therapies against cancer.Significance: The constitutively signaling C7R system developed here delivers potent IL7 stimulation to CAR T cells, increasing their persistence and antitumor activity against multiple preclinical tumor models, supporting its clinical development. Cancer Discov; 7(11); 1238-47. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1201.
Abstract 300: Alda-1 Attenuates Acute Ischemia-reperfusion Mediated Cardiac Damage in Aldehyde Dehydrogenase 2 Mutant Diabetic Mice
Authors: Guodong Pan
Journal: Circulation Research (2016)

Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme in heart, can remove 4-hydroxy-2-nonenal (4-HNE), a toxic by-products of oxidative stress induced by diabetes and ischemia-reperfusion (I/R) injury. A common inactivating mutation of ALDH2 (termed ALDH2*2) was found in 8% of the world’s population, which causes lower ALDH2 activity in mutation carriers. We hypothesized that Alda-1, the only known activator of both ALDH2 and ALDH2*2 mutation, is able to protect heart from I/R injury in diabetic mice with/without ALDH2*2 mutation. Adult male ALDH2*2 mutant and C57B6 wild-type (WT) mice at 3-4 months of age were made hyperglycemic with streptozotocin injection (150 mg/kg. i.p.). Three weeks after injection, Alzet osmotic pumps were implanted subcutaneously to deliver Alda-1 (10 mg/kg) or vehicle. Mice were sacrificed after one day of pump implantation. Hearts were isolated and subjected to 30-minute ischemic followed by 90-minute reperfusion in a Langendorff apparatus. The basal myocardial ALDH2 activity in diabetic ALDH2*2 mutant was significantly lower than in diabetic WT mice (0.50±0.23 vs 0.83±0.08 mmol/min/μg, -39.8%, p&lt;0.05). Alda-1 significantly increased myocardial ALDH2 activity in both ALDH2*2 (1.17±0.38 mmol/min/μg, +134.0%, p&lt;0.05) and WT (1.46±0.40 mmol/min/μg, +75.9%, p&lt;0.05) diabetic mice. Compared with vehicle, Alda-1 significantly improved left ventricular pressure (LVP), and decreased infarcted areas (IA) both in ALDH2*2 (LVP: 4.30±2.03 vs 15.77±8.99 mmHg, +266.7%, p&lt;0.05; IA: 75.17%±9.49 vs 40.46%±7.20, -46.2%, p&lt;0.05) and WT (LVP: 14.22±7.92 vs 21.96±4.32 mmHg, +54.4%, p&lt;0.05; IA: 42.44%±8.60 vs 28.61%±8.55, -32.6%, p&lt;0.05) subjected to I/R injury. Western-blots showed that Alda-1 decreased levels of 4-HNE protein adducts, and increased levels of mitochondrial complex V in both ALDH2*2 and WT mice. Our data suggest that one-day Alda-1 treatment can confer cardio-protective effects against I/R injury in ALDH2*2 diabetic mice possibly accelerating the detoxification of toxic 4-HNE and thereby protecting mitochondria.
An analysis of clinical trials in clinicaltrials.gov to assess the scope of NCI support and inclusion on NCI’s cancer.gov website.
Authors: Grace Miskin, Sheila Ann Prindiville, Joseph Martucci, David Loose, Gisele Agnes Sarosy
Journal: Journal of Clinical Oncology (2016)

e18029 Background: In 2008, NCI began development of the Clinical Trials Reporting Program (CTRP) to collect information about NCI-supported interventional trials. CTRP replaced NLM’s ClinicalTrials.gov website as the source of information for trials in NCI’s Cancer.gov website on 6/15/2015. The rationale was to make it easier for physicians and patients to find NCI-supported cancer trials enrolling patients, using a highly tailored search form. We report findings from an analysis of the breadth and number of trials in scope for display on Cancer.gov following this change. Methods: On 12/18/15 we ran the query previously used to identify cancer trials in ClinicalTrials.gov for display in Cancer.gov, returning trials with a cancer disease or condition or NCI as a collaborator or sponsor. In order to limit the query to active, NCI-supported interventional trials, trials were iteratively removed if they: (1) had an unknown status (had not been updated or verified within 2 years); (2) had no US sites; (3) had a non-active recruitment status; or (4) were non-interventional. Remaining trials were compared to the CTRP database. Trials not in CTRP were analyzed to see if they were NCI-supported and in scope for CTRP, defined as taking place at an NCI-designated Cancer Center or otherwise funded by NCI. Results: The initial query returned 48,158 trials. A total of 43,237 trials were removed: 19,171 unknown status; 12,060 no US sites; 11,006 non-active status; and 1,000 observational. Of the remaining 4,921 trials, 75.7% (n = 3,723) were in CTRP. Of the 24.3% (n = 1,198) not in CTRP, 12.7% (n = 623) were in scope to be added to CTRP. 11.7% (n = 575) did not indicate some form of NCI support and thus were not in scope for CTRP. Conclusions: A total of 88.4% (n = 4,346) of the active interventional US cancer trials found on ClinicalTrials.gov have some degree of NCI support and are eligible for display on Cancer.gov. Currently, 75.7% of the trials are available when searching clinical trials on the Cancer.gov website and we are working with awardees to ensure that the additional 12.7% that receive NCI support are added.
AB1202-HPR Relationship of work disability between the disease activity, depression and quality of life in housewife and working patients with rheumatoİd arthritis
Authors: S Sağ, K Nas, MS Sağ, I Tekeoğlu, A Kamanlı
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The aim of this study was to determine the work status in patients with rheumatoid arthritis (RA) while also defining the factors related to work disability. <h3>Objectives</h3> In this study, our objective was to determine the work productivity, work disability and difficulty in time-off daily activities of the housewife and working patients with rheumatoid arthritis (RA) and to investigate the relation of these parameters with disease activity, anxiety, depression and quality of life. <h3>Methods</h3> 82 patients with the diagnosis of RA (26 males, 56 females) and 29 healthy control subjects (5 males, 24 females) were included in the study. In patients with RA, DAS28 was used to evaluate the disease activity; Duruöz hand index was used to determine the functional status. In addition, HAQ (Heath assesment quality) and The Short Form (SF-36) Health Survey was used to evaluate the health status, Hospital Anxiety and Depression Scale (HADS) was used for the evaluation of depression and anxiety and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem v2.0 (WPAI:SHP) was used to evaluate the work productivity. <h3>Results</h3> Demographic characteristics such as age and gender, were comparable in both patient and control groups (p&gt;0.05). The difficulty in the time off daily activities were worse in the patient group compared with the control group (p&lt;0.05). Anxiety, were significantly higher in housewife RA group (p&lt;0.05). Difficulty in time-off daily activities was correlated with VAS-fatigue and DAS28,HAQ,Duruöz hand index was correlated. (p&lt;0.05). <h3>Conclusions</h3> Even if they are not working in housewives, we have found that as much as the least active RA patients, it is difficult for activities in daily life, that the quality of life associated with the illness is low, and that depression and anxiety are similar to employees. As a result, disease activity, quality of life and functional status control in RA patients are as important as those who are working as housewives. Particularly in increasing productivity and participation in everyday life, the mood is influential and physicians must examine their patients in this regard. There is a need for more extensive cohort studies on this topic. <h3>Disclosure of Interest</h3> None declared
Efforts to enhance blood stem cell engraftment: Recent insights from zebrafish hematopoiesis
Authors: Julie R. Perlin, Anne L. Robertson, Leonard I. Zon
Journal: The Journal of Experimental Medicine (2017)

Hematopoietic stem cell transplantation (HSCT) is an important therapy for patients with a variety of hematological malignancies. HSCT would be greatly improved if patient-specific hematopoietic stem cells (HSCs) could be generated from induced pluripotent stem cells in vitro. There is an incomplete understanding of the genes and signals involved in HSC induction, migration, maintenance, and niche engraftment. Recent studies in zebrafish have revealed novel genes that are required for HSC induction and niche regulation of HSC homeostasis. Manipulation of these signaling pathways and cell types may improve HSC bioengineering, which could significantly advance critical, lifesaving HSCT therapies.
Early, risk-adapted treatment with fludarabine in Binet stage A chronic lymphocytic leukemia patients: results of the CLL1 trial of the German CLL study group
Authors: M A Hoechstetter, R Busch, B Eichhorst, A Bühler, D Winkler, M J Eckart, U Vehling-Kaiser, H Schimke, U Jäger, H J Hurtz, G Hopfinger, F Hartmann, H Fuss, W Abenhardt, I Blau, W Freier, L Müller, M Goebeler, C M Wendtner, J Bahlo, K Fischer, M Bentz, B Emmerich, H Döhner, M Hallek, S Stilgenbauer
Journal: Leukemia (2017)
Oxygen Therapy in Suspected Acute Myocardial Infarction
Authors: Robin Hofmann, Stefan K James, Tomas Jernberg, Bertil Lindahl, David Erlinge, Nils Witt, Gabriel Arefalk, Mats Frick, Joakim Alfredsson, Lennart Nilsson, Annica Ravn-Fischer, Elmir Omerovic, Thomas Kellerth, David Sparv, Ulf Ekelund, Rickard Linder, Mattias Ekström, Jörg Lauermann, Urban Haaga, John Pernow, Ollie Östlund, Johan Herlitz, Leif Svensson
Journal: New England Journal of Medicine (2017)

The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain.In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air.A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups.Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart-Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110 .).
Longitudinal Care for Young Adults With Stroke
Authors: Lester Y. Leung, Emiliya Melkumova, David E. Thaler
Journal: JAMA Neurology (2017)

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
Abstract 110: Activation of the Homeostatic Intracellular Response Leads to Increased Myocardial Mitochondrial Turnover in Patients Undergoing Cardiac Surgery
Authors: Allen M Andres, David Sengstock, Salik Jahania, Reza Dabir, Roberta A Gottlieb, Robert M Mentzer
Journal: Circulation Research (2015)

Background: Previously we showed that the homeostatic intracellular repair response (HIR2) is activated in the hearts of patients undergoing cardiac surgery. Autophagy is a principal component of this beneficial response that clears fragile mitochondria and protein aggregates. Moreover, we have previously shown that mitochondrial elimination through autophagy (mitophagy) is a key element in ischemic preconditioning. Thus, an important mechanism of cardioprotection appears to involve the upregulation of autophagy which facilitates the clearance of vulnerable mitochondria to limit I/R injury. We hypothesized that this protective action leads to turnover of the existing mitochondrial population in the heart during the resolution of I/R injury. The purpose of this study was to examine if the mechanism of HIR2 extends to remodeling the existing mitochondrial population of the heart. Study Design: Autophagy and mitochondrial turnover were assessed in 10 patients undergoing coronary artery bypass or valve surgery requiring cardiopulmonary bypass. Biopsies of the right atrial appendage obtained before initiation and after weaning from cardiopulmonary bypass were processed to yield whole tissue lysates and mitochondria-enriched heavy membrane fractions. Samples were analyzed for autophagy by immunoblotting for LC3, Beclin-1, ATG5-12, and p62. Mitochondrial turnover was assessed by monitoring Tom70, Cox4, Drp1, p62 and Parkin in tissue lysates and heavy membrane fractions. Results: Heart surgery was associated with a robust increase in autophagy indicated by depletion of LC3, Beclin-1, ATG5-12 and p62, as well as the mitophagy and fission regulator Drp1. Parkin increased in the mitochondrial fraction after bypass. Surprisingly, post-bypass tissue lysates showed a marked increase in mitochondrial markers Tom70 and Cox4, suggesting mitochondrial biogenesis. Conclusions: These findings provide evidence for the first time in humans that coordinated mitophagy and biogenesis are part of the homeostatic response to I/R, pointing to the importance of studying this aspect of HIR2. Strategies designed to amplify HIR2 during cardiac stress may represent an entirely new approach to myocardial protection in patients undergoing heart surgery.
Pharmacists as Integral Members of the Cardiovascular Team—Reply
Authors: John E. Brush
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal
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Authors: Aneil Malhotra, Harshil Dhutia, Sabiha Gati, Tee-Joo Yeo, Helder Dores, Rachel Bastiaenen, Rajay Narain, Ahmed Merghani, Gherardo Finocchiaro, Nabeel Sheikh, Alexandros Steriotis, Abbas Zaidi, Lynne Millar, Elijah Behr, Maite Tome, Michael Papadakis, Sanjay Sharma
Journal: Journal of the American College of Cardiology (2017)
Diffusion-weighted imaging using ADC mapping as an imaging biomarker for breast cancer invasiveness.
Authors: Hubert Bickel, Wolfgang Bogner, Peter Christian Dubsky, Rupert Bartsch, Margaretha Rudas, Thomas Helbich, Katja Pinker-Domenig
Journal: Journal of Clinical Oncology (2013)

11093 Background: Recently, functional imaging techniques such as diffusion weighted imaging (DWI) have been added to routine MR and have shown great potential for improving breast cancer diagnosis. DWI depicts cellular diffusivity on a molecular level and can be quantified using the apparent diffusion coefficient (ADC). In malignant tumors diffusivity is restricted, leading to lower ADC values than benign tumors. The aim of this study was to proof, that DWI can be used to differentiate benign from malignant tumors and to elucidate if ADC can serve as an imaging biomarker for breast cancer invasiveness. Methods: In this IRB-approved study 250 patients with 267 suspicious breast lesions (BI-RADS IV-V) were included. All patients underwent routine MR at 3T. A DWI-sequence was added to a standard imaging protocol, increasing measurement time by 2:30 min. The lesions were identified in routine MR and DWI sequences and ADC values of the lesions were calculated. Histopathology was used as the standard of reference for all lesions. Appropriate statistical tests were used to compare the ADC values of benign and malignant tumors (cut-off value 1.25×10 -3 mm²/s), of invasive and non-invasive disease and between different invasive tumor subtypes. Results: There were 91 benign (mean ADC 1.58×10 -3 mm²/s) and 176 malignant (.94×10 -3 mm²/s) lesions, sensitivity and specificity were 94.3% (PPV 95.4%, CI 0.91-0.98) and 91.2% (NPV 89.2%, CI 0.81-0.94). 155 lesions were invasive cancers (median ADC .90×10 -3 mm²/s), while 21 were non-invasive ductal carcinoma in situ (1.22×10 -3 mm²/s). The invasive cancers were 130 invasive ductal (median ADC .91×10 -3 mm²/s) and 25 invasive lobular cancers (.83×10 -3 mm²/s). ADC was significantly different between benign and malignant lesions (p&lt;.001) and between invasive and non-invasive cancers (p&lt;.001), while no significant difference could be found between the invasive cancer subtypes (p=.163). Conclusions: Diffusion-weighted imaging reliably allows differentiation of benign and malignant breast tumors. The data suggest that ADC can be used as a non-invasive imaging biomarker for breast cancer invasiveness and may be of importance to treatment planning and outcome in breast cancer patients.