tbuckley/cabot-search huggingface dataset:
Characterization of the DNA Methylome during Human B-Cell Differentiation
Authors: Marta Kulis, Simon Heath, Giancarlo Castellano, Renée Beekman, Angelika Merkel, Emanuele Raineri, Anna Esteve, Ana C Queirós, Guillem Clot, Ronald Schuyler, Simone Ecker, Vera Pancaldi, Daniel Rico, Lidia Agueda, Julie Blanc, David Richardson, Laura Clarke, Avik Datta, Nuria Russiñol, Marien Pascual, Xavier Aguirre, Felipe Prosper, Diego Alignani, Bruno Paiva, Gersende Caron, Thierry Fest, Marcus O. Muench, Marina Fomin, Seung-Tae Lee, Joseph L. Wiemels, Alfonso Valencia, Marta Gut, Paul Flicek, Hendrik G. Stunnenberg, Reiner Siebert, Ralf Küppers, Ivo G. Gut, Elias Campo, José I. Martín-Subero
Journal: Blood (2014)
Role of Oxygen Radicals in Cerebral Edema Mechanisms: Rationale for the Use of Steroids
Authors: E. D. Hall, R. M. Del Maestro
Journal: Neuro-Oncology (1991)

The glucocorticoid steroids (e.g. methylprednisolone) are highly effective in the treatment of tumor-associated brain edema. However, they have been disappointing in the management of post-traumatic edema. Recently, it has been shown that methylprednisolone can beneficially affect the injured nervous system by inhibition of injury-induced free radical-mediated lipid peroxidation. However, higher doses are required to protect the injured nervous system than those needed to reduce tumor-associated edema. A novel non-glucocorticoid 21-aminosteroid tirilazad mesylate (U74006F), which more effectively inhibits lipid peroxidation and protects the injured nervous system, has been shown to be ineffective in limiting experimental tumor-associated edema. These results suggest that the mechanisms of tumor-associated edema are distinct from those involved in post-traumatic pathophysiology.
5-methyl-tetrahydrofolate increases eNOS activity by preventing peroxynitrite-induced oxidation of tetrahydrobiopterin in human vessels
Authors: C Antoniades, C Shirodaria, N Warrick, S Cai, P Leeson, C Ratnatunga, R Pillai, J De Bono, S Neubauer, K Channon
Journal: Circulation (2006)
Abstract 2025: TIMI Major Bleeding Independently Predicts Mortality in an Unselected STEMI Population: Results from the AMI-Quebec Study
Authors: Philippe L’Allier, Thao Huynh, Erick Schampaert, Simon Kouz, Mark Eisenberg, Claude Lauzon, Marc Afilalo, Robert de Larocheliere, Michel Nguyen, Claude Levesque, Jean Pierre Dery, Stephane Rinfret, Jean Claude Tardif
Journal: Circulation (2008)

Major bleeding was recently identified as an independent predictor of adverse clinical outcomes in patients with acute coronary syndromes. We sought to determine the impact of major bleeding on in-hospital mortality in patients with ST-elevation myocardial infarction (STEMI) and the clinical characteristics associated with major bleeding. AMI-QUEBEC was a retrospective cohort study of consecutive STEMI patients admitted to 17 selected acute-care hospitals in the Province of Quebec (Canada) in 2003. Research coordinators identified major bleeding complications according to the Thrombolysis In Myocardial Infarction (TIMI) classification. The cohort included 1,655 patients. Thirty-eight percent (38%) of patients were treated with fibrinolysis, 51% with primary percutaneous coronary intervention (PCI) (65% femoral approach) and 12% received no reperfusion therapy. Twenty-eight percent (28%) of patients were females, mean age was 62.3 years, mean weight was 77.5 kg, 5.1% had prior stroke, and baseline serum creatinine was 104 μmol/L. Concomitant medications included clopidogrel loading in 32%, glycoprotein IIb/IIIa inhibitor 24%, unfractionated heparin 82% and low molecular weight heparin 9%. TIMI major bleeding occurred in 7.3% of patients. Overall in-hospital mortality was 11.6%. Independent predictors of mortality were major bleeding (OR 4.36 [2.48 –7.68]) and age (OR 1.06 [1.03–1.08] per year increase). Independent predictors of TIMI major bleeding were femoral approach (OR 11.2 [3.9 –32.1]) female gender (OR 2.8 [1.5–5.1]) and peak creatinine (OR1.02 [1.01–1.03] per 1μmol/L increase). Age, weight, blood pressure, mode of reperfusion, clopidogrel, aspirin, anticoagulant, clopidogrel load, glycoprotein IIb/IIIa inhibitors, PCI within 24 hours post-fibrinolysis were not independent predictors of major bleeding. TIMI major bleeding conferred a greater than four-fold increase in risk of short-term mortality in an unselected STEMI population. The use of the femoral approach for vascular access was the most powerful predictor of major bleeding in this patient population, highlighting the impact of vascular access site selection.
Abstract 5585: Understanding Physicians’ Risk Stratification of Acute Coronary Syndromes: Insights from the Canadian ACS II Registry
Authors: Andrew T Yan, Raymond T Yan, Thao Huynh, Amparo Casanova, F. E Raimondo, David H Fitchett, Anatoly Langer, Shaun Goodman
Journal: Circulation (2008)

An important treatment-risk paradox exists in the management of acute coronary syndromes (ACS). However, the process of risk stratification by physicians and its relationship to patient management have not been well studied. Our objective was to examine patient risk assessment by physician in relation to treatment and objective risk score evaluation, and the underlying patient characteristics that physicians consider to indicate high risk. The prospective Canadian ACS II Registry recruited 1956 patients admitted for non-ST elevation ACS in 36 hospitals in Oct 2002-Dec 2003. Patient risk assessment by the treating physician and management were recorded on standardized case report forms. We calculated the TIMI, PURSUIT and GRACE risk scores for each patient. Of the 1956 ACS patients, 347 (17.8%) patients were classified as low risk, 822 (42%) as intermediate risk, and 787 (40.2%) as high risk by their treating physicians. Patients considered as high risk were more likely to receive aggressive medical therapies and to undergo coronary angiography and revascularization. However, there were only weak correlations (Kendall’s tau-b correlation coefficients ranging from 0.08 to 0.14) between risk assessment by physicians and all 3 validated risk scores. Advanced age was an independent negative predictor. Furthermore, there was no significant association between the high risk category and several established prognosticators, such as history of heart failure, hemodynamic variables, and creatinine. Contemporary risk stratification of ACS appears suboptimal and may perpetuate the treatment-risk paradox. Physicians may not recognize and incorporate the most powerful adverse prognosticators into overall patient risk assessment. Routine use of validated risk score may enhance risk stratification and facilitate more appropriate tailoring of intensive therapies towards high-risk patients.
Inv(2)(p23q35) in anaplastic large-cell lymphoma induces constitutive anaplastic lymphoma kinase (ALK) tyrosine kinase activation by fusion to ATIC, an enzyme involved in purine nucleotide biosynthesis
Authors: Zhigui Ma, Jan Cools, Peter Marynen, Xiaoli Cui, Reiner Siebert, Stefan Gesk, Brigitte Schlegelberger, Benjamin Peeters, Christiane De Wolf-Peeters, Iwona Wlodarska, Stephan W. Morris
Journal: Blood (2000)
Abstract 3698: Decreased Circulating Endothelial Progenitor Cells and Endothelial Dysfunction: a Novel Mechanism of Atherogenesis in Obesity.
Authors: Paulo F Leite, Claudia R Andrade, Santa Poppe, Luiz A Cesar, Silmara Coimbra, Protasio L Da Luz, Victor Debbas, Marisa F Goes, Francisco R Laurindo
Journal: Circulation (2007)

Underlying mechanisms of endothelial dysfunction in obesity are not fully understood. Circulating Endothelial Progenitor Cells (EPCs) are known to promote endothelial repair. Our aim was to assess the number/function of EPCs in morbid obese individuals and its correlation with endothelial function and inflammatory markers. EPCs were isolated from 33 morbid obese patients (age 47±1.8 y; men=34%; BMI=49±2.1 kg/m 2 , metabolic syndrome=84%) and 20 lean controls. Peripheral blood EPC number was significantly reduced in obese patients both with flow cytometry (KDR + /CD34 + ; 0.041±0.04 vs 0.074±0.05 %events, p&lt;0.001) and fluorescence analysis after short-term culture (49±4 vs 28±2 cells/field, p&lt;0.001). The plasma number of primitive CD 133 + cells, and concentrations of VEGF (Elisa) and nitrogen oxides (which potentially recruit EPCs), were similar to control, suggesting that reduction of EPCs occurs distally to early cell differentiation. Importantly, C-Reactive Protein (CRP), robustly increased in obese patients (0.15±0.04 vs 1.3±0.3; p=0.003), was a strong predictor of reduced EPC number at multivariate analysis (r=0.623; p &lt; 0.001). Likewise, the migratory response of EPCs to VEGF in vitro was significantly impaired in obese vs controls, despite similar VEGF receptor numbers. Multivariate analysis suggested potential roles of metabolic syndrome and leptin in such effect. Endothelial function at flow-mediated brachial artery reactivity was markedly reduced (by 60%) in obese patients, and had a significant inverse correlation with EPC number (r= 0.678; p&lt; 0.001). Carotid intimal thickness was also increased in obese patients (0.68±0.02 vs 0.58±0.08; p=0.001). On the other hand, the number of circulating endothelial cells (CD31 + /CD106 + ) was similar in both groups, suggesting that apoptosis was not enhanced in the obese. These results suggest for the first time that reduced number and migratory capacity of EPCs correlate with endothelial dysfunction or increased CRP and may be a key underlying mechanism of vascular complications and atherosclerosis in obesity.
Prognostic value of serum cardiac troponin I in ambulatory patients with chronic renal failure undergoing long-term hemodialysis
Authors: Ijaz A Khan, Norrapol Wattanasuwan, Nirav J Mehta, Aung Tun, Narpinder Singh, Harinder K Singh, Balendu C Vasavada, Terrence J Sacchi
Journal: Journal of the American College of Cardiology (2001)
Initial experience with hyperoxemic reperfusion after primary angioplasty for acute myocardial infarction
Authors: Simon R Dixon, Antonio L Bartorelli, Pamela A Marcovitz, Richard Spears, Shukri David, Issac Grinberg, Mansoor A Qureshi, Mauro Pepi, Daniela Trabattoni, Franco Fabbiocchi, Piero Montorsi, William W O’Neill
Journal: Journal of the American College of Cardiology (2002)
Abstract 15252: Desmin A191T Mutation Aggravates {delta}-Sarcoglycan-Deficient Cardiomyopathy in TO-2 Hamster
Authors: Aiji Sakamoto, Kageyoshi Ono
Journal: Circulation (2011)

Introduction: Cardiomyopathic hamsters have distinct sublines, among which BIO14.6 exhibits hypertrophic cardiomyopathy (CM) whereas TO-2 manifests severe dilated CM. An additional mutation aggrava...
Abstract 404: Catheter Based Delivery of scAAV6 Leads to High Level, Global Gene Transfer to the Canine Heart Superior to scAAV8, scAAV9, and ssAAV9
Authors: Lawrence Bish, Meg Sleeper, Benjamin Brainard, Steven Cole, Nicholas Russell, Elanor Withnall, Jason Arndt, Ellen Davison, Julio Sanmiguel, Guangping Gao, James Wilson, H L Sweeney
Journal: Circulation (2007)

Background: Heart disease is the leading cause of morbidity and mortality, and its prevalence continues to rise. As a result, novel therapies are needed. Adeno-associated virus (AAV) mediated gene transfer may be an effective strategy since the low immunogenicity of AAV favors persistent transgene expression. In addition, the recently developed self-complementary AAV (scAAV) vectors have demonstrated higher expression than traditional, single stranded AAV (ssAAV) vectors. The goal of this study was to compare cardiac gene transfer efficiency of four AAV vectors using non-invasive, catheter based delivery in the dog. Methods: Four AAV vectors expressing GFP under control of the CB promoter were evaluated in this study–ssAAV9, scAAV9, scAAV8, scAAV6 –so that comparison could be made between ss and sc vectors as well as among serotypes 9, 8, and 6. Dogs (5–10kg, n=4 per group) underwent cardiac catheterization with introduction of an injection catheter into the LV under fluoroscopy. The interventricular septum (IVS) and LV free wall (LVFW) were targeted from base to apex with 40 injections of 250 ul. The total viral dose was either 2x10 13 gc/kg (ss) or 5x10 11 gc/kg (sc). At 7–10 days post-injection, hearts were explanted and divided into four equal sections from base to apex. GFP expression was quantified in four representative areas from IVS and LVFW in each section. TaqMan PCR was used to track biodistribution. Results: GFP expression in the scAAV6 group was approximately 10-fold higher than in the scAAV8 and scAAV9 groups, and GFP expression in the scAAV9 group was approximately 10-fold higher than in the ssAAV9 group, both in terms of total positive cells and total fluorescence (p&lt;0.01). Biodistribution studies revealed that vector genome copies were at least 10 times more abundant in the heart than in any other organ for scAAV6 (p≤0.05). Conclusion: scAAV is superior to ssAAV for cardiac gene transfer, and AAV6 has a higher cardiac tropism than AAV8 and AAV9 in the canine. Catheter based delivery of scAAV6 is a safe, effective method for achieving high level, global cardiac gene transfer to the LV. scAAV6 has great potential for transferring therapeutic transgenes to the failing canine heart and may be the vector of choice for clinical trials of cardiac gene transfer.
Low dose irradiation or folate-CpG enhances the efficacy of folate-hapten targeted immunotherapy.
Authors: Emanuela Sega, Michael Ringor, Esteban Celis, Philip S. Low
Journal: Cancer Research (2006)

5563   Human cancers frequently over-express a high affinity cell surface receptor for the vitamin folic acid (Kd=10 −9 M). This same receptor has also been shown to bind folate-hapten conjugates with 10 −9 M affinity, permitting the decoration of cancer cell surfaces with highly immunogenic molecules. Using syngeneic tumors in immunocompetent mice, we have shown that targeting of folate-linked haptens (FITC, DNP) to tumors in anti-hapten-immunized hosts can lead to rapid accumulation of autologous anti-hapten antibodies on the tumor cell surfaces and subsequent tumor elimination via antibody dependent cellular cytotoxicity (ADCC). This strategy yields 100 % cures of established tumors ( 3 ) in murine cancer models if the immune system is boosted with low doses of immunostimulatory cytokines (IL-2, IFN-α). However, when subcutaneous tumors exceed 300 mm 3  (8-9 mm in diameter) before initiation of therapy, antitumor activity is decreased. In an effort to enhance the efficacy of the folate-targeted immunotherapy against large tumors, other therapies that could conceivably synergize with the hapten-targeted immunotherapy were explored. We demonstrate here that 1) strong synergy is observed between tumor irradiation and immunotherapy, and 2) this synergy is not observed with standard chemotherapy. Furthermore, the combination of immunotherapy plus radiotherapy yields an improved response from even those tumors on the same animal that were not irradiated, suggesting that the combined therapies generate a systemic and synergistic antitumor response that can suppress tumor growth of even nonirradiated tumor masses. In a separate study, co-administration of the folate-hapten immunotherapy with a folate-targeted toll-like receptor ligand (CpG, the TLR 9 ligand known to have immunostimulatory activity) was also found to substantially increase mouse survival under conditions where neither therapy alone had a strong effect. Since folate-hapten targeted immunotherapy was not observed to synergize with any classical nontargeted chemotherapy, these data suggest that the combination of immunotherapy with a few selected other therapies may be beneficial in the treatment of large metastatic folate receptor positive tumors.
Early clinical abnormalities after H1N1 influenza pneumonia
Authors: Sergio Romero-Diaz, Rafael J. Hernandez-Zenteno, Fernando Flores Trujillo, Amaya Amaya Bermudez, Carlos Espinosa de los Monteros, Raul H. Sanores, Alejandra Velazquez Montero, Luis Torre Bouscoulet, Alejandra Ramirez-Venegas
Journal: European Respiratory Journal (2011)

Rationale: The impact on lung function (LF) and quality of life (QoL) after a severe H1N1 Influenza pneumonia has not been determined.

Objective: To describe early abnormalities in LF and QoL according to the severity of pneumonia.

Methods: Clinical characteristics, and laboratory samples at the arrival to the emergency room were recorded in 135 patients with H1N1 Influenza moderate to severe pneumonia. LF and health related QoL questionnaires (HRQoL) were measured after two months of hospitalization. All subjects have no clinical antecedent of respiratory disability.

Results: Mean age was 40±11 years, 64% were males, Kyrbi Index (KI) was 243±55, the APACHE score was 11.5±5, 30% required mechanical ventilation (MV). 35% had FEV1/FVC  0.85, 31% had PaO2  30 points; 36% had in the SF-36 physical limitation domain (PLSF-36) a score ≤50; Those with MV had more affection in LF in comparison with those without MV (FVC 96±16 vs 104±16%p; TLC 89±12 vs 97±21%p; FEV1/FVC 84±6 vs 81±7; TLco 81±22 vs 96±21%p; 6MWT 431±127 vs 508±97 meters; p<0.05). The HRQoL was worse in MV vs no MV [PLSF-36= 37.5 (0-81) vs 100 (50-100), p<0.05]. KI correlated with TLco (r=0.30), p=0.003; CURB-65 with TLco (r= -0.20), p<0.04. PLSF-36 correlated with TLco (r=0.42), KI (r=0.27) and CURB-65 (r= -0.32), p< 0.02.

Conclusions: After a severe pneumonia due to H1N1 influenza, one third of the patients had the LF and HRQoL affected. Patients who required MV had greater impairment in LF and in the HRQoL.
Relationship Between Prebiopsy Multiparametric Magnetic Resonance Imaging (MRI), Biopsy Indication, and MRI-ultrasound Fusion–targeted Prostate Biopsy Outcomes
Authors: Xiaosong Meng, Andrew B Rosenkrantz, Neil Mendhiratta, Michael Fenstermaker, Richard Huang, James S Wysock, Marc A Bjurlin, Susan Marshall, Fang-Ming Deng, Ming Zhou, Jonathan Melamed, William C Huang, Herbert Lepor, Samir S Taneja
Journal: European Urology (2015)
Erratum: Responsiveness of B cells is regulated by the hinge region of IgD
Authors: Rudolf Übelhart, Eva Hug, Martina P Bach, Thomas Wossning, Marcus Dühren-von Minden, Anselm H C Horn, Dimitrios Tsiantoulas, Kohei Kometani, Tomohiro Kurosaki, Christoph J Binder, Heinrich Sticht, Lars Nitschke, Michael Reth, Hassan Jumaa
Journal: Nature Immunology (2015)
Abstract 78: Activation of A3 Adenosine Receptors Protects the Ischemic Reperfused Myocardium Via Recruitment of PI3K-AKT- iNOS Cell Survival Pathway
Authors: Patricia Karjian, Afthab Hussain, Hajar Al-Rajaibi, Helen Maddock
Journal: Circulation (2006)

Recent studies have emphasized the important role that nitric oxide (NO) plays in protecting against myocardial ischemia reperfusion injury. It has been suggested that an increase in iNOS and enhan...
Abstract 2923: AV and VV Optimization Causes Incremental Improvement in Cardiac Output and Synchrony Post Cardiac Resynchronization Treatment
Authors: Tasneem Z Naqvi, Asim M Rafique, Sanjay Verma, C Thomas Peter
Journal: Circulation (2006)

BACKGROUND: Cardiac resynchronization treatment (CRT) causes improvement in cardiac function and synchrony in heart failure. The aim of this study was to determine whether echo-guided atrioventricular optimization (AVO) and optimization of V-V timing (VVO) of biventricular (Biv) pacemaker would cause incremental improvement in cardiac output and cardiac synchrony post CRT.  METHODS: 23 pts, 65 ± 16 yrs, 78% M, 61% ischemic cardiomyopathy, 26% with LBBB, underwent CRT and then AVO and VVO 21 ± 29 days post CRT. 20 had percutaneous CRT (left ventricular (LV) lead in the posterolateral vein in 15 and in anterolateral vein in 5) and 3 had epicardial CRT. Nominal and 6 VV delays and 50–250 ms AV delays were tested in each pt. Optimal AV and VV delay was determined from the AV and VV interval corresponding to the maximum aortic velocity time interval (VTI) by pulsed wave (PW) Doppler. Tissue Doppler imaging (TDI) in the apical 4, 2 and 3 chamber views was performed pre CRT, post CRT, post AVO and post VVO using GE vivid 7 ultrasound system. Ejection septolateral delay, asynchrony index [standard deviation of time to peak systolic velocity (PSV) during aortic ejection in 12 LV segments], maximum difference in time to PSV in 12 LV segments during entire cardiac cycle, and septoposterior wall delay (SPWD) during ejection & post ejection phase were measured as criteria of mechanical asynchrony.  RESULTS: LV ejection fraction improved from 26 ± 8% to 31 ± 7% and NYHA class from 3.4 ± 0.9 to 1.94 ± 0.6 (p   CONCLUSIONS: Optimization of atrioventricular and interventricular interval of Biv pacemaker by evaluation of PW aortic VTI causes incremental improvement in cardiac output and LV synchrony in pts post CRT./>
The Influence of the Practitioner of Medicine in Guiding the Public Towards Health
Authors: Haven Emerson
Journal: Annals of Internal Medicine (1931)

Article1 July 1931The Influence of the Practitioner of Medicine in Guiding the Public Towards HealthHAVEN EMERSON, M.D.HAVEN EMERSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-5-1-57 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe terms of the title assigned to me are too ambiguous to pass without definition. By the practitioner of medicine we usually intend to include only those physicians and their professional associates who earn their living chiefly, if not entirely, by using the sciences and arts of medicine for the diagnosis and treatment of disease as it is expressed in individual patients. Such physicians are by implication distinguished from those who are concerned with the prevention of disease through the authority and resources of official and volunteer health agencies. As I understand the use of words, both groups of physicians... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York City*Delivered before the American College of Physicians, March 24, 1931, Baltimore, Maryland. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1931Volume 5, Issue 1Page: 57-64KeywordsPrevention, policy, and public health ePublished: 1 December 2008 Issue Published: 1 July 1931 PDF downloadLoading ...