tbuckley/cabot-search huggingface dataset:
Erratum: Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
Authors: Denise Harold, Richard Abraham, Paul Hollingworth, Rebecca Sims, Amy Gerrish, Marian L Hamshere, Jaspreet Singh Pahwa, Valentina Moskvina, Kimberley Dowzell, Amy Williams, Nicola Jones, Charlene Thomas, Alexandra Stretton, Angharad R Morgan, Simon Lovestone, John Powell, Petroula Proitsi, Michelle K Lupton, Carol Brayne, David C Rubinsztein, Michael Gill, Brian Lawlor, Aoibhinn Lynch, Kevin Morgan, Kristelle S Brown, Peter A Passmore, David Craig, Bernadette McGuinness, Stephen Todd, Clive Holmes, David Mann, A David Smith, Seth Love, Patrick G Kehoe, John Hardy, Simon Mead, Nick Fox, Martin Rossor, John Collinge, Wolfgang Maier, Frank Jessen, Britta Schürmann, Hendrik van den Bussche, Isabella Heuser, Johannes Kornhuber, Jens Wiltfang, Martin Dichgans, Lutz Frölich,, Harald Hampel, Michael Hüll, Dan Rujescu, Alison M Goate, John S K Kauwe, Carlos Cruchaga, Petra Nowotny, John C Morris, Kevin Mayo, Kristel Sleegers, Karolien Bettens, Sebastiaan Engelborghs, Peter P De Deyn, Christine Van Broeckhoven, Gill Livingston, Nicholas J Bass, Hugh Gurling, Andrew McQuillin, Rhian Gwilliam, Panagiotis Deloukas, Ammar Al-Chalabi, Christopher E Shaw, Magda Tsolaki, Andrew B Singleton, Rita Guerreiro, Thomas W Mühleisen, Markus M Nöthen, Susanne Moebus, Karl-Heinz Jöckel, Norman Klopp, H-Erich Wichmann, Minerva M Carrasquillo, V Shane Pankratz, Steven G Younkin, Peter A Holmans, Michael O'Donovan, Michael J Owen, Julie Williams
Journal: Nature Genetics (2009)
Abstract 190: Potential Mechanism for Improved Neurological Survival After Cardiac Arrest After Treatment with Active Compression-Decompression Cardiopulmonary Resuscitation Combined with Augmentation of Negative Intrathoracic Pressure
Authors: Anja Metzger, Scott McKnite, Demetris Yannopoulos, Keith Lurie
Journal: Circulation (2011)

Objective: Active compression decompression (ACD) CPR with augmentation of negative intrathoracic pressure using an impedance threshold device (ITD) has been previously shown to enhance refilling of the heart and improve neurologically intact survival when compared with standard (S) CPR. To study the neuroprotective effects of ACD CPR + ITD, we tested the hypothesis that this new approach improves brain perfusion by reducing intracranial pressure (ICP) during the decompression phase of CPR, thereby lowering resistance to forward flow. Methods: Following 8.5 minutes of untreated ventricular fibrillation in 9 anesthetized (100 ug/kg/min propofol) female farm pigs (29.2 ± 1.3 kg), ACD CPR + ITD or SCPR was initiated in random order for 5 minutes followed by 5 additional minutes of CPR with the alternate method. Results: Cerebral perfusion pressures (mmHg) were improved with ACD CPR + ITD (21.9 ± 1.2) versus SCPR (8.9 ± 0.8, p&lt;0.0001). The effects of the CPR on the absolute ICP values and the rate of ICP change during the decompression phase are shown in Table 1. Mean carotid blood flow (ml/min) in the ACD CPR + ITD group was also higher (12.0 ± 2.2 versus 8.0 ± 1.5, p=0.008). Conclusions: The increase in cerebral perfusion pressures and carotid blood flow observed with ACD CPR + ITD was associated with lower diastolic ICP values and a more rapid decrease in ICP during the decompression phase of CPR compared with SCPR. These findings support a dual mechanism for neuroprotection with ACD CPR + ITD: increased forward brain flow and decreased intracerebral resistance, allowing more time for cerebral perfusion.
Insulin-Like Growth Factors
Authors: Derek Le Roith
Journal: New England Journal of Medicine (1997)

The insulin-like growth factors (IGFs) participate in the growth and function of almost every organ in the body.1 Because of the wide range of their biologic effects and their therapeutic potential in a variety of clinical disorders, the IGFs have become the focus of research by an increasing number of investigators.24 The object of this seminar is to review the clinical aspects of the IGFs, including their potential therapeutic value, and to discuss briefly their structure, synthesis, regulation, and physiologic role.Basic Biochemistry and Physiologic FunctionsStructure and SynthesisThe three peptide hormones, or growth factors, in the IGF . . .
Abstract 623: GRK5 Regulates NFkB Transcription Activity in Endothelial Cells
Authors: Daniela Sorriento, Bruno Trimarco, Guido Iaccarino
Journal: Circulation (2006)

NFkB stimulates the transcription of VEGF in response to G protein coupled receptor stimulation. G protein-coupled receptors signalling is regulated by phosphorylation by G protein-coupled receptor kinases (GRKs), a family of seven serine/threonine protein kinases. Recent studies suggest the hypothesis that these kinases play multiple roles in regulating signalling. In particolar, GRK5 is able to enter the nucleus through functional nuclear localization (NLS) and exporting (NES) sequences. We have assessed the hypothesis that GRK5 regulates transcription events in the nucleus, in particular NFkB activity. In bovine aortic endothelial cells (BAEC) GRK5 associates to IkB, a NFkB inhibitor, and such interaction increases in presence of isoproterenol, β adrenergic agonist, 10 –7 M. In BAEC GRK5 overexpression causes nuclear accumulation of IkB, suggesting a possible role for GRK5 to inhibit NFkB activity. To confirm the functional implication of such interaction we used luciferase as reporter gene under the control of a NFkB-dependent promoter. GRK5 overexpression inhibits NFkB activity both in presence and absence of isoproterenol, TNFα and LPS. These data suggest an universal role of GRK5 to inhibit NFkB transcriptional activity in response to different signal transduction pathways. To evaluate the role of NLS and NES in GRK5-IkB interaction, we overexpressed GRK5 mutants lacking either NLS or NES sequences (GRK5γNLS and GRK5γNES). Both GRK5γNLS and GRK5γNES overexpression results in inhibition of NFkB activity (GRK5: -73±16%; GRK5γNLS: -42±6%; GRK5γNES: -67±12%, vs control) and nuclear accumulation of IkB thus suggesting that GRK5-IkB interaction depends on other GRK5 domains. Immunoprecipitation studies with overexpression of small peptides reproducing single domains of GRK5 (N-CAM, RGS, Catalytic domain, C-CAM) suggest that RGS is the GRK5 domain that associates to IkB. In conclusion, these results reveal a novel role of GRK5 as modulator of the activity of an important transcription factor, NFkB, that will be object of future investigations in cardiovascular disease models
Abstract 5956: Modulation of Urocortin 2 Contractile EFFects by Endocardial Endothelium
Authors: Carmen Bras-Silva, Ana Patrícia Fontes-Sousa, Mónica Almeida, Susana Mendes, Adelino F Leite-Moreira
Journal: Circulation (2008)

Purpose: The urocortin (Ucn) peptides Ucn1, Ucn2, and Ucn3 are recently isolated members of the corticotropin-releasing factor family. Ucn2 promotes positive inotropic and lusitropic effects and both endothelium-dependent and -independent vasodilatation. In the current study, we investigated the modulation of Ucn2 contractile effects by endocardial endothelium (EE). Methods: The effects of increasing concentrations of Ucn2 (10 –10 to 10 – 6M) were evaluated in isolated right papillary muscles (Krebs-Ringer: 1.8mM CaCl2, 35°C) with intact EE (n=11) and after damaging EE (0.5% Triton X-100, n=12). Reported parameters include: active tension (AT; mN/mm2) and maximum velocities of tension rise and tension decline (dT/dtmax and dT/dtmin, respectively; mN/mm2/s). Only significant results (mean±SEM, p&lt;0.05) are given, expressed as % change from baseline. Results: Ucn2 induced concentration-dependent positive inotropic and lusitropic effects in muscles with intact EE (at 10 – 6M it increased 65.6±5.2% AT, 196.9±16.7 dT/dtmax and 145.0±13.5% dT/dtmin). These effects were potentiated in papillary muscles with damaged EE. In this condition, the higher concentration of Ucn2 increased 169.1±39.2% AT, 412.5±43.9% dT/dtmax and 296.7±56.7%dT/dtmin. Conclusions: This study shows that the positive inotropic and lusitropic effects induced by Ucn2 are enhanced in the presence of endocardial endothelial dysfunction. These findings reinforce the importance of Ucn2 in the regulation of myocardial function and provide new elements for the comprehension of the pathophysiology of HF, a condition where Ucn2 levels are increased and endothelial dysfunction might be present.
Abstract 6: Inequitable Distribution of Implantable Cardioverter-Defibrillators in Ontario, Canada
Authors: Jacob A Udell, David N Juurlink, Alexander Kopp, Douglas S Lee, Jack V Tu, Muhammad M Mamdani
Journal: Circulation (2006)

BACKGROUND: Implantable cardioverter defibrillator (ICD) therapy reduces the risk of sudden death in patients with ischemic cardiomyopathy but their novelty and cost may represent barriers to utili...
Abstract 1913: Ezetimibe Effectively Prevents Atherosclerotic Plaque Formation as Demonstrated by High Field MRI
Authors: Thore Dietrich, Cosima Jahnke, Ingo Paetsch, Kirstin Atrott, Philipp Stawowy, Bernhard Schnackenburg, Kristof Graf
Journal: Circulation (2007)

Aim: To evaluate the effect of Ezetimibe (EZE) treatment on atherosclerotic plaque formation in apoE deficient (apoE−/−) mice and to determine changes in plaque size detectable by high field magnet...
Discontinuation of benzodiazepine treatment: efficacy of cognitive- behavioral therapy for patients with panic disorder
Authors: Michael W. Otto, Mark H. Pollack, Gary S. Sachs, Stewart R. Reiter, Samantha Meltzer-Brody, Jerrold F. Rosenbaum
Journal: American Journal of Psychiatry (1993)

The primary disadvantage of high-potency benzodiazepine treatment for panic disorder is the difficulty of discontinuing the treatment. During treatment discontinuation, new symptoms may emerge and anxiety may return, preventing many patients from successfully discontinuing their treatment. In this controlled, randomized trial the authors investigated the efficacy of a cognitive-behavioral program for patients with panic disorder who were attempting to discontinue treatment with high-potency benzodiazepines.Outpatients treated for panic disorder with alprazolam or clonazepam for a minimum of 6 months and expressing a desire to stop taking the medication (N = 33) were randomly assigned to one of two taper conditions: a slow taper condition alone or a slow taper condition in conjunction with 10 weeks of group cognitive-behavioral therapy.The rate of successful discontinuation of benzodiazepine treatment was significantly higher for the patients receiving the cognitive-behavioral program (13 of 17; 76%) than for the patients receiving the slow taper program alone (four of 16; 25%). There was no difference in the likelihood of discontinuation success between the patients treated with alprazolam and those who received clonazepam. At the 3-month follow-up evaluation, 77% of the patients in the cognitive-behavioral program who successfully discontinued benzodiazepine treatment remained benzodiazepine free.These findings support the efficacy of cognitive-behavioral interventions in aiding benzodiazepine discontinuation for patients with panic disorder.
Pathological response to neoadjuvant 5-FU, oxaliplatin, and docetaxel (FLOT) versus epirubicin, cisplatin, and 5-FU (ECF) in patients with locally advanced, resectable gastric/esophagogastric junction (EGJ) cancer: Data from the phase II part of the FLOT4 phase III study of the AIO.
Authors: Claudia Pauligk, Andrea Tannapfel, Johannes Meiler, Kim Barbara Luley, Hans-Georg Kopp, Nils Homann, Ralf Dieter Hofheinz, Harald Schmalenberg, Stephan Probst, Georg Martin Haag, Matthias Egger, Dirk M. Behringer, Jan Stoehlmacher, Nicole Prasnikar, Andreas Block, Jorg Trojan, Michael Koenigsmann, Wolff Schmiegel, Elke Jäger, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2015)

4016 Background: Pathological response can be a potent surrogate factor for efficacy of neoadjuvant chemotherapy. Data from our phase II/III study comparing perioperative FLOT with ECF(X) in resectable stages were analyzed for pathological response upon request of the German Cancer Aid in order to further sponsor the trial. Methods: In the FLOT4, 714 patients (pts) are stratified and randomized to either 3+3 perioperative cycles of ECF/ECX (epirubicin 50 mg/m2, d1; cisplatin 60 mg/m², d1; 5-FU 200 mg/m² (or capecitabine 1250 mg/m² p.o) d1-d21, qd21) or 4+4 cycles of perioperative FLOT (docetaxel 50mg/m2, d1; 5-FU 2600 mg/m², d1; leucovorin 200 mg/m², d1; oxaliplatin 85 mg/m², d1, qd14). Central pathology (by AT) is performed according to Becker classification. Results: Samples of 157 pts of the phase-II part of the study were analyzed. Median age was 63 yrs; 79.6% of pts were male. The primaries were gastric in 43.3%, EGJ in 56.1% and not evaluable in 0.6% of pts. In the most relevant categories complete (CR) and subtotal (SR) histopathological response, FLOT was superior to ECF with CR 12.8% vs. 5.1% and SR 16.7% vs. 10.1%, respectively, with statistical significance for CR+SR (FLOT, 29.5% vs. ECF, 15.2%, p = .036). Also, significantly more pts in the ECF-arm had no pathological regression or even did not reach surgery (ECF, 41.8% vs. FLOT, 24.4%; p = .027). See also Table. Conclusions: Perioperative FLOT shows more pathological remissions (CR + SR) than ECF/ECX in patients with resectable gastric cancer. Clinical trial information: NCT01216644.
Abstract 8230: Arachidonic 12-lipoxygenase-induced Inflammation Promotes The Development Of Diabetic Cardiomyopathy
Authors: Yosuke Kayama, Masaya Sakamoto, Hirofumi Suzuki, Taro Date, Tohru Minamino, Issei Komuro, Michihiro Yoshimura
Journal: Circulation (2011)

Diabetic mellitus increases the risk of heart failure independently of underlying coronary artery disease, and many believe that diabetes leads to cardiomyopathy. The underlying pathogenesis is partially understood, but precise mechanism underlying diabetic cardiomyopathy is still unknown. To investigate the molecular mechanisms of diabetic cardiomyopathy, we created a diabetic cardiomyopathy model (streptozotocin (STZ) injection rat) and performed microarray analysis. Echocardiography showed that STZ injection rat developed diastolic and systolic dysfunction and cardiac fibrosis was increased in STZ injection rat. Among the genes analyzed, arachidonic 12-lipoxygenase (12-LOX) was upregulated in the heart of STZ rat. Northern blotting and ELISA analysis demonstrated that mRNA level of 12-LOX and production of 12(s)-HETE, a major metabolite of 12-LOX, were upregulated in the heart of STZ rat compared to those of control rat heart. Until recently, 12-LOX has been reported to play an important role in the development of atherogenesis, diabetes, and neurogenerative disease. However, the role of 12-LOX in diabetic cardiomyopathy has not been examined. To determine the role of 12-LOX in STZ injection heart, we created STZ injection mice (WT-STZ) and compared to those of 12-LOX KO (KO-STZ) mice. Disruption of 12-LOX significantly reduced cardiac fibrosis and improving diastolic and systolic dysfunction. Moreover the expression of inflammatory cytokine genes such as MCP-1 and TNF-α and STZ-induced reactive oxygen species were significantly inhibited by disruption of 12-LOX. In vitro experiment reveal that hyperglycemia induced expression of 12-LOX as well as MCP-1 and TNF-α by neonatal cardiomyocyte. Treatment with Cinnamy1-3,4-dihydroxy-α-cyanocinnamate (CDC) , a inhibitor of 12-LOX, decreased the expression of MCP-1 and TNF-α by cardiomyocyte under high glucose stimulation. Our results suggest that cardiac 12-LOX-induced inflammation is involved in the development of diabetic cardiomyopathy and that inhibition of 12-LOX could be a novel treatment for this condition.
Predictors of colon cancer screening among low-income urban minority residents: The Cancer Risk Assessment in Baltimore (CRAB) Study
Authors: R. A. Mentor-Marcel, K. Visvanathan, M. A. Garza, Y. Xie, L. McCaffrey, J. G. Ford
Journal: Journal of Clinical Oncology (2007)

4101 Background: Colorectal cancer mortality can be reduced through early detection, using recommended screening tests (fecal occult blood test (FOBT), sigmoidoscopy, or colonoscopy). However, screening is underutilized, especially among low-income and racial/ethnic minority groups. Few studies have examined determinants of screening in these groups. Methods: We analyzed data on predictors of colon cancer screening from a cross-sectional study of Baltimore City Residents (N = 534). Participants responded to a questionnaire administered by an interviewer, on screening practices, behavioral, social and demographic factors, including income level. Eligible respondents for this analysis were age = 50, aware of colorectal screening tests, but not diagnosed with colon polyps or cancer. Multivariate techniques were used to examine predictors of having undergone any recommended colon cancer screening test. Results: The eligible population for this analysis (N=202) was 49.0 % male and 51.0 % female. The median income fell within the $12,000-$24,999 bracket. The proportion of participants that had received colon cancer screening was 34.5 % among those in the highest income bracket (i.e. =$25,000) compared to 30.0 % in the lowest income bracket (i.e. =$11,999). This difference was statistically significant after adjusting for other sociodemographic factors (odds ratio (OR)=3.12, p=0.023). Multivariate analysis indicated that screening was associated with having one (OR: 3.56, p=0.016) or more than one (OR: 7.31, p=0.006) primary health care provider. Having health care coverage, a doctor who recommended exercise, and having at least some college education, were also associated with screening. Conclusions: Negative predictors of colorectal cancer screening include: extremely low income levels (= $11,999), lack of health care coverage, primary care providers, and college education level. Provider recommendations for healthy behaviors (e.g. exercise) are associated with patient adherence to recommended cancer screenings. The design of interventions to promote use of screening tests by low-income populations should be informed by the substantial heterogeneity in patient and provider characteristics within these populations. No significant financial relationships to disclose.
Characterization of human skeletal muscle in weight-losing pancreatic cancer patients
Authors: J. M. Brell, J. Hardacre, J. Schulak, R. Onders, T. Stellato, J. Sanabria, M. Schulchter, L. Strickland, R. Sprosty, J. Pink
Journal: Journal of Clinical Oncology (2009)

9571 Background: Decreased body mass (cachexia) is a common cause of functional decline in pancreas carcinoma (PC) and other malignancies. The etiology is unknown. Characterization of human PC skeletal muscle, in regard to proteolysis and gene expression, compared to control muscle may reveal information about pathophysiology. Methods: Biopsies of rectus abdominus muscle were performed in weight-losing PC patients all stages (A) during cancer-related surgery and in cancer-free controls undergoing ventral hernia repair (B). Caspase-3, pAkt, and urinary 3-methylhistidine (u3-MH) were assessed by Western blot and high-performance liquid chromatography. Fat-free mass (FFM), body mass index (BMI), and time to progression were recorded. Muscle from five patients (median weight loss 21%) and five controls were analyzed for gene expression patterns using Affymetrix Human Genome U133 A 2.0 array chip. Two hundred differentially over- and under-expressed genes were examined in group A for potential association with cachexia. RT-PCR confirmation of six candidate genes was performed. Results: Thirty-eight patients were enrolled. Median weight loss in group A (N=27) was 14.5% (5% - 34%). No differences were noted between groups in caspase-3 and pAkt expression. Baseline u3-MH (p=0.86) and FFM (p= 0.28) did not differ; baseline BMI was lower in group A (p=0.04). BMI follow-up measurements (N=17) were significantly decreased (p=0.0005). In 65% patients, progressive disease was noted within median time of 3 months. RT-PCR established up-regulation of CHRNA1 and LMO7, but not GDF8. mRNA down-regulation for TRIM63, IGF-BP6, and MYH-1 was confirmed. Conclusions: Muscle proteolysis in human PC skeletal muscle was not demonstrated, perhaps due to unmeasurable proteolysis or use of non-informative endpoints. BMI decreased in group A with PD; further studies need tight control of BMI variables. New hypotheses about cachexia include neuromuscular junction dysfunction, as CHRNA1 has specific role in ion channel gating; this is disrupted in the paraneoplastic Eaton-Lambert syndrome. This is first study analyzing human muscle in weight-losing PC and proves symptom management multidisciplinary research is feasible in academic setting. Supported by American Cancer Society pilot grant. No significant financial relationships to disclose.
Abstract 367: Identification of the VNN1 Gene as a Novel CVD Risk Factor
Authors: Eric K Moses, Joanne E Curran, Matthew P Johnson, Harald H Goring, Thomas D Dyer, Jac Charlesworth, Shelley A Cole, Jeremy B Jowett, Lawrence A Abraham, David L Rainwater, Michael C Mahaney, Laura Almasy, Jean W MacCluer, Ahmed H Kissebah, Gregory R Collier, John Blangero
Journal: Circulation (2007)
Abstract 15972: Laparoscopic Surgery in a Young Patient With a Preexisting Patent Foramen Ovale and a Large Right-to-Left Shunt: Should a Fatal Outcome Change Our Clinical Practice?
Authors: Linda Seaver, Timothy E. Paterick, Bijoy K. Khandheria, Khawaja Afzal Ammar
Journal: Circulation (2013)

Introduction: Air embolism during laparoscopic surgery is common, but fatality is rare. There are multiple mechanisms, including pulmonary hypertension from air in the pulmonary circulation. This l...
Sequence-based and monoclonal antibody typing of Legionella pneumophila isolated from patients in Portugal during 1987-2008
Authors: M J Chasqueira, L Rodrigues, M Nascimento, T Marques
Journal: Eurosurveillance (2009)

The monoclonal antibodies and the sequence-based typing (SBT) are two methodologies widely used to characterise Legionella pneumophila strains serogroup 1 (sg1). In this study, we analysed the clinical strains received in two Portuguese laboratories since 1987, including the strains isolated in Portugal during the four years of the surveillance scheme for Legionnaires' disease implemented in 2004. In total, 63 clinical isolates of L. pneumophila sg1 were differentiated by SBT into 19 different sequence types. Ten of them were new in the SBT database of the European Working Group for Legionella Infections (EWGLI). As a result of the combination of the two methodologies, these strains were discriminated into 25 different profiles. This study enabled, for the first time in Portugal, not only to characterise the L. pneumophila sg1 clinical isolates, but also to create a database of Portuguese profiles for use in epidemiological surveillance efforts.
Abstract 172: Improved Outcomes of Cardiac Arrest in a State-Wide Integrated Resuscitation Program: Results From the Minnesota Resuscitation Consortium
Authors: Demetris Yannopoiulos, Selcuk Adabag, Lucinda Klann, Charles Lick, Brian Mahoney, Ralph J Frascone, Marc Conterato, Michael Mooney, Santiago Garcia, Kim Harkins
Journal: Circulation (2013)
Abstract 4774: Neutrophil/Lymphocyte Ratio as a Predictor of New-Onset Atrial Fibrillation Following Coronary Artery Bypass Grafting
Authors: Patrick H Gibson, Bernard L Croal, Brian H Cuthbertson, Daniela Rae, Robert R Jeffrey, Keith G Buchan, Hussein El-Shafei, George A Gibson, Graham S Hillis
Journal: Circulation (2008)

Introduction. Atrial fibrillation (AF) is a common complication in patients undergoing coronary artery bypass grafting (CABG). Prior studies demonstrate an association between peri-operative inflam...
Abstract 4712: Necrotic Core Touching the Lumen is Most Frequently Exposed to High Shear Stress in Advanced Disease
Authors: Jolanda J Wentzel, Johan C Schuurbiers, Nieves Gonzalo Lopez, Frank J Gijsen, Jurgen Ligthart, Alina G van der Giessen, Harald C Groen, Jouke Dijkstra, Patrick W Serruys
Journal: Circulation (2009)