tbuckley/cabot-search huggingface dataset:
Abstract 677: The PPARdelta Agonist GW501516: Influence on Features of the Metabolic Syndrome
Authors: Dennis L Sprecher, Ulf Riserus, Sandra Hirschberg, David Hassall, Eric J Olson, Lea Sarov-Blat, Stephen O’Rahilly, Timothy M Willson, Peter Murgatroyd, Anthony Johnson, Keith Frayn, Fredrik Karpe
Journal: Circulation (2007)

Hypertriglyceridemia and insulin resistance in the setting of obesity, i.e. the metabolic syndrome, are thought related to ectopic fat storage and impaired regulation of fat oxidation. Rodent models suggest that increased PPARdelta function may correct these abnormalities. Design/Methods: Double-blind, randomized, 3-parallel group (n = 6 in each group), 2-week study of PPARdelta agonist ( GW501516 –10mg), PPARalpha agonist ( GW590735 –20ug) and placebo. Men with a waist &gt; 95cm, BMI &gt; 27, TG &gt; 100mg/dl &lt; 400mg/dl, and HDLc &lt; 50 mg/dl were included. Blood lipids, fatty acids, serum insulin and liver fat content (MRI) were measured at baseline and termination of study, while oral 13 C-palmitate-labeled fat-feeding allowed post-meal examination of plasma NEFA metabolism and oxidation ( 13 CO 2 exhalation). Skeletal muscle biopsies were taken to monitor transcript regulation of fat oxidation pathways. Results: The PPARdelta group revealed reduction of LDLc, apoB and TG by 23%, 21%, and 31%, respectively and of plasma NEFA, without any deterioration of insulin and glucose homeostasis. Comparable TG reduction in PPARalpha (27%), with modest apoB reductions (−13%) were not accompanied by NEFA reductions. Hepatic fat was significantly reduced in the PPARdelta group only (p = 0.04). After the labeled fat meal, cumulative exhaled 13 CO 2 was increased (p = 0.03; enhanced fat catabolism) and accompanied by increased mRNA expression of skeletal muscle CPT1b only in the PPARδ group. Summary: Short term administration of a selective PPARdelta agonist decreased TG, apoB, LDL-C and NEFA concentrations. Increased peripheral fatty acid uptake and oxidation may partly explain these benefits.
Abstract 15196: Dipeptidyl peptidase IV Inhibition Improves Cardiorenal Function in Pacing-Induced Heart Failure
Authors: Kathleen Mc Entee, Nelson Gomez, Karim Touihri, Veerle Matheeussen, Myrielle Mathieu, Agnes Mendes Da Costa, Simon Scharpe, Ingrid De Meester, Jozef Bartunek, Marc Vanderheyden
Journal: Circulation (2010)
Abstract 142: Augmentation of Negative Intrathoracic Pressure Improves Hemodynamics Without Popping the Clot: A Randomized Study Comparing an Impedance Threshold Device vs Saline to Treat Severe Hemorrhage Through Permissive Hypotension in a Spontaneously Breathing Porcine Model
Authors: Anja Metzger, Jennifer Rees, Scott McKnite, Nicolas Segal, Timothy Matsuura, Victor Convertino, Keith Lurie
Journal: Circulation (2011)

Objective: An evolving concept in the field of trauma care is the prehospital management of shock associated with uncontrolled hemorrhage. Traditional prehospital care includes early and aggressive...
First-Line management of CML: a state of the art review.
Authors: Andreas Hochhaus
Journal: Journal of the National Comprehensive Cancer Network (2008)

With the advent of imatinib, an inhibitor of the fusion Bcl-Abl tyrosine kinase that is responsible for the disease phenotype, first-line treatment of chronic myelogenous leukemia (CML) has undergone rapid changes. As a consequence of the success of imatinib, allogeneic stem cell transplantation (allo-SCT) has moved from the first-line indication to an option that is usually considered for patients without optimal response to imatinib or those for whom treatment with imatinib has failed. First-line use of interferon-alpha (IFN-alpha), with or without cytarabine or hydroxyurea, is now rarely considered. Most patients with newly diagnosed chronic-phase CML experience complete cytogenetic responses during imatinib treatment, but continued treatment is necessary to prevent cytogenetic or molecular relapse. Cumulative evidence with imatinib and IFN-alpha show that experiencing early and deep responses is important in preventing progression to more advanced phases of the disease. These features emphasize the need to carefully monitor patients for residual disease and provide guidance on treatment options in the event of imatinib intolerance or failure. This article reviews the current role of allo-SCT, imatinib, and IFN-alpha in treating newly diagnosed chronic-phase CML, highlighting the benefits and challenges of long-term patient management, and discusses emerging trends.
Outcome Comparison of 600- and 300-mg Loading Doses of Clopidogrel in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction
Authors: Giuseppe Patti, György Bárczi, Dejan Orlic, Fabio Mangiacapra, Giuseppe Colonna, Vincenzo Pasceri, Emanuele Barbato, Béla Merkely, István Édes, Miodrag Ostojic, William Wijns, Germano Di Sciascio
Journal: Journal of the American College of Cardiology (2011)
End celebrity endorsement of screening, say researchers
Authors: Ray Moynihan, Liz Jakubowski
Journal: BMJ (2005)

T he convict tradition runs deep down under. When a company promoting full body computed tomography was looking for a celebrity to help sell its wares, it turned to the star of that highly successful Aussie soap opera Prisoner, Val Lehman. So on any given Sunday morning this year, many Australians leisurely flicking through the papers have found themselves face to face with the daunting image of prison heavyweight character Bea Smith urging them to go out and get screened for everything. Likewise, former Ashes winning Australian cricket captain Alan Border has been brought in to bat for an advertisement series on body scans.

Sadly for Val and Alan, the image of full body computed tomography has become a little tarnished in Australia and elsewhere. Indeed, an Australian state health authority was so concerned about the failure to properly communicate risks and benefits in some of the promotion that it issued a public health alert in 2004: “Full body scans… involve doses of radiation that health experts do not consider to be justifiable in terms of a health check.”

Until now we have had no real idea what sort of impact celebrities like Val Lehman and Alan Border have on those sleepy Sydneysiders reading their Sunday papers. Now a snappy little study just published …
Sex reassignment surgery: historical, bioethical, and theoretical issues
Authors: L M Lothstein
Journal: American Journal of Psychiatry (1982)

The reported 68%-86% overall success rates for sex reassignment surgery must be viewed cautiously; the lack of long-term follow-up studies makes these statistics misleading. There is evidence suggesting that some gender dysphoric patients benefit primarily from sex reassignment surgery. Most such patients, however, are secondary transsexuals who can benefit from various modes of psychotherapy. Sex reassignment surgery should only be considered as the last resort for a highly select group of diagnosed gender dysphoric patients. As physicians learn new ways to diagnose and treat transsexualism, either sex reassignment surgery will be abandoned as a routine treatment modality or new predictive variables for choosing suitable patients for sex reassignment surgery will be established.
妊娠糖尿病治疗的效果：系统性回顾和荟萃分析（摘要）
Authors: Karl, Horvath, Klaus, Koch, Jeifler, Eva, Matyas, Bender, Hilda, Bastian, Stefan, Lange, Andrea, Siebenhofer, 高非, 包玉倩
Journal: BMJ (2010)

目的 概述妊娠糖尿病治疗的利弊。 设计 随机对照试验的系统回顾和荟萃分析。 数据来源 2009年10月之前Ernbase、Medline、AMED、BIOSIS、CCMed、CDMS、CDSR、CENTRAL、CINAHL、DARE、HTA、NHSEED、Heclinet、SciSearch发布的数据库（Hogrefe、Karger、Kluwer、Krause和Pachemegg、Springer、Thieme）以及相关的二次引用文献。
Diagnosis of Duchenne and Becker Muscular Dystrophies by Polymerase Chain Reaction
Authors: J S Chamberlain, J R Chamberlain, R G Fenwick, P A Ward, C T Caskey, L S Dimnik, N T Bech-Hansen, D I Hoar, S Richards, A E Covone, R Govanni, S Abbs, D R Bentley, M Bobrow, G Rysiecki, P N Ray, C Boileau, C Junien, C Boehm, V L Venne, F K Fujmura, I Spiga, M Ferrari, S Tedeschi, E Bakker, A L Kneppers, G J van Ommen, K Jain, E Spector, B Crandall, A Kiuru, M L Savontaus, C T Caskey, J S Chamberlain, J R Chamberlain, G Rysiecki
Journal: JAMA (1992)

OBJECTIVE--To assess the efficiency, reliability, and ease of use of DNA diagnosis for Duchenne and Becker muscular dystrophies (DMD/BMD) using the polymerase chain reaction (PCR). DESIGN--DNA from the patients was screened for deletion mutations using multiplex PCR, and the results were compared with those obtained by Southern blot analysis. The PCR multiplex reaction detects nine specific "hot-spot" exons in the dystrophin gene while the Southern analysis detects 66 specific dystrophin gene restriction fragments. The multiplex reaction requires 50-fold less DNA than Southern analysis and thus is considerably more sensitive. SETTING--Fourteen university-affiliated and private genetic disease diagnostic laboratories. PATIENTS--Male patients with clinical signs of DMD/BMD. Cases were selected for analysis randomly, without knowledge of whether a deletion was present within the dystrophin gene. MAIN OUTCOME MEASURES--The percentage of cases that were detectable by multiplex PCR in comparison with Southern analysis, the frequency, extent, and location of the detected deletion mutations. In some cases, duplication mutations were monitored. RESULTS--The accuracy of a single PCR multiplex amplification (nine exons) was compared with Southern analysis with 10 cDNA probes that cover the full length of the gene. The multiplex PCR analytic method detected 82% of those deletions detected by Southern analysis methods. In one of 745 analyses, the multiplex method suggested a single exon deletion, which was not confirmed by Southern analysis, representing a false-positive rate of 0.013%. CONCLUSIONS--Multiplex PCR represents a sensitive and accurate method for deletion detection of 46% of all cases of DMD/BMD. The method requires 1 day for analysis, is easy to perform, and does not use radioactive tracers. As such, multiplex PCR represents an efficient and rapid method for prenatal or postnatal diagnosis of DMD/BMD.
Abstract 2410: Out-of-Hospital Surface Cooling With a Cooling-Blanket to Induce Mild Hypothermia in Humans after Cardiac Arrest. A Feasibility Trial.
Authors: Thomas Uray, Reinhard Malzer, Fritz Sterz, Jasmin Arrich, Roman Fleischhackl, Andreas Janata, Michael Holzer, Anton N Laggner, Wilhelm Behringer
Journal: Circulation (2007)
Role of performance status and comorbidities as predictors of toxicity of adjuvant chemotherapy in elderly breast cancer patients
Authors: P. Garg, F. Rana, T. H. Guthrie
Journal: Journal of Clinical Oncology (2008)

610 Background: Women older than 70 years have been underrepresented in breast cancer adjuvant chemotherapy trials due to concerns about toxicity, safety and tolerance of chemotherapy. The aim of our study was to assess the impact of performance status score and Charlson comorbidity index in elderly breast cancer patients treated with adjuvant chemotherapy. Methods: Retrospective chart review of early-stage (stages 1 and 2) breast cancer patients older than 70 years from 1998 to 2004. Patients who underwent surgery followed by adjuvant chemotherapy were included. Patients with metastatic disease, recurrent disease or prior chemotherapy were excluded. Results: A total of 62 patients, with mean age of 74.3 years, were identified. Chemotherapy was completed in 89% patients. Overall 79% completed chemotherapy without any significant side effects, dose reductions or breaks during chemotherapy. Using logistic regression model increasing age is not associated with early termination of chemotherapy (p=0.19, OR- 0.868, 95% CI- 0.7–1.076). However, increasing age, higher functional status and comorbidity index scores were associated with reduction in dose and breaks in chemotherapy. None of the patients who received pegfilgrastim prophylactically developed high-grade neutropenia. Conclusions: Our study suggests that adjuvant chemotherapy is safe in elderly patients. Patients with good functional status and low comorbidity index scores tolerate chemotherapy as well as the younger patients. Prophylactic use of pegfilgrastim may reduce occurrence of severe neutropenia and related toxicity such as febrile neutropenia in the elderly patient. No significant financial relationships to disclose.
Fodor's frame problem and relevance theory - Response
Authors: D Sperber, D Wilson
Journal: Behavioral and Brain Sciences (1996)

Chiappe & Kukla argue that relevance theory fails to solve the frame problem as defined by Fodor. They are right. They are wrong, however, to take Fodor's frame problem too seriously. Fodor's concerns, on the other hand, even though they are wrongly framed, are worth addressing. We argue that relevance theory helps address them.
Abstract 3: Administration of Injectable Oxygen Suspension Rapidly Reverses Hypoxemia via Intravenous or Intraosseous Route
Authors: John Kheir, James Reese, Katie Black, Laurie Scharp, Tony Velazquez, Lauren Danforth, Julie Cronin, Catherine Dowling, Francis McGowan
Journal: Circulation (2011)

Introduction. Hypoxemia contributes to cellular dysfunction and death in a number of critical illness states. We investigated the possibility of rapidly reversing severe hypoxemia using intravenous and intraosseous infusions of lipid-based oxygen microparticles (LOMs). Hypothesis. Arterial oxygen tensions will increase during administration of LOMs via the intravenous or intraosseous route in a rabbit model of hypoxic ventilation. Methods. We manufactured LOMs from a lipid-based solution and oxygen gas. LOM diameter was determined by light scatter and oxygen content was determined by weight differential of a set volume of suspension. Adult New Zealand rabbits were anesthetized, paralyzed and mechanically ventilated. We placed venous, arterial and intraosseous lines. Hypoxemia was induced by ventilation with 10% oxygen. Following observation for 2 minutes, infusions of LOMs were administered at varying rates over a 2 minute period via either intravenous (n=5) or intraosseous line (n=9), followed by a 1 minute observation period. Endpoints included oxyhemoglobin saturations by pulse oximetry and arterial blood gas values drawn every 30 seconds. Endpoints during infusions were compared over time using a Friedman test. Results. LOM suspensions contained 52.8±3.0 mL of oxygen gas per dL of suspension. Mean particle diameter was 6.42 microns. Oxyhemoglobin saturation by pulse oximeter rose rapidly in a dose-dependent fashion in both intravenous and intraosseous infusions (Fig A). Relative to baseline measures, arterial PO2 (Fig B) and oxyhemoglobin saturation by co-oximeter (Fig C) increased during both IV and IO infusions (PaO2 p&lt;0.0001 IO; SaO2 p&lt;0.05 IV, p&lt;0.0001 IO). There was a non-significant trend that the increase in oxyhemoglobin saturations was delayed in intraosseous infusions relative to intravenous infusions. Conclusion. Oxyhemoglobin saturation and oxygen tension can be acutely raised by intravenous or intraosseous infusion of LOMs.
Abstract B12: Circulating stroma-related molecules as potential biomarkers for pancreatic ductal adenocarcinoma
Authors: Dorina Belotti, Andrea Resovi, Giulia Taraboletti, Rita T. Lawlor, Aldo Scarpa, Raffaella Giavazzi
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options. Early diagnostic serological markers capable of detecting the disease in its asymptomatic early stage can change the fate of PDAC patients. PDAC is characterized by a relevant stroma formation. This study investigates the potential value of circulating stroma-related molecules as PDAC biomarkers. To select candidate stroma-associated biomarkers for pancreatic cancer, a review of literature regarding proteomic analysis of PDAC was performed. Eight proteomic studies of differentially expressed sera proteins in PDAC patients and in genetically engineered mice (GEM) developing cancer in the pancreas were analyzed and 176 proteins were identified as potential PDAC biomarkers. Of these, 61 were selected as potentially interesting based on: a) presence in at least 2 independent analysis and/or b) relation to tumor/stroma interaction by Gene Ontology. These included extracellular matrix proteins and proteolytic fragments, matrix-degrading enzymes and their inhibitors, growth factors and adhesion molecules. Among them, 37 proteins could be explored by ELISA (BioRad Bio-plex System) in plasma of 25 early stage PDAC patients and 16 control subjects. Fourteen molecules were significantly modulated, with ten molecules up-regulated and four down-regulated. This preliminary screening identified 14 potential plasma biomarkers. Specificity and sensitivity of these selected biomarkers are being validated on a larger number of PDAC patients and appropriate controls, including pancreatitis patients and on PDAC mouse models. A combination of some of these molecules might provide a useful tool for early PDAC diagnosis. Supported by AIRC grant n. 2172 Citation Format: Dorina Belotti, Andrea Resovi, Giulia Taraboletti, Rita T. Lawlor, Aldo Scarpa, Raffaella Giavazzi. Circulating stroma-related molecules as potential biomarkers for pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B12.
Burkitt Leukemia Involving Only the Bone Marrow Has a Better Prognosis Than Widespread Burkitt Lymphoma Involving the Bone Marrow in Adults
Authors: Joo Y Song, Girish Venkataraman, Yuri D. Fedoriw, Mir Alikhan, Young Kim, Dennis D. Weisenburger, Joyce Collins, Xueli Liu, Amy S. Duffield
Journal: Blood (2014)
A meta-analysis of results from two randomized, double-blind studies of denosumab versus zoledronic acid (ZA) for treatment of bone metastases.
Authors: A. Lipton, A. Stopeck, R. von Moos, D. H. Henry, G. E. Richardson, G. I. Rodriguez, H. P. Bourgeois, C. Ke, S. Jun, R. D. Dansey
Journal: Journal of Clinical Oncology (2010)

9015 Background: A metaanalysis of 2 pivotal trials evaluated the effect of denosumab treatment in a broad cancer population. Both studies were identically designed and analyzed, comparing denosumab vs ZA in delaying or preventing skeletal-related events (SRE) in patients with bone metastases, one in patients with breast cancer and the other in patients with advanced cancer (except breast or prostate cancer) or multiple myeloma. Methods: The effects of denosumab vs ZA were evaluated with respect to time to first on-study SRE for noninferiority (primary endpoint; synthesis method) and superiority (secondary endpoint, proportional hazards model) and time to first and subsequent SRE (secondary endpoint, superiority; Anderson-Gill approach). Results: Denosumab was superior to ZA in delaying the time to first on-study SRE by 17% (HR 0.83; 95% CI: 0.74, 0.92; P<0.0001 for noninferiority; P = 0.0008 for superiority). Median time to first on-study SRE was 21.1 months for ZA and was not reached for denosumab. Denosumab was also superior to ZA in delaying the time to first and subsequent on-study SRE (multiple event analysis) by 18% (rate ratio 0.82; 95% CI: 0.74, 0.91; P = 0.0003). Denosumab reduced the mean skeletal morbidity rate (SREs/year) vs ZA (0.64 vs 0.80; P = 0.0006). Overall rates of disease progression (HR 1.00; 95% CI: 0.92, 1.08; P = 0.90), survival (HR 0.95; 95% CI: 0.86, 1.05; P = 0.35), adverse events (AEs; 96% denosumab, 97% ZA), and serious AEs (53% denosumab, 56% ZA) were similar in both groups. Osteonecrosis of the jaw occurred in 30 (1.6%) denosumab patients and 25 (1.3%) ZA patients. ZA-treated patients had increased rates of AEs potentially associated with renal toxicity (6.5% denosumab, 9.6% ZA) and with acute phase reactions at 3 days (8.8% denosumab, 21.4% ZA). Conclusions: Denosumab was superior to ZA in delaying or preventing SREs across a broad cancer population with bone metastases. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, Novartis, Ortho Biotech, Roche, Watson Pharmaceuticals Amgen Amgen, Novartis, Ortho Biotech, Roche, Watson Pharmaceuticals Amgen, Novartis, Ortho Biotech, Watson Pharmaceuticals Novartis
Abstract 3119: Insulin Resistance is Associated with Impaired Flow-mediated Vasodilatation in a Multi-ethnic Population: The Northern Manhattan Study
Authors: Takuya Hasegawa, Marco R Di Tullio, Bernadette Boden-Albala, Zhezhen Jin, Mitchell S Elkind, Tanja Rundek, Ralph L Sacco, Shunichi Homma
Journal: Circulation (2008)

Background: Metabolic abnormalities, including diabetes mellitus, are associated with impaired endothelial function. However, the relationship between endothelial function and glucose metabolism has not been thoroughly investigated. Aim: We tested the hypothesis that insulin resistance is associated with impaired flow-mediated vasodilatation (FMD) in a population-based multi-ethnic cohort. Methods: As part of the Northern Manhattan Study, we measured fasting insulin levels and FMD during reactive hyperemia by high-resolution ultrasonography in 601 community participants without diabetes. General linear models were used to test the association of fasting insulin, as a surrogate maker of insulin resistance (IR), with FMD after adjusting for age, sex, race-ethnicity, waist circumference, systolic blood pressure, high-density lipoprotein cholesterol, smoking, and fasting glucose. Mean FMD was also compared among the following three subgroups: normal fasting glucose (NFG) with IR (NFG*IR+), NFG without IR (NFG*IR−), and impaired fasting glucose (IFG). IR was defined as the upper quartile of homeostasis model index of insulin resistance (HOMA-IR). Results: The mean age was 66±9 years; 43% were male, 15% white, 16% black, and 68% Hispanic. The mean HOMA-IR was 2.45±1.88. In multiple linear regression analyses, fasting insulin was inversely correlated with FMD (β= −0.05, SE=0.02, p=0.032), after adjustment for other covariates. Race-ethnicity was not a significant modifier of the association of fasting insulin with FMD. The mean FMD was greatest in NFG*IR− even after adjustment [FMD (95% CI) 6.28 (5.91– 6.64) for NFG*IR−, 5.21 (4.43–5.99) for NFG*IR+, and 5.04 (4.33–5.74) for IFG (p&lt;0.001)]. Conclusion: Insulin resistance was independently associated with impaired FMD. The impairment of FMD was also observed in subjects with insulin resistance even in the presence of normal fasting glucose. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont). Multivariate analysis of association of FMD with demographic and clinical variables