tbuckley/cabot-search huggingface dataset:
Identification of Serum Proton NMR Metabolomic Fingerprints Associated with Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis
Authors: Pierre Nahon, Roland Amathieu, Mohamed N. Triba, Nadia Bouchemal, Jean-Charles Nault, Marianne Ziol, Olivier Seror, Gilles Dhonneur, Jean-Claude Trinchet, Michel Beaugrand, Laurence Le Moyec
Journal: Clinical Cancer Research (2012)

Metabolomics depicts metabolic changes in biologic systems using a multiparametric analysis technique. This study assessed the metabolomic profiles of serum, obtained by proton nuclear magnetic resonance (NMR) spectroscopy, from cirrhotic patients with and without hepatocellular carcinoma (HCC).The study included 154 consecutive patients with compensated biopsy-proven alcoholic cirrhosis. Among these, 93 had cirrhosis without HCC, 28 had biopsy-proven HCC within the Milan criteria and were eligible for curative treatment (small HCC), and 33 had HCC outside the Milan criteria (large HCC). Proton spectra were acquired at 500 MHz. An orthogonal partial latent structure [orthogonal projection to latent structure (OPLS)] analysis model was built to discriminate large HCC spectra from cirrhotic spectra. Small HCC spectra were secondarily projected using previously built OPLS discriminant components.The OPLS model showed discrimination between cirrhotic and large HCC spectra. Metabolites that significantly increased with large HCC were glutamate, acetate, and N-acetyl glycoproteins, whereas metabolites that correlated with cirrhosis were lipids and glutamine. Projection of small HCC samples into the OPLS model showed a heterogeneous distribution between large HCC and cirrhotic samples. Small HCC patients with metabolomic profile similar to those of large HCC group had higher incidences of recurrence or death during follow-up.Serum NMR-based metabolomics identified metabolic fingerprints that could be specific to large HCC in cirrhotic livers. From a metabolomic standpoint, some patients with small HCC, who are eligible for curative treatments, seem to behave as patients with advanced cancerous disease. It would be useful to further prospectively investigate these patients to define a subgroup with a worse prognosis.
CARDIAC MAGNETIC RESONANCE IMAGING DERIVED RIGHT VENTRICULAR OUTFLOW TRACT SYSTOLIC FLOW ACCELERATION IS A USEFUL INDEX OF RIGHT VENTRICULAR FUNCTION IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION
Authors: Ki-Woon Kang, Hyuk-Jae Chang, Geu-Ru Hong, Dae-Hee Shin, So-Yeon Choi, Junghyun Choi, sahng lee
Journal: Journal of the American College of Cardiology (2012)
Optimal pacing strategy: from theoretical modelling to reality in 1500-m speed skating
Authors: F J Hettinga, J J De Koning, L J I Schmidt, N A C Wind, B R MacIntosh, C Foster
Journal: British Journal of Sports Medicine (2009)

Athletes are trained to choose the pace which is perceived to be correct during a specific effort, such as the 1500-m speed skating competition. The purpose of the present study was to "override" self-paced (SP) performance by instructing athletes to execute a theoretically optimal pacing profile.Seven national-level speed-skaters performed a SP 1500-m which was analysed by obtaining velocity (every 100 m) and body position (every 200 m) with video to calculate total mechanical power output. Together with gross efficiency and aerobic kinetics, obtained in separate trials, data were used to calculate aerobic and anaerobic power output profiles. An energy flow model was applied to SP, simulating a range of pacing strategies, and a theoretically optimal pacing profile was imposed in a second race (IM).Final time for IM was ∼2 s slower than SP. Total power distribution per lap differed, with a higher power over the first 300 m for IM (637.0 (49.4) vs 612.5 (50.0) W). Anaerobic parameters did not differ. The faster first lap resulted in a higher aerodynamic drag coefficient and perhaps a less effective push-off.Experienced athletes have a well-developed performance template, and changing pacing strategy towards a theoretically optimal fast start protocol had negative consequences on speed-skating technique and did not result in better performance.
Transforming Acidic Coiled-Coil-Containing Protein 2 (TACC2) in Human Breast Cancer, Expression Pattern and Clinical/Prognostic Relevance.
Authors: S. Cheng, S. Cheng, A. Douglas-Jones, R. Mansel, W. Jiang
Journal: Cancer Research (2009)

Abstract BACKGROUND: TACC2 is a member of the transforming acidic coiled-coil-containing protein family and is associated with the centrosome-spindle apparatus during cell cycling. In vivo, the TACC2 gene is expressed in various splice forms predominantly in postmitotic tissues, including heart, muscle, kidney, and brain. Recent work has shown that members of this family, including TACC2, may be involved in the progression of certain solid tumours. The aim of the current study was to identify the role of TACC2 in breast cancer and to establish if a prognostic relevance exists.MATERIALS AND METHODS: Fresh frozen primary human breast cancer tissues (n = 120) and non-neoplastic mammary tissues (n = 32) were used. The distribution and location of TACC2 was assessed using immunohistochemical staining (IHC) and imaging analysis tools. The transcript levels of TACC2 were determined using quantitative real time-PCR. The results were analyzed against the clinical, pathological and follow-up (10 years) data. Statistical analysis was by Mann-Whitney U test and Kaplan-Meier method. Shown are median transcript level.RESULTS: TACC2 protein staining was seen in both normal epithelial cells and cancer cells in mammary tissues. Increased staining of TACC2 was seen in most of the breast tumours examined when compared with normal breast tissues. Quantitative analysis of the TACC2 transcript also revealed a higher level expression in tumours compared with normal tissues (p=0.027, tumours vs normal). TACC2 expression was significantly increased in higher grade tumours compared to those in lower grade tumours (grade-3 vs grade-1, p=0.046). Using the Nottingham Prognostic Index (NPI), TACC2 transcript was significantly higher in tumours from patients with a moderate prognosis than from those with a good prognosis (p = 0.019). The expression in samples from patients with poor clinical outcome (with metastasis, recurrence and breast cancer related death) was significantly higher than that from patients who remained disease free (median (IQR) 33.8 (3.0-110.2) copies vs 6 (1.6-28.9) copies, p=0.038). This was reflected by the shorter disease-free survival for patients with high TACC2 (107 (91-122.8, 95% CI) months compared with 137 (125-150.6) months for patients with low TACC2 transcripts (p=0.019).CONCLUSION: This study shows that increased expression of TACC2 correlates with poor prognosis in patients with breast cancer. This suggests that TACC2 mediates an oncogenic effect on breast cancer cells. The findings also suggest that TACC2 may be a potential therapeutic target. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3159.
Interaction versus autonomy: A close shave
Authors: Wayne S. Murray
Journal: Behavioral and Brain Sciences (2000)

Approaches to model evaluation in terms of Occam's razor or principles of parsimony cannot avoid judgements about the relative importance of aspects of the models. Assumptions about “core processing” are usually considered more important than those related to decision components, but when the decision is related to a central feature of the processing, it becomes extremely difficult to tease apart the influences of core and decision components and to draw sensible conclusions about underlying architecture. It is preferable, where possible, to use experimental procedures that avoid the necessity for subject decisions related to critical aspects of the underlying process.
Genetics of lymphatic anomalies
Authors: Pascal Brouillard, Laurence Boon, Miikka Vikkula
Journal: Journal of Clinical Investigation (2014)

Lymphatic anomalies include a variety of developmental and/or functional defects affecting the lymphatic vessels: sporadic and familial forms of primary lymphedema, secondary lymphedema, chylothorax and chylous ascites, lymphatic malformations, and overgrowth syndromes with a lymphatic component. Germline mutations have been identified in at least 20 genes that encode proteins acting around VEGFR-3 signaling but also downstream of other tyrosine kinase receptors. These mutations exert their effects via the RAS/MAPK and the PI3K/AKT pathways and explain more than a quarter of the incidence of primary lymphedema, mostly of inherited forms. More common forms may also result from multigenic effects or post-zygotic mutations. Most of the corresponding murine knockouts are homozygous lethal, while heterozygotes are healthy, which suggests differences in human and murine physiology and the influence of other factors.
Reports from the 2010 Clinical and Translational Cancer Research Think Tank Meeting: Design Strategies for Personalized Therapy Trials
Authors: Donald A. Berry, Roy S. Herbst, Eric H. Rubin
Journal: Clinical Cancer Research (2012)

Abstract It has long been evident that cancer is a heterogeneous disease, but only relatively recently have we come to realize the extent of this heterogeneity. No single therapy is effective for every patient with tumors having the same histology. A clinical strategy based on a single-therapy approach results in overtreatment for the majority of patients. Biomarkers can be considered as knives that dissect the disease ever more finely. The future of clinical research will be based on learning whether certain therapies are more appropriate than others for biomarker-defined subsets of patients. Therapies will eventually be tailored to narrow biomarker subsets. The ability to determine which therapies are appropriate for which patients requires information from biological science as well as empirical evidence from clinical trials. Neither is easy to achieve. Here we describe some nascent approaches for designing clinical trials that are biomarker-based and adaptive. Our focus is on adaptive trials that address many questions at once. In a way, these clinical experiments are themselves part of a much larger experiment: learning how (or whether it is possible) to design experiments that match patients in small subsets of disease with therapies that are especially effective and possibly even curative for them. Clin Cancer Res; 18(3); 638–44. ©2012 AACR.
Safety and Efficacy of a Flexible Dosing Regimen of Ranibizumab in Neovascular Age-Related Macular Degeneration: The SUSTAIN Study
Authors: Frank G. Holz, Winfried Amoaku, Juan Donate, Robyn H. Guymer, Ulrich Kellner, Reinier O. Schlingemann, Andreas Weichselberger, Giovanni Staurenghi
Journal: Ophthalmology (2011)
Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial
Authors: F Follath, JGF Cleland, H Just, JGY Papp, H Scholz, K Peuhkurinen, VP Harjola, V Mitrovic, M Abdalla, E-P Sandell, L Lehtonen
Journal: The Lancet (2002)
Role of Extracellular RNA in Atherosclerotic Plaque Formation in Mice
Authors: Sakine Simsekyilmaz, Hector A. Cabrera-Fuentes, Svenja Meiler, Sawa Kostin, Yvonne Baumer, Elisa A. Liehn, Christian Weber, William A. Boisvert, Klaus T. Preissner, Alma Zernecke
Journal: Circulation (2013)

Atherosclerosis and vascular remodeling after injury are driven by inflammation and mononuclear cell infiltration. Extracellular RNA (eRNA) has recently been implicated to become enriched at sites of tissue damage and to act as a proinflammatory mediator. Here, we addressed the role of eRNA in high-fat diet-induced atherosclerosis and neointima formation after injury in atherosclerosis-prone mice.The presence of eRNA was revealed in atherosclerotic lesions from high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice in a time-progressive fashion. RNase activity in plasma increased within the first 2 weeks (44±9 versus 70±7 mU/mg protein; P=0.0012), followed by a decrease to levels below baseline after 4 weeks of high-fat diet (44±9 versus 12±2 mU/mg protein; P<0.0001). Exposure of bone marrow-derived macrophages to eRNA resulted in a concentration-dependent upregulation of the proinflammatory mediators tumor necrosis factor-α, arginase-2, interleukin-1β, interleukin-6, and interferon-γ. In a model of accelerated atherosclerosis after arterial injury in apolipoprotein E-deficient (ApoE(-/-)) mice, treatment with RNase1 diminished the increased plasma level of eRNA evidenced after injury. Likewise, RNase1 administration reduced neointima formation in comparison with vehicle-treated ApoE(-/-) controls (25.0±6.2 versus 46.9±6.9×10(3) μm(2), P=0.0339) and was associated with a significant decrease in plaque macrophage content. Functionally, RNase1 treatment impaired monocyte arrest on activated smooth muscle cells under flow conditions in vitro and inhibited leukocyte recruitment to injured carotid arteries in vivo.Because eRNA is associated with atherosclerotic lesions and contributes to inflammation-dependent plaque progression in atherosclerosis-prone mice, its targeting with RNase1 may serve as a new treatment option against atherosclerosis.
Chronic Hypoxia Stimulates Periarterial Sympathetic Nerve Development in Chicken Embryo
Authors: K. Ruijtenbeek, F. A. C. le Noble, G. M. J. Janssen, C. G. A. Kessels, G. E. Fazzi, C. E. Blanco, J. G. R. De Mey
Journal: Circulation (2000)

Background —Epidemiological findings suggest an association between low-for-age birth weight and the risk to develop coronary heart diseases in adulthood. During pregnancy, an imbalance between fetal demands and supply may result in permanent alterations of neuroendocrine development in the fetus. We evaluated whether chronic prenatal hypoxia increases arterial sympathetic innervation. Methods and Results —Chicken embryos were maintained from 0.3 to 0.9 of the 21-day incubation period under normoxic (21% O 2 ) or hypoxic conditions (15% O 2 ). At 0.9 incubation, the degree of sympathetic innervation of the embryonic femoral artery was determined by biochemical, histological, and functional (in vitro contractile reactivity) techniques. Chronic hypoxia increased embryonic mortality (32% versus 13%), reduced body weight (21.9±0.4 versus 25.4±0.6 g), increased femoral artery norepinephrine (NE) content (78.4±9.4 versus 57.5±5.0 pg/mm vessel length), and increased the density of periarterial sympathetic nerve fibers (14.4±0.7 versus 12.5±0.6 counts/10 4 μm 2 ). Arteries from hypoxic embryos were less sensitive to NE (pD 2 , 5.99±0.04 versus 6.21±0.10). In the presence of cocaine, however, differences in sensitivity were no longer present. In the embryonic heart, NE content (156.9±11.0 versus 108.1±14.7 pg/mg wet wt) was also increased after chronic hypoxia. Conclusions —In the chicken embryo, chronic moderate hypoxia leads to sympathetic hyperinnervation of the arterial system. In humans, an analogous mechanism may increase the risk for cardiovascular disease in adult life.
1290 SULFATASE-2 (SULF2) EXPRESSED IN HEPATOCYTES AND STROMAL CELLS CONTRIBUTES TO THE DEVELOPMENT OF STEATOSIS, THE PROGRESSION OF NAFLD TO FIBROSIS AND THE ADVANCEMENT OF CANCER
Authors: G.L. Patman, D. Televantou, A. Whitehead, A.-C. Piguet, J.F. Dufour, C.P. Day, A.D. Burt, D.A. Mann, H.L. Reeves
Journal: Journal of Hepatology (2013)
Measurement of respiratory impedance by forced oscillation: comparison of the standard and head generator methods
Authors: Y Iwatsubo, H Lorino, C Hubert, C Duvivier, R Peslin, Q T Pham, T Moreau, J J Hosselet, P Brochard
Journal: European Respiratory Journal (1994)

Physiological and clinical studies have shown that the standard method of measuring respiratory impedance by forced oscillation leads to less efficient control of the upper airway shunt effect than the head generator method. To test the effects of these two techniques in epidemiological studies, we compared, in a sample of 73 French agricultural workers, the values obtained with each method for five forced oscillation parameters: resistance, frequency dependence of resistance, inertance, compliance and resonant frequency. For these comparisons, subjects were classified according to four respiratory status factors: smoking status, cough, expectoration and airway obstruction assessed from the maximum expiratory flow volume curve. Logistic regression models using the set of four forced oscillation parameters (excluding resonant frequency, which is derived from compliance and inertance) were then used to analyse the ability of each method to classify the subjects in each group. Significant differences between the two methods were observed for the mean values obtained for all five parameters. However, when each parameter was considered separately, the correlations between the values for each method were significant. Each method possessed the necessary ability to separate subjects into our group classification, but the significant relationships were not always found for the same parameters. Finally, logistic regression models showed that the two methods led to almost the same classification of the subjects. According to our results, the standard method of applying forced oscillation at the mouth seems an acceptable device for measuring respiratory impedance for epidemiological purposes.
The Tangle of Nuclear Receptors that Controls Xenobiotic Metabolism and Transport: Crosstalk and Consequences
Authors: Jean-Marc Pascussi, Sabine Gerbal-Chaloin, Cédric Duret, Martine Daujat-Chavanieu, Marie-José Vilarem, Patrick Maurel
Journal: The Annual Review of Pharmacology and Toxicology (2007)

The expression of many genes involved in xenobiotic/drug metabolism and transport is regulated by at least three nuclear receptors or xenosensors: aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR). These receptors establish crosstalk with other nuclear receptors or transcription factors controlling signaling pathways that regulate the homeostasis of bile acids, lipids, glucose, inflammation, vitamins, hormones, and others. These crosstalks are expected to modify profoundly our vision of xenobiotic/drug disposition and toxicity. They provide molecular mechanisms to explain how physiopathological stimuli affect xenobiotic/drug disposition, and how xenobiotics/drugs may affect physiological functions and generate toxic responses. In addition, the possibility that xenosensors may control other signaling pathways opens the way to new pharmacological opportunities.
The Role of Anti-Inflammatory Drugs in Colorectal Cancer
Authors: Dingzhi Wang, Raymond N. DuBois
Journal: Annual Review of Medicine (2012)

A large body of evidence indicates that genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle are key risk factors for colorectal cancer (CRC). Prevention of CRC has long been considered a plausible approach for the population and individuals at high risk for developing this disease. A significant effort has been made in the development of novel drugs for both prevention and treatment over the past two decades. This review highlights recent advances in our understanding of the role of nonsteroidal anti-inflammatory drugs in CRC prevention and adjuvant treatment. Moreover, we focus on the molecular mechanisms underlying the antitumor effects of these drugs in CRC. The knowledge of how anti-inflammatory agents inhibit cancer formation and progression may provide a rationale for the development of more effective chemopreventive and chemotherapeutic agents with less toxicity.
Catalytic and regulatory properties of the Triton and trypsin forms of the brush border hydrolases.
Authors: A M Ugolev, N M Mityushova, V V Egorova, I K Gozite, G G Koltushkina
Journal: Gut (1979)

Amphipathic enzymes, invertase (EC 3.2.1.26), 8-amylase (EC 3.2.1.3), and alkaline phosphatase (EC 3.1.3.1), were purified from the rat small intestinal mucosa as trypsin and Triton forms, the catalytic and regulatory characteristics of which were compared in rats and in drosophila. Differences in the catalytic propertiis of the two enzyme forms were demonstrated, which suggested that the hydrophobic part of the enzyme was involved in maintaining optimal conformation of the catalytic part. Many modifiers have beenfound to influence the Triton rather than the trypsin form of the enzyme. It is therefore suggested that the hydrophobic sub-units of the enzymes might be involved in transmitting information from the cytoplasm into the external surface of the membrane, the cell in this way regulating the activity of surface enzymes. If this is indeed the case, it is suggested that the hydrophobic part performs functions not only of external but also of internal regulation.
THE REFRACTORY PERIOD OF THE NORMALLY-BEATING DOG'S AURICLE; WITH A NOTE ON THE OCCURRENCE OF AURICULAR FIBRILLATION FOLLOWING A SINGLE STIMULUS
Authors: E. Cowles Andrus, Edward P. Carter
Journal: The Journal of Experimental Medicine (1930)

1. A method is described for determining the refractory period of the dog's auricle during the normal sinus rhythm. The advantages of the method are: (a) The total stimulating effects of repeated induction shocks are avoided. (b) The action current is recorded from a point one millimeter or less from the point of stimulation. (c) Alterations in the spontaneous rate of the auricle do not interfere with the accurate determination of the refractory period. 2. The values obtained for the normal refractory period and the changes produced by atropine and by stimulation of the vagus agree closely with those of previous observers. 3. The automatic features of the method make possible the determination of the refractory period under adrenalin. This drug brings about a distinct shortening of the refractory period but less than that produced by stimulation of the vagus. 4. During vagal stimulation a single induction shock, introduced soon after the end of the refractory period, frequently produces auricular fibrillation. The cause of this irregularity is discussed and its relation to clinical auricular fibrillation is suggested.
No Structural Mutation in the Dopamine D2 Receptor Gene in Alcoholism or Schizophrenia
Authors: P V Gejman, A Ram, J Gelernter, E Friedman, Q Cao, D Pickar, K Blum, E P Noble, H R Kranzler, S O'Malley
Journal: JAMA (1994)

To examine the dopamine D2 receptor (DRD2) gene coding sequences for abnormalities associated with schizophrenia or alcoholism and thereby help to resolve the controversy surrounding the reported association of alcoholism with a restriction fragment length polymorphism located close to the DRD2 gene.Mutational analysis of complete DRD2 gene coding sequences by denaturing gradient gel electrophoresis followed by direct nucleotide sequencing of detected variants.Patients and controls from clinical and epidemiologic collections in the United States and Europe.A total of 253 unrelated individuals, including 106 patients with schizophrenia, 113 with alcoholism, and 34 controls. For alcoholism we included patients from previously published series in which an association of illness with allele A1 was reported (Taql site 3' to the DRD2 gene) and from other published series in which nonconfirmations of this association were reported. Nearly all persons examined were white.Frequency of nonsilent variations in DRD2 gene DNA sequences in the different diagnostic groups.We found three infrequent DNA variants that predict altered amino acid sequence of the receptor. None of these is associated with either alcoholism or schizophrenia.No structural coding abnormalities in the DRD2 gene are present in alcoholism or schizophrenia.