tbuckley/cabot-search huggingface dataset:
Leveraging data by electronic study automation: a new paradigm in pre-clinical cancer research through animal study data sharing
Authors: Eric Ibsen, David Smith, Walter Parabaniuk
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4417 

The current paradigm in cancer research for animal study data collection, management and publication has changed little in the last 50 years. However, recent technological developments have led to new possibilities among the research community to the extent that the benefits of adopting the new methods often outweigh the barriers of implementing them. Historically, animal study (AS) data are collected manually using combinations of paper notebooks and electronic spreadsheets. As a consequence, data cannot be accessed and shared effectively because: 1) data recorded in lab notebooks remain un-indexed and inaccessible once collected; 2) spreadsheets often contain only primary measurement data and are stored in data silos, 3) AS conditions, methods and model details are recorded inconsistently, in insufficient detail, and reside in multiple locations and formats. The lack of data digitization and standard content, format and storage conventions makes AS data access and cross-study comparisons impractical within and across research organizations. This constitutes a systematic, unintentional, and yet preventable waste of data, information, organizational knowledge, time and resources. The net result is that the majority of animal data are not only unavailable within the research institution itself, but to the research community at large. Many thousands of “failed” or unpublished animal studies represent billions of dollars of cumulative research that is not shared. This massive body of information is tremendously valuable yet remains entirely untapped, primarily due to three reasons: 1) the heterogeneity of data formats and forms, 2) the lack of automated data collection, and 3) the proprietary nature of data. Animal Study Management Software (ASMS) addresses these issues and provides new opportunities to the research community. ASMS automates and standardizes the organization of AS data, design, conditions, conduct details and results into a searchable database, and, in effect, solves the problems of data loss and accessibility. Additionally, ASMS standardization of data into a single, digital form could in turn enable for the first time the voluntary sharing and pooling of AS data from many research institutions into a centralized, web-based study repository. Standardization and digitized data gives investigators, journals, and institutions the opportunity to publish their non-proprietary data, both negative and positive results. By having the details on historical studies available, researchers could obviate needless repetition of studies, expedite model implementation projects, refine current animal models and build on existing work. The net result would be a significant improvement in information sharing, much more efficient use of limited research resources and ultimately a decreased time to identify, develop and market new therapeutics for cancer.
Abstract 2794: Electrocardiographic Predictors of Sudden Cardiac Death in Pediatric Hypertrophic Cardiomyopathy
Authors: Karen M Texter, Jeffrey A Towbin, Richard A Friedman, Arnold L Fenrich, Naomi J Kertesz, Sarah K Clunie, Bryan C Cannon
Journal: Circulation (2006)

Introduction: Hypertrophic cardiomyopathy (HCM) is a common cause of sudden cardiac death in young athletes. The abnormalities on electrocardiogram (ECG) seen in HCM during childhood that relate to...
Neutrophil Extracellular Traps Accumulate in Peripheral Blood Vessels and Compromise Organ Function in Tumor-Bearing Animals
Authors: Jessica Cedervall, Yanyu Zhang, Hua Huang, Lei Zhang, Julia Femel, Anna Dimberg, Anna-Karin Olsson
Journal: Cancer Research (2015)

Cancer produces a variety of collateral effects in patients beyond the malignancy itself, including threats to distal organ functions. However, the basis for such effects, associated with either primary or metastatic tumors, are generally poorly understood. In this study, we show how heart and kidney vascular function is impaired by neutrophils that accumulate in those tissues as a result of tumor formation in two different transgenic mouse models of cancer (RIP1-Tag2 model of insulinoma and MMTV-PyMT model of breast cancer). Neutrophil depletion by systemic administration of an anti-Gr1 antibody improved vascular perfusion and prevented vascular leakage in kidney vessels. We also observed the accumulation of platelet-neutrophil complexes, a signature of neutrophil extracellular traps (NET), in the kidneys of tumor-bearing mice that were completely absent from healthy nontumor-bearing littermates. NET accumulation in the vasculature was associated with upregulation of the proinflammatory adhesion molecules ICAM-1, VCAM-1, and E-selectin, as well as the proinflammatory cytokines IL1β, IL6, and the chemokine CXCL1. Administering DNase I to dissolve NETs, which have a high DNA content, restored perfusion in the kidney and heart to levels seen in nontumor-bearing mice, and also prevented vessel leakage in the blood vasculature of these organs. Taken together, our findings strongly suggest that NETs mediate the negative collateral effects of tumors on distal organs, acting to impair vascular function, and to heighten inflammation at these sites.
Editor's Note: Suppression of Tumor Cell Growth Both in Nude Mice and in Culture by n-3 Polyunsaturated Fatty Acids: Mediation through Cyclooxygenase-Independent Pathways
Authors: Mary D. Boudreau, Kyung Hee Sohn, Sang Hoon Rhee, Sam W. Lee, Jay D. Hunt, Daniel H. Hwang
Journal: Cancer Research (2019)

Dietary n-3 polyunsaturated fatty acids (PUFAs), as compared with n-6 PUFAs, suppress cellular production of prostaglandins and tumor cell growth both in vitro and in vivo. However, the mechanism by which n-3 PUFAs suppress tumor growth is not understood. We investigated whether the suppression of tumor cell growth by dietary n-3 PUFAs is mediated through inhibition of cyclooxygenase (COX). A colon tumor cell line, HCT-116, that does not express COX was stably transfected with the constitutively expressed COX-1 or the inducible COX-2 cDNA using a retroviral transfection and infection system. Athymic nude mice transplanted with the cells expressing enzymatically active COX were fed isocaloric diets containing either safflower oil or fish oil for 2 weeks before the start of the experiment and for an additional 21 days after transplantation. Both tumor volume and tumor burden (tumor volume/body weight) were significantly reduced in mice fed the fish oil diet as compared with safflower oil-fed mice. This reduction occurred even in control mice that received injections with cells infected with the retroviral vector without COX-1 or COX-2 cDNA. The growth of tumor cells expressing COX was not different from the growth of those transfected with the vector alone in the nude mice and in soft agar. N-3 PUFAs, as compared with linoleic acid, also inhibited the growth of these cells in culture. This growth inhibition by n-3 PUFAs was not affected by COX-1 or COX-2 overexpression. Contrary to general belief, these results indicate that the suppression of tumor growth by dietary n-3 PUFAs is mediated through COX-independent pathways.
Significance of first arterial carbon dioxide pressure in patients hospitalized with community acquired pneumonia
Authors: Soheil Peiman, Hamidreza Abtahi, Zeynab Yassin
Journal: European Respiratory Journal (2014)

Introduction : Despite high incidence of community acquired pneumonia (CAP), there is little data about significance of the arterial carbon dioxide pressure (PaCO 2 ) in prediction of CAP prognosis. This study prospectively evaluated the outcome of hospital admitted CAP based on the first PaCO2.   Method : From April 2013 to January 2014, CAP patients that admitted in a tertiary university hospital entered in the study. The relation between the first PaCO2 group ( 45) and CURB-65 obtained in emergency ward with duration of hospitalization ( 2weeKs), ICU admission and mortality within 28 days in these patients were analyzed by Mann-Whitney test.   Results : Seventy five patients (mean Age: 59.8±17.9; Male: 42/75) were included. The frequencies of ICU admission and mortality were 21% and 8% respectively. Mean values for PaCO2, and duration of hospitalization were 41.01±12.8 mmHg, and 13.1±11.8 days respectively. Although PaCO2 had week correlation with duration of hospitalization (r: 0.361; P: 0.004), the relation between PaCO2 with duration of hospitalization, ICU admission, and mortality was not significant (P: 0.708, 0.437, and 0.412 respectively). CURB-65 had significant correlation to duration of hospitalization, ICU admission and mortality (P: 0.01, 0.005 and 0.002 respectively).   Conclusion : First PaCO2 level during hospitalization could not be used as a predictor in hospitalized CAP patients. In contrast, CURB-65 is a reliable predictor of outcome in these patients.
Abstract 1241: Nkx2 5 Regulates Cell Fate Decisions in the Developing Embryo
Authors: Arianna Caprioli, Anwarul Ferdous, Amanda M Masino, Cindy M Martin, Teresa D Gallardo, Justin Kallhoff, Nan Jiang, Michael Kyba, Richard P Harvey, Eric N Olson, Daniel J Garry
Journal: Circulation (2006)
A randomised, placebo-controlled study of the CXCR2 antagonist AZD5069 in bronchiectasis
Authors: Anthony De Soyza, Ian Pavord, J. Stuart Elborn, David Smith, Heather Wray, Margareta Puu, Bengt Larsson, Robert Stockley
Journal: European Respiratory Journal (2015)

This randomised double-blind placebo-controlled parallel-group multicentre phase IIa study evaluated the effect of the CXCR2 antagonist AZD5069 on sputum neutrophil counts in adults with bronchiectasis. Patients were randomised 1:1 to receive AZD5069 80 mg or placebo orally twice daily for 28 days. Assessments included blood cell counts, inflammatory markers in blood, morning spontaneous sputum, lung function, safety and tolerability and patients completed daily BronkoTest diary cards. The primary outcome measure was the change in absolute sputum neutrophil count. Of 52 randomised patients, 45 completed treatment, 20 (76.9%) out of 26 receiving AZD5069 and 25 (96.2%) out of 26 receiving placebo. AZD5069 reduced the absolute neutrophil cell count in morning sputum by 69% versus placebo (p=0.004); percentage sputum neutrophil count was reduced by 36% (p=0.008). The number of infections/exacerbations was similar with AZD5069 and placebo (nine versus eight), but these led to more study discontinuations with AZD5069 (four versus zero). Sputum interleukin (IL)-6 and growth-regulated oncogene (GRO)-α and serum GRO-α, IL-1ß and IL-8 levels increased with AZD5069 versus placebo (all p&lt;0.001), while serum high-sensitivity C-reactive protein levels did not change. AZD5069 was well tolerated. AZD5069 markedly reduced absolute sputum neutrophil counts in bronchiectasis patients, although this was not associated with improvements in clinical outcomes in this exploratory study.
Sensitization to Cat Allergen Is Associated with Asthma in Older Men and Predicts New-onset Airway Hyperresponsiveness
Authors: AUGUSTO A. LITONJUA, DAVID SPARROW, SCOTT T. WEISS, GEORGE T. O'CONNOR, AIDAN A. LONG, JOHN L. OHMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To explore the relationship between sensitization to inhalant allergens and adult asthma, we performed two nested case-control studies of men being followed in the VA Normative Aging Study. In Study A, 46 subjects (mean age, 61.2 ± 8.1 yr) with symptoms of asthma and an abnormal methacholine challenge test (cases) were compared with 92 age- and smoking-history-matched subjects, who denied symptoms and had normal methacholine challenge tests (controls). The age of onset of wheezing symptoms for the cases was 49.0 ± 15.7 yr. Serum IgE reactivity to the aeroallergens Der p 1 and 2, cat, ragweed, and mouse was compared in cases and controls. Cases were more likely to be sensitized to cat allergen (23.9% versus 4.4%, p < 0.001) than were controls. Prevalences of sensitization to Der p 1, Der p 2, ragweed, and mouse were low and similar in the two groups. In Study B, 33 cases who developed new onset airway hyperresponsiveness on methacholine challenge testing were compared with 66 age-matched controls who maintained normal methacholine challenge tests. Cases had a higher prevalence of serum IgE reactivity to cat allergen (18.2% versus 6.1%, p = 0.059) and Der p 2 (21.2% versus 10.6%, p = 0.153) measured in serum obtained 3 yr before the development of airway hyperresponsiveness. These results suggest that in older men, sensitization to cat allergen is associated with asthma and that sensitization predates airway hyperresponsiveness to methacholine.
Abstract 17004: Nociceptive Signalling Contributes to Progenitor Cells Activation and Mobilization in Ischemia
Authors: Silvia Amadesi, Marco Meloni, Carlotta Reni, Orazio Fortunato, Paolo Madeddu
Journal: Circulation (2010)

Background:  Pain is an essential component of the alarm response to tissue injury. We hypothesised that neuropeptides substance P (SP) and Calcitonin Gene-Releated Peptide (CGRP), released from nociceptive fibres, contribute to progenitor cells (PC) mobilization in ischemia.   Methods and Results:  By immunostaining, we confirmed the expression of SP and CGRP within vesicles of fibre-like structures in mouse bone marrow (BM). Moreover, we found that NK1 and CLR/RAMP-1 (SP and CGRP receptors) were expressed on cells of the osteoblastic and vascular niches and co-expressed in PC with ckit, Sca-1 and Flk1. In  in vitro  migration assays, SP and CGRP attracted BM PC (SP, 1 nM: 1.8±0.2 fold; CGRP, 1 nM: 1.9±0.3 fold increase in migration; p=0.04 for both comparisons vs. control; N=3). Mouse dorsal root ganglia neurons (mDRGN) or their conditioned medium (CM) had similar promigratory effects (mDRGN: 2.1±0.2 fold, p pos /Flk1 pos  PC fraction showed higher level of RAMP-1 (1.37 fold, p=0.05) and NK1 (1.11 fold, p=0.08) after ischemia. RAMP-1 and NK1 expression also increased in peripheral blood (PB) cKit pos /Flk1 pos  PC (1.21 and 1.24 fold). Furthermore, we found that NK1 and CLR/RAMP-1 were expressed in human PB PC and that acute myocardial infarction (aMI) and chronic angina (CA) increased CD34 pos /KDR pos  PC co-expressing RAMP-1 (control 0.004±0.001% of total mononuclear cells; aMI 0.008±0.001%, p pos /KDR pos  PC fraction (RAMP-1: control 9.2±0.6%; aMI 15.5±1.8%, p   Conclusion:  Our results suggest that neurogenic mechanisms regulate PC mobilization in ischemia. Nociceptive signalling might represent a novel target for modulation of BM-mediated reparative response.
An Age-Calibrated Classification of Chronic Kidney Disease
Authors: Richard Glassock, Pierre Delanaye, Meguid El Nahas
Journal: JAMA (2015)

This Viewpoint discusses the ramifications of using a glomerular filtration rate of less than 60 mL/min/1.73 m2 for patients of all ages and proteinuria (albuminuria) for chronic kidney disease classification.
Anorexia Nervosa: therapy and theory
Authors: Hilde Bruch
Journal: American Journal of Psychiatry (1982)

The reciprocal interaction between psychotherapy and theoretical assumptions is illustrated through observations of anorexia nervosa. Traditional psychoanalysis, with its emphasis on interpretation of unconscious processes, was found to be rather ineffective, whereas an approach evoking active participation on the part of the patient led to better treatment results. The experience of being listened to appeared to be of utmost importance. The characteristic deficits in self-concept and body awareness could be related to a paucity or an absence of confirming responses in the early mother-child interactions. This concept reinforced the focus on encouragement of initiative and autonomy during therapy.
Association of age, sex, cognitive dysfunction, and disability with major depressive symptoms in an elderly sample
Authors: Y Forsell, A F Jorm, B Winblad
Journal: American Journal of Psychiatry (1994)

Previous studies have yielded conflicting results regarding the association of age, sex, and cognitive deficit with depression in the elderly. However, there is agreement about a relationship between depressive symptoms and disability. The authors previously conducted a factor analysis of the symptoms of major depression in elderly subjects and found that the symptoms clustered into factors of mood disturbance and motivation disturbance. The aim of the present study was to replicate these findings in a larger population sample and relate some of the variables possibly associated with depression to these two factors.A population sample of 1,304 persons aged 75 years or older registered in a parish of Stockholm were examined by physicians to determine DSM-III-R depressive symptoms and disability in activities of daily living. The Mini-Mental State examination was also performed.Factor analysis showed factors of mood and motivation symptoms, and these were related differently to the associated variables. When the other associated variables were controlled for, age was unrelated to both types of symptoms. Women had more mood disturbance, but men had slightly more motivation disturbance. As cognitive function declined, mood disturbance first increased, then decreased. Motivation symptoms increased sharply with decreasing cognitive function. A relationship was found between increasing disability and both the mood and motivation symptoms.In the elderly, symptoms of depression involve either mood or motivation disturbance and the two types of symptoms are associated with different variables.
Abstract 18802: Sex Differences in the Risk of 1-year Re-hospitalization in Young Women and Men following Acute Myocardial Infarction
Authors: Rachel P Dreyer, Chileshe Nkonde-Price, Kevin Kennedy, Viola Vaccarino, Susmita Parashar, Kumar Dharmarajan, Gmerice Hammond, Judith H Lichtman, Kim G Smolderen, Donna M Buchanan, John A Spertus, Harlan M Krumholz
Journal: Circulation (2014)

Background: It is currently unknown whether young women (≤55 yrs) have a greater risk of all cause-re-hospitalization following AMI than similarly aged men. This is an important subgroup to study considering younger women’s higher post-AMI mortality compared with age-matched men. We determined if there are sex differences in the 1-year re-hospitalization rate, including factors associated with this outcome. Methods: Young AMI patients (N=1414, 28% women) were identified from the 24-center prospective, observational TRIUMPH study. Patient data was abstracted from medical records and health status was collected through interviews at the time of the AMI [Short Form 12 (SF-12), and the Seattle Angina Questionnaire (SAQ)]. Physicians adjudicated each re-hospitalization the year after discharge. We compared sexes using t-test/x2 and Cox proportional hazards analysis, sequentially adjusting for important covariates. Results: The crude 1-yr re-hospitalization rate was higher in women vs. men (32% vs. 23%, P&lt;0.001), and women also had more hypertension (64% vs. 53%), diabetes (34% vs. 22%), lung disease (9% vs. 3%), and depression (14% vs. 6%; P&lt;0.0001 for all). At presentation, women had worse general health scores (SF-12 physical summary=41±12 vs. 44±11, mental summary= 45±13vs.49±11, P&lt;0.0001 for all), more angina (SAQ angina frequency=83±22 vs. 87±19), poorer physical function (SAQ physical limitation=82±24 vs. 89±19) and worse quality of life (57±23 vs. 62±23; P&lt;0.001 for all). In the fully adjusted model, female sex was no longer significantly associated with 1-year re-hospitalization post AMI (HR=1.20, 95%CI = 0.93, 1.56). Conclusion: Young women have a higher crude rate of 1-year re-hospitalization post AMI compared with men, however this effect was attenuated following adjustment. In addition to conventional risk factors, health status/psychosocial issues may be contributing factors in the risk of re-hospitalization among these young patients.
Abstract 3380: Acetylation-dependent Regulation Of Notch1 Signaling In Endothelial Cells
Authors: Virginia Guarani, Franck Dequiedt, Andreas M Zeiher, Stefanie Dimmeler, Michael Potente
Journal: Circulation (2008)

The Notch signaling pathway is a versatile regulator of cell fate decisions and plays an essential role for embryonic and postnatal vascular development. As only modest differences in Notch pathway activity suffice to determine dramatic differences in blood vessel development, this pathway is tightly regulated by a variety of molecular mechanisms. Reversible acetylation has emerged as an important post-translational modification of several non-histone proteins, which are targeted by histone deacetylases (HDACs). Here, we report that specifically the Notch1 intracellular domain (NICD) is itself an acetylated protein and that its acetylation level is tightly regulated by the SIRT1 deacetylase, which we have previously identified as a key regulator of endothelial angiogenic functions during vascular growth. Coexpression of NICD with histone acetyltransferases such as p300 or PCAF induced a dose- and time-dependent acetylation of NICD. Blocking HDAC activity using the class III HDAC inhibitor nicotinamid (NAM), but not the class I/II HDAC inhibior trichostatin A, resulted in a significant increase of NICD acetylation suggesting that NICD is targetd by class III HDACs for deacetylation. Among the class III HDACs with deacetylase activity (SIRT1, 2, 3, 5), knock down of specifically SIRT1 resulted in enhanced acetylation of NICD. Moreover, wild type SIRT1, but not a catalytically inactive mutant catalyzed the deacetylation of NICD in a nicotinamid-dependent manner. SIRT1, but SIRT2, SIRT3 or SIRT5, associated with NICD through its catalytic domain demonstrating that SIRT1 is a direct NICD deacetylase. Enhancing NICD acetylation by either overexpression of p300 or inhibition of SIRT1 activity using NAM or RNAi-mediated knock down resulted in enhanced NICD protein stability by blocking its ubiquitin-mediated degradation. Consistent with these results, loss of SIRT1 amplified Notch target gene expression in endothelial cells in response to NICD overexpression or treatment with the Notch ligand Dll4. In summary, our results identify reversible acetylation of NICD as a novel molecular mechanism to control Notch signaling and suggest that deacetylation of NICD by SIRT1 plays a key role in the dynamic regulation of Notch signaling in endothelial cells.
Prognostic Relevance of Gene-Environment Interactions in Patients With Dilated Cardiomyopathy
Authors: Mark R. Hazebroek, Suzanne Moors, Robert Dennert, Arthur van den Wijngaard, Ingrid Krapels, Marije Hoos, Job Verdonschot, Jort J. Merken, Bart de Vries, Petra F. Wolffs, Harry J.G.M. Crijns, Hans-Peter Brunner-La Rocca, Stephane Heymans
Journal: Journal of the American College of Cardiology (2015)