tbuckley/cabot-search huggingface dataset:
Single leg balance test to identify risk of ankle sprains
Authors: T H Trojian, D B McKeag
Journal: British Journal of Sports Medicine (2006)

Background: Ankle sprains are a common and potentially disabling injury. Successful prediction of susceptibility to ankle sprain injury with a simple test could allow ankle sprain prevention protocols to be initiated and help prevent disability in the athletic population. Objective: To investigate the ability of the single leg balance (SLB) test, carried out at preseason physical examination, to predict an ankle sprain during the autumn sports season. Design: Prospective cohort study Setting: High school varsity athletics and intercollegiate athletics. Main outcome measure: Ankle sprains in athletes with positive SLB tests. Results: The association between a positive SLB test and future ankle sprains was significant. Controlling for confounding variables, the relative risk for an ankle sprain with a positive SLB test was 2.54 (95% confidence interval, 1.02 to 6.03). Athletes with a positive SLB test who did not tape their ankles had an increased likelihood of developing ankle sprains. The relative risk for ankle sprain for a positive SLB test and negative taping was 8.82 (1.07 to 72.70). A history of previous ankle injury was not associated with future ankle sprains in this study. The κ value for interrater reliability for the SLB test was 0.898 (p&lt;0.001). Conclusions: An association was demonstrated between a positive SLB test and ankle sprain. In athletes with a positive SLB test, not taping the ankle imposed an increased risk of sprain. The SLB test is a reliable and valid test for predicting ankle sprains.
Systematic Analysis of Challenge-Driven Improvements in Molecular Prognostic Models for Breast Cancer
Authors: Adam A. Margolin, Erhan Bilal, Erich Huang, Thea C. Norman, Lars Ottestad, Brigham H. Mecham, Ben Sauerwine, Michael R. Kellen, Lara M. Mangravite, Matthew D. Furia, Hans Kristian Moen Vollan, Oscar M. Rueda, Justin Guinney, Nicole A. Deflaux, Bruce Hoff, Xavier Schildwachter, Hege G. Russnes, Daehoon Park, Veronica O. Vang, Tyler Pirtle, Lamia Youseff, Craig Citro, Christina Curtis, Vessela N. Kristensen, Joseph Hellerstein, Stephen H. Friend, Gustavo Stolovitzky, Samuel Aparicio, Carlos Caldas, Anne-Lise Børresen-Dale
Journal: Science Translational Medicine (2013)

Although molecular prognostics in breast cancer are among the most successful examples of translating genomic analysis to clinical applications, optimal approaches to breast cancer clinical risk prediction remain controversial. The Sage Bionetworks-DREAM Breast Cancer Prognosis Challenge (BCC) is a crowdsourced research study for breast cancer prognostic modeling using genome-scale data. The BCC provided a community of data analysts with a common platform for data access and blinded evaluation of model accuracy in predicting breast cancer survival on the basis of gene expression data, copy number data, and clinical covariates. This approach offered the opportunity to assess whether a crowdsourced community Challenge would generate models of breast cancer prognosis commensurate with or exceeding current best-in-class approaches. The BCC comprised multiple rounds of blinded evaluations on held-out portions of data on 1981 patients, resulting in more than 1400 models submitted as open source code. Participants then retrained their models on the full data set of 1981 samples and submitted up to five models for validation in a newly generated data set of 184 breast cancer patients. Analysis of the BCC results suggests that the best-performing modeling strategy outperformed previously reported methods in blinded evaluations; model performance was consistent across several independent evaluations; and aggregating community-developed models achieved performance on par with the best-performing individual models.
The Transcriptional Coregulator RIP140 Represses E2F1 Activity and Discriminates Breast Cancer Subtypes
Authors: Aurélie Docquier, Pierre-Olivier Harmand, Samuel Fritsch, Maïa Chanrion, Jean-Marie Darbon, Vincent Cavaillès
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Receptor-interacting protein of 140 kDa (RIP140) is a transcriptional cofactor for nuclear receptors involved in reproduction and energy homeostasis. Our aim was to investigate its role in the regulation of E2F1 activity and target genes both in breast cancer cell lines and in tumor biopsies. Experimental Design: Glutathione S-transferase pull-down assays, coimmunoprecipitation experiments, and chromatin immunoprecipitation analysis were used to evidence interaction between RIP140 and E2F1. The effects of RIP140 expression on E2F1 activity were determined using transient transfection and quantification of E2F target mRNAs by quantitative real-time PCR. The effect on cell cycle was assessed by fluorescence-activated cell sorting analysis on cells overexpressing green fluorescent protein–tagged RIP140. A tumor microarray data set was used to investigate the expression of RIP140 and E2F1 target genes in 170 breast cancer patients. Results: We first evidenced the complex interaction between RIP140 and E2F1 and showed that RIP140 represses E2F1 transactivation on various transiently transfected E2F target promoters and inhibits the expression of several E2F1 target genes (such as CCNE1 and CCNB2). In agreement with a role for RIP140 in the control of E2F activity, we show that increasing RIP140 levels results in a reduction in the proportion of cells in S phase in various human cell lines. Finally, analysis of human breast cancers shows that low RIP140 mRNA expression was associated with high E2F1 target gene levels and basal-like tumors. Conclusion: This study shows that RIP140 is a regulator of the E2F pathway, which discriminates luminal- and basal-like tumors, emphasizing the importance of these regulations for a clinical cancer phenotype. Clin Cancer Res; 16(11); 2959–70. ©2010 AACR.
A CLINICAL EVALUATION OF PIPERACETAZINE IN THE TREATMENT OF CHRONIC SCHIZOPHRENIA
Authors: JAMES E. KIRKHAM, JOHN KINROSS-WRIGHT
Journal: American Journal of Psychiatry (1964)

This study indicates that Quide is a useful addition to the armamentarium of the physician faced with the difficult problem of treating the chronic hospitalized patient with a schizophrenic illness. Side effects of the drug were generally mild, and there was no evidence that it would produce blood dyscrasias or liver impairment. As a result of the circumscribed nature of this study it would be difficult to determine the long-term effects of the drug. However, the drug has shown no chronic untoward effects in previous studies and no chronic effects from the drug were expected. At the end of the study most of the patients were removed from maintenance doses of the drug. Of the total group one patient was discharged on an indefinite furlough. Another was discharged on a temporary furlough. The remainder of the patients in the study continued in the hospital.
The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation
Authors: Sahar El Aidy, Claire A Merrifield, Muriel Derrien, Peter van Baarlen, Guido Hooiveld, Florence Levenez, Joel Doré, Jan Dekker, Elaine Holmes, Sandrine P Claus, Dirk-Jan Reijngoud, Michiel Kleerebezem
Journal: Gut (2012)

<h3>Objective</h3> Proper interactions between the intestinal mucosa, gut microbiota and nutrient flow are required to establish homoeostasis of the host. Since the proximal part of the small intestine is the first region where these interactions occur, and since most of the nutrient absorption occurs in the jejunum, it is important to understand the dynamics of metabolic responses of the mucosa in this intestinal region. <h3>Design</h3> Germ-free mice aged 8–10 weeks were conventionalised with faecal microbiota, and responses of the jejunal mucosa to bacterial colonisation were followed over a 30-day time course. Combined transcriptome, histology, <sup>1</sup>H NMR metabonomics and microbiota phylogenetic profiling analyses were used. <h3>Results</h3> The jejunal mucosa showed a two-phase response to the colonising microbiota. The acute-phase response, which had already started 1 day after conventionalisation, involved repression of the cell cycle and parts of the basal metabolism. The secondary-phase response, which was consolidated during conventionalisation (days 4–30), was characterised by a metabolic shift from an oxidative energy supply to anabolic metabolism, as inferred from the tissue transcriptome and metabonome changes. Detailed transcriptome analysis identified tissue transcriptional signatures for the dynamic control of the metabolic reorientation in the jejunum. The molecular components identified in the response signatures have known roles in human metabolic disorders, including insulin sensitivity and type 2 diabetes mellitus. <h3>Conclusion</h3> This study elucidates the dynamic jejunal response to the microbiota and supports a prominent role for the jejunum in metabolic control, including glucose and energy homoeostasis. The molecular signatures of this process may help to find risk markers in the declining insulin sensitivity seen in human type 2 diabetes mellitus, for instance.
Retiree Health Benefits
Authors: M. A. Morrisey
Journal: Annual Review of Public Health (1993)

Some 80% of elderly Medicare beneficiaries have private supplemental insurance. Approximately 50% of these have some form of medigap of privately purchased coverage. Those holding private coverage tend to be younger, more highly educated, and white. Women are more likely to hold medigap type plans, and men are more likely to have employment related coverage. The extent of multiple coverage is relatively rare. One estimate puts multiple coverage at about 20% of those with private supplemental coverage. Contrary to conventional wisdom, those with multiple coverage are not the very old and poorly educated. Rather, they tend to be younger and more highly educated. Also, women are more likely to have both employer-sponsored and medigap coverage, maybe because of the uncertainty about whether a wife will continue to have employer-sponsored post-retirement coverage after her husband has died. Medigap-type health insurance is heavy on first dollar coverage; the Medicare deductibles and copayments are covered. Provisions of OBRA 1990 will homogenize this coverage even more. Employer-sponsored health benefits are common. Some 8.4 million elderly Medicare beneficiaries have employer-sponsored coverage. A large but undetermined number of early retirees also have coverage. These recipients have generally been the workers in very large firms. However, the future will not look like the past. Two thirds of current workers are promised health benefits upon retirement. The benefits provided under these plans are both broad and deep. The nature of benefit coordination between these plans and Medicare can reduce the size of the apparent benefits. The carve-out method of coordination is the most common and can result in sizable out-of-pocket payments by the beneficiary. However, it is not obvious that employer-sponsored plans have been designed to exploit this opportunity. There is little information on the conditions under which a worker is vested for health benefits. The sketchy evidence that does exist suggests that a worker must retire from the firm and have had time in service about equal to that required for the firm's pension plan. Firms apparently can change their retiree benefit plans if they have explicitly retained the right to do so. There are sound economic reasons to suggest that many firms would honor their commitments, even in the absence of legal requirements. Supplemental retiree coverage leads to additional use of health services, particularly by those in poorer health and particularly by those with plans that feature first-dollar coverage. The increased use of services as a result of supplemental coverage also increases Medicare's costs.(ABSTRACT TRUNCATED AT 400 WORDS)
Collapsed scrums and collision tackles: what is the injury risk?
Authors: Simon P Roberts, Grant Trewartha, Mike England, Keith A Stokes
Journal: British Journal of Sports Medicine (2014)

Aim To establish the propensity for specific contact events to cause injury in rugby union. Methods Medical staff at participating English community-level rugby clubs reported any injury resulting in the absence for one match or more from the day of the injury during the 2009/2010 (n=46), 2010/2011 (n=67) and 2011/2012 (n=76) seasons. Injury severity was defined as the number of matches missed. Thirty community rugby matches were filmed and the number of contact events (tackles, collision tackles, rucks, mauls, lineouts and scrums) recorded. Results Of 370 (95% CI 364 to 378) contact events per match, 141 (137 to 145) were tackles, 115 (111 to 119) were rucks and 32 (30 to 33) were scrums. Tackles resulted in the greatest propensity for injury (2.3 (2.2 to 2.4) injuries/1000 events) and the greatest severity (16 (15 to 17) weeks missed/1000 events). Collision tackles (illegal tackles involving a shoulder charge) had a propensity for injury of 15 (12.4 to 18.3) injuries/1000 events and severity was 92 (75 to 112) weeks missed/1000 events, both of which were higher than any other event. Additional scrum analysis showed that only 5% of all scrums collapsed, but the propensity for injury was four times higher (2.9 (1.5 to 5.4) injuries/1000 events) and the severity was six times greater (22 (12 to 42) weeks missed/1000 events) than for non-collapsed scrums. Conclusions Injury prevention in the tackle should focus on technique with strict enforcement of existing laws for illegal collision tackles. The scrum is a relatively controllable event and further attempts should be made to reduce the frequency of scrum collapse.
Cardiac structural remodelling after treatment of spontaneously hypertensive rats with nifedipine or nisoldipine
Authors: S. E Campbell, Z. Turek, K. Rakusan, S. Kazda
Journal: Cardiovascular Research (1993)

Objective: The aim was to determine if long term treatment with nifedipine or nisoldipine affects structural remodelling of cardiac myocytes and is effective in attenuating or preventing reparative and reactive myocardial fibrosis in essential hypertension. Methods: Five and a half month old male spontaneously hypertensive rats and Wistar Kyoto (WKY) rats received either 1000 ppm nifedipine or nisoldipine or no treatment (controls) for 22 weeks. Haemodynamic variables were measured and hearts recovered from animals of each group. Cardiac myocytes were isolated by retrograde coronary perfusion with collagenase. Cell volume was determined by Coulter analysis, cell length by direct measurement, and cross sectional area by volume/length. Cardiac myocyte number was calculated for both ventricles. Tissue sections from perfusion fixed hearts were stained with picrosirius red and myocardial collagen was analysed. Reparative fibrosis was assessed by the presence of microscopic scarring and reactive (interstitial and perivascular) fibrosis was quantified. Results: Nifedipine and nisoldipine significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats, although normotensive pressures did not result. Left ventricular weight relative to body weight was significantly decreased in nifedipine and nisoldipine treated compared with untreated spontaneously hypertensive rats, although values remained significantly greater than WKY controls. Cardiac myocyte volume was slightly decreased with attenuation of blood pressure in spontaneously hypertensive rats, but no significant differences were found. Cardiac myocyte number for each ventricle was similar between groups. Microscopic scarring was significantly decreased in nifedipine and nisoldipine treated compared with untreated spontaneously hypertensive rats and interstitial and perivascular fibrosis were substantially reduced. Conclusions: Nifedipine and nisoldipine: (a) attenuate hypertension and decrease left ventricular mass in spontaneously hypertensive rats, but the associated decrease in myocyte size was not significant; (b) are cardioprotective as indicated by a significant decrease in the incidence of microscopic scarring; and (c) decrease the extent of reactive, both interstitial and perivascular, fibrosis normally found in untreated spontaneously hypertensive rats. Nifedipine and nisoldipine have the potential to positively alter myocardial pathology in essential hypertension. Cardiovascular Research 1993;27:1350-1358
Age at First Alcohol Use: A Risk Factor for the Development of Alcohol Disorders
Authors: David J. DeWit, Edward M. Adlaf, David R. Offord, Alan C. Ogborne
Journal: American Journal of Psychiatry (2000)

This study aimed to describe the natural course of DSM-III-R alcohol disorders as a function of age at first alcohol use and to investigate the influence of early use as a risk factor for progression to the development of alcohol disorders, exclusive of the effect of confounding influences.Data were obtained from a community sample (N=5,856) of lifetime drinkers participating in the 1990-1991 Mental Health Supplement of the Ontario Health Survey.Survival analyses revealed a rapid progression to alcohol-related harm among those who reported having their first drink at ages 11-14. After 10 years, 13.5% of the subjects who began to drink at ages 11 and 12 met the criteria for a diagnosis of alcohol abuse, and 15.9% had a diagnosis of dependence. Rates for subjects who began to drink at ages 13 and 14 were 13.7% and 9.0%, respectively. In contrast, rates for those who started drinking at ages 19 and older were 2.0% and 1.0%. Unexpectedly, a delay in progression to harm was observed for the youngest drinkers (ages 10 and under). Hazard regression analyses revealed a nonlinear effect of age at first alcohol use, marked by an elevated risk of developing disorders among subjects first using alcohol at ages 11-14.First use of alcohol at ages 11-14 greatly heightens the risk of progression to the development of alcohol disorders and therefore is a reasonable target for intervention strategies that seek to delay first use as a means of averting problems later in life.
Book Review: The Pocketbook of Drug Eruptions and Interactions, 2nd edition
Authors: Barry Monk
Journal: Journal of the Royal Society of Medicine (2001)

Dermatologists are all too familiar with the challenge presented by an ill patient on a medical or surgical ward whose condition is compounded by an extensive rash; is it a drug eruption and if so which of the patient's recent or current medications is at fault? The unravelling of such a puzzle is rarely assisted by the manufacturer's data sheet, which almost inevitably lists `rash' among a long list of potential side-effects and adverse reactions. Helpful information is indeed remarkably difficult to find. In a very few instances we now know why some people react adversely to a medication and others do not; marrow suppression from azathioprine, for example, is known to be almost entirely confined to those who lack the enzyme thiopurine methyltransferase (which can be readily measured). Occasionally the pattern of eruption is distinctive, as in fixed drug eruption, or erythema multiforme. Sometimes a pattern of adverse reaction may be predicted; for example, since penicillamine can induce a pemphigus-like eruption we might expect the structurally related molecule captopril to do likewise.
Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens
Authors: Deepak P. Srivastava, Kevin M. Woolfrey, Peter Penzes
Journal: Pharmacological Reviews (2013)

Converging evidence from cellular, electrophysiological, anatomic, and behavioral studies suggests that the remodeling of synapse structure and function is a critical component of cognition. This modulation of neuroplasticity can be achieved through the actions of numerous extracellular signals. Moreover, it is thought that it is the integration of different extracellular signals regulation of neuroplasticity that greatly influences cognitive function. One group of signals that exerts powerful effects on multiple neurologic processes is estrogens. Classically, estrogens have been described to exert their effects over a period of hours to days. However, there is now increasing evidence that estrogens can rapidly influence multiple behaviors, including those that require forebrain neural circuitry. Moreover, these effects are found in both sexes. Critically, it is now emerging that the modulation of cognition by rapid estrogenic signaling is achieved by activation of specific signaling cascades and regulation of synapse structure and function, cumulating in the rewiring of neural circuits. The importance of understanding the rapid effects of estrogens on forebrain function and circuitry is further emphasized as investigations continue to consider the potential of estrogenic-based therapies for neuropathologies. This review focuses on how estrogens can rapidly influence cognition and the emerging mechanisms that underlie these effects. We discuss the potential sources and the biosynthesis of estrogens within the brain and the consequences of rapid estrogenic-signaling on the remodeling of neural circuits. Furthermore, we argue that estrogens act via distinct signaling pathways to modulate synapse structure and function in a manner that may vary with cell type, developmental stage, and sex. Finally, we present a model in which the coordination of rapid estrogenic-signaling and activity-dependent stimuli can result in long-lasting changes in neural circuits, contributing to cognition, with potential relevance for the development of novel estrogenic-based therapies for neurodevelopmental or neurodegenerative disorders.
The Raji cell radioimmune assay for detecting immune complexes in human sera.
Authors: A N Theofilopoulos, C B Wilson, F J Dixon
Journal: Journal of Clinical Investigation (1976)

A sensitivie and simple procedure for the detection and quantitation of soluble complement (C)- fixing immune complexes in sera of patients with various disease states has been developed by utilizing C receptors on Raji cells. These cells lack membrane-bound immunoglobulin but have receptors for IgG Fc, C3b, C3d, and possibly with other C proteins. Uptake experiments showed that both aggregated human gamma globulin (AHG) and 7S IgG bound to receptors for IgG Fc; however, AHG reacted with C bound to cells only via receptors for C and this binding was much more efficient than via IgG Fc receptors. AHG was used as an in vitro model of human immune complexes and its uptake by Raji cells was quantitated by 125I-radiolabeled antihuman IgG. The limit of sensitivity of this test was 6 mug AHG/ml serum. The ability of Raji cells to detect AHG in serum depended on the amount of radioactive antibody used and the size of aggregates. The presence of an excess of C somewhat inhibited binding of AHG containing C to Raji cells. The efficient binding of AHG by receptors for C on Raji cells was used for the detection and quantitation of immune complexes in human sera. Raji cells were incubated with sera to be tested and then reacted with excess radiolabeled antihuman IgG; the amount of radioactivity bound to the washed cells was determined and referred to a standard curve of radioactive antibody uptake by cells previously incubated with increasing amounts of AHG in serum. Thereby immune complexes were detected and quantitated in serum hepatitis, systemic lupus erythematosus, vasculitis, subacute sclerosing panencephalitis, dengue hemorrhagic fever, and malignancies.