tbuckley/cabot-search huggingface dataset:
Prognostic evaluation of COPD patients: GOLD 2011 versus BODE and the COPD comorbidity index COTE
Authors: Juan P de Torres, Ciro Casanova, Jose M Marín, Victor Pinto-Plata, Miguel Divo, Javier J Zulueta, Juan Berto, Jorge Zagaceta, Pablo Sanchez-Salcedo, Carlos Cabrera, Santiago Carrizo, Claudia Cote, Bartolome R Celli
Journal: Thorax (2014)

<h3>Background</h3> The Global Obstructive Lung Disease (GOLD) 2011 revision recommends the multidimensional assessment of COPD including comorbidities and has developed a disease categories system (ABCD) attempting to implement this strategy. The added value provided by quantifying comorbidities and integrating them to multidimensional indices has not been explored. <h3>Objective</h3> Compare the prognostic value of the GOLD ABCD categories versus the BMI, Obstruction, Dyspnea, Exercise (BODE) index, and explore the added prognostic value of comorbidities evaluation to this multidimensional assessment. <h3>Methods</h3> From the patients who have been enrolled in the BODE study, we selected the most recent ones who had the available information needed to classify them by the ABCD GOLD categories. Cox proportional hazards ratios for all-cause mortality were performed for GOLD categories and BODE index. The added value of the comorbidity Copd cO-morbidity TEst (COTE) index was also explored using receiver operating curves (ROC) values. <h3>Results</h3> 707 patients were followed for 50±30 months including all degrees of airway limitation and BODE index severity. ABCD GOLD predicted global mortality (HR: 1.47; 95% CI 1.28 to 1.70) as did the BODE index (HR: 2.02; 95% CI 1.76 to 2.31). Area under the curve (AUC) of ROC for ABCD GOLD was 0.68; (95% CI 0.64 to 0.73) while for the BODE index was 0.71 (95% CI 0.67 to 0.76). The C statistics value was significantly higher for the observed difference. Adding the COTE index to the BODE index improved its AUC to 0.81 (95% CI 0.77 to 0.85), (χ<sup>2</sup>=40.28, p&lt;0.001). <h3>Conclusions</h3> In this population of COPD patients, the BODE index had a better survival prediction than the ABCD GOLD categories. Adding the COTE to the BODE index was complimentary and significantly improved outcome prediction.
Induction of junB expression, but not c-jun, by granulocyte colony-stimulating factor or macrophage colony-stimulating factor in the proliferative response of human myeloid leukemia cells.
Authors: K Adachi, H Saito
Journal: Journal of Clinical Investigation (1992)

The proliferative effects of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) on human hematopoietic cells have been reported, but the intranuclear mechanism of early signal response to these mitogenic stimuli remains unknown. Using an established human myeloid leukemia cell line (NKM-1) which can grow in serum-free medium in response to G-CSF or M-CSF, we examined expressions of the jun family genes, c-jun, junB, and junD, which are coexpressed by various growth factors in many tissues. In parallel with regrowth from the G0/G1 resting state by addition of recombinant human G-CSF or M-CSF after serum deprivation, NKM-1 cells showed the transient expression of the junB gene with a peak of ninefold above the basal level between 40 and 60 min. In contrast, c-jun expression was not stimulated by these CSFs. JunD expression was constitutively observed at detectable levels. Furthermore, c-fos mRNA was rapidly induced to a peak of 14-fold after CSF stimulation. Transcriptional run-on assays revealed that treatment of serum-starved NKM-1 with 50 ng/ml G-CSF or M-CSF increased the transcription rate of the junB gene and the c-fos gene by 1.8-fold and 2.9-fold, respectively, but did not induce any transcript of the c-jun gene. The results indicate that the expression of the junB and c-fos genes is activated, at least in part, at the transcriptional level in response to these CSFs. These findings suggest that the signal activating c-jun expression might not be involved in the proliferative action of G-CSF and M-CSF but junB may be one of important elements in early response events of the signal transduction system in human CSF-responsive hematopoietic cells.
Doxepin Rinse Versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Head and Neck Radiotherapy With or Without Chemotherapy: A Phase III, Randomized, Double-Blind Trial (NCCTG-N09C6 [Alliance])
Authors: James L. Leenstra, Robert C. Miller, Rui Qin, James A. Martenson, Kenneth J. Dornfeld, James D. Bearden, Dev R. Puri, Philip J. Stella, Miroslaw A. Mazurczak, Marie D. Klish, Paul J. Novotny, Robert L. Foote, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2014)

Painful oral mucositis (OM) is a significant toxicity during radiotherapy for head and neck cancers. The aim of this randomized, double-blind, placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain.In all, 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain. Patients received a single dose of doxepin or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day. Pain questionnaires were administered at baseline and at 5, 15, 30, 60, 120, and 240 minutes. Patients were then given the option to continue doxepin. The primary end point was pain reduction as measured by the area under the curve (AUC) of the pain scale using data from day 1.Primary end point analysis revealed that the AUC for mouth and throat pain reduction was greater for doxepin (-9.1) than for placebo (-4.7; P < .001). Crossover analysis of patients completing both phases confirmed that patients experienced greater mouth and throat pain reduction with doxepin (intrapatient changes of 4.1 for doxepin-placebo arm and -2.8 for placebo-doxepin arm; P < .001). Doxepin was associated with more stinging or burning, unpleasant taste, and greater drowsiness than the placebo rinse. More patients receiving doxepin expressed a desire to continue treatment than did patients with placebo after completion of each of the randomized phases of the study.A doxepin rinse diminishes OM pain. Further studies are warranted to determine its role in the management of OM.
Should We Use a Case-Crossover Design?
Authors: M. Maclure, and M. A. Mittleman
Journal: Annual Review of Public Health (2000)

▪ Abstract The first decade of experience with case-crossover studies has shown that the design applies best if the exposure is intermittent, the effect on risk is immediate and transient, and the outcome is abrupt. However, this design has been used to study single changes in exposure level, gradual effects on risk, and outcomes with insidious onsets. To estimate relative risk, the exposure frequency during a window just before outcome onset is compared with exposure frequencies during control times rather than in control persons. One or more control times are supplied by each of the cases themselves, to control for confounding by constant characteristics and self-confounding between the trigger's acute and chronic effects. This review of published case-crossover studies is designed to help the reader prepare a better research proposal by understanding triggers and deterrents, target person times, alternative study bases, crossover cohorts, induction times, effect and hazard periods, exposure windows, the exposure opportunity fallacy, a general likelihood formula, and control crossover analysis.
Effect of Simvastatin on Cognitive Functioning in Children With Neurofibromatosis Type 1
Authors: Lianne C. Krab, Arja de Goede-Bolder, Femke K. Aarsen, Saskia M. F. Pluijm, Marlies J. Bouman, Jos N. van der Geest, Maarten Lequin, Coriene E. Catsman, Willem Frans M. Arts, Steven A. Kushner, Alcino J. Silva, Chris I. de Zeeuw, Henriëtte A. Moll, Ype Elgersma
Journal: JAMA (2008)

EUROFIBROMATOSIS TYPE 1 (NF1) is a common autosomal-dominant genetic disorder (incidence 1:3000) 1 caused by a mutation in the gene encoding neurofibromin, a protein that activates the hydrolysis of RAS-bound guanosine triphosphate. 2Neurofibromatosis type 1 is characterized by various neurocutaneous manifestations, problems in fine and gross motor functioning, 3 as well as the frequent occurrence of cognitive disabilities.5][6][7] These problems have a large
Sturge–Weber Syndrome and Port-Wine Stains Caused by Somatic Mutation in<i>GNAQ</i>
Authors: Matthew D. Shirley, Hao Tang, Carol J. Gallione, Joseph D. Baugher, Laurence P. Frelin, Bernard Cohen, Paula E. North, Douglas A. Marchuk, Anne M. Comi, Jonathan Pevsner
Journal: New England Journal of Medicine (2013)

The Sturge–Weber syndrome is a sporadic congenital neurocutaneous disorder characterized by a port-wine stain affecting the skin in the distribution of the ophthalmic branch of the trigeminal nerve, abnormal capillary venous vessels in the leptomeninges of the brain and choroid, glaucoma, seizures, stroke, and intellectual disability. It has been hypothesized that somatic mosaic mutations disrupting vascular development cause both the Sturge–Weber syndrome and port-wine stains, and the severity and extent of presentation are determined by the developmental time point at which the mutations occurred. To date, no such mutation has been identified.
Modification of concentration-response curves to inhaled methacholine after the pollen season in subjects with pollen induced rhinitis.
Authors: L Prieto, M Lopez, J M Berto, A Peris
Journal: Thorax (1994)

The effect of cessation of exposure to pollen on the concentration-response curves to inhaled methacholine was investigated.Methacholine inhalation challenges (up to 200 mg/ml) were performed in 13 non-asthmatic patients with grass and/or Parietaria pollen-induced rhinitis during the pollen season, and one and four months after it. Concentration-response curves were characterised by their PC20, position, and plateau.Geometric mean methacholine PC20 increased from 6.4 mg/ml during the pollen season to 28.2 mg/ml and 54.9 mg/ml one and four months after the end of season, respectively. The mean (SE) level of the plateau decreased from 30.5 (4.3%) in the pollen season to 23.3 (3.7)% and 20.1 (3.3)% one and four months after the end of pollen season, respectively. Although the methacholine concentration that produced 50% of the maximal response increased from 2.9 mg/ml to 4.3 mg/ml and 6.0 mg/ml, the differences were not significant.In non-asthmatic patients with pollen-induced rhinitis cessation of exposure to pollen is associated with significant modifications in the methacholine threshold value and level of plateau, and with a small shift in the concentration-response curves to the right.
Distinct Methylation Patterns of Benign and Malignant Liver Tumors Revealed by Quantitative Methylation Profiling
Authors: Ulrich Lehmann, Ina Berg-Ribbe, Luzie U. Wingen, Kai Brakensiek, Thomas Becker, Jürgen Klempnauer, Brigitte Schlegelberger, Hans Kreipe, Peer Flemming
Journal: Clinical Cancer Research (2005)

A comparative quantitative methylation profiling of hepatocellular carcinoma and the most frequent benign liver tumor, hepatocellular adenoma, was set up for the identification of tumor-specific methylation patterns.The quantitative methylation levels of nine genes (RASSF1A, cyclinD2, p16INK4a, DAP-K, APC, RIZ-1, HIN-1, GSTpi1, SOCS-1) were analyzed in hepatocellular carcinoma and adjacent normal tissue (n = 41), hepatocellular adenoma and adjacent normal tissue (n = 26), focal nodular hyperplasia (n = 10), and unrelated normal liver tissue (n = 28). Accumulated methylation data were analyzed using various statistical algorithms, including hierarchical clustering, to detect tumor-specific methylation patterns.Cluster analysis revealed that hepatocellular adenoma displays a methylation profile much more similar to that found in normal liver tissue and focal nodular hyperplasia than to that found in hepatocellular carcinoma. Many characteristic differences were not detected when using mere qualitative methylation assays. The cyclinD2 gene was identified as a new and frequent target for aberrant hypermethylation in hepatocellular carcinoma (68%). In the control group of 28 liver specimens from healthy donors, a clear correlation between age of patient and frequency and level of aberrant methylation was seen, which could not be detected in the group of hepatocellular carcinoma specimens.Methylation profiling can clearly contribute to the unequivocal classification of suspicious lesions, but only if done in a quantitative manner applying cell type and gene-specific thresholds. In hepatocellular carcinoma, the altered methylation patterns accompanying malignant transformation override the age-dependent increase in gene methylation.
CD27 Promotes Survival of Activated T Cells and Complements CD28 in Generation and Establishment of the Effector T Cell Pool
Authors: Jenny Hendriks, Yanling Xiao, Jannie Borst
Journal: The Journal of Experimental Medicine (2003)

CD27, like CD28, acts in concert with the T cell receptor to support T cell expansion. Using CD27−/− mice, we have shown earlier that CD27 determines the magnitude of primary and memory T cell responses to influenza virus. Here, we have examined the relative contributions of CD27 and CD28 to generation of the virus-specific effector T cell pool and its establishment at the site of infection (the lung), using CD27−/−, CD28−/−, and CD27/CD28−/− mice. We find that primary and memory CD8+ T cell responses to influenza virus are dependent on the collective contribution of both receptors. In the primary response, CD27 and CD28 impact to a similar extent on expansion of virus-specific T cells in draining lymph nodes. CD27 is the principle determinant for accumulation of virus-specific T cells in the lung because it can sustain this response in CD28−/− mice. Unlike CD28, CD27 does not affect cell cycle activity, but promotes survival of activated T cells throughout successive rounds of division at the site of priming and may do so at the site of infection as well. CD27 was found to rescue CD28−/− T cells from death at the onset of division, explaining its capacity to support a T cell response in absence of CD28.
Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells
Authors: Andries Zijlstra, Marco Seandel, Tatyana A. Kupriyanova, Juneth J. Partridge, Mark A. Madsen, Elizabeth A. Hahn-Dantona, James P. Quigley, Elena I. Deryugina
Journal: Blood (2005)
Influence of Hormone Replacement Therapy on Tamoxifen-Induced Vasomotor Symptoms
Authors: Ivana Sestak, Roseann Kealy, Robert Edwards, John Forbes, Jack Cuzick
Journal: Journal of Clinical Oncology (2006)

Purpose Tamoxifen is an effective drug, but its role in prevention is limited by its adverse effect profile. Non–life-threatening adverse effects, such as vasomotor symptoms, have an important influence in its use for prevention. Vasomotor symptoms were evaluated according to follow-up time, severity, and use of hormone replacement therapy (HRT) in a retrospective analysis. Patients and Methods In the International Breast Cancer Intervention Study-I study, 7,154 women at increased risk of breast cancer were randomly assigned to either tamoxifen 20 mg/d or placebo for 5 years. Women gave detailed information on any vasomotor symptoms at each 6-month follow-up visit. Results Hot flushes were reported more often in the tamoxifen group than in the placebo group (70.6% v 57.1%, respectively; odds ratio, 1.80; 95% CI, 1.63 to 1.99). Severe hot flushes were more strongly related to tamoxifen. In the tamoxifen arm, more women taking HRT at entry experienced hot flushes in the first 6 months than those who did not take HRT (60.8% v 49.2%, respectively; P = .09). In contrast, women on placebo taking HRT at entry experienced fewer hot flushes than women who stopped HRT (22.9% v 34.3%, respectively; P = .03). Furthermore, for women who first began HRT in the first 6 months of the trial compared with women who did not begin HRT, HRT seemed to be much more effective in controlling hot flushes in months 6 to 12 in the placebo arm (47.9% v 20.4%, respectively) than in the tamoxifen arm (51.4% v 39.0%, respectively). Conclusion HRT use at entry or during the trial was not effective in alleviating hot flushes for women in the tamoxifen arm. Our retrospective study suggests that estrogen-based HRT has limited effectiveness among women receiving tamoxifen.
Deletion and anergy of polyclonal B cells specific for ubiquitous membrane-bound self-antigen
Authors: Justin J. Taylor, Ryan J. Martinez, Philip J. Titcombe, Laura O. Barsness, Stephanie R. Thomas, Na Zhang, Shoshana D. Katzman, Marc K. Jenkins, Daniel L. Mueller
Journal: The Journal of Experimental Medicine (2012)

B cell tolerance to self-antigen is critical to preventing antibody-mediated autoimmunity. Previous work using B cell antigen receptor transgenic animals suggested that self-antigen-specific B cells are either deleted from the repertoire, enter a state of diminished function termed anergy, or are ignorant to the presence of self-antigen. These mechanisms have not been assessed in a normal polyclonal repertoire because of an inability to detect rare antigen-specific B cells. Using a novel detection and enrichment strategy to assess polyclonal self-antigen-specific B cells, we find no evidence of deletion or anergy of cells specific for antigen not bound to membrane, and tolerance to these types of antigens appears to be largely maintained by the absence of T cell help. In contrast, a combination of deleting cells expressing receptors with high affinity for antigen with anergy of the undeleted lower affinity cells maintains tolerance to ubiquitous membrane-bound self-antigens.
Double-blind randomised placebo-controlled trial of bolus-dose vitamin D<sub>3</sub>supplementation in adults with asthma (ViDiAs)
Authors: Adrian R Martineau, Beverley D MacLaughlin, Richard L Hooper, Neil C Barnes, David A Jolliffe, Claire L Greiller, Kate Kilpin, David McLaughlin, Gareth Fletcher, Charles A Mein, Mimoza Hoti, Robert Walton, Jonathan Grigg, Peter M Timms, Raj K Rajakulasingam, Angshu Bhowmik, Marion Rowe, Timothy R Venton, Aklak B Choudhury, David E Simcock, Zia Sadique, William R Monteiro, Christopher J Corrigan, Catherine M Hawrylowicz, Christopher J Griffiths
Journal: Thorax (2015)

<h3>Rationale</h3> Asthma exacerbations are commonly precipitated by viral upper respiratory infections (URIs). Vitamin D insufficiency associates with susceptibility to URI in patients with asthma. Trials of vitamin D in adults with asthma with incidence of exacerbation and URI as primary outcome are lacking. <h3>Objective</h3> To conduct a randomised controlled trial of vitamin D<sub>3</sub> supplementation for the prevention of asthma exacerbation and URI (coprimary outcomes). <h3>Measurements and methods</h3> 250 adults with asthma in London, UK were allocated to receive six 2-monthly oral doses of 3 mg vitamin D<sub>3</sub> (n=125) or placebo (n=125) over 1 year. Secondary outcomes included asthma control test and St George9s Respiratory Questionnaire scores, fractional exhaled nitric oxide and concentrations of inflammatory markers in induced sputum. Subgroup analyses were performed to determine whether effects of supplementation were modified by baseline vitamin D status or genotype for 34 single nucleotide polymorphisms in 11 vitamin D pathway genes. <h3>Main results</h3> 206/250 participants (82%) were vitamin D insufficient at baseline. Vitamin D<sub>3</sub> did not influence time to first severe exacerbation (adjusted HR 1.02, 95% CI 0.69 to 1.53, p=0.91) or first URI (adjusted HR 0.87, 95% CI 0.64 to 1.16, p=0.34). No clinically important effect of vitamin D<sub>3</sub> was seen on any of the secondary outcomes listed above. The influence of vitamin D<sub>3</sub> on coprimary outcomes was not modified by baseline vitamin D status or genotype. <h3>Conclusions</h3> Bolus-dose vitamin D<sub>3</sub> supplementation did not influence time to exacerbation or URI in a population of adults with asthma with a high prevalence of baseline vitamin D insufficiency. <h3>Trial registration number</h3> NCT00978315 (ClinicalTrials.gov).
Effect of pre-exercise protein ingestion upon VO2, R and perceived exertion during treadmill running.
Authors: J Wiles, R Woodward, S R Bird
Journal: British Journal of Sports Medicine (1991)

The study investigated the effect of pre-exercise protein ingestion upon the oxygen consumption (VO2), respiratory exchange ratio (R) and perceived exertion (PE) of athletes during treadmill running at intensities of approximately 60, 80, 90 and 100% of their VO2max. Seventeen female athletes aged between 17 and 22 years participated in the study. Subjects completed six assessment sessions, each being preceded by one of the following dietary regimens: a protein solution ingested 3h before assessment (P3), a protein solution ingested 1 h before assessment (P1) and the ingestion of water 1-3 h before assessment (B). The subjects' VO2, R and PE were measured at all exercise intensities using standardized procedures. The results showed that P1 produced significantly higher values for VO2 (P less than 0.05) at all exercise intensities and was associated with an increased PE (P less than 0.01). The findings could have implications for athletes when considering the composition of their pre-exercise meal, especially if performing in activities which require the participants to exercise close to or at their VO2max.
Monitoring of nonlinear respiratory elastance using a multiple linear regression analysis
Authors: K. Muramatsu, K. Yukitake, M. Nakamura, I. Matsumoto, Y. Motohiro
Journal: European Respiratory Journal (2001)

The elastic pressure/volume (P/V) curve obtained by the multiple linear regression (MLR) technique using a new model, was compared with the quasi-static P/V points obtained by the rapid airway occlusion technique. Seven infants were studied during mechanical ventilation using a pressure controlled mode. The resistive pressure was subtracted from airway opening pressure, thus determining the elastance related pressure, which was then plotted against the volume to make an MLR-elastance curve. Quasi-static P/V curves of the rapid occlusion technique were constructed by plotting the different inspiratory and expiratory volumes against the corresponding values of the quasi-static airway pressure. The calculated MLR-elastance curves closely fit the experimental quasi-static P/V points obtained by the occlusion technique. There were, however, some discrepancies due to the viscoelastic behaviour of the respiratory system. Although slightly altered by these discrepancies, the multiple linear regression-elastance curves did fit the observed quasi-static pressure/volume characteristics for use in clinical practice. The multiple linear regression technique may prove to be clinically useful by continuous monitoring of respiratory system mechanics during mechanical ventilation.
Mechanisms of Therapeutic Activity for Gallium
Authors: Lawrence R. Bernstein
Journal: Pharmacological Reviews (1998)

Gallium, a semi-metallic element in group 13 (IIIa) of the periodic table, has shown efficacy in the treatment of several apparently diverse disorders. These disorders can be broadly categorized as: ( a ) accelerated bone resorption, with or without elevated plasma calcium; ( b ) autoimmune disease