tbuckley/cabot-search huggingface dataset:
Validation of CAT as an independent assessment tool in pulmonary rehabilitation (PR) for chronic obstructive pulmonary disease (COPD)
Authors: Shakila Devi Perumal, Cormac McCarthy, Mary Frances O'Driscoll, Timothy J. McDonnell
Journal: European Respiratory Journal (2012)

The benefits of PR in COPD are well recognised but the practical assessment of patients undergoing PR can be complex. The COPD assessment test (CAT) is a recently introduced simple, validated 8-item questionnaire designed to assess the impact of COPD symptoms on quality of life (QOL). We hypothesized that CAT could be used as a screening tool and outcome measure to assess QOL in COPD.

60 patients with COPD enrolled in 8 weeks outpatient PR between January 2011 and October 2011 were studied. Patients completed CAT score, chronic respiratory disease questionnaire (CRDQ), hospital anxiety and depression (HAD) at baseline and at 8 weeks. Functional status (6 min walk test (6MWT) and incremental shuttle walk test (ISWT)), dyspnoea (MRCD) and body mass index (BMI) were measured.

52 COPD patients completed the 8 weeks PR and data were available for 37 patients with mean (SD) age 68.7 (9.2) yrs and FEV1 48.64 (20.79) % predicted. There was a significant difference in 6MWT (47.03m), ISWT (47.84m), MRCD (0.3 points), CRDQ (-3.02 points), Anxiety (1.5points), depression (0.6points) and CAT (3.63 points) post PR. CAT correlated closely with CRDQ at baseline and following PR whereas there was good correlation only with ISWT, anxiety and depression post PR.

CAT is an independent, simple and highly responsive outcome measure that can also be utilized for screening patients with COPD for PR.
Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia
Authors: Teresa Palomero, Duncan T. Odom, Jennifer O'Neil, Adolfo A. Ferrando, Adam Margolin, Donna S. Neuberg, Stuart S. Winter, Richard S. Larson, Wei Li, X. Shirley Liu, Richard A. Young, A. Thomas Look
Journal: Blood (2006)
The Role of Clinical Uncertainty in Treatment Decisions for Diabetic Patients with Uncontrolled Blood Pressure
Authors: Eve A. Kerr, Brian J. Zikmund-Fisher, Mandi L. Klamerus, Usha Subramanian, Mary M. Hogan, Timothy P. Hofer
Journal: Annals of Internal Medicine (2008)

Background: Factors underlying failure to intensify therapy in response to elevated blood pressure have not been systematically studied. Objective: To examine the process of care for diabetic patients with elevated triage blood pressure (≥140/90 mm Hg) during routine primary care visits to assess whether a treatment change occurred and to what degree specific patient and provider factors correlated with the likelihood of treatment change. Design: Prospective cohort study. Setting: 9 Veterans Affairs facilities in 3 midwestern states. Participants: 1169 diabetic patients with scheduled visits to 92 primary care providers from February 2005 to March 2006. Measurements: Proportion of patients who had a change in a blood pressure treatment (medication intensification or planned follow-up within 4 weeks). Predicted probability of treatment change was calculated from a multilevel logistic model that included variables assessing clinical uncertainty, competing demands and prioritization, and medication-related factors (controlling for blood pressure). Results: Overall, 573 (49%) patients had a blood pressure treatment change at the visit. The following factors made treatment change less likely: repeated blood pressure by provider recorded as less than 140/90 mm Hg versus 140/90 mm Hg or greater or no recorded repeated blood pressure (13% vs. 61%; P < 0.001); home blood pressure reported by patients as less than 140/90 mm Hg versus 140/90 mm Hg or greater or no recorded home blood pressure (18% vs. 52%; P < 0.001); provider systolic blood pressure goal greater than 130 mm Hg versus 130 mm Hg or less (33% vs. 52%; P = 0.002); discussion of conditions unrelated to hypertension and diabetes versus no discussion (44% vs. 55%; P = 0.008); and discussion of medication issues versus no discussion (23% vs. 52%; P < 0.001). Limitation: Providers knew that the study pertained to diabetes and hypertension, and treatment change was assessed for 1 visit per patient. Conclusion: Approximately 50% of diabetic patients presenting with a substantially elevated triage blood pressure received treatment change at the visit. Clinical uncertainty about the true blood pressure value was a prominent reason that providers did not intensify therapy.
Correlation between annual change in health status and computer tomography derived lung density in subjects with 1-antitrypsin deficiency
Authors: J Stolk
Journal: Thorax (2003)

There is increasing recognition that questionnaires of health status and lung density measurements are more sensitive tools for assessing progression of emphysema than forced expiratory volume in 1 second (FEV(1)) and transfer coefficient (KCO). A study was undertaken to investigate prospectively the correlation between annual change in health status and computer tomography (CT) derived lung density in subjects with alpha(1)-antitrypsin deficiency.Twenty two patients of mean (SD) age 40.7 (9.2) years with ZZ type alpha(1)-antitrypsin deficiency were investigated at baseline and 30 months later by FEV(1) and KCO, St George Respiratory Questionnaire (SGRQ), and by a spiral CT scan of the chest. CT data of chest images were analysed using software designed for automated lung contour detection and lung density measurements. The density data were corrected for changes in inspiration levels.Changes in lung density, expressed as 15th percentile point or relative area below -950 HU, correlated well with changes in health status (SGRQ total score): R = -0.56, p = 0.007 or R = 0.6, p = 0.003. Neither changes in health status nor changes in lung density correlated significantly with changes in FEV(1) or changes in KCO.The SGRQ total score (which is a global measure in COPD) and lung density (a specific measure of emphysema) are sensitive to deterioration in patients with alpha(1)-antitrypsin deficiency. This finding may facilitate future studies with new drugs specific for emphysema, a frequently occurring component of COPD.
Does Blood Glucose Monitoring Increase Prior to Clinic Visits in Children With Type 1 Diabetes?
Authors: Kimberly A. Driscoll, Suzanne Bennett Johnson, Yuanyuan Tang, Fang Yang, Larry C. Deeb, Janet H. Silverstein
Journal: Diabetes Care (2011)

To assess the occurrence of white coat adherence in families with children who have type 1 diabetes.Blood glucose data were downloaded from meters of 72 children, aged 2-11 years, with type 1 diabetes at four consecutive clinic visits. Generalized estimating equations were used to analyze patterns of blood glucose monitoring (BGM) during the 28 days before each clinic visit.More frequent BGM was associated with better glycemic control. Evidence of a white coat adherence effect, with BGM frequency increasing before a clinic visit, was found only among children with low A1C levels.Highly motivated families who frequently monitor their child's blood glucose increased the frequency of BGM before the child's clinic visit. The additional monitoring may benefit the child by providing the physician with a wealth of blood glucose information to guide recommendations.
Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study
Authors: Y Benhamou, M Bochet, V Thibault, V Calvez, MH Fievet, P Vig, CS Gibbs, C Brosgart, J Fry, H Namini, C Katlama, T Poynard
Journal: The Lancet (2001)
Distinct Roles of Nonmuscle Myosin II Isoforms in the Regulation of MDA-MB-231 Breast Cancer Cell Spreading and Migration
Authors: Venkaiah Betapudi, Lucila S. Licate, Thomas T. Egelhoff
Journal: Cancer Research (2006)

Abstract Initial stages of tumor cell metastasis involve an epithelial-mesenchyme transition that involves activation of amoeboid migration and loss of cell-cell adhesion. The actomyosin cytoskeleton has fundamental but poorly understood roles in these events. Myosin II, an abundant force-producing protein, has roles in cell body translocation and retraction of the posterior of the cell during migration. Recent studies have suggested that this protein may also have roles in leading edge protrusive events. The metastasis-promoting protein metastasin-1, a regulator of myosin II assembly, colocalizes with myosin IIA at the leading edge of cancer cells, suggesting direct roles for myosin II in metastatic behavior. We have assessed the roles of specific myosin II isoforms during lamellar spreading of MDA-MB-231 breast cancer cells on extracellular matrix. We find that the two major myosin II isoforms IIA and IIB are both expressed in these cells, and both are recruited dramatically to the lamellar margin during active spreading on fibronectin. There is also a transient increase in regulatory light chain phosphorylation that correlates the recruitment of myosin IIA and myosin IIB into this spreading margin. Pharmacologic inhibition of myosin II or myosin light chain kinase dramatically reduced spreading. Depletion of myosin IIA via small interfering RNA impaired migration but enhanced lamellar spreading, whereas depletion of myosin IIB impaired not only migration but also impaired initial rates of lamellar spreading. These results indicate that both isoforms are critical for the mechanics of cell migration, with myosin IIB seeming to have a preferential role in the mechanics of lamellar protrusion. (Cancer Res 2006; 66(9): 4725-33)
Aspirin-Resistant Thromboxane Biosynthesis and the Risk of Myocardial Infarction, Stroke, or Cardiovascular Death in Patients at High Risk for Cardiovascular Events
Authors: John W. Eikelboom, Jack Hirsh, Jeffrey I. Weitz, Marilyn Johnston, Qilong Yi, Salim Yusuf
Journal: Circulation (2002)

We studied whether aspirin resistance, defined as failure of suppression of thromboxane generation, increases the risk of cardiovascular events in a high-risk population.Baseline urine samples were obtained from 5529 Canadian patients enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study. Using a nested case-control design, we measured urinary 11-dehydro thromboxane B2 levels, a marker of in vivo thromboxane generation, in 488 cases treated with aspirin who had myocardial infarction, stroke, or cardiovascular death during 5 years of follow-up and in 488 sex- and age-matched control subjects also receiving aspirin who did not have an event. After adjustment for baseline differences, the odds for the composite outcome of myocardial infarction, stroke, or cardiovascular death increased with each increasing quartile of 11-dehydro thromboxane B2, with patients in the upper quartile having a 1.8-times-higher risk than those in the lower quartile (OR, 1.8; 95% CI, 1.2 to 2.7; P=0.009). Those in the upper quartile had a 2-times-higher risk of myocardial infarction (OR, 2.0; 95% CI, 1.2 to 3.4; P=0.006) and a 3.5-times-higher risk of cardiovascular death (OR, 3.5; 95% CI, 1.7 to 7.4; P<0.001) than those in the lower quartile.In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B2 predict the future risk of myocardial infarction or cardiovascular death. These findings raise the possibility that elevated urinary 11-dehydro thromboxane B2 levels identify patients who are relatively resistant to aspirin and who may benefit from additional antiplatelet therapies or treatments that more effectively block in vivo thromboxane production or activity.
Maintenance of T Cell Specification and Differentiation Requires Recurrent Notch Receptor–Ligand Interactions
Authors: Thomas M. Schmitt, Maria Ciofani, Howard T. Petrie, Juan Carlos Zúñiga-Pflücker
Journal: The Journal of Experimental Medicine (2004)

Notch signaling has been shown to play a pivotal role in inducing T lineage commitment. However, T cell progenitors are known to retain other lineage potential long after the first point at which Notch signaling is required. Thus, additional requirements for Notch signals and the timing of these events relative to intrathymic differentiation remain unknown. Here, we address this issue by culturing subsets of CD4 CD8 double negative (DN) thymocytes on control stromal cells or stromal cells expressing Delta-like 1 (Dll1). All DN subsets were found to require Notch signals to differentiate into CD4+ CD8+ T cells. Using clonal analyses, we show that CD44+ CD25+ (DN2) cells, which appeared committed to the T cell lineage when cultured on Dll1-expressing stromal cells, nonetheless gave rise to natural killer cells with a progenitor frequency similar to that of CD44+ CD25− (DN1) thymocytes when Notch signaling was absent. These data, together with the observation that Dll1 is expressed on stromal cells throughout the thymic cortex, indicates that Notch receptor–ligand interactions are necessary for induction and maintenance of T cell lineage specification at both the DN1 and DN2 stages of T cell development, suggesting that the Notch-induced repression of the B cell fate is temporally separate from Notch-induced commitment to the T lineage.
Biomarkers in GIST: Partly Ready for Prime-Time Use
Authors: Charles D. Blanke
Journal: Clinical Cancer Research (2009)

Gastrointestinal stromal tumors, or GISTs, are now among the most treatable of solid malignancies. Assessing actual tumor response remains challenging; however, in this issue of Clinical Cancer Research, two articles discuss biomarkers potentially helpful in predicting response or other long-term benefits with standard tyrosine kinase therapy use.
Chemo-Electrical Transduction in Insect Olfactory Receptors
Authors: Karl-Ernst Kaissling
Journal: Annual Review of Neuroscience (1986)

Insect behavior can be controlled by a single odor  or by a blend of a few components in an exact ratio of concentrations. These odor compounds or odor mixtures are called pheromones if used for intraspecific communication. Each of the pheromone components is perceived by a particular type of receptor cell that is specifically tuned to its key compound and may respond to single odor molecules by firing single nerve impulses. The entire response range of a receptor cell may cover many decades of stimulus intensities. Each olfactory receptor cell is a bipolar neuron. Its dendrite innervates a specialized cuticular structure, usually a hollow cuticular hair that captures the stimulus molecules. The axon runs directly to the deutocerebrum-the first synaptic relay station of the central nervous system. Chemo-electrical transduction in these organs comprises the processes leading from the adsorption of odor molecules on the cuticular surface via stimulus transport to the generation of receptor potentials and nerve impulses and, eventually, to the inactivation of the stimulus molecules. The interconnections of these processes and their influences on the ultimate impulse response of the receptor cells are largely unknown. This review covers electrophysiological investigations of cellular response charac­ teristics as well as biophysical and biochemical work, much of which is based on radiolabeled pheromone compounds. These studies employed a few species of insects, mainly of moths with olfactory organs that are relatively large and accessible for experimental work. The olfactory hairs of
Mutant p53 Disrupts the Stress MAPK Activation Circuit Induced by ASK1-Dependent Stabilization of Daxx
Authors: Tetsuya Kitamura, Yayoi Fukuyo, Masahiro Inoue, Nobuko T. Horikoshi, Masanobu Shindoh, Buck E. Rogers, Anny Usheva, Nobuo Horikoshi
Journal: Cancer Research (2009)

Daxx is a regulatory protein for apoptosis signal-regulating kinase 1 (ASK1) which activates c-Jun NH2-terminal kinase (JNK) and p38 pathways in response to stressors such as tumor necrosis factor-alpha (TNFalpha). Here, we show that TNFalpha treatment induces the accumulation of Daxx protein through ASK1 activation by preventing its proteasome-dependent degradation. ASK1 directly phosphorylates Daxx at Ser(176) and Ser(184) and Daxx is required for the sustained activation of JNK. Tumorigenic mutant p53, which binds to Daxx and inhibits Daxx-dependent activation of ASK1, prevents Daxx phosphorylation and stabilization. When mutant p53 was depleted in cancer cells, Daxx was accumulated and the cell-killing effect of TNFalpha was restored. Our results indicate that Daxx not only activates ASK1 but also is a downstream target of ASK1 and that accumulated Daxx further activates ASK1. Thus, the Daxx-ASK1 positive feedback loop amplifying JNK/p38 signaling plays an important role in the cell-killing effects of stressors, such as TNFalpha. Tumorigenic mutant p53 disrupts this circuit and makes cells more tolerable to stresses, as its gain-of-function mechanism.
B cell epitopes of the heterogeneous nuclear ribonucleoprotein A2: identification of a new specific antibody marker for active lupus disease
Authors: G Schett, H Dumortier, E Hoefler, S Muller, G Steiner
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: Autoantibody formation and T cell reactivity against the heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2) has been observed in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Since no differences in epitope recognition were reported and the usefulness of anti-hnRNP-A2 antibodies as diagnostic markers of SLE is unknown, it was our objective to characterise linear B cell epitopes of hnRNP-A2 and to relate the anti-hnRNP-A2 antibody responses to disease activity and clinical features of SLE. Methods: Sequential serum samples from 15 patients with SLE and sera from patients with other rheumatic diseases and healthy subjects were investigated by ELISA for autoantibody reactivities against a set of 13 overlapping peptides spanning the RNA-binding region of hnRNP-A2. Antibody reactivity against the complete protein was determined by western immunoblotting and ELISA. SLE disease activity was assessed by European Consensus Lupus Activity Measure scores, by SLE Index scores and the British Isles Lupus Assessment index. Results: Anti-peptide antibody reactivities were found in 60% of SLE sera but in only 5% of control samples, and were mainly directed to four peptides, one of which (p155–175) appeared to be immunodominant. Antibodies to p155–175 were exclusively seen in patients with SLE and correlated with clinical disease activity as well as kidney and skin involvement. No correlations were found for the other anti-peptide antibody responses. Conclusion: Peptide p155–175 encompasses a disease-specific immunodominant epitope of hnRNP-A2. Since antibodies to p155–175 correlate with disease activity and nephritis, they may be useful as markers for active SLE.
500 EMERGENCE OF HBSAG ESCAPE MUTATIONS IS ASSOCIATED WITH USE OF NUCLEOS(T)IDE ANALOGUES IN CHRONIC HEPATITIS B PATIENTS
Authors: S. Mahinrousta, A. Pouryasin, S.M. Alavian, B. Behnava, H. Sharafi, O. Kheradvar, M. Zareiy
Journal: Journal of Hepatology (2012)
Clinical Importance of <i>Alternaria</i> Exposure in Children
Authors: SARA H. DOWNS, TERESA Z. MITAKAKIS, GUY B. MARKS, N. GEORGE CAR, ELENA G. BELOUSOVA, JÖRG D. LEÜPPI, WEI XUAN, SUE R. DOWNIE, AURELIO TOBIAS, JENNIFER K. PEAT
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The fungus Alternaria is known to be allergenic and is one of the most common fungi worldwide. We investigated the extent to which exposure to Alternaria increases the severity of asthma. We undertook a prospective cohort study in Australia of 399 school children who had positive skin tests to one or more aeroallergens. Airway responsiveness to histamine, wheeze, and bronchodilator use in 1 mo was measured five times between 1997 and 1999. Airway hyperresponsiveness was defined as PD(20)FEV(1) = 3.9 micromol histamine. Airborne concentrations of Alternaria spores were measured throughout the study, and mean daily concentrations over 1 mo ranged from 2.2 to 307.7 spores/m(3) of ambient air. Using generalized estimating equations, we found that airway responsiveness, wheeze, and bronchodilator use increased significantly in association with increased spore concentrations and that the increase in airway responsiveness was greater in children sensitized to Alternaria than in other children (p = 0.01). The odds ratio for airway hyperresponsiveness in children sensitized to Alternaria was 1.26 (95% CI, 1.14 to 1.39) after an increase in mean exposure of 100 spore/m(3)/d over 1 mo. These results suggest that Alternaria allergens contribute to severe asthma in regions where exposure to the fungus is high.
Arsenic trioxide (As2O3)-induced apoptosis and differentiation in retinoic acid-resistant acute promyelocytic leukemia model in hGM-CSF-producing transgenic SCID mice
Authors: K Kinjo, M Kizaki, A Muto, Y Fukuchi, A Umezawa, K Yamato, T Nishihara, J Hata, M Ito, Y Ueyama, Y Ikeda
Journal: Leukemia (2000)
Confidential Enquiries into Perinatal Deaths.
Authors: T Walsh
Journal: BMJ (1982)

Stress and illness SIR,-I would like to comment on Minerva's point (6 February, p 426) that whenever careful epidemiological research is done into the effects of stress on illness the answers tend to be negative.Even careful research cannot always come up with the right answer.Lifeevent scales are a very unsatisfactory way of evaluating the effects of stress for they omit exploration of one of the most potentially stressful areas of life-that is, family relationships.The only dimension of such relationships that life-event scales explore is frequency of arguments.Arguments, however, are not neccssarily the most stressful aspects of family life.Indeed, there is considerable evidence now that avoidance of argument and detouring of conflict is far more stressful.1Indeed, conflict avoidance is one of the main features in families containing "psychosomatic" illness.Other associated family characteristics are over- involvement, overprotectiveness, and rigidity.None of these are explored in the life-event scales.Further, it should be noted that once such family problems are treated there is often dramatic improvement in the illness.2
Peripheral Chemoreceptor Hypersensitivity
Authors: Piotr Ponikowski, Tuan Peng Chua, Stefan D. Anker, Darrel P. Francis, Wolfram Doehner, Waldemar Banasiak, Phillip A. Poole-Wilson, Massimo F. Piepoli, Andrew J.S. Coats
Journal: Circulation (2001)

Peripheral chemoreceptor hypersensitivity is a feature of abnormal cardiorespiratory reflex control in chronic heart failure (CHF) and may contribute to sympathetic overactivity, attenuated baroreflex sensitivity (BRS), and excessive ventilation during exercise. We studied whether augmented peripheral chemosensitivity carries independent prognostic significance.We assessed peripheral chemosensitivity (ventilatory response to hypoxia using transient inhalation of pure nitrogen) and BRS (phenylephrine and spectral methods) in 80 consecutive CHF patients (age 58+/-9 years; left ventricular ejection fraction [LVEF] 24+/-12%; peak oxygen consumption [peak VO(2)] 18+/-7 mL(-1). min(-1)). CHF patients demonstrated augmented peripheral chemosensitivity and decreased BRS (all P<0.01 versus reference values). During follow-up (median 41 months, >3 years in all survivors), 37 patients died. High peripheral chemosensitivity (>0.72 L. min(-1). %SaO(2)(-1)) predicted impaired survival (hazard ratio 3.2, 95% CI 1.6 to 6.0, P=0.0006). In the 27 patients (34%) with high peripheral chemosensitivity, 3-year survival was 41% (95% CI 22% to 60%) compared with 77% (66% to 89%) in 53 patients with normal chemosensitivity (P=0.0002). In multivariate analyses, augmented chemosensitivity independently predicted death (hazard ratio 2.8, 95% CI 1.5 to 5.5, adjusted for age, peak VO(2), and VE/VCO(2) [P=0.002]; hazard ratio 2.6, 95% CI 1.3 to 5.1, adjusted for age, LVEF, and peak VO(2) [P=0.008]). Depressed BRS was related to unfavorable prognosis in univariate analysis (P=0.05) but not in multivariate analyses.Hypersensitivity of the peripheral chemoreceptors independently predicts adverse prognosis in ambulatory patients with CHF. This hyperactive excitatory reflex, through its inhibitory effect on the baroreflex, may be the reason for the previously observed prognostic association of the latter.