tbuckley/cabot-search huggingface dataset:
Understanding asthma-specific quality of life: moving beyond asthma symptoms and severity
Authors: Brian D. Stucky, Cathy D. Sherbourne, Maria Orlando Edelen, Nicole K. Eberhart
Journal: European Respiratory Journal (2015)

This study identifies the unique contributions of asthma severity, symptoms, control and generic measures of quality of life (QoL) to asthma-specific QoL, as measured by the 12-item RAND Negative Impact of Asthma on Quality of Life scale (RAND-IAQL-12). Using a sample of 2032 adults with asthma, we conducted multiple regression analyses that sequentially examined hypothesised predictors of asthma-specific QoL. The change in variance accounted for and total unique variance accounted for is calculated as hypothesised predictors are added in each step. Our results indicate that asthma severity and asthma symptoms are strong predictors of asthma-specific QoL only when not controlling for aspects of asthma control. In regression models that include other aspects of asthma control, the contributions of both asthma symptoms and severity were substantially reduced, with asthma control and aspects of QoL related to social roles and activities emerging as the strongest predictors of asthma-specific QoL. These findings suggest that researchers measuring the impact of asthma on QoL should also consider the importance of asthma control as measured by the RAND Asthma Control Measure (RAND-ACM) and generic QoL scales that measure aspects of daily life that are uniquely affected by asthma.
Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B
Authors: Pietro Lampertico, Mauro Viganò, Giovan Giuseppe Di Costanzo, Evangelista Sagnelli, Massimo Fasano, Vito Di Marco, Sara Boninsegna, Patrizia Farci, Silvia Fargion, Tiziana Giuberti, Claudio Iannacone, Loredana Regep, Benedetta Massetto, Floriana Facchetti, Massimo Colombo
Journal: Gut (2012)

<h3>Objective</h3> Treatment with peginterferon α-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population. <h3>Methods</h3> 128 HBeAg-negative patients (120 genotype D) were randomised to weekly 180 μg PegIFN for 48 weeks (group A, n=51), 180 μg PegIFN for 48 weeks followed by 135 μg weekly for an additional 48 weeks (group B, n=52) or 180 μg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 μg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalisation plus HBV DNA &lt;3400 IU/ml (primary), HBV DNA &lt;2000 IU/ml and HBsAg clearance at 48 weeks after treatment. <h3>Results</h3> Forty-eight weeks after treatment, six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA &lt;3400 IU/ml (11.8% vs 25.0%, p=0.08), 6 vs 15 patients had HBV DNA &lt;2000 IU/ml (11.8% vs 28.8%, p=0.03), 0 vs 3 achieved HBsAg clearance (0% vs 5.8%, p=0.24) and 0 vs 5 had HBsAg &lt;10 IU/ml (0% vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent predictor of response, the combination with lamivudine did not improve responses. Discontinuation rates were similar among the groups (19.6%, 23.1%, 32.0%, p=0.81) and were mostly due to PegIFN-related adverse events. <h3>Conclusions</h3> In HBeAg-negative genotype D patients with chronic hepatitis B, PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment. <h3>Trial registration number</h3> http://ClinicalTrials.gov registration number: NCT01095835.
Intake of Coffee, Decaffeinated Coffee, or Tea Does Not Affect Risk for Pancreatic Cancer: Results From the European Prospective Investigation into Nutrition and Cancer Study
Authors: Nirmala Bhoo–Pathy, Cuno S.P.M. Uiterwaal, Vincent K. Dik, Suzanne M. Jeurnink, Bodil H. Bech, Kim Overvad, Jytte Halkjær, Anne Tjønneland, Marie–Christine Boutron–Ruault, Guy Fagherazzi, Antoine Racine, Verena A. Katzke, Kuanrong Li, Heiner Boeing, Anna Floegel, Anna Androulidaki, Christina Bamia, Antonia Trichopoulou, Giovanna Masala, Salvatore Panico, Paolo Crosignani, Rosario Tumino, Paolo Vineis, Petra H.M. Peeters, Oxana Gavrilyuk, Guri Skeie, Elisabete Weiderpass, Eric J. Duell, Marcial Arguelles, Esther Molina–Montes, Carmen Navarro, Eva Ardanaz, Miren Dorronsoro, Björn Lindkvist, Peter Wallström, Malin Sund, Weimin Ye, Kay–Tee Khaw, Nick Wareham, Timothy J. Key, Ruth C. Travis, Talita Duarte–Salles, Heinz Freisling, Idlir Licaj, Valentina Gallo, Dominique S. Michaud, Elio Riboli, H. Bas Bueno–De–Mesquita
Journal: Clinical Gastroenterology and Hepatology (2013)
Does Snoring Predict Sleepiness Independently of Apnea and Hypopnea Frequency?
Authors: DANIEL J. GOTTLIEB, QING YAO, SUSAN REDLINE, TAUQEER ALI, MARK W. MAHOWALD
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Obstructive apneas and hypopneas during sleep are a well recognized cause of excessive daytime sleepiness. Snoring is also associated with excess sleepiness, although it is not known whether this reflects an independent effect of snoring or whether snoring is simply a marker for obstructive sleep apnea. To further explore the relation of snoring to sleepiness, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study. The study sample comprises 2,737 men and 3,040 women with a mean age of 64 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Snoring history was obtained via a self-completion questionnaire. The respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, was measured during in-home polysomnography. The ESS score increased progressively with increasing RDI, from a mean of 7.1 (4.2) in subjects with RDI < 1.5 to 8.8 (4.8) in subjects with RDI >/= 15 (p < 0.001). A progressive increase in ESS score was also seen across five categories of snoring frequency, from 6.4 (4.2) in current nonsnorers to 9.3 (4.8) in subjects who snored six to seven nights per week (p < 0.001). The prevalence of excessive daytime sleepiness, defined as an ESS score >/= 11, increased from 15% in never-snorers to 39% in those who snored six to seven nights per week. The relation of snoring to sleepiness was seen at all levels of RDI, with no significant change in the relation of snoring to ESS score after adjustment for RDI in multivariate models. The effects of snoring and RDI on sleepiness were little affected by adjustment for age, sex, race, body mass index, or questionnaire evidence of insufficient sleep time or nocturnal leg jerks or cramps. We conclude that both snoring and RDI are independently associated with excess sleepiness in community-dwelling, middle-aged and older adults.
Lung imaging during acute chest syndrome in sickle cell disease: computed tomography patterns and diagnostic accuracy of bedside chest radiograph
Authors: Armand Mekontso Dessap, Jean-François Deux, Anoosha Habibi, Nour Abidi, Bertrand Godeau, Serge Adnot, Christian Brun-Buisson, Alain Rahmouni, Frederic Galacteros, Bernard Maitre
Journal: Thorax (2013)

<h3>Introduction</h3> The lung computed tomography (CT) features of acute chest syndrome (ACS) in sickle cell disease patients is not well described, and the diagnostic performance of bedside chest radiograph (CR) has not been tested. Our objectives were to describe CT features of ACS and evaluate the reproducibility and diagnostic performance of bedside CR. <h3>Methods</h3> We screened 127 consecutive patients during 166 ACS episodes and 145 CT scans (in 118 consecutive patients) were included in the study. <h3>Results</h3> Among the 145 CT scans, 139 (96%) exhibited a new pulmonary opacity and 84 (58%) exhibited at least one complete lung segment consolidation. Consolidations were predominant as compared with ground-glass opacities and atelectasis. Lung parenchyma was increasingly consolidated from apex to base; the right and left inferior lobes were almost always involved in patients with a new complete lung segment consolidation on CT scan (98% and 95% of cases, respectively). Patients with a new complete lung segment consolidation on CT scan had a more severe presentation and course as compared with others. The sensitivity of bedside CR for the diagnosis of ACS using CT as a reference was good (&gt;85%), whereas the specificity was weak (&lt;60%). <h3>Conclusions</h3> ACS more frequently presented on CT as a consolidation pattern, predominating in lung bases. The reproducibility and diagnostic capacity of bedside CR were far from perfect. These findings may help improve the bedside imaging diagnosis of ACS.
Frequency and significance of granulomas in a cohort of incident cases of Crohn's disease
Authors: D Heresbach
Journal: Gut (2005)

<b>Background and aims:</b> Epithelioid granulomas is one of the best histological criterion for distinguishing Crohn’s disease (CD) from other inflammatory bowel diseases. Few data are available on the time of occurrence of epithelioid granulomas, and the value of epithelioid granulomas in predicting outcome has been determined only in cohorts of prevalent CD cases. Our objective was to evaluate epithelioid granuloma occurrence in incident CD cases and to examine the associations between epithelioid granulomas and outcome. <b>Patients and methods:</b> We reviewed the histological reports of endoscopic and surgical specimens in a cohort of 188 consecutive incident CD cases seen in 1994 and 1995, and recorded the occurrence of epithelioid granulomas, isolated giant cells, and microgranulomas. Kaplan-Meier curves were plotted for time from CD diagnosis to immunosuppressive treatment or surgery, and associations between epithelioid granulomas and outcome were evaluated in a multivariate analysis. Follow up was at least five years. <b>Results:</b> Granulomas were found in 69 (37%) patients, including 46 (25%) at presentation. Median time from CD diagnosis to epithelioid granuloma detection was 0.16 (0–63) months overall, and 9.59 (0.1–63) months in 23 patients who became epithelioid granuloma positive during follow up. Isolated giant cells were found in 6% of patients and microgranulomas in 12%. Epithelioid granuloma detection increased with the number of endoscopic sampling procedures; sampling site had no influence. By multivariate analysis, epithelioid granulomas were associated with surgical resection but not immunosuppressive therapy. <b>Conclusions:</b> Epithelioid granulomas may separate CD into two pathological subsets and may indicate aggressive disease.
Regulation of primordial follicle assembly and development
Authors: Michael K. Skinner
Journal: Human Reproduction Update (2005)

The assembly of the primordial follicles early in ovarian development and the subsequent development and transition of the primordial follicle to the primary follicle are critical processes in ovarian biology. These processes directly affect the number of oocytes available to a female throughout her reproductive life. Once the pool of primordial follicles is depleted a series of physiological changes known as menopause occur. The inappropriate coordination of these processes contributes to ovarian pathologies such as premature ovarian failure (POF) and infertility. Primordial follicle assembly and development are coordinated by locally produced paracrine and autocrine growth factors. Endocrine factors such as progesterone have also been identified that influence follicular assembly. Locally produced factors that promote the primordial to primary follicle transition include growth factors such as kit ligand (KL), leukaemia inhibitory factor (LIF), bone morphogenic proteins (BMP's), keratinocyte growth factor (KGF) and basic fibroblast growth factor (bFGF). Factors mediating both precursor theca–granulosa cell interactions and granulosa–oocyte interactions have been identified. A factor produced by preantral and antral follicles, Müllerian inhibitory substance, can act to inhibit the primordial to primary follicle transition. Observations suggest that a complex network of cell–cell interactions is required to control the primordial to primary follicle transition. Elucidation of the molecular and cellular control of primordial follicle assembly and the primordial to primary follicle transition provides therapeutic targets to regulate ovarian function and treat ovarian disease.
Regression based quasi-experimental approach when randomisation is not an option: interrupted time series analysis
Authors: E. Kontopantelis, T. Doran, D. A. Springate, I. Buchan, D. Reeves
Journal: BMJ (2015)

Interrupted time series analysis is a quasi-experimental design that can evaluate an intervention effect, using longitudinal data. The advantages, disadvantages, and underlying assumptions of various modelling approaches are discussed using published examples
Mutations in Alpha-Actinin-2 Cause Hypertrophic Cardiomyopathy
Authors: Christine Chiu, Richard D. Bagnall, Jodie Ingles, Laura Yeates, Marina Kennerson, Jennifer A. Donald, Mika Jormakka, Joanne M. Lind, Christopher Semsarian
Journal: Journal of the American College of Cardiology (2009)
Effect of smoking on comparative efficacy of antiplatelet agents: systematic review, meta-analysis, and indirect comparison
Authors: Joshua J Gagne, Katsiaryna Bykov, Niteesh K Choudhry, Timothy J Toomey, John G Connolly, Jerry Avorn
Journal: BMJ (2013)

<b>Objective</b> To evaluate whether smoking status is associated with the efficacy of antiplatelet treatment in the prevention of cardiovascular events. <b>Design</b> Systematic review, meta-analysis, and indirect comparisons. <b>Data sources</b> Medline (1966 to present) and Embase (1974 to present), with supplementary searches in databases of abstracts from major cardiology conferences, the Cumulative Index to Nursing and Allied Health (CINAHL) and the CAB Abstracts databases, and Google Scholar. <b>Study selection</b> Randomized trials of clopidogrel, prasugrel, or ticagrelor that examined clinical outcomes among subgroups of smokers and nonsmokers. <b>Data extraction</b> Two authors independently extracted all data, including information on the patient populations included in the trials, treatment types and doses, definitions of clinical outcomes and duration of follow-up, definitions of smoking subgroups and number of patients in each group, and effect estimates and 95% confidence intervals for each smoking status subgroup. <b>Results</b> Of nine eligible randomized trials, one investigated clopidogrel compared with aspirin, four investigated clopidogrel plus aspirin compared with aspirin alone, and one investigated double dose compared with standard dose clopidogrel; these trials include 74 489 patients, of whom 21 717 (29%) were smokers. Among smokers, patients randomized to clopidogrel experienced a 25% reduction in the primary composite clinical outcome of cardiovascular death, myocardial infarction, and stroke compared with patients in the control groups (relative risk 0.75, 95% confidence interval 0.67 to 0.83). In nonsmokers, however, clopidogrel produced just an 8% reduction in the composite outcome (0.92, 0.87 to 0.98). Two studies investigated prasugrel plus aspirin compared with clopidogrel plus aspirin, and one study investigated ticagrelor plus aspirin compared with clopidogrel plus aspirin. In smokers, the relative risk was 0.71 (0.61 to 0.82) for prasugrel compared with clopidogrel and 0.83 (0.68 to 1.00) for ticagrelor compared with clopidogrel. Corresponding relative risks were 0.92 (0.83 to 1.01) and 0.89 (0.79 to 1.00) among nonsmokers. <b>Conclusions</b> In randomized clinical trials of antiplatelet drugs, the reported clinical benefit of clopidogrel in reducing cardiovascular death, myocardial infarction, and stroke was seen primarily in smokers, with little benefit in nonsmokers.
Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production
Authors: Mee Rhan Kim, Raffi Manoukian, Richard Yeh, Scott M. Silbiger, Dimitry M. Danilenko, Sheila Scully, Jilin Sun, Margaret L. DeRose, Marina Stolina, David Chang, Gwyneth Y. Van, Kristie Clarkin, Hung Q. Nguyen, Yan Bin Yu, Shuqian Jing, Giorgio Senaldi, Gary Elliott, Eugene S. Medlock
Journal: Blood (2002)
From guidance to practice: Why NICE is not enough
Authors: Thomas H S Dent, Mike Sadler
Journal: BMJ (2002)

We investigated whether cigarette smoking is negatively associated with Alzheimer9s disease (AD) in a population-based, frequency-matched, case-control study of 152 AD patients and 180 controls. Ever having smoked was associated with lower risk of AD (adjusted odds ratio = 0.61; 95% confidence interval: 0.37–0.99). Additional multivariate analyses demonstrated that education and history of hypertension modified this association. The direction of the modification was for higher education level and history of hypertension to further reduce the risk. The “dose response” pattern showed the greatest risk reduction among those who smoked least and suggests a biologic mechanism of a dose-dependent up-regulation of nicotinic (cholinergic) brain receptors. These data, although consistent with current opinion about pathophysiology of AD, do not suggest smoking should be used as a preventive strategy for AD.
PROBLEMS IN THE CORRELATION OF PSYCHOPATHOLOGY WITH ELECTROENCEPHALOGRAPHIC ABNORMALITIES
Authors: RONALD R. KOEGLER, EDWARD G. COLBERT, RICHARD D. WALTER
Journal: American Journal of Psychiatry (1961)

1. Frequency analysis has been available for nearly 15 years, but its inherent disadvantages have limited its use in correlating the EEG with clinical data. Auto-correlation and cross-correlation techniques are more recent and hold considerable promise. 2. The use of these techniques will add little to our present knowledge unless we also improve our methods of quantifying behavior and psychopathology. 3. Most studies of EEG abnormalities in psychiatric syndromes have little value because of lack of controls and poorly-defined EEG and behavioral criteria. This has been true in studies of the significance of 14 and 6 per second positive spiking. 4. Research should be directed toward developing techniques which will enable us to quantify behavior and emotional impulses in a more accurate and scientific manner.
Combination of the ABL kinase inhibitor imatinib with the Janus kinase 2 inhibitor TG101348 for targeting residual BCR-ABL-positive cells
Authors: Seiichi Okabe, Tetsuzo Tauchi, Seiichiro Katagiri, Yuko Tanaka, Kazuma Ohyashiki
Journal: Journal of Hematology & Oncology (2014)

The ABL kinase inhibitor imatinib is highly effective in treating most, but not all, patients with chronic myeloid leukemia (CML). This is because residual CML cells are generally present in the bone marrow microenvironment and are refractory to imatinib. Hematopoietic cytokine receptor signaling is mediated by Janus kinases (JAKs) and their downstream transcription factor, signal transducer and activator of transcription (STAT). TG101348 (SAR302503) is an oral inhibitor of JAK2. We investigated the efficacy of imatinib and TG101348 using the break point cluster region-c-Abelson (BCR-ABL)-positive cell line and primary CML samples wherein leukemia cells were protected by a feeder cell line (HS-5). Imatinib treatment resulted in partial inhibition of cell growth in HS-5-conditioned medium. Furthermore, combined treatment with imatinib and TG101348 abrogated the protective effects of HS-5-conditioned medium on K562 cells. Phosphorylation of Crk-L, a BCR-ABL substrate, decreased considerably, while apoptosis increased. In addition, the combined treatment of CD34-positive primary samples resulted in considerably increased cytotoxicity, decreased Crk-L phosphorylation, and increased apoptosis. We also investigated TG101348 activity against feeder cells and observed that STAT5 phosphorylation, granulocyte macrophage colony-stimulating factor, and interleukin 6 levels decreased, indicating reduced cytokine production in HS-5 cells treated with TG101348. These results showed that JAK inhibitors may enhance the cytotoxic effect of imatinib against residual CML cells and that a combined approach may be a powerful strategy against the stroma-associated drug resistance of Philadelphia chromosome-positive cells.
Cyclin D1 in Breast Cancer Pathogenesis
Authors: Andrew Arnold, Alexandros Papanikolaou
Journal: Journal of Clinical Oncology (2005)

Taking a perspective on available evidence that emphasizes relevance to human disease, cyclin D1 is solidly established as an oncogene with an important pathogenetic role in breast cancer and other human tumors. However, the precise cellular mechanisms through which aberrant cyclin D1 expression drives human neoplasia are less well established. Indeed, emerging evidence suggests that cyclin D1 might act, predominantly or at least in part, through pathways that do not involve its widely accepted function as a cell cycle regulator. Although therapeutic exploitation of the role of cyclin D1 as a molecular driver of breast cancer carries great promise, it is also suggested that direct targeting of the cyclin D1 gene or gene products may prove more successful than approaches that rely on arguably incomplete knowledge of the oncogenic mechanisms of cyclin D1.
Immunostimulation of Highly Immunogenic Target Tumor Cells by Lymphoid Cells in Vitro2
Authors: Liisa M. Prehn
Journal: JNCI Journal of the National Cancer Institute (1976)

A highly immunogenic mouse tumor was studied with the use of the microcytotoxicity test, performed at lymphoid cell: target tumor cell ratios ranging from 1:1 to 1,000:1 at various times during tumor growth and after tumor excision. Although the tumor was highly immunogenic, in vitro lymphoid cell-mediated cytotoxicity was shown only with lymphoid cells from hyperimmunized mice, i.e., mice that had “seen” the tumor more than once. Instead, the lymphoid cells harvested 2 and 3 weeks after tumor inoculation, as well as after excision of the tumor, stimulated the target cells. At 4 weeks after inoculation of the tumor, there appeared to be neither stimulation nor inhibition of the target tumor cells, though at this point the growth of this highly immunogenic tumor had been arrested in vivo.
Reoxygenation of Hypoxic Glioblastoma Multiforme Cells Potentiates the Killing Effect of an Interleukin-13-Based Cytotoxin
Authors: Tie Fu Liu, Jiaozhong Cai, Denise M. Gibo, Waldemar Debinski
Journal: Clinical Cancer Research (2008)

Hypoxia is a cause for resistance to cancer therapies. Molecularly targeted recombinant cytotoxins have shown clinical efficacy in the treatment of patients with primary brain tumors, glioblastoma multiforme, but it is not known whether hypoxia influences their antitumor effect.We have exposed glioblastoma multiforme cells, such as U-251 MG, U-373 MG, SNB-19, and A-172 MG, to either anoxia or hypoxia and then reoxygenated them while treating with an interleukin (IL)-13-based diphtheria toxin (DT)-containing cytotoxin, DT-IL13QM. We measured the levels of immunoreactive IL-13Ralpha2, a receptor that mediates IL-13-cytotoxin cell killing, and the levels of active form of furin, a protease that activates the bacterial toxin portion in a cytotoxin.We found that anoxia/hypoxia significantly alters the responsiveness of glioblastoma multiforme cells to DT-IL13QM. Interestingly, bringing these cells back to normoxia caused them to become even more susceptible to the cytotoxin than the cells maintained under normoxia. Anoxia/hypoxia caused a highly prominent decrease in the immunoreactive levels of both IL-13R and active forms of furin, and reoxygenation not only restored their levels but also became higher than that in normoxic glioblastoma multiforme cells.Our results show that a recombinant cytotoxin directed against glioblastoma multiforme cells kills these cells much less efficiently under anoxic/hypoxic conditions. The reoxygenation brings unexpected additional benefit of making glioblastoma multiforme cells even more responsive to the killing effect of a cytotoxin.