tbuckley/cabot-search huggingface dataset:
Plasma MicroRNA Panel to Diagnose Hepatitis B Virus–Related Hepatocellular Carcinoma
Authors: Jian Zhou, Lei Yu, Xue Gao, Jie Hu, Jiping Wang, Zhi Dai, Jie-Fei Wang, Zhiyong Zhang, Shaohua Lu, Xiaowu Huang, Zheng Wang, Shuangjian Qiu, Xiaoying Wang, Guohuan Yang, Huichuan Sun, Zhaoyou Tang, Ying Wu, Hongguang Zhu, Jia Fan
Journal: Journal of Clinical Oncology (2011)

More than 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapy as a result of late clinical presentation and diagnosis. We aimed to identify plasma microRNAs for diagnosing hepatitis B virus (HBV) -related HCC.Plasma microRNA expression was investigated with three independent cohorts including 934 participants (healthy, chronic hepatitis B, cirrhosis, and HBV-related HCC), recruited between August 2008 and June 2010. First, we used microarray to screen 723 microRNAs in 137 plasma samples for diagnosing HCC. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n = 407) and then validated using an independent cohort (n = 390). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy.We identified a microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) that provided a high diagnostic accuracy of HCC (AUC = 0.864 and 0.888 for training and validation data set, respectively). The satisfactory diagnostic performance of the microRNA panel persisted regardless of disease status (AUCs for Barcelona Clinic Liver Cancer stages 0, A, B, and C were 0.888, 0.888, 0.901, and 0.881, respectively). The microRNA panel can also differentiate HCC from healthy (AUC = 0.941), chronic hepatitis B (AUC = 0.842), and cirrhosis (AUC = 0.884), respectively.We found a plasma microRNA panel that has considerable clinical value in diagnosing early-stage HCC. Thus, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy.
Anaplastic Lymphoma Kinase–Positive Diffuse Large B-Cell Lymphoma: A Rare Clinicopathologic Entity With Poor Prognosis
Authors: Camille Laurent, Catherine Do, Randy D. Gascoyne, Laurence Lamant, Loïc Ysebaert, Guy Laurent, Georges Delsol, Pierre Brousset
Journal: Journal of Clinical Oncology (2009)

Anaplastic lymphoma kinase (ALK) -positive diffuse large B-cell lymphoma (DLBCL) is a rare variant of DLBCL that has been described only in small case reports. To shed more light on the clinical and pathologic features and outcome of these tumors, we reviewed data from 38 patients.We retrospectively analyzed 38 patients with ALK-positive DLBCL treated with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or CHOP-like regimens from different institutions to better define the presenting features, clinical course, and response to treatment.The histologic findings in all patients were similar. All patients expressed ALK fusion proteins, but virtually all were CD30 and CD20 negative. The median age was 43 years with a 5:1 ratio of males to females. Most patients (60%) followed an aggressive clinical course with advanced stage at diagnosis, frequent marrow infiltration, and poor outcome. Overall survival was 20.3 months (95% CI, 12.2 to 42.6 months). Of note, the median survival was only 12.2 months (95% CI, 9.1 to 32.5 months) in patients with advanced-stage disease.ALK-positive DLBCLs display clinicopathologic features that distinguish them from common DLBCL. Conventional therapy, as used for typical DLBCL, is of limited efficacy. Recognition of this new entity and the characteristic lack of CD20 expression are paramount. Novel front-line intensive chemotherapy regimens should be evaluated in this group of patients.
398 CHARACTERIZATION OF THE INACTIVE HBSAG CARRIER STATE WITH 3 YEAR FOLLOW-UP
Authors: M. Yakut, M. Bektas, G. Seven, G. Kabaçam, E. Karatayli, S. Karatayli, A.M. Bozdayi, R. Idilman, C. Yurdaydin
Journal: Journal of Hepatology (2011)
Notch Signaling in Cardiac Development
Authors: Kyle Niessen, Aly Karsan
Journal: Circulation Research (2008)

The Notch signaling pathway has been demonstrated to play a critical role during mammalian cardiac development based on recent findings from gene-targeted mice. In addition, mutations in the Notch signaling pathway have been associated with human congenital heart defects such as Alagille syndrome, bicuspid aortic valve disease, calcification of the heart valves, and ventricular septal defects. Recently, it was demonstrated that Notch activation in the endocardium regulates ventricular myocardial development and that the Notch downstream target genes Hey1 and Hey2 are required for the establishment of the atrioventricular canal myocardial boundary. The Notch pathway has previously been implicated in regulating endothelial-to-mesenchymal transition during development of the heart valves, and recent reports further dissect the role of individual Notch downstream target genes during this process. In addition, a role for the Notch pathway during cardiac neural crest cell development has been identified, which provides a potential mechanism for the findings seen in Alagille syndrome. This review focuses on recently reported findings that elucidate mechanisms regulated by the Notch pathway during ventricular, atrioventricular canal, and outflow tract development.
The GALS locomotor screen and disability.
Authors: M J Plant, S Linton, E Dodd, P W Jones, P T Dawes
Journal: Annals of the Rheumatic Diseases (1993)

Examination of the locomotor system is frequently neglected. Therefore, the GALS locomotor screen (Gait, Arms, Legs, Spine) has been proposed by Doherty et al as a practical method of identifying functionally important problems. This study was designed to test whether this screen reflects functional impairment, as measured by accepted health status measures.Two observers performed the GALS screen in a total of 83 patients with a variety of musculoskeletal conditions. The examination components of GALS were rated by a simple 0 to 3 scale. Physical ability was further assessed by Health Activity Questionnaire (HAQ), Barthel index and Steinbrocker's ARA classification.For the total patient group, Spearman correlations between GALS and the three functional indices were good (r = 0.62 to 0.71, p < 0.001). Correlations were equally good for rheumatoid arthritis patients alone (r = 0.65 to 0.70, p < 0.001), but less good although still significant for the other miscellaneous rheumatic conditions (r = 0.31 to 0.46, p < 0.05). Observed proportional agreement between the two observers for the individual scores was > 70%, with a kappa statistic k = 0.49 to 0.74.The GALS screen is a reliable and valid measure of functional ability, compared with standard accepted indices in a variety of musculoskeletal diseases. This supports the proposal for its use as a screening test by general practitioners and medical students.
The α-Mannosidases: Phylogeny and Adaptive Diversification
Authors: Daniel S. Gonzalez, I. King Jordan
Journal: Molecular Biology and Evolution (2000)

alpha-Mannosidase enzymes comprise a class of gylcoside hydrolases involved in the maturation and degradaton of glycoprotein-linked oligosaccharides. Various alpha-mannosidase enzymatic activities are encoded by an ancient and ubiquitous gene superfamily. A comparative sequence analysis was employed here to characterize the evolutionary relationships and dynamics of the alpha-mannosidase superfamily. A series of lineage-specific BLAST searches recovered the first ever recognized archaean and eubacterial alpha-mannosidase sequences, in addition to numerous eukaryotic sequences. Motif-based alignment and subsequent phylogenetic analysis of the entire superfamily revealed the presence of three well-supported monophyletic clades that represent discrete alpha-mannosidase families. The comparative method was used to evaluate the phylogenetic distribution of alpha-mannosidase functional variants within families. Results of this analysis demonstrate a pattern of functional diversification of alpha-mannosidase paralogs followed by conservation of function among orthologs. Nucleotide polymorphism among the most closely related pair of duplicated genes was analyzed to evaluate the role of natural selection in the functional diversification of alpha-mannosidase paralogs. Ratios of nonsynonymous and synonymous variation show an increase in the rate of nonsynonymous change after duplication and a relative excess of fixed nonsynonymous changes between the two groups of paralogs. These data point to a possible role for positive Darwinian selection in the evolution of alpha-mannosidase functional diversification following gene duplication.
Mediators and Mechanisms of Change in Psychotherapy Research
Authors: Alan E. Kazdin
Journal: Annual Review of Clinical Psychology (2007)

There has been enormous progress in psychotherapy research. This has culminated in recognition of several treatments that have strong evidence in their behalf. Even so, after decades of psychotherapy research, we cannot provide an evidence-based explanation for how or why even our most well studied interventions produce change, that is, the mechanism(s) through which treatments operate. This chapter presents central requirements for demonstrating mediators and mechanisms of change and reviews current data-analytic and designs approaches and why they fall short of meeting these requirements. The role of the therapeutic alliance in psychotherapy and cognitive changes in cognitive therapy for depression are highlighted to illustrate key issues. Promising lines of work to identify mediators and mechanisms, ways of bringing to bear multiple types of evidence, recommendations to make progress in understanding how therapy works, and conceptual and research challenges in evaluating mediators and mechanisms are also presented.
Therapeutic vaccinationin chronic hepatitis B: qualitative and quantitative analysis of the virusspecific immune response
Authors: M.-C. Jung, N. Grüner, R. Zachoval, W. Schraut, T. Gerlach, H. Diepolder, A. Schirren, M. Page, J. Trojan, S. Zeuzem, G.R. Pape
Journal: Journal of Hepatology (2001)
Imatinib Treatment for Idiopathic Pulmonary Fibrosis
Authors: Craig E. Daniels, Joseph A. Lasky, Andrew H. Limper, Kathleen Mieras, Edith Gabor, Darrell R. Schroeder
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no known efficacious therapy. Imatinib is a tyrosine kinase inhibitor with potential efficacy to treat fibrotic lung disease.To investigate the safety and clinical effects of imatinib in patients with IPF.We studied 119 patients in an investigator-initiated, multicenter, multinational, double-blind clinical trial to receive imatinib or placebo for 96 weeks.Over 96 weeks of follow-up, imatinib did not differ significantly from placebo (log rank P = 0.89) for the primary endpoint defined as time to disease progression (10% decline in percent predicted FVC from baseline) or time to death. There was no effect of imatinib therapy on change in FVC at 48, 72, or 96 weeks (P > or = 0.39 at all time points) or change in diffusing capacity of carbon monoxide at 48, 72, or 96 weeks (P > or = 0.26 at all time points). Change in resting Pa(O(2)) favored imatinib therapy at 48 weeks (P = 0.005) but not at 96 weeks (P = 0.074). During the 96-week trial there were 8 deaths in the imatinib group and 10 deaths in the placebo group (log rank test P = 0.64). Thirty-five (29%) patients discontinued the study without reaching the primary endpoint (imatinib, 32%; placebo, 27%; P = 0.51). Serious adverse events (SAEs) were not more common in the imatinib group (imatinib, 18 SAEs in 17 patients; placebo, 19 SAEs in 18 patients).In a randomized, placebo-controlled trial of patients with mild to moderate IPF followed for 96 weeks, imatinib did not affect survival or lung function. Clinical trial registered with www.clinicaltrials.gov (NCT00131274).
Prevalence of Cardiovascular Autonomic Neuropathy in a Cohort of Patients With Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS)
Authors: Giacomo Zoppini, Vittorio Cacciatori, Daniele Raimondo, Marialuisa Gemma, Maddalena Trombetta, Marco Dauriz, Corinna Brangani, Isabella Pichiri, Carlo Negri, Vincenzo Stoico, Corinna Bergamini, Giovanni Targher, Lorenza Santi, Karl Thomaseth, Federico Bellavere, Riccardo C. Bonadonna, Enzo Bonora
Journal: Diabetes Care (2015)

OBJECTIVE Cardiovascular autonomic diabetic neuropathy (CAN) is a serious complication of diabetes. No reliable data on the prevalence of CAN among patients with newly diagnosed type 2 diabetes are available. Therefore, the aim of this study was to estimate the prevalence of CAN among patients with newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS A cohort of 557 patients with newly diagnosed type 2 diabetes with cardiovascular autonomic test results available was selected. Early and confirmed neuropathy were assessed using a standardized methodology and their prevalences determined. A multivariate logistic regression analysis was modeled to study the factors associated with CAN. RESULTS In the entire cohort, the prevalence of confirmed CAN was 1.8%, whereas that of early CAN was 15.3%. Prevalence did not differ between men and women. In the multivariate analyses BMI results were independently and significantly associated with CAN after adjusting for age, sex, hemoglobin A1c, pulse pressure, triglyceride-to-HDL cholesterol ratio, kidney function parameters, and antihypertensive treatment. CONCLUSIONS CAN could be detected very early in type 2 diabetes. This study may suggest the importance of performing standardized cardiovascular autonomic tests after diagnosis of type 2 diabetes.
Asthma, atopy and tuberculin responses in Chinese schoolchildren in Hong Kong
Authors: G W Wong, D S Hui, C M Tam, H H Chan, T F Fok, M Chan-Yeung, C K Lai
Journal: Thorax (2001)

<h3>BACKGROUND</h3> The prevalence rates of asthma and other atopic disorders have increased steadily in many developed countries over the past few decades. Recent epidemiological and animal studies have suggested that BCG vaccination might be beneficial in reducing the subsequent development of atopy. This study investigates the relationship between asthma, allergic symptoms, atopy, and tuberculin response in Chinese schoolchildren who received BCG vaccination at birth. <h3>METHODS</h3> A total of 3110 schoolchildren aged 10 years were recruited for the Hong Kong arm of the phase II International Study of Asthma and Allergies in Childhood. Of the 2599 children born in Hong Kong and vaccinated with BCG after birth, 2201 had tuberculin testing performed at a mean (SD) age of 8.4 (1.4) years. A random subsample of 980 children was also recruited for skin prick testing. <h3>RESULTS</h3> The prevalence rates of asthma ever, wheeze ever, current wheeze, current rhinoconjunctivitis, and current flexural eczema were not significantly different between tuberculin positive and negative subjects. The mean (SE) tuberculin response was 3.4 (0.2) mm in atopic subjects and 3.3 (0.2) mm in non-atopic subjects (difference not significant). Logistic regression analyses did not reveal any significant relationship between asthma ever, current wheeze, atopy, and positive tuberculin responses. <h3>CONCLUSIONS</h3> This study did not find any relationship between asthma, allergic symptoms, atopy, and positive tuberculin reactivity in Chinese schoolchildren vaccinated with BCG at birth.
Glucose Measurement: Confounding Issues in Setting Targets for Inpatient Management
Authors: John Mahoney, John Ellison
Journal: Diabetes Care (2007)

We thank Dungan et al. (1) for their recent review of the potential factors that can adversely affect inpatient glucose measurements. Their review is timely and provides a much-needed overview of an important and complex subject, especially now that hospitals are using point-of-care devices to monitor intensive insulin protocols.

However, we feel that the information listed in Table 1 of their study is potentially misleading. First, the presence …
A Human-Specific Deletion in Mouse <i>Cmah</i> Increases Disease Severity in the mdx Model of Duchenne Muscular Dystrophy
Authors: Kumaran Chandrasekharan, Jung Hae Yoon, Ying Xu, Sarah deVries, Marybeth Camboni, Paulus M. L. Janssen, Ajit Varki, Paul T. Martin
Journal: Science Translational Medicine (2010)

A mouse model for Duchenne muscular dystrophy engineered to produce human-like glycosylation mimics the human disease better than existing models.
Effect of pattern of preceding inspiration on FEV1 in asthmatic children
Authors: L Sette, G Del Col, A Comis, J Milic-Emili, A Rossi, AL Boner
Journal: European Respiratory Journal (1996)

In adults, both peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) are significantly influenced by the time course of the inspiration preceding the forced expiration. The aim of this study was to evaluate the effects of three different inspiratory manoeuvres on PEF, FEV1, and forced vital capacity (FVC) in asthmatic children. Twenty five symptomless asthmatic children performed forced expiration preceded by three different inspiratory manoeuvres, which consisted of: a rapid inspiration with a 2 s end-inspiratory breathhold (Manoeuvre No. 1); a rapid inspiration without an end-inspiratory breathhold (Manoeuvre No. 2); and a slow inspiration lasting about 5 s with an end-inspiratory breathhold of at least 4 s (Manoeuvre No. 3). All manoeuvres were performed in a randomly assigned sequence each morning for three consecutive days. In each session, the manoeuvres were repeated three times and the highest value was chosen. Both FVC and FEV1 obtained with Manoeuvre No. 3 were significantly lower than the corresponding values obtained with Manoeuvre Nos. 1 and 2. The mean (SD) FVC values were 2.76 (0.66) L with Manoeuvre No. 1, 2.67 (0.58) L with Manoeuvre No. 2 and 2.52 (0.52) L with Manoeuvre No. 3. The corresponding values of FEV1 were 2.25 (0.53), 2.22 (0.53) and 2.07 (0.44) L, respectively. By contrast, the values of PEF, obtained with a portable peak flow meter, were similar with the three different inspiratory manoeuvres. The results of this study show that in symptomless asthmatic children the preceding inspiratory manoeuvre may influence forced vital capacity and forced expiratory volume in one second. Hence, in order to reduce variability due to interference by physiological factors and so improve reproducibility of pulmonary function tests, the inspiratory manoeuvres must be accurately standardized.
Presentation on websites of possible benefits and harms from screening for breast cancer: cross sectional study
Authors: K. J. Jorgensen
Journal: BMJ (2004)

<b>Objective</b> To investigate whether information on mammographic screening presented on websites by interest groups is balanced, is independent of source of funding, and reflects recent findings. <b>Design</b> Cross sectional study using a checklist with 17 information items. <b>Setting</b> 27 websites in Scandinavian and English speaking countries. <b>Results</b> The 13 sites from advocacy groups and the 11 from governmental institutions all recommended mammographic screening, whereas the three from consumer organisations questioned screening (P = 0.0007). All the advocacy groups accepted industry funding, apparently without restrictions. In contrast the three consumer organisations acknowledged the risk of bias related to industry funding, and two of them did not accept such funding at all. Advocacy groups and governmental organisations favoured information items that shed positive light on screening. The major harms of screening, overdiagnosis and overtreatment, were mentioned by only four of these groups, but by all three sites from consumer organisations (P = 0.02). In addition, the chosen information was often misleading or erroneous. The selection of information items for websites did not reflect recent findings, apart from the consumer sites, which were much more balanced and comprehensive than other sites (median of 9 information items <i>v</i>3 items, P = 0.03). <b>Conclusions</b> The information material provided by professional advocacy groups and governmental organisations is information poor and severely biased in favour of screening. Few websites live up to accepted standards for informed consent such as those stated in the General Medical Council9s guidelines.
Underuse of Radiotherapy in Lung Cancer Has Negative Consequences for Patients
Authors: Isabel Tovar, José Expósito, Javier Jaén, Enrique Alonso
Journal: Journal of Thoracic Oncology (2012)

Introduction:Radiotherapy has proven to be an effective treatment when used alone or with other therapies. However, underuse of radiotherapy has been observed in various studies. The objective of this investigation was to assess the use of radiotherapy as initial treatment for lung cancer in a southern region of Europe.Methods:A systematic review of lung cancer treatment guidelines and observational studies was performed to estimate expected radiation rates and the associated survival outcomes. We then reviewed the clinical and treatment records of all patients undergoing radiotherapy for lung cancer during 2007 in all the 12 public hospitals in Andalusia with radiotherapy facilities. Data were grouped according to type of hospital, patient, treatment characteristics, histological type, and tumor stage.Results:In 2007, of the 3051 patients estimated to be diagnosed with lung cancer, 610 were treated with initial radiotherapy with an overall radiation rate of 20%, which significantly differed among provinces (range, 8.5%–25.6%, p < 0.001). Given the expected radiation rate of 1383 patients, 773 more patients of lung cancer (25%) should have been treated. According to the literature, the maximum increased survival attributable to the use of radiotherapy in patients diagnosed with non–small-cell lung cancer ranges from 1.8 to 14.1 months. The underuse estimated in the region would correspond to a loss of more than 3000 months in survival time.Conclusions:The observed underuse of radiotherapy in lung cancer in our region should be a matter of concern, given its negative and measurable impact on the survival of the patients.
Perfluorinated Chemicals and Fetal Growth: A Study within the Danish National Birth Cohort
Authors: Chunyuan Fei, Joseph K. McLaughlin, Robert E. Tarone, Jørn Olsen
Journal: Environmental Health Perspectives (2007)

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are man-made, persistent organic pollutants widely spread throughout the environment and human populations. They have been found to interfere with fetal growth in some animal models, but whether a similar effect is seen in humans is uncertain.We investigated the association between plasma levels of PFOS and PFOA in pregnant women and their infants' birth weight and length of gestation.We randomly selected 1,400 women and their infants from the Danish National Birth Cohort among those who completed all four computer-assisted telephone interviews, provided the first blood samples between gestational weeks 4 and 14, and who gave birth to a single live-born child without congenital malformation. PFOS and PFOA were measured by high performance liquid chromatography-tandem mass spectrometer.PFOS and PFOA levels in maternal plasma were on average 35.3 and 5.6 ng/mL, respectively. Only PFOA levels were inversely associated with birth weight (adjusted beta = -10.63 g; 95% confidence interval, -20.79 to -0.47 g). Neither maternal PFOS nor PFOA levels were consistently associated with the risk for preterm birth or low birth weight. We observed no adverse effects for maternal PFOS or PFOA levels on small for gestational age.Our nationwide cohort data suggest an inverse association between maternal plasma PFOA levels and birth weight. Because of widespread exposure to these chemicals, our findings may be of potential public health concern.