tbuckley/cabot-search huggingface dataset:
Src Family Kinase Activity Is Up-Regulated in Hormone-Refractory Prostate Cancer
Authors: Oleg Tatarov, Thomas J. Mitchell, Morag Seywright, Hing Y. Leung, Valerie G. Brunton, Joanne Edwards
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Although Src family kinase (SFK) inhibitors are now in clinical trials for the treatment of androgen-independent prostate cancer (AIPC), there are no studies relating SFK activation to patient survival. This study was designed to determine if SFK activation was up-regulated with the development of AIPC and if patients could be selected who were more likely to respond to therapy. Experimental Design: A unique cohort of matched prostate tumor samples, taken before hormone deprivation therapy and following hormone relapse, was used to determine by immunohistochemistry on an individual patient basis if SFK activity changed with progression to AIPC and whether this related to patient outcome measures. Using matched, hormone-sensitive and hormone-refractory cell lines, we determined if hormone status affected the way prostate cancer cells respond to suppression of SFK activity by the small-molecule inhibitor dasatinib. Results: In the current study, 28% of patients with AIPC exhibited an increase in SFK activity in prostate cancer tissue, these patients had significantly shorter overall survival (P&amp;lt;0.0001), and activated SFK expression correlated with the presence of distant metastases. Dasatinib inhibited phosphorylation of Src and Lyn and the downstream substrate FAK in hormone-sensitive and hormone-refractory cell lines. Although migration was reduced by dasatinib in both cell lines, proliferation of hormone-refractory cells only was inhibited. Conclusion: Appropriate patient selection may allow better targeting of prostate cancer patients who are likely to respond to the treatment with SFK inhibitors at the same time improving the outcome of clinical trials.
Long-term peptic ulcer rebleeding risk estimation in patients undergoing haemodialysis: a 10-year nationwide cohort study
Authors: C.-Y. Wu, M.-S. Wu, K. N. Kuo, C.-B. Wang, Y.-J. Chen, J.-T. Lin
Journal: Gut (2011)

<h3>Objective</h3> We aimed to study 1-, 5- and 10-year risks of peptic ulcer rebleeding among end-stage renal disease (ESRD) patients with regular haemodialysis, to identify the high-risk subpopulation, and to estimate the number needed to harm (NNH) to increase a peptic ulcer rebleeding in different periods. <h3>Design</h3> A nationwide cohort study. <h3>Setting</h3> Data from the Taiwan National Health Insurance Research Database. <h3>Patients</h3> Uraemic cohort and matched controls were selected from among hospitalised patients with a primary diagnosis of peptic ulcer bleeding. In total, 6447 uraemic patients and 25 788 age-, gender- and gastroprotective agent use-matched controls were selected. <h3>Intervention</h3> No. <h3>Main outcome measures</h3> Cumulative incidences and HRs. <h3>Results</h3> The cumulative incidences of ESRD patients were significantly higher than the cumulative incidences of matched controls (1 year: 18.8% vs 14.2%; 5 years: 38.5% vs 31.4%; and 10 years: 46.3% vs 39.4%; all p&lt;0.001). The NNH to increase a peptic ulcer rebleeding by ESRD at 1, 5 and 10 years were 22, 15 and 15, respectively. On multivariate analysis, ESRD (HR=1.38, p&lt;0.0001) was an independent risk factor for rebleeding. Compared with matched controls, ESRD was associated with higher risk of rebleeding especially in patients using ulcerogenic agents (HR=1.33–1.45), indication to prescribe gastroprotective agents (HR=1.44) and with liver cirrhosis (HR=1.45). <h3>Conclusions</h3> ESRD patients had higher long-term risk of peptic ulcer rebleeding, especially in certain populations. The enhanced risk gradually decreased after the first year and stabilised after the fifth year.
Life and times of the impact factor: retrospective analysis of trends for seven medical journals (1994-2005) and their Editors’ views
Authors: Mabel Chew, Elmer V Villanueva, Martin B Van Der Weyden
Journal: Journal of the Royal Society of Medicine (2007)

(1) To analyse trends in the journal impact factor (IF) of seven general medical journals (Ann Intern Med, BMJ, CMAJ, JAMA, Lancet, Med J Aust and N Engl J Med) over 12 years; and (2) to ascertain the views of these journals' past and present Editors on factors that had affected their journals' IFs during their tenure, including direct editorial policies.Retrospective analysis of IF data from ISI Web of Knowledge Journal Citation Reports-Science Edition, 1994 to 2005, and interviews with Editors-in-Chief.Medical journal publishing.Ten Editors-in-Chief of the journals, except Med J Aust, who served between 1999 and 2004. MAIN OUTCOME MEASURES IFs and component numerator and denominator data for the seven general medical journals (1994 to 2005) were collected. IFs are calculated using the formula: (Citations in year z to articles published in years x and y)/(Number of citable articles published in years x and y), where z is the current year and x and y are the previous two years. Editors' views on factors that had affected their journals' IFs were also obtained.IFs generally rose over the 12-year period, with the N Engl J Med having the highest IF throughout. However, percentage rises in IF relative to the baseline year of 1994 were greatest for CMAJ (about 500%) and JAMA (260%). Numerators for most journals tended to rise over this period, while denominators tended to be stable or to fall, although not always in a linear fashion. Nine of ten eligible editors were interviewed. Possible reasons given for rises in citation counts included: active recruitment of high-impact articles by courting researchers; offering authors better services; boosting the journal's media profile; more careful article selection; and increases in article citations. Most felt that going online had not affected citations. Most had no deliberate policy to publish fewer articles (lowering the IF denominator), which was sometimes the unintended result of other editorial policies. The two Editors who deliberately published fewer articles did so as they realized IFs were important to authors. Concerns about the accuracy of ISI counting for the IF denominator prompted some to routinely check their IF data with ISI. All Editors had mixed feelings about using IFs to evaluate journals and academics, and mentioned the tension between aiming to improve IFs and 'keeping their constituents [clinicians] happy.'IFs of the journals studied rose in the 12-year period due to rising numerators and/or falling denominators, to varying extents. Journal Editors perceived that this occurred for various reasons, including deliberate editorial practices. The vulnerability of the IF to editorial manipulation and Editors' dissatisfaction with it as the sole measure of journal quality lend weight to the need for complementary measures.
Effect of beer consumption on plasma magnesium: randomized comparison with mineral water
Authors: S Gorinstein, M Zemser, I Libman, S Trakhtenberg, A Caspi
Journal: Journal of the Royal Society of Medicine (1998)

Moderate consumption of ethanol lowers mortality from coronary artery disease, and one of the possible mechanisms is an antiarrhythmic action. We therefore investigated the effect of a small daily dose of beer on plasma electrolytes. 52 men who seldom drank alcohol, clinically stable more than one year after coronary bypass surgery, were randomized to drink either 330 mL beer (containing about 20 g ethanol) or mineral water with similar potassium, magnesium, calcium and sodium content daily for 30 days. Plasma electrolytes and liver function indices, and also heart rate, blood pressure and weight, were measured before and after the trial period. The only significant before-and-after difference was in the group consuming beer, whose plasma magnesium rose from 0.89 (SD 0.01) to 0.98 (SD 0.02) mmol/L (P < 0.0025). This level of beer consumption did no obvious harm to liver function and its possibly beneficial effect on plasma magnesium deserves further investigation.
Isoniazid or Moxifloxacin in Rifapentine-based Regimens for Experimental Tuberculosis?
Authors: Ian M. Rosenthal, Ming Zhang, Deepak Almeida, Jacques H. Grosset, Eric L. Nuermberger
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Recent studies have demonstrated that combined substitutions of rifapentine for rifampin and moxifloxacin for isoniazid in the standard, daily, short-course regimen of rifampin, isoniazid, and pyrazinamide produces stable cure in 12 weeks or less. This study was designed to more precisely evaluate the contribution of moxifloxacin and isoniazid to rifapentine-based regimens.Objectives: We compared bactericidal activity and treatment-shortening potential between regimens consisting of isoniazid or moxifloxacin plus rifapentine and pyrazinamide administered either thrice-weekly or daily.Methods: Using a mouse model of tuberculosis, we assessed bactericidal activity by performing quantitative cultures of lung homogenates over the first 12 weeks of treatment. Relapse rates were assessed after completing 8, 10, and 12 weeks of treatment to determine the duration of treatment necessary for stable cure.Measurements and Main Results: After 4 weeks of treatment, daily and thrice-weekly therapy with rifapentine, moxifloxacin, and pyrazinamide was significantly more active than treatment with rifapentine, isoniazid, and pyrazinamide. By 8 weeks of treatment, all mice receiving the moxifloxacin-containing regimens were lung culture negative, whereas those mice receiving the isoniazid-containing regimens continued to be lung culture positive. However, the duration of treatment necessary to achieve stable cure was 10 weeks for daily regimens and 12 weeks for thrice-weekly regimens, regardless of whether isoniazid or moxifloxacin was used. All mice receiving standard daily therapy with rifampin, isoniazid, and pyrazinamide relapsed after 12 weeks of treatment.Conclusions: These results suggest that regimens consisting of isoniazid or moxifloxacin plus rifapentine and pyrazinamide may dramatically shorten the duration of treatment needed to cure human tuberculosis.
MEDLINE: A Guide to Effective Searching
Authors: J A TIBBLE
Journal: Gut (2000)

MEDLINE: A Guide to Effective Searching . Edited by Katcher BS (Pp147; $29.00) US: Ashbury Press, 1999. ISBN 0 9673445 0 6.

Many specialist registrars embarking on a period of research are faced with the task of writing grant proposals requiring a comprehensive understanding of a subject, but often begin from a point of relative ignorance. The first port of call for many will be to delve into MEDLINE, a vast bibliographic database indexing over 4000 journals. Now freely accessible through the internet, MEDLINE can be used to search for subject …
Developed world is robbing African countries of health staff
Authors: Rebecca Coombes
Journal: BMJ (2005)

Entire African countries are being left with less than 500 doctors each because of the ongoing “brain drain” of healthcare staff to the developed world. Developed countries find it cheaper to recruit from abroad than to train enough of their own citizens, delegates were told at a BMA conference last week.

The meeting of delegates from the United States, Canada, Africa, the Commonwealth, and the United Kingdom was convened to discuss the growing crisis in developing countries caused by the escalating migration of doctors and nurses.

James Johnson, chairman of BMA council, criticised developed nations for failing to make …
Phase II Trial of Carboplatin, Paclitaxel, Cetuximab, and Bevacizumab Followed by Cetuximab and Bevacizumab in Advanced Nonsquamous Non–Small-Cell Lung Cancer: SWOG S0536
Authors: Edward S. Kim, James Moon, Roy S. Herbst, Mary W. Redman, Shaker R. Dakhil, Mario R. Velasco, Fred R. Hirsch, Philip C. Mack, Karen Kelly, John V. Heymach, David R. Gandara
Journal: Journal of Thoracic Oncology (2013)
A novel cause for bronchiolitis obliterans organizing pneumonia: exposure to paint aerosols in textile workshops
Authors: P Camus, B Nemery
Journal: European Respiratory Journal (1998)

In this issue of the Journal, ROMERO et al. [1] describe 14 patients with severe organizing pneumonia (OP), which resulted from occupational exposure to aerosolized paint in the textile industry in Spain.This spectacular and highly unusual outbreak of occupational lung disease, of which six workers died, took place in the spring of 1992 in the region of Alcoi in the Autonomous Community of Valencia [2].This highlights the possible emergence of novel lung diseases from inhalation of toxic substances in the industrial setting, and points to an additional aetiological context for bronchiolitis obliterans organizing pneumonia (BOOP), apart from many other causes for this clinicalpathological entity [3][4][5].
Sepsis severity predicts outcome in community-acquired pneumococcal pneumonia
Authors: B. Schaaf, J. Kruse, J. Rupp, R. R. Reinert, D. Droemann, P. Zabel, S. Ewig, K. Dalhoff
Journal: European Respiratory Journal (2007)

Easily performed prognostic rules are helpful for guiding the intensity of monitoring and treatment of patients. The aim of the present study was to compare the predictive value of the sepsis score and the Confusion, Respiratory rate (≥30 breaths·min −1 ), Blood pressure (systolic value &lt;90 mmHg or diastolic value ≤60 mmHg) and age ≥65 yrs (CRB-65) score in 105 patients with community-acquired pneumococcal pneumonia. In addition, the influence of timing of the antimicrobial treatment on outcome was investigated. The sepsis and the CRB-65 scores were used to allocate patients to subgroups with low, intermediate and high risk. Comparable, highly predictive values for mortality were found for both scores (sepsis score versus CRB-65): 1) low-risk group, 0 versus 0%; 2) intermediate-risk group, 0 versus 8.6%; 3) high-risk group, 30.6 versus 40%, with an area under the curve of 0.867 versus 0.845. Patients with ambulatory antibiotic pre-treatment had less severe disease with a lower acute physiology score, lower white blood cell count and a faster decline of C-reactive protein levels. No pre-treated patient died. In summary, both scores performed equally well in predicting mortality. The prediction of survival in the intermediate-risk group might be more accurate with the sepsis score. Pre-hospital antibiotic treatment was associated with less severe disease.
Epstein-Barr Virus-Positive Gastric Carcinoma Has a Distinct Protein Expression Profile in Comparison with Epstein-Barr Virus-Negative Carcinoma
Authors: Hye Seung Lee, Mee Soo Chang, Han-Kwang Yang, Byung Lan Lee, Woo Ho Kim
Journal: Clinical Cancer Research (2004)

EBV has been detected in 2-16% of gastric carcinomas. However, there is little information available about the gene expression profile of EBV-positive gastric carcinomas.EBV infection was examined using EBV-encoded small RNAs (EBERs) in situ hybridization, and 63 (5.6%) of 1127 consecutive gastric carcinomas were found to be EBV-positive. The expressions of 27 tumor-associated proteins were evaluated immunohistochemically in 63 EBV-positive gastric carcinomas and 287 EBV-negative carcinomas using the tissue array method. In addition, the genotype of EBV was investigated by PCR amplification of LMP1 (latent membrane protein 1), Epstein-Barr nuclear antigen 2 (EBNA2), and EBNA3B genes.EBV-positive gastric carcinomas are characterized by the presence of lymphoid stroma, proximal location, and predominance in males. In comparison with EBV-negative carcinomas, EBV-positive carcinomas showed frequent loss of expression of p16, smad4, FHIT, and KAI-1 (kangai 1; P < 0.05), but retained the expression of APC (adenomatous polyposis coli), DCC (deleted in colorectal cancer), and some DNA repair proteins (P < 0.05). There was negative association between EBV infection and the expression of MUC1, MUC2, MUC5AC, p53, CEA, C-erbB2, and smad7. Using hierarchical cluster analysis, we divided EBV-positive gastric carcinomas into two clusters. Those patients with cluster 1 (42 cases) carcinomas had a better prognosis than those with cluster 2 (12 cases; P = 0.0002) or those with EBV-negative carcinomas (280 cases; P = 0.0251). Fifty-one (92.7%) of 55 EBV-positive carcinomas demonstrated the 30-bp deletion in LMP1 gene, and 53 (96.4%) of 55 cases were type 1 for EBNA2 and EBNA3B genes.EBV-positive gastric carcinomas have a distinct protein expression profile as well as distinct clinicopathological features, as compared with EBV-negative carcinomas. The subclassification of EBV-positive carcinomas, by hierarchical cluster analysis, is significantly associated with patient survival.
Sensitivity of Mouse Tumor Cells to the Antiviral Action of Interferon&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: I. Hellström
Journal: JNCI Journal of the National Cancer Institute (1964)

The sensitivity of tumor cells to the antiviral action of interferon was determined by a study of the inhibition of vaccinia-plaque formation after the addition of interferon, prepared from the lungs of PR8 virus-infected mice. Sixteen tumor lines were used, derived from 4 different mouse tumors. All tumor lines, except 1, were found interferon-sensitive, sometimes to a higher degree than normal cells from 13- to 18-day mouse embryos. The data showed, in agreement with certain previous findings, that resistance to the antiviral action of interferon, as found with many long-transplanted tumor lines, is no general characteristic of tumor cells as such.
Impact of climate change on ozone-related mortality and morbidity in Europe
Authors: Hans Orru, Camilla Andersson, Kristie L. Ebi, Joakim Langner, Christofer Åström, Bertil Forsberg
Journal: European Respiratory Journal (2012)

Ozone is a highly oxidative pollutant formed from precursors in the presence of sunlight, associated with respiratory morbidity and mortality. All else being equal, concentrations of ground-level ozone are expected to increase due to climate change. Ozone-related health impacts under a changing climate are projected using emission scenarios, models and epidemiological data. European ozone concentrations are modelled with the model of atmospheric transport and chemistry (MATCH)-RCA3 (50×50 km). Projections from two climate models, ECHAM4 and HadCM3, are applied under greenhouse gas emission scenarios A2 and A1B, respectively. We applied a European-wide exposure–response function to gridded population data and country-specific baseline mortality and morbidity. Comparing the current situation (1990–2009) with the baseline period (1961–1990), the largest increase in ozone-associated mortality and morbidity due to climate change (4–5%) have occurred in Belgium, Ireland, the Netherlands and the UK. Comparing the baseline period and the future periods (2021–2050 and 2041–2060), much larger increases in ozone-related mortality and morbidity are projected for Belgium, France, Spain and Portugal, with the impact being stronger using the climate projection from ECHAM4 (A2). However, in Nordic and Baltic countries the same magnitude of decrease is projected. The current study suggests that projected effects of climate change on ozone concentrations could differentially influence mortality and morbidity across Europe.
A Meta-Analysis of Cognitive Remediation for Schizophrenia: Methodology and Effect Sizes
Authors: Til Wykes, Vyv Huddy, Caroline Cellard, Susan R. McGurk, Pál Czobor
Journal: American Journal of Psychiatry (2011)

Objective: Cognitive remediation therapy for schizophrenia was developed to treat cognitive problems that affect functioning, but the treatment effects may depend on the type of trial methodology adopted. The present meta-analysis will determine the effects of treatment and whether study method or potential moderators influence the estimates. Method: Electronic databases were searched up to June 2009 using variants of the key words "cognitive," "training," "remediation," "clinical trial," and "schizophrenia." Key researchers were contacted to ensure that all studies meeting the criteria were included. This produced 109 reports of 40 studies in which ≥70% of participants had a diagnosis of schizophrenia, all of whom received standard care. There was a comparison group and allocation procedure in these studies. Data were available to calculate effect sizes on cognition and/or functioning. Data were independently extracted by two reviewers with excellent reliability. Methodological moderators were extracted through the Clinical Trials Assessment Measure and verified by authors in 94% of cases. Results: The meta-analysis (2,104 participants) yielded durable effects on global cognition and functioning. The symptom effect was small and disappeared at follow-up assessment. No treatment element (remediation approach, duration, computer use, etc.) was associated with cognitive outcome. Cognitive remediation therapy was more effective when patients were clinically stable. Significantly stronger effects on functioning were found when cognitive remediation therapy was provided together with other psychiatric rehabilitation, and a much larger effect was present when a strategic approach was adopted together with adjunctive rehabilitation. Despite variability in methodological rigor, this did not moderate any of the therapy effects, and even in the most rigorous studies there were similar small-to-moderate effects. Conclusions: Cognitive remediation benefits people with schizophrenia, and when combined with psychiatric rehabilitation, this benefit generalizes to functioning, relative to rehabilitation alone. These benefits cannot be attributed to poor study methods.
Vascular endothelial growth factor aggravates fibrosis and vasculopathy in experimental models of systemic sclerosis
Authors: Britta Maurer, Alfiya Distler, Yossra A Suliman, Renate E Gay, Beat A Michel, Steffen Gay, Jörg H W Distler, Oliver Distler
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> High levels of vascular endothelial growth factor (VEGF), a key angiogenic factor, are present in patients with systemic sclerosis (SSc), but its role in the pathogenesis of fibrosis and its contribution to the disturbed angiogenesis of SSc remains hypothetical. <h3>Methods</h3> Mono (+/−) and double (+/+) VEGF transgenic (tg) mice and their wildtype (wt) controls were analysed. The bleomycin model was applied to VEGF tg mice to evaluate effects of VEGF under proinflammatory conditions. Additionally, tight skin (TSK) 1/VEGF+/+ mice were generated to mimic later non-inflammatory stages of SSc. <h3>Results</h3> VEGF+/+, but not VEGF+/− tg mice, spontaneously developed significant skin fibrosis, indicating profibrotic effect of VEGF in a gene-dosing manner. In the proinflammatory bleomycin model, the profibrotic effect became more pronounced with induction of skin fibrosis in VEGF+/− tg mice and even more enhanced fibrosis in VEGF+/+ tg mice. Analysis in TSK1/VEGF+/+ mice showed similar profibrotic effects of VEGF also under non-inflammatory in vivo conditions. In vitro analysis revealed that VEGF is able to directly induce collagen synthesis in dermal fibroblasts. Additionally, there was an inverse gene-dosing effect on the efficacy of angiogenesis in that a higher number of microvessels was observed in VEGF+/− tg mice than in VEGF+/+ tg mice. <h3>Conclusions</h3> These data provide the first evidence for VEGF as a novel molecular link between fibrosis and vasculopathy in the pathogenesis of SSc. They suggest that high levels of VEGF potently induce fibrosis in inflammatory and non-inflammatory stages, and also contribute to the relatively insufficient angiogenesis characteristic for SSc.