tbuckley/cabot-search huggingface dataset:
Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin
Authors: Leander Grode, Peter Seiler, Sven Baumann, Jürgen Hess, Volker Brinkmann, Ali Nasser Eddine, Peggy Mann, Christian Goosmann, Silke Bandermann, Debbie Smith, Gregory J. Bancroft, Jean-Marc Reyrat, Dick van Soolingen, Bärbel Raupach, Stefan H. E. Kaufmann
Journal: Journal of Clinical Investigation (2005)

The tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guérin (BCG) was equipped with the membrane-perforating listeriolysin (Hly) of Listeria monocytogenes, which was shown to improve protection against Mycobacterium tuberculosis. Following aerosol challenge, the Hly-secreting recombinant BCG (hly+ rBCG) vaccine was shown to protect significantly better against aerosol infection with M. tuberculosis than did the parental BCG strain. The isogenic, urease C–deficient hly+ rBCG (ΔureC hly+ rBCG) vaccine, providing an intraphagosomal pH closer to the acidic pH optimum for Hly activity, exhibited still higher vaccine efficacy than parental BCG. ΔureC hly+ rBCG also induced profound protection against a member of the M. tuberculosis Beijing/W genotype family while parental BCG failed to do so consistently. Hly not only promoted antigen translocation into the cytoplasm but also apoptosis of infected macrophages. We concluded that superior vaccine efficacy of ΔureC hly+ rBCG as compared with parental BCG is primarily based on improved cross-priming, which causes enhanced T cell–mediated immunity.
Piecing together the key players of fibrosis in chronic hepatitis C: what roles do non-hepatic liver resident cell types play?
Authors: Birke Bartosch
Journal: Gut (2014)

WHO estimates suggest that worldwide 150–200 million people are chronic carriers of HCV. Of these up to 30% will develop chronic liver inflammation and fibrosis and progress to cirrhosis or hepatocellular carcinoma (HCC) in the long term. New HCV infections are still occurring, and most HCV carriers are unaware of their status. Therefore incidences of HCV-induced liver disease and cancer are predicted to rise in the coming decade in spite of important recent progress in the development of direct antiviral agents. These new treatments appear to have greatly improved efficacies and safety profiles combined with a high genetic barrier and they are likely to introduce an era of interferon-free therapy in the near future.1 Virological cure in the form of a sustained virological response (SVR) is predicted to become attainable for most patients, including HCV carriers that were previously difficult to treat.1 A number of clinical studies have now shown that therapeutically obtained SVR improves inflammation and fibrosis, decreases the risk for end-stage liver disease and improves quality of life.2 However, in a minority of patients with SVR (up to 12%) fibrosis levels do not reverse and can even progress to cirrhosis.3 Furthermore, HCC can still occur in patients with SVR long periods after treatment and an advanced pretreatment fibrosis stage is considered as a risk factor.4 Obtaining a better understanding of the molecular biology underlying fibrosis in chronic hepatitis C thus remains an important issue, particularly as antifibrotic treatment is not yet available.

Fibrosis is the result of excessive accumulation of collagen-rich extracellular matrix (ECM), or scar tissue in response to hepatic injury, which will distort the architecture of the liver and lead to progressive loss of organ function in the long term.5 The predominant cell type responsible for deposition of the collagen-rich …
Quantitative assessment of molecular remission after high-dose therapy with autologous stem cell transplantation predicts long-term remission in mantle cell lymphoma
Authors: Christiane Pott, Carsten Schrader, Stefan Gesk, Lana Harder, Markus Tiemann, Thorsten Raff, Monika Brüggemann, Matthias Ritgen, Benedikt Gahn, Michael Unterhalt, Martin Dreyling, Wolfgang Hiddemann, Reiner Siebert, Peter Dreger, Michael Kneba
Journal: Blood (2005)
Palliative care for patients with non-malignant end stage respiratory disease
Authors: K M HILL
Journal: Thorax (2000)

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the United Kingdom; 28 000 people in England and Wales died of the disease in 1999, a figure comparable with lung cancer which killed 29 000 people in the same year.1Equal numbers of patients with COPD and lung cancer are therefore experiencing preterminal disease and are likely to require similar medical and social services. The UK Department of Health's expert report published in 19922 advocated the extension of palliative care services to all who need them, whatever their diagnosis. Since then, the availability and provision of holistic supportive care to patients dying from non-malignant disease has become a topical issue for palliative medicine.3 However, while countries such as the USA admit a high proportion of non-cancer patients to hospice inpatient units (30% in 1994–5),4the UK lags far behind, concentrating these services mainly on cancer patients with only a small proportion of hospice inpatients (4% in 1995) suffering from diseases other than cancer.5 

Severe COPD and advanced lung cancer are both progressive diseases which are often managed by the same health care professionals such as primary care teams. However, the palliative care needs of patients with these two diseases have never previously been compared. The publication of the paper by Gore et al in this issue of Thorax is therefore of interest because it provides further evidence that the care needs of patients with severe COPD should be considered in the same way as those with lung cancer.6 This is an important message for medical practice where the relevance of palliative care skills to patients with terminal non-malignant conditions is recognised but where the framework for extending these services beyond cancer patients is still in need of development.7 

The aim …
Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General Practitioners' oral contraception study
Authors: V. Beral, C. Hermon, C. Kay, P. Hannaford, S. Darby, G. Reeves
Journal: BMJ (1999)

To describe the long term effects of the use of oral contraceptives on mortality.Cohort study with 25 year follow up. Details of oral contraceptive use and of morbidity and mortality were reported six monthly by general practitioners. 75% of the original cohort was "flagged" on the NHS central registers.1400 general practices throughout Britain.46 000 women, half of whom were using oral contraceptives at recruitment in 1968-9. Median age at end of follow up was 49 years.Relative risks of death adjusted for age, parity, social class, and smoking.Over the 25 year follow up 1599 deaths were reported. Over the entire period of follow up the risk of death from all causes was similar in ever users and never users of oral contraceptives (relative risk=1.0, 95% confidence interval 0.9 to 1.1; P=0.7) and the risk of death for most specific causes did not differ significantly in the two groups. However, among current and recent (within 10 years) users the relative risk of death from ovarian cancer was 0.2 (0.1 to 0.8; P=0.01), from cervical cancer 2.5 (1.1 to 6.1; P=0.04), and from cerebrovascular disease 1.9 (1.2 to 3.1, P=0.009). By contrast, for women who had stopped use >/= 10 years previously there were no significant excesses or deficits either overall or for any specific cause of death.Oral contraceptives seem to have their main effect on mortality while they are being used and in the 10 years after use ceases. Ten or more years after use ceases mortality in past users is similar to that in never users.The Royal College of General Practitioners' oral contraception (OC) study was launched in 1968 to monitor the health of women who had used OCs. The results of the 25-year follow-up of a cohort of OC users are presented with regard to the effect of PC use upon mortality over the long term. Over 14 months from May 1968, 1400 general practitioners throughout the UK recruited to the study 23,000 women who were using OCs and a similar number who had never used them. The median age of study participants at the end of follow-up was 49 years. Over the follow-up period, 1599 deaths were reported. Over the entire period of follow-up, the risk of death from all causes was similar in ever users and never users of OCs, while the risk of death from most specific causes did not differ significantly in the 2 groups. However, among current users and those who had used OCs within the past 10 years, the relative risk of death from ovarian cancer was 0.2, 2.5 from cervical cancer, and 1.9 from cerebrovascular disease. The P-values for these relative risks are 0.01, 0.04, and 0.009, respectively. Among women who had stopped OC use at least 10 years ago, no significant excesses or deficits were observed either overall or for any specific cause of death. OCs therefore appear to have their main effect upon mortality while they are being used and in the 10 years after use is terminated.
Who Comes to Voluntary, Community-Based Alcohol Screening? Results of the First Annual National Alcohol Screening Day, 1999
Authors: Shelly F. Greenfield, Anne Keliher, Dawn Sugarman, Rene Kozloff, Joelle Meszler Reizes, Barbara Kopans, Douglas Jacobs
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The feasibility of the 1999 voluntary, community-based National Alcohol Screening Day (NASD) was assessed by determining 1) the extent to which community and college sites were registered to hold screenings and the extent to which the subjects came to participate, 2) the demographic and clinical characteristics of the participants at these screening sites, and 3) the extent to which individuals who were referred for evaluation and treatment adhered to follow-up recommendations. METHOD: Registered community and college sites were documented. Screening forms returned by the participants were analyzed. A subgroup of randomly selected participants from community and college sites was contacted by telephone. RESULTS: A total of 1,218 community sites and 499 college sites participated in NASD. At the 1,089 sites that reported results, 32,876 people participated, 18,043 were screened, and 5,959 were referred for treatment. Forty-three percent of those screened at these sites had a score of 8 or more on the Alcohol Use Disorders Identification Test (AUDIT), indicating harmful or hazardous drinking. Only 13% of those screened had previous alcohol treatment. In the subgroup that participated in the follow-up survey (N=704), community participants (N=337) had higher mean scores on the AUDIT than the college participants (N=337). Approximately 50% of the community participants and 20% of the college participants adhered to the recommendation to pursue follow-up. CONCLUSIONS: Voluntary, community-based screening for alcohol problems is feasible and offers education, screening, and referral for many individuals with harmful or hazardous drinking behavior.
Phase II Study of Low-Dose Paclitaxel and Cisplatin in Combination With Split-Course Concomitant Twice-Daily Reirradiation in Recurrent Squamous Cell Carcinoma of the Head and Neck: Results of Radiation Therapy Oncology Group Protocol 9911
Authors: Corey J. Langer, Jonathan Harris, Eric M. Horwitz, Nicos Nicolaou, Merrill Kies, Walter Curran, Stuart Wong, Kian Ang
Journal: Journal of Clinical Oncology (2007)

Recurrent squamous cell carcinoma of the head and neck (SCCHN) or new second primary tumor (SPT) in a previous radiation field, if not curable by surgery or radiation, is almost always fatal. Chemotherapy alone yields a median survival time (MST) of no more than 10 months and 1-year overall survival (OS) of 35% at best. Concurrent reirradiation and chemotherapy is an alternative strategy.Eligibility for Radiation Therapy Oncology Group (RTOG) protocol 9911 stipulated recurrent SCCHN or SPT in a previous radiation field. Patients received twice-daily radiation (1.5 Gy per fraction bid x 5 days every 2 weeks x4), plus cisplatin 15 mg/m2 intravenously (IV) daily x 5 and paclitaxel 20 mg/m2 IV daily x 5 every 2 weeks x4. Granulocyte colony-stimulated factor was administered days 6 through 13 of each 2-week cycle.One hundred five patients were enrolled from March 2000 through June 2003; 23% had SPT. Oropharynx (40%) and oral cavity (27%) were the predominant primary sites. Median prior radiation dose was 65.4 Gy. Seventy-four percent of patients completed chemotherapy. Grade 4 or worse acute toxicity occurred in 28%, grade 4 or worse acute hematologic toxicity in 21%. Eight treatment-related deaths (8%) occurred: five in the acute setting, three late (including two carotid hemorrhages). MST was 12.1 months, with estimated 1- and 2-year OS rates of 50.2% and 25.9%.Despite a high incidence of grade 5 toxicity, 1- and 2-year OS rates for split-course bid radiation therapy and concurrent cisplatin/paclitaxel exceed results generally seen with chemotherapy alone.
Identification of 14-3-3𝛉 as an Antigen that Induces a Humoral Response in Lung Cancer
Authors: Sandra R. Pereira-Faca, Rork Kuick, Eric Puravs, Qing Zhang, Alexei L. Krasnoselsky, Douglas Phanstiel, Ji Qiu, David E. Misek, Robert Hinderer, Martin Tammemagi, Maria Teresa Landi, Neil Caporaso, Ruth Pfeiffer, Cim Edelstein, Gary Goodman, Matt Barnett, Mark Thornquist, Dean Brenner, Samir M. Hanash
Journal: Cancer Research (2007)

Abstract We have implemented a strategy to identify tumor antigens that induce a humoral immune response in lung cancer based on the analysis of tumor cell proteins. Chromatographically fractionated protein extracts from three lung cancer cell lines were subjected to Western blotting and hybridization with individual sera to determine serum antibody binding. Two sets of sera were initially investigated. One set consisted of sera from 19 newly diagnosed subjects with lung adenocarcinoma and 19 matched controls. A second independent set consisted of sera from 26 newly diagnosed subjects with lung adenocarcinoma and 24 controls matched for age, gender, and smoking history. One protein that exhibited significant reactivity with both sets of cancer sera (P = 0.0008) was confidently identified by mass spectrometry as 14-3-3𝛉. Remarkably, significant autoantibody reactivity against 14-3-3𝛉 was also observed in an analysis of a third set consisting of 18 prediagnostic lung cancer sera collected as part of the Beta-Carotene and Retinol Efficacy Trial cohort study, relative to 19 matched controls (P = 0.0042). A receiver operating characteristic curve constructed with a panel of three proteins consisting of 14-3-3𝛉 identified in this study, plus annexin 1 and protein gene product 9.5 proteins previously identified as associated with autoantibodies in lung cancer, gave a sensitivity of 55% at 95% specificity (area under the curve, 0.838) in discriminating lung cancer at the preclinical stage from matched controls. [Cancer Res 2007;67(24):12000–6]
Towards the development of EU/EEA Standards for Tuberculosis Care (ESTC)
Authors: G.B. Migliori, G. Sotgiu, F. Blasi, A. Zumla, R. Loddenkemper, M.C. Raviglione, I. Abubakar, A. Sandgren, D. Manissero
Journal: European Respiratory Journal (2011)

Tuberculosis (TB) continues to pose a public-health threat to the people of the member states of the European Union (EU) and European Economic Area (EEA). EU/EEA countries comprise Austria, Belgium, Bulgaria, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, the Republic of Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, the Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the UK. In 2009, almost 80,000 TB cases were notified in the EU/EEA, and while several countries are progressing towards achieving and sustaining low levels of TB incidence, the contrasts in TB disease burden remain great within the EU/EEA [1]. Some countries are faced with a significant burden of drug-resistant TB, and multidrug-resistant (MDR)-TB. In 2009, 5.3% of all active TB cases reported in the EU/EEA were MDR-TB, and 14.1% were resistant to any of the first-line TB drugs [1]. HIV co-infection is still low, with an overall proportion of 2.3% of TB cases being HIV-seropositive, although accurate surveillance data reporting is suboptimal in many countries [1–3].

The EU/EEA member states were proactive in adopting the existing global strategies for TB control, including Directly Observed Treatment Short Course (DOTS) and the Stop TB Strategy [4]. The stepwise adoption of these principles was facilitated by the development of a set of European-specific, consensus-based documents born within the Wolfheze initiative [5]. A European group of experts, country representatives and international organisations (World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and the KNCV Tuberculosis Foundation) developed guidance and policy documents on TB control and elimination, surveillance, screening and management of immigrants, treatment outcome monitoring, drug susceptibility testing [6–10] and, more recently, contact tracing [11]. The whole package …
Just Toxicity, or Toxicity As a Biomarker of Efficacy of Ramucirumab in Breast Cancer?
Authors: Hyo Jin Lee, Hyewon Ryu, Yoon Seok Choi, Ik-Chan Song, Hwan-Jung Yun, Deog-Yeon Jo, Samyong Kim
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: Mackey et al reported the results of ROSE/ TRIO-012 (Ramucirumab Overall Survival Evaluation/Translational Research in Oncology 012), a randomized, placebo-controlled, phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer. The study did not meet its primary end point of investigator-assessed progression-free survival (PFS), although PFS numerically favored the ramucirumab group (median PFS, 9.5 v 8.2 months; hazard ratio, 0.88; P .077). An important question was raised as to why the antiangiogenic strategy targeting vascular endothelial growth factor receptor 2 signaling in breast cancer failed to improve survival, whereas similar studies with ramucirumab in other solid tumors have shown significant survival benefits. In addition, is there any population that will benefit from this antiangiogenic treatment for breast cancer, as the authors mentioned in their Discussion section? In light of these questions, it is a critical challenge to identify relevant biomarkers, especially at the cellular or molecular level, that may help to identify molecularly defined populations with ramucirumab-sensitive disease. Alternatively, the occurrence of adverse events might act as surrogate biomarkers of drug activity, enabling the prediction of outcome during treatment, because the occurrence of treatment-related toxic effects is associated with a pharmacodynamic effect of the drug. Recently, it has been suggested that there are correlations between hypertension and outcome with ramucirumab in patients with advanced hepatocellular carcinoma. Therefore, it would be interesting to know whether the large prospective data set reported by Mackey et al shows a correlation between the development of hypertension and treatment outcome. The investigators could help to address this issue by providing survival curves related to the emergence of hypertension as an adverse event. Such data could help clinicians make better treatment decisions and could shed light on the future development of targeted therapy for breast cancer.
Gentamicin supplementation of polyvinylidenfluoride mesh materials for infection prophylaxis
Authors: Karsten Junge, Raphael Rosch, Uwe Klinge, Carsten Krones, Bernd Klosterhalfen, Peter R. Mertens, Petra Lynen, Dagmar Kunz, Achim Preiß, Heidrun Peltroche-Llacsahuanga, Volker Schumpelick
Journal: Biomaterials (2004)
Alveolar nitric oxide and its role in asthma control assessment
Authors: Olaia Sardon, Paula Corcuera, Ane Aldasoro, Javier Korta, Javier Mintegui, Jose Ignacio Emparanza, Eduardo G. Pérez-Yarza
Journal: European Respiratory Journal (2013)

Background: Nitric oxide (NO) can be measured at multiple flow rates to determine proximal [maximum airway NO flux (J'awNO)] and distal inflammation [alveolar NO concentration (CANO)].

Objectives: To measure the alveolar NO in healthy controls and to study the association among symptoms, lung function and NO in asthmatic children.

Methods: A cross-sectional study was performed in healthy and asthmatic children. Exhaled NO at multiple flow rates (50, 100, 200ml/s) was measured. According to the two-compartment model, CANO and J'awNO were calculated. In asthmatic patients, a questionnaire for asthma control (CAN) was completed and a forced spirometry was performed. The reproducibility of CANO and J'awNO was studied. In controls, differences between the sexes for CANO and J'awNO and their correlation with height were studied. The correlation among fractional exhaled NO (FENO,50), CANO, J'awNO, forced expiratory volume in one second (FEV1) and CAN was measured and the degree of agreement regarding asthma control assessment was studied using Cohen’s kappa (Kc).

Results: We studied 162 children; 49 were healthy (group1), 23 were asthmatic without treatment (group2) and 80 were asthmatic treated with inhaled corticosteroid (group3). CANO (ppb) was 2.2 (0.1-4.5); 3 (0.2-9.2) and 2.45 (0.1-24) respectively. J'awNO (pl/s) was 516 (98.3-1470); 2356.67 (120-6110) and 1426 (156-11805) respectively.The degree of agreement between FENO,50 and J'awNO was very good in group 2 (Kc=0.89) and good in group 3.

Conclusions: The results for CANO and J'awNO in healthy controls were similar to those found in other reports. There was no agreement among the three measurement instruments analyzed to assess asthma control (FEV1,CAN,CANO, J'awNO).
Activation and inactivation of cAMP-response element-mediated gene transcription in cardiac myocytes
Authors: F Müller
Journal: Cardiovascular Research (2001)

Objective: Chronic β-adrenergic stimulation of the cAMP-dependent signalling pathway is implicated in functionally relevant expressional changes in congestive heart failure. We studied activation and inactivation of the cardiac gene transcription mediated by the cAMP-response element (CRE) and the CRE-binding protein (CREB) as an important mechanism of a cAMP-dependent gene regulation. Methods: We investigated the transcriptional activation by forskolin, an activator of the adenylyl cyclase, in chick embryonic cardiomyocytes transfected with a CRE-controlled luciferase construct in comparison to the phosphorylation and expression of CREB determined on immunoblots. Results: Forskolin (10 μmol/l; 8 h) increased CRE-mediated transcription and phosphorylation of CREB 13- and 1.5-fold, respectively. The phosphorylation was further elevated in combination with cantharidin, an inhibitor of type 1+2A protein phosphatases. The transcriptional response to forskolin was desensitized by pretreatment with forskolin (1 μmol/l; 24 h) while CREB phosphorylation was increased. In forskolin-pretreated cells, total CREB protein levels were decreased. Cantharidin did not restore the attenuated transcriptional response. Conclusions: In cardiomyocytes, there is an activation of the CRE-mediated gene transcription by forskolin that is attenuated after prolonged stimulation, and this attenuation is not dependent from a dephosphorylation of CREB. We suggest that attenuation of the CRE-mediated transcription through chronic stimulation of the cAMP-pathway, e.g. by elevated catecholamines, contributes to the altered expressional regulation in congestive heart failure.