tbuckley/cabot-search huggingface dataset:
Assessment of physical activity with accelerometer in Brazilian asthmatic children
Authors: Andrey Sousa, Anna Cabral, Milton Martins, Celso Carvalho
Journal: European Respiratory Journal (2011)

Background:  Although it is widely accepted that asthmatic children are physically unconditioned, however there are few reports quantifying the level of physical activity, especially in developing countries.   Objective:  To evaluate the level of physical activity in asthmatic children and to compare among asthma severities.   Methods:  Sixty-nine children (50M/19F, 18.8±3.1 lkg/m 2 ) with persistent mild (n=27), moderate (n=20) and severe (n=22) asthma were evaluated. Children worn an accelerometer for 6 days (4week and 2weekend) and the total steps per day (TStp) and steps walked at either moderate or vigorous intensities (>100 steps/minute) were evaluated.   Results:  Our results show that 71% of all asthmatic children were considered physically active (male>12,000 and female>10,000 steps per day). The level of activity at moderate or vigorous intensities in physically active children represented around 45% of total step counting and they showed higher activity levels during week compared with weekend days (p 0.05).   Conclusion:  Contrary to popular belief, most asthmatic children were considered physically active and those patients with moderate and severe asthma are still more active.
Increasing use of radical prostatectomy for lower-risk prostate cancer in Denmark.
Authors: M. Andreas Roeder, Klaus Brasso, Ib Jarle Christensen, Jorgen Johansen, Niels Christian Langkilde, Helle Hvarness, Henrik Jakobsen, Steen Carlsson, Michael Borre, Peter Iversen
Journal: Journal of Clinical Oncology (2014)

149 Background: Denmark introduced radical prostatectomy (RP) as the last Nordic country in 1995. Since then, a rapid increment in the Danish incidence of prostate cancer (PCa) is indicative of increasing opportunistic prostate-specific antigen (PSA) testing. We hypothesized that an increasing proportion of men undergo RP for lower-risk PCa. Methods: All patients undergoing RP in Denmark between 1995 and 2011 were included. Changes over time in age at surgery, preoperative PSA, clinical T-category, biopsy Gleason score (GS) are described. Tests for statistically significant changes in trends were performed using linear regression and Cochran-Armitage trend test. Results: Median age at surgery increased from 61.4 to 64.8 (p&lt;0.0001) during the 16 year period. Median preoperative PSA declined from 11.5 to 7.9 ng/ml (p&lt;0.0001). Distribution of biopsy GS changed significantly, especially after 2005. Biopsy GS=7 was found in 20.2% of the patients in 2005 compared to 57.1% in 2011. The proportion of T1 disease increased from 32% to 56%. The proportion of patients above age 65 increased from 26.8% to 48.3% in the 16 year period studied. To adjust for grade, PSA, and age migration, we analyzed changes in the proportion of men age over age 65, with PSA less than or equal to 10 ng/ml, biopsy GS≤3+4, and clinical T1 disease over time. In the 16 year period, this proportion increased from 2% to 16% (p&lt;0-001) of the cohort undergoing RP in Denmark. Conclusions: Significant preoperative age, stage, and Gleason grade migration was found in this complete Danish nation-wide cohort of patients undergoing RP during the past 16 years. This has occurred in the absence of any major changes to the national Danish guidelines for diagnosis and treatment of localized PCa. This effect is likely attributed to an increasing use of PSA although national guidelines recommend against PSA screening. Further, new guidelines from the International Society of Urological Pathology have had a major impact on risk classification. According to recently published randomized trials, the risk of overtreatment of localized PCa with RP is an increasing problem in Denmark.
Interleukin 27 (IL27) as a novel therapeutic tool in lung cancer immune therapy
Authors: Tomasz Wandtke, Marek Jankowski, Ewelina Wedrowska, Karina Szablowska, Joanna Golinska, Joanna Wielikdzien, Janusz Kowalewski, Piotr Kopinski
Journal: European Respiratory Journal (2013)

Introduction: IL27 is a cytokine secreted by antigen presenting cells and responsible mainly for the Th1 immune polarization and cytotoxic response. Because of its properties, IL27 may be a potential therapeutic tool for lung cancer immune therapy. Previously we constructed a plasmid encoding IL27 (pXMs-IL27).

Aim: To evaluate a clinical potential of pXMs-IL27 as a therapeutic tool applied to human small- (H82) and non-small (A549) cell lung cancer lines.

Materials and Methods: The expression of IL27 was performed by cell lines (A549 and H82) transfection with a pXMs-IL27 and empty control plasmid. Transfection efficacy was proved by RT-PCR and anti-IL27 indirect immunostaining. Additionally, the expression of CD80, CD83, CD86, CD120a, CD120b, CD178 molecules after transfection with plasmids was studied by direct immunofluorescence and analyzed by flow cytometry.

Results: RT-PCR and flow cytometry confirmed the expression of IL27 in transfected cells (A549: 79%; H82: 56%, median of 5 experiments). With use of flow cytometry the baseline expression of IL27 was found in both cell lung cancer lines, particularly in A549 (40%). Tumor cells transfected with pXMs-IL27 plasmid showed in microscopic observations intense apoptosis, as compared with empty plasmid control.

Conclusions: Cell lines were successfully transfected with pXMs-IL27 plasmid. Phenotypic changes and increased apoptosis rate in transfected cells suggest that IL27 will be useful in future immune therapy of lung cancer.
Abstract 2991: Triple combination of bevacizumab, anti-DLL4 (delta like ligand 4) and trebananib gives enhanced therapeutic effects in three xenograft tumor models
Authors: Bethany Mattson, Jodi Moriguchi, H. Toni Jun, Angela Coxon, Dave Cordover, Steve Kaufman, Jon Oliner, Charlie Starnes
Journal: Cancer Research (2014)

Abstract Bevacizumab is a monoclonal antibody targeting VEGF that is clinically approved for the treatment of multiple indications in oncology, including colorectal, lung and renal cancer as well as glioblastoma. Clinical activity has also been demonstrated in breast and ovarian cancer as well, however, the time periods of benefit for all of these indications is in months (1-5). Multiple pathways are known to participate in the process of angiogenesis, and the limited effects of bevacizumab may represent the maximum activity of targeting just one of them. The purpose of the present study was to examine the effect of simultaneously targeting multiple angiogenic axes including angiopoietins 1 and 2, Dll4 and VEGF. Trebananib is a recombinant peptide-Fc fusion protein that selectively blocks the Tie2 interactions of both Ang1 and Ang2. Trebananib, as well as a recombinant antibody to Dll4 were produced at Amgen, Inc., Thousand Oaks, CA. Bevacizumab was purchased from a local pharmacy. These reagents were employed in the combination treatment of three different preclinical murine tumor models (U87, glioblastoma; MiaPaca and BxPC3, pancreatic carcinoma), one of which (BxPC3) was specifically selected for its relative resistance to VEGF/KDR inhibition. Harlan Athymic nu/nu female mice at 6-7 weeks of age were injected subcutaneously on the right flank with 5 x 106 tumor cells in the presence of Matrigel and treated when the tumors were approximately 300 mm3. The results, as supported by histomorphometric analysis (percent blood vessel area, viable tumor burden), demonstrate that under conditions of optimal biological dosing, the addition of trebananib to a two-way combination of bevacizumab and anti-Dll4 resulted in a statistically significant enhancement of therapeutic effect for the three-way combination, an observation made consistently over 3 different tumor models and 3 different dose levels of bevacizumab and anti-Dll4 (p = or &amp;lt; 0.0024; RMANOVA). Furthermore, the therapeutic effect in all three models approximated prolonged stasis, the ultimate theoretical goal of antiangiogenesis in the treatment of cancer. 1. NEJM, vol. 350, p. 2335, 2004. 2. NEJM, vol. 355, p. 2542, 2006. 3. Lancet, vol. 370, p. 2103, 2007. 4. NEJM, vol. 357, p. 2666, 2007. 5. J. Clin. Oncol., vol. 30, p. 2039, 2012. Citation Format: Bethany Mattson, Jodi Moriguchi, H. Toni Jun, Angela Coxon, Dave Cordover, Steve Kaufman, Jon Oliner, Charlie Starnes. Triple combination of bevacizumab, anti-DLL4 (delta like ligand 4) and trebananib gives enhanced therapeutic effects in three xenograft tumor models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2991. doi:10.1158/1538-7445.AM2014-2991
Abstract 41: Liquid Convection Surface Cooling Leads to High Rate of Recovery of Post-VT/VF Patients
Authors: Paul McMullan, Daniel Howes, William Ohley, Paul Dorian, Robert Freedman, Robert B Schock, Michael Holzer
Journal: Circulation (2011)

Introduction: Therapeutic hypothermia is an accepted standard of care for patients resuscitated from VT (ventricular tachycardia) and/or VF (ventricular fibrillation). Some prior studies have suggested that a faster time to target temperature may improve the chances of favorable neurological recovery. Hypothesis: We hypothesized that rapid cooling of post VT/VF patients using liquid convection surface cooling would lead to a high rate of recovery of such patients, compared to historical results with slower cooling methods. Methods: The Life Recovery Systems ThermoSuit System® was used to induce therapeutic hypothermia (approximately 33°C, maintained for 12 to 24 hours) in 37 post-resuscitation patients in 4 hospitals. Patient temperatures were monitored with an esophageal probe. Results were retrospectively analyzed for cooling rates, cardiac rhythm of VT/VF, favorable neurologic recovery (CPC 1 or 2), and adverse events. Results: Of the 37 patients, the mean cooling rate was 3.4 °C/hr (range 1.3-8.8). Of the 37 patients, 20 were resuscitated from VT or VF. Of these, 17 (85%) survived with favorable outcomes following the ThermoSuit treatment. There were no adverse events. Conclusions: Rapid induction of therapeutic hypothermia with the ThermoSuit System was associated with a very high rate of favorable neurologic recovery and an absence of adverse events in post-VT/VF patients. When compared with results of similar studies of slower cooling methods, these results suggest an advantage of faster cooling methods for the treatment of post-VT/VF patients.
Long-term results from TAX324: A phase III trial of sequential therapy comparing TPF to PF in locally advanced (LA) squamous cell cancer of the head and neck (HNC).
Authors: J. H. Lorch, M. R. Posner, O. Goloubeva, K. J. Cullen, N. J. Sarlis, R. B. Tishler, R. I. Haddad
Journal: Journal of Clinical Oncology (2010)

5512 Background: The original TAX 324 study established TPF induction therapy administered prior to carboplatin-based chemoradiotherapy as a treatment standard for patients (pts) with LA HNC, based on a statistically significant 30% improvement in overall survival (OS) for TPF vs. PF after a minimum follow-up (FU) of 2 years (yrs). The long term outcomes of the TAX324 study with a minimum pt FU of 5 yrs are presented. Methods: After IRB approval, data on OS, progression-free survival (PFS) and functional outcomes were collected through December 1, 2008 and were analyzed by summary statistics. Results: FU data of 425 of 501 subjects (85%) included in TAX 324 were collected. With a median FU of 71 months (mo) and a minimum FU of 5 yrs, the median OS in the TPF arm remained significantly longer than in the PF arm (71 vs. 35 mo; p=0.013). Mortality was reduced by 26% with TPF compared with PF (HR 0.74; 95% CI 0.58-0.94). At 5 yrs, 52% and 42% of the TPF and PF pts were alive, respectively. Subset analysis showed that pts older than the study's median age of 55 yrs had a significantly better OS with TPF vs. PF (p=0.04), while there was no significant difference between treatment arms for pts <55 yrs old. Furthermore, the significant improvement in progression-free survival (PFS) with TPF in hypopharynx and larynx cancer pts was sustained at 5 years (p=0.037). Interestingly, the OS benefit for pts with oropharynx (OP) tumors after TPF increased over time and reached statistical significance at 5 years: Median OS was not reached with TPF, while it was 65 mo with PF (p= 0.045, HR 0.69; CI 0.48-0.99). There was a low rate of tracheostomy and gastric feeding tube dependence in both arms. Conclusions: The survival benefit of sequential therapy with TPF remains significantly superior to PF beyond 5 yrs of continuing FU. Patients over age 55 appear to benefit more from treatment with TPF (vs. PF) than younger patients and the benefit of TPF becomes more apparent with longer FU in patients with oropharynx tumors. These data support the long-term efficacy of TPF sequential therapy in the management of appropriate patients with LA HNC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis
Systemic characterization of macrophage phenotypes in allergic airway inflammation
Authors: Wilhelm Bertrams, Kerstin Seidel, Alexandra Sittka, Annalisa Marsico, Stefanie Hagner-Benes, Holger Garn, Harald Renz, Martin Vingron, Bernd Schmeck
Journal: European Respiratory Journal (2014)

Macrophages are central players in lung pathology. Besides the M1 subtype (classic activation), alternatively activated M2 macrophages have been described. Recently, microRNAs (miRNAs) have emerged as a regulatory network with great impact on cellular organization. We investigate the role of miRNAs in macrophage polarization and associated diseases. Here, we analyzed the systemic RNA phenotype of murine lung macrophages in allergic airway inflammation. We aim to compare these findings to prototypical  in vitro  polarized human blood-derived macrophages to assess the disease-associated polarization status in the mouse model.  Different macrophage subsets were purified by FACS sorting.  In vitro  polarized human macrophages were isolated by CD80 (M1) or CD23 (M2) positive selection. Macrophages from the bronchoalveolar lavage fluid (BALF) and lung homogenate of mice with acute eosinophilic airway inflammation were sorted on the basis of CD11 and SiglecF. We investigated the global miRNA profile of the alveolar and interstitial macrophages by Taqman Low Density Array (TLDA). A principal component analysis (PCA) of these data was used to define the macrophage status in the lungs of healthy and asthmatic mice. Differential miRNA expression could be observed that seems to be tissue- and asthma dependent. We validated individual miRNAs that were significantly regulated in the context of asthma as determined. Up-regulation of miR-21a-5p and down-regulation of miR-126-3p, as well as down-regulation of the M1-associated miR-146a-5p was observed in interstitial macrophages. This signature suggests a M2-like polarization profile, which is in line with the T H 2-skewed environment in eosinophilic airway inflammation.
The contribution of respiratory function tests to clinical diagnosis
Authors: G Laszlo, G N Lance, G T Lewis, A O Hughes
Journal: European Respiratory Journal (1993)

The purpose of this study was to investigate the amount of diagnostic information contained in a set of routine lung function studies and to attempt to determine which tests could be omitted without significant loss of discrimination. Cluster analysis was performed on a set of physiological and questionnaire data, collected prospectively in 1,542 male patients, referred consecutively for measurement of forced expired volumes, static lung volumes and measurements of the transfer factor for carbon monoxide. A respiratory questionnaire was completed for each patient. A physician assigned the patients to a rigorously defined diagnostic category, based on supporting clinical information, as well as pulmonary function, apart from 241 patients with unusual diagnoses and those in whom the criteria did not apply satisfactorily. This diagnosis was never included as a classification variable. Basing the classification on three independent measurements, total lung capacity, the ratio of forced expiratory volume in one second (FEV1) to vital capacity, and the transfer factor for carbon monoxide, the computer generated six groups: one normal, one showing an isolated gas exchange defect, and four with varying degrees of restriction and obstruction. This classification performed well in separating the patients with the clinical diagnoses of chronic airflow obstruction, bronchial asthma and interstitial lung disease from those with ischaemic and valvular heart disease and other miscellaneous disorders. Omitting total lung capacity resulted in some loss of specificity, but valid information was still obtained. The inclusion of all the static and dynamic lung volumes and of carbon monoxide transfer coefficient made little difference.(ABSTRACT TRUNCATED AT 250 WORDS)
Attitudes of Research Participants and the General Public Regarding Disclosure of Alzheimer Disease Research Results
Authors: Jonathan Gooblar, Catherine M. Roe, Natalie J. Selsor, Matthew J. Gabel, John C. Morris
Journal: JAMA Neurology (2015)

Results of Alzheimer disease (AD) research assessments typically are not disclosed to participants. Recent research has suggested interest in disclosure, but, to our knowledge, few studies have accounted for awareness of potential benefits and limitations of disclosure.To determine the attitudes of cognitively normal research participants and members of the general public regarding disclosure of AD research results.Participants in a longitudinal aging study (Alzheimer Disease Research Center [ADRC]) were given preintervention and postintervention surveys about disclosure attitudes. In a general public sample (The American Panel Survey), participants responded to a similar survey about disclosure attitudes.Participants in the ADRC sample were randomly assigned to a group (n = 119) that read an education intervention about the usefulness of AD biomarkers or to a placebo group (n = 100) that read as its intervention general information about the ADRC. Participants in the general public sample read a brief vignette describing participation in a longitudinal AD study.Interest in disclosure of AD research results.Cognitively normal ADRC participants (n = 219) were 60.7% (n = 133) female, 83.6% (n = 183) of white race, and reported a mean of 15.91 years of education. Twenty-nine individuals refused participation. The American Panel Survey participants (n = 1418) indicated they did not have AD and were 50.5% (n = 716) female, 76.7% (n = 1087) of white race, and reported a mean of 13.85 years of education. Overall, 77.6% of eligible participants (1583 of 2041) completed the survey in July 2014. Interest in disclosure was high among the ADRC participants (55.1% [119 of 216] were "extremely interested"). Viewing the education intervention predicted lower interest in disclosure (odds ratio, 2.01; 95% CI, 1.15-3.53; P = .02). High subjective risk of AD, a family history of AD, and minimal attendance at research meetings were associated with high interest after the intervention. In the general public, interest was lower overall (12.5% [174 of 1389] were "extremely interested"), but the subset of participants most likely to join an AD research study reported higher interest (43.5% [40 of 92] were extremely interested).Experience with AD appears to increase interest in disclosure of AD research results. Learning about potential limitations of disclosure somewhat tempered interest. These findings should inform the development of disclosure policies for asymptomatic individuals in AD studies.
Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model
Authors: Mi Jin Kim, Meeyoung Park, Dae Won Kim, Min Jea Shin, Ora Son, Hyo Sang Jo, Hyeon Ji Yeo, Su Bin Cho, Jung Hwan Park, Chi Hern Lee, Duk-Soo Kim, Oh-Shin Kwon, Joon Kim, Kyu Hyung Han, Jinseu Park, Won Sik Eum, Soo Young Choi
Journal: Biomaterials (2015)
Baseline and change from baseline in tumor burden compared with patient outcomes
Authors: L. Kaiser, J. Fridlyand, G. Fyfe
Journal: Journal of Clinical Oncology (2009)

e17530 Background: The impact of baseline tumor burden (bTB) and percentage reduction in tumor burden (dTB) on patient outcome has not been systematically studied in oncology clinical trials. We assess the relationship between both bTB and dTB and objective response (OR), progression free and overall survival (PFS and OS) in bevacizumab (B) and trastuzumab (T) trials. Methods: We analyzed 3 B and 1 T Ph 3 mBC and mCRC trials of &gt; 1800 patients total. We used correlations and Cox models for the relationships between pairs of variables and multivariate Cox models to evaluate TB and PFS as independent predictors of OS. Here, we present the minimum dTB value until progression. Results: bTB is not related to dTB, OR rate or PFS time; it is negatively related to OS. dTB shows a strong positive relationship with PFS and OS. TB and PFS are independent predictors of OS, with PFS the better predictor. Results at earlier dTB assessments and within treatment arms are similar. Conclusions: Patients with high bTB are equally likely to respond to treatment and to have prolonged PFS as those with lower bTB, but high bTB is a negative predictor for OS. In contrast, greater percentage reductions in TB are strongly associated with better PFS and OS outcomes. Tumor burden and PFS are independent predictors of OS. Owing to these relationships, assessing bTB and dTB, as well as OR, PFS and OS, may improve the interpretation of phase II data. [Table: see text] [Table: see text]
A study of inhaled arsenic-74 in man.
Authors: Robert H. Holland, Mary Sue McCall, Henry C. Lanz
Journal: Cancer Research (1959)

In an attempt to determine the amount of uptake distribution and rates of absorption and elimination of inhaled arsenic-74 in man 11 volunteers who had terminal lung cancer were studied.  8 inhaled smoke in their usual manner from a cigarette impregnated in its distal 1/2 with 250 muc. of arsenic-74 in the form of a solution of sodium arsenite.  The other 3 inhaled 200-300 muc. of arsenic-74 in an aerosol solution from an intermittent positive pressure machine.  Within the past 12 years many reports have revealed that the inhalation of arsenic dusts and fumes can be an etiological agent of lung cancer.  When smoke from cigarettes adulterated with arsenic-74 was inhaled uptakes of from 4.8-8.8% of the total radioactivity were found.  Uptakes of aerosol solution of arsenic-74 in 2 patients were 32 and 62% respectively.  Distribution of the inhaled arsenic-74 as determined with a scinti-scanner showed a diffuse uptake in 7 patients and a tendancy to pick up a greater amount in the perihilar areas in 4 patients.  The absorption rate from the bronchial tree was rapid for the 1st several days and then tapered off slowly.  In 3 patients an average of 45% of the inhaled arsenic was eliminated in the urine in 10 days and 2.5% in the stoool.
Evidence Against Routine Testing of Patients With Functional Gastrointestinal Disorders for Celiac Disease: A Population-based Study
Authors: Rok Seon Choung, Alberto Rubio-Tapia, Brian D. Lahr, Robert A. Kyle, Michael J. Camilleri, G. Richard Locke, Nicholas J. Talley, Joseph A. Murray
Journal: Clinical Gastroenterology and Hepatology (2015)