tbuckley/cabot-search huggingface dataset:
Breast irradiation postlumpectomy: development and evaluation of a decision instrument.
Authors: T J Whelan, M N Levine, A Gafni, H Lukka, E A Mohide, M Patel, D L Streiner
Journal: Journal of Clinical Oncology (1995)

To develop an instrument to help clinicians inform patients about the benefits and risks of breast irradiation following lumpectomy and to help an informed patient decide whether she prefers this treatment.A Decision Board consisting of written material and visual aids was developed. It provides the patient with detailed information about her choices (breast irradiation or not), outcomes (breast recurrence and survival), probability of those outcomes, and quality of life associated with treatment and outcome. We studied the decision-making process in 82 consecutive node-negative lumpectomy patients who were seen in consultation by a radiation oncologist and oncology nurse. The Decision Board was used in the last 30 patients in the cohort.Patient comprehension following the consultation without the Decision Board was greater than 65% for all questions addressed, except for poor understanding of the lack of survival benefit associated with breast irradiation (12% of patients answered correctly) and that it could not be repeated (15% of patients answered correctly). Comprehension following the consultation with the Decision Board was similar, but understanding regarding the repetition of radiation (83%) was improved. Only 70% of patients in the no-Decision Board group felt they were offered a choice. This was increased to 97% in the Decision-Board group. Overall, 95% of patients chose breast irradiation, and this did not differ between groups. Patients reported several reasons for choosing breast irradiation, all of equal importance.The Decision Board facilitated shared decision making in node-negative lumpectomy patients who chose breast irradiation, but it did not affect a patient's choice to select breast irradiation.
Long‐term (6 and 12 months) follow‐up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF‐200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis
Authors: T. Dirschka, P. Radny, R. Dominicus, H. Mensing, H. Brüning, L. Jenne, L. Karl, M. Sebastian, C. Oster‐Schmidt, W. Klövekorn, U. Reinhold, M. Tanner, D. Gröne, M. Deichmann, M. Simon, F. Hübinger, G. Hofbauer, G. Krähn‐Senftleben, F. Borrosch, K. Reich, C. Berking, P. Wolf, P. Lehmann, M. Moers‐Carpi, H. Hönigsmann, K. Wernicke‐Panten, S. Hahn, G. Pabst, D. Voss, M. Foguet, B. Schmitz, H. Lübbert, R.‐M. Szeimies
Journal: British Journal of Dermatology (2012)

Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates.To evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo.The follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT.Recurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported.The FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy.
Smoking Control Is a Priority to Promote Heart, Lung, Blood, and Sleep Health
Authors: Carlos A. Jimenez-Ruiz, Jean-Paul Sculier, Bo Lundback, Constantine Vardavas, Jose Ignacio De Granda Orive, Paraskevi Katsaounou, Patricia Haslam, Dick J. J. Heederik, Sofia Ravara, Dan Smyth, Fernando Martin, Christina Gratziou
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

In their nice editorial in the March issue of the Journal, Kiley and colleagues (1) list the strategic priorities and procedures of the National Heart, Lung, and Blood Institute (NHLBI) to streamline human health research up to 2025.From a historical perspective, we all recognize the significant achievements of the U.S. National Institutes of Health and the NHLBI, with decades of success, that have facilitated breakthroughs in promoting health and fighting disease by funding key research both internally and extramurally, including internationally.However, we were surprised that the (magical) keyword "tobacco" was not mentioned at all within this short document, so anyone might wonder, what if . . . the NHLBI considers tobacco?Likely, beyond your pages, some readers in the sister, simultaneous publications in the American Journal of Public Health, Blood, Circulation, or the Journal of the American College of Cardiology might consider that tobacco affects patients in most (all?) respiratory and nonrespiratory conditions.We must keep reminding ourselves that tobacco is the first and foremost causal, avoidable risk factor for human disease.Perhaps it has been neglected too often in the past in many medical venues (2, 3).Therefore, the NHLBI should welcome initiatives on key tobacco-related translational issues as well as on the efficacy and the effectiveness of any smoking reduction and/or avoidance interventions, in addition to initiatives on any other risk factors to help define smoking issues at the population and individual levels.Well past the so-called cigarette century (4), tobacco is still causally linked to an increasing number of diseases (5).Although there have been some recent successes in the West, there are more smokers nowadays than ever before in human history, causing far too many premature deaths and disabilities (6).We strongly believe that research drives all health advocacy and that the final solution to the tobacco problem will be through legislation (7).Rephrasing the introductory paragraphs of the editorial, "Imagine a world with no tobacco, and later, perhaps only one generation after, a no-tobacco-related-disease world."Wouldn't it be nice?We can set this objective within our lifetime, and certainly we will participate in this process (8).
Cloning and analysis of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase genes HsHDR1 and HsHDR2 in Huperzia serrate
Authors: Haizhou Lv, Xin Zhang, Baosheng Liao, Wanjing Liu, Liu He, Jingyuan Song, Chao Sun, Hongmei Luo, Shilin Chen
Journal: Acta Pharmaceutica Sinica B (2015)

We cloned and analyzed the two genes of the 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (HDR) gene family from Huperzia serrate. The two transcripts coding HDR, named HsHDR1 and HsHDR2, were discovered in the transcriptome dataset of H. serrate and were cloned by reverse transcription-polymerase chain reaction (RT-PCR). The physicochemical properties, protein domains, protein secondary structure, and 3D structure of the putative HsHDR1 and HsHDR2 proteins were analyzed. The full-length cDNA of the HsHDR1 gene contained 1431 bp encoding a putative protein with 476 amino acids, whereas the HsHDR2 gene contained 1428 bp encoding a putative protein of 475 amino acids. These two proteins contained the conserved domain of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (PF02401), but without the transmembrane region and signal peptide. The most abundant expression of HsHDR1 and HsHDR2 was detected in H. serrate roots, followed by the stems and leaves. Our results provide a foundation for exploring the function of HsHDR1 and HsHDR2 in terpenoid and sterol biosynthesis in Huperziaceae plants.
Simvastatin attenuates cigarette smoke extract induced extracellular matrix
Authors: Brian Oliver, Janette Burgess, Judy Black, David Krimmer
Journal: European Respiratory Journal (2011)

Introduction: Production of extracellular matrix (ECM) proteins is increased in the small airway walls of patients with chronic obstructive pulmonary disease (COPD). Current pharmacotherapies are unable to reduce or attenuate ECM in vivo. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, is emerging as a new potential therapy for COPD. In this study we investigated if simvastatin could affect cigarette smoke extract (CSE) induced ECM and cytokine production from human lung fibroblasts.

Methods: Primary human lung fibroblasts were stimulated with 5% CSE in the presence of 0.5 and 5μg/ml simvastatin, or relevant concentrations of vehicle control, for 72 hours. Supernatants were collected and assessed for pro-inflammatory cytokine and matrix metalloproteinase (MMP) release. Cells were removed by addition of NH4OH and the relative deposition of the ECM proteins fibronectin and perlecan was analysed using an ECM ELISA. The concentration of interleukin (IL)-6 in the supernatant was measured using ELISA.

Results: Treatment of human lung fibroblasts with 5% CSE upregulated the deposition of fibronectin and perlecan, and the release of IL-6 into the supernatant. Addition of simvastatin at 5μg/ml significantly attenuated 5% CSE induced deposition of fibronectin by 43% and perlecan by 41.5% (p<0.05, n=6). 5% CSE induced IL-6 release was also attenuated by 31% with the addition of simvastatin at 5μg/ml.

Conclusions: Inhibition of the HMG-CoA reductase pathway may alter the deposition of ECM proteins and release of inflammatory cytokines in COPD.
Assessment of physical functioning in surgical candidates with non-small cell lung cancer: Preliminary comparison of performance status to symptom-limited cardiopulmonary exercise testing
Authors: Michael A. Roman, Neil D. Eves, Lee W. Jones
Journal: European Respiratory Journal (2011)

Background:  Performance status (PS) scoring systems are used routinely by clinicians to guide management of patients with non-small cell lung cancer (NSCLC). However, PS scoring systems are subjective with poor inter-rater reliability and do not provide an objective measure of functional status. The aim of this study was to compare the variability in an objective measure of cardiorespiratory fitness (VO 2peak ), among surgical candidates with histologically confirmed NSCLC across different PS categories as assessed by the Eastern Cooperative Oncology Group (ECOG) score.   Methods:  Using a cross-sectional design, 389 subjects underwent an incremental cardiopulmonary exercise test with expired gas analysis to determine VO 2peak  prior to surgical resection.   Results:  Mean VO 2peak  significantly declined across increasing ECOG categories (Table 1). There was a wide range in VO 2peak  in each ECOG category with similar ranges in VO 2peak  within groups, in particular in subjects classified as ECOG 1 and 2.   Conclusions:  VO 2peak  may provide a more sensitive evaluation of physical functioning than ECOG. Accurate assessment of functional status may have important implications for mortality risk and therapeutic management in the oncology setting.
Abstract 3689: Loss of Myeloid Related Protein-8/14 Exacerbates Cardiac Allograft Rejection
Authors: Koichi Shimizu, Peter Libby, Viviane Z Rocha, Eduardo J Folco, Rica Shubiki, Kevin J Croce, Nancy Hogg, Richard N Mitchell, Daniel I Simon
Journal: Circulation (2008)

Background: The S100 calcium-binding proteins MRP-8 (S100A8) and MRP-14 (S100A9) heterodimerize to form MRP-8/14 complexes that regulate myeloid cell function, control inflammatory responses, and serve as an early serum marker for monitoring acute allograft rejection. Despite functioning as a putative pro-inflammatory mediator, the pathophysiological role of MRP-8/14 in cardiovascular disease remains unknown. This study used murine cardiac transplantation to investigate the role of MRP-14 in cardiac allograft rejection using MRP-14-deficient mice (MRP14−/−) lacking MRP-8/14 complexes. Results: In major histocompatibility complex class II allomismatched cardiac transplantation (bm12 donor hearts and C57BL/6 recipients), allograft survival averaged 5.9 ± 2.9 weeks (n=10) in MRP14−/ −recipients compared to &gt; 12 weeks (n = 15, p&lt;0.0001) in wild-type (WT) recipients. At 2 week post-transplantation, allografts in MRP14−/ − recipients had significantly higher parenchymal rejection (PR) scores (2.8 ± 0.8, n=8) than WT recipients (0.8 ± 0.8, n=12, p&lt;0.0001). MRP14−/ − recipients had significantly increased allograft accumulation of T cells and macrophages and mRNA levels of IFN-γ and IFN-γ–associated chemokines (IP-10, Mig, and I-TAC) compared to WT recipients. The MRP14−/− recipients also had significantly more lymphocytes in draining lymph nodes than WT recipients (cell number per lymph nodes: 23.7 ± 0.7 x 105 for MRP14−/− vs. 6.0 ± 0.2 x 105 for WT, p &lt; 0.0001). MRP14−/− dendritic cells (DC) stimulated with IFN-γ expressed significantly higher levels of the co-stimulatory molecules CD86 and ICOSL, and mixed leukocyte reaction using allo-EC-primed MRP14−/− DC resulted in significantly higher antigen-presenting function than WT DC. Conclusion: Taken together, these observations indicate that MRP-8/14 complexes participate in acute allograft rejection by modulating dendritic cell antigen presentation and T cell priming. The unexpected finding that deficiency of MRP-8/14 complexes exacerbates acute allograft rejection indicates that MRP-8/14 has distinct roles in modulating immune cell functions, such as migration and antigen presentation. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Airflow reversibility on long term outcomes of patients with COPD
Authors: Virginia Moya, Ana Boldova, Elisa Minchole, Santiago Carrizo, Cristina Navarro, Allan Sam, Marc Miravitlles, Jose María Marin
Journal: European Respiratory Journal (2014)

Rationale. In COPD, post-bronchodilator spirometry is mandatory to diagnose the disease. It is uncertain whether the response to short-acting bronchodilators may also predict long-term outcomes such as hospitalisations and mortality.  Methods. In the frame of BODE international cohort we studied a total of 1203 consecutive COPD patients without significant co-morbidities including a clinical diagnosis of asthma (Charlson index=0). Subjects were classified at baseline into those with positive (FEV 1  >12 % and > 200ml) or negative bronchodilator test (BDT) and also in quartiles of absolute bronchodilator response to 400 mg of salbutamol. Hospital visits and overall mortality were the end points.   Results.  A positive BDT test was observed in 332 (27.6%) of patients. During a mean (±SD) of 69.1± 39.4 months of follow-up there were 73 (21.9%) deaths in patients with positive BDT versus 253 (28.7%) in those with negative BDT (p=0.04). In adjusted Cox regression analysis a positive BDT was significantly associated with a prolonged time to first hospitalization. When the population was divided into quartiles of response to BDT, there was a dose-response relationship with the best outcomes observed in the quartile with highest level of airflow reversibility, even after controlling for age, sex, BMI, smoking status and baseline post-bronchodilator FEV1.  Conclusions.In a large population of well characterised COPD patients without significant comorbidities, those who demonstrated higher levels of reversibility after treatment with a short-acting beta-2 agonist presented better long-term outcomes even after controlling for other known prognostic factors.
Supervised Exercise, Stent Revascularization, or Medical Therapy for Claudication Due to Aortoiliac Peripheral Artery Disease
Authors: Timothy P. Murphy, Donald E. Cutlip, Judith G. Regensteiner, Emile R. Mohler, David J. Cohen, Matthew R. Reynolds, Joseph M. Massaro, Beth A. Lewis, Joselyn Cerezo, Niki C. Oldenburg, Claudia C. Thum, Michael R. Jaff, Anthony J. Comerota, Michael W. Steffes, Ingrid H. Abrahamsen, Suzanne Goldberg, Alan T. Hirsch
Journal: Journal of the American College of Cardiology (2015)
A Novel Insight into Adaptive Immunity in Chronic Obstructive Pulmonary Disease
Authors: Francesca Polverino, Simonetta Baraldo, Erica Bazzan, Simone Agostini, Graziella Turato, Francesca Lunardi, Elisabetta Balestro, Marco Damin, Alberto Papi, Piero Maestrelli, Fiorella Calabrese, Marina Saetta
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Chronic obstructive pulmonary disease (COPD) is a disorder characterized by an abnormal inflammatory response that persists even after smoking cessation, yet the underlying mechanisms are not fully understood.To investigate the expression of B-cell activating factor of tumor necrosis factor family (BAFF), a crucial mediator in the crosstalk between innate and adaptive immune responses, in patients with COPD and to explore its correlation with disease severity.Using immunohistochemistry, expression of BAFF was examined in lung specimens from 21 smokers with COPD (FEV(1) = 57 ± 5% predicted), 14 control smokers (FEV(1) = 99 ± 2% predicted) and 8 nonsmokers (FEV(1) = 104 ± 4% predicted). BAFF was quantified in alveolar macrophages and alveolar walls, in bronchiolar and parenchymal lymphoid follicles, and in peripheral airways and pulmonary arterioles.In alveolar macrophages and parenchymal lymphoid follicles, BAFF expression was increased in smokers with COPD compared with control smokers and nonsmokers (P < 0.05 for all comparisons). In both compartments, BAFF was also up-regulated in control smokers as compared with nonsmokers (P = 0.03 and P = 0.01). Moreover, BAFF was overexpressed in bronchiolar lymphoid follicles, alveolar walls, peripheral airways, and pulmonary arterioles from smokers with COPD compared with nonsmokers (P < 0.05 for all). Among patients with COPD, BAFF(+) macrophages were inversely related to FEV(1) (P = 0.03, Spearman's rho [r(S)] = -0.48), FEV(1)/FVC (P = 0.02, r(S) = -0.50), and Pa(O(2)) values (P = 0.01, r(S) = -0.55).This study demonstrated overexpression of BAFF in peripheral lung of patients with COPD, mainly in alveolar macrophages and lymphoid follicles. Moreover, BAFF expression was correlated to the degree of lung function impairment and hypoxia, suggesting that it may have a possible impact on disease severity.
Role of Adjuvant Chemotherapy in the Treatment of Surgically Resected Pediatric Nonrhabdomyosarcomatous Soft Tissue Sarcomas: A Pediatric Oncology Group Study
Authors: Charles B. Pratt, Alberto S. Pappo, Peter Gieser, Jesse J. Jenkins, Arnold Salzberg,†, James Neff, Bhaskar Rao, Dan Green, Patrick Thomas, Robert Marcus, David Parham, Harold Maurer
Journal: Journal of Clinical Oncology (1999)

To prospectively study the value of adjuvant chemotherapy in pediatric patients with surgically resected nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS).From June 1986 to May 1992, after complete surgical resection (+/-radiotherapy) of their NRSTS, 81 eligible patients either received adjuvant chemotherapy comprising vincristine, dactinomycin, cyclophosphamide, and doxorubicin or were observed. Only 30 patients accepted randomization, and 15 were assigned to each regimen. Of the remaining 51 patients, 19 elected adjuvant chemotherapy and 32 elected observation.Patients were predominantly male, and 69% of all patients were white. The median age at diagnosis was 12.3 years (range, 9.2 to 20.7 years). For the 81 eligible patients, the 5-year overall survival estimate was 84.5% +/- 4.4% and event-free survival was 72.2% +/- 5.4%. Among randomized patients, the 5-year estimated overall survival rate was 93.3% +/- 7%, and the event-free survival rate was 86.7% +/- 9.5% for the observation group, compared with 69.2% +/- 13% and 40.7% +/- 14%, respectively, for those who received chemotherapy. The significantly worse outcome of patients who received adjuvant chemotherapy disappeared when survival was stratified by tumor grade. Among all patients, a grade 3 lesion conferred a significant disadvantage with respect to event-free survival (P =.0001).The administration of adjuvant chemotherapy according to the schedule and dosages used in our trial did not improve the outcome of children with resected NRSTS. In this study, tumor grade was the most important predictor of clinical outcome in patients with resected NRSTS, and this factor should be incorporated into the stratification of patients in future trials.
Differentiation of the Mononuclear Phagocyte System During Mouse Embryogenesis: The Role of Transcription Factor PU.1
Authors: Agnieszka M. Lichanska, Catherine M. Browne, Gregory W. Henkel, Kathleen M. Murphy, Michael C. Ostrowski, Scott R. McKercher, Richard A. Maki, David A. Hume
Journal: Blood (1999)
Exposure to household air pollution and respiratory symptoms in Nepal: A cross-sectional study
Authors: Om P Kurmi, Santosh Gaihre, Jon G Ayres
Journal: European Respiratory Journal (2014)

Background: Exposure to household air pollution (HAP) is associated with respiratory health problems in low and middle income countries. The aim of this study was to assess the association between respiratory symptoms and exposure to wood smoke in rural area of Nepal.

Methods: A cross-sectional study of adults (16+ years) in a rural population (n=846) exposed to wood smoke and a non-exposed urban population (n=802) in Nepal. Validated questionnaire including that of respiratory symptoms, spirometry data were acquired along with indoor air quality (PM2.5 and CO) and outdoor PM2.5 measurement.

Results: Rural females were significantly more likely to complain of ever having wheezed (32.8 % vs. 23.8%; p<0.001) compared to their male counterparts with smoking being a major risk factor. Women exposed to HAP were more likely to complain of dyspnoea not induced by exercise (OR=3.3, 95% CI 1.46-7.57), dyspnoea with wheeze (4.91, 2.49-9.69), ever wheeze (4.62, 2.71-7.87) and chest tightness (3.18, 1.53-6.61) but were not more likely to complain of productive cough. 24-hour PM2.5 measurement was positively associated with breathlessness and wheeze in women. Urban males exposed to outdoor air pollution were more likely to report ever wheeze (3.06, 1.28-7.31) and wheeze on most days and night (3.30, 1.35-8.13). There was a high negative correlation between lung function indices (FEV1, FEF25-75 and FEV1/FVC) and the presence of respiratory symptoms in those exposed to HAP.

Conclusion: The study suggests that women exposed to HAP reported more respiratory symptoms but males exposed to outdoor air pollution not HAP reported more symptoms.