bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality control ofDL,COinstruments in global clinical trials
Authors: Jensen R. , Leyk M. , Crapo R. , Muchmore D. , Berclaz P. Y. 
Published: January 2009

High inter- and intra-laboratory variability exists for the single-breath diffusing capacity of the lung for carbon monoxide (DL,CO) test. To detect small changes in diffusing capacity in multicentre clinical trials, accurate measurements are essential. The present study assessed whether regularDL,COsimulator testing maintained or improved instrument accuracy and reduced variability in multicentre trials.The 125 pulmonary function testing laboratories that participated in clinical trials for AIR® Inhaled Insulin validated and monitored the accuracy of theirDL,COmeasuring devices using aDL,COsimulator, which creates known target values for any device. Devices measuring a simulatedDL,COdifferent from target by >3 mL·min-1·mmHg−1failed testing and were serviced. Device accuracy was assessed over time and with respect to differences in several variables.</emph>Initially, 31 (25%) laboratories had aDL,COdevice that failed simulator testing. After fixing or replacing devices, 124 (99%) laboratories had passing devices. The percentage of failed tests significantly decreased over time. Differences in geographical region, device type, breath-hold time, temperature and pressure were not associated with meaningful differences inDL,COdevice accuracy.Regular diffusing capacity of the lung for carbon monoxide simulator testing allows pulmonary function testing laboratories to maintain the accuracy of their diffusing capacity measurements, leading to reduced variability across laboratories in multicentre clinical trials.
Different respiratory phenotypes are associated with isocyanate exposure in spray painters
Authors: Pronk A. , Preller L. , Doekes G. , Wouters I. M. , Rooijackers J. , Lammers J-W. , Heederik D. 
Published: January 2009

Associations have been observed between exposure to isocyanates, consisting mainly of oligomers, and respiratory symptoms and isocyanate specific sensitisation in spray painters. The aim of the present study was to assess associations between isocyanate exposure and more objective respiratory effect measures such as bronchial hyperresponsiveness (BHR), baseline spirometry and exhaled nitric oxide (eNO) in a subset of spray painters.Methacholine challenge and eNO measurements were performed in 229 workers. Questionnaires and blood samples were obtained. Specific immunoglobulin (Ig)E and IgG to hexamethylene di-isocyanate were assessed in serum using various assays. Personal exposure was estimated by combining personal task-based inhalatory exposure measurements and time-activity information.Workers with higher isocyanate exposure were more often hyperresponsive (prevalence ratio comparing the 75thversus25th percentile of exposure 1.8). In addition, significant exposure-related decreased forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio and flow–volume parameters independent of BHR were found. BHR was more prevalent among sensitised workers. This was statistically significant for only IgG-ImmunoCAP (Phadia, Uppsala, Sweden) positive workers. eNO was not associated with exposure although slightly elevated eNO levels in specific IgG positive subjects were found.The current study provides evidence that exposure to isocyanate oligomers is related to asthma with bronchial hyperresponsiveness as a hallmark, but also shows independent chronic obstructive respiratory effects resulting from isocyanate exposure.
Pleural plaques and asbestosis: dose– and time–response relationships based on HRCT data
Authors: Paris C. , Thierry S. , Brochard P. , Letourneux M. , Schorle E. , Stoufflet A. , Ameille J. , Conso F. , Pairon J. C. ,   the National APEXS Members
Published: January 2009

Most studies on asbestos-related diseases are based on chest radiographs, and dose–response relationships are still controversial. The aim of this study was to describe the most relevant parameters of asbestos exposure linked to pleural plaques and asbestosis diagnosed by high-resolution computed tomography (HRCT).A large screening programme including systematic HRCT examinations was organised from 2003 to 2005 in France for formerly asbestos-exposed workers. The time since first exposure (TSFE), level, duration and cumulative exposure to asbestos were used in adjusted unconditional logistic regression to model the relationships of the two diseases.Analysis of a population of 5,545 subjects demonstrated that TSFE (p<0.0001) and cumulative exposure (p = 0.02) (or level, depending on the models used), were independently associated with the frequency of pleural plaques. Only cumulative exposure (p<0.0001) or level of exposure (p = 0.02) were significantly associated with asbestosis. All trend tests were significant for these parameters.To date and to our knowledge, this study is the largest programme based on HRCT for the screening of asbestos-exposed subjects. Both time–response and dose–response relationships were demonstrated for pleural plaques, while only dose–response relationships were demonstrated for asbestosis. These parameters must be included in the definition of high-risk populations for HRCT-based screening programmes.
Effect of formoterol with or without budesonide in repeated low-dose allergen challenge
Authors: Dahlén B. , Lantz A-S. , Ihre E. , Skedinger M. , Henriksson E. , Jörgensen L. , Ekström T. , Dahlén S-E. , Larsson K. 
Published: January 2009

The use of combination therapy in mild asthma is debated. The current authors evaluated the effects of formoterol alone and a formoterol/budesonide combination inhaler on asthma deterioration induced by repeated low-dose allergen exposure.In total, 15 subjects with intermittent allergic asthma inhaled low doses of allergen on seven consecutive weekdays in a three-period, crossover, double-blind, double-dummy comparison between formoterol 4.5 μg TurbuhalerTM, budesonide 160 μg/formoterol 4.5 μg TurbuhalerTMand placebo, each taken as two puffs 30 min after allergen dosing. The outcome variables were: provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20), exhaled nitric oxide fraction (FeNO), sputum eosinophils and prostaglandin D2, and diary card recordings of symptoms (on a scale of 0–10), short-acting β2-agonist use and evening forced expiratory volume in one second (FEV1).With placebo treatment, allergen exposure caused significant increases in airway hyperresponsiveness (geometric mean (coefficient of variation) PD20: 397 (98) μg beforeversus168 (82) μg after),FeNO(mean±sd46±31 ppb beforeversus73±46 ppb after) and asthma symptom score (mean±sd0.39±0.55 beforeversus0.68±0.67 after). Budesonide/formoterol abolished these changes and significantly improved baseline FEV1. Formoterol alone, while providing symptom relief, was no better than placebo in protecting against the allergen-induced increase in airway inflammation.Signs of deteriorating asthma, provoked by low-dose allergen, are prevented by short-term use of budesonide/formoterol but not by temporary use of formoterol alone.
Efficacy of confronting smokers with airflow limitation for smoking cessation
Authors: Kotz D. , Wesseling G. , Huibers M. J. H. , van Schayck O. C. P. 
Published: January 2009

The objective of the present study was to test whether confronting smokers with previously undetected chronic obstructive pulmonary disease (COPD) increases the rate of smoking cessation.In total, 296 smokers with no prior diagnosis of COPD were detected with mild-to-moderate airflow limitation by means of spirometry and randomly allocated to: confrontational counselling by a nurse with nortriptyline for smoking cessation (experimental group); regular counselling by a nurse with nortriptyline (control group 1); or “care as usual” for smoking cessation by the general practitioner (control group 2). Only the experimental group was confronted with their abnormal spirometry (mean forced expiratory volume in one second (FEV1) post-bronchodilator 80.5% predicted, mean FEV1/forced vital capacity post-bronchodilator 62.5%).There was no difference in cotinine-validated prolonged abstinence rate between the experimental group (11.2%) and control group 1 (11.6%) from week 5–52 (odds ratio (OR) 0.96, 95% confidence interval (CI) 0.43–2.18). The abstinence rate was approximately twice as high in the experimental group compared with control group 2 (5.9%), but this difference was not statistically significant (OR 2.02, 95% CI 0.63–6.46).The present study did not provide evidence that the confrontational approach increases the rate of long-term abstinence from smoking compared with an equally intensive treatment in which smokers were not confronted with spirometry. The high failure rates (≥88%) highlight the need for treating tobacco addiction as a chronic relapsing disorder.
Maternal smoking during pregnancy induces airway remodelling in mice offspring
Authors: Blacquière M. J. , Timens W. , Melgert B. N. , Geerlings M. , Postma D. S. , Hylkema M. N. 
Published: January 2009

Children from smoking mothers have an increased risk of developing asthma for reasons largely unknown. The effects of maternal smoking during pregnancy on remodelling, allergic airway inflammation and hyperresponsiveness in offspring were investigated in an experimental asthma model.Mice were exposed to fresh air or cigarette smoke from 3 weeks prior to conception until birth. Offspring were exposed to house dust mite (HDM) or PBS intranasally four times per week from week 5 to week 10 after birth onwards.Maternal smoking increased airway smooth muscle layer, collagen III deposition and HDM-induced goblet cell numbers in offspring. It additionally increased methacholine responsiveness, which correlated significantly with increased airway smooth muscle layer and collagen deposition. Maternal smoking increased HDM-induced numbers of neutrophils and mast cells in lung tissue. No further effects were observed.Smoking during pregnancy induces airway remodelling in mice offspring, which may contribute to increased methacholine responsiveness. This takes place irrespective of allergen exposure but may worsen the outcome of the allergic stimulus, resulting in higher methacholine responsiveness in house dust mite-exposed offspring from smoking mothers when compared to nonsmoking mothers. The results provide a possible mechanism behind the association between maternal smoking and asthma.
Large-scale prediction of long disordered regions in proteins using random forests
Authors: Han Pengfei , Zhang Xiuzhen , Norton Raymond S , Feng Zhi-Ping 
Published: January 2009

Abstract

Background
Many proteins contain disordered regions that lack fixed three-dimensional (3D) structure under physiological conditions but have important biological functions. Prediction of disordered regions in protein sequences is important for understanding protein function and in high-throughput determination of protein structures. Machine learning techniques, including neural networks and support vector machines have been widely used in such predictions. Predictors designed for long disordered regions are usually less successful in predicting short disordered regions. Combining prediction of short and long disordered regions will dramatically increase the complexity of the prediction algorithm and make the predictor unsuitable for large-scale applications. Efficient batch prediction of long disordered regions alone is of greater interest in large-scale proteome studies.

Results
A new algorithm, IUPforest-L, for predicting long disordered regions using the random forest learning model is proposed in this paper. IUPforest-L is based on the Moreau-Broto auto-correlation function of amino acid indices (AAIs) and other physicochemical features of the primary sequences. In 10-fold cross validation tests, IUPforest-L can achieve an area of 89.5% under the receiver operating characteristic (ROC) curve. Compared with existing disorder predictors, IUPforest-L has high prediction accuracy and is efficient for predicting long disordered regions in large-scale proteomes.

Conclusion
The random forest model based on the auto-correlation functions of the AAIs within a protein fragment and other physicochemical features could effectively detect long disordered regions in proteins. A new predictor, IUPforest-L, was developed to batch predict long disordered regions in proteins, and the server can be accessed from http://dmg.cs.rmit.edu.au/IUPforest/IUPforest-L.php
Genes involved in arsenic transformation and resistance associated with different levels of arsenic-contaminated soils
Authors: Cai Lin , Liu Guanghui , Rensing Christopher , Wang Gejiao 
Published: January 2009

Abstract

Background
Arsenic is known as a toxic metalloid, which primarily exists in inorganic form [As(III) and As(V)] and can be transformed by microbial redox processes in the natural environment. As(III) is much more toxic and mobile than As(V), hence microbial arsenic redox transformation has a major impact on arsenic toxicity and mobility which can greatly influence the human health. Our main purpose was to investigate the distribution and diversity of microbial arsenite-resistant species in three different arsenic-contaminated soils, and further study the As(III) resistance levels and related functional genes of these species.

Results
A total of 58 arsenite-resistant bacteria were identified from soils with three different arsenic-contaminated levels. Highly arsenite-resistant bacteria (MIC > 20 mM) were only isolated from the highly arsenic-contaminated site and belonged to Acinetobacter, Agrobacterium, Arthrobacter, Comamonas, Rhodococcus, Stenotrophomonas and Pseudomonas. Five arsenite-oxidizing bacteria that belonged to Achromobacter, Agrobacterium and Pseudomonas were identified and displayed a higher average arsenite resistance level than the non-arsenite oxidizers. 5 aoxB genes encoding arsenite oxidase and 51 arsenite transporter genes [18 arsB, 12 ACR3(1) and 21 ACR3(2)] were successfully amplified from these strains using PCR with degenerate primers. The aoxB genes were specific for the arsenite-oxidizing bacteria. Strains containing both an arsenite oxidase gene (aoxB) and an arsenite transporter gene (ACR3 or arsB) displayed a higher average arsenite resistance level than those possessing an arsenite transporter gene only. Horizontal transfer of ACR3(2) and arsB appeared to have occurred in strains that were primarily isolated from the highly arsenic-contaminated soil.

Conclusion
Soils with long-term arsenic contamination may result in the evolution of highly diverse arsenite-resistant bacteria and such diversity was probably caused in part by horizontal gene transfer events. Bacteria capable of both arsenite oxidation and arsenite efflux mechanisms had an elevated arsenite resistance level.
A multiple-method approach reveals a declining amount of chloroplast DNA during development in Arabidopsis
Authors: Rowan Beth A , Oldenburg Delene J , Bendich Arnold J 
Published: January 2009

Abstract

Background
A decline in chloroplast DNA (cpDNA) during leaf maturity has been reported previously for eight plant species, including Arabidopsis thaliana. Recent studies, however, concluded that the amount of cpDNA during leaf development in Arabidopsis remained constant.

Results
To evaluate alternative hypotheses for these two contradictory observations, we examined cpDNA in Arabidopsis shoot tissues at different times during development using several methods: staining leaf sections as well as individual isolated chloroplasts with 4',6-diamidino-2-phenylindole (DAPI), real-time quantitative PCR with DNA prepared from total tissue as well as from isolated chloroplasts, fluorescence microscopy of ethidium-stained DNA molecules prepared in gel from isolated plastids, and blot-hybridization of restriction-digested total tissue DNA. We observed a developmental decline of about two- to three-fold in mean DNA per chloroplast and two- to five-fold in the fraction of cellular DNA represented by chloroplast DNA.

Conclusion
Since the two- to five-fold reduction in cpDNA content could not be attributed to an artifact of chloroplast isolation, we conclude that DNA within Arabidopsis chloroplasts is degraded in vivo as leaves mature.
A prospective, non-randomized phase II trial of Trastuzumab and Capecitabine in patients with HER2 expressing metastasized pancreatic cancer
Authors: Mihaljevic Andre , Büchler Peter , Harder Jan , Hofheinz Ralf , Gregor Michael , Kanzler Stephan , Schmiegel Wolff , Heinemann Volker , Endlicher Esther , Klöppel Günter , Seufferlein Thomas , Geissler Michael 
Published: January 2009

Abstract

Background
Pancreatic cancer is the fourth most common cause of cancer related death in Western countries. Advantages in surgical techniques, radiation and chemotherapy had almost no impact on the long term survival of affected patients. Therefore, the need for better treatment strategies is urgent. HER2, a receptor tyrosine kinase of the EGFR family, involved in signal transduction pathways leading to cell growth and differentiation is overexpressed in a number of cancers, including breast and pancreatic cancer. While in breast cancer HER2 has already been successfully used as a treatment target, there are only limited data evaluating the effects of inhibiting HER2 tyrosine kinases in patients with pancreatic cancer.

Methods
Here we report the design of a prospective, non-randomized multi-centered Phase II clinical study evaluating the effects of the Fluoropyrimidine-carbamate Capecitabine (Xeloda ®) and the monoclonal anti-HER2 antibody Trastuzumab (Herceptin®) in patients with non-resectable, HER2 overexpressing pancreatic cancer. Patients eligible for the study will receive Trastuzumab infusions on day 1, 8 and 15 concomitant to the oral intake of Capecitabine from day 1 to day 14 of each three week cylce. Cycles will be repeated until tumor progression. A total of 37 patients will be enrolled with an interim analysis after 23 patients.

Discussion
Primary end point of the study is to determine the progression free survival after 12 weeks of bimodal treatment with the chemotherapeutic agent Capecitabine and the anti-HER2 antibody Trastuzumab. Secondary end points include patient's survival, toxicity analysis, quality of life, the correlation of HER2 overexpression and clinical response to Trastuzumab treatment and, finally, the correlation of CA19-9 plasma levels and progression free intervals.
Albumin fibrillization induces apoptosis via integrin/FAK/Akt pathway
Authors: Huang Chun-Yung , Liang Chi-Ming , Chu Chiao-Li , Liang Shu-Mei 
Published: January 2009

Abstract

Background
Numerous proteins can be converted to amyloid-like fibrils to increase cytotoxicity and induce apoptosis, but the methods generally require a high concentration of protein, vigorous shaking, or fibril seed. As well, the detailed mechanism of the cytotoxic effects is not well characterized. In this study, we have developed a novel process to convert native proteins into the fibrillar form. We used globular bovine serum albumin (BSA) as a model protein to verify the properties of the fibrillar protein, investigated its cellular effects and studied the signaling cascade induced by the fibrillar protein.

Results
We induced BSA, a non-cytotoxic globular protein, to become fibril by a novel process involving Superdex-200 column chromatography in the presence of anionic or zwittergenic detergent(s). The column pore size was more important than column matrix composite in fibril formation. The fibrillar BSA induced apoptosis in BHK-21 cell as well as breast cancer cell line T47D. Pre-treating cells with anti-integrin antibodies blocked the apoptotic effect. Fibrillar BSA, but not globular BSA, bound to integrin, dephosphorylated focal adhesion kinase (FAK), Akt and glycogen synthase kinase-3β (GSK-3β).

Conclusion
We report on a novel process for converting globular proteins into fibrillar form to cause apoptosis by modulating the integrin/FAK/Akt/GSK-3β/caspase-3 signaling pathway. Our findings may be useful for understanding the pathogenesis of amyloid-like fibrils and applicable for the development of better therapeutic agents that target the underlying mechanism(s) of the etiologic agents.
Learning about protein solubility from bacterial inclusion bodies
Authors: Martínez-Alonso Mónica , González-Montalbán Nuria , García-Fruitós Elena , Villaverde Antonio 
Published: January 2009

Abstract
The progressive solving of the conformation of aggregated proteins and the conceptual understanding of the biology of inclusion bodies in recombinant bacteria is providing exciting insights on protein folding and quality. Interestingly, newest data also show an unexpected functional and structural complexity of soluble recombinant protein species and picture the whole bacterial cell factory scenario as more intricate than formerly believed.
Distribution of antibody titer against Salmonella enterica among healthy individuals in nepal
Authors: Pokhrel Bharat M , Karmacharya Rajendra , Mishra Shyam K , Koirala Janak 
Published: January 2009

AbstractBackgroundEnteric fever is an endemic problem in Nepal and Widal agglutination test is widely used for its diagnosis but a normal baseline titer in healthy population and cutoff values have not been established.MethodsWe measured average baseline antibody titers against "O" and "H" antigens ofSalmonella entericaserotypeTyphiand "H" antigens of serotypesParatyphi AandParatyphi Bamong apparently healthy blood donors in Nepal. The antibody titers were measured using Standard Widal Confirmatory Quantitative Tube test.ResultsAmong the 100 blood samples collected from healthy volunteers, 62 individuals had significant antibody titers (≥ 1:20) against one of the four antigens againstS. enterica. Among 54 samples with an anti-O titer against serotypeTyphi, 15 and 36 samples had titers of ≥ 1:60 and ≥ 1:40, respectively. A significant proportion (12% of all) had anti-O titer of ≥ 1:80. Similarly, among the 59 samples demonstrating anti-H titers of ≥ 1:20 toS. entericaserotypeTyphi, 29 had a titer of ≥ 1:80 and 12 had 1:160. ForS. entericaserotypesParatyphi AandB, anti-H titers of ≥ 1:20 were found only in 12% and 3%, respectively, of all samples tested.ConclusionWhen a single Widal agglutination titer is used for the diagnosis of enteric fever, it will be more appropriate to change the currently used cutoff levels againstS. entericaserotype Typhito > 1:80 for anti-O and > 1:160 for anti-H titers for Nepal.