bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wrist-actigraphic estimation of sleep time under nCPAP treatment in sleep apnoea patients
Authors: Gagnadoux F. , Nguyen X.L. , Rakotonanahary D. , Vidal S. , Fleury B. 
Published: September 2008

The aim of this study was to correlate daily use of nasal continuous positive airway pressure (nCPAP) with total sleep time (TST) evaluated by home actigraphy.Actigraphy was validated by comparing TST determined by actigraphy (aTST) and polysomnography (pTST) in 24 untreated patients with suspected sleep apnoea. The % sleep time spent under nCPAP was estimated on 3 consecutive days in 28 patients receiving long-term nCPAP, by comparing machine-use periods with sleep periods identified by home actigraphy.The mean difference between pTST and aTST was 2.5 min. The correlation coefficient between aTST and pTST was 0.90. Daily use of nCPAP over the 3 study days was 388±114 min. nCPAP was used 41–100% (82±17% (mean±sd)) of sleep time detected by actigraphy. Some patients used nCPAP during nonsleep periods.In conclusion, comparison of nasal continuous positive airway pressure use with sleep time estimated by home actigraphy shows marked individual differences in the % sleep time under nasal continuous positive airway pressure. These results suggest that actigraphic estimation of sleep time under nasal continuous positive airway pressure could provide a better index than simple daily use of the device to evaluate the impact of treatment in sleep apnoea.
Spontaneous pneumomediastinum in patients with severe acute respiratory syndrome
Authors: Chu C.M. , Leung Y.Y. , Hui J.Y.H. , Hung I.F.N. , Chan V.L. , Leung W.S. , Law K.I. , Chan C.S. , Chan K.S. , Yuen K.Y. 
Published: September 2008

Spontaneous pneumomediastinum (SP) unrelated to assisted ventilation is a newly recognised complication of severe acute respiratory syndrome (SARS). The objective of the present study was to examine the incidence, risk factors and the outcomes of SP in a cohort of SARS victims from a community outbreak.Data were retrieved from a prospectively collected database of virologically confirmed SARS patients. One hundred and twelve cases were analysable, with 13 patients developing SP (11.6%) at a mean±sd of 19.6±4.6 days from symptom onset.Peak lactate dehydrogenase level was associated with the development of SP. SP was associated with increased intubation and a trend towards death. Drainage was required in five cases. For patients who survived, the SP and/or the associated pneumothoraces took a median of 28 days (interquartile range: 15–45 days) to resolve completely.In conclusion, spontaneous pneumomediastinum appeared to be a frequent complication of severe acute respiratory syndrome. Further research is needed to investigate its pathogenesis.
CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge
Authors: Pilette C. , Francis J.N. , Till S.J. , Durham S.R. 
Published: September 2008

T-helper (Th) 2 cytokines are thought to mediate most features of allergic inflammation in atopic asthma. However, it remains unclear whether chemokine pathways direct selective recruitment of Th2 cells to the airways during human allergic responses.Bronchoalveolar lavage (BAL) was performed in 15 nonsmoking mild atopic asthmatics before and 24 h after a fibreoptic segmental allergen challenge, and chemokines related to T-cell recruitment were assayed by ELISA.The Th2-related C-C chemokine (CCR)4 ligands, macrophage-derived chemokine/C-C chemokine ligand (CCL)22 and thymus and activation-regulated chemokine/CCL17, were increased in BAL after challenge. These chemokines correlated significantly with lymphocyte numbers and with interleukin (IL)‐5 and IL‐13 in post-challenge BAL. In contrast, two out of three putative Th1-related chemokines did not change. There were no alterations in monokine induced by interferon (IFN)‐γ/CXC chemokine ligand (CXCL)9 or macrophage inflammatory protein‐1α/CCL3; whereas a significant increase in IFN-induced protein-10kDa/CXCL10 was observed, which did not correlate with the T-cell influx. In peripheral mononuclear cells from atopic donors, CCL22 and CCL17 were induced by IL‐4 and IL‐13, further supporting the relationship between CCL22/CCL17 and Th2 cytokines. Finally, CCL22 was able to trigger actin polymerisation in peripheral CD4+ T-cells expressing CCR4.Thus, C-C chemokine receptor 4 ligands are up-regulated in the airways of atopic asthmatics following allergen exposure, contribute to the T-cell influx to the airways and are closely related to the Th2-cytokine response.
Increased gastro-oesophageal reflux disease in patients with severe COPD
Authors: Casanova C. , Baudet J.S. , del Valle Velasco M. , Martin J.M. , Aguirre-Jaime A. , Pablo de Torres J. , Celli B.R. 
Published: September 2008

The prevalence and clinical consequences of gastro-oesophageal reflux disease (GERD) in chronic obstructive pulmonary disease (COPD) are not well characterised.The present study prospectively studied 42 males with COPD (forced expiratory volume in one second % predicted: 35%, range 20–49) and 16 healthy volunteers of similar age without respiratory or gastro-oesophageal symptoms. The diagnosis of GERD was confirmed using oesophageal 24 h pH monitoring. In the current study group, reflux symptoms were measured using the Vigneri score, cough and dyspnoea with the modified Medical Research Council questionnaire, and pulmonary function with bronchodilator response and health status using St George's Respiratory Questionnaire.Pathological reflux was documented in 26 out of 42 patients (62%) and in three volunteers (19%). In patients with GERD, 15 patients (58%) did not report any reflux symptoms. There were no differences in symptoms, health status, bronchodilator treatment and pulmonary function test between patients with and without GERD. Oxygen desaturation coincided with episodes of increased oesophageal acidity in 40% of patients with GERD.Patients with severe chronic obstructive pulmonary disease have a high prevalence of asymptomatic gastro-oesophageal reflux. The association between this reflux and oxygen desaturation deserves further attention.
High altitude impairs nasal transepithelial sodium transport in HAPE-prone subjects
Authors: Sartori C. , Duplain H. , Lepori M. , Egli M. , Maggiorini M. , Nicod P. , Scherrer U. 
Published: September 2008

High-altitude pulmonary oedema (HAPE) occurs in predisposed individuals at altitudes >2,500 m. Defective alveolar fluid clearance secondary to a constitutive impairment of the respiratory transepithelial sodium transport contributes to its pathogenesis. Hypoxia impairs the transepithelial sodium transport in alveolar epithelial type II cellsin vitro. If this impairment is also presentin vivo, high-altitude exposure could aggravate the constitutive defect in sodium transport in HAPE-prone subjects, and thereby further facilitate pulmonary oedema.Therefore, the aim of the current study was to measure the nasal potential difference (PD) in 21 HAPE-prone and 29 HAPE-resistant subjects at low altitude and 30 h after arrival at high altitude (4,559 m).High-altitude exposure significantly decreased the mean±sd nasal PD in HAPE-prone (18.0±6.2versus12.5±6.8 mV) but not in HAPE-resistant subjects (25.6±9.4versus22.9±9.2 mV). This altitude-induced decrease was not associated with an altered amiloride-sensitive fraction, but was associated with a significantly lower amiloride-insensitive fraction of the nasal PD.These findings provide evidencein vivothat an environmental factor may impair respiratory transepithelial sodium transport in humans. They are consistent with the concept that in high-altitude pulmonary oedema-susceptible subjects, the combination of a constitutive and an acquired defect in this transport mechanism facilitates the development of pulmonary oedema during high-altitude exposure.
Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD
Authors: O'Donnell D.E. , Flüge T. , Gerken F. , Hamilton A. , Webb K. , Aguilaniu B. , Make B. , Magnussen H. 
Published: September 2008

The aim of this study was to test the hypothesis that use of tiotropium, a new long-acting anticholinergic bronchodilator, would be associated with sustained reduction in lung hyperinflation and, thereby, would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease.A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 187 patients (forced expiratory volume in one second 44±13% pred): 96 patients received 18 µg tiotropium and 91 patients received placebo once daily for 42 days. Spirometry, plethysmographic lung volumes, cycle exercise endurance and exertional dyspnoea intensity at 75% of each patient's maximal work capacity were compared.On day 42, the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo: vital capacity and inspiratory capacity (IC) increased, with inverse decreases in residual volume and functional residual capacity. Tiotropium increased post-dose exercise endurance time by 105±40 s (21%) as compared to placebo on day 42. At a standardised time near end-exercise (isotime), IC, tidal volume and minute ventilation all increased, whilst dyspnoea decreased by 0.9±0.3 Borg scale units.In conclusion, the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise. Resultant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance.
Endobronchial ultrasound to assess airway wall thickening: validationin vitroandin vivo
Authors: Shaw T.J. , Wakely S.L. , Peebles C.R. , Mehta R.L. , Turner J.M. , Wilson S.J. , Howarth P.H. 
Published: September 2008

Endobronchial ultrasound (EBUS) allows identification of airway wall structures and could potentially be utilised forin vivostudies of airway thickening in asthma. The present study investigated whether inflation of the fluid-filled balloon sheath over the transducer (necessary to provide sonic coupling with the airway wall) influencedin vitromeasurements.In vivocomparability of EBUS with high resolution computed tomography scanning (HRCT), an established method for measuring wall thickness, was determined in control subjects.The airway diameter and wall thickness were studied using EBUS in 24 cartilaginous airways obtained from four sheep, before and after balloon sheath inflation during immersion in saline. To assess EBUSversusHRCT comparability of airway measuresin vivo, 12 control subjects underwent imaging of the posterior basal bronchus of the right lower lobe by both techniques. Intra- and interobserver agreement were also assessed.Results with and without the balloon sheath gave comparable measures of airway internal diameter and wall thicknessin vitro. Statistical analysis showed agreement between EBUS and HRCT, and intra- and interobserver variabilityin vivo.The current study concludes that endobronchial ultrasound, which does not present a radiation risk, could be utilised in thein vivostudy of cartilaginous airway wall remodelling in respiratory diseases, such as asthma.
caBIG™ VISDA: Modeling, visualization, and discovery for cluster analysis of genomic data
Authors: Zhu Yitan , Li Huai , Miller David J , Wang Zuyi , Xuan Jianhua , Clarke Robert , Hoffman Eric P , Wang Yue 
Published: September 2008

AbstractBackgroundThe main limitations of most existing clustering methods used in genomic data analysis include heuristic or random algorithm initialization, the potential of finding poor local optima, the lack of cluster number detection, an inability to incorporate prior/expert knowledge, black-box and non-adaptive designs, in addition to the curse of dimensionality and the discernment of uninformative, uninteresting cluster structure associated with confounding variables.ResultsIn an effort to partially address these limitations, we develop the VIsual Statistical Data Analyzer (VISDA) for cluster modeling, visualization, and discovery in genomic data. VISDA performs progressive, coarse-to-fine (divisive) hierarchical clustering and visualization, supported by hierarchical mixture modeling, supervised/unsupervised informative gene selection, supervised/unsupervised data visualization, and user/prior knowledge guidance, to discover hidden clusters within complex, high-dimensional genomic data. The hierarchical visualization and clustering scheme of VISDA uses multiple local visualization subspaces (one at each node of the hierarchy) and consequent subspace data modeling to reveal both global and local cluster structures in a "divide and conquer" scenario. Multiple projection methods, each sensitive to a distinct type of clustering tendency, are used for data visualization, which increases the likelihood that cluster structures of interest are revealed. Initialization of the full dimensional model is based on first learning models with user/prior knowledge guidance on data projected into the low-dimensional visualization spaces. Model order selection for the high dimensional data is accomplished by Bayesian theoretic criteria and user justification applied via the hierarchy of low-dimensional visualization subspaces. Based on its complementary building blocks and flexible functionality, VISDA is generally applicable for gene clustering, sample clustering, and phenotype clustering (wherein phenotype labels for samples are known), albeit with minor algorithm modifications customized to each of these tasks.ConclusionVISDA achieved robust and superior clustering accuracy, compared with several benchmark clustering schemes. The model order selection scheme in VISDA was shown to be effective for high dimensional genomic data clustering. On muscular dystrophy data and muscle regeneration data, VISDA identified biologically relevant co-expressed gene clusters. VISDA also captured the pathological relationships among different phenotypes revealed at the molecular level, through phenotype clustering on muscular dystrophy data and multi-category cancer data.
Improving peptide-MHC class I binding prediction for unbalanced datasets
Authors: Sales Ana Paula , Tomaras Georgia D , Kepler Thomas B 
Published: September 2008

AbstractBackgroundEstablishment of peptide binding to Major Histocompatibility Complex class I (MHCI) is a crucial step in the development of subunit vaccines and prediction of such binding could greatly reduce costs and accelerate the experimental process of identifying immunogenic peptides. Many methods have been applied to the prediction of peptide-MHCI binding, with some achieving outstanding performance. Because of the experimental methods used to measure binding or affinity between peptides and MHCI molecules, however, available datasets are enriched for nonbinders, and thus highly unbalanced. Although there is no consensus on the ideal class distribution for training sets, extremely unbalanced datasets can be detrimental to the performance of prediction algorithms.ResultsWe have developed a decision-theoretic framework to construct cost-sensitive trees to predict peptide-MHCI binding and have used them to 1) Assess the impact of the training data's class distribution on classifier accuracy, and 2) Compare resampling and cost-sensitive methods as approaches to compensate for training data imbalance. Our results confirm that highly unbalanced training sets can reduce the accuracy of classifier predictions and show that, in the peptide-MHCI binding context, resampling methods do not improve the classifier performance. In contrast, cost-sensitive methods significantly improve accuracy of decision trees. Finally, we propose the use of a training scheme that, when the training set is enriched for nonbinders, consistently improves the overall classifier accuracy compared to cost-insensitive classifiers and, in particular, increases the sensitivity of the classifiers. This method minimizes the expected classification cost for large datasets.ConclusionOur method consistently improves the performance of decision trees in predicting peptide-MHC class I binding by using cost-balancing techniques to compensate for the imbalance in the training dataset.
An in vivo reporter of BMP signaling in organogenesis reveals targets in the developing kidney
Authors: Blank Ulrika , Seto Marianne L , Adams Derek C , Wojchowski Don M , Karolak Michele J , Oxburgh Leif 
Published: September 2008

Abstract

Background
Bone morphogenetic proteins (BMPs) regulate essential processes during organogenesis, and a functional understanding of these secreted proteins depends on identification of their target cells. In this study, we generate a transgenic reporter for organogenesis studies that we use to define BMP pathway activation in the developing kidney.

Results
Mouse strains reporting on BMP pathway activation were generated by transgenically expressing β-galactosidase under the control of BMP responsive elements from Id1. Reporter expression corresponds well with immunoassays for pathway activation in all organs studied, validating the model. Using these reporters we have generated a detailed map of cellular targets of BMP signaling in the developing kidney. We find that SMAD dependent BMP signaling is active in collecting duct trunks, but not tips. Furthermore, glomerular endothelial cells, and proximal nephron tubules from the renal vesicle stage onward show pathway activation. Surprisingly, little activation is detected in the nephrogenic zone of the kidney, and in organ culture BMP treatment fails to activate SMAD dependent BMP signaling in nephron progenitor cells. In contrast, signaling is efficiently induced in collecting duct tips.

Conclusion
Transgenic reporters driven by control elements from BMP responsive genes such as Id1 offer significant advantages in sensitivity and consistency over immunostaining for studies of BMP pathway activation. They also provide opportunities for analysis of BMP signaling in organ and primary cell cultures subjected to experimental manipulation. Using such a reporter, we made the surprising finding that SMAD dependent BMP signaling is inactive in nephron progenitors, and that these cells are refractory to activation by applied growth factors. Furthermore, we find that the BMP pathway is not normally active in collecting duct tips, but that it can be ectopically activated by BMP treatment, offering a possible explanation for the inhibitory effects of BMP treatment on collecting duct growth and branching.
Interspecies data mining to predict novel ING-protein interactions in human
Authors: Gordon Paul MK , Soliman Mohamed A , Bose Pinaki , Trinh Quang , Sensen Christoph W , Riabowol Karl 
Published: September 2008

Abstract

Background
The IN hibitor of G rowth (ING) family of type II tumor suppressors (ING1–ING5) is involved in many cellular processes such as cell aging, apoptosis, DNA repair and tumorigenesis. To expand our understanding of the proteins with which the ING proteins interact, we designed a method that did not depend upon large-scale proteomics-based methods, since they may fail to highlight transient or relatively weak interactions. Here we test a cross-species (yeast, fly, and human) bioinformatics-based approach to identify potential human ING-interacting proteins with higher probability and accuracy than approaches based on screens in a single species.

Results
We confirm the validity of this screen and show that ING1 interacts specifically with three of the three proteins tested; p38MAPK, MEKK4 and RAD50. These novel ING-interacting proteins further link ING proteins to cell stress and DNA damage signaling, providing previously unknown upstream links to DNA damage response pathways in which ING1 participates. The bioinformatics approach we describe can be used to create an interaction prediction list for any human proteins with yeast homolog(s).

Conclusion
None of the validated interactions were predicted by the conventional protein-protein interaction tools we tested. Validation of our approach by traditional laboratory techniques shows that we can extract value from the voluminous weak interaction data already elucidated in yeast and fly databases. We therefore propose that the weak (low signal to noise ratio) data from large-scale interaction datasets are currently underutilized.
Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families
Authors: Peric Barbara , Cerkovnik Petra , Novakovic Srdjan , Zgajnar Janez , Besic Nikola , Hocevar Marko 
Published: September 2008

AbstractBackgroundTwo high-risk genes have been implicated in the development of CM (cutaneous melanoma). Germline mutations of the CDKN2A gene are found in < 25% of melanoma-prone families and there are only seven families with mutation of theCDK4gene reported to date. Beside those high penetrance genes, certain allelic variants of theMC1Rgene modify the risk of developing the disease.The aims of our study were: to determine the prevalence of germlineCDKN2Amutations and variants in members of families with familial CM and in patients with multiple primary CM; to search for possibleCDK4mutations, and to determine the frequency of variations in theMC1Rgene.MethodsFrom January 2001 until January 2007, 64 individuals were included in the study. The group included 28 patients and 7 healthy relatives belonging to 25 families, 26 patients with multiple primary tumors and 3 children with CM. Additionally 54 healthy individuals were included as a control group. Mutations and variants of the melanoma susceptibility genes were identified by direct sequencing.ResultsSeven families with CDKN2A mutations were discovered (7/25 or 28.0%). The L94Q mutation found in one family had not been previously reported in other populations. The D84N variant, with possible biological impact, was discovered in the case of patient without family history but with multiple primary CM. Only one mutation carrier was found in the control group. Further analysis revealed that c.540C>T heterozygous carriers were more common in the group of CM patients and their healthy relatives (11/64 vs. 2/54). One p14ARF variant was discovered in the control group and no mutations of theCDK4gene were found.Most frequently found variants of theMC1Rgene were T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the group of patients and their relatives than in the group of controls, but the difference was statistically insignificant.ConclusionThe present study has shown high prevalence of p16INK4A mutations in Slovenian population of familial melanoma patients (37%) and an absence of p14ARF orCDK4mutations.