bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bronchial fistulae in ARDS patients: management with an extracorporeal lung assist device
Authors: Hommel M. , Deja M. , von Dossow V. , Diemel K. , Heidenhain C. , Spies C. , Weber-Carstens S. 
Published: November 2008

Patients with bronchial tree lesions feature, in particular, a high risk for developing bronchial fistulae after surgical repair when the clinical situation is complicated by acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mechanical ventilation is needed. The current authors hypothesised that extracorporeal carbon dioxide removal would significantly decrease inspiratory airway pressures, thus promoting the protection of surgical bronchial reconstruction.Four patients were studied after surgical reconstruction of bronchial fistulae in whom ALI/ARDS developed and mechanical ventilation with positive end-expiratory pressure was required. Gas exchange, tidal volumes, airway pressures, respiratory frequency, vasopressor and sedation requirements were analysed before and after initiation of a pumpless extracorporeal lung assist device (pECLA; NovaLung®, Talheim, Germany). Initiation of pECLA treatment enabled a reduction of inspiratory plateau airway pressures from 32.4 to 28.6 cmH2O (3.2 to 2.8 kPa), effectively treated hypercapnia (from 73.6 to 53.4 mmHg (9.8 to 7.1 kPa)) and abolished respiratory acidosis (from pH 7.24 to 7.41). All patients survived and were discharged to rehabilitation clinics.In patients after surgical bronchial reconstruction that was complicated by acute lung injury/acute respiratory distress syndrome, use of pumpless extracorporeal carbon dioxide removal was safe and efficient. Initiation of a pumpless extracorporeal lung assist device enabled a less invasive ventilator management, which may have contributed to healing of surgical bronchial repair.
The classification, natural history and radiological/histological appearance of idiopathic pulmonary fibrosis and the other idiopathic interstitial pneumonias
Authors: Raghu G. , Nicholson A. G. , Lynch D. 
Published: November 2008

The idiopathic interstitial pneumonias (IIPs) are a heterogeneous group of rare interstitial lung diseases (ILDs) or diffuse parenchymal lung diseases, which, as their name implies, are of unknown aetiology. The past 10 yrs have seen important advances in the classification of the IIPs into idiopathic pulmonary fibrosis (IPF) and its corresponding histopathological pattern of usual interstitial pneumonia (UIP), plus six non-IPF IIP subtypes.The present article will look at the current classification of IIPs, arising from the Consensus Statement of the American Thoracic Society and European Respiratory Society, and discusses the importance of differential diagnosis of IPF from the non-IPF IIP subtypes, especially nonspecific interstitial pneumonia. Diagnosis of IIPs is a dynamic process involving close collaboration between pulmonologists, radiologists and pathologists.Increasingly accurate diagnosis of IPF has been made possible by the use of high-resolution computed tomography (HRCT) and refinements in surgical lung biopsy. In IPF, a lung HRCT will typically reveal irregular reticular opacities, traction bronchiestasis and, most importantly, peripheral honeycombing. In contrast, histological examination shows evidence of UIP manifesting as typically subpleural and paraseptal established fibrosis, often with honeycomb changes, associated with mild chronic inflammation and varying numbers of fibroblastic foci in continuity with the edges of areas of established fibrosis.Despite these advances, obtaining a consistent and uniform diagnosis of idiopathic interstitial pneumonias is difficult, with studies showing significant disagreement in the diagnosis of interstitial lung diseases between academic centres of expertise and community-based clinicians. Greater interaction between academic and community clinicians, together with improved education, is needed to bridge this gap.
Recent clinical trials in idiopathic pulmonary fibrosis and the BUILD-1 study
Authors: Brown K. K. , Wells A. U. 
Published: November 2008

Idiopathic pulmonary fibrosis (IPF), the most common of the interstitial pneumonias, is a progressive, life-limiting disease for which there are no truly effective therapies. In patients with biopsy-confirmed IPF, median survival is still <3 yrs. Although potent immunosuppressive therapy has underpinned the treatment of IPF in recent years and remains the standard of care, there is little quality evidence to support the efficacy and safety of traditional therapeutic strategies.This has spurred the search for new treatments for IPF and has led to a series of clinical trials of new therapies, seven of which are reviewed herein. They include the Bosentan Use in Interstitial Lung Disease (BUILD)-1 trial, the results of which are discussed in detail, the European Idiopathic Pulmonary Fibrosis International Group Exploring N-acetylcysteine 1 Annual (IFIGENIA) trial, the interferon gamma (GIPF-001) trial and the INSPIRE trial, as well as trials of anticoagulant therapy, pirfenidone and etanercept.Treatment trials in IPF are hindered by difficulties in achieving a secure diagnosis of IPF and the lack of validated outcome measures that represent either improvement or progression of disease. These and other limitations are discussed in the present article, as well as how some of these problems might be addressed in future trials.Although few of the seven studies met their primary end-points, marginal trends either on primary end-points or statistically significant trends on exploratory end-points were a recurrent theme in most trials. In the BUILD-1 trial, for example, a trend in favour of bosentan was observed on time-to-disease progression or death.
Abnormal wound healing responses in pulmonary fibrosis: focus on coagulation signalling
Authors: Chambers R. C. 
Published: November 2008

The normal response of tissue to injury involves a sequence of overlapping events, which need to occur in a timely and controlled manner for successful tissue repair and restoration of normal function. Failure to control the healing process can lead to considerable tissue remodelling and the replacement of functional tissue with permanent fibrous scar tissue.It is proposed that pulmonary fibrosis arises from repetitive, widespread epithelial injury. However, the nature of the insult for the most common and most fatal form of pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), is currently unknown and the pathogenetic pathways leading to IPF remain to be fully elucidated. Increasing evidence suggests that abnormalities in a number of pathways involved in the wound healing response may play central roles.The present article will briefly review the pathways involved in wound healing focusing on the control of fibroblast/myofibroblast function and the coagulation cascade actingviathe family of signalling receptors, the proteinase activated receptors, which influence a range of cellular responses implicated in the development of pulmonary fibrosis.Understanding the involvement of these pathways in the aberrant wound repair-response in pulmonary fibrosis may lead to the identification of new targets and strategies for therapeutic intervention.
The role of apoptosis in pulmonary fibrosis
Authors: Uhal B. D. 
Published: November 2008

Apoptosis has been defined as “gene-directed cellular self-destruction” and is an active process that is tightly regulated by a number of gene products, which promote or block cell death. Apoptotic death can be triggered by a wide variety of stimuli and, importantly, not all cells necessarily undergo apoptosis in response to the same stimulus. Abnormal regulation of apoptosis has been implicated in a wide range of diseases and approaches to modifying apoptosis represent important future therapeutic strategies.Idiopathic pulmonary fibrosis (IPF) is a progressive and relentless disease involving scarring of the lung, which has been recognised as the most lethal interstitial lung disease. In the lungs of IPF patients, increased epithelial apoptosis, together with decreased apoptosis of myofibroblasts, represents persistent findings (particularly in areas of collagen deposition) supporting an interaction between altered apoptosis and the pathogenesis of the disease.Data from human tissues and animal models are refining current knowledge of the processes involved in this pathogenesis. This has challenged the dogma that IPF is purely a disease of unresolved inflammation by emphasising the central roles played by the alveolar epithelial cell and myofibroblasts and, as part of that role, the importance of altered apoptosis.Evidence suggests blockade of epithelial cell apoptosis can prevent subsequent collagen deposition, and induction of myofibroblast apoptosis, at least theoretically, would be expected to resolve ongoing fibrosis. These two concepts raise the prospect of therapeutic intervention aimed at modifying apoptosis and, thus, fibrosis in idiopathic pulmonary fibrosis.
Role of endothelin in lung fibrosis
Authors: Abraham D. 
Published: November 2008

Accumulating evidence suggests that idiopathic pulmonary fibrosis (IPF) results from lung injury primarily following an abnormal wound healing response towards epithelial cell damage. Thus, rather than resulting from chronic inflammation, as thought previously, the inflammatory response acts as a modifier of the fibrogenic response, which can also be influenced by the host’s genetic background and environmental triggers. Several key mediators, including endothelin (ET)-1, have been implicated in the fibrosis and scarring associated with IPF.Elevated levels of ET-1 have been detected in bronchoalveolar lavage fluid and serum from patients with IPF and increased expression of ET-1 has been detected in small pulmonary blood vessels and macrophages.In vitrodata show that ET-1 influences matrix production and degradation by promoting synthesis of collagen type I and III, inhibiting expression of matrix metalloproteinase-1 and promoting matrix remodelling. In addition, ET-1 promotes fibroblast differentiation to a myofibroblastic cell type, inducing the expression of proteins that contribute to a contractile phenotype including α-smooth muscle actin. Moreover, ET-1 has been shown to initiate alveolar epithelial cell transition into fibroblast-like cells, a process termed epithelial–mesenchymal transition, and thereby contribute to pulmonary fibrosis. Furthermore, recently reported data from the BUILD (Bosentan Use in Interstitial Lung Disease)-1 trial showed a trend towards a delay in time to disease progression or death following treatment with the endothelin receptor antagonist, bosentan, which was especially prominent in patients with biopsy-proven IPF. This adds to the evidence that ET-1 plays an important role in IPF.The present article examines recent evidence for the role of endothelin-1 in pulmonary fibrosis, and particularly, in the control of the function and differentiation of fibroblasts and myofibroblasts.
The role of integrins in pulmonary fibrosis
Authors: Sheppard D. 
Published: November 2008

Integrins are a large family of transmembrane glycoprotein receptors initially identified as mediators of cell adhesion and tissue integrity. However, it is now known that the primary function of integrins in mammals is to act as signalling proteins.Signals from integrins are known to play critical roles in virtually every aspect of the behaviour of epithelial cells and in the development of certain pathological conditions, including pulmonary fibrosis. In this respect, the interaction between transforming growth factor-β, which is known to be pivotal in the development of pulmonary fibrosis, and the integrin αVβ6 is of particular interest.Integrin αVβ6 is responsible for the activation of constitutively expressed latent transforming growth factor-β by a mechanism that allows for temporal and spatial activity control.There is increasing evidence that this mechanism plays a critical role in the pathological activity of transforming growth factor-β. Although other activation mechanisms have been identified, studies suggest that αVβ6-mediated activation of transforming growth factor-β is necessary for the development of fibrosis in lung-disease models. The data from such studies imply that integrins may be attractive targets for intervention in pulmonary fibrotic diseases, such as idiopathic pulmonary fibrosis.
Neurotransmitter alterations in embryonic succinate semialdehyde dehydrogenase (SSADH) deficiency suggest a heightened excitatory state during development
Authors: Jansen Erwin EW , Struys Eduard , Jakobs Cornelis , Hager Elizabeth , Snead O Carter , Gibson K Michael 
Published: November 2008

Abstract

Background
SSADH (aldehyde dehydrogenase 5a1 (Aldh5a1); γ-hydroxybutyric (GHB) aciduria) deficiency is a defect of GABA degradation in which the neuromodulators GABA and GHB accumulate. The human phenotype is that of nonprogressive encephalopathy with prominent bilateral discoloration of the globi pallidi and variable seizures, the latter displayed prominently in Aldh5a1-/- mice with lethal convulsions. Metabolic studies in murine neural tissue have revealed elevated GABA [and its derivatives succinate semialdehyde (SSA), homocarnosine (HC), 4,5-dihydroxyhexanoic acid (DHHA) and guanidinobutyrate (GB)] and GHB [and its analogue D-2-hydroxyglutarate (D-2-HG)] at birth. Because of early onset seizures and the neurostructural anomalies observed in patients, we examined metabolite features during Aldh5a1-/- embryo development.

Methods
Embryos were obtained from pregnant dams sacrificed at E (embryo day of life) 10–13, 14–15, 16–17, 18–19 and newborn mice. Intact embryos were extracted and metabolites quantified by isotope dilution mass spectrometry (n = 5–15 subjects, Aldh5a1+/+ and Aldh5a1-/-) for each gestational age group. Data was evaluated using the t test and one-way ANOVA with Tukey post hoc analysis. Significance was set at the 95th centile.

Results
GABA and DHHA were significantly elevated at all gestational ages in Aldh5a1-/- mice, while GB was increased only late in gestation; SSA was not elevated at any time point. GHB and D-2-HG increased in an approximately linear fashion with gestational age. Correlative studies in human amniotic fluid from SSADH-deficient pregnancies (n = 5) also revealed significantly increased GABA.

Conclusion
Our findings indicate early GABAergic alterations in Aldh5a1-/- mice, possibly exacerbated by other metabolites, which likely induce a heightened excitatory state that may predispose neural networks to epilepsy in these animals.
Two sisters in the same dress: Heliconius cryptic species
Authors: Giraldo Nathalia , Salazar Camilo , Jiggins Chris D , Bermingham Eldredge , Linares Mauricio 
Published: November 2008

AbstractBackgroundSister species divergence and reproductive isolation commonly results from ecological adaptation. In mimeticHeliconiusbutterflies, shifts in colour pattern contribute to pre- and post-mating reproductive isolation and are commonly correlated with speciation. Closely related mimetic species are therefore not expected, as they should lack several important sources of reproductive isolation.ResultsHere we present phenotypic, behavioral and genetic evidence for the coexistence of two sympatric 'cryptic' species near Florencia in the eastern Andes of Colombia that share the same orange rayed colour pattern. These representH. melpomene malletiand a novel taxon in theH. cydnogroup, here designated as novel race ofHeliconius timareta,Heliconius timareta florencia. No-choice mating experiments show that these sympatric forms have strong assortative mating (≈96%) despite great similarity in colour pattern, implying enhanced divergence in pheromonal signals.ConclusionWe hypothesize that these species might have resulted from recent convergence in colour pattern, perhaps facilitated by hybrid introgression of wing pattern genes.
Genome plasticity of Vibrio parahaemolyticus: microevolution of the 'pandemic group'
Authors: Han Haihong , Wong Hin-chung , Kan Biao , Guo Zhaobiao , Zeng Xiaotao , Yin Shengjun , Liu Xiumei , Yang Ruifu , Zhou Dongsheng 
Published: November 2008

Abstract

Background
Outbreak of V. parahaemolyticus infections occurred since 1996 was linked to a proposed clonal complex, the pandemic group. The whole genome sequence provides an unprecedented opportunity for dissecting genome plasticity and phylogeny of the populations of V. parahaemolyticus. In the present work, a whole-genome cDNA microarray was constructed to compare the genomic contents of a collection of 174 strains of V. parahaemolyticus.

Results
Genes that present variably in the genome accounted for about 22% of the whole gene pool on the genome. The phylogenetic analysis of microarray data generated a minimum spanning tree that depicted the phylogenetic structure of the 174 strains. Strains were assigned into five complexes (C1 to C5), and those in each complex were related genetically and phylogenetically. C3 and C4 represented highly virulent clinical clones. C2 and C3 constituted two different clonal complexes 'old-O3:K6 clone' and 'pandemic clone', respectively. C3 included all the 39 pandemic strains tested (trh
-, tdh
+ and GS-PCR+), while C2 contained 12 pre-1996 'old' O3:K6 strains (trh
+, tdh
- and GS-PCR-) tested herein. The pandemic clone (post-1996 'new' O3:K6 and its derivates O4:K68, O1:K25, O1:KUT and O6:K18) might be emerged from the old-O3:K6 clone, which was promoted by acquisition of toxRS/new sequence and genomic islands. A phylogenetic intermediate O3:K6 clade (trh
-, tdh
- and GS-PCR+) was identified between the pandemic and old-O3:K6 clones.

Conclusion
A comprehensive overview of genomic contents in a large collection of global isolates from the microarray-based comparative genomic hybridization data enabled us to construct a phylogenetic structure of V. parahaemolyticus and an evolutionary history of the pandemic group (clone) of this pathogen.
Dissecting an alternative splicing analysis workflow for GeneChip®Exon 1.0 ST Affymetrix arrays
Authors: Della Beffa Cristina , Cordero Francesca , Calogero Raffaele A 
Published: November 2008

Abstract

Background
A new microarray platform (GeneChip® Exon 1.0 ST) has recently been developed by Affymetrix http://www.affymetrix.com. This microarray platform changes the conventional view of transcript analysis since it allows the evaluation of the expression level of a transcript by querying each exon component. The Exon 1.0 ST platform does however raise some issues regarding the approaches to be used in identifying genome-wide alternative splicing events (ASEs). In this study an exon-level data analysis workflow is dissected in order to detect limit and strength of each step, thus modifying the overall workflow and thereby optimizing the detection of ASEs.

Results
This study was carried out using a semi-synthetic exon-skipping benchmark experiment embedding a total of 268 exon skipping events. Our results point out that summarization methods (RMA, PLIER) do not affect the efficacy of statistical tools in detecting ASEs. However, data pre-filtering is mandatory if the detected number of false ASEs are to be reduced. MiDAS and Rank Product methods efficiently detect true ASEs but they suffer from the lack of multiple test error correction. The intersection of MiDAS and Rank Product results efficiently moderates the detection of false ASEs.

Conclusion
To optimize the detection of ASEs we propose the following workflow: i) data pre-filtering, ii) statistical selection of ASEs using both MiDAS and Rank Product, iii) intersection of results derived from the two statistical analyses in order to moderate family-wise errors (FWER).
Functional characterization of a small heat shock protein from Mycobacterium leprae
Authors: Lini Nirmala , Rehna Elengikal Abdul Azeez , Shiburaj Sugathan , Maheshwari Jayapal Jeya , Shankernarayan Nallakandy Panagadan , Dharmalingam Kuppamuthu 
Published: November 2008

AbstractBackgroundSmall heat shock proteins are ubiquitous family of stress proteins, having a role in virulence and survival of the pathogen.M. leprae, the causative agent of leprosy is an uncultivable organism in defined media, hence the biology and function of proteins were examined by cloningM. lepraegenes in heterologous hosts. The study on sHsp18 was carried out as the knowledge about the functions of this major immunodominant antigen ofM. lepraeis scanty.ResultsThe gene encodingMycobacterium lepraesmall heat shock protein (sHsp18) was amplified from biopsy material of leprosy patients, and cloned and expressed inE. coli. The localization andin vitrocharacterization of the protein are detailed in this report. Data show that major portion of the protein is localized in the outer membrane ofE. coli. The purified sHsp18 functions as an efficient chaperone as shown by their ability to prevent thermal inactivation of restriction enzymesSmaI andNdeI. Physical interaction of the chaperone with target protein is also demonstrated. Size exclusion chromatography of purified protein shows that the protein can form multimeric complexes underin vitroconditions as is demonstrated for several small heat shock proteins.ConclusionThe small heat shock protein sHsp18 ofM. lepraeis a chaperone and shows several properties associated with other small heat shock proteins. Membrane association andin vitrochaperone function of sHsp18 shows that the protein may play a role in the virulence and survival ofM. lepraein infected host.
A randomized controlled trial of tea tree oil (5%) body wash versus standard body wash to prevent colonization with methicillin-resistant Staphylococcus aureus (MRSA) in critically ill adults: research protocol
Authors: Thompson Gillian , Blackwood Bronagh , McMullan Ronan , Alderdice Fiona A , Trinder T John , Lavery Gavin G , McAuley Danny F 
Published: November 2008

Abstract

Background
Over the past ten years MRSA has become endemic in hospitals and is associated with increased healthcare costs. Critically ill patients are most at risk, in part because of the number of invasive therapies that they require in the intensive care unit (ICU). Washing with 5% tea tree oil (TTO) has been shown to be effective in removing MRSA on the skin. However, to date, no trials have evaluated the potential of TTO body wash to prevent MRSA colonization or infection. In addition, detecting MRSA by usual culture methods is slow. A faster method using a PCR assay has been developed in the laboratory, but requires evaluation in a large number of patients.

Methods/Design
This study protocol describes the design of a multicentre, phase II/III prospective open-label randomized controlled clinical trial to evaluate whether a concentration of 5% TTO is effective in preventing MRSA colonization in comparison with a standard body wash (Johnsons Baby Softwash) in the ICU. In addition we will evaluate the cost-effectiveness of TTO body wash and assess the effectiveness of the PCR assay in detecting MRSA in critically ill patients. On admission to intensive care, swabs from the nose and groin will be taken to screen for MRSA as per current practice. Patients will be randomly assigned to be washed with the standard body wash or TTO body wash. On discharge from the unit, swabs will be taken again to identify whether there is a difference in MRSA colonization between the two groups.

Discussion
If TTO body wash is found to be effective, widespread implementation of such a simple colonization prevention tool has the potential to impact on patient outcomes, healthcare resource use and patient confidence both nationally and internationally.

Trial Registration
[ISRCTN65190967]