bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fixation Versus Replacement in Geriatric Hip Fractures
Authors: Palanisamy Arul Murugan , Doshi H. K. , Selvaraj Dahshaini , Chan William , Naidu G. , Ramason R. 
Published: August 2015

Introduction: Although there is evidence of improved functional outcomes with our “integrated care pathway” for geriatric hip fractures, we do not know if there is a significant difference in functional recovery of activities of daily living and attainment of independence in self-care between patients who underwent fixation and those treated with arthroplasty. Objective: To determine whether such a difference exists in surgically fixed hip fractures. Materials and Methods: Patients with hip fracture treated surgically were divided into group A (internal fixation, n = 213) and group B (arthroplasty, n = 199). Demographic data, Charlson comorbidity index (CCI) score, time to surgery, and length of stay were recorded. Inpatient complications and mortality rates were also documented. Modified Barthel Index (MBI) scores were recorded for the following intervals: prefall, discharge, 6-month, and at 1-year follow-up. Results: The mean age (A: 80 years and B: 81years), CCI (A: 5.41 and B: 5.43), and length of stay (A: 13.6 days and B: 15.2 days) were not significantly different. However, there was a significant difference ( P < .05) in time to surgery (A: 102.2 hours and B: 86.6 hours). Complication rates were about 6% in both groups (A = 6.57%: urinary infections = 13, wound infections = 1 and B = 6.03%: urinary infections = 10, wound infections = 1, pressure ulcer = 1). The preinjury MBI scores were significantly different ( P < .05; A: 91.65 and B: 88.19), however, there was no significant difference in scores measured at discharge (A: 60.79 and B: 59.39), 6 months (A: 77.65 and B: 77.47) and 1 year (A: 80.71 and B: 83.03). Patients who underwent surgery for hip fracture had overall recovered 90.9% of their preinjury function (overall MBI at 1 year: 81.83). Conclusion: The MBI scores reflect the extent of attainment of independence in self-care, and actual functional recovery is gauged from the percentage of recovery of preinjury function at 1 year postsurgery. We conclude that the type of surgery may not be a significant factor in determining independence in self-care although patients who had arthroplasty had recovered more function at 1 year postsurgery than those who underwent fixation (percentage recovery of preinjury function—A: 88.1% and B: 94.1%).
The Importance of the Intercondylar Notch in Anterior Cruciate Ligament Tears
Authors: Fernández-Jaén Tomás , López-Alcorocho Juan Manuel , Rodriguez-Iñigo Elena , Castellán Fabián , Hernández Juan Carlos , Guillén-García Pedro 
Published: August 2015

Background The factors associated with anterior cruciate ligament (ACL) tears are not completely clear. Some studies have shown that patients with a narrow intercondylar notch have a predisposition for ACL tears. Purpose To determine the relationship between the α angle and intercondylar notch width measurements and ACL tears. Study Design Case-control study; Level of evidence, 3. Methods A total of 530 patients (308 with ACL rupture, 222 with healthy ACLs) were included in this study. The α angle and intercondylar width were measured from magnetic resonance images (MRIs). Binary logistic regression analysis was performed to determine the influence of the variables on ACL status (normal or torn). Odds ratios (ORs) and their respective 95% CIs were also calculated. Results No significant differences in patient age and the affected knee were found between patients with normal or torn ACLs. The mean α angle was higher in patients with a torn ACL than in those with an intact one (57.5° ± 5.5° vs 56.2° ± 4.5°; P = .009). Intercondylar width was significantly lower in patients with a torn ACL than in those with an intact one (18.2 ± 3.1 vs 19.5 ± 3.6 mm; P < .001). A highly significant difference between men and women was found for mean intercondylar notch width (19.3 ± 3.3 vs 17.4 ± 3.1 mm; P < .001). In a logistic regression model, sex, intercondylar width, and α angle were statistically significant when adjusted for age. Conclusion Study results suggest that the ACL tears are associated with a narrow intercondylar notch and a high α angle, and that tears occur more frequently in men than in women. Clinical Relevance The model proposed in this study could be used by the physician in the medical office as a tool to identify the risk factors that may predispose a patient for a potential ACL tear.
Increased alveolar soluble annexin V promotes lung inflammation and fibrosis
Authors: Buckley Susan , Shi Wei , Xu Wei , Frey Mark R. , Moats Rex , Pardo Annie , Selman Moises , Warburton David 
Published: August 2015

The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesised that alveolar soluble annexin V contributes to lung fibrosis, based on the observation that human IPF bronchoalveolar lavage fluid (BALF) containing high annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when annexin V was depleted from the BALF.Conditioned medium from annexin V-treated alveolar epithelial type 2 cells (AEC2), but not annexin Vper se, induced proliferation of human fibroblasts and contained pro-fibrotic, IPF-associated proteins, as well as pro-inflammatory cytokines that were found to correlate tightly (r>0.95) with annexin V levels in human BALF. ErbB2 receptor tyrosine kinase in AECs was activated by annexin V, and blockade reduced the fibrotic potential of annexin V-treated AEC-conditioned medium.In vivo, aerosol delivery of annexin V to mouse lung induced inflammation, fibrosis and increased hydroxyproline, with activation of Wnt, transforming growth factor-β, mitogen-activated protein kinase and nuclear factor-κB signalling pathways, as seen in IPF.Chronically increased alveolar annexin V levels, as reflected in increased IPF BALF levels, may contribute to the progression of IPF by inducing the release of pro-fibrotic mediators.
miR-17 overexpression in cystic fibrosis airway epithelial cells decreases interleukin-8 production
Authors: Oglesby Irene K. , Vencken Sebastian F. , Agrawal Raman , Gaughan Kevin , Molloy Kevin , Higgins Gerard , McNally Paul , McElvaney Noel G. , Mall Marcus A. , Greene Catherine M. 
Published: August 2015

Interleukin (IL)-8 levels are higher than normal in cystic fibrosis (CF) airways, causing neutrophil infiltration and non-resolving inflammation. Overexpression of microRNAs that target IL-8 expression in airway epithelial cells may represent a therapeutic strategy for cystic fibrosis.IL-8 protein and mRNA were measured in cystic fibrosis and non-cystic fibrosis bronchoalveolar lavage fluid and bronchial brushings (n=20 per group). miRNAs decreased in the cystic fibrosis lung and predicted to target IL-8 mRNA were quantified in βENaC-transgenic, cystic fibrosis transmembrane conductance regulator (Cftr)-/-and wild-type mice, primary cystic fibrosis and non-cystic fibrosis bronchial epithelial cells and a range of cystic fibrosisversusnon-cystic fibrosis airway epithelial cell lines or cells stimulated with lipopolysaccharide,Pseudomonas-conditioned medium or cystic fibrosis bronchoalveolar lavage fluid. The effect of miRNA overexpression on IL-8 protein production was measured.miR-17 regulates IL-8 and its expression was decreased in adult cystic fibrosis bronchial brushings, βENaC-transgenic mice and bronchial epithelial cells chronically stimulated withPseudomonas-conditioned medium. Overexpression of miR-17 inhibited basal and agonist-induced IL-8 protein production in F508del-CFTR homozygous CFTE29o−tracheal, CFBE41o−and/or IB3 bronchial epithelial cells.These results implicate defective CFTR, inflammation, neutrophilia and mucus overproduction in regulation of miR-17. Modulating miR-17 expression in cystic fibrosis bronchial epithelial cells may be a novel anti-inflammatory strategy for cystic fibrosis and other chronic inflammatory airway diseases.
COPD comorbidities network
Authors: Divo Miguel J. , Casanova Ciro , Marin Jose M. , Pinto-Plata Victor M. , de-Torres Juan P. , Zulueta Javier J. , Cabrera Carlos , Zagaceta Jorge , Sanchez-Salcedo Pablo , Berto Juan , Davila Rebeca Baz , Alcaide Ana B. , Cote Claudia , Celli Bartolome R. 
Published: August 2015

Multimorbidity frequently affects the ageing population and their co-existence may not occur at random. Understanding their interactions and that with clinical variables could be important for disease screening and management.In a cohort of 1969 chronic obstructive pulmonary disease (COPD) patients and 316 non-COPD controls, we applied a network-based analysis to explore the associations between multiple comorbidities. Clinical characteristics (age, degree of obstruction, walking, dyspnoea, body mass index) and 79 comorbidities were identified and their interrelationships quantified. Using network visualisation software, we represented each clinical variable and comorbidity as a node with linkages representing statistically significant associations.The resulting COPD comorbidity network had 428, 357 or 265 linkages depending on the statistical threshold used (p≤0.01, p≤0.001 or p≤0.0001). There were more nodes and links in COPD compared with controls after adjusting for age, sex and number of subjects. In COPD, a subset of nodes had a larger number of linkages representing hubs. Four sub-networks or modules were identified using an inter-linkage affinity algorithm and their display provided meaningful interactions not discernible by univariate analysis.COPD patients are affected by larger number of multiple interlinked morbidities which clustering pattern may suggest common pathobiological processes or be utilised for screening and/or therapeutic interventions.
Neutrophil proteases alter the interleukin-22-receptor-dependent lung antimicrobial defence
Authors: Guillon Antoine , Jouan Youenn , Brea Deborah , Gueugnon Fabien , Dalloneau Emilie , Baranek Thomas , Henry Clémence , Morello Eric , Renauld Jean-Christophe , Pichavant Muriel , Gosset Philippe , Courty Yves , Diot Patrice , Si-Tahar Mustapha 
Published: August 2015

Chronic obstructive pulmonary disease (COPD) is punctuated by episodes of infection-driven acute exacerbations. Despite the life-threatening nature of these exacerbations, the underlying mechanisms remain unclear, although a high number of neutrophils in the lungs of COPD patients is known to correlate with poor prognosis. Interleukin (IL)-22 is a cytokine that plays a pivotal role in lung antimicrobial defence and tissue protection. We hypothesised that neutrophils secrete proteases that may have adverse effects in COPD, by altering the IL-22 receptor (IL-22R)-dependent signalling.Usingin vitroandin vivoapproaches as well as reverse transcriptase quantitative PCR, flow cytometry and/or Western blotting techniques, we first showed that pathogens such as the influenza virus promoteIL-22Rexpression in human bronchial epithelial cells, whereasPseudomonas aeruginosa, bacterial lipopolysaccharide or cigarette smoke do not. Most importantly, neutrophil proteases cleave IL-22R and impair IL-22-dependent immune signalling and expression of antimicrobial effectors such as β-defensin-2. This proteolysis resulted in the release of a soluble fragment of IL-22R, which was detectable both in cellular and animal models as well as in sputa from COPD patients with acute exacerbations.Hence, our study reveals an unsuspected regulation by the proteolytic action of neutrophil enzymes of IL-22-dependent lung host response. This process probably enhances pathogen replication, and ultimately COPD exacerbations.
An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features
Authors: Fischer Aryeh , Antoniou Katerina M. , Brown Kevin K. , Cadranel Jacques , Corte Tamera J. , du Bois Roland M. , Lee Joyce S. , Leslie Kevin O. , Lynch David A. , Matteson Eric L. , Mosca Marta , Noth Imre , Richeldi Luca , Strek Mary E. , Swigris Jeffrey J. , Wells Athol U. , West Sterling G. , Collard Harold R. , Cottin Vincent 
Published: August 2015

Many patients with an idiopathic interstitial pneumonia (IIP) have clinical features that suggest an underlying autoimmune process but do not meet established criteria for a connective tissue disease (CTD). Researchers have proposed differing criteria and terms to describe these patients, and lack of consensus over nomenclature and classification limits the ability to conduct prospective studies of a uniform cohort.The “European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease” was formed to create consensus regarding the nomenclature and classification criteria for patients with IIP and features of autoimmunity.The task force proposes the term “interstitial pneumonia with autoimmune features” (IPAF) and offers classification criteria organised around the presence of a combination of features from three domains: a clinical domain consisting of specific extra-thoracic features, a serologic domain consisting of specific autoantibodies, and a morphologic domain consisting of specific chest imaging, histopathologic or pulmonary physiologic features.A designation of IPAF should be used to identify individuals with IIP and features suggestive of, but not definitive for, a CTD. With IPAF, a sound platform has been provided from which to launch the requisite future research investigations of a more uniform cohort.
A summary of the new GINA strategy: a roadmap to asthma control
Authors: Reddel Helen K. , Bateman Eric D. , Becker Allan , Boulet Louis-Philippe , Cruz Alvaro A. , Drazen Jeffrey M. , Haahtela Tari , Hurd Suzanne S. , Inoue Hiromasa , de Jongste Johan C. , Lemanske Robert F. , Levy Mark L. , O'Byrne Paul M. , Paggiaro Pierluigi , Pedersen Soren E. , Pizzichini Emilio , Soto-Quiroz Manuel , Szefler Stanley J. , Wong Gary W.K. , FitzGerald J. Mark 
Published: August 2015

Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence.This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma−chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations.
Pulmonary hypertension in idiopathic pulmonary fibrosis with mild-to-moderate restriction
Authors: Raghu Ganesh , Nathan Steven D. , Behr Juergen , Brown Kevin K. , Egan James J. , Kawut Steven M. , Flaherty Kevin R. , Martinez Fernando J. , Wells Athol U. , Shao Lixin , Zhou Huafeng , Henig Noreen , Szwarcberg Javier , Gillies Hunter , Montgomery Alan B. , O'Riordan Thomas G. 
Published: August 2015

The clinical course of pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) is not known except in advanced disease.488 subjects in a placebo-controlled study of ambrisentan in IPF with mild–moderate restriction in lung volume, underwent right heart catheterisation (RHC) at baseline and 117 subjects (24%) had repeated haemodynamic measurements at 48 weeks.The subjects were categorised into a) World Health Organization (WHO) Group 3 PH (PH associated with pulmonary disease), n=68 (14%); b) WHO Group 2 PH (PH associated with left-sided cardiac disease), n=25 (5%); c) no PH but elevated pulmonary artery wedge pressure (PAWP), n=21 (4%); and d) no PH but without elevation of PAWP, n=374 (77%). The WHO Group 3 PH subjects had a lower diffusion capacity, 6MWD and oxygen saturation compared to the subjects with no PH. There was no significant change in mean pulmonary arterial pressure with ambrisenten or placebo after 12 months.Subjects with IPF associated with WHO Group 3 PH had impaired gas exchange and exercise capacity compared to patients without PH. An additional 9% of the subjects had haemodynamic evidence of subclinical left-ventricular dysfunction. Pulmonary artery pressures remained stable over 1 year in the majority of the cohort.
Unravelling the complexity of COPD by microRNAs: it's a small world after all
Authors: Osei Emmanuel T. , Florez-Sampedro Laura , Timens Wim , Postma Dirkje S. , Heijink Irene H. , Brandsma Corry-Anke 
Published: August 2015

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease and is currently the fourth leading cause of death worldwide. Chronic inflammation and repair processes in the small airways are characteristic of COPD. Despite extensive efforts from researchers and industry, there is still no cure for COPD, hence an urgent need for new therapeutic alternatives. MicroRNAs are such an option; they are small noncoding RNAs involved in gene regulation. Their importance has been shown with respect to maintaining the balance between health and disease. Although previous reviews have discussed the expression of microRNAs related to lung disease, a detailed discussion regarding the function of differential miRNA expression in the pathogenesis of COPD is lacking.In this review we link the expression of microRNAs to different features of COPD and explain their importance in the pathogenesis of this disease. We further discuss their potential to contribute to the development of future therapeutic strategies.
Simulator training for endobronchial ultrasound: a randomised controlled trial
Authors: Konge Lars , Clementsen Paul Frost , Ringsted Charlotte , Minddal Valentina , Larsen Klaus Richter , Annema Jouke T. 
Published: August 2015

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is very operator dependent and has a long learning curve. Simulation-based training might shorten the learning curve, and an assessment tool with solid validity evidence could ensure basic competency before unsupervised performance.A total of 16 respiratory physicians, without EBUS experience, were randomised to either virtual-reality simulator training or traditional apprenticeship training on patients, and then each physician performed EBUS-TBNA procedures on three patients. Three blinded, independent assessor assessed the video recordings of the procedures using a newly developed EBUS assessment tool (EBUSAT).The internal consistency was high (Cronbach's α=0.95); the generalisability coefficient was good (0.86), and the tool had discriminatory ability (p<0.001). Procedures performed by simulator-trained novices were rated higher than procedures performed by apprenticeship-trained novices: mean±sdare 24.2±7.9 points and 20.2±9.4 points, respectively; p=0.006. A pass/fail standard of 28.9 points was established using the contrasting groups method, resulting in 16 (67%) and 20 (83%) procedures performed by simulator-trained novices and apprenticeship-trained novices failing the test, respectively; p<0.001.The endobronchial ultrasound assessment tool could be used to provide reliable and valid assessment of competence in EBUS-TBNA, and act as an aid in certification. Virtual-reality simulator training was shown to be more effective than traditional apprenticeship training.
Knowledge-based analysis of genetic associations of rheumatoid arthritis to inform studies searching for pleiotropic genes: a literature review and network analysis
Authors: Zheng Weiying , Rao Shaoqi 
Published: August 2015

Abstract
Introduction
Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. Gene variants directly affect the normal processes of a series of physiological and biochemical reactions, and therefore cause a variety of diseases traits to be changed accordingly. Moreover, a shared genetic susceptibility mechanism may exist between different diseases. Therefore, shared genes, with pleiotropic effects, are important to understand the sharing pathogenesis and hence the mechanisms underlying comorbidity.

Methods
In this study, we proposed combining genome-wide association studies (GWAS) and public knowledge databases to search for potential pleiotropic genes associated with rheumatoid arthritis (RA) and eight other related diseases. Here, a GWAS-based network analysis is used to recognize risk genes significantly associated with RA. These RA risk genes are re-extracted as potential pleiotropic genes if they have been proved to be susceptible genes for at least one of eight other diseases in the OMIM or PubMed databases.

Results
In total, we extracted 116 potential functional pleiotropic genes for RA and eight other diseases, including five hub pleiotropic genes, BTNL2, HLA-DRA, NOTCH4, TNXB, and C6orf10, where BTNL2, NOTCH4, and C6orf10 are novel pleiotropic genes identified by our analysis.

Conclusions
This study demonstrates that pleiotropy is a common property of genes associated with disease traits. Our results ascertained the shared genetic risk profiles that predisposed individuals to RA and other diseases, which could have implications for identification of molecular targets for drug development, and classification of diseases.
Immunological events in chronic spontaneous urticaria
Authors: Ferrer Marta 
Published: August 2015

AbstractChronic spontaneous urticaria (CSU) is a highly debilitating skin disease associated with systemic features. We have made significant progress in several aspects relating to this condition. However, the exact physiopathology remains unknown. There is mounting evidence for an autoimmune basis, demonstrated by the CSU serum ability to activate healthy donors skin mast cells and blood basophils. However, it is only seen among 35–40% of patients. Mast cells and basophils play an important role in this skin condition. Both cells in CSU patients have unique features that differentiate them from basophils and mast cells from healthy donors. In the case of basophils, basopenia is typically found in CSU patients. Basophils from CSU patients also tend to be hyporesponsive to stimuli that act through the IgE receptor, responsive to other stimuli as MCP‐1 or C5a, and hyperesponsive when incubated with sera. Eosinophils are also present in CSU skin biopsies, yet their exact role has not yet been defined. Likewise, endothelial cells also play a function, as indirectly demonstrated by an increase of vasoactive peptides in skin and plasma of CSU patients’ samples. All these facts orchestrate a systemic inflammation response producing a significant increase of several inflammatory markers. Unfortunately, we lack a unitary model that could explain the exact role of each of these players. In this review, we will describe the history and discover the pathway to the present knowledge on the immunological facts of this disease.