bluuebunny/crossref_metadata_2025_split huggingface dataset:
FAQs about the GOLD 2011 assessment proposal of COPD: a comparative analysis of four different cohorts
Authors: Agusti Alvar , Hurd Suzanne , Jones Paul , Fabbri Leonardo M. , Martinez Fernando , Vogelmeier Claus , Vestbo Jørgen , Rodriguez-Roisin Robert 
Published: May 2013

Since the publication of the new Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposal for the assessment of chronic obstructive lung disease (COPD), four studies have used existing cohorts to explore the characteristics, temporal variability and/or relationship with outcomes of the four resulting patient categories (A, B, C and D).Here, we compare their results and address a number of frequently asked questions (FAQs) on the topic.The most salient findings were that: 1) the prevalence of these four groups depends on the specific population studied, C being the least prevalent; 2) comorbidities are particularly prevalent in the two “high-symptom” groups (B and D); 3) patients classifiedZ as A or D tend to remain in the same group over time, whereas those classified as B or C change substantially during follow-up; 4) mortality at 3 years was lowest in A and worst in D but surprisingly similar (and intermediate) in B and C; and 5) the incidence of exacerbations during follow-up increases progressively from A to D but that of hospitalisations behave similarly to mortality.These results identify several strengths and shortcomings of the new GOLD assessment proposal, particularly that group B is associated with more morbidity and high mortality.
Plasma advanced glycation end-products and skin autofluorescence are increased in COPD
Authors: Gopal Poornima , Reynaert Niki L. , Scheijen Jean L.J.M. , Engelen Lean , Schalkwijk Casper G. , Franssen Frits M.E. , Wouters Emiel F.M. , Rutten Erica P.A. 
Published: May 2013

Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and oxidative stress. These conditions may lead to the formation of advanced glycation end-products (AGEs).In this study we investigated in 88 COPD patients and 55 control subjects (80% ex-smokers) the association of the plasma protein-bound AGEs Nϵ-(carboxymethyl)lysine (CML), pentosidine, Nϵ-(carboxyethyl)lysine (CEL), and AGE accumulation in skin by skin autofluorescence (AFR), with lung function.Mean±sdplasma CML was decreased (COPD 61.6±15.6 nmol·mmol−1lysine, never-smokers 80.7±19.8 nmol·mmol−1lysine and ex-smokers 82.9±19.3 nmol·mmol−1lysine) and CEL (COPD 39.1±10.9 nmol·mmol−1lysine, never-smokers 30.4±5.0 nmol·mmol−1lysine and ex-smokers 27.7±6.4 nmol·mmol−1lysine) and AFR (COPD 3.33±0.67 arbitrary units (AU), never-smokers 2.24±0.45 AU and ex-smokers 2.31±0.47 AU) were increased in COPD patients compared to controls. Disease state was inversely associated with CML, and linearly associated with CEL and AFR. Performing regression analyses in the total group, CEL and AFR showed a negative association and CML a positive association with lung function, even after correction for potential confounders.In conclusion, CEL and AFR were negatively and CML was positively associated with disease state. In the total group only the AGEs showed an association with forced expiratory volume in 1 s. Our data suggest that AGEs are involved in the pathophysiology of COPD, although their exact role remains to be determined.
Lung adenocarcinoma subtypes based on expression of human airway basal cell genes
Authors: Fukui Tomoya , Shaykhiev Renat , Agosto-Perez Francisco , Mezey Jason G. , Downey Robert J. , Travis William D. , Crystal Ronald G. 
Published: May 2013

Lung cancer, including lung adenocarcinoma, is a heterogeneous disease, which evolves from molecular alterations in the airway epithelium. This study explores whether a subtype of lung adenocarcinomas expresses the unique molecular features of human airway basal cells (BCs), and how expression of the airway BC features correlates with the molecular, pathological and clinical phenotype of lung adenocarcinoma.Three independent lung adenocarcinoma data sets were analysed for expression of genes that constitute the airway BC signature. Expression of the BC signature in lung adenocarcinoma was then correlated to clinical and biological parameters.Remarkable enrichment of airway BC signature genes was found in lung adenocarcinomas. A subset of lung adenocarcinomas (BC-high adenocarcinoma) exhibited high expression of BC signature genes in association with poorer tumour grade, higher frequency of vascular invasion and shorter survival than adenocarcinomas with lower expression of these genes. At the molecular level, BC-high adenocarcinomas displayed a higher frequency ofKRASmutations, activation of transcriptional networks and pathways related to cell cycle, extracellular matrix organisation, and a distinct differentiation pattern with suppression of ciliated and exocrine bronchiolar cell (Clara cell)-related genes.Activation of the airway BC programme is a molecular feature of a distinct, aggressive subtype of lung adenocarcinoma.
Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation
Authors: Hostettler Katrin E. , Halter Jörg P. , Gerull Sabine , Lardinois Didier , Savic Spasenija , Roth Michael , Tamm Michael 
Published: May 2013

Bronchiolitis obliterans is a complication after allogeneic haematopoietic stem cell transplantation (HSCT). Management of bronchiolitis obliterans comprises intensive immunosuppression, but treatment response is poor. We investigated the effect of cyclosporine A (CsA), tacrolimus (FK506), methylprednisolone (mPRED), mycophenolate mofetil (MMF) and everolimus on the proliferation of primary lung myofibroblasts from HSCT patients with bronchiolitis obliterans syndrome (BOS).Cells were isolated from surgical lung biopsies of eight HSCT patients with BOS. Proliferation was assessed by [3H]-thymidine incorporation.Biopsies revealed constrictive bronchiolitis obliterans in three patients and lymphocytic bronchiolitis in five patients. CsA and FK506 significantly induced proliferation of myofibroblasts. mPRED and MMF caused a significant inhibition of proliferation, whereas everolimus had no effect. Costimulation with FK506, mPRED and MMF significantly inhibited proliferation. Serial pulmonary function tests over 12 months after lung biopsy and under triple therapy demonstrated that patients with lymphocytic bronchiolitis had a significant improvement in forced expiratory volume in 1 s (FEV1), whereas FEV1of patients with bronchiolitis obliterans was unchanged.Our data demonstrate a pro-proliferative effect of calcineurin inhibitors on primary human lung myofibroblasts obtained from patients with BOS after HSCT. In contrast, based on the observed antiproliferative capacity of MMFin vitro, MMF-based calcineurin inhibitor-free treatment strategies should be further evaluated in patients with bronchiolitis obliterans after HSCT.
Serum uric acid as a predictor of mortality and future exacerbations of COPD
Authors: Bartziokas Konstantinos , Papaioannou Andriana I. , Loukides Stelios , Papadopoulos Alexandros , Haniotou Aikaterini , Papiris Spyridon , Kostikas Konstantinos 
Published: May 2013

Serum uric acid is increased in respiratory disease, especially in the presence of hypoxia and systemic inflammation. We evaluated serum uric acid as a biomarker for prediction of mortality and future acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Serum uric acid was measured in 314 eligible consecutive patients on admission for AECOPD. Patients were evaluated monthly for 1 year.Uric acid levels were higher in patients with more severe airflow limitation and in those experiencing frequent exacerbations. High uric acid levels (≥6.9 mg·dL−1) were an independent predictor of 30-day mortality in multivariate Cox regression analysis (HR 1.317, 95% CI 1.011–1.736; p=0.044), but not of 1-year mortality. Patients with high serum uric acid required more prolonged hospitalisation, and more often needed noninvasive ventilation and admission to the intensive care unit within 30 days. In addition, high uric acid levels were associated with increased risk and hospitalisation for AECOPD in 1 year in multivariate Poisson regression analysis (incidence rate ratio 1.184 (95% CI 1.125–1.246) and 1.190 (95% CI 1.105–1.282), respectively; both p<0.001).Serum uric acid is associated with increased 30-day mortality and risk for AECOPD and hospitalisations in 1-year follow-up. This low-cost biomarker may be useful in the identification of high-risk chronic obstructive pulmonary disease patients that could benefit from intensive management.
Proteomic analyses and identification of arginine methylated proteins differentially recognized by autosera from anti-Sm positive SLE patients
Authors: Chang Hong-How , Hu Huan-Hsuan , Lee Yu-Jen , Wei Hung-Ming , Fan-June Ming-Chun , Hsu Tsai-Ching , Tsay Gregory J , Li Chuan 
Published: May 2013

Abstract

Background
Antibodies against spliceosome Sm proteins (anti-Sm autoantibodies) are specific to the autoimmune disease systemic lupus erythematosus (SLE). Anti-Sm autosera have been reported to specifically recognize Sm D1 and D3 with symmetric di-methylarginines (sDMA). We investigated if anti-Sm sera from local SLE patients can differentially recognize Sm proteins or any other proteins due to their methylation states.

Results
We prepared HeLa cell proteins at normal or hypomethylation states (treated with an indirect methyltransferase inhibitor adenosine dialdehyde, AdOx). A few signals detected by the anti-Sm positive sera from typical SLE patients decreased consistently in the immunoblots of hypomethylated cell extracts. The differentially detected signals by one serum (Sm1) were pinpointed by two-dimensional electrophoresis and identified by mass spectrometry. Three identified proteins: splicing factor, proline- and glutamine-rich (SFPQ), heterogeneous nuclear ribonucleoprotein D-like (hnRNP DL) and cellular nucleic acid binding protein (CNBP) are known to contain methylarginines in their glycine and arginine rich (GAR) sequences. We showed that recombinant hnRNP DL and CNBP expressed in Escherichia coli can be detected by all anti-Sm positive sera we tested. As CNBP appeared to be differentially detected by the SLE sera in the pilot study, differential recognition of arginine methylated CNBP protein by the anti-Sm positive sera were further examined. Hypomethylated FLAG-CNBP protein immunopurified from AdOx-treated HeLa cells was less recognized by Sm1 compared to the CNBP protein expressed in untreated cells. Two of 20 other anti-Sm positive sera specifically differentiated the FLAG-CNBP protein expressed in HeLa cells due to the methylation. We also observed deferential recognition of methylated recombinant CNBP proteins expressed from E. coli by some of the autosera.

Conclusion
Our study showed that hnRNP DL and CNBP are novel antigens for SLE patients and the recognition of CNBP might be differentiated dependent on the level of arginine methylation.
Genome wide analysis of the complete GlnR nitrogen-response regulon in Mycobacterium smegmatis
Authors: Jenkins Victoria A , Barton Geraint R , Robertson Brian D , Williams Kerstin J 
Published: May 2013

Abstract

Background
Nitrogen is an essential element for bacterial growth and an important component of biological macromolecules. Consequently, responding to nitrogen limitation is critical for bacterial survival and involves the interplay of signalling pathways and transcriptional regulation of nitrogen assimilation and scavenging genes. In the soil dwelling saprophyte Mycobacterium smegmatis the OmpR-type response regulator GlnR is thought to mediate the transcriptomic response to nitrogen limitation. However, to date only ten genes have been shown to be in the GlnR regulon, a vastly reduced number compared to other organisms.

Results
We investigated the role of GlnR in the nitrogen limitation response and determined the entire GlnR regulon, by combining expression profiling of M. smegmatis wild type and glnR deletion mutant, with GlnR-specific chromatin immunoprecipitation and high throughput sequencing. We identify 53 GlnR binding sites during nitrogen limitation that control the expression of over 100 genes, demonstrating that GlnR is the regulator controlling the assimilation and utilisation of nitrogen. We also determine a consensus GlnR binding motif and identify key residues within the motif that are required for specific GlnR binding.

Conclusions
We have demonstrated that GlnR is the global nitrogen response regulator in M. smegmatis, directly regulating the expression of more than 100 genes. GlnR controls key nitrogen stress survival processes including primary nitrogen metabolism pathways, the ability to utilise nitrate and urea as alternative nitrogen sources, and the potential to use cellular components to provide a source of ammonium. These studies further our understanding of how mycobacteria survive nutrient limiting conditions.
Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs
Authors: Christoforides Alexis , Carpten John D , Weiss Glen J , Demeure Michael J , Von Hoff Daniel D , Craig David W 
Published: May 2013

Abstract

Background
The field of cancer genomics has rapidly adopted next-generation sequencing (NGS) in order to study and characterize malignant tumors with unprecedented resolution. In particular for cancer, one is often trying to identify somatic mutations – changes specific to a tumor and not within an individual’s germline. However, false positive and false negative detections often result from lack of sufficient variant evidence, contamination of the biopsy by stromal tissue, sequencing errors, and the erroneous classification of germline variation as tumor-specific.

Results
We have developed a generalized Bayesian analysis framework for matched tumor/normal samples with the purpose of identifying tumor-specific alterations such as single nucleotide mutations, small insertions/deletions, and structural variation. We describe our methodology, and discuss its application to other types of paired-tissue analysis such as the detection of loss of heterozygosity as well as allelic imbalance. We also demonstrate the high level of sensitivity and specificity in discovering simulated somatic mutations, for various combinations of a) genomic coverage and b) emulated heterogeneity.

Conclusion
We present a Java-based implementation of our methods named Seurat, which is made available for free academic use. We have demonstrated and reported on the discovery of different types of somatic change by applying Seurat to an experimentally-derived cancer dataset using our methods; and have discussed considerations and practices regarding the accurate detection of somatic events in cancer genomes. Seurat is available at https://sites.google.com/site/seuratsomatic.
Functional transcriptomic analysis of the role of MAB-5/Hox in Q neuroblast migration in Caenorhabditis elegans
Authors: Tamayo Joel V , Gujar Mahekta , Macdonald Stuart J , Lundquist Erik A 
Published: May 2013

Abstract

Background
Directed cell migration is a fundamental process in normal development and in tumor metastasis. In C. elegans the MAB-5/Hox transcription factor is a determinant of posterior migration of the Q neuroblast descendants. In this work, mab-5 transcriptional targets that control Q descendant migration are identified by comparing RNA-seq profiles in wild type and mab-5 mutant backgrounds.

Results
Transcriptome profiling is a widely-used and potent tool to identify genes involved in developmental and pathological processes, and is most informative when RNA can be isolated from individual cell or tissue types. Cell-specific RNA samples can be difficult to obtain from invertebrate model organisms such as Drosophila and C. elegans. Here we test the utility of combining a whole organism RNA-seq approach with mab-5 loss and gain-of-function mutants and functional validation using RNAi to identify genes regulated by MAB-5 to control Q descendant migration. We identified 22 genes whose expression was controlled by mab-5 and that controlled Q descendant migration. Genes regulated by mab-5 were enriched for secreted and transmembrane molecules involved in basement membrane interaction and modification, and some affected Q descendant migration.

Conclusions
Our results indicate that a whole-organism RNA-seq approach, when combined with mutant analysis and functional validation, can be a powerful method to identify genes involved in a specific developmental process, in this case Q descendant posterior migration. These genes could act either autonomously in the Q cells, or non-autonomously in other cells that express MAB-5. The identities of the genes regulated by MAB-5 indicate that MAB-5 acts by modifying interactions with the basement membrane, resulting in posterior versus anterior migration.
When the group practice breaks up: a qualitative study
Authors: Marechal François , Schmidt Dorothée , Lasserre Evelyne , Letrilliart Laurent 
Published: May 2013

Abstract

Background
Group practices are increasingly common for primary care physicians worldwide. Although breakups are likely to happen frequently within group practices, their process has not been studied to date. The aims of this study were therefore to explore the reasons for breakups of group practices of general practitioners and to describe the associated feelings.

Methods
We conducted a qualitative study consisting of in-depth interviews of 21 general practitioners and one secretary from past group practices in the Rhône-Alpes region, France, who experienced a breakup.

Results
When getting started in group practice for the first time, young doctors did not feel ready and supported, and did not necessarily share the same expectations as their partners. The reasons for the breakups involved imbalances within the groups, contrasting working and management styles, and breakdowns in communication. The breakup process often generated long-persistent feelings of suffering and failure for almost every partner who experienced a breakup, particularly for the partner who was leaving.

Conclusions
Weakening factors exist from the very beginning of a partnership, and problems are likely to increase at every change or event occurring in the group. We provide several recommendations, including fair management, a shared project based on a precise contract, the consultation of third parties as necessary and, in the worst case scenario, leaving the group practice in time.
Clinical and economic burden of invasive pneumococcal disease in adults: a multicenter hospital-based study
Authors: Song Joon Young , Choi Jun Yong , Lee Jin Soo , Bae In-Gyu , Kim Young Keun , Sohn Jang Wook , Jo Yu Mi , Choi Won Suk , Lee Jacob , Park Kyung Hwa , Kim Woo Joo , Cheong Hee Jin 
Published: May 2013

Abstract

Background

Streptococcus pneumoniae causes a broad spectrum of illnesses ranging from mild upper respiratory tract infections to invasive pneumococcal disease (IPD). Quantitative data on the burden of pneumococcal disease, important for the establishment of appropriate vaccination strategies, is currently lacking in adults.

Methods
This multicenter, retrospective cohort study was designed to estimate the clinical and economic burden of IPD in adults over the last decade. Data were collected from patients with IPD at 10 university hospitals in South Korea. We estimated the proportion of IPD among all hospitalized patients, the case fatality rate, and the direct medical costs of IPD. Data were further analyzed according to age and risk groups.

Results
During the study period, 970 patients with IPD were identified. The mean age for all patients was 60.9 years; patients aged 50–64 years (33.0%) were most numerous, followed by those aged 65–74 years (27.4%). Overall, the proportion of IPD was 0.36 cases/1000 hospitalized patients and the case fatality rate was 30.9%, which increased significantly with age (p < 0.01). The mean direct medical costs were estimated to be US $7,452 without a difference between age and risk groups. On multivariate analysis, old age, advanced ECOG performance status, bacteremic pneumonia, and nosocomial infection were independent risk factors of 30-day case fatality.

Conclusions
The clinical disease burden of IPD increased significantly with age and direct medical costs from IPD were substantial, regardless of age and co-morbid conditions. The current age-based vaccination strategy appears to be appropriate.
Factors associated with cervical cancer screening uptake among Inuit women in Nunavik, Quebec, Canada
Authors: Cerigo Helen , Coutlée Francois , Franco Eduardo L , Brassard Paul 
Published: May 2013

Abstract

Background
The Canadian circumpolar Inuit population has a higher incidence rate of cervical cancer than the general population and the majority of cases occur among underscreened women. The objectives of this study were to determine Pap smear utilization rates and to determine factors associated with time-inappropriate use of cervical cancer screening among a cohort of Inuit women from Nunavik, Quebec, Canada.

Methods
This study utilizes baseline information collected from a cohort formed between January 2002 and December 2007 to study the natural history of HPV among Inuit women aged 21–69 years in Nunavik, Quebec. Cervical cancer screening history and other variables were obtained from a baseline questionnaire and medical chart review. Unconditional logistic regression was used to estimate the odds ratios and 95% confidence intervals for potential predictors of not having a Pap smear within the previous 3 years prior to cohort entry.

Results
A total of 403 Inuit women who had a baseline questionnaire and chart review were included. The mean age of the study population was 34.2 years. In the three years prior to study entry, 25% of women did not have a Pap smear. Older age and never giving birth were significant predictors of time-inappropriate Pap smear use.

Conclusions
Our results suggest that older women and women who are not accessing reproductive care have a lower compliance with time-appropriate cervical cancer screening and future research should address potential strategies to increase screening coverage among this group.