bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in plasma and sputum biomarkers between COPD and COPD–asthma overlap
Authors: Iwamoto Hiroshi , Gao Jing , Koskela Jukka , Kinnula Vuokko , Kobayashi Hideo , Laitinen Tarja , Mazur Witold 
Published: June 2013

The pathophysiological features of chronic obstructive pulmonary disease(COPD)–asthma overlap are poorly understood and there has been no study of plasma or sputum biomarkers in overlap patients. In order to clarify the similarity and differences between overlap and COPD or asthma, we have investigated four potential biomarkers of COPD: surfactant protein A (SP-A), soluble receptor for advanced glycation end-products (sRAGE), myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL). SP-A and sRAGE are pneumocyte-derived markers. MPO and NGAL are neutrophil-derived molecules, but NGAL can also be expressed by respiratory epithelial cells.Plasma levels of SP-A and sRAGE and induced sputum levels of MPO and NGAL were measured by enzyme immunoassay/ELISA in 134 subjects: nonsmokers (n=26), smokers (n=23), asthma (n=32), COPD (n=39) and COPD–asthma overlap patients (n=14).In patients with COPD–asthma overlap, sputum MPO and plasma SP-A were significantly elevated whereas plasma sRAGE levels were reduced compared with asthma patients. Only sputum NGAL was significantly elevated in COPD–asthma overlap compared with COPD (p=0.00016) and could be used to differentiate patients with overlap from those with COPD.Increased induced sputum levels of NGAL might be a characteristic feature of overlap, suggesting enhanced neutrophilic airway inflammation and/or airway epithelial injury in COPD–asthma overlap.
Zero reference level for right heart catheterisation
Authors: Kovacs Gabor , Avian Alexander , Olschewski Andrea , Olschewski Horst 
Published: June 2013

Although in the pulmonary circulation small pressure differences may alter the categorisation of patients, there is no consensus on a standard zero reference level (ZRL). In the supine position, ZRL is mostly set at “5 cm below anterior thorax surface”, “1/3 thoracic diameter below anterior thorax surface”, “mid-thoracic level” or “10 cm above table level”.We retrospectively assessed the distance of these four ZRLs from computed tomography-derived right and left atrial centre levels and from one another in patients undergoing right heart catheterisation and calculated the respective differences in pressure readings.We included 196 consecutive patients. The ZRL at “1/3 thoracic diameter” was most often (98.5%) level with the right atrium, and the ZRL at “mid-thoracic level” was level with the left atrium (97.4%), revealing a median (range) pressure difference of -0.3 (-3.0–1.3) and 0.2 (-2.0–1.3) mmHg from the right and left atrial centre level, respectively. The largest differences (8.0 (2.0–15.4) mmHg) were found between the ZRLs “5 cm below anterior thorax surface” and “10 cm above table level”. Accordingly, 59%versus80% of patients would be classified with pulmonary hypertension and 7%versus38% with elevated left heart pressures.The choice of ZRL strongly influences pulmonary pressure readings and pulmonary hypertension classification. 1/3 thoracic diameter mostly represents the right atrium while the left atrium is best represented by the mid-thoracic level.
Adrenomedullin refines mortality prediction by the BODE index in COPD: the “BODE-A” index
Authors: Stolz Daiana , Kostikas Kostantinos , Blasi Francesco , Boersma Wim , Milenkovic Branislava , Lacoma Alicia , Louis Renaud , Aerts Joachim G. , Welte Tobias , Torres Antoni , Rohde Gernot G.U. , Boeck Lucas , Rakic Janko , Scherr Andreas , Hertel Sabine , Giersdorf Sven , Tamm Michael 
Published: June 2013

The BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index is well-validated for mortality prediction in chronic obstructive pulmonary disease (COPD). Concentrations of plasma pro-adrenomedullin, a surrogate for mature adrenomedullin, independently predicted 2-year mortality among inpatients with COPD exacerbation.We compared accuracy of initial pro-adrenomedullin level, BODE and BODE components, alone or combined, in predicting 1-year or 2-year all-cause mortality in a multicentre, multinational observational cohort with stable, moderate to very severe COPD.Pro-adrenomedullin was significantly associated (p<0.001) with 1-year mortality (4.7%) and 2-year mortality (7.8%) and comparably predictive to BODE regarding both (C statistics 0.691versus0.745 and 0.635versus0.679, respectively). Relative to using BODE alone, adding pro-adrenomedullin significantly improved 1-year and 2-year mortality prognostication (C statistics 0.750 and 0.818, respectively; both p<0.001). Pro-adrenomedullin plus BOD was more predictive than the original BODE including 6-min walk distance. In multivariable analysis, pro-adrenomedullin (likelihood ratio Chi-squared 13.0, p<0.001), body mass index (8.5, p=0.004) and 6-min walk distance (7.5, p=0.006) independently foretold 2-year survival, but modified Medical Research Council dyspnoea score (2.2, p=0.14) and forced expiratory volume in 1 s % predicted (0.3, p=0.60) did not.Pro-adrenomedullin plus BODE better predicts mortality in COPD patients than does BODE alone; pro-adrenomedullin may substitute for 6-min walk distance in BODE when 6-min walk testing is unavailable.
The effect of peroxisome proliferator-activated receptor-γ ligands onin vitroandin vivomodels of COPD
Authors: Lea Simon , Plumb Jonathan , Metcalfe Hannah , Spicer Dianne , Woodman Paul , Fox J. Craig , Singh Dave 
Published: June 2013

Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in alveolar macrophages. The anti-inflammatory potential of the PPAR-γ ligands rosiglitazone and pioglitazone were investigated usingin vitroalveolar macrophage models andin vivoanimal models relevant to chronic obstructive pulmonary disease (COPD).PPAR-γ protein and gene expression in COPD alveolar macrophages was compared with control smokers and never-smokers. COPD macrophages were used to investigate the effects of PPAR-γ ligands and corticosteroids on lipopolysaccharide-induced cytokine production, alternative macrophage activation (M2) gene expression and efferocytosis. The effects of PPAR-γ ligands in a subchronic tobacco smoke model in mice were investigated.PPAR-γ protein expression was similar in COPD patients compared to controls, although increased gene expression levels were observed in COPD patients and control smokers compared to never-smokers. PPAR-γ ligands reduced tumour necrosis factor-α and CC chemokine ligand-5, but not CXC chemokine ligand-8, in COPD alveolar macrophages; these effects were generally less than those of the corticosteroid dexamethasone. Rosiglitazone increased M2 gene expression and enhanced efferocytosis of apoptotic neutrophils. Rosiglitazone and pioglitazone attenuated airway neutrophilia in a corticosteroid-resistant mouse model of pulmonary inflammation.We show biological actions of PPAR-γ agonists on corticosteroid-resistant disease, tobacco smoke-induced pulmonary inflammation, skewing of macrophage phenotype and clearance of apoptotic neutrophils.
Prediction of gene-phenotype associations in humans, mice, and plants using phenologs
Authors: Woods John O , Singh-Blom Ulf Martin , Laurent Jon M , McGary Kriston L , Marcotte Edward M 
Published: June 2013

Abstract

Background
Phenotypes and diseases may be related to seemingly dissimilar phenotypes in other species by means of the orthology of underlying genes. Such “orthologous phenotypes,” or “phenologs,” are examples of deep homology, and may be used to predict additional candidate disease genes.

Results
In this work, we develop an unsupervised algorithm for ranking phenolog-based candidate disease genes through the integration of predictions from the k nearest neighbor phenologs, comparing classifiers and weighting functions by cross-validation. We also improve upon the original method by extending the theory to paralogous phenotypes. Our algorithm makes use of additional phenotype data — from chicken, zebrafish, and E. coli, as well as new datasets for C. elegans — establishing that several types of annotations may be treated as phenotypes. We demonstrate the use of our algorithm to predict novel candidate genes for human atrial fibrillation (such as HRH2, ATP4A, ATP4B, and HOPX) and epilepsy (e.g., PAX6 and NKX2-1). We suggest gene candidates for pharmacologically-induced seizures in mouse, solely based on orthologous phenotypes from E. coli. We also explore the prediction of plant gene-phenotype associations, as for the Arabidopsis response to vernalization phenotype.

Conclusions
We are able to rank gene predictions for a significant portion of the diseases in the Online Mendelian Inheritance in Man database. Additionally, our method suggests candidate genes for mammalian seizures based only on bacterial phenotypes and gene orthology. We demonstrate that phenotype information may come from diverse sources, including drug sensitivities, gene ontology biological processes, and in situ hybridization annotations. Finally, we offer testable candidates for a variety of human diseases, plant traits, and other classes of phenotypes across a wide array of species.
The complete mitochondrial genomes of three parasitic nematodes of birds: a unique gene order and insights into nematode phylogeny
Authors: Liu Guo-Hua , Shao Renfu , Li Jia-Yuan , Zhou Dong-Hui , Li Hu , Zhu Xing-Quan 
Published: June 2013

Abstract

Background
Analyses of mitochondrial (mt) genome sequences in recent years challenge the current working hypothesis of Nematoda phylogeny proposed from morphology, ecology and nuclear small subunit rRNA gene sequences, and raise the need to sequence additional mt genomes for a broad range of nematode lineages.

Results
We sequenced the complete mt genomes of three Ascaridia species (family Ascaridiidae) that infest chickens, pigeons and parrots, respectively. These three Ascaridia species have an identical arrangement of mt genes to each other but differ substantially from other nematodes. Phylogenetic analyses of the mt genome sequences of the Ascaridia species, together with 62 other nematode species, support the monophylies of seven high-level taxa of the phylum Nematoda: 1) the subclass Dorylaimia; 2) the orders Rhabditida, Trichinellida and Mermithida; 3) the suborder Rhabditina; and 4) the infraorders Spiruromorpha and Oxyuridomorpha. Analyses of mt genome sequences, however, reject the monophylies of the suborders Spirurina and Tylenchina, and the infraorders Rhabditomorpha, Panagrolaimomorpha and Tylenchomorpha. Monophyly of the infraorder Ascaridomorpha varies depending on the methods of phylogenetic analysis. The Ascaridomorpha was more closely related to the infraorders Rhabditomorpha and Diplogasteromorpha (suborder Rhabditina) than they were to the other two infraorders of the Spirurina: Oxyuridorpha and Spiruromorpha. The closer relationship among Ascaridomorpha, Rhabditomorpha and Diplogasteromorpha was also supported by a shared common pattern of mitochondrial gene arrangement.

Conclusions
Analyses of mitochondrial genome sequences and gene arrangement has provided novel insights into the phylogenetic relationships among several major lineages of nematodes. Many lineages of nematodes, however, are underrepresented or not represented in these analyses. Expanding taxon sampling is necessary for future phylogenetic studies of nematodes with mt genome sequences.
Global transcriptome profiles of Camellia sinensis during cold acclimation
Authors: Wang Xin-Chao , Zhao Qiong-Yi , Ma Chun-Lei , Zhang Zong-Hong , Cao Hong-Li , Kong Yi-Meng , Yue Chuan , Hao Xin-Yuan , Chen Liang , Ma Jian-Qiang , Jin Ji-Qiang , Li Xuan , Yang Ya-Jun 
Published: June 2013

Abstract

Background
Tea is the most popular non-alcoholic health beverage in the world. The tea plant (Camellia sinensis (L.) O. Kuntze) needs to undergo a cold acclimation process to enhance its freezing tolerance in winter. Changes that occur at the molecular level in response to low temperatures are poorly understood in tea plants. To elucidate the molecular mechanisms of cold acclimation, we employed RNA-Seq and digital gene expression (DGE) technologies to the study of genome-wide expression profiles during cold acclimation in tea plants.

Results
Using the Illumina sequencing platform, we obtained approximately 57.35 million RNA-Seq reads. These reads were assembled into 216,831 transcripts, with an average length of 356 bp and an N50 of 529 bp. In total, 1,770 differentially expressed transcripts were identified, of which 1,168 were up-regulated and 602 down-regulated. These include a group of cold sensor or signal transduction genes, cold-responsive transcription factor genes, plasma membrane stabilization related genes, osmosensing-responsive genes, and detoxification enzyme genes. DGE and quantitative RT-PCR analysis further confirmed the results from RNA-Seq analysis. Pathway analysis indicated that the “carbohydrate metabolism pathway” and the “calcium signaling pathway” might play a vital role in tea plants’ responses to cold stress.

Conclusions
Our study presents a global survey of transcriptome profiles of tea plants in response to low, non-freezing temperatures and yields insights into the molecular mechanisms of tea plants during the cold acclimation process. It could also serve as a valuable resource for relevant research on cold-tolerance and help to explore the cold-related genes in improving the understanding of low-temperature tolerance and plant-environment interactions.
Ambushing the ambush hypothesis: predicting and evaluating off-frame codon frequencies in Prokaryotic Genomes
Authors: Morgens David W , Chang Charlotte H , Cavalcanti Andre RO 
Published: June 2013

Abstract

Background
In this paper, we address the evidence for the Ambush Hypothesis. Proposed by Seligmann and Pollock, this hypothesis posits that there exists a selection for off-frame stop codons (OSCs) to counteract the possible deleterious effects of translational frameshifts, including the waste of resources and potential cytotoxicity. Two main types of study have been used to support the hypothesis. Some studies analyzed codon usage and showed that codons with more potential to create OSCs seem to be favored over codons with lower potential; they used this finding to support the Ambush Hypothesis. Another study used 342 bacterial genomes to evaluate the hypothesis directly, finding significant excesses of OSCs in these genomes.

Results
We repeated both analyses with newer datasets and searched for other factors that could explain the observed trends. In the first case, the relative frequency of codons with the potential to create OSCs is directly correlated with the GC content of organisms, as stop codons are GC-poor. When evaluating the frequency of OSCs directly in 1,976 bacterial genomes we also detected a significant excess. However, when comparing the excess of OSCs with similarly obtained results for the frequency of out-of-frame sense codons, some sense codons have a more significant excess than stop codons.

Conclusions
Two avenues of study have been used to support the Ambush Hypothesis. Using the same methods as these previous studies, we demonstrate that the evidence in support of the Ambush Hypothesis does not hold up against more rigorous testing.
All-trans retinoic acid attenuates airway inflammation by inhibiting Th2 and Th17 response in experimental allergic asthma
Authors: Wu Jinhong , Zhang Yanjie , Liu Qi , Zhong Wenwei , Xia Zhenwei 
Published: June 2013

Abstract

Background
Airway inflammation is mainly mediated by T helper 2 cells (Th2) that characteristically produce interleukin (IL)-4, IL-5, and IL-13. Epidemiological studies have revealed an inverse association between the dietary intake of vitamin A and the occurrence of asthma. Serum vitamin A concentrations are significantly lower in asthmatic subjects than in healthy control subjects. It has been reported that all-trans retinoic acid (ATRA), a potent derivative of vitamin A, regulates immune responses. However, its role in Th2-mediated airway inflammation remains unclear. We investigated the effects of ATRA in a mouse model of allergic airway inflammation.

Results
We found that ATRA treatment attenuated airway inflammation and decreased mRNA levels of Th2- and Th17-related transcription factors. The data showed that airway inflammation coincided with levels of Th2- and Th17-related cytokines. We also showed that ATRA inhibited Th17 and promoted inducible regulatory T-cell differentiation, whereas it did not induce an obvious effect on Th2 differentiation in vitro. Our data suggest that ATRA may interfere with the in vivo Th2 responses via T-cell extrinsic mechanisms.

Conclusions
Administration of ATRA dramatically attenuated airway inflammation by inhibiting Th2 and Th17 differentiation and/or functions. ATRA may have potential therapeutic effects for airway inflammation in asthmatic patients.
Fetal brain genomic reprogramming following asphyctic preconditioning
Authors: Cox-Limpens Kimberly EM , Vles Johan SH , Schlechter Jana , Zimmermann Luc JI , Strackx Eveline , Gavilanes Antonio WD 
Published: June 2013

AbstractBackgroundFetal asphyctic (FA) preconditioning is effective in attenuating brain damage incurred by a subsequent perinatal asphyctic insult. Unraveling mechanisms of this endogenous neuroprotection, activated by FA preconditioning, is an important step towards new clinical strategies for asphyctic neonates. Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of preconditioning. Therefore we investigated whole genome differential gene expression in the preconditioned rat brain. FA preconditioning was induced on embryonic day 17 by reversibly clamping uterine circulation. Male control and FA offspring were sacrificed 96 h after FA preconditioning. Whole genome transcription was investigated with Affymetrix Gene1.0ST chip.ResultsData were analyzed with the Bioconductor Limma package, which showed 53 down-regulated and 35 up-regulated transcripts in the FA-group. We validated these findings with RT-qPCR foradh1,edn1,leptin,rdh2, andsmad6. Moreover, we investigated differences in gene expression across different brain regions. In addition, we performed Gene Set Enrichment Analysis (GSEA) which revealed 19 significantly down-regulated gene sets, mainly involved in neurotransmission and ion transport. 10 Gene sets were significantly up-regulated, these are mainly involved in nucleosomal structure and transcription, including genes such asmecp2.ConclusionsHere we identify for the first time differential gene expression after asphyctic preconditioning in fetal brain tissue, with the majority of differentially expressed transcripts being down-regulated. The observed down-regulation of cellular processes such as neurotransmission and ion transport could represent a restriction in energy turnover which could prevent energy failure and subsequent neuronal damage in an asphyctic event. Up-regulated transcripts seem to exert their function mainly within the cell nucleus, and subsequent Gene Set Enrichment Analysis suggests that epigenetic mechanisms play an important role in preconditioning induced neuroprotection.
Global end-diastolic volume increases to maintain fluid responsiveness in sepsis-induced systolic dysfunction
Authors: Trof Ronald J , Danad Ibrahim , Groeneveld AB Johan 
Published: June 2013

Abstract

Background
Sepsis-induced cardiac dysfunction may limit fluid responsiveness and the mechanism thereof remains unclear. Since cardiac function may affect the relative value of cardiac filling pressures, such as the recommended central venous pressure (CVP), versus filling volumes in guiding fluid loading, we studied these parameters as determinants of fluid responsiveness, according to cardiac function.

Methods
A delta CVP-guided, 90 min colloid fluid loading protocol was performed in 16 mechanically ventilated patients with sepsis-induced hypotension and three 30 min consecutive fluid loading steps of about 450 mL per patient were evaluated. Global end-diastolic volume index (GEDVI), cardiac index (CI) and global ejection fraction (GEF) were assessed from transpulmonary dilution. Baseline and changes in CVP and GEDVI were compared among responding (CI increase ≥10% and ≥15%) and non-responding fluid loading steps, in patient with low (<20%, n = 9) and near-normal (≥20%) GEF (n = 7) at baseline.

Results
A low GEF was in line with other indices of impaired cardiac (left ventricular) function, prior to and after fluid loading. Of 48 fluid loading steps, 9 (of 27) were responding when GEF <20% and 6 (of 21) when GEF ≥20. Prior to fluid loading, CVP did not differ between responding and non-responding steps and levels attained were 23 higher in the latter, regardless of GEF (P = 0.004). Prior to fluid loading, GEDVI (and CI) was higher in responding (1007 ± 306 mL/m2) than non-responding steps (870 ± 236 mL/m2) when GEF was low (P = 0.002), but did not differ when GEF was near-normal. Increases in GEDVI were associated with increases in CI and fluid responsiveness, regardless of GEF (P < 0.001).

Conclusions
As estimated from transpulmonary dilution, about half of patients with sepsis-induced hypotension have systolic cardiac dysfunction. During dysfunction, cardiac dilation with a relatively high baseline GEDVI maintains fluid responsiveness by further dilatation (increase in GEDVI rather than of CVP) as in patients without dysfunction. Absence of fluid responsiveness during systolic cardiac dysfunction may be caused by diastolic dysfunction and/or right ventricular dysfunction.