bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eplerenone in Patients With Systolic Heart Failure and Mild Symptoms
Authors: Rogers Jennifer K. , McMurray John J.V. , Pocock Stuart J. , Zannad Faiez , Krum Henry , van Veldhuisen Dirk J. , Swedberg Karl , Shi Harry , Vincent John , Pitt Bertram 
Published: October 2012

Background—
Eplerenone is known to reduce time to first hospitalization for heart failure or cardiovascular death in patients with heart failure and mild symptoms. In chronic diseases such as heart failure, characterized by repeat hospitalizations, analyzing all heart failure hospitalizations, not just the first, should give a more complete picture of treatment benefits.

Methods and Results—

The Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF) trial compared eplerenone with placebo in 2737 patients with mild heart failure, followed for a median 2.08 years (interquartile range, 1.08–3.10 years). Data were collected on all hospitalizations, with a focus on those due to heart failure. Heart failure hospitalization rates in the eplerenone and placebo groups were 10.70 and 16.99 per 100 patient-years, respectively. Allowing for skewness in the frequency of hospitalizations by using the negative binomial generalized linear model, the rate ratio (eplerenone versus placebo) was 0.53 (95% confidence interval, 0.42–0.66;
P
<0.0001). A plot of cumulative hospitalization rates over time revealed that most of the reduced risk on eplerenone occurred in the first year of follow-up. Several baseline variables strongly predicted the risk of hospitalization. More complex statistical methods, adjusting for mortality (as informative censoring), made a negligible difference in these findings.

Conclusions—
Eplerenone markedly reduces the risk of heart failure hospitalizations in patients with heart failure and mild symptoms to a greater extent than is captured by only studying the time to first hospitalization. Future clinical trials in heart failure would gain from incorporating repeat hospitalizations into their primary evaluation of treatment effects.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00232180.
Genetic Heritability of Ischemic Stroke and the Contribution of Previously Reported Candidate Gene and Genomewide Associations
Authors: Bevan Steve , Traylor Matthew , Adib-Samii Poneh , Malik Rainer , Paul Nicola L. M. , Jackson Caroline , Farrall Martin , Rothwell Peter M. , Sudlow Cathie , Dichgans Martin , Markus Hugh S. 
Published: October 2012

Background and Purpose—
The contribution of genetics to stroke risk, and whether this differs for different stroke subtypes, remainsuncertain. Genomewide complex trait analysis allows heritability to be assessed from genomewide association study (GWAS) data. Previous candidate gene studies have identified many associations with stoke but whether these are important requires replication in large independent data sets. GWAS data sets provide a powerful resource to perform replication studies.

Methods—
We applied genomewide complex trait analysis to a GWAS data set of 3752 ischemic strokes and 5972 controls and determined heritability for all ischemic stroke and the most common subtypes: large-vessel disease, small-vessel disease, and cardioembolic stroke. By systematic review we identified previous candidate gene and GWAS associations with stroke and previous GWAS associations with related cardiovascular phenotypes (myocardial infarction, atrial fibrillation, and carotid intima-media thickness). Fifty associations were identified.

Results—

For all ischemic stroke, heritability was 37.9%. Heritability varied markedly by stroke subtype being 40.3% for large-vessel disease and 32.6% for cardioembolic but lower for small-vessel disease (16.1%). No previously reported candidate gene was significant after rigorous correction for multiple testing. In contrast, 3 loci from related cardiovascular GWAS studies were significant:
PHACTR1
in large-vessel disease (
P
=2.63e
−6
),
PITX2
in cardioembolic stroke (
P
=4.78e
−8
), and
ZFHX3
in cardioembolic stroke (
P
=5.50e
−7
).

Conclusions—
There is substantial heritability for ischemic stroke, but this varies for different stroke subtypes. Previous candidate gene associations contribute little to this heritability, but GWAS studies in related cardiovascular phenotypes are identifying robust associations. The heritability data, and data from GWAS, suggest detecting additional associations will depend on careful stroke subtyping.
A Risk Score Based on Get With the Guidelines–Stroke Program Data Works in Patients With Acute Ischemic Stroke in China
Authors: Zhang Ning , Liu Gaifen , Zhang Guohua , Fang Jiming , Wang Yilong , Zhao Xingquan , Guo Li , Wang Yongjun 
Published: October 2012

Background and Purpose—
There are few validated models for prediction of in-hospital mortality after acute ischemic stroke. In 2010, Smith et al developed and internally validated models for predicting in-hospital mortality based on Get With the Guidelines–Stroke program data. We demonstrate the applicability of this Get With the Guidelines risk model in Chinese patients.

Methods—
The prognostic model was used to predict survival in 7015 patients with acute ischemic stroke from China National Stroke Registry data set. Model discrimination was quantified by calculating C statistic. To clarify the role of National Institutes of Health Stroke Scale (NIHSS), we also calculated the C statistics for NIHSS alone and for the model without NIHSS.

Results—

The C statistic was 0.867 (95% CI, 0.839–0.895) through the Get With the Guidelines risk model, suggesting good discrimination in the China National Stroke Registry. The model without NIHSS produced significantly lower C statistic (0.735; 95% CI, 0.701–0.770;
P
<0.001), indicating the important role of NIHSS in the prediction of survival. Furthermore, a model with NIHSS alone also provided significant discrimination (C statistic, 0.847; 95% CI, 0.816–0.879). A plot of observed versus predicted mortality showed excellent model calibration in the external validation sample from the China National Stroke Registry.

Conclusions—
The Get With the Guidelines risk model could correctly predict in-hospital mortality in Chinese patients with ischemic stroke. In addition, the NIHSS provides substantial incremental information on a patient’s short-term mortality risk and is the strongest predictor of mortality.
The Optimality of Potential Rescaling Approaches in Land Data Assimilation
Authors: Yilmaz M. Tugrul , Crow Wade T. 
Published: October 2012

AbstractIt is well known that systematic differences exist between modeled and observed realizations of hydrological variables like soil moisture. Prior to data assimilation, these differences must be removed in order to obtain an optimal analysis. A number of rescaling approaches have been proposed for this purpose. These methods include rescaling techniques based on matching sampled temporal statistics, minimizing the least squares distance between observations and models, and the application of triple collocation. Here, the authors evaluate the optimality and relative performances of these rescaling methods both analytically and numerically and find that a triple collocation–based rescaling method results in an optimal solution, whereas variance matching and linear least squares regression approaches result in only approximations to this optimal solution.
Development and Evaluation of the DECIDE to Move! Physical Activity Educational Video
Authors: Majid Haseeb M. , Schumann Kristina P. , Doswell Angela , Sutherland June , Hill Golden Sherita , Stewart Kerry J. , Hill-Briggs Felicia 
Published: October 2012

Purpose To develop a video that provides accessible and usable information about the importance of physical activity to type 2 diabetes self-management and ways of incorporating physical activity into everyday life. Conclusion A 15-minute physical activity educational video narrated by US Surgeon General Dr Regina Benjamin was developed and evaluated. The video addresses the following topics: the effects of exercise on diabetes, preparations for beginning physical activity, types of physical activity, safety considerations (eg, awareness of symptoms of hypoglycemia during activity), and goal setting. Two patient screening groups were held for evaluation and revision of the video. Patient satisfaction ratings ranged 4.6 to 4.9 out of a possible 5.0 on dimensions of overall satisfaction, how informative they found the video to be, how well the video held their interest and attention, how easy the video was to understand, and how easy the video was to see and hear. Patients reported the educational video effective in empowering them to take strides toward increasing and maintaining physical activity in their lives. The tool is currently used in a clinical research trial, Project DECIDE, as one component of a diabetes and cardiovascular disease self-management program.
Systematic Review of Effects of Adenotonsillectomy on Cardiovascular Parameters in Children with Obstructive Sleep Apnea
Authors: Teo Dawn T. , Mitchell Ron B. 
Published: October 2012

ObjectiveTo systematically review current studies on the effects of adenotonsillectomy (T&A) for obstructive sleep apnea (OSA) on cardiovascular parameters in children.Data SourcesPubMed database.Review MethodsA comprehensive PubMed MeSH search was done between 1970 and 2012.ResultsFourteen articles were included. The total number of children was 418. The mean sample size was 30 (range, 1‐62), and the mean age of the sample population was 6 years (range, 2‐10 years). Criteria used for the diagnosis of OSA ranged from full‐night polysomnography (PSG) to clinical parameters. Three studies had results from preoperative and postoperative PSG. Cardiovascular parameters studied included blood pressure, heart rate, cardiac morphology, and cardiac function. All studies reported an improvement in cardiovascular parameters and OSA symptoms after surgery. Three studies reported improvement in blood pressure, 6 reported improvement in mean pulmonary artery pressures, 7 reported improvement in echocardiographic findings, and 1 reported a decrease in pulse rate and pulse rate variability after T&A for OSA.ConclusionThere is evidence that cardiovascular morbidities associated with OSA are potentially reversible. T&A may have a significant role in reversing the cardiovascular sequelae of OSA. However, there is a paucity of well‐designed and powered studies to address this issue.
The Challenge of the Object – the CIHA Congress 2012 in Nuremberg
Authors: Grossmann G. Ulrich 
Published: October 2012

AbstractFor the first time since 1871, the International Art History Congress was held on invitation at a museum. From the 15th to the 20th of July, 2012 the “Object” has been the focus of 21 sections and up to 400 lectures. The aim of the Congress was to discuss and redefine the object’s role and meaning as a basis and subject matter of art history.Today’s media not only facilitates worldwide communication, but also the “virtualisation” of art history. What consequences does this have for the object itself? What chance and what risks ensue in the virtualisation of our profession? In addition to the virtualisation, we are also experiencing the extraordinary effect of the object itself. Long queues of visitors form to view one piece of art. During war, artworks are protected by international conventions, in particular the amount of damage they are exposed to. Ruined world-heritage sites, and also artwork that is taken hostage, belong to daily politics (looted art).Up until now, art history has, notably in Europe, had European artwork in focus. Non-European art was often measured with other criterion. Methodical comparative research of artwork from different lands is sensible. How can such research be conducted in the future? Is there a line between a “High Culture”, in which art history is interested, and “Folk Culture”, toward which ethnology strives?The sections of the 33rd International Art History Congress are structured around the questions in the dealings and the roles of the object, not on categories, epochs or continents. The fundamental approach of art history research of an object is not dependent on category, age or land of origin. We want, therefore, to compare and correlate similar questions and developments in cooperation with the different cultures, and determine the role of the object in the future of art history.
Evolution of transcriptional regulation in closely related bacteria
Authors: Tsoy Olga V , Pyatnitskiy Mikhail A , Kazanov Marat D , Gelfand Mikhail S 
Published: October 2012

Abstract

Background
The exponential growth of the number of fully sequenced genomes at varying taxonomic closeness allows one to characterize transcriptional regulation using comparative-genomics analysis instead of time-consuming experimental methods. A transcriptional regulatory unit consists of a transcription factor, its binding site and a regulated gene. These units constitute a graph which contains so-called “network motifs”, subgraphs of a given structure. Here we consider genomes of closely related Enterobacteriales and estimate the fraction of conserved network motifs and sites as well as positions under selection in various types of non-coding regions.

Results
Using a newly developed technique, we found that the highest fraction of positions under selection, approximately 50%, was observed in synvergon spacers (between consecutive genes from the same strand), followed by ~45% in divergon spacers (common 5’-regions), and ~10% in convergon spacers (common 3’-regions). The fraction of selected positions in functional regions was higher, 60% in transcription factor-binding sites and ~45% in terminators and promoters. Small, but significant differences were observed between Escherichia coli and Salmonella enterica. This fraction is similar to the one observed in eukaryotes.
The conservation of binding sites demonstrated some differences between types of regulatory units. In E. coli, strains the interactions of the type “local transcriptional factor ➝ gene” turned out to be more conserved in feed-forward loops (FFLs) compared to non-motif interactions. The coherent FFLs tend to be less conserved than the incoherent FFLs. A natural explanation is that the former imply functional redundancy.

Conclusions
A naïve hypothesis that FFL would be highly conserved turned out to be not entirely true: its conservation depends on its status in the transcriptional network and also from its usage. The fraction of positions under selection in intergenic regions of bacterial genomes is roughly similar to that of eukaryotes. Known regulatory sites explain 20±5% of selected positions.
Complete genome sequence and metabolic potential of the quinaldine-degrading bacterium Arthrobacter sp. Rue61a
Authors: Niewerth Heiko , Schuldes Jörg , Parschat Katja , Kiefer Patrick , Vorholt Julia A , Daniel Rolf , Fetzner Susanne 
Published: October 2012

Abstract

Background
Bacteria of the genus Arthrobacter are ubiquitous in soil environments and can be considered as true survivalists. Arthrobacter sp. strain Rue61a is an isolate from sewage sludge able to utilize quinaldine (2-methylquinoline) as sole carbon and energy source. The genome provides insight into the molecular basis of the versatility and robustness of this environmental Arthrobacter strain.

Results
The genome of Arthrobacter sp. Rue61a consists of a single circular chromosome of 4,736,495 bp with an average G + C content of 62.32%, the circular 231,551-bp plasmid pARUE232, and the linear 112,992-bp plasmid pARUE113 that was already published. Plasmid pARUE232 is proposed to contribute to the resistance of Arthrobacter sp. Rue61a to arsenate and Pb2+, whereas the linear plasmid confers the ability to convert quinaldine to anthranilate. Remarkably, degradation of anthranilate exclusively proceeds via a CoA-thioester pathway. Apart from quinaldine utilization, strain Rue61a has a limited set of aromatic degradation pathways, enabling the utilization of 4-hydroxy-substituted aromatic carboxylic acids, which are characteristic products of lignin depolymerization, via ortho cleavage of protocatechuate. However, 4-hydroxyphenylacetate degradation likely proceeds via meta cleavage of homoprotocatechuate. The genome of strain Rue61a contains numerous genes associated with osmoprotection, and a high number of genes coding for transporters. It encodes a broad spectrum of enzymes for the uptake and utilization of various sugars and organic nitrogen compounds. A. aurescens TC-1 is the closest sequenced relative of strain Rue61a.

Conclusions
The genome of Arthrobacter sp. Rue61a reflects the saprophytic lifestyle and nutritional versatility of the organism and a strong adaptive potential to environmental stress. The circular plasmid pARUE232 and the linear plasmid pARUE113 contribute to heavy metal resistance and to the ability to degrade quinaldine, respectively.
GeneFriends: An online co-expression analysis tool to identify novel gene targets for aging and complex diseases
Authors: van Dam Sipko , Cordeiro Rui , Craig Thomas , van Dam Jesse , Wood Shona H , de Magalhães João Pedro 
Published: October 2012

AbstractBackgroundAlthough many diseases have been well characterized at the molecular level, the underlying mechanisms are often unknown. Nearly half of all human genes remain poorly studied, yet these genes may contribute to a number of disease processes. Genes involved in common biological processes and diseases are often co-expressed. Using known disease-associated genes in a co-expression analysis may help identify and prioritize novel candidate genes for further study.ResultsWe have created an online tool, called GeneFriends, which identifies co-expressed genes in over 1,000 mouse microarray datasets. GeneFriends can be used to assign putative functions to poorly studied genes. Using a seed list of disease-associated genes and a guilt-by-association method, GeneFriends allows users to quickly identify novel genes and transcription factors associated with a disease or process. We tested GeneFriends using seed lists for aging, cancer, and mitochondrial complex I disease. We identified several candidate genes that have previously been predicted as relevant targets. Some of the genes identified are already being tested in clinical trials, indicating the effectiveness of this approach. Co-expressed transcription factors were investigated, identifying C/ebp genes as candidate regulators of aging. Furthermore, several novel candidate genes, that may be suitable for experimental or clinical follow-up, were identified. Two of the novel candidates of unknown function that were co-expressed with cancer-associated genes were selected for experimental validation. Knock-down of their human homologs (C1ORF112 and C12ORF48) in HeLa cells slowed growth, indicating that these genes of unknown function, identified by GeneFriends, may be involved in cancer.ConclusionsGeneFriends is a resource for biologists to identify and prioritize novel candidate genes involved in biological processes and complex diseases. It is an intuitive online resource that will help drive experimentation. GeneFriends is available online at:http://genefriends.org/.
Effect of sample stratification on dairy GWAS results
Authors: Ma Li , Wiggans George R , Wang Shengwen , Sonstegard Tad S , Yang Jing , Crooker Brian A , Cole John B , Van Tassell Curtis P , Lawlor Thomas J , Da Yang 
Published: October 2012

Abstract

Background
Artificial insemination and genetic selection are major factors contributing to population stratification in dairy cattle. In this study, we analyzed the effect of sample stratification and the effect of stratification correction on results of a dairy genome-wide association study (GWAS). Three methods for stratification correction were used: the efficient mixed-model association expedited (EMMAX) method accounting for correlation among all individuals, a generalized least squares (GLS) method based on half-sib intraclass correlation, and a principal component analysis (PCA) approach.

Results
Historical pedigree data revealed that the 1,654 contemporary cows in the GWAS were all related when traced through approximately 10–15 generations of ancestors. Genome and phenotype stratifications had a striking overlap with the half-sib structure. A large elite half-sib family of cows contributed to the detection of favorable alleles that had low frequencies in the general population and high frequencies in the elite cows and contributed to the detection of X chromosome effects. All three methods for stratification correction reduced the number of significant effects. EMMAX method had the most severe reduction in the number of significant effects, and the PCA method using 20 principal components and GLS had similar significance levels. Removal of the elite cows from the analysis without using stratification correction removed many effects that were also removed by the three methods for stratification correction, indicating that stratification correction could have removed some true effects due to the elite cows. SNP effects with good consensus between different methods and effect size distributions from USDA’s Holstein genomic evaluation included the DGAT1-NIBP region of BTA14 for production traits, a SNP 45kb upstream from PIGY on BTA6 and two SNPs in NIBP on BTA14 for protein percentage. However, most of these consensus effects had similar frequencies in the elite and average cows.

Conclusions
Genetic selection and extensive use of artificial insemination contributed to overlapped genome, pedigree and phenotype stratifications. The presence of an elite cluster of cows was related to the detection of rare favorable alleles that had high frequencies in the elite cluster and low frequencies in the remaining cows. Methods for stratification correction could have removed some true effects associated with genetic selection.
Excessive daytime sleepiness assessed by the Epworth Sleepiness Scale and its association with health related quality of life: a population-based study in China
Authors: Wu Shunquan , Wang Rui , Ma Xiuqiang , Zhao Yanfang , Yan Xiaoyan , He Jia 
Published: October 2012

Abstract

Background
Excessive daytime sleepiness (EDS) is a common condition worldwide that has many negative effects on people who were afflicted with it, especially on their health-related quality of life (HRQOL). The Epworth Sleepiness Scale (ESS) is a commonly used method for evaluating EDS in English-speaking countries. This paper reported the prevalence of subjective EDS in China as assessed by the Mandarin version of the ESS; tested the scale’s response rate, reliability and validity; and investigated the relationship between ESS scores and HRQOL.

Methods
A population-based sample of 3600 residents was selected randomly in five cities in China. The demographic information was collected, subjective EDS was assessed by the Mandarin version of the ESS (ESS scores >10), and HRQOL was evaluated by the Mandarin version of the 36-item Short Form Health Survey (SF-36).

Results
The Mandarin version of ESS had very few missing responses, and the average response rate of its eight items was 97.92%. The split-half reliability coefficient and Cronbach’s α coefficient were 0.81 and 0.80, respectively. One factor was identified by factor analysis with an eigenvalue of 2.78. The ESS scores showed positive skewness in the selected sample, with a median (Q1, Q3) of 6 (3, 0). 644 (22.16%) respondents reported subjective EDS, and all of the scores of the eight dimensions of the SF-36 were negatively correlated with ESS scores.

Conclusions
The Mandarin version of ESS is an acceptable, reliable, and valid tool for measuring EDS. In addition, subjective EDS is common in China, based on the ESS results, and impairs HRQOL.