bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood volume-monitored regulation of ultrafiltration in fluid-overloaded hemodialysis patients: study protocol for a randomized controlled trial
Authors: Hecking Manfred , Antlanger Marlies , Winnicki Wolfgang , Reiter Thomas , Werzowa Johannes , Haidinger Michael , Weichhart Thomas , Polaschegg Hans-Dietrich , Josten Peter , Exner Isabella , Lorenz-Turnheim Katharina , Eigner Manfred , Paul Gernot , Klauser-Braun Renate , Hörl Walter H , Sunder-Plassmann Gere , Säemann Marcus D 
Published: June 2012

Abstract

Background
Data generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients.

Methods/design
BCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, ‘final’ dry weight is set to normohydration weight −7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters).

Discussion
Patients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients.

Trial registration
ClinicalTrials.gov, NCT01416753
Pulsed electromagnetic fields for the treatment of tibial delayed unions and nonunions. A prospective clinical study and review of the literature
Authors: Assiotis Aggelos , Sachinis Nick P , Chalidis Byron E 
Published: June 2012

AbstractBackgroundPulsed electromagnetic fields (PEMF) stimulation for the treatment of bone nonunion or delayed union have been in use for several years, but on a limited basis. The aim of this study was to assess the overall efficacy of the method in tibial delayed unions and nonunions and identify factors that could affect the final outcome.MethodsWe prospectively reviewed 44 patients (27 men) with a mean age of 49.6 ± 18.4 years that received PEMF therapy due to tibial shaft delayed union or nonunion. In all cases, fracture gap was less than 1 cm and infection or soft tissue defects were absent.ResultsFracture union was confirmed in 34 cases (77.3%). No relationship was found between union rate and age (p = 0.819), fracture side (left or right) (p = 0.734), fracture type (simple or comminuted, open or closed) (p = 0.111), smoking (p = 0.245), diabetes (p = 0.68) and initial treatment method applied (plates, nail, plaster of paris) (p = 0.395). The time of treatment onset didn’t affect the incidence of fracture healing (p = 0.841). Although statistical significance was not demonstrated, longer treatment duration showed a trend of increased probability of union (p = 0.081).ConclusionPEMF stimulation is an effective non-invasive method for addressing non-infected tibial union abnormalities. Its success is not associated with specific fracture or patient related variables and it couldn’t be clearly considered a time-dependent phenomenon.
Normal sulfation levels regulate spinal cord neural precursor cell proliferation and differentiation
Authors: Karus Michael , Samtleben Samira , Busse Claudia , Tsai Teresa , Dietzel Irmgard D , Faissner Andreas , Wiese Stefan 
Published: June 2012

Abstract

Background
Sulfated glycosaminoglycan chains are known for their regulatory functions during neural development and regeneration. However, it is still unknown whether the sulfate residues alone influence, for example, neural precursor cell behavior or whether they act in concert with the sugar backbone. Here, we provide evidence that the unique 473HD-epitope, a representative chondroitin sulfate, is expressed by spinal cord neural precursor cells in vivo and in vitro, suggesting a potential function of sulfated glycosaminoglycans for spinal cord development.

Results
Thus, we applied the widely used sulfation inhibitor sodium chlorate to analyze the importance of normal sulfation levels for spinal cord neural precursor cell biology in vitro. Addition of sodium chlorate to spinal cord neural precursor cell cultures affected cell cycle progression accompanied by changed extracellular signal-regulated kinase 1 or 2 activation levels. This resulted in a higher percentage of neurons already under proliferative conditions. In contrast, the relative number of glial cells was largely unaffected. Strikingly, both morphological and electrophysiological characterization of neural precursor cell-derived neurons demonstrated an attenuated neuronal maturation in the presence of sodium chlorate, including a disturbed neuronal polarization.

Conclusions
In summary, our data suggest that sulfation is an important regulator of both neural precursor cell proliferation and maturation of the neural precursor cell progeny in the developing mouse spinal cord.
Batch correction of microarray data substantially improves the identification of genes differentially expressed in Rheumatoid Arthritis and Osteoarthritis
Authors: Kupfer Peter , Guthke Reinhard , Pohlers Dirk , Huber Rene , Koczan Dirk , Kinne Raimund W 
Published: June 2012

Abstract

Background
Batch effects due to sample preparation or array variation (type, charge, and/or platform) may influence the results of microarray experiments and thus mask and/or confound true biological differences. Of the published approaches for batch correction, the algorithm “Combating Batch Effects When Combining Batches of Gene Expression Microarray Data” (ComBat) appears to be most suitable for small sample sizes and multiple batches.

Methods
Synovial fibroblasts (SFB; purity > 98%) were obtained from rheumatoid arthritis (RA) and osteoarthritis (OA) patients (n = 6 each) and stimulated with TNF-α or TGF-β1 for 0, 1, 2, 4, or 12 hours. Gene expression was analyzed using Affymetrix Human Genome U133 Plus 2.0 chips, an alternative chip definition file, and normalization by Robust Multi-Array Analysis (RMA). Data were batch-corrected for different acquiry dates using ComBat and the efficacy of the correction was validated using hierarchical clustering.

Results
In contrast to the hierarchical clustering dendrogram before batch correction, in which RA and OA patients clustered randomly, batch correction led to a clear separation of RA and OA. Strikingly, this applied not only to the 0 hour time point (i.e., before stimulation with TNF-α/TGF-β1), but also to all time points following stimulation except for the late 12 hour time point. Batch-corrected data then allowed the identification of differentially expressed genes discriminating between RA and OA. Batch correction only marginally modified the original data, as demonstrated by preservation of the main Gene Ontology (GO) categories of interest, and by minimally changed mean expression levels (maximal change 4.087%) or variances for all genes of interest. Eight genes from the GO category “extracellular matrix structural constituent” (5 different collagens, biglycan, and tubulointerstitial nephritis antigen-like 1) were differentially expressed between RA and OA (RA > OA), both constitutively at time point 0, and at all time points following stimulation with either TNF-α or TGF-β1.

Conclusion
Batch correction appears to be an extremely valuable tool to eliminate non-biological batch effects, and allows the identification of genes discriminating between different joint diseases. RA-SFB show an upregulated expression of extracellular matrix components, both constitutively following isolation from the synovial membrane and upon stimulation with disease-relevant cytokines or growth factors, suggesting an “imprinted” alteration of their phenotype.
Visually integrating and exploring high throughput Phenome-Wide Association Study (PheWAS) results using PheWAS-View
Authors: Pendergrass Sarah A , Dudek Scott M , Crawford Dana C , Ritchie Marylyn D 
Published: June 2012

Abstract

Background
Phenome-Wide Association Studies (PheWAS) can be used to investigate the association between single nucleotide polymorphisms (SNPs) and a wide spectrum of phenotypes. This is a complementary approach to Genome Wide Association studies (GWAS) that calculate the association between hundreds of thousands of SNPs and one or a limited range of phenotypes. The extensive exploration of the association between phenotypic structure and genotypic variation through PheWAS produces a set of complex and comprehensive results. Integral to fully inspecting, analysing, and interpreting PheWAS results is visualization of the data.

Results
We have developed the software PheWAS-View for visually integrating PheWAS results, including information about the SNPs, relevant genes, phenotypes, and the interrelationships between phenotypes, that exist in PheWAS. As a result both the fine grain detail as well as the larger trends that exist within PheWAS results can be elucidated.

Conclusions
PheWAS can be used to discover novel relationships between SNPs, phenotypes, and networks of interrelated phenotypes; identify pleiotropy; provide novel mechanistic insights; and foster hypothesis generation – and these results can be both explored and presented with PheWAS-View. PheWAS-View is freely available for non-commercial research institutions, for full details see http://ritchielab.psu.edu/ritchielab/software.
The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines
Authors: Sanvictores Diozele Hazel M , Lucero Marilla G , Nohynek Hanna , Tallo Veronica L , Tanskanen Antti , Nillos Leilani T , Williams Gail ,   and the ARIVAC Consortium
Published: June 2012

Abstract

Background
A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted.

Results
We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently.

Conclusions
There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff.

Trial registration
Current Controlled Trials ISRCTN62323832
A method for improved clustering and classification of microscopy images using quantitative co-localization coefficients
Authors: Singan Vasanth R , Handzic Kenan , Curran Kathleen M , Simpson Jeremy C 
Published: June 2012

Abstract

Background
The localization of proteins to specific subcellular structures in eukaryotic cells provides important information with respect to their function. Fluorescence microscopy approaches to determine localization distribution have proved to be an essential tool in the characterization of unknown proteins, and are now particularly pertinent as a result of the wide availability of fluorescently-tagged constructs and antibodies. However, there are currently very few image analysis options able to effectively discriminate proteins with apparently similar distributions in cells, despite this information being important for protein characterization.

Findings
We have developed a novel method for combining two existing image analysis approaches, which results in highly efficient and accurate discrimination of proteins with seemingly similar distributions. We have combined image texture-based analysis with quantitative co-localization coefficients, a method that has traditionally only been used to study the spatial overlap between two populations of molecules. Here we describe and present a novel application for quantitative co-localization, as applied to the study of Rab family small GTP binding proteins localizing to the endomembrane system of cultured cells.

Conclusions
We show how quantitative co-localization can be used alongside texture feature analysis, resulting in improved clustering of microscopy images. The use of co-localization as an additional clustering parameter is non-biased and highly applicable to high-throughput image data sets.
Microarray Я US: a user-friendly graphical interface to Bioconductor tools that enables accurate microarray data analysis and expedites comprehensive functional analysis of microarray results
Authors: Dai Yilin , Guo Ling , Li Meng , Chen Yi-Bu 
Published: June 2012

Abstract

Background
Microarray data analysis presents a significant challenge to researchers who are unable to use the powerful Bioconductor and its numerous tools due to their lack of knowledge of R language. Among the few existing software programs that offer a graphic user interface to Bioconductor packages, none have implemented a comprehensive strategy to address the accuracy and reliability issue of microarray data analysis due to the well known probe design problems associated with many widely used microarray chips. There is also a lack of tools that would expedite the functional analysis of microarray results.

Findings
We present Microarray Я US, an R-based graphical user interface that implements over a dozen popular Bioconductor packages to offer researchers a streamlined workflow for routine differential microarray expression data analysis without the need to learn R language. In order to enable a more accurate analysis and interpretation of microarray data, we incorporated the latest custom probe re-definition and re-annotation for Affymetrix and Illumina chips. A versatile microarray results output utility tool was also implemented for easy and fast generation of input files for over 20 of the most widely used functional analysis software programs.

Conclusion
Coupled with a well-designed user interface, Microarray Я US leverages cutting edge Bioconductor packages for researchers with no knowledge in R language. It also enables a more reliable and accurate microarray data analysis and expedites downstream functional analysis of microarray results.
Delivery type not associated with global methylation at birth
Authors: Virani Shama , Dolinoy Dana C , Halubai Sindhu , Jones Tamara R , Domino Steve E , Rozek Laura S , Nahar Muna S , Padmanabhan Vasantha 
Published: June 2012

Abstract

Background
Birth by cesarean delivery (CD) as opposed to vaginal delivery (VD) is associated with altered health outcomes later in life, including respiratory disorders, allergies and risk of developing type I diabetes. Epigenetic gene regulation is a proposed mechanism by which early life exposures affect later health outcomes. Previously, type of delivery has been found to be associated with differences in global methylation levels, but the sample sizes have been small. We measured global methylation in a large birth cohort to identify whether type of delivery is associated with epigenetic changes.

Methods
DNA was isolated from cord blood collected from the University of Michigan Women’s & Children Hospital and bisulfite-converted. The Luminometric Methylation Assay (LUMA) and LINE-1 methylation assay were run on all samples in duplicate.

Results
Global methylation data at CCGG sites throughout the genome, as measured by LUMA, were available from 392 births (52% male; 65% CD), and quantitative methylation levels at LINE-1 repetitive elements were available for 407 births (52% male; 64% CD). LUMA and LINE-1 methylation measurements were negatively correlated in this population (Spearman’s r = −0.13, p =0.01). LUMA measurements were significantly lower for total CD and planned CD, but not emergency CD when compared to VD (median VD = 74.8, median total CD = 74.4, p = 0.03; median planned CD = 74.2, p = 0.02; median emergency CD = 75.3, p = 0.39). However, this association did not persist when adjusting for maternal age, maternal smoking and infant gender. Furthermore, total CD deliveries, planned CD and emergency CD deliveries were not associated with LINE-1 measurements as compared to VD (median VD = 82.2, median total CD = 81.9, p = 0.19; median planned CD = 81.9, p = 0.19; median emergency CD = 82.1, p = 0.52). This lack of association held when adjusting for maternal age, maternal smoking and infant gender in a multivariable model.

Conclusions
Type of delivery was not associated with global methylation in our population, even after adjustment for maternal age, maternal smoking, and infant gender. While type of birth may be associated with later health outcomes, our data suggest that it does not do so through changes in global genomic methylation.
Locusts use a composite of resilin and hard cuticle as an energy store for jumping and kicking
Authors: Burrows Malcolm , Sutton Gregory P 
Published: June 2012

SummaryLocusts jump and kick by using a catapult mechanism in which energy is first stored and then rapidly released to extend the large hind legs. The power is produced by a slow contraction of large muscles in the hind femora that bend paired semi-lunar processes in the distal part of each femur and store half the energy needed for a kick. We now show that these energy storage devices are composites of hard cuticle and the rubber-like protein resilin. The inside surface of a semi-lunar process consists of a layer of resilin, particularly thick along an inwardly pointing ridge and tightly bonded to the external, tanned, black cuticle. From the outside, resilin is visible only as a distal and ventral triangular area that tapers proximally. To reproduce the bending of the semi-lunar processes that occurs during kicking and jumping, the extensor tibiae muscle was stimulated electrically in a pattern that mimicked the normal sequence of its fast motor spikes recorded in natural kicking. Externally visible resilin was compressed and wrinkled as a semi-lunar process was bent by the muscular contraction without moving the hind leg. It then sprung back to restore the semi-lunar process rapidly to its natural shape. Each nymphal stages jumped and kicked and had a similar distribution of resilin in their semi-lunar processes as adults; the resilin was shed with the cuticle at each moult. It is suggested that composite storage devices that combine the elastic properties of resilin with the stiffness of hard cuticle, allow energy to be stored by bending hard cuticle by only a small amount and without fracturing. In this way all the stored energy is returned and the natural shape of the femur is restored rapidly so that a jump or kick can be repeated.
The neural and peptidergic control of gut contraction in Locusta migratoria: the effect of an FGLa/AST
Authors: Robertson Lisa , Rodriguez E. Patricia , Lange Angela B. 
Published: June 2012

Summary
The regulation of insect gut physiology is complex and involves the interactions of a number of mechanisms, including the neural regulation of gut contraction by altering neural input and the modulation of gut contractions by neuropeptides directly affecting the muscle. The FGLa-type allatostatins (FGLa/ASTs) are known brain/gut peptides with numerous physiological roles, including modulation of gut contraction and neural input. To further investigate the pleiotropic roles of FGLa/AST peptides in Locusta migratoria, we have examined the role of a locust FGLa/AST (Scg-AST-6) in the gut. Proctolin and Scg-AST-6 have opposing effects on gut contraction, where proctolin dose-dependently increases gut muscle tension, while Scg-AST-6 inhibits both muscle tension and spontaneous and neurogenic contractions in a dose-dependent manner. Results from neurophysiological recordings indicate that there may be a central pattern generator (CPG) within the ventricular ganglia regulated by descending inhibition, and the addition of Scg-AST-6 dose-dependently modulates this ventricular ganglion CPG. This work provides a comprehensive picture of how FGLa/ASTs may modulate and coordinate each region of the locust gut, and shows that FGLa/ASTs have both central effects, on the ventricular ganglion CPG, and peripheral effects on the gut muscle. Overall, this work shows how FGLa/ASTs contribute to the complex regulation and fine tuning of gut contraction.
Rhombohedral-Orthorhombic Phase Transition Induced Enhancement on the Electrical Behavior of (K0.5Na0.5)NbO3-BiScO3-BiCoO3 Lead-free Piezoelectric Ceramics
Authors: Wu Wenjuan , Xiao Dingquan , Wu Jiagang , Li Jing , Liang Wenfeng , Zhu Jianguo 
Published: June 2012

ABSTRACT(1-x)K0.5Na0.5NbO3-x(0.97BiScO3-0.03BiCoO3) (KNN-xBSC) piezoelectric ceramics were prepared by the conventional solid-state method, and effects of the BSC addition on the phase structure, relaxor behavior, and electrical properties of KNN ceramics were systematically investigated. The rhombohedral to orthorhombic phase transition around room temperature was identified for the KNN-xBSC ceramics in the composition range of 0.015≤ x ≤0.0175, and improved electrical properties (d33∼205 pC/N, kp∼0.43, εr∼1315, and tan δ∼0.054) were observed for the ceramic with x=0.015 because of the involvement of such a phase transition at room temperature. Moreover, a relaxor ferroelectric behavior is demonstrated for these KNN-xBSC ceramics because of a more complex occupation of A and B sites in the ABO3 perovskite structure, together with a weak ferromagnetic order at room temperature.