bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of the fish oil inhibition of stenosis in hemodialysis grafts (FISH) study
Authors: Lok Charmaine E. , Allon Michael , Donnelly Sandra , Dorval Marc , Hemmelgarn Brenda , Moist Louise , Oliver Matthew J. , Tonelli Marcello , Stanley Kenneth 
Published: September 2007

Background Arteriovenous grafts (AVG) are the predominant form of permanent vascular access used among hemodialysis (HD) patients in North America but suffer from high intervention and complication rates associated with vascular stenosis. The fish oil inhibition of stenosis in hemodialysis grafts (FISH) study evaluates the efficacy of fish oil in improving HD graft patency. Methods This study is a multi-center, randomized, double blind placebo-controlled clinical trial of 232 chronic HD patients who require a new graft access. Participants are randomized to fish oil versus placebo post-operatively. The primary endpoint is the proportion of AVG with loss of native patency within 12 months of creation. Secondary endpoints are aimed to determine the effect of fish oil on factors that may promote stenosis and thrombosis. Cumulative patency rates, survival analysis, and analysis of inflammatory markers and adverse events will provide a better understanding of the potential effect of fish oil on a patient's vascular access and cardiovascular system. The FISH study is registered at current controlled trials (www.controlled-trials.com) ISRCTN: 15838383. Results Details of the study protocol are described including mechanisms of reducing bias through randomization and double blinding, sample size determination, evaluation of patient adherence, access monitoring, and the safety of using fish oil. The main challenges of designing and implementing this study, including using a natural supplement as an intervention in modern medical practice and recruitment of graft recipients in the `fistula first' environment are discussed. Conclusion This is the first large, multicenter, randomized controlled trial of a natural supplement in preventing HD graft stenosis and thrombosis. Clinical Trials 2007; 4: 357—367. http://ctj.sagepub.com
Applying the law of iterated logarithm to control type I error in cumulative meta-analysis of binary outcomes
Authors: Hu Mingxiu , Cappelleri Joseph C , Lan K K Gordon 
Published: September 2007

Background Cumulative meta-analysis typically involves performing an updated meta-analysis every time when new trials are added to a series of similar trials, which by definition involves multiple inspections. Neither the commonly used random effects model nor the conventional group sequential method can control the type I error for many practical situations. In our previous research, Lan et al. (Lan KKG, Hu M-X, Cappelleri JC. Applying the law of iterated logarithm to cumulative meta-analysis of a continuous endpoint. Statistica Sinica 2003; 13: 1135—45) proposed an approach based on the law of iterated logarithm (LIL) to this problem for the continuous case. Purpose The study is an extension and generalization of our previous research to binary outcomes. Although it is based on the same LIL principle, we found the discrete case much more complex and the results from the continuous case do not apply to the binary case. The simulation study presented here is also more extensive. Methods The LIL based method `penalizes' the Z-value of the test statistic to account for multiple tests and for the estimation of heterogeneity in treatment effects across studies. It involves an adjustment factor, which is directly related to the control of type I error and determined through extensive simulations under various conditions. Results With an adjustment factor of 2, the LIL-based test statistics controls the overall type I error when odds ratio or relative risk is the parameter of interest. For risk difference, the adjustment factor can be reduced to 1.5. More inspections may require a larger adjustment factor, but the required adjustment factor stabilizes after 25 inspections. Limitations It will be ideal if the adjustment factor can be obtained theoretically through a statistical model. Unfortunately, real life data are too complex and we have to solve the problem through simulation. However, for large number of inspections, the adjustment factor will have a limited effect and the type I error is controlled mainly by the LIL. Conclusions The LIL method controls the overall type I error for a very broad range of practical situations with a binary outcome, and the LIL works properly in controlling the type I error rates as the number of inspections becomes large. Clinical Trials 2007; 4: 329—340. http://ctj.sagepub.com
The intention-to-treat approach in randomized controlled trials: Are authors saying what they do and doing what they say?
Authors: Gravel Jocelyn , Opatrny Lucie , Shapiro Stan 
Published: September 2007

Background Intention-to-treat (ITT) is an approach to the analysis of randomized controlled trials (RCT) in which patients are analyzed as randomized regardless of the treatment actually received. Purpose To ascertain the proportion of RCT reporting the use of intention-to-treat and the accuracy of that report and to examine the distribution and analysis of missing data for the studies reporting an ITT analysis. Method We conducted a cross-sectional literature review of RCTs reported in 10 medical journals in 2002. All articles were assessed using a standardized form. Two evaluators independently reviewed a 10% sample of articles to assess reliability. Subsequently, one evaluator reviewed the remaining articles. The proportion of articles reporting the use of ITT was calculated. Among these, the proportion of articles that `analyzed patients as randomized' and the proportion and analysis of missing data were evaluated using standardized definitions. Results Of the 403 articles, 249 (62%) reported the use of ITT. Among these, available patients were clearly analyzed as randomized in 192 (77%). Authors used a modified ITT in 23 (9%); clearly violated a major component of ITT in 17 (7%), and the approach used was unclear in 17 (7%). More than 60% of articles had missing data in their primary analysis. Few articles reported a strategy for missing data. The main reason for missing data was loss to follow-up. Limitations A single evaluator evaluated most articles, but the high concordance obtained during the inter-rater evaluation suggests that the assessments were consistent. In addition, the small spectrum of journals limits generalizability. Finally, there could be a difference between what was reported and what was performed. Conclusions This study emphasizes that authors use the label `intention-to-treat' quite differently. The most common use refers to the analysis of all available subjects as randomized regardless of the missing data aspect. Clinical Trials 2007; 4: 350—356. http://ctj.sagepub.com
Estimation of treatment effect adjusting for dependent censoring using the IPCW method: an application to a large primary prevention study for coronary events (MEGA study)
Authors: Yoshida Mizuki , Matsuyama Yutaka , Ohashi Yasuo 
Published: September 2007

Background The MEGA study is a randomized controlled trial conducted in Japan to evaluate the primary preventive effect of pravastatin against coronary heart disease (CHD), in which 8214 subjects are randomized to diet or diet plus pravastatin. Pravastatin reduces the incidence of CHD (hazard ratio = 0.67; 95%CI: 0.49—0.91). In the MEGA study, in addition to the usual loss to follow-up cases, there is another problem of drop-outs due to the refusal of further follow-up at 5 years. Purpose To estimate the treatment effect adjusting for some types of dependent censorings observed in the MEGA study and to assess the sensitivity of standard analysis results for these censoring cases. Methods The proposed method is a straightforward extension of the inverse probability of censoring weighted (IPCW) method for settings with more than one reason for censoring, where the propensities for drop-outs are modeled separately for each reason. Simulation studies are also conducted to compare the properties of the IPCW estimate with the standard analysis assuming independent censorings. Results Simulation studies show that the IPCW estimate can correct for selection bias due to dependent censoring that can be explained by measured factors, while the standard analysis is biased. Applying the proposed method to the MEGA study data, several prognostic factors are associated with the censoring processes, and after adjusting for these dependent censorings, slightly larger treatment effects for pravastatin are observed for both CHD (primary endpoint) and stroke (secondary endpoint) events. Limitations The method developed is based on the fundamental assumption of sequentially ignorable censoring. Conclusions Our proposed method provides a valuable approach for estimating treatment effect adjusting for several types of dependent censorings. Dependent censorings observed in the MEGA study did not cause a severe selection bias attributable to the covariates and the results from the standard analysis were robust in relation to the censorings. Clinical Trials 2007; 4: 318—328. http:// ctj.sagepub.com
Witness, Democracy and Civil Society: Reflections on John Howard Yoder's Exilic Ecclesiology
Authors: Bourne Richard 
Published: September 2007

AbstractThis article examines the compatibility between an ecclesial focus in contemporary theological ethics and an account of democratic citizenship. It focuses on the work of the Mennonite theologian John Howard Yoder. It explores the use of a motif that appeared with increasing frequency in Yoder's later writings, and has yet to receive much substantial academic attention — that of exilic citizenship. It then notes parallels between this exilic ecclesiology and contemporary understandings of civil society. It concludes that an exilic reading of Christian witness provides a fruitful basis for a theology of democratic participation.
Dynamic expression of ancient and novel molluscan shell genes during ecological transitions
Authors: Jackson Daniel J , Wörheide Gert , Degnan Bernard M 
Published: September 2007

Abstract

Background
The Mollusca constitute one of the most morphologically and ecologically diverse metazoan phyla, occupying a wide range of marine, terrestrial and freshwater habitats. The evolutionary success of the molluscs can in part be attributed to the evolvability of the external shell. Typically, the shell first forms during embryonic and larval development, changing dramatically in shape, colour and mineralogical composition as development and maturation proceeds. Major developmental transitions in shell morphology often correlate with ecological transitions (e.g. from a planktonic to benthic existence at metamorphosis). While the genes involved in molluscan biomineralisation are beginning to be identified, there is little understanding of how these are developmentally regulated, or if the same genes are operational at different stages of the mollusc's life.

Results
Here we relate the developmental expression of nine genes in the tissue responsible for shell production – the mantle – to ecological transitions that occur during the lifetime of the tropical abalone Haliotis asinina (Vetigastropoda). Four of these genes encode evolutionarily ancient proteins, while four others encode secreted proteins with little or no identity to known proteins. Another gene has been previously described from the mantle of another haliotid vetigastropod. All nine genes display dynamic spatial and temporal expression profiles within the larval shell field and juvenile mantle.

Conclusion
These expression data reflect the regulatory complexity that underlies molluscan shell construction from larval stages to adulthood, and serves to highlight the different ecological demands placed on each stage. The use of both ancient and novel genes in all stages of shell construction also suggest that a core set of shell-making genes was provided by a shared metazoan ancestor, which has been elaborated upon to produce the range of molluscan shell types we see today.
Comparative phylogenomic analyses of teleost fish Hox gene clusters: lessons from the cichlid fish Astatotilapia burtoni
Authors: Hoegg Simone , Boore Jeffrey L , Kuehl Jennifer V , Meyer Axel 
Published: September 2007

Abstract

Background
Teleost fish have seven paralogous clusters of Hox genes stemming from two complete genome duplications early in vertebrate evolution, and an additional genome duplication during the evolution of ray-finned fish, followed by the secondary loss of one cluster. Gene duplications on the one hand, and the evolution of regulatory sequences on the other, are thought to be among the most important mechanisms for the evolution of new gene functions. Cichlid fish, the largest family of vertebrates with about 2500 species, are famous examples of speciation and morphological diversity. Since this diversity could be based on regulatory changes, we chose to study the coding as well as putative regulatory regions of their Hox clusters within a comparative genomic framework.

Results
We sequenced and characterized all seven Hox clusters of Astatotilapia burtoni, a haplochromine cichlid fish. Comparative analyses with data from other teleost fish such as zebrafish, two species of pufferfish, stickleback and medaka were performed. We traced losses of genes and microRNAs of Hox clusters, the medaka lineage seems to have lost more microRNAs than the other fish lineages. We found that each teleost genome studied so far has a unique set of Hox genes. The hoxb7a gene was lost independently several times during teleost evolution, the most recent event being within the radiation of East African cichlid fish. The conserved non-coding sequences (CNS) encompass a surprisingly large part of the clusters, especially in the HoxAa, HoxCa, and HoxDa clusters. Across all clusters, we observe a trend towards an increased content of CNS towards the anterior end.

Conclusion
The gene content of Hox clusters in teleost fishes is more variable than expected, with each species studied so far having a different set. Although the highest loss rate of Hox genes occurred immediately after whole genome duplications, our analyses showed that gene loss continued and is still ongoing in all teleost lineages. Along with the gene content, the CNS content also varies across clusters. The excess of CNS at the anterior end of clusters could imply a stronger conservation of anterior expression patters than those towards more posterior areas of the embryo.
The Fangshan/Family-based Ischemic Stroke Study In China (FISSIC) protocol
Authors: Tang Xun , Hu Yonghua , Chen Dafang , Zhan Siyan , Zhang Zongxin , Dou Huidong 
Published: September 2007

Abstract

Background
The exact etiology of ischemic stroke remains unclear, because multiple genetic predispositions and environmental risk factors may be involved, and their interactions dictate the complexity. Family-based studies provide unique features in design, while they are currently underrepresented for studies of ischemic stroke in developing countries. The Fangshan/Family-based Ischemic Stroke Study In China (FISSIC) program aims to conduct a genetic pedigree study of ischemic stroke in rural communities of China.

Methods/Design
The pedigrees of ischemic stroke with clear documentation are recruited by using the proband-initiated contact method, based on the stroke registry in hospital and communities. Blood samples and detailed information of pedigrees are collected through the health care network in the rural area, and prospective follow-up of the pedigrees cohort is scheduled. Complementary strategies of both family-based design and matched case-spousal control design are used, and comprehensive statistical methods will be implemented to ascertain potential complex genetic and environmental factors and their interactions as well.

Discussion
This study is complementary to other genetic pedigree studies of ischemic stroke, such as the Siblings With Ischemic Stroke Study (SWISS), which are established in developed countries. We describe the protocol of this family-based genetic epidemiological study that may be used as a new practical guideline and research paradigm in developing countries and facilitate initiatives of stroke study for international collaborations.
New active site oriented glyoxyl-agarose derivatives of Escherichia colipenicillin G acylase
Authors: Cecchini Davide A , Serra Immacolata , Ubiali Daniela , Terreni Marco , Albertini Alessandra M 
Published: September 2007

Abstract

Background
Immobilized Penicillin G Acylase (PGA) derivatives are biocatalysts that are industrially used for the hydrolysis of Penicillin G by fermentation and for the kinetically controlled synthesis of semi-synthetic β-lactam antibiotics. One of the most used supports for immobilization is glyoxyl-activated agarose, which binds the protein by reacting through its superficial Lys residues. Since in E. coli PGA Lys are also present near the active site, an immobilization that occurs through these residues may negatively affect the performance of the biocatalyst due to the difficult diffusion of the substrate into the active site. A preferential orientation of the enzyme with the active site far from the support surface would be desirable to avoid this problem.

Results
Here we report how it is possible to induce a preferential orientation of the protein during the binding process on aldehyde activated supports. A superficial region of PGA, which is located on the opposite side of the active site, is enriched in its Lys content. The binding of the enzyme onto the support is consequently forced through the Lys rich region, thus leaving the active site fully accessible to the substrate. Different mutants with an increasing number of Lys have been designed and, when active, immobilized onto glyoxyl agarose. The synthetic performances of these new catalysts were compared with those of the immobilized wild-type (wt) PGA. Our results show that, while the synthetic performance of the wt PGA sensitively decreases after immobilization, the Lys enriched mutants have similar performances to the free enzyme even after immobilization.
We also report the observations made with other mutants which were unable to undergo a successful maturation process for the production of active enzymes or which resulted toxic for the host cell.

Conclusion
The desired orientation of immobilized PGA with the active site freely accessible can be obtained by increasing the density of Lys residues on a predetermined region of the enzyme. The newly designed biocatalysts display improved synthetic performances and are able to maintain a similar activity to the free enzymes. Finally, we found that the activity of the immobilized enzyme proportionally improves with the number of introduced Lys.
Modulation by decitabine of gene expression and growth of osteosarcoma U2OS cells in vitro and in xenografts: Identification of apoptotic genes as targets for demethylation
Authors: Al-Romaih Khaldoun , Somers Gino R , Bayani Jane , Hughes Simon , Prasad Mona , Cutz Jean-Claude , Xue Hui , Zielenska Maria , Wang Yuzhuo , Squire Jeremy A 
Published: September 2007

Abstract

Background
Methylation-mediated silencing of genes is one epigenetic mechanism implicated in cancer. Studies regarding the role of modulation of gene expression utilizing inhibitors of DNA methylation, such as decitabine, in osteosarcoma (OS) have been limited. A biological understanding of the overall effects of decitabine in OS is important because this particular agent is currently undergoing clinical trials. The objective of this study was to measure the response of the OS cell line, U2OS, to decitabine treatment both in vitro and in vivo.

Results
Microarray expression profiling was used to distinguish decitabine-dependent changes in gene expression in U2OS cells, and to identify responsive loci with demethylated CpG promoter regions. U2OS xenografts were established under the sub-renal capsule of immune-deficient mice to study the effect of decitabine in vivo on tumor growth and differentiation. Reduced nuclear methylation levels could be detected in xenografts derived from treated mice by immunohistochemistry utilizing a 5-methylcytidine antibody. Decitabine treatment reduced tumor xenograft size significantly (p < 0.05). Histological analysis of treated U2OS xenograft sections revealed a lower mitotic activity (p < 0.0001), increased bone matrix production (p < 0.0001), and a higher number of apoptotic cells (p = 0.0329). Microarray expression profiling of U2OS cultured cells showed that decitabine treatment caused a significant induction (p < 0.0025) in the expression of 88 genes. Thirteen had a ≥2-fold change, 11 of which had CpG-island-associated promoters. Interestingly, 6 of these 11 were pro-apoptotic genes and decitabine resulted in a significant induction of cell death in U2OS cells in vitro (p < 0.05). The 6 pro-apoptotic genes (GADD45A, HSPA9B, PAWR, PDCD5, NFKBIA, and TNFAIP3) were also induced to ≥2-fold in vivo. Quantitative methylation pyrosequencing confirmed that the tested pro-apoptotic genes had CpG-island DNA demethylationas a result of U2OS decitabine treatment both in vitro and in xenografts

Conclusion
These data provide new insights regarding the use of epigenetic modifiers in OS, and have important implications for therapeutic trials involving demethylation drugs. Collectively, these data have provided biological evidence that one mode of action of decitabine may be the induction of apoptosis utilizing promoter-CpG demethylation of specific effectors in cell death pathways in OS.
Spectrocolorimetric assessment of cartilage plugs after autologous osteochondral grafting: correlations between color indices and histological findings in a rabbit model
Authors: Hattori Koji , Uematsu Kota , Tanikake Yohei , Habata Takashi , Tanaka Yasuhito , Yajima Hiroshi , Takakura Yoshinori 
Published: September 2007

AbstractWe investigated the use of a commercial spectrocolorimeter and the application of two color models (L* a* b* colorimetric system and spectral reflectance distribution) to describe and quantify cartilage plugs in a rabbit model of osteochondral autografting. Osteochondral plugs were removed and then replaced in their original positions in Japanese white rabbits. The rabbits were sacrificed at 4 or 12 weeks after the operation and cartilage samples were assessed using a spectrocolorimeter. The samples were retrospectively divided into two groups on the basis of the histological findings (group H: hyaline cartilage, successful; group F: fibrous tissue or fibrocartilage, failure) and investigated for possible significant differences in the spectrocolorimetric analyses between the two groups. Moreover, the relationships between the spectrocolorimetric indices and the Mankin histological score were examined. In the L* a* b* colorimetric system, the L* values were significantly lower in group H than in group F (P = 0.02), whereas the a* values were significantly higher in group H than in group F (P = 0.006). Regarding the spectral reflectance distribution, the spectral reflectance percentage 470 (SRP470) values, as a coincidence index for the spectral reflectance distribution (400 to 470 nm in wavelength) of the cartilage plugs with respect to intact cartilage, were 99.8 ± 6.7% in group H and 119.8 ± 10.6% in group F, and the difference between these values was significant (P = 0.005). Furthermore, the a* values were significantly correlated with the histological score (P = 0.004, r = -0.76). The SRP470 values were also significantly correlated with the histological score (P = 0.01, r = 0.67). Our findings demonstrate the ability of spectrocolorimetric measurements to predict the histological findings of cartilage plugs after autologous osteochondral grafting. In particular, the a* values and SRP470 values can be used to judge the surface condition of an osteochondral plug on the basis of objective data. Therefore, spectrocolorimetry may contribute to orthopedics, rheumatology and related research in arthritis, and arthroscopic use of this method may potentially be preferable for in vivo assessment.