bluuebunny/crossref_metadata_2025_split huggingface dataset:
PathSys: integrating molecular interaction graphs for systems biology
Authors: Baitaluk Michael , Qian Xufei , Godbole Shubhada , Raval Alpan , Ray Animesh , Gupta Amarnath 
Published: February 2006

Abstract

Background
The goal of information integration in systems biology is to combine information from a number of databases and data sets, which are obtained from both high and low throughput experiments, under one data management scheme such that the cumulative information provides greater biological insight than is possible with individual information sources considered separately.

Results
Here we present PathSys, a graph-based system for creating a combined database of networks of interaction for generating integrated view of biological mechanisms. We used PathSys to integrate over 14 curated and publicly contributed data sources for the budding yeast (S. cerevisiae) and Gene Ontology. A number of exploratory questions were formulated as a combination of relational and graph-based queries to the integrated database. Thus, PathSys is a general-purpose, scalable, graph-data warehouse of biological information, complete with a graph manipulation and a query language, a storage mechanism and a generic data-importing mechanism through schema-mapping.

Conclusion
Results from several test studies demonstrate the effectiveness of the approach in retrieving biologically interesting relations between genes and proteins, the networks connecting them, and of the utility of PathSys as a scalable graph-based warehouse for interaction-network integration and a hypothesis generator system. The PathSys's client software, named BiologicalNetworks, developed for navigation and analyses of molecular networks, is available as a Java Web Start application at http://brak.sdsc.edu/pub/BiologicalNetworks.
HotSwap for bioinformatics: A STRAP tutorial
Authors: Gille Christoph , Robinson Peter N 
Published: February 2006

Abstract

Background
Bioinformatics applications are now routinely used to analyze large amounts of data. Application development often requires many cycles of optimization, compiling, and testing. Repeatedly loading large datasets can significantly slow down the development process. We have incorporated HotSwap functionality into the protein workbench STRAP, allowing developers to create plugins using the Java HotSwap technique.

Results
Users can load multiple protein sequences or structures into the main STRAP user interface, and simultaneously develop plugins using an editor of their choice such as Emacs. Saving changes to the Java file causes STRAP to recompile the plugin and automatically update its user interface without requiring recompilation of STRAP or reloading of protein data. This article presents a tutorial on how to develop HotSwap plugins. STRAP is available at http://strapjava.de and http://www.charite.de/bioinf/strap.

Conclusion
HotSwap is a useful and time-saving technique for bioinformatics developers. HotSwap can be used to efficiently develop bioinformatics applications that require loading large amounts of data into memory.
Evolution of the NANOG pseudogene family in the human and chimpanzee genomes
Authors: Fairbanks Daniel J , Maughan Peter J 
Published: February 2006

Abstract

Background
The NANOG gene is expressed in mammalian embryonic stem cells where it maintains cellular pluripotency. An unusually large family of pseudogenes arose from it with one unprocessed and ten processed pseudogenes in the human genome. This article compares the NANOG gene and its pseudogenes in the human and chimpanzee genomes and derives an evolutionary history of this pseudogene family.

Results
The NANOG gene and all pseudogenes except NANOGP8 are present at their expected orthologous chromosomal positions in the chimpanzee genome when compared to the human genome, indicating that their origins predate the human-chimpanzee divergence. Analysis of flanking DNA sequences demonstrates that NANOGP8 is absent from the chimpanzee genome.

Conclusion
Based on the most parsimonious ordering of inferred source-gene mutations, the deduced evolutionary origins for the NANOG pseudogene family in the human and chimpanzee genomes, in order of most ancient to most recent, are NANOGP6, NANOGP5, NANOGP3, NANOGP10, NANOGP2, NANOGP9, NANOGP7, NANOGP1, and NANOGP4. All of these pseudogenes were fixed in the genome of the human-chimpanzee common ancestor. NANOGP8 is the most recent pseudogene and it originated exclusively in the human lineage after the human-chimpanzee divergence. NANOGP1 is apparently an unprocessed pseudogene. Comparison of its sequence to the functional NANOG gene's reading frame suggests that this apparent pseudogene remained functional after duplication and, therefore, was subject to selection-driven conservation of its reading frame, and that it may retain some functionality or that its loss of function may be evolutionarily recent.
Adaptive evolution of chloroplast genome structure inferred using a parametric bootstrap approach
Authors: Cui Liying , Leebens-Mack Jim , Wang Li-San , Tang Jijun , Rymarquis Linda , Stern David B , dePamphilis Claude W 
Published: February 2006

Abstract

Background
Genome rearrangements influence gene order and configuration of gene clusters in all genomes. Most land plant chloroplast DNAs (cpDNAs) share a highly conserved gene content and with notable exceptions, a largely co-linear gene order. Conserved gene orders may reflect a slow intrinsic rate of neutral chromosomal rearrangements, or selective constraint. It is unknown to what extent observed changes in gene order are random or adaptive. We investigate the influence of natural selection on gene order in association with increased rate of chromosomal rearrangement. We use a novel parametric bootstrap approach to test if directional selection is responsible for the clustering of functionally related genes observed in the highly rearranged chloroplast genome of the unicellular green alga Chlamydomonas reinhardtii, relative to ancestral chloroplast genomes.

Results
Ancestral gene orders were inferred and then subjected to simulated rearrangement events under the random breakage model with varying ratios of inversions and transpositions. We found that adjacent chloroplast genes in C. reinhardtii were located on the same strand much more frequently than in simulated genomes that were generated under a random rearrangement processes (increased sidedness; p < 0.0001). In addition, functionally related genes were found to be more clustered than those evolved under random rearrangements (p < 0.0001). We report evidence of co-transcription of neighboring genes, which may be responsible for the observed gene clusters in C. reinhardtii cpDNA.

Conclusion
Simulations and experimental evidence suggest that both selective maintenance and directional selection for gene clusters are determinants of chloroplast gene order.
Selecting cases from nuclear families for case-control association analysis
Authors: Moore Rachael M , Pinel Tracy , Zhao Jing Hua , March Ruth , Jawaid Ansar 
Published: February 2006

Abstract
We examine the efficiency of a number of schemes to select cases from nuclear families for case-control association analysis using the Genetic Analysis Workshop 14 simulated dataset. We show that with this simulated dataset comparing all affected siblings with unrelated controls is considerably more powerful than all of the other approaches considered. We find that the test statistic is increased by almost 3-fold compared to the next best sampling schemes of selecting all affected sibs only from families with affected parents (AFaff), one affected sib with most evidence of allele-sharing from each family (SF), and all affected sibs from families with evidence for linkage (AFL). We consider accounting for biological relatedness of samples in the association analysis to maintain the correct type I error. We also discuss the relative efficiencies of increasing the ratio of unrelated cases to controls, methods to confirm associations and issues to consider when applying our conclusions to other complex disease datasets.
Resampling methods to reduce the selection bias in genetic effect estimation in genome-wide scans
Authors: Wu Long Yang , Lee Sophia SF , Shi Haijiang Steven , Sun Lei , Bull Shelley B 
Published: February 2006

Abstract
Using the simulated data of Problem 2 for Genetic Analysis Workshop 14 (GAW14), we investigated the ability of three bootstrap-based resampling estimators (a shrinkage, an out-of-sample, and a weighted estimator) to reduce the selection bias for genetic effect estimation in genome-wide linkage scans. For the given marker density in the preliminary genome scans (7 cM for microsatellite and 3 cM for SNP), we found that the two sets of markers produce comparable results in terms of power to detect linkage, localization accuracy, and magnitude of test statistic at the peak location. At the locations detected in the scan, application of the three bootstrap-based estimators substantially reduced the upward selection bias in genetic effect estimation for both true and false positives. The relative effectiveness of the estimators depended on the true genetic effect size and the inherent power to detect it. The shrinkage estimator is recommended when the power to detect the disease locus is low. Otherwise, the weighted estimator is recommended.
Regulation of the human LAT gene by the Elf-1 transcription factor
Authors: Finco Timothy S , Justice-Healy Geri E , Patel Shivani J , Hamilton Victoria E 
Published: February 2006

AbstractBackgroundTheLATgene encodes an intracellular adaptor protein that links cell-surface receptor engagement to numerous downstream signalling events, and thereby plays an integral role in the function of cell types that express the gene, including T cells, mast cells, natural killer cells, and platelets. To date, the mechanisms responsible for the transcriptional regulation of this gene have not been investigated.ResultsIn this study we have mapped the transcriptional start sites for the humanLATgene and localized the 5' and 3' boundaries of the proximal promoter. We find that the promoter contains both positive and negative regulatory regions, and that two binding sites for the Ets family of transcription factors have a strong, positive effect on gene expression. Each site binds the Ets family member Elf-1, and overexpression of Elf-1 augmentsLATpromoter activity. The promoter also contains a Runx binding site adjacent to one of the Ets sites. This site, which is shown to bind Runx-1, has an inhibitory effect on gene expression. Finally, data is also presented indicating that the identified promoter may regulate cell-type specific expression.ConclusionCollectively, these results provide the first insights into the transcriptional regulation of theLATgene, including the discovery that the Ets transcription factor Elf-1 may play a central role in its expression.
The association between processes, structures and outcomes of secondary prevention care among VA ischemic heart disease patients
Authors: Ho P Michael , Prochazka Allan V , Magid David J , Sales Anne E , Grunwald Gary K , Hammermeister Karl E , Rumsfeld John S 
Published: February 2006

Abstract

Background
Hyperlipidemia and hypertension are well-established risk factors for recurrent cardiovascular events among patients with ischemic heart disease (IHD). Despite national recommendations, concordance with guidelines for LDL cholesterol and blood pressure remains inadequate. The objectives of this study were to 1) determine concordance rates with LDL cholesterol and BP recommendations; and 2) identify patient factors, processes and structures of care associated with guideline concordance among VA IHD patients.

Methods
This was a cross sectional study of veterans with IHD from 8 VA hospitals. Outcomes were concordance with LDL guideline recommendations (LDL<100 mg/dl), and BP recommendations (<140/90 mm Hg). Cumulative logit and hierarchical logistic regression analyses were performed to identify patient factors, processes, and structures of care independently associated with guideline concordance.

Results
Of 14,114 veterans with IHD, 55.7% had hypertension, 71.5% had hyperlipidemia, and 41.6% had both conditions. Guideline concordance for LDL and BP were 38.9% and 53.4%, respectively. However, only 21.9% of the patients achieved both LDL <100 mg/dl and BP <140/90 mm Hg. In multivariable analyses, patient factors including older age and the presence of vascular disease were associated with worse guideline concordance. In contrast, diabetes was associated with better guideline concordance. Several process of care variables, including higher number of outpatient visits, higher number of prescribed medications, and a recent cardiac hospitalization were associated with better guideline concordance. Among structures of care, having on-site cardiology was associated with a trend towards better guideline concordance.

Conclusion
Guideline concordance with secondary prevention measures among IHD patients remains suboptimal. It is hoped that the findings of this study can serve as an impetus for quality improvement efforts to improve upon secondary prevention measures and reduce the morbidity and mortality of patients with known IHD.
Setting directions for capacity building in primary health care: a survey of a research network
Authors: Ried Karin , Farmer Elizabeth A , Weston Kathryn M 
Published: February 2006

Abstract

Background
The South Australian Research Network 'SARNet' aims to build research capacity in primary health care, as part of a national government-funded strategy to integrate research into clinical practice. Internationally, research networks have been a fundamental part of research culture change, and a variety of network models exist. The 'SARNet' model uses a whole system, multidisciplinary approach to capacity building and supports individuals and groups. We undertook a descriptive baseline survey in order to understand the background and needs of SARNet members and to tailor network activities towards those needs.

Methods
A questionnaire survey, assessing members' professional background, research experience, and interest in research development and training, was sent to all members who joined the network in its first year. The visual 'research spider' tool was used to ascertain members' experience in ten core research skills, as well as their interest in developing these skills. Individuals were asked to classify themselves into one of four categories of researchers, based on previous research experience. These self-assessment categories ranged from non-participant to academic.

Results
Network membership was diverse. Of the 89 survey participants, 55% were general practitioners or allied health professionals. Overall, most survey respondents indicated little to moderate experience in 7 out of the 10 skills depicted in the 'research spider'. In comparison, respondents were generally highly interested in developing their research skills in all areas. Respondents' research skills correlated significantly with their self-assessed category of research participation (Spearman rank correlation, r = 0.82, p < 0.0005). Correlations between research category and publication record (Gamma association, γ = 0.53, p < 0.0005) or funding record (Gamma association, γ = 0.62, p < 0.0005) supported the internal validity of the survey instrument.

Conclusion
Literature describing evaluation of the impact of networks is scarce. Our survey questionnaire could provide a useful instrument for evaluation of both networks and capacity building initiatives. The survey including the 'research spider' tool provided valuable information about members' needs and interest in strategies to develop their research skills. Initial needs analyses as well as on-going evaluation of network activities are important to include into the business plans of research networks, in order to ensure the network's effectiveness and support of its membership.
Automated extraction protocol for quantification of SARS-Coronavirus RNA in serum: an evaluation study
Authors: Chiu Rossa WK , Jin Yongjie , Chung Grace TY , Lui Wing-bong , Chan Anthony TC , Lim Wilina , Dennis Lo YM 
Published: February 2006

Abstract

Background
We have previously developed a test for the diagnosis and prognostic assessment of the severe acute respiratory syndrome (SARS) based on the detection of the SARS-coronavirus RNA in serum by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). In this study, we evaluated the feasibility of automating the serum RNA extraction procedure in order to increase the throughput of the assay.

Methods
An automated nucleic acid extraction platform using the MagNA Pure LC instrument (Roche Diagnostics) was evaluated. We developed a modified protocol in compliance with the recommended biosafety guidelines from the World Health Organization based on the use of the MagNA Pure total nucleic acid large volume isolation kit for the extraction of SARS-coronavirus RNA. The modified protocol was compared with a column-based extraction kit (QIAamp viral RNA mini kit, Qiagen) for quantitative performance, analytical sensitivity and precision.

Results
The newly developed automated protocol was shown to be free from carry-over contamination and have comparable performance with other standard protocols and kits designed for the MagNA Pure LC instrument. However, the automated method was found to be less sensitive, less precise and led to consistently lower serum SARS-coronavirus concentrations when compared with the column-based extraction method.

Conclusion
As the diagnostic efficiency and prognostic value of the serum SARS-CoV RNA RT-PCR test is critically associated with the analytical sensitivity and quantitative performance contributed both by the RNA extraction and RT-PCR components of the test, we recommend the use of the column-based manual RNA extraction method.
The GCC repeat length in the 5'UTR of MRP1 gene is polymorphic: a functional characterization of its relevance for cystic fibrosis
Authors: Nicolis Elena , Pasetto Matteo , Cigana Cristina , Pradal Ugo , Assael Baroukh M , Melotti Paola 
Published: February 2006

Abstract

Background
Among the members of the ATP binding cassette transporter superfamily, MRPs share the closest homology with the CFTR protein, which is defective in CF disease. MRP1 has been proposed as a potential modifier gene and/or as novel target for pharmacotherapy of CF to explain the clinical benefits observed in some CF patients treated with the macrolide AZM. The 5'UTR of the MRP1 gene contains a GCC triplet repeat that could represent a polymorphic site and affect the activity of the promoter.

Methods
The MRP1 5' flanking region was amplified by PCR from 36 CF patients and 100 non-CF subjects and the number of GCC triplets of each allele was determined by sequence and electrophoretic analysis. We performed gene reporter studies in CF airway epithelial cells 16HBE14o-AS3, in basal conditions and in the presence of AZM.

Results
We found that the GCC repeat is polymorphic, ranging from 7 to 14 triplets either in CF or in non-CF subjects. Our data are preliminary and have to be confirmed on a larger population of CF subjects. The transcriptional activity of the proximal MRP1 5' regulatory region revealed no statistically significant correlations between the number of repeats and treatment with AZM.

Conclusion
We identified a novel polymorphism in the 5'UTR of MRP1 gene that provides multiple alleles in a gene relevant for multidrug resistance as well as for CF, determining that this region is transcriptionally active and that this activity does not appear to be influenced by AZM treatment.
Are mild head injuries as mild as we think? Neurobehavioral concomitants of chronic post-concussion syndrome
Authors: Sterr Annette , Herron Katherine A , Hayward Chantal , Montaldi Daniela 
Published: February 2006

Abstract

Background
Mild traumatic brain injury (MTBI) can sometimes lead to persistent postconcussion symptoms. One well accepted hypothesis claims that chronic PCS has a neural origin, and is related to neurobehavioral deficits. But the evidence is not conclusive. In the attempt to characterise chronic MTBI consequences, the present experiment used a group comparison design, which contrasted persons (a) with MTBI and PCS, (b) MTBI without PCS, and (c) matched controls. We predicted that participants who have experienced MTBI but show no signs of PCS would perform similar to controls. At the same time, a subgroup of MTBI participants would show PCS symptoms and only these volunteers would have poorer cognitive performance. Thereby, the performance deficits should be most noticeable in participants with highest PCS severity.

Method
38 patients with a single MTBI that had occurred at least 12 month prior to testing, and 38 matched controls, participated in the experiment. A combination of questionnaires and neuropsychological test batteries were used to assess the extent of PCS and related deficits in neurobehavioral performance.

Results
11 out of 38 MTBI participants (29%) were found to suffer from PCS. This subgroup of MTBI patients performed poorly on neuropsychological test batteries. Thereby, a correlation was found between PCS symptom severity and test performance suggesting that participants with more pronounced PCS symptoms performed worse in cognitive tasks. In contrast, MTBI patients with no PCS showed performed similar to matched control. We further found that loss of consciousness, a key criterion for PCS diagnosis, was not predictive of sustained PCS.

Conclusion
The results support the idea that MTBI can have sustained consequences, and that the subjectively experienced symptoms and difficulties in everyday situations are related to objectively measurable parameters in neurocognitive function.
Understanding the attitudes of the elderly towards enrolment into cancer clinical trials
Authors: Townsley Carol A , Chan Kelvin K , Pond Gregory R , Marquez Christine , Siu Lillian L , Straus Sharon E 
Published: February 2006

Abstract

Background
The optimal cancer treatment for an older population is largely unknown because of the low numbers of elderly patients accrued into clinical trials. This project focuses on the attitudes of the elderly about participation in clinical trials to determine if this is one of the barriers to the involvement of this population in clinical trials.

Methods
The first phase of this study was a self-administered questionnaire mailed to 425 elderly persons with cancer, selected from Princess Margaret Hospital oncology clinics. The second phase consisted of individual semi-structured interviews with cancer patients to assess their attitudes towards cancer, its management and enrolment into cancer clinical trials.

Results
Ninety-four patients responded to the survey giving a response rate of 22.1%. Three quarters of respondents stated that they would be willing to participate in a clinical trial. The factors that most influenced older patients' willingness to participate in a cancer study were recommendations from a cancer doctor and the chance that the study treatment may help them feel better. Seventeen survey responders participated in interviews. Common themes from these interviews included patient-physician communication, the referral process, and the role of age in cancer care decision-making.

Conclusion
Most elderly people, who responded to this survey, are willing to consider participation in cancer clinical trials however, elderly patients do not appear to actively seek clinical trials and few were informed of the availability of clinical trials. Physician barriers and availability of appropriate clinical trials may play a bigger role in preventing accrual of elderly cancer patients into trials.