bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis
Authors: Tran Bich NH , Nguyen Nguyen D , Eisman John A , Nguyen Tuan V 
Published: June 2008

Abstract

Background
The low-density lipoprotein receptor-related protein 5 gene (LRP5) was identified to be linked to the variation in BMD in high bone mass pedigrees. Subsequent population-based studies of the association between the LRP5 gene and BMD have yielded conflicting results. The present study was aimed at examining the association between LRP5 gene and BMD by using meta-analysis.

Methods
A systematic electronic search of literature was conducted to identify all published studies in English on the association between LRP5 gene and osteoporosis-related phenotypes, including bone mineral density and fracture. BMD data were summarized from individual studies by LRP5 genotype, and a synthesis of data was performed with random-effects meta-analyses. After excluding studies on animal and review papers, there were 19 studies for the synthesis. Among these studies, 10 studies used the rs3736228 (A1330V) polymorphism and reported BMD values.

Results
The 10 eligible studies comprised 16,705 individuals, with the majority being women (n = 8444), aged between 18 – 81 years. The overall distribution of genotype frequencies was: AA, 68%, AV and VV, 32%. However, the genotype frequency varied significantly within as well as between ethnic populations. On random-effects meta-analysis, lumbar spine BMD among individuals with the AA genotype was on average 0.018 (95% confidence interval [CI]: 0.012 to 0.023) g/cm2 higher than those with either AV or VV genotype. Similarly, femoral neck BMD among carriers of the AA genotype was 0.011 (95%CI: 0.004 to 0.017) g/cm2 higher than those without the genotype. While there was no significant heterogeneity in the association between the A1330V polymorphism and lumbar spine BMD (p = 0.55), the association was heterogeneous for femoral neck BMD (p = 0.05). The probability that the difference is greater than one standard deviation was 0.34 for femoral neck BMD and 0.54 for lumbar spine BMD.

Conclusion
These results suggest that there is a modest effect of the A1330V polymorphism on BMD in the general population, and that the modest association may limit its clinical use.
Colombo Twin and Singleton Study (CoTASS): A description of a population based twin study of mental disorders in Sri Lanka
Authors: Siribaddana Sisira H , Ball Harriet A , Hewage Suwin N , Glozier Nick , Kovas Yulia , Dayaratne DARK , Sumathipala Athula , McGuffin Peter , Hotopf Matthew 
Published: June 2008

Abstract

Background
The Sri Lankan twin registry is one of the first to be established in a developing country, and its design has ensured sampling from a wide range of environmental conditions. It thus has great potential to examine environmental and genetic influences on diverse phenotypes, including psychiatric disorders, in the context of a diversity of environmental exposures, which may not have been fully explored in previous twin studies in developed countries. This paper presents the rationale for the study, describes its context, and the methods for twin ascertainment and data collection.

Methods
A population-based twin register was established in the Colombo district of Sri Lanka using infrastructure designed to periodically update the electoral register. We invited a subsample from this register to participate in the project on common mental disorders, using random ascertainment. A separate non-twin sample was randomly selected from the geographical areas where twins were found. Home interviewers collected diagnostic information on common mental disorders, as well as environmental exposures including life events, socio-economic conditions, and the impact of the civil war and the Tsunami of 2004.

Results
We identified 19,302 individuals in the creation of the population based twin register. We randomly selected a subsample, of whom 4,387 were eligible to participate and 4,024 agreed to be interviewed (including data on 1,954 complete pairs of twins and 5 sets of triplets). Those who refused consent had a similar mean age and sex ratio to those who were interviewed. We invited 2,485 singletons to participate and 2,019 were interviewed.

Conclusion
Initial exploration of the data suggests the samples are very representative of the Colombo district of Sri Lanka, so we have created a unique resource for understanding the influences on mental disorders in developing countries, and to compare to the influences found in developed countries.
Pregnancy success of lactating Holstein cows after a single administration of a sustained-release formulation of recombinant bovine somatotropin
Authors: Bell A , Rodríguez OA , de Castro e Paula LA , Padua MB , Hernández-Cerón J , Gutiérrez CG , De Vries A , Hansen PJ 
Published: June 2008

Abstract

Background
Results regarding the use of bovine somatotropin for enhancing fertility in dairy cattle are variable. Here, the hypothesis was tested that a single injection of a sustained-release preparation of bovine somatotropin (bST) during the preovulatory period would improve pregnancy success of lactating dairy cows at first service.

Results
The first experiment was conducted in a temperate region of Mexico. Cows inseminated following natural estrus or timed artificial insemination were given a single injection of bST or a placebo injection at insemination (n = 100 cows per group). There was no significant difference between bST and control groups in the proportion of inseminated cows diagnosed pregnant (29 vs 31% pregnant). The second experiment was performed during heat stress in Florida. Cows were subjected to an ovulation synchronization regimen for first insemination. Cows treated with bST received a single injection at 3 days before insemination. Controls received no additional treatment. As expected, bST did not increase vaginal temperature. Treatment with bST did not significantly increase the proportion of inseminated cows diagnosed pregnant although it was numerically greater for the bST group (24.2% vs 17.8%, 124–132 cows per group). There was a tendency (p = 0.10) for a smaller percent of control cows to have high plasma progesterone concentrations (≥ 1 ng/ml) at Day 7 after insemination than for bST-treated cows (72.6 vs 81.1%). When only cows that were successfully synchronized were considered, the magnitude of the absolute difference in the percentage of inseminated cows that were diagnosed pregnant between bST and control cows was reduced (24.8 vs 22.4% pregnant for bST and control).

Conclusion
Results failed to indicate a beneficial effect of bST treatment on fertility of lactating dairy cows.
Pericardial effusion as the only manifestation of infection with Francisella tularensis: a case report
Authors: Landais Cécile , Levy Pierre-Yves , Habib Gilbert , Raoult Didier 
Published: June 2008

Abstract

Introduction

Francisella tularensis, a facultative intracellular Gram-negative bacterium, has rarely been reported as an agent of pericarditis, generally described as a complication of tularemia sepsis. F. tularensis is a fastidious organism that grows poorly on standard culture media and diagnosis is usually based on serological tests. However, cross-reactions may occur. Western blotting allows the correct diagnosis.

Case presentation
A non-smoking 53-year-old woman was admitted to hospital with a large posterior pericardial effusion. Serological tests showed a seroconversion in antibody titers to F. tularensis (IgG titer = 400) and Legionella pneumophila (IgG titer = 512). F. tularensis was identified by Western immunoblotting following cross-adsorption. The patient reported close contact with rabbits 2 weeks prior to the beginning of symptoms of pericarditis.

Conclusion
We report a rare case of pericardial effusion as the only manifestation of infection by F. tularensis. The etiological diagnosis is based on serology. Western blotting and cross-adsorption allow differential diagnosis.
Behavioral recovery from traumatic brain injury after membrane reconstruction using polyethylene glycol
Authors: Koob Andrew O , Colby Julia M , Borgens Richard B 
Published: June 2008

Abstract
Polyethylene glycol (PEG; 2000 MW, 30% by volume) has been shown to mechanically repair damaged cellular membranes and reduce secondary axotomy after traumatic brain and spinal cord injury (TBI and SCI respectively). This repair is achieved following spontaneous reassembly of cell membranes made possible by the action of targeted hydrophilic polymers which first seal the compromised portion of the plasmalemma, and secondarily, allow the lipidic core of the compromised membranes to resolve into each other. Here we compared PEG-treated to untreated rats using a computer-managed open-field behavioral test subsequent to a standardized brain injury. Animals were evaluated after a 2-, 4-, and 6-hour delay in treatment after TBI. Treated animals receive a single subcutaneous injection of PEG. When treated within 2 hours of the injury, injured PEG-treated rats showed statistically significant improvement in their exploratory behavior recorded in the activity box when compared to untreated but brain-injured controls. A delay of 4 hours reduced this level of achievement, but a statistically significant improvement due to PEG injection was still clearly evident in most outcome measures compared at the various evaluation times. A further delay of 2 more hours, however, eradicated the beneficial effects of PEG injection as revealed using this behavioral assessment. Thus, there appears to be a critical window of time in which PEG administration after TBI can provide neuroprotection resulting in an enhanced functional recovery. As is often seen in clinically applied acute treatments for trauma, the earlier the intervention can be applied, the better the outcome.
PMC42, a breast progenitor cancer cell line, has normal-like mRNA and microRNA transcriptomes
Authors: Git Anna , Spiteri Inmaculada , Blenkiron Cherie , Dunning Mark J , Pole Jessica CM , Chin Suet-Feung , Wang Yanzhong , Smith James , Livesey Frederick J , Caldas Carlos 
Published: June 2008

Abstract
Introduction
The use of cultured cell lines as model systems for normal tissue is limited by the molecular alterations accompanying the immortalisation process, including changes in the mRNA and microRNA (miRNA) repertoire. Therefore, identification of cell lines with normal-like expression profiles is of paramount importance in studies of normal gene regulation.

Methods
The mRNA and miRNA expression profiles of several breast cell lines of cancerous or normal origin were measured using printed slide arrays, Luminex bead arrays, and real-time reverse transcription-polymerase chain reaction.

Results
We demonstrate that the mRNA expression profiles of two breast cell lines are similar to that of normal breast tissue: HB4a, immortalised normal breast epithelium, and PMC42, a breast cancer cell line that retains progenitor pluripotency allowing in-culture differentiation to both secretory and myoepithelial fates. In contrast, only PMC42 exhibits a normal-like miRNA expression profile. We identified a group of miRNAs that are highly expressed in normal breast tissue and PMC42 but are lost in all other cancerous and normal-origin breast cell lines and observed a similar loss in immortalised lymphoblastoid cell lines compared with healthy uncultured B cells. Moreover, like tumour suppressor genes, these miRNAs are lost in a variety of tumours. We show that the mechanism leading to the loss of these miRNAs in breast cancer cell lines has genomic, transcriptional, and post-transcriptional components.

Conclusion
We propose that, despite its neoplastic origin, PMC42 is an excellent molecular model for normal breast epithelium, providing a unique tool to study breast differentiation and the function of key miRNAs that are typically lost in cancer.
A critical assessment of Mus musculusgene function prediction using integrated genomic evidence
Authors: Peña-Castillo Lourdes , Tasan Murat , Myers Chad L , Lee Hyunju , Joshi Trupti , Zhang Chao , Guan Yuanfang , Leone Michele , Pagnani Andrea , Kim Wan Kyu , Krumpelman Chase , Tian Weidong , Obozinski Guillaume , Qi Yanjun , Mostafavi Sara , Lin Guan Ning , Berriz Gabriel F , Gibbons Francis D , Lanckriet Gert , Qiu Jian , Grant Charles , Barutcuoglu Zafer , Hill David P , Warde-Farley David , Grouios Chris , Ray Debajyoti , Blake Judith A , Deng Minghua , Jordan Michael I , Noble William S , Morris Quaid , Klein-Seetharaman Judith , Bar-Joseph Ziv , Chen Ting , Sun Fengzhu , Troyanskaya Olga G , Marcotte Edward M , Xu Dong , Hughes Timothy R , Roth Frederick P 
Published: June 2008

Abstract
Background:
Several years after sequencing the human genome and the mouse genome, much remains to be discovered about the functions of most human and mouse genes. Computational prediction of gene function promises to help focus limited experimental resources on the most likely hypotheses. Several algorithms using diverse genomic data have been applied to this task in model organisms; however, the performance of such approaches in mammals has not yet been evaluated.

Results:
In this study, a standardized collection of mouse functional genomic data was assembled; nine bioinformatics teams used this data set to independently train classifiers and generate predictions of function, as defined by Gene Ontology (GO) terms, for 21,603 mouse genes; and the best performing submissions were combined in a single set of predictions. We identified strengths and weaknesses of current functional genomic data sets and compared the performance of function prediction algorithms. This analysis inferred functions for 76% of mouse genes, including 5,000 currently uncharacterized genes. At a recall rate of 20%, a unified set of predictions averaged 41% precision, with 26% of GO terms achieving a precision better than 90%.

Conclusion:
We performed a systematic evaluation of diverse, independently developed computational approaches for predicting gene function from heterogeneous data sources in mammals. The results show that currently available data for mammals allows predictions with both breadth and accuracy. Importantly, many highly novel predictions emerge for the 38% of mouse genes that remain uncharacterized.
Predicting gene function in a hierarchical context with an ensemble of classifiers
Authors: Guan Yuanfang , Myers Chad L , Hess David C , Barutcuoglu Zafer , Caudy Amy A , Troyanskaya Olga G 
Published: June 2008

Abstract
Background:
The wide availability of genome-scale data for several organisms has stimulated interest in computational approaches to gene function prediction. Diverse machine learning methods have been applied to unicellular organisms with some success, but few have been extensively tested on higher level, multicellular organisms. A recent mouse function prediction project (MouseFunc) brought together nine bioinformatics teams applying a diverse array of methodologies to mount the first large-scale effort to predict gene function in the laboratory mouse.

Results:
In this paper, we describe our contribution to this project, an ensemble framework based on the support vector machine that integrates diverse datasets in the context of the Gene Ontology hierarchy. We carry out a detailed analysis of the performance of our ensemble and provide insights into which methods work best under a variety of prediction scenarios. In addition, we applied our method to Saccharomyces cerevisiae and have experimentally confirmed functions for a novel mitochondrial protein.

Conclusion:
Our method consistently performs among the top methods in the MouseFunc evaluation. Furthermore, it exhibits good classification performance across a variety of cellular processes and functions in both a multicellular organism and a unicellular organism, indicating its ability to discover novel biology in diverse settings.
GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function
Authors: Mostafavi Sara , Ray Debajyoti , Warde-Farley David , Grouios Chris , Morris Quaid 
Published: June 2008

Abstract
Background:
Most successful computational approaches for protein function prediction integrate multiple genomics and proteomics data sources to make inferences about the function of unknown proteins. The most accurate of these algorithms have long running times, making them unsuitable for real-time protein function prediction in large genomes. As a result, the predictions of these algorithms are stored in static databases that can easily become outdated. We propose a new algorithm, GeneMANIA, that is as accurate as the leading methods, while capable of predicting protein function in real-time.

Results:
We use a fast heuristic algorithm, derived from ridge regression, to integrate multiple functional association networks and predict gene function from a single process-specific network using label propagation. Our algorithm is efficient enough to be deployed on a modern webserver and is as accurate as, or more so than, the leading methods on the MouseFunc I benchmark and a new yeast function prediction benchmark; it is robust to redundant and irrelevant data and requires, on average, less than ten seconds of computation time on tasks from these benchmarks.

Conclusion:
GeneMANIA is fast enough to predict gene function on-the-fly while achieving state-of-the-art accuracy. A prototype version of a GeneMANIA-based webserver is available at http://morrislab.med.utoronto.ca/prototype.
Combining guilt-by-association and guilt-by-profiling to predict Saccharomyces cerevisiaegene function
Authors: Tian Weidong , Zhang Lan V , Taşan Murat , Gibbons Francis D , King Oliver D , Park Julie , Wunderlich Zeba , Cherry J Michael , Roth Frederick P 
Published: June 2008

Abstract
Background:
Learning the function of genes is a major goal of computational genomics. Methods for inferring gene function have typically fallen into two categories: 'guilt-by-profiling', which exploits correlation between function and other gene characteristics; and 'guilt-by-association', which transfers function from one gene to another via biological relationships.

Results:
We have developed a strategy ('Funckenstein') that performs guilt-by-profiling and guilt-by-association and combines the results. Using a benchmark set of functional categories and input data for protein-coding genes in Saccharomyces cerevisiae, Funckenstein was compared with a previous combined strategy. Subsequently, we applied Funckenstein to 2,455 Gene Ontology terms. In the process, we developed 2,455 guilt-by-profiling classifiers based on 8,848 gene characteristics and 12 functional linkage graphs based on 23 biological relationships.

Conclusion:
Funckenstein outperforms a previous combined strategy using a common benchmark dataset. The combination of 'guilt-by-profiling' and 'guilt-by-association' gave significant improvement over the component classifiers, showing the greatest synergy for the most specific functions. Performance was evaluated by cross-validation and by literature examination of the top-scoring novel predictions. These quantitative predictions should help prioritize experimental study of yeast gene functions.
An en masse phenotype and function prediction system for Mus musculus
Authors: Taşan Murat , Tian Weidong , Hill David P , Gibbons Francis D , Blake Judith A , Roth Frederick P 
Published: June 2008

Abstract
Background:
Individual researchers are struggling to keep up with the accelerating emergence of high-throughput biological data, and to extract information that relates to their specific questions. Integration of accumulated evidence should permit researchers to form fewer - and more accurate - hypotheses for further study through experimentation.

Results:
Here a method previously used to predict Gene Ontology (GO) terms for Saccharomyces cerevisiae (Tian et al.: Combining guilt-by-association and guilt-by-profiling to predict Saccharomyces cerevisiae gene function. Genome Biol 2008, 9(Suppl 1):S7) is applied to predict GO terms and phenotypes for 21,603 Mus musculus genes, using a diverse collection of integrated data sources (including expression, interaction, and sequence-based data). This combined 'guilt-by-profiling' and 'guilt-by-association' approach optimizes the combination of two inference methodologies. Predictions at all levels of confidence are evaluated by examining genes not used in training, and top predictions are examined manually using available literature and knowledge base resources.

Conclusion:
We assigned a confidence score to each gene/term combination. The results provided high prediction performance, with nearly every GO term achieving greater than 40% precision at 1% recall. Among the 36 novel predictions for GO terms and 40 for phenotypes that were studied manually, >80% and >40%, respectively, were identified as accurate. We also illustrate that a combination of 'guilt-by-profiling' and 'guilt-by-association' outperforms either approach alone in their application to M. musculus.
The Need for Leadership and Vision in Dentistry. A Personal View
Authors: Holt Vernon P 
Published: June 2008

This paper considers how dentistry has developed in the United Kingdom (UK) over the last 60 years and concludes that dentists have failed to be proactive and to shape the systems for the delivery of an optimal level of care to the population. It suggests that there is a need for far better leadership and for dentists, as individuals and as a profession, to rediscover the sense of vision that they once had and to shape their destinies, rather than accepting the current situation. The author goes on to explain how this might be done. Since the inception of the National Health Service (NHS), the dental profession in the UK has, to a large extent, been dominated by the politics of the NHS, by changing fee structures and contracts, by reports from the Review Body on Doctors’ and Dentists’ Remuneration (DDRB), and by strategies adopted by successive governments, especially during the last two decades. These strategies have resulted in cohorts of disillusioned dental practitioners reducing their commitment to, or opting out of, NHS contracts and committing themselves, to a greater or lesser extent, to private practice.1 It is now over three years since, for the first time, the proportion of dentistry provided under private contact in the UK, as measured by gross fees, exceeded that provided under NHS contract. The profession has shown a remarkable lack of imagination in organising itself to provide the best kind of care for patients. Instead of being proactive and visionary, it has allowed itself to become a political football. This has led to the progressive deskilling of many practitioners, and a manifest failure to secure the long-term oral health of patients. This paper considers how the situation could be improved and looks at four aspects, which are: 1. 21st century dentistry: state of the art versus reality? The contrast between what is clinically possible and what the profession currently delivers. 2. What are we here for? The need for a new vision for dentistry, the profession and the future, and the need for a new sense of mission. 3. A responsibility for the profession. The responsibility of the profession for providing patients (and funding bodies) with advice. 4. Leading the way: a new-look personal development plan. The personal development needs of dentists, with much more emphasis on interpersonal and leadership skills.