bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cohort Study of p27 Localization in Colon Cancer, Body Mass Index, and Patient Survival
Authors: Ogino Shuji , Shima Kaori , Nosho Katsuhiko , Irahara Natsumi , Baba Yoshifumi , Wolpin Brian M. , Giovannucci Edward L. , Meyerhardt Jeffrey A. , Fuchs Charles S. 
Published: June 2009

Abstract
Energy balance and the AKT pathway are important in colorectal cancer development and regulate p27 (cyclin-dependent kinase inhibitor-1B/CDKN1B/KIP1), which plays a role in preventing cell cycle progression. However, little is known on the clinical outcome or prognostic significance of p27 alterations in relation to patient body mass index (BMI). Among 630 colon cancers (stage I-IV) in two prospective cohort studies, we detected p27 alterations (cytoplasmic p27 localization or p27 loss) in 500 tumors (79%) by immunohistochemistry. The remaining 130 (21%) tumors were “p27-nuclear+.” Cox proportional hazard models computed hazard ratios (HR) of deaths, adjusted for patient and tumoral characteristics, including p53, p21, cyclin D1, KRAS, BRAF, PIK3CA, cyclooxygenase-2, fatty acid synthase (FASN), β-catenin, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and long interspersed nucleotide element-1 (LINE-1) hypomethylation. Compared with p27-nuclear+ patients, p27-altered patients experienced low colon cancer–specific [adjusted HR, 0.63; 95% confidence interval (95% CI), 0.42-0.94] and overall mortality (adjusted HR, 0.70; 95% CI, 0.51-0.95), independent of FASN, MSI, CIMP, LINE-1 methylation, and other potential confounders. The effect of p27 alteration on overall mortality significantly differed by BMI (Pinteraction = 0.013); adjusted HR (p27-altered versus p27-nuclear+ tumors) was 0.28 (95% CI, 0.13-0.59) for BMI ≥30 kg/m2, 0.67 (95% CI, 0.40-1.14) for BMI 25 to 29 kg/m2, and 0.91 (95% CI, 0.57-1.46) for BMI &lt;25 kg/m2. Obesity was associated with inferior overall survival among p27-nuclear+ cases (adjusted HR, 3.07; 95% CI, 1.49-6.32; versus nonobese cases), but not among p27-altered cases (adjusted HR, 1.08). In conclusion, p27 alterations in colon cancer are associated with superior prognosis. Adverse prognostic effect of obesity seems limited to patients with nuclear p27 expression, suggesting a host-tumor interaction. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1849–58)
Use of Thiazolidinediones Does Not Affect Prostate-Specific Antigen Levels in Men with Diabetes
Authors: Pini Tunghi M. , Griffin Marie R. , Roumie Christianne L. , Huizinga Mary Margaret , Fowke Jay H. , Greevy Robert , Liu Xulei , Murff Harvey J. 
Published: June 2009

Abstract
Thiazolidinediones (TZD) have been shown to down-regulate prostate-specific antigen (PSA) levels in prostate cancer cell lines and decrease PSA velocity among prostate cancer patients; however, the effect of TZDs on serum PSA levels among men with diabetes at risk for prostate cancer is unknown. We conducted a retrospective cohort study of veterans receiving care for diabetes between 1999 and 2005 to determine if TZD use affects PSA levels in veterans at risk for prostate cancer. Eligible patients were male, ≥45 years old, taking at least one oral antidiabetic medication, and with two or more recorded PSA values. Patients with a prior history of prostate cancer or prostatectomy were excluded. Of the 13,791 patients included in the adjusted analysis, 2,016 (14.6%) were prescribed a TZD. No effect of cumulative TZD dose on change in PSA was detected (P = 0.26). Increased TZD exposure was not associated with a change in PSA, suggesting that TZD treatment for diabetes is unlikely to affect prostate cancer detection. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1937–8)
Three-Dimensional Free Vibration Analysis of Cross-Ply Laminated Rectangular Plates with Free Edges Through a Displacement-Based Approach
Authors: Messina Arcangelo , Rollo Giosuè 
Published: June 2009

This paper presents a model belonging to a theory that recently appeared in the literature dealing with accurate solutions of freely vibrating laminated plates. The present model, which is derived from a displacement-based variational approach, investigates both free edge boundary conditions and the possibility of obtaining accurate results without explicitly incorporating stress interlaminar continuity conditions where they are in principle requested. These investigations are carried out within the frame of multi-layered plates where the literature is lacking in relevant three-dimensional results. In spite of the multi-layer nature of the plate, the model is developed as if the same plate were virtually made of a single layer because a suitable set of piecewise-smooth functions is used. Once the model is theoretically introduced, natural frequencies are evaluated for the case of plates with simply supported and free edge boundaries. The evaluations are compared with those few existing values of exact or approximate three-dimensional models, new results are provided for future comparisons and, finally, the performance of the model is tested with respect to extreme cases which could also deal with interesting engineering applications without reverting to non-immediate numerical schemes.
myGRN: a database and visualisation system for the storage and analysis of developmental genetic regulatory networks
Authors: Bacha Jamil , Brodie James S , Loose Matthew W 
Published: June 2009

Abstract

Background
Biological processes are regulated by complex interactions between transcription factors and signalling molecules, collectively described as Genetic Regulatory Networks (GRNs). The characterisation of these networks to reveal regulatory mechanisms is a long-term goal of many laboratories. However compiling, visualising and interacting with such networks is non-trivial. Current tools and databases typically focus on GRNs within simple, single celled organisms. However, data is available within the literature describing regulatory interactions in multi-cellular organisms, although not in any systematic form. This is particularly true within the field of developmental biology, where regulatory interactions should also be tagged with information about the time and anatomical location of development in which they occur.

Description
We have developed myGRN (http://www.myGRN.org), a web application for storing and interrogating interaction data, with an emphasis on developmental processes. Users can submit interaction and gene expression data, either curated from published sources or derived from their own unpublished data. All interactions associated with publications are publicly visible, and unpublished interactions can only be shared between collaborating labs prior to publication. Users can group interactions into discrete networks based on specific biological processes. Various filters allow dynamic production of network diagrams based on a range of information including tissue location, developmental stage or basic topology. Individual networks can be viewed using myGRV, a tool focused on displaying developmental networks, or exported in a range of formats compatible with third party tools. Networks can also be analysed for the presence of common network motifs. We demonstrate the capabilities of myGRN using a network of zebrafish interactions integrated with expression data from the zebrafish database, ZFIN.

Conclusion
Here we are launching myGRN as a community-based repository for interaction networks, with a specific focus on developmental networks. We plan to extend its functionality, as well as use it to study networks involved in embryonic development in the future.
Generation and analysis of transcriptomic resources for a model system on the rise: the sea anemone Aiptasia pallida and its dinoflagellate endosymbiont
Authors: Sunagawa Shinichi , Wilson Emily C , Thaler Michael , Smith Marc L , Caruso Carlo , Pringle John R , Weis Virginia M , Medina Mónica , Schwarz Jodi A 
Published: June 2009

Abstract

Background
The most diverse marine ecosystems, coral reefs, depend upon a functional symbiosis between cnidarian hosts and unicellular dinoflagellate algae. The molecular mechanisms underlying the establishment, maintenance, and breakdown of the symbiotic partnership are, however, not well understood. Efforts to dissect these questions have been slow, as corals are notoriously difficult to work with. In order to expedite this field of research, we generated and analyzed a collection of expressed sequence tags (ESTs) from the sea anemone Aiptasia pallida and its dinoflagellate symbiont (Symbiodinium sp.), a system that is gaining popularity as a model to study cellular, molecular, and genomic questions related to cnidarian-dinoflagellate symbioses.

Results
A set of 4,925 unique sequences (UniSeqs) comprising 1,427 clusters of 2 or more ESTs (contigs) and 3,498 unclustered ESTs (singletons) was generated by analyzing 10,285 high-quality ESTs from a mixed host/symbiont cDNA library. Using a BLAST-based approach to predict which unique sequences derived from the host versus symbiont genomes, we found that the contribution of the symbiont genome to the transcriptome was surprisingly small (1.6–6.4%). This may reflect low levels of gene expression in the symbionts, low coverage of alveolate genes in the sequence databases, a small number of symbiont cells relative to the total cellular content of the anemones, or failure to adequately lyse symbiont cells. Furthermore, we were able to identify groups of genes that are known or likely to play a role in cnidarian-dinoflagellate symbioses, including oxidative stress pathways that emerged as a prominent biological feature of this transcriptome. All ESTs and UniSeqs along with annotation results and other tools have been made accessible through the implementation of a publicly accessible database named AiptasiaBase.

Conclusion
We have established the first large-scale transcriptomic resource for Aiptasia pallida and its dinoflagellate symbiont. These data provide researchers with tools to study questions related to cnidarian-dinoflagellate symbioses on a molecular, cellular, and genomic level. This groundwork represents a crucial step towards the establishment of a tractable model system that can be utilized to better understand cnidarian-dinoflagellate symbioses. With the advent of next-generation sequencing methods, the transcriptomic inventory of A. pallida and its symbiont, and thus the extent of AiptasiaBase, should expand dramatically in the near future.
Effect of voluntary running on adult hippocampal neurogenesis in cholinergic lesioned mice
Authors: Ho New Fei , Han Siew Ping , Dawe Gavin S 
Published: June 2009

Abstract

Background
Cholinergic neuronal dysfunction of the basal forebrain is observed in patients with Alzheimer's disease and dementia, and has been linked to decreased neurogenesis in the hippocampus, a region involved in learning and memory. Running is a robust inducer of adult hippocampal neurogenesis. This study aims to address the effect of running on hippocampal neurogenesis in lesioned mice, where septohippocampal cholinergic neurones have been selectively eliminated in the medial septum and diagonal band of Broca of the basal forebrain by infusion of mu-p75-saporin immunotoxin.

Results
Running increased the number of newborn cells in the dentate gyrus of the hippocampus in cholinergic denervated mice compared to non-lesioned mice 24 hours after injection of bromodeoxyuridine (BrdU). Although similar levels of surviving cells were present in cholinergic depleted animals and their respective controls four weeks after injection of BrdU, the majority of progenitors that proliferate in response to the initial period of running were not able to survive beyond one month without cholinergic input. Despite this, the running-induced increase in the number of surviving neurones was not affected by cholinergic depletion.

Conclusion
The lesion paradigm used here models aspects of the cholinergic deficits associated with Alzheimer's Disease and aging. We showed that running still increased the number of newborn cells in the adult hippocampal dentate gyrus in this model of neurodegenerative disease.
The clinicopathologic observation, c-KIT gene mutation and clonal status of gastrointestinal stromal tumor in the sacrum
Authors: Gong Li , Li Yan-Hong , Zhao Hua-Dong , Zhao Jian-Ye , Zhang Wei 
Published: June 2009

Abstract

Background
It is very rare that gastrointestinal stromal tumor (GIST) occurs in the sacrum. Only one case of GIST occuring in the sacral region, with intracranial metastasis, has been reported in the literature. Moreover, only few cases have been published in literature about its clonal origin.

Case presentation
In this report, we present a rare case of GIST occuring in the sacrum and describe its clinicopathologic features, c-KIT gene mutation and clonal status. Microscopically, the lesion was composed of spindle cells arranged in cords, knitted and whirlpool patterns. Trabecula of bone were found in the lesion. The cytoplasm of tumor cells were abundant, and the nuclei were fusiform. Mitotic figures were rare. Immunohistochemically, the tumor cells showed positive reactivity for CD117 and CD34. On mutation analysis, a c-KIT gene mutation was found in exon 11. The result of clonal analysis demonstrated that the GIST was monoclonal.

Conclusion
In summary, we showed that tumor material, phenotypically identical with GISTs was found in the sacrum. It is difficult to differentiate GISTs from other spindle cell tumors, hence the need for immunohistochemistry, the examination of c-KIT gene amplification and sequencing.
A human glomerular SAGE transcriptome database
Authors: Nyström Jenny , Fierlbeck Wolfgang , Granqvist Anna , Kulak Stephen C , Ballermann Barbara J 
Published: June 2009

Abstract

Background
To facilitate in the identification of gene products important in regulating renal glomerular structure and function, we have produced an annotated transcriptome database for normal human glomeruli using the SAGE approach.

Description
The database contains 22,907 unique SAGE tag sequences, with a total tag count of 48,905. For each SAGE tag, the ratio of its frequency in glomeruli relative to that in 115 non-glomerular tissues or cells, a measure of transcript enrichment in glomeruli, was calculated. A total of 133 SAGE tags representing well-characterized transcripts were enriched 10-fold or more in glomeruli compared to other tissues. Comparison of data from this study with a previous human glomerular Sau3A-anchored SAGE library reveals that 47 of the highly enriched transcripts are common to both libraries. Among these are the SAGE tags representing many podocyte-predominant transcripts like WT-1, podocin and synaptopodin. Enrichment of podocyte transcript tags SAGE library indicates that other SAGE tags observed at much higher frequencies in this glomerular compared to non-glomerular SAGE libraries are likely to be glomerulus-predominant. A higher level of mRNA expression for 19 transcripts represented by glomerulus-enriched SAGE tags was verified by RT-PCR comparing glomeruli to lung, liver and spleen.

Conclusion
The database can be retrieved from, or interrogated online at http://cgap.nci.nih.gov/SAGE. The annotated database is also provided as an additional file with gene identification for 9,022, and matches to the human genome or transcript homologs in other species for 1,433 tags. It should be a useful tool for in silico mining of glomerular gene expression.
Cognitive behavioral therapy and physical exercise for climacteric symptoms in breast cancer patients experiencing treatment-induced menopause: design of a multicenter trial
Authors: Duijts Saskia FA , Oldenburg Hester SA , van Beurden Marc , Aaronson Neil K 
Published: June 2009

Abstract

Background
Premature menopause is a major concern of younger women undergoing adjuvant therapy for breast cancer. Hormone replacement therapy is contraindicated in women with a history of breast cancer. Non-hormonal medications show a range of bothersome side-effects. There is growing evidence that cognitive behavioral therapy (CBT) and physical exercise can have a positive impact on symptoms in naturally occurring menopause. The objective of this study is to investigate the efficacy of these interventions among women with breast cancer experiencing treatment-induced menopause.

Methods/design
In a randomized, controlled, multicenter trial, we are evaluating the effectiveness of CBT/relaxation, of physical exercise and of these two program elements combined, in reducing menopausal symptoms, improving sexual functioning, reducing emotional distress, and in improving the health-related quality of life of younger breast cancer patients who experience treatment-induced menopause. 325 breast cancer patients (aged < 50) are being recruited from hospitals in the Amsterdam region, and randomly allocated to one of the three treatment groups or a 'waiting list' control group. Self-administered questionnaires are completed by the patients at baseline, and at 12 weeks (T1) and 6 months (T2) post-study entry. Upon completion of the study, women assigned to the control group will be given the choice of undergoing either the CBT or physical exercise program.

Discussion
Cognitive behavioral therapy and physical exercise are potentially useful treatments among women with breast cancer undergoing treatment-induced, premature menopause. For these patients, hormonal and non-hormonal therapies are contraindicated or have a range of bothersome side-effects. Hence, research into these interventions is needed, before dissemination and implementation in the current health care system can take place.

Trial registration
The study is registered at the Netherlands Trial Register (NTR1165) and ClinicalTrials.gov (NCT00582244).
A cross-country review of strategies of the German development cooperation to strengthen human resources
Authors: Windisch Ricarda , Wyss Kaspar , Prytherch Helen 
Published: June 2009

Abstract

Background
Recent years have seen growing awareness of the importance of human resources for health in health systems and with it an intensifying of the international and national policies in place to steer a response. This paper looks at how governments and donors in five countries – Cameroon, Indonesia, Malawi, Rwanda and Tanzania – have translated such policies into action. More detailed information with regard to initiatives of German development cooperation brings additional depth to the range and entry doors of human resources for health initiatives from the perspective of donor cooperation.

Methods
This qualitative study systematically presents different approaches and stages to human resources for health development in a cross-country comparison. An important reference to capture implementation at country level was grey literature such as policy documents and programme reports. In-depth interviews along a predefined grid with national and international stakeholders in the five countries provided information on issues related to human resources for health policy processes and implementation.

Results
All five countries have institutional entities in place and have drawn up national policies to address human resources for health. Only some of the countries have translated policies into strategies with defined targets and national programmes with budgets and operational plans. Traditional approaches of supporting training for individual health professionals continue to dominate. In some cases partners have played an advocacy and technical role to promote human resources for health development at the highest political levels, but usually they still focus on the provision of ad hoc training within their programmes, which may not be in line with national human resources for health development efforts or may even be counterproductive to them. Countries that face an emergency, such as Malawi, have intensified their efforts within a relatively short time and by using donor funding support also through new initiatives such as the Global Fund to Fight AIDS, Tuberculosis and Malaria.

Conclusion
The country case studies illustrate the range of initiatives that have surged in recent years and some main trends in terms of donor initiatives. Though attention and priority attributed to human resources for health is increasing, there is still a focus on single initiatives and programmes. This can be explained in part by the complexity of the issue, and in part by its need to be addressed through a long-term approach including public sector and salary reforms that go beyond the health sector.
Assessment of methods for prediction of human West Nile virus (WNV) disease from WNV-infected dead birds
Authors: Veksler Anna , Eidson Millicent , Zurbenko Igor 
Published: June 2009

Abstract
Background
West Nile virus (WNV) is currently the leading cause of arboviral-associated encephalitis in the U.S., and can lead to long-term neurologic sequelae. Improvements in dead bird specimen processing time, including the availability of rapid field laboratory tests, allows reassessment of the effectiveness of using WNV-positive birds in forecasting human WNV disease.

Methods
Using New York State integrated WNV surveillance data from transmissions seasons in 2001–2003, this study determined which factors associated with WNV-positive dead birds are most closely associated with human disease. The study also addressed the 'delay' period between the distribution of the dead bird variable and the distribution of the human cases. In the last step, the study assessed the relative risk of contracting WNV disease for people who lived in counties with a 'signal' value of the predictor variable versus people who lived in counties with no 'signal' value of the predictor variable.

Results
The variable based on WNV-positive dead birds [(Positive/Tested)*(Population/Area)] was identified as the optimum variable for predicting WNV human disease at a county level. The delay period between distribution of the variable and human cases was determined to be approximately two weeks. For all 3 years combined, the risk of becoming a WNV case for people who lived in 'exposed' counties (those with levels of the positive dead bird variable above the signal value) was about 2 times higher than the risk for people who lived in 'unexposed' counties, but risk varied by year.

Conclusion
This analysis develops a new variable based on WNV-positive dead birds, [(Positive/Tested)*(Population/Area)] to be assessed in future real-time studies for forecasting the number of human cases in a county. A delay period of approximately two weeks between increases in this variable and the human case onset was identified. Several threshold 'signal' values were assessed and found effective at indicating human case risk, although specific thresholds are likely to vary by region and surveillance system differences.