bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antineoplastic activity of lentiviral vectors expressing interferon-α in a preclinical model of primary effusion lymphoma
Authors: Calabrò Maria Luisa , Gasperini Paola , Di Gangi Iole Maria , Indraccolo Stefano , Barbierato Massimo , Amadori Alberto , Chieco-Bianchi Luigi 
Published: February 2009

AbstractThe peculiar site of development of primary effusion lymphoma (PEL) highlights a specific role of body cavities in the pathogenesis of this neoplasia. We used a xenograft murine model of PEL to characterize the contribution of the host microenvironment to PEL growth. The activity of a murine (ie, host-specific) interferon-α1 (IFN-α1)–expressing lentiviral vector (mIFN-α1-LV) was compared with that of a human (h) IFN-α2b-LV. LVs efficiently delivered the transgene to PEL cells and conferred long-term transgene expression in vitro and in vivo. Treatment of PEL-injected severe combined immunodeficiency mice with hIFN-α2b-LV significantly prolonged mice survival and reduced ascites development. Interestingly, mIFN-α1-LV showed an antineoplastic activity comparable with that observed with hIFN-α2b-LV. As mIFN-α1 retained species-restricted activity in vitro, it probably acted in vivo on the intracavitary murine milieu. mIFN-α1–treated murine mesothelial cells were found to express tumor necrosis factor–related apoptosis-inducing ligand and to significantly trigger apoptosis of cocultured PEL cells in a tumor necrosis factor–related apoptosis-inducing ligand-dependent manner. These data suggest that the interaction between lymphomatous and mesothelial cells lining the body cavities may play a key role in PEL growth control and also indicate that the specific targeting of microenvironment may impair PEL development.
Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a “vaccinal effect” of rituximab
Authors: Hilchey Shannon P. , Hyrien Ollivier , Mosmann Tim R. , Livingstone Alexandra M. , Friedberg Jonathan W. , Young Faith , Fisher Richard I. , Kelleher Raymond J. , Bankert Richard B. , Bernstein Steven H. 
Published: February 2009

Abstract
The incorporation of rituximab, a chimeric anti-CD20 monoclonal antibody, into the therapeutic armamentarium for patients with follicular lymphoma (FL) has significantly improved treatment outcome for such patients. Despite the almost universal application of this therapy, however, its exact mechanism of action has not been completely defined. One proposed mechanism is that of a “vaccinal” effect, whereby FL cell kill by rituximab results in the elicitation of an FL-specific T-cell response. The demonstration that rituximab can even elicit such a response in patients has, to our knowledge, never been shown. We analyzed the response against the immunoglobulin expressed by the FL before and after rituximab monotherapy in 5 FL patients and found an increase in FL idiotype–specific T cells after rituximab in 4 of 5 patients. Our data thus provide “proof of principle” for the ability of passive immunotherapy with rituximab to elicit an active FL-specific cellular response.
Robust methods for accurate diagnosis using pan-microbiological oligonucleotide microarrays
Authors: Liu Yang , Sam Lee , Li Jianrong , Lussier Yves A 
Published: February 2009

Abstract

Background
To address the limitations of traditional virus and pathogen detection methodologies in clinical diagnosis, scientists have developed high-throughput oligonucleotide microarrays to rapidly identify infectious agents. However, objectively identifying pathogens from the complex hybridization patterns of these massively multiplexed arrays remains challenging.

Methods
In this study, we conceived an automated method based on the hypergeometric distribution for identifying pathogens in multiplexed arrays and compared it to five other methods. We evaluated these metrics: 1) accurate prediction, whether the top ranked prediction(s) match the real virus(es); 2) four accuracy scores.

Results
Though accurate prediction and high specificity and sensitivity can be achieved with several methods, the method based on hypergeometric distribution provides a significant advantage in term of positive predicting value with two to sixty folds the positive predicting values of other methods.

Conclusion
The proposed multi-specie array analysis based on the hypergeometric distribution addresses shortcomings of previous methods by enhancing signals of positively hybridized probes.
Leveraging existing biological knowledge in the identification of candidate genes for facial dysmorphology
Authors: Tipney Hannah J , Leach Sonia M , Feng Weiguo , Spritz Richard , Williams Trevor , Hunter Lawrence 
Published: February 2009

Abstract

Background
In response to the frequently overwhelming output of high-throughput microarray experiments, we propose a methodology to facilitate interpretation of biological data in the context of existing knowledge. Through the probabilistic integration of explicit and implicit data sources a functional interaction network can be constructed. Each edge connecting two proteins is weighted by a confidence value capturing the strength and reliability of support for that interaction given the combined data sources. The resulting network is examined in conjunction with expression data to identify groups of genes with significant temporal or tissue specific patterns. In contrast to unstructured gene lists, these networks often represent coherent functional groupings.

Results
By linking from shared functional categorizations to primary biological resources we apply this method to craniofacial microarray data, generating biologically testable hypotheses and identifying candidate genes for craniofacial development.

Conclusion
The novel methodology presented here illustrates how the effective integration of pre-existing biological knowledge and high-throughput experimental data drives biological discovery and hypothesis generation.
Phenotype forecasting with SNPs data through gene-based Bayesian networks
Authors: Malovini Alberto , Nuzzo Angelo , Ferrazzi Fulvia , Puca Annibale A , Bellazzi Riccardo 
Published: February 2009

AbstractBackgroundBayesian networks are powerful instruments to learn genetic models from association studies data. They are able to derive the existing correlation between genetic markers and phenotypic traits and, at the same time, to find the relationships between the markers themselves. However, learning Bayesian networks is often non-trivial due to the high number of variables to be taken into account in the model with respect to the instances of the dataset. Therefore, it becomes very interesting to use an abstraction of the variable space that suitably reduces its dimensionality without losing information. In this paper we present a new strategy to achieve this goal by mapping the SNPs related to the same gene to one meta-variable. In order to assign states to the meta-variables we employ an approach based on classification trees.ResultsWe applied our approach to data coming from a genome-wide scan on 288 individuals affected by arterial hypertension and 271 nonagenarians without history of hypertension. After pre-processing, we focused on a subset of 24 SNPs. We compared the performance of the proposed approach with the Bayesian network learned with SNPs as variables and with the network learned with haplotypes as meta-variables. The results were obtained by running a hold-out experiment five times. The mean accuracy of the new method was 64.28%, while the mean accuracy of the SNPs network was 58.99% and the mean accuracy of the haplotype network was 54.57%.ConclusionThe new approach presented in this paper is able to derive a gene-based predictive model based on SNPs data. Such model is more parsimonious than the one based on single SNPs, while preserving the capability of highlighting predictive SNPs configurations. The prediction performance of this approach was consistently superior to the SNP-based and the haplotype-based one in all the test sets of the evaluation procedure. The method can be then considered as an alternative way to analyze the data coming from association studies.
PhenoGO: an integrated resource for the multiscale mining of clinical and biological data
Authors: Sam Lee T , Mendonça Eneida A , Li Jianrong , Blake Judith , Friedman Carol , Lussier Yves A 
Published: February 2009

Abstract
The evolving complexity of genome-scale experiments has increasingly centralized the role of a highly computable, accurate, and comprehensive resource spanning multiple biological scales and viewpoints. To provide a resource to meet this need, we have significantly extended the PhenoGO database with gene-disease specific annotations and included an additional ten species. This a computationally-derived resource is primarily intended to provide phenotypic context (cell type, tissue, organ, and disease) for mining existing associations between gene products and GO terms specified in the Gene Ontology Databases Automated natural language processing (BioMedLEE) and computational ontology (PhenOS) methods were used to derive these relationships from the literature, expanding the database with information from ten additional species to include over 600,000 phenotypic contexts spanning eleven species from five GO annotation databases. A comprehensive evaluation evaluating the mappings (n = 300) found precision (positive predictive value) at 85%, and recall (sensitivity) at 76%. Phenotypes are encoded in general purpose ontologies such as Cell Ontology, the Unified Medical Language System, and in specialized ontologies such as the Mouse Anatomy and the Mammalian Phenotype Ontology. A web portal has also been developed, allowing for advanced filtering and querying of the database as well as download of the entire dataset http://www.phenogo.org.
Comparative analysis of methods for gene transcription profiling data derived from different microarray technologies in rat and mouse models of diabetes
Authors: Wilder Steven P , Kaisaki Pamela J , Argoud Karène , Salhan Anita , Ragoussis Jiannis , Bihoreau Marie-Thérèse , Gauguier Dominique 
Published: February 2009

AbstractBackgroundMicroarray technologies are widely used to quantify the abundance of transcripts corresponding to thousands of genes. To maximise the robustness of transcriptome results, we have tested the performance and reproducibility of rat and mouse gene expression data obtained with Affymetrix, Illumina and Operon platforms.ResultsWe present a thorough analysis of the degree of reproducibility provided by analysing the transcriptomic profile of the same animals of several experimental groups under different popular microarray technologies in different tissues. Concordant results from inter- and intra-platform comparisons were maximised by testing many popular computational methods for generating fold changes and significances and by only considering oligonucleotides giving high expression levels. The choice of Affymetrix signal extraction technique was shown to have the greatest effect on the concordance across platforms. In both species, when choosing optimal methods, the agreement between data generated on the Affymetrix and Illumina was excellent; this was verified using qRT-PCR on a selection of genes present on all platforms.ConclusionThis study provides an extensive assessment of analytical methods best suited for processing data from different microarray technologies and can assist integration of technologically different gene expression datasets in biological systems.
Understanding Haemophilus parasuis infection in porcine spleen through a transcriptomics approach
Authors: Chen Hongbo , Li Changchun , Fang Mingdi , Zhu Mengjin , Li Xinyun , Zhou Rui , Li Kui , Zhao Shuhong 
Published: February 2009

AbstractBackgroundHaemophilus parasuis(HPS) is an important swine pathogen that causes Glässer's disease, which is characterized by fibrinous polyserositis, meningitis and arthritis. The molecular mechanisms that underlie the pathogenesis of the disease remain poorly understood, particularly the resistance of porcine immune system to HPS invasion. In this study, we investigated the global changes in gene expression in the spleen following HPS infection using the Affymetrix Porcine Genechip™.ResultsA total of 931 differentially expressed (DE) transcripts were identified in the porcine spleen 7 days after HPS infection; of these, 92 unique genes showed differential expression patterns based on analysis using BLASTX and Gene Ontology. The DE genes involved in the immune response included genes for inflammasomes (RETN,S100A8,S100A9,S100A12), adhesion molecules (CLDN3,CSPG2,CD44,LGALS8), transcription factors (ZBTB16,SLC39A14,CEBPD,CEBPB), acute-phase proteins and complement (SAA1,LTF,HP,C3), differentiation genes for epithelial cells and keratinocytes (TGM1,MS4A8B,CSTA), and genes related to antigen processing and presentation (HLA-B,HLA-DRB1). Further immunostimulation analyses indicated that mRNA levels ofS100A8,S100A9, andS100A12in porcine PK-15 cells increased within 48 h and were sustained after administration of lipopolysaccharide (LPS) and Poly(I:C) respectively. In addition, mapping of DE genes to porcine health traits QTL regions showed that 70 genes were distributed in 7 different known porcine QTL regions. Finally, 10 DE genes were validated by quantitative PCR.ConclusionOur findings demonstrate previously unrecognized changes in gene transcription that are associated with HPS infectionin vivo, and many potential cascades identified in the study clearly merit further investigation. Our data provide new clues to the nature of the immune response in mammals, and we have identified candidate genes that are related to resistance to HPS.
Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarization
Authors: van Riet Elly , Everts Bart , Retra Kim , Phylipsen Marion , van Hellemond Jaap J , Tielens Aloysius GM , van der Kleij Desiree , Hartgers Franca C , Yazdanbakhsh Maria 
Published: February 2009

AbstractBackgroundRecognition of pathogens by dendritic cells (DCs) through interaction with pattern recognition receptors, including Toll like receptors (TLR), is crucial for the initiation of appropriate polarized T helper (Th) cell responses. Yet, the characteristics and differences in molecular profiles of DCs with different T cell polarizing capacities are still poorly defined. To address this issue, the molecular profile of human monocyte derived DCs was characterized after exposure to TLR4 ligand LPS in combination with the Th1 promoting bacterial extracts fromListeria monocytogenesandEscherichia colior the Th2 promoting helminth derived phospholipids fromSchistosoma mansoniandAscaris lumbricoides, all with TLR2 activating capacity.ResultsWith regard to the signalling pathways activated upon exposure to LPS and the TLR2 activating compounds, we find that the ratio of activated Mitogen Activated Protein Kinases (MAPK)p-ERK/p-p38 is lower in DCs stimulated with the bacterial products compared to DCs stimulated with the helminth products, which correlates with the Th1 and Th2 polarizing capacity of these compounds. Furthermore, analysis of the mRNA expression levels of a set of 25 carefully selected genes potentially involved in modulation of T cell polarization revealed that the mRNA expression of notch ligand delta-4 and transcription factor c-fos are differentially regulated and show a strong correlation with Th1 and Th2 polarization, respectively.ConclusionThis study shows that combined TLR2 and TLR4 activation in the context of different antigen sources can induce very distinct molecular profiles in DCs and suggests that the Th1/Th2 polarizing capacity of compounds can be predicted with the molecular signature they induce in DCs.
DNA restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolates from HIV-seropositive and HIV-seronegative patients in Kampala, Uganda
Authors: Asiimwe Benon B , Joloba Moses L , Ghebremichael Solomon , Koivula Tuija , Kateete David P , Katabazi Fred A , Pennhag Alexander , Petersson Ramona , Kallenius Gunilla 
Published: February 2009

Abstract

Background
The identification and differentiation of strains of Mycobacterium tuberculosis by DNA fingerprinting has provided a better understanding of the epidemiology and tracing the transmission of tuberculosis. We set out to determine if there was a relationship between the risk of belonging to a group of tuberculosis patients with identical mycobacterial DNA fingerprint patterns and the HIV sero-status of the individuals in a high TB incidence peri-urban setting of Kampala, Uganda.

Methods
One hundred eighty three isolates of Mycobacterium tuberculosis from 80 HIV seropositive and 103 HIV seronegative patients were fingerprinted by standard IS6110-RFLP. Using the BioNumerics software, strains were considered to be clustered if at least one other patient had an isolate with identical RFLP pattern.

Results
One hundred and eighteen different fingerprint patterns were obtained from the 183 isolates. There were 34 clusters containing 54% (99/183) of the patients (average cluster size of 2.9), and a majority (96.2%) of the strains possessed a high copy number (≥ 5 copies) of the IS6110 element. When strains with <5 bands were excluded from the analysis, 50.3% (92/183) were clustered, and there was no difference in the level of diversity of DNA fingerprints observed in the two sero-groups (adjusted odds ratio [aOR] 0.85, 95%CI 0.46–1.56, P = 0.615), patients aged <40 years (aOR 0.53, 95%CI 0.25–1.12, P = 0.100), and sex (aOR 1.12, 95%CI 0.60–2.06, P = 0.715).

Conclusion
The sample showed evidence of a high prevalence of recent transmission with a high average cluster size, but infection with an isolate with a fingerprint found to be part of a cluster was not associated with any demographic or clinical characteristics, including HIV status.
Incidence of bacterial meningitis (2001–2005) in Lazio, Italy: the results of a integrated surveillance system
Authors: Giorgi Rossi Paolo , Mantovani Jessica , Ferroni Eliana , Forcina Antonio , Stanghellini Elena , Curtale Filippo , Borgia Piero 
Published: February 2009

Abstract

Background
Monitoring the incidence of bacterial meningitis is important to plan and evaluate preventive polices. The study's aim was to estimate the incidence of bacterial meningitis by aetiological agent in the period 2001–2005, in Lazio Italy (5.3 mln inhabitants).

Methods
Data collected from four sources – hospital surveillance of bacterial meningitis, laboratory information system, the mandatory infectious diseases notifications, and hospital information system – were combined into a single archive.

Results
944 cases were reported, 89% were classified as community acquired. S. pneumoniae was the most frequent aetiological agent in Lazio, followed by N. meningitis. Incidence of H. influenzae decreased during the period. 17% of the cases had an unknown aetiology and 13% unspecified bacteria. The overall incidence was 3.7/100,000. Children under 1 year were most affected (50.3/100.000), followed by 1–4 year olds (12.5/100,000). The percentage of meningitis due to aetiological agents included in the vaccine targets, not considering age, is 31%. Streptococcus spp. was the primary cause of meningitis in the first three months of life. The capture-recapture model estimated underreporting at 17.2% of the overall incidence.

Conclusion
Vaccine policies should be planned and monitored based on these results. The integrated surveillance system allowed us to observe a drop in H. influenzae b meningitis incidence consequent to the implementation of a mass vaccination of newborns.
How do medical students value health on the EQ-5D? Evaluation of hypothetical health states compared to the general population
Authors: Barbist Maria-Theresa , Renn Daniela , Noisternig Bianca , Rumpold Gerhard , Höfer Stefan 
Published: February 2009

AbstractBackgroundMedical students gain a particular perspective on health problems during their medical education. This article describes how medical students value 10 hypothetical health states using the EQ-5D compared to the general population.MethodsBased on a sample of 161 medical students (male: 41%) we compared valuations of 10 hypothetical EQ-5D health states collected in face to face interviews with the valuations of the general population. Self-reported health on the EQ-5D was also collected.ResultsEvery third health state was valuated higher by the medical students compared to data of the general population. The differences were independent of the severity of the hypothetical health state. Concerning the self-reported health, the majority of the students (66%) reported no problems in the five EQ-5D domains (EQ-5D VAS M = 87.3 ± 9.6 SD). However, when compared to an age-matched sample the medical students show significantly more problems in the area of pain/discomfort and anxiety/depression.ConclusionMedical students have a tendency to value health states higher than the general public. Medical professionals should be continuously aware that their assessment of the patients health state can differ from the valuations of the general population.
Drugs targeting the mitochondrial pore act as citotoxic and cytostatic agents in temozolomide-resistant glioma cells
Authors: Lena Annalisa , Rechichi Mariarosa , Salvetti Alessandra , Bartoli Barbara , Vecchio Donatella , Scarcelli Vittoria , Amoroso Rosina , Benvenuti Lucia , Gagliardi Rolando , Gremigni Vittorio , Rossi Leonardo 
Published: February 2009

AbstractBackgroundHigh grade gliomas are one of the most difficult cancers to treat and despite surgery, radiotherapy and temozolomide-based chemotherapy, the prognosis of glioma patients is poor. Resistance to temozolomide is the major barrier to effective therapy. Alternative therapeutic approaches have been shown to be ineffective for the treatment of genetically unselected glioma patients. Thus, novel therapies are needed. Mitochondria-directed chemotherapy is an emerging tool to combat cancer, and inner mitochondrial permeability transition (MPT) represents a target for the development of cytotoxic drugs. A number of agents are able to induce MPT and some of them target MPT-pore (MPTP) components that are selectively up-regulated in cancer, making these agents putative cancer cell-specific drugs.ObjectiveThe aim of this paper is to report a comprehensive analysis of the effects produced by selected MPT-inducing drugs (Betulinic Acid, Lonidamine, CD437) in a temozolomide-resistant glioblastoma cell line (ADF cells).MethodsEGFRvIII expression has been assayed by RT-PCR. EGFR amplification and PTEN deletion have been assayed by differential-PCR. Drugs effect on cell viability has been tested by crystal violet assay. MPT has been tested by JC1 staining. Drug cytostatic effect has been tested by mitotic index analysis. Drug cytotoxic effect has been tested by calcein AM staining. Apoptosis has been assayed by Hoechst incorporation and Annexine V binding assay. Authophagy has been tested by acridine orange staining.ResultsWe performed a molecular and genetic characterization of ADF cells and demonstrated that this line does not express the EGFRvIII and does not show EGFR amplification. ADF cells do not show PTEN mutation but differential PCR data indicate a hemizygous deletion of PTEN gene. We analyzed the response of ADF cells to Betulinic Acid, Lonidamine, and CD437. Our data demonstrate that MPT-inducing agents produce concentration-dependent cytostatic and cytotoxic effects in parallel with MPT induction triggered through MPTP. CD437, Lonidamine and Betulinic acid trigger apoptosis as principal death modality.ConclusionThe obtained data suggest that these pharmacological agents could be selected as adjuvant drugs for the treatment of high grade astrocytomas that resist conventional therapies or that do not show any peculiar genetic alteration that can be targeted by specific drugs.