Publication trends in the medical informatics literature: 20 years of "Medical Informatics" in MeSH

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to identify publication output, and research areas, as well as descriptively and quantitatively characterize the field of medical informatics through publication trend analysis over a twenty year period (1987–2006).</p> <p>Methods</p> <p>A bibliometric analysis of medical informatics citations indexed in Medline was performed using publication trends, journal frequency, impact factors, MeSH term frequencies and characteristics of citations.</p> <p>Results</p> <p>There were 77,023 medical informatics articles published during this 20 year period in 4,644 unique journals. The average annual article publication growth rate was 12%. The 50 identified medical informatics MeSH terms are rarely assigned together to the same document and are almost exclusively paired with a non-medical informatics MeSH term, suggesting a strong interdisciplinary trend. Trends in citations, journals, and MeSH categories of medical informatics output for the 20-year period are summarized. Average impact factor scores and weighted average impact factor scores increased over the 20-year period with two notable growth periods.</p> <p>Conclusion</p> <p>There is a steadily growing presence and increasing visibility of medical informatics literature over the years. Patterns in research output that seem to characterize the historic trends and current components of the field of medical informatics suggest it may be a maturing discipline, and highlight specific journals in which the medical informatics literature appears most frequently, including general medical journals as well as informatics-specific journals.</p

Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk

INTRODUCTION: The association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk remains unclear. Inconsistencies in previously reported findings may be partly due to differences in expression of cyclooxygenase (COX)-2. We hypothesized that genetic polymorphisms (COX-2 .926, COX-2 .5209, and COX-2 .8473) may reduce overall breast cancer risk or risk for subtypes of breast cancer by modulating the inflammatory response and may interact with aspirin or any NSAID use. METHODS: We conducted a population-based, case-control study in which we genotyped 1,067 breast cancer cases and 1,110 control individuals included in the Long Island Breast Cancer Study Project. RESULTS: No major effects of the three COX-2 variant alleles on breast cancer risk were found. A total of eight distinct haplotypes and 18 diplotypes were observed in the population. Overall, no significant associations between COX-2 haplotypes/diplotypes and breast cancer risk were observed. Among women who used aspirin or any NSAID there was little evidence for an interaction with the at-risk COX-2 genotypes, with one exception. Among women with hormone receptor positive breast cancer, the reduced risk for any NSAID use was only evident among those who had at least one variant C allele of COX-2 .8473 (odds ratio = 0.7, 95% confidence interval = 0.5 to 1.0; P for the interaction = 0.02). There was no corresponding interaction for aspirin use, possibly because of limited power. CONCLUSION: These data provide modest evidence that the C allele of COX-2 .8473 may interact with NSAIDs to reduce risk for hormone receptor positive breast cancer

Human Cytomegalovirus UL29/28 Protein Interacts with Components of the NuRD Complex Which Promote Accumulation of Immediate-Early RNA

Histone deacetylation plays a pivotal role in regulating human cytomegalovirus gene expression. In this report, we have identified candidate HDAC1-interacting proteins in the context of infection by using a method for rapid immunoisolation of an epitope-tagged protein coupled with mass spectrometry. Putative interactors included multiple human cytomegalovirus-coded proteins. In particular, the interaction of pUL38 and pUL29/28 with HDAC1 was confirmed by reciprocal immunoprecipitations. HDAC1 is present in numerous protein complexes, including the HDAC1-containing nucleosome remodeling and deacetylase protein complex, NuRD. pUL38 and pUL29/28 associated with the MTA2 component of NuRD, and shRNA-mediated knockdown of the RBBP4 and CHD4 constituents of NuRD inhibited HCMV immediate-early RNA and viral DNA accumulation; together this argues that multiple components of the NuRD complex are needed for efficient HCMV replication. Consistent with a positive acting role for the NuRD elements during viral replication, the growth of pUL29/28- or pUL38-deficient viruses could not be rescued by treating infected cells with the deacetylase inhibitor, trichostatin A. Transient expression of pUL29/28 enhanced activity of the HCMV major immediate-early promoter in a reporter assay, regardless of pUL38 expression. Importantly, induction of the major immediate-early reporter activity by pUL29/28 required functional NuRD components, consistent with the inhibition of immediate-early RNA accumulation within infected cells after knockdown of RBBP4 and CHD4. We propose that pUL29/28 modifies the NuRD complex to stimulate the accumulation of immediate-early RNAs

Herpesvirus Glycoproteins Undergo Multiple Antigenic Changes before Membrane Fusion

Herpesvirus entry is a complicated process involving multiple virion glycoproteins and culminating in membrane fusion. Glycoprotein conformation changes are likely to play key roles. Studies of recombinant glycoproteins have revealed some structural features of the virion fusion machinery. However, how the virion glycoproteins change during infection remains unclear. Here using conformation-specific monoclonal antibodies we show in situ that each component of the Murid Herpesvirus-4 (MuHV-4) entry machinery—gB, gH/gL and gp150—changes in antigenicity before tegument protein release begins. Further changes then occurred upon actual membrane fusion. Thus virions revealed their final fusogenic form only in late endosomes. The substantial antigenic differences between this form and that of extracellular virions suggested that antibodies have only a limited opportunity to block virion membrane fusion

Computational study of associations between histone modification and protein-DNA binding in yeast genome by integrating diverse information

<p>Abstract</p> <p>Background</p> <p>In parallel with the quick development of high-throughput technologies, <it>in vivo (vitro) </it>experiments for genome-wide identification of protein-DNA interactions have been developed. Nevertheless, a few questions remain in the field, such as how to distinguish true protein-DNA binding (functional binding) from non-specific protein-DNA binding (non-functional binding). Previous researches tackled the problem by integrated analysis of multiple available sources. However, few systematic studies have been carried out to examine the possible relationships between histone modification and protein-DNA binding. Here this issue was investigated by using publicly available histone modification data in yeast.</p> <p>Results</p> <p>Two separate histone modification datasets were studied, at both the open reading frame (ORF) and the promoter region of binding targets for 37 yeast transcription factors. Both results revealed a distinct histone modification pattern between the functional protein-DNA binding sites and non-functional ones for almost half of all TFs tested. Such difference is much stronger at the ORF than at the promoter region. In addition, a protein-histone modification interaction pathway can only be inferred from the functional protein binding targets.</p> <p>Conclusions</p> <p>Overall, the results suggest that histone modification information can be used to distinguish the functional protein-DNA binding from the non-functional, and that the regulation of various proteins is controlled by the modification of different histone lysines such as the protein-specific histone modification levels.</p

Murine Gammaherpesvirus-68 Inhibits Antigen Presentation by Dendritic Cells

Dendritic cells (DCs) play a central role in initiating adaptive immunity. Murine gammaherpesvirus-68 (MHV-68), like many persistent viruses, infects DCs during normal host colonization. It therefore provides a means to understanding what host and viral genes contribute to this aspect of pathogenesis. The infected DC phenotype is likely to depend on whether viral gene expression is lytic or latent and whether antigen presentation is maintained. For MHV-68, neither parameter has been well defined. Here we show that MHV-68 infects immature but not mature bone marrow-derived DCs. Infection was predominantly latent and these DCs showed no obvious defect in antigen presentation. Lytically infected DCs were very different. These down-regulated CD86 and MHC class I expression and presented a viral epitope poorly to CD8+ T cells. Antigen presentation improved markedly when the MHV-68 K3 gene was disrupted, indicating that K3 fulfils an important function in infected DCs. MHV-68 infects only a small fraction of the DCs present in lymphoid tissue, so K3 expression is unlikely to compromise significantly global CD8+ T cell priming. Instead it probably helps to maintain lytic gene expression in DCs once CD8+ T cell priming has occurred

A Cis-Regulatory Map of the Drosophila Genome

Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide1, 2 has successfully identified specific subtypes of regulatory elements3. In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements4, chromatin states5, transcription factor binding sites6, 7, 8, 9, RNA polymerase II regulation8 and insulator elements10; however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships

Occupancy maps of 208 chromatin-associated proteins in one human cell type

Transcription factors are DNA-binding proteins that have key roles in gene regulation. Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes. However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–seq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP–seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium

Connecting the dots between brand experience and brand loyalty: The mediating role of brand personality and brand relationships

This article critically examines consumer–brand relationships from the perspective of interpersonal relationship theory. Specifically, the authors investigate the relationship between brand experience and the two components of brand loyalty, namely purchase brand loyalty and attitudinal brand loyalty. The study also examines the link between brand experience and brand relationship variables, brand trust, brand attachment and brand commitment. In addition, the mediating role of brand personality and brand commitment in the relationship between brand experience and brandloyalty is investigated. Drawing on the results of an empirical cross-brand study from three product categories, the authors demonstrate that brand experience, brand personality and brand relationship variables (brand attachment and brand commitment) all affect the degree to which a consumer is loyal to a brand. On the basis of the findings, the authors offer guidelines to managers on how to build and sustain purchase and attitudinal brand loyalty by enhancing brand experience. The theoretical and managerial significance of the findings together with directions for future research are discussed