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Advancement of biomarker discovery and validation through the HUPO plasma proteome project.

The Human Proteome Organization (HUPO) Plasma Proteome Project has mounted a Pilot Phase focussed on key problems essential for standardization of specimen collection, specimen handling, choice of fractionation and analysis technologies, and search engines and databases for protein identifications. This international collaboration will lay the groundwork for many large-scale clinical and epidemiological studies of health and disease.

Biomarkers↗

Diabetes and the internet.

This paper examines what the World Wide Web has to offer patients, families and professionals in relation to diabetes. The potential pitfalls and dangers are discussed, leading to a wider debate on how the Internet can be expected to impact upon diabetes and other health care provision in the near future, and how health care professionals' practices will have to change. Themes include: the World Wide Web (finding material, assessing authenticity, pitfalls for patients, personalized pages, chat rooms, security); e-mail consultation (benefits, risks, minimizing risk, what to tell patients, legal constraints, security); telemedicine (telemetry, surveillance, security); search engines (journals, etc.); looking ahead (digital television, web-based medical records).

Diabetes Mellitus↗

Mass spectrometric identification of proteins in complex post-genomic projects. Soluble proteins of the metabolically versatile, denitrifying 'Aromatoleum' sp. strain EbN1.

The rapidly developing proteomics technologies help to advance the global understanding of physiological and cellular processes. The lifestyle of a study organism determines the type and complexity of a given proteomic project. The complexity of this study is characterized by a broad collection of pathway-specific subproteomes, reflecting the metabolic versatility as well as the regulatory potential of the aromatic-degrading, denitrifying bacterium 'Aromatoleum' sp. strain EbN1. Differences in protein profiles were determined using a gel-based approach. Protein identification was based on a progressive application of MALDI-TOF-MS, MALDI-TOF-MS/MS and LC-ESI-MS/MS. This progression was result-driven and automated by software control. The identification rate was increased by the assembly of a project-specific list of background signals that was used for internal calibration of the MS spectra, and by the combination of two search engines using a dedicated MetaScoring algorithm. In total, intelligent bioinformatics could increase the identification yield from 53 to 70% of the analyzed 5,050 gel spots; a total of 556 different proteins were identified. MS identification was highly reproducible: most proteins were identified more than twice from parallel 2DE gels with an average sequence coverage of >50% and rather restrictive score thresholds (Mascot >or=95, ProFound >or=2.2, MetaScore >or=97). The MS technologies and bioinformatics tools that were implemented and integrated to handle this complex proteomic project are presented. In addition, we describe the basic principles and current developments of the applied technologies and provide an overview over the current state of microbial proteome research.

Amino Acid Sequence↗

Survey of Internet web sites on circumcision.

Information on circumcision is available on the Internet, which is available for parents to review. The purpose of this study is to sample and summarize the Internet's informational content on circumcision. One hundred web sites were identified using the Google search engine on February 15, 2003. The informational content of each site was reviewed and tabulated. Seventy-three of the 100 web sites were appropriate for review. Ten agreed with recommending circumcision, 4 agreed under limited circumstances, 37 recommended against circumcision, and 4 recommended against circumcision under limited circumstances. Eighteen did not take a stance for or against. Thirteen agreed that circumcision reduces the risk of urinary tract infection, and 16 disagreed with this. Fifteen agreed that circumcision reduces the risk of penile cancer and 14 disagreed with this. Fifty-one percent of web sites surveyed were against circumcision, 14% of the web sites surveyed recommended circumcision, and 25% of surveyed web sites had no opinion.

Circumcision, Male↗

Exploring the connection between self-efficacy and effective diabetes self-management.

PURPOSE: The purpose of this study was to review the existing empirical evidence about factors that contribute to effective diabetes self-management as indicated by healthy outcomes in persons with the disease, with a specific focus on self-efficacy, to determine the link between learned self-efficacy and effective diabetes self-management in adults. METHODS: A systematic review was conducted of the extant literature from 1985-2001 that described factors related to effective self-management of diabetes. The review included theoretical and empirical articles. The search engines included CINAHL, MEDLINE, PUBMED, and COCHRANE. RESULTS: Empirical evidence supports the following factors to improve the education outcomes for adults with diabetes: involve people with diabetes in their own care, guide them in actively learning about the disease, explore their feelings about having the disease, and teach them the skills necessary to adjust their behavior to control their own health outcomes. Thus, the goal for educating people with diabetes is to improve their individual self-efficacy and, accordingly, their self-management ability. CONCLUSIONS: Education sessions need to involve fewer lectures and more practical, interactive exercises that focus on developing specific skills. Follow-up contact is a valuable method for helping people make a healthy adjustment to living with diabetes.

Adaptation, Psychological↗

Provider impact in diabetes education. What we know, what we would like to know, paradigms for asking.

PURPOSE: A literature search from 1985 to the present was performed using Web-based search engines to identify evidence-based studies of diabetes education. METHODS: Twelve studies were identified in which a provider characteristic was defined as a discriminate variable associated with impact or efficacy of the education intervention. Provider was defined as all those participating in diabetes care and education (e.g., patient, education and care teams, funding and policy agencies). The Certified Diabetes Educator credential also was described. RESULTS: Specialty or discipline of the provider/care team, technology when used to assist providers, and physician practice patterns have been assessed. There is a paucity of research that assesses provider impact or the specific impact of provider characteristics on diabetes outcomes in a controlled and scientifically rigorous fashion. CONCLUSIONS: Suggestions for evaluating provider impact based on literature concerning psychotherapy and healthcare education outcomes are: identify provider characteristics/attitudes/skills and link them to outcomes, define therapeutic alliance in diabetes care/education and assess its contribution to outcomes; and use performance measures as provider characteristics.

Diabetes Mellitus↗

New trends in the cyber and street market of recreational drugs? The case of 2C-T-7 ('Blue Mystic').

2C-T-7 ('Blue Mystic'), an illicit compound which shows similarities with MDMA and other designer drugs, has been only occasionally identified in the EU, but discussion on the Internet between experimenters has recently grown significantly. We aimed at collecting together in a review the available information on 2C-T-7, both at the cyber and at the street market level. 2C-T-7 was first synthesized in 1986; its desired effects include both a sense of empathy and of well-being. Hallucinations, nausea, anxiety, panic attacks and paranoid ideation are anecdotally reported. According to the different European sources here approached, the availability of 2C-T-7 at street level seems to be currently very low, although one death related to a mono-intoxication with 2C-T-7 has been documented in the USA. With respect to information on 2C-T-7 available online, due to both redundancy and relevance issues the initial identified sample of 360 was reduced to 118 websites. In 14 (11.9%) websites, the detailed description of the 2C-T-7 synthesis was given. Harm Reduction websites appeared significantly earlier in the search engines results' list than Anti drugs (p 0.006) websites. Five (4.2%) websites apparently offered 2C-T-7 for sale. The large body of knowledge available online seems to contrast with small numbers of seizures at street level; an exhaustive web mapping of drug-related issues may be of interest for the clinician. Projects aimed at designing more 'attractive' prevention websites should be planned and future studies should better assess the characteristics of those consumers who take advantage of the online information of hallucinogenic compounds.

Affect↗

The Internet's impact on the practice of psychiatry.

OBJECTIVE: In the past decade, the Internet has rapidly evolved into a mainstream communication and information resource. During this period, health care resources and databases have been developed. This paper reviews the literature on e-mail communication and on-line health care information resources to determine the impact on psychiatry. METHOD: The Medline electronic database and the search engines Altavista and Google were used to review the literature discussing on-line guidelines, clinical trials, and continuing medical education (CME) resources, as well as the literature on Internet usage, e-journals, and e-mail communication. CONCLUSIONS: The Internet has accelerated psychiatrists' access to new research findings and other information pertinent to clinical practice. It has eliminated distance barriers and offered psychiatrists and the general public equal access to scientific articles, clinical trials, and guidelines. The literature shows that the general public is using the Internet to obtain information and, to a lesser extent, to communicate with health care professionals. In terms of health outcomes, the effectiveness of patient on-line access to information is still uncertain, and further research is necessary. Although physicians have embraced on-line journals, further work is required before they embrace on-line CME. The Internet has developed to a point where it is important for psychiatrists to understand the issues and pitfalls in its use, to be able to access the resources available, and to be in a position to mentor patients who want to research their condition further.

Education, Medical, Continuing↗

Vaginal douching.

OBJECTIVE: To review current literature on vaginal douching. DATA SOURCES: MEDLINE, CINAHL, and Cochrane databases from 1997 to 2001, using keywords douche or douching; 2001 Web sites of the Centers for Disease Control and Prevention; and Internet search engines for information about current retail sales of douches. STUDY SELECTION: MEDUNE included 67 records, CINAHL 18, and Cochrane 2. Abstracts of articles in English were reviewed, and those pertaining to vaginal douching practices were included. MEDLINE had 44 pertinent articles, CINAHL 11, and Cochrane 1. References from these articles were reviewed and included when appropriate. DATA EXTRACTION: Articles were reviewed and summarized. DATA SYNTHESIS: Vaginal douching is a common practice for women in the United States. Douching is associated with adverse reproductive and gynecologic outcomes including bacterial vaginosis, preterm birth, low-birth-weight infants, pelvic inflammatory disease, chlamydial infection, tubal pregnancy, higher rates of HIV transmission, and cervical cancer. Cultural beliefs and educational factors strongly influence douching practices. CONCLUSIONS: Nursing assessment of women should include information on vaginal douching practices and beliefs. Nurses should use culturally appropriate educational strategies to discourage women of all ages from using vaginal douches as part of routine feminine hygiene because of the associated risks. Further research is needed on factors that influence women's beliefs and douching practices.

Attitude to Health↗

Pharmacogenomic effect of cytochrome P450 2C9 polymorphisms in different populations.

Presently, warfarin sodium or coumadin is the therapeutic drug of choice for maintenance anticoagualtion therapy. One of several factors underlying the variability in warfarin dose response in the patients receiving this oral anticoagulant is a genetic predisposition, especially the CYP2C9 polymorphisms. The pharmacogenomic effect of CYP2C9 polymorphisms is assessed in different racial populations. A retrospective review was performed with an electronic search engine on this topic to get the data for further meta-analysis. A significant correlation between population ethnicity and gene frequencies was detected in this study. A significant low frequency of CYP2C9 variants among the Asian can be demonstrated. The clinical correlation between CYP2C9 polymorphism and warfarin metabolism was also assessed. Four available case-control reports were selected for this meta-analysis. CYP2C9 variants are strongly associated with low-dose warfarin requirement. In summary, the CYP2C9 variants strongly affect the warfarin dose requirement. This phenomenon is ethnically dependent. Due to the high variant frequency among whites in the West, the investigation for CYP2C9 might be useful for this population, not the Asians, whose variant frequency is very low.

Anticoagulants↗

PEDro: a database of randomised controlled trials in physiotherapy.

PEDro is a database of clinical trials designed to assist the practice of evidence-based physiotherapy. When complete, it will contain bibliographic details, abstracts and quality assessment scores of all published randomised controlled trials in physiotherapy. Trials on the database will be rated on the basis of their methodological quality, so that users of the database can be guided to those trials which provide the most methodologically sound sources of evidence. The database has been made freely available on the world wide web, where it can be searched with a powerful and user-friendly search engine.

Australia↗

PASS2: an automated database of protein alignments organised as structural superfamilies.

BACKGROUND: The functional selection and three-dimensional structural constraints of proteins in nature often relates to the retention of significant sequence similarity between proteins of similar fold and function despite poor sequence identity. Organization of structure-based sequence alignments for distantly related proteins, provides a map of the conserved and critical regions of the protein universe that is useful for the analysis of folding principles, for the evolutionary unification of protein families and for maximizing the information return from experimental structure determination. The Protein Alignment organised as Structural Superfamily (PASS2) database represents continuously updated, structural alignments for evolutionary related, sequentially distant proteins. DESCRIPTION: An automated and updated version of PASS2 is, in direct correspondence with SCOP 1.63, consisting of sequences having identity below 40% among themselves. Protein domains have been grouped into 628 multi-member superfamilies and 566 single member superfamilies. Structure-based sequence alignments for the superfamilies have been obtained using COMPARER, while initial equivalencies have been derived from a preliminary superposition using LSQMAN or STAMP 4.0. The final sequence alignments have been annotated for structural features using JOY4.0. The database is supplemented with sequence relatives belonging to different genomes, conserved spatially interacting and structural motifs, probabilistic hidden markov models of superfamilies based on the alignments and useful links to other databases. Probabilistic models and sensitive position specific profiles obtained from reliable superfamily alignments aid annotation of remote homologues and are useful tools in structural and functional genomics. PASS2 presents the phylogeny of its members both based on sequence and structural dissimilarities. Clustering of members allows us to understand diversification of the family members. The search engine has been improved for simpler browsing of the database. CONCLUSIONS: The database resolves alignments among the structural domains consisting of evolutionarily diverged set of sequences. Availability of reliable sequence alignments of distantly related proteins despite poor sequence identity and single-member superfamilies permit better sampling of structures in libraries for fold recognition of new sequences and for the understanding of protein structure-function relationships of individual superfamilies. PASS2 is accessible at http://www.ncbs.res.in/~faculty/mini/campass/pass2.html

Amino Acid Sequence↗

MitoRes: a resource of nuclear-encoded mitochondrial genes and their products in Metazoa.

BACKGROUND: Mitochondria are sub-cellular organelles that have a central role in energy production and in other metabolic pathways of all eukaryotic respiring cells. In the last few years, with more and more genomes being sequenced, a huge amount of data has been generated providing an unprecedented opportunity to use the comparative analysis approach in studies of evolution and functional genomics with the aim of shedding light on molecular mechanisms regulating mitochondrial biogenesis and metabolism. In this context, the problem of the optimal extraction of representative datasets of genomic and proteomic data assumes a crucial importance. Specialised resources for nuclear-encoded mitochondria-related proteins already exist; however, no mitochondrial database is currently available with the same features of MitoRes, which is an update of the MitoNuc database extensively modified in its structure, data sources and graphical interface. It contains data on nuclear-encoded mitochondria-related products for any metazoan species for which this type of data is available and also provides comprehensive sequence datasets (gene, transcript and protein) as well as useful tools for their extraction and export. DESCRIPTION: MitoRes http://www2.ba.itb.cnr.it/MitoRes/ consolidates information from publicly external sources and automatically annotates them into a relational database. Additionally, it also clusters proteins on the basis of their sequence similarity and interconnects them with genomic data. The search engine and sequence management tools allow the query/retrieval of the database content and the extraction and export of sequences (gene, transcript, protein) and related sub-sequences (intron, exon, UTR, CDS, signal peptide and gene flanking regions) ready to be used for in silico analysis. CONCLUSION: The tool we describe here has been developed to support lab scientists and bioinformaticians alike in the characterization of molecular features and evolution of mitochondrial targeting sequences. The way it provides for the retrieval and extraction of sequences allows the user to overcome the obstacles encountered in the integrative use of different bioinformatic resources and the completeness of the sequence collection allows intra- and interspecies comparison at different biological levels (gene, transcript and protein).

Animals↗

Automatic document classification of biological literature.

BACKGROUND: Document classification is a wide-spread problem with many applications, from organizing search engine snippets to spam filtering. We previously described Textpresso, a text-mining system for biological literature, which marks up full text according to a shallow ontology that includes terms of biological interest. This project investigates document classification in the context of biological literature, making use of the Textpresso markup of a corpus of Caenorhabditis elegans literature. RESULTS: We present a two-step text categorization algorithm to classify a corpus of C. elegans papers. Our classification method first uses a support vector machine-trained classifier, followed by a novel, phrase-based clustering algorithm. This clustering step autonomously creates cluster labels that are descriptive and understandable by humans. This clustering engine performed better on a standard test-set (Reuters 21578) compared to previously published results (F-value of 0.55 vs. 0.49), while producing cluster descriptions that appear more useful. A web interface allows researchers to quickly navigate through the hierarchy and look for documents that belong to a specific concept. CONCLUSION: We have demonstrated a simple method to classify biological documents that embodies an improvement over current methods. While the classification results are currently optimized for Caenorhabditis elegans papers by human-created rules, the classification engine can be adapted to different types of documents. We have demonstrated this by presenting a web interface that allows researchers to quickly navigate through the hierarchy and look for documents that belong to a specific concept.

Abstracting and Indexing↗

MICA: desktop software for comprehensive searching of DNA databases.

BACKGROUND: Molecular biologists work with DNA databases that often include entire genomes. A common requirement is to search a DNA database to find exact matches for a nondegenerate or partially degenerate query. The software programs available for such purposes are normally designed to run on remote servers, but an appealing alternative is to work with DNA databases stored on local computers. We describe a desktop software program termed MICA (K-Mer Indexing with Compact Arrays) that allows large DNA databases to be searched efficiently using very little memory. RESULTS: MICA rapidly indexes a DNA database. On a Macintosh G5 computer, the complete human genome could be indexed in about 5 minutes. The indexing algorithm recognizes all 15 characters of the DNA alphabet and fully captures the information in any DNA sequence, yet for a typical sequence of length L, the index occupies only about 2L bytes. The index can be searched to return a complete list of exact matches for a nondegenerate or partially degenerate query of any length. A typical search of a long DNA sequence involves reading only a small fraction of the index into memory. As a result, searches are fast even when the available RAM is limited. CONCLUSION: MICA is suitable as a search engine for desktop DNA analysis software.

Algorithms↗

GeneSeer: a sage for gene names and genomic resources.

BACKGROUND: Independent identification of genes in different organisms and assays has led to a multitude of names for each gene. This balkanization makes it difficult to use gene names to locate genomic resources, homologs in other species and relevant publications. METHODS: We solve the naming problem by collecting data from a variety of sources and building a name-translation database. We have also built a table of homologs across several model organisms: H. sapiens, M. musculus, R. norvegicus, D. melanogaster, C. elegans, S. cerevisiae, S. pombe and A. thaliana. This allows GeneSeer to draw phylogenetic trees and identify the closest homologs. This, in turn, allows the use of names from one species to identify homologous genes in another species. A website http://geneseer.cshl.org/ is connected to the database to allow user-friendly access to our tools and external genomic resources using familiar gene names. CONCLUSION: GeneSeer allows access to gene information through common names and can map sequences to names. GeneSeer also allows identification of homologs and paralogs for a given gene. A variety of genomic data such as sequences, SNPs, splice variants, expression patterns and others can be accessed through the GeneSeer interface. It is freely available over the web http://geneseer.cshl.org/ and can be incorporated in other tools through an http-based software interface described on the website. It is currently used as the search engine in the RNAi codex resource, which is a portal for short hairpin RNA (shRNA) gene-silencing constructs.

Alternative Splicing↗

Information resource preferences by general pediatricians in office settings: a qualitative study.

BACKGROUND: Information needs and resource preferences of office-based general pediatricians have not been well characterized. METHODS: Data collected from a sample of twenty office-based urban/suburban general pediatricians consisted of: (a) a demographic survey about participants' practice and computer use, (b) semi-structured interviews on their use of different types of information resources and (c) semi-structured interviews on perceptions of information needs and resource preferences in response to clinical vignettes representing cases in Genetics and Infectious Diseases. Content analysis of interviews provided participants' perceived use of resources and their perceived questions and preferred resources in response to vignettes. RESULTS: Participants' average time in practice was 15.4 years (2-28 years). All had in-office online access. Participants identified specialist/generalist colleagues, general/specialty pediatric texts, drug formularies, federal government/professional organization Websites and medical portals (when available) as preferred information sources. They did not identify decision-making texts, evidence-based reviews, journal abstracts, medical librarians or consumer health information for routine office use.In response to clinical vignettes in Genetics and Infectious Diseases, participants identified Question Types about patient-specific (diagnosis, history and findings) and general medical (diagnostic, therapeutic and referral guidelines) information. They identified specialists and specialty textbooks, history and physical examination, colleagues and general pediatric textbooks, and federal and professional organizational Websites as information sources. Participants with access to portals identified them as information resources in lieu of texts. For Genetics vignettes, participants identified questions about prenatal history, disease etiology and treatment guidelines. For Genetics vignettes, they identified patient history, specialists, general pediatric texts, Web search engines and colleagues as information sources. For Infectious Diseases (ID) vignettes, participants identified questions about patients' clinical status at presentation and questions about disease classification, diagnosis/therapy/referral guidelines and sources of patient education. For ID vignettes, they identified history, laboratory results, colleagues, specialists and personal experience as information sources. CONCLUSION: Content analysis of office-based general pediatricians' responses to clinical vignettes provided a qualitative description of their perceptions of information needs and preferences for information resource for cases in Genetics and Infectious Diseases. This approach may provide complementary information for discovering practitioner's information needs and resource preferences in different contexts.

Adolescent↗

Cyclophilin nomenclature problems, or, 'a visit from the sequence police'.

Why is agreement on one particular name for each gene important? As one genome after another becomes sequenced, it is imperative to consider the complexity of genes, genetic architecture, gene expression, gene-gene and gene-product interactions and evolutionary relatedness across species. To agree on a particular gene name not only makes one's own research easier, it aids automated text-mining algorithms and search engines, which are increasingly employed to find relationships in the millions of abstracts in the medical research literature and sequence databases. A common nomenclature system will also be helpful to the present generation, as well as future generations, of graduate students and postdoctoral fellows who are about to enter genomics research. In this paper, the authors present some problems that arose when two separate research communities decided to choose the same root, CYP, for naming their gene families. They then offer a logical solution, by renaming the cyclophilin genes with a common root, such as cyn- in Caenorhabditis and CYN- in mammals (Cyn in mouse), and using evolutionary divergence to cluster genes of the highest level of relatedness.

Amino Acid Sequence↗