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SemanticEye: a semantic web application to rationalize and enhance chemical electronic publishing.

SemanticEye, an ontology with associated tools, improves the classification and open accessibility of chemical information in electronic publishing. In a manner analogous to digital music management, RDF metadata encoded as Adobe XMP can be extracted from a variety of document formats, such as PDF, and managed in an RDF repository called Sesame. Users upload electronic documents containing XMP to a central server by "dropping" them into WebDAV folders. The documents can then be navigated in a Web browser via their metadata, and multiple documents containing identical metadata can then be aggregated. SemanticEye does not actually store any documents. By including unique identifiers within the XMP, such as the DOI, associated documents can be retrieved from the Web with the help of resolving agents. The power of this metadata driven approach is illustrated by including, within the XMP, InChI identifiers for molecular structures and finding relationships between articles based on their InChIs. SemanticEye will become increasingly more comprehensive as usage becomes more widespread. Furthermore, following the Semantic Web architecture enables the reuse of open software tools, provides a "semantically intuitive" alternative to search engines, and fosters a greater sense of trust in Web-based scientific information.

Journal Article↗

DBParser: web-based software for shotgun proteomic data analyses.

We describe a web-based program called 'DBParser' for rapidly culling, merging, and comparing sequence search engine results from multiple LC-MS/MS peptide analyses. DBParser employs the principle of parsimony to consolidate redundant protein assignments and derive the most concise set of proteins consistent with all of the assigned peptide sequences observed in an experiment or series of experiments. The resulting reports summarize peptide and protein identifications from multidimensional experiments that may contain a single data set or combine data from a group of data sets, all related to a single analytical sample. Additionally, the results of multiple experiments, each of which may contain several data sets, can be compared in reports that identify features that are common or different. DBParser actively links to the primary mass spectral data and to public online databases such as NCBI, GO, and Swiss-Prot in order to structure contextually specific reports for biologists and biochemists.

Amino Acid Sequence↗

Lumbar cerebrospinal fluid proteome in multiple sclerosis: characterization by ultrafiltration, liquid chromatography, and mass spectrometry.

Neurological diseases, including multiple sclerosis (M.S.), often provoke changes in the functioning of the endothelial and epithelial brain barriers and give rise to disease-associated alterations of the cerebrospinal fluid (CSF) proteome. In the present study, pooled and ultrafiltered CSF of M.S. and non-M.S. patients was digested with trypsin and analyzed by off-line strong cation-exchange chromatography (SCX) coupled to on-line reversed-phase LC-ESI-MS/MS. In an alternative approach, the trypsin-treated subproteomes were analyzed directly by LC-ESI-MS/MS and gas-phase fractionation in the mass spectrometer. Taken together, both proteomic approaches in combination with a three-step evaluation process including the search engines Sequest and Mascot, and the validation software Scaffold, resulted in the identification of 148 proteins. Sixty proteins were identified in CSF for the first time by mass spectrometry. For validation purposes, the concentration of cystatin A was determined in individual CSF and serum samples of M.S. and non-M.S. patients using ELISA.

Adult↗

Multi-Q: a fully automated tool for multiplexed protein quantitation.

The iTRAQ labeling method combined with shotgun proteomic techniques represents a new dimension in multiplexed quantitation for relative protein expression measurement in different cell states. To expedite the analysis of vast amounts of spectral data, we present a fully automated software package, called Multi-Q, for multiplexed iTRAQ-based quantitation in protein profiling. Multi-Q is designed as a generic platform that can accommodate various input data formats from search engines and mass spectrometer manufacturers. To calculate peptide ratios, the software automatically processes iTRAQ's signature peaks, including peak detection, background subtraction, isotope correction, and normalization to remove systematic errors. Furthermore, Multi-Q allows users to define their own data-filtering thresholds based on semiempirical values or statistical models so that the computed results of fold changes in peptide ratios are statistically significant. This feature facilitates the use of Multi-Q with various instrument types with different dynamic ranges, which is an important aspect of iTRAQ analysis. The performance of Multi-Q is evaluated with a mixture of 10 standard proteins and human Jurkat T cells. The results are consistent with expected protein ratios and thus demonstrate the high accuracy, full automation, and high-throughput capability of Multi-Q as a large-scale quantitation proteomics tool. These features allow rapid interpretation of output from large proteomic datasets without the need for manual validation. Executable Multi-Q files are available on Windows platform at http://ms.iis.sinica.edu.tw/Multi-Q/.

Chromatography, Liquid↗

Mass spectrometric identification of serum peptides employing derivatized poly(glycidyl methacrylate/divinyl benzene) particles and mu-HPLC.

Biomarkers play a key role in preclinical screening and diagnosis of a disease. Various support materials are utilized for this task, in combination with MALDI-TOF-MS. The way to effectively bind serum contents and their profiling is well-elaborated by the material-enhanced laser desorption ionization (MELDI) approach. In this particular work, focus is placed on the development of a strategy to identify low molecular weight serum peptides. Poly(GMA/DVB) is derivatized in a way to achieve an affinity termed as immobilized metal ion affinity chromatography (IMAC). Iminodiacetic acid (IDA) is used as a chelating ligand, whereas copper (Cu2+) acts as a metal ion for complexing peptides and proteins out of blood serum. Polymer binds the serum compounds over a broad mass range, which includes low mass peptides and high mass albumin (66 kDa). Bound contents are eluted from material by an acetonitrile/trifluoroacetic acid mixture, which proves the reversible nature of metal and amino acid linkage. Polystyrene/divinyl benzene (PS/DVB) monolithic capillary column is used for fractionation through RP-HPLC, prior to the target spotting. The tandem TOF fragment ion mass spectra of each fraction is acquired and used to search against the Swiss-Prot database, using the Mascot search engine for the identification of peptides.

Amino Acid Sequence↗

The origins and consequences of patient autonomy: a 25-year retrospective.

This essay explores the evolution of the tension between the principles of autonomy and beneficence in American health care over the past several decades. In retrospect it is clear that the social movements of the 1960s and 70s set the tone and the goals for the emergence of a new emphasis on patient autonomy. Indeed, the impact of civil liberties-minded lawyers on the promotion of a commitment to autonomy is far more vital than the term "bioethics" commonly suggests. Tracing the impact of this principle on clinical encounters over the past 25 years makes apparent that consumers have extended their influence over a wide range of treatment decisions. This influence is now being reinforced by an extraordinary information revolution, which includes the computer, the web, the dot.coms, the search engines, and such novel practices as Direct-to-Consumer advertising by pharmaceutical companies. The impact of these developments may be seen in such diverse issues as physician-assisted suicide and the failure of national health insurance initiatives.

Advertising↗

A multiagent architecture for developing medical information retrieval agents.

Information that is available on the world wide web (WWW) is already more vast than can be comprehensibly studied by individuals and this quantity is increasing at a staggering pace. The quality of service delivered by physicians is dependent on the availability of current information. The agent paradigm offers a means for enabling physicians to filter information and retrieve only information that is relevant to current patient treatments. As with many specialized domains, agent-based information retrieval in medical domains must satisfy several domain-dependent constraints. A multiple agent architecture is developed and described in detail to efficiently provide agent-based information retrieval from the WWW and other explicit information resources. A simulation of the proposed multiple agent architecture shows a 97% decrease in information overload and an 85% increase in information relevancy over existing meta-search tools (with even larger gains over standard search engines).

Artificial Intelligence↗

A new look at information retrieval evaluation: proposal for solutions.

This is the fourth and the final in the series of the papers on an application of the systems analytic approach to evaluation of information retrieval (IR). In the previous papers terminological and evaluation problems associated with IR were identified and discussed, and it was proposed that the systems analytic approach could provide solutions to these problems. A review of existing systems analytic approaches in IR was given, and a conceptual framework and two models of IR were presented. This paper discusses how the proposed conceptual framework and the models can be used to improve terminology of IR, to analyze the relevance-based method of recall and precision, and to propose new approaches to evaluate relevance relationships and search engines. The proposed evaluation approaches are compared amongst each other and with the existing methods. The paper is concluded by a summary of the contributions of the research and an identification of the directions for a future research in IR evaluation.

Canada↗

The use of the terms 'lifestyle medicines' or 'lifestyle drugs'.

AIM: over the last 10 decades, 'lifestyle medicines' or 'lifestyle drugs' have been used with increasing frequency by journalists, politicians, authorities and to some extent by scientists. The objective of this paper is to analyse the quantity and quality of the use of these terms and discuss the implications associated with the labelling of indications and products as lifestyle medicines or lifestyle drugs. METHODS: The findings in this paper are based on an extensive literature review in the databases Medline, Pubmed, Embase and the two most frequently used search engines altavista.com and google.com, as well as the media database LexisNexis. RESULTS: In the period 1978 to August 2003, the term 'lifestyle medicines/drugs' has appeared 3174 times in English language media. In total, 23 different definitions are presented in the scientific literature. CONCLUSIONS: The review of the scientific literature shows that no widely accepted definition of the terms 'lifestyle medicines' or 'lifestyle drugs' exists. Nevertheless the terms have appeared more than 3000 times in the media (2600 times since 1998), which means that in most cases, the use of the terms 'lifestyle medicines' or 'lifestyle drugs' are based on the authors' own assumptions and values. This is problematic, not only in terms of a discourse, where no one knows what forms the basis of the discussion, but also because this at best leads to an uninformed discussion and at worst to harmful conclusions that might stigmatise and discriminate patients. Based on these findings, this paper argues that a clear, widely accepted definition of the terms 'lifestyle medicines' or 'lifestyle drugs' is essential to avoid potential misunderstandings that might lead to discrimination in the rationing of healthcare resources or stigmatisation of patients.

Denmark↗

Decisions and the evolution of memory: multiple systems, multiple functions.

Memory evolved to supply useful, timely information to the organism's decision-making systems. Therefore, decision rules, multiple memory systems, and the search engines that link them should have coevolved to mesh in a coadapted, functionally interlocking way. This adaptationist perspective suggested the scope hypothesis: When a generalization is retrieved from semantic memory, episodic memories that are inconsistent with it should be retrieved in tandem to place boundary conditions on the scope of the generalization. Using a priming paradigm and a decision task involving person memory, the authors tested and confirmed this hypothesis. The results support the view that priming is an evolved adaptation. They further show that dissociations between memory systems are not--and should not be--absolute: Independence exists for some tasks but not others.

Biological Evolution↗

The adoption history project: A new on-line resource.

The author offers a brief description of The Adoption History Project, a Web site launched on June 1, 2003, that covers the people and organizations, issues, and studies, that shaped adoption in theory and practice throughout the 20th century. The Adoption History Project offers many brief biographical and topical sketches, a wealth of primary texts (excerpted from published and unpublished sources), numerous images, a timeline, bibliography, and a search engine. Historians of psychology will be especially interested in how the consolidation of professional communities (in psychology, social work, and medicine) influenced family formation and in the history of the adoption research industry.

Adoption↗

Web searches for laboratory animal medicine: using the "mouse" for access to online resources.

Laboratory animal medicine professionals must be able to integrate information from a variety of sources to make sound decisions. To address concerns from preveterinary and veterinary students that information about the specialty is difficult to locate, the authors examined the utility of electronic search engines to provide links to appropriate websites of significant educational value to the field. They assembled this reference document to assist veterinary students, residents, and postdoctoral fellows in the acquisition of online texts, journals, newsletters, government regulations, and other sources of current information as they relate specifically to laboratory animal medicine.

Animals↗

The Connectivity Map: a new tool for biomedical research.

The ultimate objective of biomedical research is to connect human diseases with the genes that underlie them and drugs that treat them. But this remains a daunting task, and even the most inspired researchers still have to resort to laborious screens of genetic or chemical libraries. What if at least some parts of this screening process could be systematized and centralized? And hits found and hypotheses generated with something resembling an internet search engine? These are the questions the Connectivity Map project set out to answer.

Algorithms↗

Breast cancer: patient information needs reflected in English and German web sites.

Individual belief and knowledge about cancer were shown to influence coping and compliance of patients. Supposing that the Internet information both has impact on patients and reflects patients' information needs, breast cancer web sites in English and German language were evaluated to assess the information quality and were compared with each other to identify intercultural differences. Search engines returned 10 616 hits related to breast cancer. Of these, 4590 relevant hits were analysed. In all, 1888 web pages belonged to 132 English-language web sites and 2702 to 65 German-language web sites. Results showed that palliative therapy (4.5 vs 16.7%; P=0.004), alternative medicine (18.2 vs 46.2%; P<0.001), and disease-related information (prognosis, cancer aftercare, self-help groups, and epidemiology) were significantly more often found on German-language web sites. Therapy-related information (including the side effects of therapy and new studies) was significantly more often given by English-language web sites: for example, details about surgery, chemotherapy, radiotherapy, hormone therapy, immune therapy, and stem cell transplantation. In conclusion, our results have implications for patient education by physicians and may help to improve patient support by tailoring information, considering the weak points in information provision by web sites and intercultural differences in patient needs.

Breast Neoplasms↗

Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells.

We and others have reported the presence of novel progastrin (PG)/gastrin receptors on normal and cancerous intestinal cells. We had earlier reported the presence of 33-36 kDa gastrin-binding proteins on cellular membranes of colon cancer cells. The goal of the current study was to identify the protein(s) in the 33-36 kDa band, and analyse its functional significance. A carbodiimide crosslinker was used for crosslinking radio-labeled gastrins to membrane proteins from gastrin/PG responsive cell lines. Native membrane proteins, crosslinked to the ligand, were solubulized and enriched by >1000-fold, and analysed by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry. The peptide masses were researched against the NCBInr database using the ProFound search engine. Annexin II (ANX II) was identified, and confirmed by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. As HCT-116 cells express autocrine PG, the in situ association of PG with ANX II was demonstrated in pulldown assays. Direct binding of PG with ANX II was confirmed in an in vitro binding assay. In order to confirm a functional importance of these observations, sense and anti-sense (AS) ANX II RNA-expressing clones of intestinal epithelial (IEC-18) and human colon cancer (HCT-116) cell lines were generated. AS clones demonstrated a significant loss in the growth response to exogenous (IEC-18) and autocrine (HCT-116) PG. We have thus discovered that membrane-associated ANX II binds PG/gastrins, and partially mediates growth factor effects of the peptides.

Animals↗

Paracetamol poisoning: which nomogram should we use?

OBJECTIVES: To determine the type of paracetamol nomograms used in Australasian EDs. To review the literature to determine the evidence base for existing nomograms. METHODS: A cross sectional descriptive study via postal survey of all Australasian EDs accredited for specialist emergency medicine training by the Australasian College for Emergency Medicine (ACEM). A literature review using Knowledge Finder search engine was employed. RESULTS: The response rate was 87%. The most commonly used nomogram had a four-hour treatment level of 1300 mumol/L (69%). A total of 22% of respondents used a four-hour treatment level of 1000 mumol/L. Two departments (3%) treated all patients above the 660 mumol/L line. Eleven departments (15%) did not have a treatment line below 1300 mumol/L. CONCLUSION: Practice varies in Australasian EDs. Patients with paracetamol levels below the 1300 mumol/L have been reported in the literature to develop hepatotoxicity, and deaths have been documented. N-acetylcysteine is extremely safe when used in the recommended dosages.

Acetaminophen↗

Chemoprevention of gastrointestinal malignancies.

BACKGROUND: There has been considerable interest in the use of chemical or dietary agents to suppress or inhibit the development of tumours in the early stages of carcinogenesis. This concept is known as chemoprevention and although the potential for such agents is tremendous, evaluating their clinical benefit is beset with difficulties. AIMS: Using selected agents, such as curcumin and indole-3-carbinol, as examples, the present review will discuss the possible mechanisms of chemoprevention and the problems encountered in developing these agents into clinical drugs. METHODS: A review of the published literature from 1985 to the present day was performed using Medline and Web of Science search engines. Key words used were 'gastrointestinal cancer' and 'chemoprevention'. CONCLUSION: A huge number of agents with possible chemopreventive action has been identified. Pilot trials using molecular signatures of cancer activity can be used to select which agents should be included in large-scale phase III clinical trials. Publications concerning chemoprevention are concentrated in the scientific and oncological literature but surgeons with their greater exposure to premalignant gastrointestinal disease need to be aware of current concepts in this rapidly expanding field. This knowledge would allow collaboration between oncologists and surgeons in clinical trials to further evaluate chemopreventive compounds and ascertain their clinical impact.

Anticarcinogenic Agents↗

Urology and the Internet: an evaluation of internet use by urology patients and of information available on urological topics.

OBJECTIVE: To determine the use of the Internet by urological patients for obtaining information about their disease, and to conduct an evaluation of urological websites to determine the quality of information available. PATIENTS AND METHODS: Questionnaires about Internet use were completed by 180 patients attending a general urological outpatient clinic and by 143 patients attending a prostate cancer outpatient clinic. The Internet evaluation was conducted by reviewing 50 websites listed by the Hotbottrade mark search engine for two urological topics, prostate cancer and testicular cancer, and recording details such as authorship, information content, references and information scores. RESULTS: Of the patients actively seeking further information about their health, 19% of the general urological outpatient group and 24% of the prostate cancer group used the Internet to obtain this information. Most websites were either academic or biomedical (62%), provided conventional information (95%), and were not referenced (71%). The information score (range 10-100) was 44.3 for testicular cancer and 50.7 for prostate cancer; the difference in scores was not significant. CONCLUSION: The use of the Internet by patients is increasing, with > 20% of urology patients using the Internet to obtain further information about their health. Most Internet websites for urological topics provide conventional and good quality information. Urologists should be aware of the need to familiarize themselves with urological websites. Patients can then be directed to high-quality sites to allow them to educate themselves and to help them avoid misleading or unconventional websites.

Female↗