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Literature-based evaluation of the potential risks associated with impregnation of medical devices and implants with triclosan.

BACKGROUND: This report is a review of the published literature for studies of triclosan that address mechanism of action, efficacy on skin and in the oral cavity, and the potential for development of resistance. METHODS: Triclosan citations from the past three decades were searched using Medline and other search engines. The techniques used in these studies included in vitro antimicrobial sensitivity, molecular genetics, and enzyme and membrane biochemistry. Oral cavity efficacy and resistance studies were conducted in human volunteers in trials lasting up to 7 months. Efficacy on skin was reported in clinical trials lasting up to 12 months. RESULTS: The minimal inhibitory concentration of triclosan against Staphylococcus aureus and Escherichia coli is reported to be 0.1 and 5.0 microg/mL, respectively. Triclosan acts by blocking enoyl acyl carrier protein reductase, an enzyme essential for fatty acid biosynthesis. Its biocidal activity involves a plethora of nonspecific perturbations of cellular structural elements, including the cell membrane. In the oral cavity, triclosan use was associated with significant reductions in recoverable flora; there was no evidence of resistance or emergence of opportunistic pathogens. On skin, in a neonatal intensive care unit, triclosan use was associated with a significant reduction in methicillin-resistant S. aureus (MRSA) infections, a diminished need for antibiotics, and a decreased incidence of nosocomial infections. CONCLUSION: There is currently no evidence that long-term application of triclosan products to the skin or oral cavity selects for triclosan-resistant populations. Given the short-term nature of suture use, it is highly unlikely that such use would do other than reduce the risks of postoperative infection.

Anti-Infective Agents, Local↗

Visual BLAST and visual FASTA: graphic workbenches for interactive analysis of full BLAST and FASTA outputs under MICROSOFT WINDOWS 95/NT.

MOTIVATION: When routinely analysing protein sequences, detailed analysis of database search results made with BLAST and FASTA becomes exceedingly time consuming and tedious work, as the resultant file may contain a list of hundreds of potential homologies. The interpretation of these results is usually carried out with a text editor which is not a convenient tool for this analysis. In addition, the format of data within BLAST and FASTA output files makes them difficult to read. RESULTS: To facilitate and accelerate this analysis, we present for the first time, two easy-to-use programs designed for interactive analysis of full BLAST and FASTA output files containing protein sequence alignments. The programs, Visual BLAST and Visual FASTA, run under Microsoft Windows 95 or NT systems. They are based on the same intuitive graphical user interface (GUI) with extensive viewing, searching, editing, printing and multithreading capabilities. These programs improve the browsing of BLAST/FASTA results by offering a more convenient presentation of these results. They also implement on a computer several analytical tools which automate a manual methodology used for detailed analysis of BLAST and FASTA outputs. These tools include a pairwise sequence alignment viewer, a Hydrophobic Cluster Analysis plot alignment viewer and a tool displaying a graphical map of all database sequences aligned with the query sequence. In addition. Visual Blast includes tools for multiple sequence alignment analysis (with an amino acid patterns search engine), and Visual FASTA provides a GUI to the FASTA program.

Amino Acid Sequence↗

DaliLite workbench for protein structure comparison.

SUMMARY: DaliLite is a program for pairwise structure comparison and for structure database searching. It is a standalone version of the search engine of the popular Dali server. A web interface is provided to view the results, multiple alignments and 3D superimpositions of structures.

Computational Biology↗

PATMAT: a searching and extraction program for sequence, pattern and block queries and databases.

A program has been developed that provides molecular biologists with multiple tools for searching databases, yet uses a very simple interface. PATMAT can use protein or (translated) DNA sequences, patterns or blocks of aligned proteins as queries of databases consisting of amino acid or nucleotide sequences, patterns or blocks. The ability to search databases of blocks by 'on-the-fly' conversion to scoring matrices provides a new tool for detection and evaluation of distant relationships. PATMAT uses a pull-down, menu-driven interface to carry out its multiple searching, extraction and viewing functions. Each query or database type is recognized, reported, and the appropriate search carried out, with matches and alignments reported in windows as they occur. Any of the high scoring matches can be exported to a file, viewed and recalled as a query using only a few keystrokes or mouse selections. Searches of multiple database files are carried out by user selection within a window. PATMAT runs under DOS; the searching engine also runs under UNIX.

Amino Acid Sequence↗

Foundation model enables interpretable open and error-tolerant searching for mass spectrometry-based proteomics.

MOTIVATION: Mass spectrometry-based proteomics allows studying all proteins of a sample on a molecular level. However, mass spectra are noisy and contain complex patterns, making them inherently challenging to analyze with algorithmic approaches. In terms of the protein sequence landscape, most recent bottom-up MS-based proteomics studies consider either a diverse pool of post-translational modifications, employ large databases-as in metaproteomics or proteogenomics, study multiple isoforms of proteins, include unspecific cleavage sites or even combinations thereof. All this makes peptide and protein identifications challenging. RESULTS: Here, we present a foundation model, called yHydra, that jointly embeds spectra and peptides. This allows us to implement various downstream tasks and search modes in Euclidean space. We implement an open search which allows querying multiple ten-thousands of spectra against millions of peptides. Furthermore, we implement an error-tolerant search for identifying additional proteoforms that are not included in off-the-shelf reference proteomes. Our foundation model provides meaningful embeddings, as we interpret learned peptide embeddings in comparison to the peptide's physico-chemical properties. Hydra's open search, assigns delta masses to each identification which allows to unrestrictedly characterize post-translational modifications. The error-tolerant mode of yHydra can be used as post-processing to existing search engines or as a standalone. yHydra is evaluated on several real life data sets for the identification of modified peptide sequences and shows up to 25% increase in peptide identification at constant false discovery rate compared to the current state-of-the-art. AVAILABILITY AND IMPLEMENTATION: Code is available on Gitlab: https://gitlab.com/dacs-hpi/yHydra, and https://gitlab.com/dacs-hpi/yHydra_train.

Proteomics↗

Fast tandem mass spectra-based protein identification regardless of the number of spectra or potential modifications examined.

MOTIVATION: Comparing tandem mass spectra (MSMS) against a known dataset of protein sequences is a common method for identifying unknown proteins; however, the processing of MSMS by current software often limits certain applications, including comprehensive coverage of post-translational modifications, non-specific searches and real-time searches to allow result-dependent instrument control. This problem deserves attention as new mass spectrometers provide the ability for higher throughput and as known protein datasets rapidly grow in size. New software algorithms need to be devised in order to address the performance issues of conventional MSMS protein dataset-based protein identification. METHODS: This paper describes a novel algorithm based on converting a collection of monoisotopic, centroided spectra to a new data structure, named 'peptide finite state machine' (PFSM), which may be used to rapidly search a known dataset of protein sequences, regardless of the number of spectra searched or the number of potential modifications examined. The algorithm is verified using a set of commercially available tryptic digest protein standards analyzed using an ABI 4700 MALDI TOFTOF mass spectrometer, and a free, open source PFSM implementation. It is illustrated that a PFSM can accurately search large collections of spectra against large datasets of protein sequences (e.g. NCBI nr) using a regular desktop PC; however, this paper only details the method for identifying peptide and subsequently protein candidates from a dataset of known protein sequences. The concept of using a PFSM as a peptide pre-screening technique for MSMS-based search engines is validated by using PFSM with Mascot and XTandem. AVAILABILITY: Complete source code, documentation and examples for the reference PFSM implementation are freely available at the Proteome Commons, http://www.proteomecommons.org and source code may be used both commercially and non-commercially as long as the original authors are credited for their work.

Algorithms↗

iGNM: a database of protein functional motions based on Gaussian Network Model.

MOTIVATION: The knowledge of protein structure is not sufficient for understanding and controlling its function. Function is a dynamic property. Although protein structural information has been rapidly accumulating in databases, little effort has been invested to date toward systematically characterizing protein dynamics. The recent success of analytical methods based on elastic network models, and in particular the Gaussian Network Model (GNM), permits us to perform a high-throughput analysis of the collective dynamics of proteins. RESULTS: We computed the GNM dynamics for 20 058 structures from the Protein Data Bank, and generated information on the equilibrium dynamics at the level of individual residues. The results are stored on a web-based system called iGNM and configured so as to permit the users to visualize or download the results through a standard web browser using a simple search engine. Static and animated images for describing the conformational mobility of proteins over a broad range of normal modes are accessible, along with an online calculation engine available for newly deposited structures. A case study of the dynamics of 20 non-homologous hydrolases is presented to illustrate the utility of the iGNM database for identifying key residues that control the cooperative motions and revealing the connection between collective dynamics and catalytic activity.

Algorithms↗

NdPASA: a pairwise sequence alignment server for distantly related proteins.

SUMMARY: NdPASA is a web server specifically designed to optimize sequence alignment between distantly related proteins. The program integrates structure information of the template sequence into a global alignment algorithm by employing neighbor-dependent propensities of amino acids as a unique parameter for alignment. NdPASA optimizes alignment by evaluating the likelihood of a residue pair in the query sequence matching against a corresponding residue pair adopting a particular secondary structure in the template sequence. NdPASA is most effective in aligning homologous proteins sharing low percentage of sequence identity. The server is designed to aid homologous protein structure modeling. A PSI-BLAST search engine was implemented to help users identify template candidates that are most appropriate for modeling the query sequences.

Algorithms↗

SNP Function Portal: a web database for exploring the function implication of SNP alleles.

MOTIVATION: Finding the potential functional significance of SNPs is a major bottleneck in understanding genome-wide SNP scanning results, as the related functional data are distributed across many different databases. The SNP Function Portal is designed to be a clearing house for all public domain SNP functional annotation data, as well as in-house functional annotations derived from different data sources. It currently contains SNP functional annotations in six major categories including genomic elements, transcription regulation, protein function, pathway, disease and population genetics. Besides extensive SNP functional annotations, the SNP Function Portal includes a powerful search engine that accepts different types of genetic markers as input and identifies all genetically related SNPs based on the HapMap Phase II data as well as the relationship of different markers to known genes. As a result, our system allows users to identify the potential biological impact of genetic markers and complex relationships among genetic markers and genes, and it greatly facilitates knowledge discovery in genome-wide SNP scanning experiments. AVAILABILITY: http://brainarray.mbni.med.umich.edu/Brainarray/Database/SearchSNP/snpfunc.aspx.

Alleles↗

Searching for cochlear implant information on the internet maze: implications for parents and professionals.

The present study has three purposes: (a) to determine who disseminates information on cochlear implants on the Web; (b) to describe a representative sample of Web sites that disseminate information on cochlear implants, with a focus on the content topics and their relevance to parents of deaf children; and (c) to discuss the practical issues of Web-based information and its implications for professionals working with parents of deaf children. Using the terms "cochlear implants" and "children," the first 10 sites generated by the four most popular search engines (Google, Yahoo, Microsoft's MSN, and America Online) at two points in time were selected for analysis, resulting in a sample of 31 Web sites. The majority of Web sites represented medically oriented academic departments and government organizations, although a wide variety of other sources containing information about cochlear implants were also located. Qualitative analysis revealed that the content tended to fall into eight categories; however, the important issues of educational concerns, habilitation following surgery, and communication methods were either addressed minimally or neglected completely. Using analytical tools that had been developed to evaluate "user friendliness" in other domains, each Web site was assessed for its stability, service/design features and ease of use. In general, wide variability was noted across the Web sites for each of these factors. The strong recommendation is made that professionals understand and enhance their knowledge of both the advantages and limitations of incorporating the new technology into their work with parents.

Cochlear Implants↗

A systematic review of the prevalence of Chlamydia trachomatis among European women.

The study aim was to establish by systematic review the prevalence of asymptomatic Chlamydia trachomatis infection of the lower female genital tract in Europe and also to assess the extent and effect of screening. The search process was wide ranging, using the electronic databases Medline, Embase and Aidsline and the Internet using the search engines Netscape and Euro-ferret. Studies published in any language during 1980-2000 were included if they unambiguously reported prevalence of C. trachomatis infection in asymptomatic women, and were assessed qualitatively. From >300 papers which quantified C. trachomatis urogenital infection, only 14 studies met the inclusion criteria: four from the UK, two from Sweden, two from The Netherlands, and one each from Bulgaria, France, Finland, Hungary, Italy and Spain. In only one study had screening taken place. The prevalence of C. trachomatis in unscreened asymptomatic women in Europe ranges from 1.7 to 17% depending upon the setting, context and country. The mode was -6% for women seeking contraception, and 4% for women having cervical smears. In conclusion, this review confirms high prevalence rates of C. trachomatis infection among asymptomatic women in many European settings.

Chlamydia Infections↗

A full review of online education resources available on antifungal stewardship.

BACKGROUND AND OBJECTIVES: Antifungal resistance represents an increasing global threat, driven by the rising burden of fungal disease. Antifungal stewardship (AFS) is a critical component of broader antimicrobial resistance (AMR) efforts, but education in this area remains less established than antibacterial stewardship initiatives. The scope and characteristics of the current landscape of online AFS resources have not yet been systematically described. To identify and evaluate online educational resources focused on fungal disease management and AFS, and assess their accessibility, format, educational design and implementation focus. METHODS: A structured search of internet search engines, distribution platforms and organizational websites was conducted to identify English-language web-based resources related to fungal disease management and stewardship. Resources were evaluated using predefined criteria including access model, format, length, educational design, interactivity and AFS content. An overall educational value score (1-10) was assigned. RESULTS: Twenty-three educational resources were identified. Most were delivered as online unfacilitated courses (11, 48%) and were short (<4&#x2005;h) (12, 52%). Most focused on guidelines and syndromic management (18, 78%) and targeted doctors and/or nurses/midwives (22, 96%). Limited interactivity was reported in nine (39%) courses. Five courses (22%) had either a substantial or comprehensive focus on AFS. CONCLUSIONS: Online AFS educational resources are available and support awareness and knowledge development. However, they remain relatively few in number. Greater emphasis on implementation-focused learning, behaviour change components and broader global representation may enhance their impact.

Journal Article↗

PAH Mutation Analysis Consortium Database: 1997. Prototype for relational locus-specific mutation databases.

PAHdb (http://www.mcgill.ca/pahdb ) is a curated relational database (Fig. 1) of nucleotide variation in the human PAH cDNA (GenBank U49897). Among 328 different mutations by state (Fig. 2) the majority are rare mutations causing hyperphenylalaninemia (HPA) (OMIM 261600), the remainder are polymorphic variants without apparent effect on phenotype. PAHdb modules contain mutations, polymorphic haplotypes, genotype-phenotype correlations, expression analysis, sources of information and the reference sequence; the database also contains pages of clinical information and data on three ENU mouse orthologues of human HPA. Only six different mutations account for 60% of human HPA chromosomes worldwide, mutations stratify by population and geographic region, and the Oriental and Caucasian mutation sets are different (Fig. 3). PAHdb provides curated electronic publication and one third of its incoming reports are direct submissions. Each different mutation receives a systematic (nucleotide) name and a unique identifier (UID). Data are accessed both by a Newsletter and a search engine on the website; integrity of the database is ensured by keeping the curated template offline. There have been >6500 online interrogations of the website.

Animals↗

MMDB: Entrez's 3D structure database.

The three dimensional structures for representatives of nearly half of all protein families are now available in public databases. Thus, no matter which protein one investigates, it is increasingly likely that the 3D structure of a homolog will be known and may reveal unsuspected structure-function relationships. The goal of Entrez's 3D-structure database is to make this information accessible and usable by molecular biologists (http://www.ncbi.nlm.nih.gov/Entrez). To this end Entrez provides two major analysis tools, a search engine based on sequence and structure 'neighboring' and an integrated visualization system for sequence and structure alignments. From a protein's sequence 'neighbors' one may rapidly identify other members of a protein family, including those where 3D structure is known. By comparing aligned sequences and/or structures in detail, using the visualization system, one may identify conserved features and perhaps infer functional properties. Here we describe how these analysis tools may be used to investigate the structure and function of newly discovered proteins, using the PTEN gene product as an example.

Amino Acid Sequence↗

The Homeodomain Resource: sequences, structures and genomic information.

The Homeodomain Resource is a comprehensive collection of sequence, structure and genomic information on the homeodomain protein family. Available through the Resource are both full-length and domain-only sequence data, as well as X-ray and NMR structural data for proteins and protein-DNA complexes. Also available is information on human genetic diseases and disorders in which proteins from the homeodomain family play an important role; genomic information includes relevant gene symbols, cytogenetic map locations, and specific mutation data. Search engines are provided to allow users to easily query the component databases and assemble specialized data sets. The Homeodomain Resource is available through the World Wide Web at http://genome.nhgri.nih.gov/homeodomain

Animals↗

Extension of CyanoBase. CyanoMutants: repository of mutant information on Synechocystis sp. strain PCC6803.

CyanoBase provides internet access to the complete genomic information of the cyanobacterium Synechocystis sp. strain PCC6803. CyanoBase contains annotations to each protein-coding gene, deduced from the entire nucleotide sequence of the genome, gene classification lists, keywords and similarity search engines. The present paper describes a recent extension of CyanoBase, named CyanoMutants. CyanoMutants is a repository database of mutant information on PCC6803. Each entry contains a dataset which describes a gene identifier, mutant information, and an address for correspondence. Two closely-linked databases, CyanoBase and CyanoMutants, connect information obtained from computational analysis to experimental analysis resulting in the clarification of the functions of hypothetical genes of the cyanobacterial genome. CyanoMutants can be accessed at http://www.kazusa.or. jp/cyano/mutants/

Computational Biology↗

The imprinted gene and parent-of-origin effect database.

The database of imprinted genes and parent-of-origin effects in animals (http://www.otago.ac.nz/IGC ) is a collation of genes and phenotypes for which parent-of-origin effects have been reported. The database currently includes over 220 entries, which describe over 40 imprinted genes in human, mouse and other animals. In addition a wide variety of other parent-of-origin effects, such as transmission of human disease phenotypes, transmission of QTLs, uniparental disomies and interspecies crosses are recorded. Data are accessed through a search engine and references are hyperlinked to PubMed.

Alleles↗

The Homeodomain Resource: sequences, structures, DNA binding sites and genomic information.

The Homeodomain Resource is an annotated collection of non-redundant protein sequences, three-dimensional structures and genomic information for the homeodomain protein family. Release 3.0 contains 795 full-length homeodomain-containing sequences, 32 experimentally-derived structures and 143 homeo-box loci implicated in human genetic disorders. Entries are fully hyperlinked to facilitate easy retrieval of the original records from source databases. A simple search engine with a graphical user interface is provided to query the component databases and assemble customized data sets. A new feature for this release is the addition of DNA recognition sites for all human homeodomain proteins described in the literature. The Homeodomain Resource is freely available through the World Wide Web at http://genome.nhgri.nih.gov/homeodomain.

Animals↗