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HepSEQ: International Public Health Repository for Hepatitis B.

HepSEQ is a repository for an extensive library of public health and molecular data relating to hepatitis B virus (HBV) infection collected from international sources. It is hosted by the Centre for Infections, Health Protection Agency (HPA), England, United Kingdom. This repository has been developed as a web-enabled, quality-controlled database to act as a tool for surveillance, HBV case management and for research. The web front-end for the database system can be accessed from http://www.hpa-bioinfodatabases.org.uk/hepatitis_open/main.php. The format of the database system allows for comprehensive molecular, clinical and epidemiological data to be deposited into a functional database, to search and manipulate the stored data and to extract and visualize the information on epidemiological, virological, clinical, nucleotide sequence and mutational aspects of HBV infection through web front-end. Specific tools, built into the database, can be utilized to analyse deposited data and provide information on HBV genotype, identify mutations with known clinical significance (e.g. vaccine escape, precore and antiviral-resistant mutations) and carry out sequence homology searches against other deposited strains. Further mechanisms are also in place to allow specific tailored searches of the database to be undertaken.

Databases, Factual↗

Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector.

With the widespread appearance of antibiotic-resistant bacteria, there is an increasing demand for novel strategies to control infectious diseases. Furthermore, it has become apparent that the bacterial life style also contributes significantly to this problem. Bacteria living in the biofilm mode of growth tolerate conventional antimicrobial treatments. The discovery that many bacteria use quorum-sensing (QS) systems to coordinate virulence and biofilm development has pointed out a new, promising target for antimicrobial drugs. We constructed a collection of screening systems, QS inhibitor (QSI) selectors, which enabled us to identify a number of novel QSIs among natural and synthetic compound libraries. The two most active were garlic extract and 4-nitro-pyridine-N-oxide (4-NPO). GeneChip-based transcriptome analysis revealed that garlic extract and 4-NPO had specificity for QS-controlled virulence genes in Pseudomonas aeruginosa. These two QSIs also significantly reduced P. aeruginosa biofilm tolerance to tobramycin treatment as well as virulence in a Caenorhabditis elegans pathogenesis model.

4-Butyrolactone↗

Coordinated series of studies to evaluate characteristics and mechanisms of acute coronary syndromes in high-risk patients randomly assigned to enoxaparin or unfractionated heparin: design and rationale of the SYNERGY Library.

Clinical trials and accompanying substudies in patients with acute coronary syndromes (ACS) have over the last several years yielded a wealth of knowledge about the pathophysiology and management of this high-risk condition. The Superior Yield of the New strategy of Enoxaparin, Revascularization, and GlYcoprotein IIb/IIIa inhibitors (SYNERGY) trial is a large-scale, randomized, controlled trial evaluating the effect of enoxaparin and unfractionated heparin on death and myocardial infarction in high-risk patients presenting with non-ST-segment elevation ACS. The SYNERGY Library has been designed as a coordinated series of investigations with simultaneous data acquisition on the same cohort of approximately 500 SYNERGY patients at 60 centers in North America. Specifically, electrocardiograms, coronary arteriograms, inflammatory markers, coagulation studies, and genetic samples will be collected and processed at core laboratory facilities, and the results will be stored in a central repository. This novel strategy for substudy investigation is unprecedented in cardiovascular clinical trials. The goal is to gain significant understanding about this patient population, discover new principles of pathophysiology, identify novel pharmacologic targets, and streamline further drug development. It is hoped that the SYNERGY Library will serve as a model for future substudy design to maximize academic insight within the framework of a large-scale, multicenter trial.

Angina, Unstable↗

Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus.

We attempted to characterize the genes expression of CD4+ T lymphocytes for the pathogenesis of systemic lupus erythematosus (SLE). Genomewide gene expression profiles of CD4+ T cells, which were isolated from the disease severe activity (T4-1s) and nonactivity (T4-2s) with an SLE patient by using long serial analysis of gene expression (LongSAGE). We picked out 289 genes matching to Unigene cluster with different expression more than four copies between T4-1s and T4-2s libraries and analyzed their roles from the collectedly published articles of PubMed by genes functional clustering. The genes functions were related to a diverse cellular process including: (1) most of these genes were associated with CD4+ T cells functions, particularly related to cellular developments; (2) Ras pathway genes as RANBP10, GMIP, RASGRP2 and ARL5 might be responsible for the abnormal development of CD4+ T cells of SLE; (3) HIG2, TCF7, KHSRP, WWP1, SMAD3, TLK2, AES, CCNI and PIM2 belong to Wnt/beta-catenin way, they could play roles in modulating proliferation and differentiation of T lymphocytes; (4) uncertain viral infections may initiate autoimmunity because high levels expression genes were detected in T4-1s such as TRIM22, IER2, ABCE1, DUT, G1P2, G1P3, HNRPUL1, EVER2, IFNAR1, TNFSF14, TMP21 and PVRL2; and (5) apoptosis relating genes as EIF3S8, SH3BGRL3, GPX4, TOSO, PFDN5, BIN1, XIAPAF1, TEGT and CUGBP2 may contribute to over uploading of selfantigens in SLE cells. Abnormalities findings of multiple genes expression involving with a variety of CD4+ T cells process might be meaningful to understanding the pathogenesis of SLE, and immature CD4+ T cells may be responsible for SLE.

Adult↗

Historical review of malarial control in southern African with emphasis on the use of indoor residual house-spraying.

Indoor residual house-spraying (IRS) mainly with dichlorodiphenyltrichloroethane (DDT) was the principal method by which malaria was eradicated or greatly reduced in many countries in the world between the 1940s and 1960s. In sub-Saharan Africa early malarial eradication pilot projects also showed that malaria is highly responsive to vector control by IRS but transmission could not be interrupted in the endemic tropical and lowland areas. As a result IRS was not taken to scale in most endemic areas of the continent with the exception of southern Africa and some island countries such as Reunion, Mayotte, Zanzibar, Cape Verde and Sao Tome. In southern Africa large-scale malarial control operations based on IRS with DDT and benzene hexachloride (BHC) were initiated in a number of countries to varying degrees. The objective of this review was to investigate the malarial situation before and after the introduction of indoor residual insecticide spraying in South Africa, Swaziland, Botswana, Namibia, Zimbabwe and Mozambique using historical malarial data and related information collected from National Malaria Control Programmes, national archives and libraries, as well as academic institutions in the respective countries. Immediately after the inception of IRS with insecticides, dramatic reductions in malaria and its vectors were recorded. Countries that developed National Malaria Control Programmes during this phase and had built up human and organizational resources made significant advances towards malarial control. Malaria was reduced from hyper- to meso-endemicity and from meso- to hypo-endemicity and in certain instances to complete eradication. Data are presented on the effectiveness of IRS as a malarial control tool in six southern African countries. Recent trends in and challenges to malarial control in the region are also discussed.

Africa, Southern↗

High-throughput techniques for compound characterization and purification.

A new paradigm in drug discovery is the synthesis of structurally diverse collections of compounds, so-called libraries, followed by high-throughput biological screening. High-throughput characterization and purification techniques are required to provide high-quality compounds and reliable biological data, which has led to the development of faster methods, system automation and parallel approaches. This review summarizes recent advances in support of analytical characterization and preparative purification technologies. Notably, mass spectrometry (MS) and supercritical fluid chromatography (SFC) are among the areas where new developments have had a major impact on defining these high-throughput applications.

Chromatography↗

[Combinatorial synthesis: an important methodology in medicinal chemistry].

From the stand point of the synthetic chemist, Combinatorial Synthesis involves the use of processes (solid phase synthesis) and strategies (hundreds or thousands of simultaneous reactions) which allow the preparation, in a short time, of big, organized collections of organic compounds, the so called molecular libraries. Without isolation or purification of individual compounds, deconvolution allows the evaluation of mixtures for biological activity. These libraries, if smartly designed, are becoming an essential source in the discovery and development of new molecules for pharmacology. The structurally diverse compounds are submitted to high throughput screening in a rapid search for lead compounds. On the other hand, the so called parallel combinatorial synthesis offers an efficient route for the structural optimisation obtaining, individually but simultaneously, a wide variety of derivatives of the lead compound.

Chemistry, Pharmaceutical↗

A library for the fifteenth through the twenty-first centuries.

The University of California, San Francisco (UCSF), began developing a program for a new library in 1977, started the design in 1985, began construction in 1988, and opened the library in September 1990. The primary objectives were to design and build a facility that would house print collections under optimal conditions, allow for ten years' growth, be flexible enough to permit future reconfiguration, support present and future technologies, and provide beautiful spaces in which to study. The planning process is summarized, planning concepts are outlined, and considerations for the electronic library are briefly reviewed.

Computer Systems↗

Mapping the literature of perfusion.

Perfusionists select and operate the equipment necessary for monitoring, supporting, or temporarily replacing the patient's circulatory or respiratory function. There are over 3,000 perfusionists working in U.S. hospitals, medical and perfusionist groups, and as independent contractors. The purpose of this study was to identify the core literature of perfusion and to determine which major databases provide the most thorough access to this literature. This paper is part of the Medical Library Association Nursing and Allied Health Resource Section's project to map the literature of the allied health professions. It uses a bibliometric methodology to identify core journals. A group of forty-three journals was determined to make up the core journal literature of perfusion. MEDLINE provided the best overall indexing coverage for these journals, but librarians and perfusionists will wish to supplement its use with the Cumulative Index to Nursing and Allied Health Literature in order to access the journals written primarily for perfusionists. The study results can guide purchasing and database searching decisions of collection development and reference librarians, encourage the database producer to increase coverage of titles that are unindexed or underindexed, and advise perfusionists of the best access to their core literature.

Abstracting and Indexing↗

Optimization of experimental antimitotic agents: classical and combinatorial methods.

Compounds that affect the progress of the cell cycle have served as useful tools for elucidating biological function and as leads for pharmacological agents. Historically, natural products derived from terrestrial and aquatic organisms have been the richest source of lead compounds and novel pharmacophores. Discovery and development of lead compounds from natural products has traditionally involved isolation of a natural product with the biochemical activity of interest, elucidation of its structure, development of chemical or biosynthetic methods for producing the compound and related compounds in larger quantities, and eventually examination of structure-activity relationships and pharmacological properties. Combinatorial chemistry has emerged as a powerful tool for the assembly of large collections of synthetic molecules; as such, it has been adopted in grand style by the pharmaceutical industry. Combinatorial chemistry can be applied in two modes: a diversity-generating mode, where known or novel scaffolds are elaborated into libraries and screened for new activities; or a focused mode, where attention is centered on a particular site in an effort to enhance a particular property (activity, selectivity, solubility, stability, bioavailability). In either mode, identification and development of compounds of interest is dependent on iterative rounds of compound optimization based on efficient and reliable biochemical, cellular, and phenotypic assays.

Animals↗

A collection of tri- and tetranucleotide repeat markers used to generate high quality, high resolution human genome-wide linkage maps.

We report a collection of tri- and tetranucleotide repeat sequence polymorphic markers used to construct genome-wide human linkage maps. Using a strategy of marker selection to create libraries highly enriched for the presence of specific tandem repeat elements, we have developed over 2000 high heterozygosity, easy-to-use tri- and tetranucleotide short tandem repeat polymorphisms (STRPs). To date, over 1300 of these markers have been genotyped on the CEPH reference families. Additional STRPs were assigned to chromosomes using human monochromosomal somatic cell hybrids. The linkage maps constructed with these markers have been integrated with other CEPH genotypes into a comprehensive high density linkage map. These STRPs have been shown to be robust for genotyping in a variety of laboratories using a variety of methods. The high quality of these STRPs makes them ideal candidates for use in genome-wide linkage searches. The integration of these markers with physical mapping reagents and other genetic markers will create a resource for moving from genome-wide linkage searches to rapid sublocalization of disease loci.

Base Sequence↗

[A study on the Menghe medical sect].

From the late Ming to modern age, famous physicians in Menghe came forth in large numbers, contributing to the formation of the Menghe scholarly sect with the four families of the Fei, Ma, Chao, and Ding as its representatives, featuring erudite academic knowledge, rich clinical experiences with distinguished contributions to the development of TCM. The materials presented in this article include investigation from over 100 kinds of genealogies, works of the Menghe sect collected from over 100 works written by the Menghe physicians, local chronicles, family tree collected in all major libraries in China and those in Europe, the US, Hong Kong and Taiwan, as well as through interviews with over 200 persons, including descendants of the Menghe sect, physicians related to the sect. Like a shinning star, the Menghe sect illuminated the medical province during the late Qing dynasty and early republican periods and even today as well.

China↗

Internet access in the libraries of the National Network of Libraries of Medicine.

As the National Library of Medicine expands access to its products and services by making them available on the Internet, more accurate information about current and future access in medical libraries is needed. The National Network Office of the National Library of Medicine conducted a survey of all network member libraries to determine the extent of connectivity and the barriers preventing 100% connectivity. Respondents called a toll-free number and, using interactive voice technology, answered questions concerning Internet access in their library. Seventy-eight percent of the network member libraries responded. Four percent of academic libraries, 27% of hospital libraries, and 10% of "other" libraries reported that they were not connected. Computer cost, lack of in-house expertise, and lack of management support were the highest ranked barriers to connecting. The National Library of Medicine and the Regional Medical Libraries will use information from this survey to develop strategies to help all member libraries achieve full connectivity.

Computer Communication Networks↗

Development of a chicken 5 K microarray targeted towards immune function.

BACKGROUND: The development of microarray resources for the chicken is an important step in being able to profile gene expression changes occurring in birds in response to different challenges and stimuli. The creation of an immune-related array is highly valuable in determining the host immune response in relation to infection with a wide variety of bacterial and viral diseases. RESULTS: Here we report the development of chicken immune-related cDNA libraries and the subsequent construction of a microarray containing 5190 elements (in duplicate). Clones on the array originate from tissues known to contain high levels of cells related to the immune system, namely Bursa, Peyers patch, thymus and spleen. Represented on the array are genes that are known to cluster with existing chicken ESTs as well as genes that are unique to our libraries. Some of these genes have no known homologies and represent novel genes in the chicken collection. A series of reference genes (ie. genes of known immune function) are also present on the array. Functional annotation data is also provided for as many of the genes on the array as is possible. CONCLUSION: Six new chicken immune cDNA libraries have been created and nearly 10,000 sequences submitted to GenBank [GenBank: AM063043-AM071350; AM071520-AM072286; AM075249-AM075607]. A 5 K immune-related array has been developed from these libraries. Individual clones and arrays are available from the ARK-Genomics resource centre.

Animals↗

16S rDNA directed PCR primers and detection of methanogens in the bovine rumen.

AIMS: To assess the diversity of ruminal methanogens in a grazing cow, and develop PCR primers targeting the predominant methanogens. METHODS AND RESULTS: DNA was extracted from rumen contents collected from a cow grazing pasture. Archaeal 16S rRNA genes were amplified by PCR using two pairs of archaea-specific primers, and clone libraries prepared. Selected clones were sequenced. Phylogenetic analysis revealed that for one primer pair, most sequences clustered with Methanobrevibacter spp. whereas with the other primer pair most clustered with Methanosphaera stadtmanae. One sequence belonged to the Crenarcheota. PCR primers were designed to detect Msp. stadtmanae and differentiate between Mbb. ruminantium and Mbb. smithii and successfully tested. CONCLUSIONS: The ruminal methanogens included Mbb. ruminantium, Mbb. smithii, Mbb. thaueri and methanogens similar to Msp.stadtmanae. The study showed that apparent methanogen diversity can be affected by selectivity from the archaea-specific primers used to create clone libraries. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed a greater diversity of ruminal methanogens in grazing cows than previously recognized. It also shows the need for care in interpreting methanogen diversity using PCR-based analyses. The new PCR primers will enable more information to be obtained on Msp. stadtmanae and Methanobrevibacter spp. in the rumen.

Animals↗

Exploring ligand-DNA space using type IIS restriction enzymes.

Investigating ligand-DNA interactions using type IIS restriction enzymes (IISRE) as footprinting reagents is reviewed and contemplated. Ligand binding at a IISRE's cleavage but not sequence recognition site protects DNA from strand scission. This spatial arrangement has been exploited in the development of qualitative (combinatorial) and quantitative ligand-DNA investigative methods collectively termed Type IIS Restriction Enzyme Footprinting (cIISREF and qIISREF respectively). In cIISREF, the consensus binding sequence of a ligand is sought by using a IISRE to segregate combinatorial library members that are bound by ligand from those that are not. A PCR is performed following the segregation step to enrich the library in ligand binding (i.e. uncut) sequences. It might be possible that diversities approaching 10(30) unique sequences could be simultaneously searched using this homogeneous and biologically relevant method. For qIISREF, a ligand-DNA equilibrium constant is measured by quantifying the amounts of target and control DNA IISRE cleavage products as a function of ligand concentration. The control sequence is engineered to not bind ligand. Along with illustrating these methods by reviewing published works, current concerns and future prospects for IISREF are discussed.

Base Sequence↗

Use of Internet audience measurement data to gauge market share for online health information services.

BACKGROUND: The transition to a largely Internet and Web-based environment for dissemination of health information has changed the health information landscape and the framework for evaluation of such activities. A multidimensional evaluative approach is needed. OBJECTIVE: This paper discusses one important dimension of Web evaluation-usage data. In particular, we discuss the collection and analysis of external data on website usage in order to develop a better understanding of the health information (and related US government information) market space, and to estimate the market share or relative levels of usage for National Library of Medicine (NLM) and National Institutes of Health (NIH) websites compared to other health information providers. METHODS: The primary method presented is Internet audience measurement based on Web usage by external panels of users and assembled by private vendors-in this case, comScore. A secondary method discussed is Web usage based on Web log software data. The principle metrics for both methods are unique visitors and total pages downloaded per month. RESULTS: NLM websites (primarily MedlinePlus and PubMed) account for 55% to 80% of total NIH website usage depending on the metric used. In turn, NIH.gov top-level domain usage (inclusive of NLM) ranks second only behind WebMD in the US domestic home health information market and ranks first on a global basis. NIH.gov consistently ranks among the top three or four US government top-level domains based on global Web usage. On a site-specific basis, the top health information websites in terms of global usage appear to be WebMD, MSN Health, PubMed, Yahoo! Health, AOL Health, and MedlinePlus. Based on MedlinePlus Web log data and external Internet audience measurement data, the three most heavily used cancer-centric websites appear to be www.cancer.gov (National Cancer Institute), www.cancer.org (American Cancer Society), and www.breastcancer.org (non-profit organization). CONCLUSIONS: Internet audience measurement has proven useful to NLM, with significant advantages compared to sole reliance on usage data from Web log software. Internet audience data has helped NLM better understand the relative usage of NLM and NIH websites in the intersection of the health information and US government information market sectors, which is the primary market intersector for NLM and NIH. However important, Web usage is only one dimension of a complete Web evaluation framework, and other primary research methods, such as online user surveys, usability tests, and focus groups, are also important for comprehensive evaluation that includes qualitative elements, such as user satisfaction and user friendliness, as well as quantitative indicators of website usage.

Humans↗

User support for a library-managed online database search service: the BMA Library free MEDLINE service.

This paper discusses user support in the context of a library-managed online database search service. Experience is drawn from the British Medical Association (BMA) Library's Free MEDLINE Service. More than 9,600 BMA members, who are largely unfamiliar with computer communications and database searching, have registered as users of the service. User support has played a significant role in the development of the service and has comprised four main aspects: an information pack, a help desk, online help, and MEDLINE courses. The paper includes an analysis of help desk usage statistics collected from January 1996 through June 1996, and highlights other relevant research. Plans for further service enhancements and their implications in terms of future user support are discussed.

Computer User Training↗