Novel citation-based search method for scientific literature: application to meta-analyses.

BACKGROUND: Finding eligible studies for meta-analysis and systematic reviews relies on keyword-based searching as the gold standard, despite its inefficiency. Searching based on direct citations is not sufficiently comprehensive. We propose a novel strategy that ranks articles on their degree of co-citation with one or more "known" articles before reviewing their eligibility. METHOD: In two independent studies, we aimed to reproduce the results of literature searches for sets of published meta-analyses (n = 10 and n = 42). For each meta-analysis, we extracted co-citations for the randomly selected 'known' articles from the Web of Science database, counted their frequencies and screened all articles with a score above a selection threshold. In the second study, we extended the method by retrieving direct citations for all selected articles. RESULTS: In the first study, we retrieved 82% of the studies included in the meta-analyses while screening only 11% as many articles as were screened for the original publications. Articles that we missed were published in non-English languages, published before 1975, published very recently, or available only as conference abstracts. In the second study, we retrieved 79% of included studies while screening half the original number of articles. CONCLUSIONS: Citation searching appears to be an efficient and reasonably accurate method for finding articles similar to one or more articles of interest for meta-analysis and reviews.

Phenopedia and Genopedia: disease-centered and gene-centered views of the evolving knowledge of human genetic associations.

SUMMARY: We developed web-based applications that encourage the exploration of the literature on human genetic associations by using a database that is continuously updated from PubMed. These applications provide user-friendly interfaces for searching summarized information on human genetic associations, using either genes or diseases as the starting point. AVAILABILITY: Phenopedia and Genopedia can be freely accessed at http://www.hugenavigator.net/HuGENavigator/startPagePhenoPedia.do and http://www.hugenavigator.net/HuGENavigator/startPagePedia.do, respectively.

Complete genome sequence of Treponema pallidum, the syphilis spirochete.

The complete genome sequence of Treponema pallidum was determined and shown to be 1,138,006 base pairs containing 1041 predicted coding sequences (open reading frames). Systems for DNA replication, transcription, translation, and repair are intact, but catabolic and biosynthetic activities are minimized. The number of identifiable transporters is small, and no phosphoenolpyruvate:phosphotransferase carbohydrate transporters were found. Potential virulence factors include a family of 12 potential membrane proteins and several putative hemolysins. Comparison of the T. pallidum genome sequence with that of another pathogenic spirochete, Borrelia burgdorferi, the agent of Lyme disease, identified unique and common genes and substantiates the considerable diversity observed among pathogenic spirochetes.

Complete genome sequence of Neisseria meningitidis serogroup B strain MC58.

The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.

Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1.

The complete genome sequence of the radiation-resistant bacterium Deinococcus radiodurans R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (177,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284, 156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of D. radiodurans to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified. Deinococcus radiodurans represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell.

Complete genome sequence of a virulent isolate of Streptococcus pneumoniae.

The 2,160,837-base pair genome sequence of an isolate of Streptococcus pneumoniae, a Gram-positive pathogen that causes pneumonia, bacteremia, meningitis, and otitis media, contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA. Extracellular enzyme systems for the metabolism of polysaccharides and hexosamines provide a substantial source of carbon and nitrogen for S. pneumoniae and also damage host tissues and facilitate colonization. A motif identified within the signal peptide of proteins is potentially involved in targeting these proteins to the cell surface of low-guanine/cytosine (GC) Gram-positive species. Several surface-exposed proteins that may serve as potential vaccine candidates were identified. Comparative genome hybridization with DNA arrays revealed strain differences in S. pneumoniae that could contribute to differences in virulence and antigenicity.

Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39.

The genome sequences of Chlamydia trachomatis mouse pneumonitis (MoPn) strain Nigg (1 069 412 nt) and Chlamydia pneumoniae strain AR39 (1 229 853 nt) were determined using a random shotgun strategy. The MoPn genome exhibited a general conservation of gene order and content with the previously sequenced C.trachomatis serovar D. Differences between C.trachomatis strains were focused on an approximately 50 kb 'plasticity zone' near the termination origins. In this region MoPn contained three copies of a novel gene encoding a >3000 amino acid toxin homologous to a predicted toxin from Escherichia coli O157:H7 but had apparently lost the tryptophan biosyntheis genes found in serovar D in this region. The C. pneumoniae AR39 chromosome was >99.9% identical to the previously sequenced C.pneumoniae CWL029 genome, however, comparative analysis identified an invertible DNA segment upstream of the uridine kinase gene which was in different orientations in the two genomes. AR39 also contained a novel 4524 nt circular single-stranded (ss)DNA bacteriophage, the first time a virus has been reported infecting C. pneumoniae. Although the chlamydial genomes were highly conserved, there were intriguing differences in key nucleotide salvage pathways: C.pneumoniae has a uridine kinase gene for dUTP production, MoPn has a uracil phosphororibosyl transferase, while C.trachomatis serovar D contains neither gene. Chromosomal comparison revealed that there had been multiple large inversion events since the species divergence of C.trachomatis and C.pneumoniae, apparently oriented around the axis of the origin of replication and the termination region. The striking synteny of the Chlamydia genomes and prevalence of tandemly duplicated genes are evidence of minimal chromosome rearrangement and foreign gene uptake, presumably owing to the ecological isolation of the obligate intracellular parasites. In the absence of genetic analysis, comparative genomics will continue to provide insight into the virulence mechanisms of these important human pathogens.

The Gene Ontology (GO) database and informatics resource.

The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.

Geographic variation of HIV infection in childbearing women with syphilis in the United States.

OBJECTIVES: Substantial biologic and epidemiologic data indicate the importance of syphilis as a potential cofactor for sexual transmission of HIV infection, but few detailed data exist on the geographic covariation of these two important sexually transmitted infections. DESIGN: HIV prevalence in childbearing women and primary and secondary (P&S) syphilis data from 29 states were examined to explore the importance of the epidemiology of syphilis as a factor in facilitating HIV transmission. METHOD: The spatial relationship between P&S syphilis and HIV infection in the health districts of 29 states was analyzed and adjusted for demographic and socioeconomic factors such as racial composition, income, housing, education levels, and access to medical services using the 1990 US census, and geographic location. RESULTS: In 29 states and the District of Colombia, 448 health districts, representing more than 75% of the US population, reported HIV prevalence rates for mothers' district of residence. The HIV seroprevalence ranged from 0 to 1258/10 000 in these health districts. The incidence of P&S syphilis from 1984-1994 in these districts ranged from 0 to 87/100 000. The P&S syphilis incidence was positively associated with the prevalence of HIV infection among childbearing women (P < 0.0001). CONCLUSIONS: Syphilis that persists in communities in the United States appears to represent a 'sentinel public health event' reflecting risk for sexual HIV transmission. These findings, along with other biologic and epidemiologic information, reinforce the importance of syphilis as an indicator for targeting HIV prevention efforts generally, as well as syphilis control as a specific HIV-prevention strategy.

HIV/AIDS among African Americans: progress or progression?

OBJECTIVES: To review data on the extent of HIV infection and associated risk behaviors, the occurrence of AIDS, and HIV-related mortality in African Americans and to suggest what can be done to reduce HIV exposure and infection in this population. DESIGN/METHODS: Review of epidemiologic, published, multisite data on HIV infection in, and related behaviors of, African Americans. RESULTS: On every epidemiologic measure in common use, African Americans, compared with the four other federally recognized racial/ethnic groups, have the most severe epidemic. The trend data show continuing growth in the African American epidemic despite the availability of effective behavioral interventions and biomedical treatments. Few published intervention studies with African American populations have been adequately evaluated; nor have they focused proportionately on men who have sex with men, a group in the African American community with continuing high rates of infection. CONCLUSIONS: Rates of HIV transmission and disease among African Americans are high, disproportionate, and are not declining as significantly in response to effective interventions as they are among whites. Attention is urgently needed to increase our understanding of risk behaviors, social networks, and specific factors in the African American community that can be altered to reduce HIV infection. Macroenvironmental factors--poverty, social class, racism--need to be studied to suggest possible intervention components to reduce rates of HIV transmission and to increase the use of therapies that are more effectively slowing disease progression and lowering death rates among whites.

Urban-nonurban distribution of HIV infection in childbearing women in the United States.

Women account for an increasing proportion of AIDS cases in the United States, and the number reported from small cities and rural areas is growing. To better describe the geographic characteristics of the human immunodeficiency virus (HIV) epidemic in women, we analyzed data for more than 1.6 million newborn specimens tested for maternal antibody to HIV-1 in 35 states in 1989. To provide comparable geographic units for analysis, seroprevalence rates were calculated for state-designated health districts, which are groups of counties defined for the planning and delivery of health services. Health districts with > or = 75% of the population residing in urban areas as defined by the 1990 census were considered urban. Prevalence of HIV infection ranged from 0 to 12.2 per 1,000, with the highest rates found in urban health districts, primarily those on the East coast; however, high rates were also found in some nonurban districts, particularly in the South. Rates among black women were three to 35 times higher than in white women in nine states, regardless of urbanicity. These findings should be used to focus prevention activities and direct health care planners to urban and rural areas in need of HIV-related services for women.

HIV-1 serologic test results for one million newborn dried-blood specimens: assay performance and implications for screening.

In a population-based national survey conducted in 1988-90, more than one million neonatal dried-blood specimens were tested for maternal antibody to human immunodeficiency virus type 1 (HIV-1). Enzyme immunoassays (EIA) and Western blot tests were performed in 20 state laboratories following standardized procedures. The observed predictive value of a repeatedly reactive EIA results closely coincided with that expected on the basis of manufacturer's estimates of test sensitivity and specificity for dried-blood specimens. Of the 2,845 EIA-reactive specimens tested by Western blot, 1,323 (47%) were positive, 1,270 (45%) were negative, and 252 (9%) were indeterminate. False-positive EIA and indeterminate Western blot results occurred at rates independent of seroprevalence. These data help characterize the results to be expected from screening of similar low-seroprevalence populations and constitute a base line for the detection of systematic testing errors.

Factors influencing HIV-1 banding patterns in miniaturized western blot testing of dried blood spot specimens.

In the HIV Seroprevalence Survey among Childbearing Women (SCBW), antibodies to human immunodeficiency virus type 1 are detected using enzyme immunoassays (EIA) and Western blot (WB) methods modified to accommodate samples of blood dried on special collection paper. Dried blood spot (DBS) eluates positive by EIA are tested by one of two WB methods, the miniblot technique using equipment from Immunetics Corporation and the PBS Integra assay (pageblot) from Genetic Systems. In this report we compared the performance of the two WB methods. The identity and position of the viral proteins on the WB were identified using monoclonal antibodies and monospecific antisera. The blots differed substantially in their composition and concentration of viral glycoproteins. Performance of the WB assays with DBS elution buffers from different EIA kits was equivalent except for samples eluted in the Abbott buffer, which reduced detection of antibodies to the p31, p51, p55, and p66 viral proteins. Case classification of DBS, positive sera, dilution curve samples, and seroconversion panels was equivalent by both tests in the presence of all elution buffers. Proficiency evaluation panels sent to SCBW participating laboratories over a 3-year period were used to note the differences between the two WB methods in detection of antibodies to the viral glycoproteins.

DNA uptake signal sequences in naturally transformable bacteria.

The naturally transformable bacterium Haemophilus influenzae Rd contains 1471 copies of the DNA uptake signal sequence (USS) 5'-AAGTGCGGT in its genome. Neisseria meningitidis contains 1891 copies of the USS sequence 5'-GCCGTCTGAA. The USSs are often found in the base paired stem of transcription terminators.

Pregnancy, breast feeding, and oral contraceptives and the risk of epithelial ovarian cancer.

To quantify the effects of cumulative months of pregnancy, breast feeding, and oral contraceptive use on the risk of developing epithelial ovarian cancer, the authors used data collected for the Cancer and Steroid Hormone Study--a multicenter, population-based, case-control study. Detailed reproductive histories were obtained from 436 women aged 20-54 with epithelial ovarian cancer newly diagnosed between December 1980 and December 1982, and from 3833 women aged 20-54 selected at random from the same geographic areas. Estimated relative risks of epithelial ovarian cancer were 0.6 (95% confidence interval (CI) 0.5-0.8) for women who had ever been pregnant, 0.6 (95% CI 0.5-0.8) for women who had ever breast fed, and 0.5 (95% CI 0.5-0.7) for women who had ever used oral contraceptives. Logistic regression analysis revealed a strong trend in decreasing risk of epithelial ovarian cancer with increasing cumulative months of pregnancy; this effect was less pronounced in women aged 50-54 than in younger women. In contrast, a marked reduction in risk was associated with ever having breast fed or used oral contraceptives, while the decrease in risk from additional months of either of these exposures was less than that for pregnancy.

Epidemiology of pediatric human immunodeficiency virus infection in the United States.

HIV infection is an important cause of morbidity and mortality in the pediatric population. Providers of health care to children need to be aware of the problem and the characteristics of the most affected populations. Early diagnosis of HIV infection is critical for initiating appropriate antiviral therapy and prophylactic treatment for opportunistic infections. Attending to the myriad of social problems these families face is equally important for providing an optimal chance for prolonged survival and a reasonably high quality of life.

Publicly funded HIV counseling and testing in the United States, 1992-1995.

Data are collected and reported through the Centers for Disease Control and Prevention (CDC) Counseling and Testing System (CTS) on episodes of publicly funded counseling and HIV testing in the Unites States. The objective of this analysis is to describe testing data reported from 1992 through 1995. In 1992, 2,689,056 tests were performed, and 55,024 (2.0%) were positive; in 1995, 2,491,434 tests were performed, of which 40,605 (1.6%) were positive. Among tests reported with client-level data, the proportion of tests of men and women at higher risk for HIV infection remained stable or declined; the proportion of tests of persons who had been previously tested increased each year; and in 1995, the proportion of tests that included posttest counseling was 86% for anonymous and 70% for confidential tests. Although information collected through CTS could be improved by changing the system so that individuals could be distinguished from testing episodes, the CTS does provide important monitoring information to local and state health departments.

Single nucleotide polymorphisms of the N-formyl peptide receptor in localized juvenile periodontitis.

BACKGROUND: Neutrophils from patients with localized juvenile periodontitis (LJP) exhibit decreased binding and responsiveness to various chemotactic agents, including N-formyl-1-methionyl-1-leucyl-1-phenylalanine (FMLP). This altered reaction of neutrophils is thought to account in part for the increased susceptibility of LJP patients to infections by periodontal organisms. Receptors for FMLP are involved in the activation and the subsequent response to certain chemotactic stimuli. METHODS: In order to determine if this decreased response is due to a genetic variation in the receptor, we directly compared DNA encoding the FMLP receptor from controls matched for gender and race and LJP patients by single-strand conformation polymorphism analysis (SSCP). RESULTS: Using this technique, we observed a characteristic SSCP pattern in 29 out of 30 patient samples in the FMLP receptor DNA. This pattern differed from those obtained from the 20 control subjects as well as 31 patients with adult periodontitis. DNA sequencing of 30 patients indicated single nucleotide polymorphisms (SNPs) in the FMLP receptor DNA from the LJP patients when compared to 20 controls (P = 0.0005). Two single nucleotide base alterations were consistently seen: either a thymine to cytosine substitution at base 329 in 17 LJP patients or a cytosine to guanine substitution at base 378 in 5 LJP patients. A combination of both alterations were seen in 7 LJP patients. Both alterations resulted in amino acid changes in the second intracellular loop of the receptor, specifically phenylalanine to serine at residue 110 and cysteine to tryptophan at residue 126. This region of the FMLP receptor has recently been shown to play a role in ligand binding and G-protein activation. CONCLUSIONS: This study suggests that a molecular alteration in the second intracellular loop of the FMLP receptor molecules in LP patients may play a role in the decreased chemotactic activity reported for some LJP patients.

Applications of data from the CDC Family of Surveys.

The CDC Family of Surveys is a national serologic surveillance system set up to characterize the extent of human immunodeficiency virus (HIV) infection in the United States. The now Centers for Disease Control and Prevention (CDC) and participating State and local health departments began the system in 1987. HIV seroprevalence data are collected by unlinked (anonymous) surveys of particular components of the population that include childbearing women; clients of sexually transmitted disease clinics; injecting drug users; tuberculosis patients; and several special populations, such as adolescents, prisoners, and homeless persons. The data obtained have been used extensively on both national and local levels to assist HIV-prevention programs. Data from the surveys have been used to identify specific demographic groups at risk for HIV infection so that health education programs may be planned and made available to them in clinical settings. Local serosurvey results have been used in planning and implementing prevention programs and in planning health services for HIV-positive persons. The completeness, or coverage, of HIV counseling and testing programs has been evaluated by comparing seroprevalences among clients tested voluntarily with those tested in the unlinked survey. Survey data are used in formulating recommendations and standards of care for health practitioners, in allocating resources, and in carrying out long-range planning for HIV prevention and treatment services for at-risk groups. Such data are essential to the decision-making process in forming public health policy and recommending practices involving the HIV epidemic.