OpCitance: Citation contexts identified from the PubMed Central open access articles.

OpCitance contains all the sentences from 2 million PubMed Central open-access (PMCOA) articles, with 137 million inline citations annotated (i.e., the "citation contexts"). Parsing out the references and citation contexts from the PMCOA XML files was non-trivial due to the diversity of referencing style. Only 0.5% citation contexts remain unidentified due to technical or human issues, e.g., references unmentioned by the authors in the text or improper XML nesting, which is more common among older articles (pre-2000). PubMed IDs (PMIDs) linked to inline citations in the XML files compared to citations harvested using the NCBI E-Utilities differed for 70.96% of the articles. Using an in-house citation matcher, called Patci, 6.84% of the referenced PMIDs were supplemented and corrected. OpCitance includes fewer total number of articles than the Semantic Scholar Open Research Corpus, but OpCitance has 160 thousand unique articles, a higher inline citation identification rate, and a more accurate reference mapping to PMIDs. We hope that OpCitance will facilitate citation context studies in particular and benefit text-mining research more broadly.

The Citation Cloud of a biomedical article: a free, public, web-based tool enabling citation analysis.

BACKGROUND: An article's citations are useful for finding related articles that may not be readily found by keyword searches or textual similarity. Citation analysis is also important for analyzing scientific innovation and the structure of the biomedical literature. We wanted to facilitate citation analysis for the broad community by providing a user-friendly interface for accessing and analyzing citation data for biomedical articles. CASE PRESENTATION: We seeded the Citation Cloud dataset with over 465 million open access citations culled from six different sources: PubMed Central, Microsoft Academic Graph, ArnetMiner, Semantic Scholar, Open Citations, and the NIH iCite dataset. We implemented a free, public extension to PubMed that allows any user to visualize and analyze the entire citation cloud around any paper of interest A: the set of articles cited by A, those which cite A, those which are co-cited with A, and those which are bibliographically coupled to A. CONCLUSIONS: Citation Cloud greatly enables the study of citations by the scientific community, including relatively advanced analyses (co-citations and bibliographic coupling) that cannot be undertaken using other available tools. The tool can be accessed by running any PubMed query on the Anne O'Tate value-added search interface and clicking on the Citations button next to any retrieved article.

Building a PubMed knowledge graph.

PubMed® is an essential resource for the medical domain, but useful concepts are either difficult to extract or are ambiguous, which has significantly hindered knowledge discovery. To address this issue, we constructed a PubMed knowledge graph (PKG) by extracting bio-entities from 29 million PubMed abstracts, disambiguating author names, integrating funding data through the National Institutes of Health (NIH) ExPORTER, collecting affiliation history and educational background of authors from ORCID®, and identifying fine-grained affiliation data from MapAffil. Through the integration of these credible multi-source data, we could create connections among the bio-entities, authors, articles, affiliations, and funding. Data validation revealed that the BioBERT deep learning method of bio-entity extraction significantly outperformed the state-of-the-art models based on the F1 score (by 0.51%), with the author name disambiguation (AND) achieving an F1 score of 98.09%. PKG can trigger broader innovations, not only enabling us to measure scholarly impact, knowledge usage, and knowledge transfer, but also assisting us in profiling authors and organizations based on their connections with bio-entities.

Self-citation is the hallmark of productive authors, of any gender.

It was recently reported that men self-cite >50% more often than women across a wide variety of disciplines in the bibliographic database JSTOR. Here, we replicate this finding in a sample of 1.6 million papers from Author-ity, a version of PubMed with computationally disambiguated author names. More importantly, we show that the gender effect largely disappears when accounting for prior publication count in a multidimensional statistical model. Gender has the weakest effect on the probability of self-citation among an extensive set of features tested, including byline position, affiliation, ethnicity, collaboration size, time lag, subject-matter novelty, reference/citation counts, publication type, language, and venue. We find that self-citation is the hallmark of productive authors, of any gender, who cite their novel journal publications early and in similar venues, and more often cross citation-barriers such as language and indexing. As a result, papers by authors with short, disrupted, or diverse careers miss out on the initial boost in visibility gained from self-citations. Our data further suggest that this disproportionately affects women because of attrition and not because of disciplinary under-specialization.

Spatiotemporal analysis of tropical disease research combining Europe PMC and affiliation mapping web services.

BACKGROUND: Tropical medicine appeared as a distinct sub-discipline in the late nineteenth century, during a period of rapid European colonial expansion in Africa and Asia. After a dramatic drop after World War II, research on tropical diseases have received more attention and research funding in the twenty-first century. METHODS: We used Apache Taverna to integrate Europe PMC and MapAffil web services, containing the spatiotemporal analysis workflow from a list of PubMed queries to a list of publication years and author affiliations geoparsed to latitudes and longitudes. The results could then be visualized in the Quantum Geographic Information System (QGIS). RESULTS: Our workflows automatically matched 253,277 affiliations to geographical coordinates for the first authors of 379,728 papers on tropical diseases in a single execution. The bibliometric analyses show how research output in tropical diseases follow major historical shifts in the twentieth century and renewed interest in and funding for tropical disease research in the twenty-first century. They show the effects of disease outbreaks, WHO eradication programs, vaccine developments, wars, refugee migrations, and peace treaties. CONCLUSIONS: Literature search and geoparsing web services can be combined in scientific workflows performing a complete spatiotemporal bibliometric analyses of research in tropical medicine. The workflows and datasets are freely available and can be used to reproduce or refine the analyses and test specific hypotheses or look into particular diseases or geographic regions. This work exceeds all previously published bibliometric analyses on tropical diseases in both scale and spatiotemporal range.

Predicting MeSH Beyond MEDLINE.

Medical subject headings (MeSH) are a flexible and useful tool for describing biomedical concepts. Here, we present MeSHier, a tool for assigning MeSH terms to biomedical documents based on abstract similarity and references to MEDLINE records. When applied to PubMedCentral papers, NIH grants, and USPTO patents we find that these two sources of information produce largely disjoint sets of related MEDLINE records, albeit with some overlap in MeSH. When combined they provide an enriched topical annotation that would not have been possible with either alone. MeSHier is available as a demo tool that can take as input IDs of PubMed papers, USPTO patents, and NIH grants: http://abel.lis.illinois.edu/cgi-bin/meshier/search.py.

Geographical Distribution of Biomedical Research in the USA and China.

We analyze nearly 20 million geocoded PubMed articles with author affiliations. Using K-means clustering for the lower 48 US states and mainland China, we find that the average published paper is within a relatively short distance of a few centroids. These centroids have shifted very little over the past 30 years, and the distribution of distances to these centroids has not changed much either. The overall country centroids have gradually shifted south (about 0.2° for the USA and 1.7° for China), while the longitude has not moved significantly. These findings indicate that there are few large scientific hubs in the USA and China and the typical investigator is within geographical reach of one such hub. This sets the stage to study centralization of biomedical research at national and regional levels across the globe, and over time.

Quantifying Conceptual Novelty in the Biomedical Literature.

We introduce several measures of novelty for a scientific article in MEDLINE based on the temporal profiles of its assigned Medical Subject Headings (MeSH). First, temporal profiles for all MeSH terms (and pairs of MeSH terms) were characterized empirically and modelled as logistic growth curves. Second, a paper's novelty is captured by its youngest MeSH (and pairs of MeSH) as measured in years and volume of prior work. Across all papers in MEDLINE published since 1985, we find that individual concept novelty is rare (2.7% of papers have a MeSH ≤ 3 years old; 1.0% have a MeSH ≤ 20 papers old), while combinatorial novelty is the norm (68% have a pair of MeSH ≤ 3 years old; 90% have a pair of MeSH ≤ 10 papers old). Furthermore, these novelty measures exhibit complex correlations with article impact (as measured by citations received) and authors' professional age.

Kin of coauthorship in five decades of health science literature.

Family background-kinship-can propagate careers. The evidence for academic nepotism is littered with complex associations and disputed causal inferences. Surname clustering, albeit with very careful consideration of surnames' flows across regions and time periods, can be used to reflect family ties. We examined surname patterns in the health science literature, by country, across five decades. Over 21 million papers indexed in the MEDLINE/PubMed database were analyzed. We identified relevant country-specific kinship trends over time and found that authors who are part of a kin tend to occupy central positions in their collaborative networks. Just as kin build potent academic networks with their own resources, societies may do well to provide equivalent support for talented individuals with fewer resources, on the periphery of networks.

MapAffil: A Bibliographic Tool for Mapping Author Affiliation Strings to Cities and Their Geocodes Worldwide.

Bibliographic records often contain author affiliations as free-form text strings. Ideally one would be able to automatically identify all affiliations referring to any particular country or city such as Saint Petersburg, Russia. That introduces several major linguistic challenges. For example, Saint Petersburg is ambiguous (it refers to multiple cities worldwide and can be part of a street address) and it has spelling variants (e.g., St. Petersburg, Sankt-Peterburg, and Leningrad, USSR). We have designed an algorithm that attempts to solve these types of problems. Key components of the algorithm include a set of 24,000 extracted city, state, and country names (and their variants plus geocodes) for candidate look-up, and a set of 1.1 million extracted word n-grams, each pointing to a unique country (or a US state) for disambiguation. When applied to a collection of 12.7 million affiliation strings listed in PubMed, ambiguity remained unresolved for only 0.1%. For the 4.2 million mappings to the USA, 97.7% were complete (included a city), 1.8% included a state but not a city, and 0.4% did not include a state. A random sample of 300 manually inspected cases yielded six incompletes, none incorrect, and one unresolved ambiguity. The remaining 293 (97.7%) cases were unambiguously mapped to the correct cities, better than all of the existing tools tested: GoPubMed got 279 (93.0%) and GeoMaker got 274 (91.3%) while MediaMeter CLIFF and Google Maps did worse. In summary, we find that incorrect assignments and unresolved ambiguities are rare (< 1%). The incompleteness rate is about 2%, mostly due to a lack of information, e.g. the affiliation simply says "University of Illinois" which can refer to one of five different campuses. A search interface called MapAffil has been developed at the University of Illinois in which the longitude and latitude of the geographical city-center is displayed when a city is identified. This not only helps improve geographic information retrieval but also enables global bibliometric studies of proximity, mobility, and other geo-linked data.

Has large-scale named-entity network analysis been resting on a flawed assumption?

The assumption that a name uniquely identifies an entity introduces two types of errors: splitting treats one entity as two or more (because of name variants); lumping treats multiple entities as if they were one (because of shared names). Here we investigate the extent to which splitting and lumping affect commonly-used measures of large-scale named-entity networks within two disambiguated bibliographic datasets: one for co-author names in biomedicine (PubMed, 2003-2007); the other for co-inventor names in U.S. patents (USPTO, 2003-2007). In both cases, we find that splitting has relatively little effect, whereas lumping has a dramatic effect on network measures. For example, in the biomedical co-authorship network, lumping (based on last name and both initials) drives several measures down: the global clustering coefficient by a factor of 4 (from 0.265 to 0.066); degree assortativity by a factor of ∼13 (from 0.763 to 0.06); and average shortest path by a factor of 1.3 (from 5.9 to 4.5). These results can be explained in part by the fact that lumping artificially creates many intransitive relationships and high-degree vertices. This effect of lumping is much less dramatic but persists with measures that give less weight to high-degree vertices, such as the mean local clustering coefficient and log-based degree assortativity. Furthermore, the log-log distribution of collaborator counts follows a much straighter line (power law) with splitting and lumping errors than without, particularly at the low and the high counts. This suggests that part of the power law often observed for collaborator counts in science and technology reflects an artifact: name ambiguity.

MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects.

BACKGROUND: Recent studies suggest that alterations in expression of genes, including those which regulate neural and structural plasticity, may be crucial in the pathogenesis of depression. MicroRNAs (miRNAs) are newly discovered regulators of gene expression that have recently been implicated in a variety of human diseases, including neuropsychiatric diseases. METHODOLOGY/PRINCIPAL FINDINGS: The present study was undertaken to examine whether the miRNA network is altered in the brain of depressed suicide subjects. Expression of miRNAs was measured in prefrontal cortex (Brodmann Area 9) of antidepressant-free depressed suicide (n = 18) and well-matched non-psychiatric control subjects (n = 17) using multiplex RT-PCR plates. We found that overall miRNA expression was significantly and globally down-regulated in prefrontal cortex of depressed suicide subjects. Using individual tests of statistical significance, 21 miRNAs were significantly decreased at p = 0.05 or better. Many of the down-regulated miRNAs were encoded at nearby chromosomal loci, shared motifs within the 5'-seeds, and shared putative mRNA targets, several of which have been implicated in depression. In addition, a set of 29 miRNAs, whose expression was not pairwise correlated in the normal controls, showed a high degree of co-regulation across individuals in the depressed suicide group. CONCLUSIONS/SIGNIFICANCE: The findings show widespread changes in miRNA expression that are likely to participate in pathogenesis of major depression and/or suicide. Further studies are needed to identify whether the miRNA changes lead to altered expression of prefrontal cortex mRNAs, either directly (by acting as miRNA targets) or indirectly (e.g., by affecting transcription factors).

MicroRNA expression in rat brain exposed to repeated inescapable shock: differential alterations in learned helplessness vs. non-learned helplessness.

MicroRNA (miRNA) expression was measured within frontal cortex of male Holtzman rats subjected to repeated inescapable shocks at days 1 and 7, tested for learned helplessness (LH) at days 2 and 8, and sacrificed at day 15. We compared rats that did vs. did not exhibit LH, as well as rats that were placed in the apparatus and tested for avoidance but not given shocks (tested controls, TC). Non-learned helpless (NLH) rats showed a robust adaptive miRNA response to inescapable shock whereas LH rats showed a markedly blunted response. One set of 12 miRNAs showed particularly large, significant down-regulation in NLH rats relative to tested controls (mir-96, 141, 182, 183, 183*, 298, 200a, 200a*, 200b, 200b*, 200c, 429). These were encoded at a few shared polycistronic loci, suggesting that the down-regulation was coordinately controlled at the level of transcription. Most of these miRNAs are enriched in synaptic fractions. Moreover, almost all of these share 5'-seed motifs with other members of the same set, suggesting that they will hit similar or overlapping sets of target mRNAs. Finally, half of this set is predicted to hit Creb1 as a target. We also identified a core miRNA co-expression module consisting of 36 miRNAs that are highly correlated with each other across individuals of the LH group (but not in the NLH or TC groups). Thus, miRNAs participate in the alterations of gene expression networks that underlie the normal (NLH) as well as aberrant (LH) response to repeated shocks.

Olfactory discrimination training up-regulates and reorganizes expression of microRNAs in adult mouse hippocampus.

Adult male mice (strain C57Bl/6J) were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: olfactory discrimination training (exposed to two odours with reward contingent upon correctly responding to one odour) or pseudo-training (exposed to two odours with reward not contingent upon response). These were run in yoked fashion and killed when the discrimination-trained mouse reached a learning criterion of 70% correct responses in 20 trials, occurring after three sessions (a total of approximately 40 min of training). The hippocampus was dissected bilaterally from each mouse (N = 7 in each group) and profiling of 585 miRNAs (microRNAs) was carried out using multiplex RT-PCR (reverse transcription-PCR) plates. A significant global up-regulation of miRNA expression was observed in the discrimination training versus pseudo-training comparison; when tested individually, 29 miRNAs achieved significance at P = 0.05. miR-10a showed a 2.7-fold increase with training, and is predicted to target several learning-related mRNAs including BDNF (brain-derived neurotrophic factor), CAMK2b (calcium/calmodulin-dependent protein kinase IIß), CREB1 (cAMP-response-element-binding protein 1) and ELAVL2 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like; Hu B]. Analysis of miRNA pairwise correlations revealed the existence of several miRNA co-expression modules that were specific to the training group. These in vivo results indicate that significant, dynamic and co-ordinated changes in miRNA expression accompany early stages of learning.

Arrowsmith two-node search interface: a tutorial on finding meaningful links between two disparate sets of articles in MEDLINE.

The Arrowsmith two-node search is a strategy that is designed to assist biomedical investigators in formulating and assessing scientific hypotheses. More generally, it allows users to identify biologically meaningful links between any two sets of articles A and C in PubMed, even when these share no articles or authors in common and represent disparate topics or disciplines. The key idea is to relate the two sets of articles via title words and phrases (B-terms) that they share. We have created a free, public web-based version of the two-node search tool (http://arrowsmith.psych.uic.edu), have described its development and implementation, and have presented analyses of individual two-node searches. In this paper, we provide an updated tutorial intended for end-users, that covers the use of the tool for a variety of potential scientific use case scenarios. For example, one can assess a recent experimental, clinical or epidemiologic finding that connects two disparate fields of inquiry--identifying likely mechanisms to explain the finding, and choosing promising follow-up lines of investigation. Alternatively, one can assess whether the existing scientific literature lends indirect support to a hypothesis posed by the user that has not yet been investigated. One can also employ two-node searches to search for novel hypotheses. Arrowsmith provides a service that cannot be carried out feasibly via standard PubMed searches or by other available text mining tools.

Author Name Disambiguation in MEDLINE.

BACKGROUND: We recently described "Author-ity," a model for estimating the probability that two articles in MEDLINE, sharing the same author name, were written by the same individual. Features include shared title words, journal name, coauthors, medical subject headings, language, affiliations, and author name features (middle initial, suffix, and prevalence in MEDLINE). Here we test the hypothesis that the Author-ity model will suffice to disambiguate author names for the vast majority of articles in MEDLINE. METHODS: Enhancements include: (a) incorporating first names and their variants, email addresses, and correlations between specific last names and affiliation words; (b) new methods of generating large unbiased training sets; (c) new methods for estimating the prior probability; (d) a weighted least squares algorithm for correcting transitivity violations; and (e) a maximum likelihood based agglomerative algorithm for computing clusters of articles that represent inferred author-individuals. RESULTS: Pairwise comparisons were computed for all author names on all 15.3 million articles in MEDLINE (2006 baseline), that share last name and first initial, to create Author-ity 2006, a database that has each name on each article assigned to one of 6.7 million inferred author-individual clusters. Recall is estimated at ~98.8%. Lumping (putting two different individuals into the same cluster) affects ~0.5% of clusters, whereas splitting (assigning articles written by the same individual to >1 cluster) affects ~2% of articles. IMPACT: The Author-ity model can be applied generally to other bibliographic databases. Author name disambiguation allows information retrieval and data integration to become person-centered, not just document-centered, setting the stage for new data mining and social network tools that will facilitate the analysis of scholarly publishing and collaboration behavior. AVAILABILITY: The Author-ity 2006 database is available for nonprofit academic research, and can be freely queried via http://arrowsmith.psych.uic.edu.

Natural antisense transcripts are co-expressed with sense mRNAs in synaptoneurosomes of adult mouse forebrain.

Natural antisense transcripts and overlapping sense transcripts are expressed in a variety of tissues, including adult mouse brain. Here we show that a subset of mRNA-like sense-antisense transcript pairs are co-expressed within synaptoneurosomes of adult mouse forebrain, a subcellular fraction that is enriched in pinched-off dendritic spines of pyramidal neurons. Several of these pairs involve mRNAs that have been implicated in synaptic functions and in Alzheimer disease pathways. This study provides evidence that a new class of noncoding RNAs (natural antisense transcripts) are expressed near synapses, and encourages further studies of their roles in neuronal function.

Expression of microRNAs and their precursors in synaptic fractions of adult mouse forebrain.

We have characterized the expression of microRNAs and selected microRNA precursors within several synaptic fractions of adult mouse forebrain, including synaptoneurosomes, synaptosomes and isolated post-synaptic densities (PSDs), using methods of microRNA microarray, real time qRT-PCR, Northern blotting and immunopurification using anti-PSD95 antibody. The majority of brain microRNAs (especially microRNAs known to be expressed in pyramidal neurons) are detectably expressed in synaptic fractions, and a subset of microRNAs is significantly enriched in synaptic fractions relative to total forebrain homogenate. MicroRNA precursors are also detectable in synaptic fractions at levels that are comparable to whole tissue. Whereas mature microRNAs are predominantly associated with soluble components of the synaptic fractions, microRNA precursors are predominantly associated with PSDs. For seven microRNAs examined, there was a significant correlation between the relative synaptic enrichment of the precursor and the relative synaptic enrichment of the corresponding mature microRNA. These findings support the proposal that microRNAs are formed, at least in part, via processing of microRNA precursors locally within dendritic spines. Dicer is expressed in PSDs but is enzymatically inactive until conditions that activate calpain cause its liberation; thus, we propose that synaptic stimulation may lead to local processing of microRNA precursors in proximity to the synapse.

Anne O'Tate: A tool to support user-driven summarization, drill-down and browsing of PubMed search results.

BACKGROUND: PubMed is designed to provide rapid, comprehensive retrieval of papers that discuss a given topic. However, because PubMed does not organize the search output further, it is difficult for users to grasp an overview of the retrieved literature according to non-topical dimensions, to drill-down to find individual articles relevant to a particular individual's need, or to browse the collection. RESULTS: In this paper, we present Anne O'Tate, a web-based tool that processes articles retrieved from PubMed and displays multiple aspects of the articles to the user, according to pre-defined categories such as the "most important" words found in titles or abstracts; topics; journals; authors; publication years; and affiliations. Clicking on a given item opens a new window that displays all papers that contain that item. One can navigate by drilling down through the categories progressively, e.g., one can first restrict the articles according to author name and then restrict that subset by affiliation. Alternatively, one can expand small sets of articles to display the most closely related articles. We also implemented a novel cluster-by-topic method that generates a concise set of topics covering most of the retrieved articles. CONCLUSION: Anne O'Tate is an integrated, generic tool for summarization, drill-down and browsing of PubMed search results that accommodates a wide range of biomedical users and needs. It can be accessed at 4. Peer review and editorial matters for this article were handled by Aaron Cohen.

A quantitative model for linking two disparate sets of articles in MEDLINE.

BACKGROUND: Identifying information that implicitly links two disparate sets of articles is a fundamental and intuitive data mining strategy that can help investigators address real scientific questions. The Arrowsmith two-node search finds title words and phrases (so-called B-terms) that are shared across two sets of articles within MEDLINE and displays them in a manner that facilitates human assessment. A serious stumbling-block has been the lack of a quantitative model for predicting which of the hundreds if not thousands of B-terms computed for a given search are most likely to be relevant to the investigator. METHODOLOGY/PRINCIPAL FINDINGS: Using a public two-node search interface, field testers devised a set of two-node searches under real life conditions and a certain number of B-terms were marked relevant. These were employed as 'gold standards;' each B-term was characterized according to eight complementary features that were strongly correlated with relevance. A logistic regression model was developed that permits one to estimate the probability of relevance for each B-term, to rank B-terms according to their likely relevance, and to estimate the overall number of relevant B-terms inherent in a given two-node search. CONCLUSIONS/SIGNIFICANCE: The model greatly simplifies and streamlines the process of carrying out a two-node search, and may be applicable to a number of other literature-based discovery applications, including the so-called one-node search and related gene-centric strategies that incorporate implicit links to predict how genes may be related to each other and to human diseases. This should encourage much wider exploration of text mining for implicit information among the general scientific community. AVAILABILITY: Two-node searches can be carried out freely at http://arrowsmith.psych.uic.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.