The BioLexicon: a large-scale terminological resource for biomedical text mining

Background

Due to the rapidly expanding body of biomedical literature, biologists require increasingly sophisticated and efficient systems to help them to search for relevant information. Such systems should account for the multiple written variants used to represent biomedical concepts, and allow the user to search for specific pieces of knowledge (or events) involving these concepts, e.g., protein-protein interactions. Such functionality requires access to detailed information about words used in the biomedical literature. Existing databases and ontologies often have a specific focus and are oriented towards human use. Consequently, biological knowledge is dispersed amongst many resources, which often do not attempt to account for the large and frequently changing set of variants that appear in the literature. Additionally, such resources typically do not provide information about how terms relate to each other in texts to describe events.

Results

This article provides an overview of the design, construction and evaluation of a large-scale lexical and conceptual resource for the biomedical domain, the BioLexicon. The resource can be exploited by text mining tools at several levels, e.g., part-of-speech tagging, recognition of biomedical entities, and the extraction of events in which they are involved. As such, the BioLexicon must account for real usage of words in biomedical texts. In particular, the BioLexicon gathers together different types of terms from several existing data resources into a single, unified repository, and augments them with new term variants automatically extracted from biomedical literature. Extraction of events is facilitated through the inclusion of biologically pertinent verbs (around which events are typically organized) together with information about typical patterns of grammatical and semantic behaviour, which are acquired from domain-specific texts. In order to foster interoperability, the BioLexicon is modelled using the Lexical Markup Framework, an ISO standard.

Conclusions

The BioLexicon contains over 2.2 M lexical entries and over 1.8 M terminological variants, as well as over 3.3 M semantic relations, including over 2 M synonymy relations. Its exploitation can benefit both application developers and users. We demonstrate some such benefits by describing integration of the resource into a number of different tools, and evaluating improvements in performance that this can bring.     

The dynamics of health and return migration

The increasing importance and complexity of migration globally also implies a global increase in return migration, and thus an increased interest in the health of returning migrants. The health of returning migrants is impacted by the cumulative exposure to social determinants and risk factors of health during the migration process, during the return movement, and following return. Circular migration often occurs among the diaspora, which can result in the transfer of knowledge and skills that contribute to development, including health system strengthening. Migrants with dual nationality often return to countries with better health services than their country of origin when they are sick and can not get care at home. To maintain and improve the health of returning migrants, multi-sectoral policies at global and national levels should facilitate access to appropriate and equitable health services, social services, and continuity of care across and within borders.     

E3 ubiquitin ligases and abscisic acid signaling

The ubiquitin proteasome system is involved in the regulation of nearly every aspect of plant growth and development. Protein ubiquitination involves the covalent attachment of ubiquitin to target proteins through a cascade catalyzed by three enzymes known as E1, E2 and E3. E3s are of particular interest as they confer substrate specificity during ubiquitination through their diverse substrate recognition domains. Recently, a number of E3s have been identified that actively participate in abscisic acid hormone biology, including regulation of biosynthesis, de-repression or activation of abscisic acid response and degradation of signaling components. In this review, we summarize recent exciting studies of the different types of E3s that target specific mediators of abscisic acid signaling or affect the plants response to the hormone.Key words: abscisic acid, E3 ubiquitin ligase, proteasome, ubiquitinationPost-translational control of protein degradation by the ubiquitin proteasome system (UPS) is a highly regulated process essential for the proper growth and development of all eukaryotes through removing abnormal proteins and most short-lived regulatory proteins.^1,2 Plants utilize the UPS to alter their proteome to mediate cellular changes required for growth, development and responses to biotic and abiotic stress. Plants also rely a great deal on hormones to induce changes in growth and development in response to a wide range of environmental stimuli. Hormone biosynthesis, perception, signaling and response can be exquisitely regulated through modulating protein levels via the UPS. Regulation of the abscisic acid (ABA) signaling pathway, like auxin, gibberellin, jasmonate and ethylene, have been linked to UPS components with the application of biochemical, genetic and genomic approaches.^3–5 Although some aspects of ABA signaling have been elucidated, the involvement of the UPS, especially E3 ubiquitin ligases, help us gain further insight into the entire network of ABA signal transduction. In this review we focus on recently identified E3s that play a variety of roles in ABA signaling. A number of articles are available that provide a comprehensive review of the role of E3 ligases in the biosynthesis, perception and signaling by other hormones such as auxin and ethylene.^3–5     

Mining metabolites: extracting the yeast metabolome from the literature

Text mining methods have added considerably to our capacity to extract biological knowledge from the literature. Recently the field of systems biology has begun to model and simulate metabolic networks, requiring knowledge of the set of molecules involved. While genomics and proteomics technologies are able to supply the macromolecular parts list, the metabolites are less easily assembled. Most metabolites are known and reported through the scientific literature, rather than through large-scale experimental surveys. Thus it is important to recover them from the literature. Here we present a novel tool to automatically identify metabolite names in the literature, and associate structures where possible, to define the reported yeast metabolome. With ten-fold cross validation on a manually annotated corpus, our recognition tool generates an f-score of 78.49 (precision of 83.02) and demonstrates greater suitability in identifying metabolite names than other existing recognition tools for general chemical molecules. The metabolite recognition tool has been applied to the literature covering an important model organism, the yeast Saccharomyces cerevisiae, to define its reported metabolome. By coupling to ChemSpider, a major chemical database, we have identified structures for much of the reported metabolome and, where structure identification fails, been able to suggest extensions to ChemSpider. Our manually annotated gold-standard data on 296 abstracts are available as supplementary materials. Metabolite names and, where appropriate, structures are also available as supplementary materials.     

Variation in effects of non-Hodgkin lymphoma risk factors according to the human leukocyte antigen (HLA)-DRB1*01:01 allele and ancestral haplotype 8.1

Genetic variations in human leukocyte antigens (HLA) are critical in host responses to infections, transplantation, and immunological diseases. We previously identified associations with non-Hodgkin lymphoma (NHL) and the HLA-DRB1*01:01 allele and extended ancestral haplotype (AH) 8.1 (HLA-A*01-B*08-DR*03-TNF-308A). To illuminate how HLA alleles and haplotypes may influence NHL etiology, we examined potential interactions between HLA-DRB1*01:01 and AH 8.1, and a wide range of NHL risk factors among 685 NHL cases and 646 controls from a United States population-based case-control study. We calculated odds ratios and 95% confidence intervals by HLA allele or haplotype status, adjusted for sex, age, race and study center for NHL and two major subtypes using polychotomous unconditional logistic regression models. The previously reported elevation in NHL risk associated with exposures to termite treatment and polychlorinated biphenyls were restricted to individuals who did not possess HLA-DRB1*01:01. Previous associations for NHL and DLBCL with decreased sun exposure, higher BMI, and autoimmune conditions were statistically significant only among those with AH 8.1, and null among those without AH 8.1. Our results suggest that NHL risk factors vary in their association based on HLA-DRB1*01:01 and AH 8.1 status. Our results further suggest that certain NHL risk factors may act through a common mechanism to alter NHL risk. Finally, control participants with either HLA-DRB1*01:01 or AH 8.1 reported having a family history of NHL twice as likely as those who did not have either allele or haplotype, providing the first empirical evidence that HLA associations may explain some of the well-established relationship between family history and NHL risk.     

A RCT of a transdiagnostic internet-delivered treatment for three anxiety disorders: examination of support roles and disorder-specific outcomes

Background

Anxiety disorders share common vulnerabilities and symptoms. Disorder-specific treatment is efficacious, but few access evidence-based care. Administering transdiagnostic cognitive-behavioral therapy via the internet (iCBT) may increase access to evidence-based treatment, with a recent randomized controlled trial (RCT) providing preliminary support for this approach. This study extends those findings and aims to answer three questions: Is a transdiagnostic iCBT program for anxiety disorders efficacious and acceptable? Does it result in change for specific disorders? Can good clinical outcomes be obtained when guidance is provided via a Coach rather than a Clinician?

Method

RCT (N = 131) comparing three groups: Clinician-supported (CL) vs. Coach-supported (CO) vs. waitlist control (Control). Individuals met DSM-IV criteria for a principal diagnosis of generalized anxiety disorder (GAD), social phobia (SP) or panic disorder with or without agoraphobia (Pan/Ag). Treatment consisted of an 8-lesson/10 week iCBT program with weekly contact from a Clinician or Coach, and follow-up at 3-months post-treatment.

Results

Outcomes for the pooled treatment groups (CL+CO) were superior to the Control group on measures of anxiety, depression and disability, were associated with medium to large effect sizes (Cohen''s d = .76 – 1.44) (response rate = 89–100%), and were maintained at follow-up. Significant reductions were found on disorder-specific outcomes for each of the target diagnoses, and were associated with large effect sizes. CO participants achieved similar outcomes to CL participants at post-treatment, yet had significantly lower symptom severity scores on general anxiety, panic-disorder, depression and disability at follow-up (d = .45 – .46). Seventy-four percent of CO and 76% of CL participants completed the program. Less than 70 minutes of Clinician or Coach time was required per participant during the program.

Discussion

This transdiagnostic iCBT course for anxiety appears to be efficacious, associated with significant change for three target disorders, and is efficacious when guided by either a Clinician or Coach.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12610000242022     

Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice

Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh)/Kit(W-sh) mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh)/Kit(W-sh) mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.     

The acceptability of Internet-based treatment and characteristics of an adult sample with obsessive compulsive disorder: an Internet survey

Background

Obsessive-compulsive disorder (OCD) is a disabling anxiety disorder, but most individuals delay seeking treatment. Internet-based cognitive behavioural therapy (iCBT) is an innovative service delivery method that may help to improve access to care, but the acceptability to consumers of such programs has not yet been established.

Methodology

People with symptoms of OCD were invited to complete an online survey enquiring about demographic characteristics, symptom severity, and acceptability of Internet-based treatment. Demographic and symptom severity data were compared with people with OCD identified in a national epidemiological survey and with a sample of patients with OCD from a specialist outpatient anxiety clinic.

Participants

129 volunteers to an online Internet survey, 135 patients at a specialist anxiety disorders outpatient clinic, and 297 cases identified in a national epidemiological survey.

Main Measures

Demographic characteristics, and severity of symptoms as measured by the Kessler 10-Item scale, the 12-item World Health Organisation Disability Assessment Schedule - Second Edition and the Yale Brown Obsessive Compulsive Scale - Self Report Version.

Principal Findings

The Internet sample was similar demographically but reported more severe symptoms than the comparison groups, although had similar severity of symptoms of OCD compared with other clinical samples reported in the literature. Participants reported Internet-based treatment for OCD would be highly acceptable.

Conclusions

Internet-based treatment may reduce barriers to accessing treatment to people with OCD. Individuals in this study were similar demographically to other samples and had similar severity of symptoms as those identified in other clinical samples, suggesting that Internet-based treatment using techniques employed in face-to-face treatment may be effective in this group. Internet-based treatments for OCD need to be developed and evaluated.