CEDAR OnDemand: a browser extension to generate ontology-based scientific metadata.

BACKGROUND: Public biomedical data repositories often provide web-based interfaces to collect experimental metadata. However, these interfaces typically reflect the ad hoc metadata specification practices of the associated repositories, leading to a lack of standardization in the collected metadata. This lack of standardization limits the ability of the source datasets to be broadly discovered, reused, and integrated with other datasets. To increase reuse, discoverability, and reproducibility of the described experiments, datasets should be appropriately annotated by using agreed-upon terms, ideally from ontologies or other controlled term sources. RESULTS: This work presents "CEDAR OnDemand", a browser extension powered by the NCBO (National Center for Biomedical Ontology) BioPortal that enables users to seamlessly enter ontology-based metadata through existing web forms native to individual repositories. CEDAR OnDemand analyzes the web page contents to identify the text input fields and associate them with relevant ontologies which are recommended automatically based upon input fields' labels (using the NCBO ontology recommender) and a pre-defined list of ontologies. These field-specific ontologies are used for controlling metadata entry. CEDAR OnDemand works for any web form designed in the HTML format. We demonstrate how CEDAR OnDemand works through the NCBI (National Center for Biotechnology Information) BioSample web-based metadata entry. CONCLUSION: CEDAR OnDemand helps lower the barrier of incorporating ontologies into standardized metadata entry for public data repositories. CEDAR OnDemand is available freely on the Google Chrome store https://chrome.google.com/webstore/search/CEDAROnDemand.

Modeling community standards for metadata as templates makes data FAIR.

It is challenging to determine whether datasets are findable, accessible, interoperable, and reusable (FAIR) because the FAIR Guiding Principles refer to highly idiosyncratic criteria regarding the metadata used to annotate datasets. Specifically, the FAIR principles require metadata to be "rich" and to adhere to "domain-relevant" community standards. Scientific communities should be able to define their own machine-actionable templates for metadata that encode these "rich," discipline-specific elements. We have explored this template-based approach in the context of two software systems. One system is the CEDAR Workbench, which investigators use to author new metadata. The other is the FAIRware Workbench, which evaluates the metadata of archived datasets for their adherence to community standards. Benefits accrue when templates for metadata become central elements in an ecosystem of tools to manage online datasets-both because the templates serve as a community reference for what constitutes FAIR data, and because they embody that perspective in a form that can be distributed among a variety of software applications to assist with data stewardship and data sharing.

Universal process-based CBT for positive mental health in early adolescence: A cluster randomized controlled trial.

Early adolescence is a key developmental phase for promoting positive mental health and preventing psychological difficulties. Despite calls to develop the evidence base for universal interventions in early adolescence and the promise of process-based CBT, the literature is devoid of empirical investigations of the efficacy of universal process-based CBT in this cohort. This cluster randomized controlled trial aimed to extend the empirical literature by evaluating the efficacy of a six-session universal process-based CBT intervention in elementary schools. Twenty-nine schools were randomly allocated to intervention or waiting list control groups. Six hundred four participants completed measures of positive mental health, resilience, emotional literacy, and mindfulness at baseline, post-intervention, and six-week follow-up. Although participants reported that the intervention was satisfactory, it did not yield significantly superior growth rates on the outcome measures than the control condition at post-intervention or follow-up. Implications of the findings and directions for future research are discussed.

Semantic reasoning with XML-based biomedical information models.

The Extensible Markup Language (XML) is increasingly being used for biomedical data exchange. The parallel growth in the use of ontologies in biomedicine presents opportunities for combining the two technologies to leverage the semantic reasoning services provided by ontology-based tools. There are currently no standardized approaches for taking XML-encoded biomedical information models and representing and reasoning with them using ontologies. To address this shortcoming, we have developed a workflow and a suite of tools for transforming XML-based information models into domain ontologies encoded using OWL. In this study, we applied semantics reasoning methods to these ontologies to automatically generate domain-level inferences. We successfully used these methods to develop semantic reasoning methods for information models in the HIV and radiological image domains.

Randomized Controlled Trial of a Smartphone Application as an Adjunct to Acceptance and Commitment Therapy for Smoking Cessation.

There is a major public health need for innovative and efficacious behavioral and cognitive interventions for smoking cessation. This randomized controlled trial evaluated the efficacy of an acceptance and commitment therapy (ACT) smartphone application in augmenting ACT group treatment for smoking cessation. One hundred fifty adults smoking 10 or more cigarettes per day were randomly assigned to 6 weekly group sessions of behavioral support, ACT, or ACT combined with the smartphone application. Access to the app was provided from the start of the in-person treatment until the 6-month follow-up assessment. Participants were encouraged to make their quit attempts after the third session, and the posttreatment assessment occurred 3 weeks later. Measures of smoking status and ACT processes were obtained at baseline, posttreatment, and 6-month follow-up. Biochemically verified quit rates in the combined, ACT, and behavioral support groups were 36% (p = .079 relative to ACT; p = .193 relative to behavioral support), 20% (p = .630 relative to behavioral support) and 24% at posttreatment, as compared with 24% (p = .630 relative to behavioral support), 24% (p = .630 relative to behavioral support) and 20% at follow-up. There was no significant difference (p = > .999) in the primary outcome of biochemically verified 7-day point-prevalence abstinence at 6-month follow-up between the combined and ACT groups. The combined group reported significantly greater smoking reduction, acceptance and present-moment awareness than the behavioral support group at posttreatment, but not at follow-up. There were no significant differences between the groups in positive mental health. Contrary to hypotheses, the ACT group did not display significant improvements in positive mental health or ACT processes relative to the behavioral support group at posttreatment or follow-up. Implications and directions for future research are discussed.

[Post-Normal Pandemics: why CoViD-19 requires a new approach to science.] / Pandemie post-normali. Perché CoViD-19 richiede un nuovo approccio alla scienza.

In addressing pandemics, science has never seemed more needed and useful, while at the same time limited and powerless. The existing contract between science and society is falling apart. A new covenant is urgently needed to navigate the days ahead.

Using association rule mining and ontologies to generate metadata recommendations from multiple biomedical databases.

Metadata-the machine-readable descriptions of the data-are increasingly seen as crucial for describing the vast array of biomedical datasets that are currently being deposited in public repositories. While most public repositories have firm requirements that metadata must accompany submitted datasets, the quality of those metadata is generally very poor. A key problem is that the typical metadata acquisition process is onerous and time consuming, with little interactive guidance or assistance provided to users. Secondary problems include the lack of validation and sparse use of standardized terms or ontologies when authoring metadata. There is a pressing need for improvements to the metadata acquisition process that will help users to enter metadata quickly and accurately. In this paper, we outline a recommendation system for metadata that aims to address this challenge. Our approach uses association rule mining to uncover hidden associations among metadata values and to represent them in the form of association rules. These rules are then used to present users with real-time recommendations when authoring metadata. The novelties of our method are that it is able to combine analyses of metadata from multiple repositories when generating recommendations and can enhance those recommendations by aligning them with ontology terms. We implemented our approach as a service integrated into the CEDAR Workbench metadata authoring platform, and evaluated it using metadata from two public biomedical repositories: US-based National Center for Biotechnology Information BioSample and European Bioinformatics Institute BioSamples. The results show that our approach is able to use analyses of previously entered metadata coupled with ontology-based mappings to present users with accurate recommendations when authoring metadata.

Unleashing the value of Common Data Elements through the CEDAR Workbench.

Developing promising treatments in biomedicine often requires aggregation and analysis of data from disparate sources across the healthcare and research spectrum. To facilitate these approaches, there is a growing focus on supporting interoperation of datasets by standardizing data-capture and reporting requirements. Common Data Elements (CDEs)-precise specifications of questions and the set of allowable answers to each question-are increasingly being adopted to help meet these standardization goals. While CDEs can provide a strong conceptual foundation for interoperation, there are no widely recognized serialization or interchange formats to describe and exchange their definitions. As a result, CDEs defined in one system cannot be easily be reused by other systems. An additional problem is that current CDE-based systems tend to be rather heavyweight and cannot be easily adopted and used by third-parties. To address these problems, we developed extensions to a metadata management system called the CEDAR Workbench to provide a platform to simplify the creation, exchange, and use of CDEs. We show how the resulting system allows users to quickly define and share CDEs and to immediately use these CDEs to build and deploy Web-based forms to acquire conforming metadata. We also show how we incorporated a large CDE library from the National Cancer Institute's caDSR system and made these CDEs publicly available for general use.

Understanding detection performance in public health surveillance: modeling aberrancy-detection algorithms.

OBJECTIVE: Statistical aberrancy-detection algorithms play a central role in automated public health systems, analyzing large volumes of clinical and administrative data in real-time with the goal of detecting disease outbreaks rapidly and accurately. Not all algorithms perform equally well in terms of sensitivity, specificity, and timeliness in detecting disease outbreaks and the evidence describing the relative performance of different methods is fragmented and mainly qualitative. DESIGN: We developed and evaluated a unified model of aberrancy-detection algorithms and a software infrastructure that uses this model to conduct studies to evaluate detection performance. We used a task-analytic methodology to identify the common features and meaningful distinctions among different algorithms and to provide an extensible framework for gathering evidence about the relative performance of these algorithms using a number of evaluation metrics. We implemented our model as part of a modular software infrastructure (Biological Space-Time Outbreak Reasoning Module, or BioSTORM) that allows configuration, deployment, and evaluation of aberrancy-detection algorithms in a systematic manner. MEASUREMENT: We assessed the ability of our model to encode the commonly used EARS algorithms and the ability of the BioSTORM software to reproduce an existing evaluation study of these algorithms. RESULTS: Using our unified model of aberrancy-detection algorithms, we successfully encoded the EARS algorithms, deployed these algorithms using BioSTORM, and were able to reproduce and extend previously published evaluation results. CONCLUSION: The validated model of aberrancy-detection algorithms and its software implementation will enable principled comparison of algorithms, synthesis of results from evaluation studies, and identification of surveillance algorithms for use in specific public health settings.

The Efficacy and Acceptability of Third-Wave Behavioral and Cognitive eHealth Treatments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

eHealth is an innovative method of delivering therapeutic content with the potential to improve access to third-wave behaviural and cognitive therapies. This systematic review and meta-analysis aimed to determine the efficacy and acceptability of third-wave eHealth treatments in improving mental health outcomes. A comprehensive search of electronic bibliographic databases including PubMed, PsycINFO, Web of Science, and CENTRAL was conducted to identify randomized controlled trials of third-wave treatments in which eHealth was the main component. Twenty-one studies were included in the review. Meta-analyses revealed that third-wave eHealth significantly outperformed inactive control conditions in improving anxiety, depression, and quality-of-life outcomes and active control conditions in alleviating anxiety and depression with small to medium effect sizes. No statistically significant differences were found relative to comparison interventions. Findings from a narrative synthesis of participant evaluation outcomes and meta-analysis of participant attrition rates provided preliminary support for the acceptability of third-wave eHealth. Third-wave eHealth treatments are efficacious in improving mental health outcomes including anxiety, depression, and quality of life, but not more so than comparison interventions. Preliminary evidence from indices of participant evaluation and attrition rates supports the acceptability of these treatments.

The CAIRR Pipeline for Submitting Standards-Compliant B and T Cell Receptor Repertoire Sequencing Studies to the National Center for Biotechnology Information Repositories.

The adaptation of high-throughput sequencing to the B cell receptor and T cell receptor has made it possible to characterize the adaptive immune receptor repertoire (AIRR) at unprecedented depth. These AIRR sequencing (AIRR-seq) studies offer tremendous potential to increase the understanding of adaptive immune responses in vaccinology, infectious disease, autoimmunity, and cancer. The increasingly wide application of AIRR-seq is leading to a critical mass of studies being deposited in the public domain, offering the possibility of novel scientific insights through secondary analyses and meta-analyses. However, effective sharing of these large-scale data remains a challenge. The AIRR community has proposed minimal information about adaptive immune receptor repertoire (MiAIRR), a standard for reporting AIRR-seq studies. The MiAIRR standard has been operationalized using the National Center for Biotechnology Information (NCBI) repositories. Submissions of AIRR-seq data to the NCBI repositories typically use a combination of web-based and flat-file templates and include only a minimal amount of terminology validation. As a result, AIRR-seq studies at the NCBI are often described using inconsistent terminologies, limiting scientists' ability to access, find, interoperate, and reuse the data sets. In order to improve metadata quality and ease submission of AIRR-seq studies to the NCBI, we have leveraged the software framework developed by the Center for Expanded Data Annotation and Retrieval (CEDAR), which develops technologies involving the use of data standards and ontologies to improve metadata quality. The resulting CEDAR-AIRR (CAIRR) pipeline enables data submitters to: (i) create web-based templates whose entries are controlled by ontology terms, (ii) generate and validate metadata, and (iii) submit the ontology-linked metadata and sequence files (FASTQ) to the NCBI BioProject, BioSample, and Sequence Read Archive databases. Overall, CAIRR provides a web-based metadata submission interface that supports compliance with the MiAIRR standard. This pipeline is available at http://cairr.miairr.org, and will facilitate the NCBI submission process and improve the metadata quality of AIRR-seq studies.

Knowledge-level querying of temporal patterns in clinical research systems.

Managing time-stamped data is essential to clinical research activities and often requires the use of considerable domain knowledge. Adequately representing this domain knowledge is difficult in relational database systems. As a result, there is a need for principled methods to overcome the disconnect between the database representation of time-oriented research data and corresponding knowledge of domain-relevant concepts. In this paper, we present a set of methodologies for undertaking knowledge level querying of temporal patterns, and discuss its application to the verification of temporal constraints in clinical-trial applications. Our approach allows knowledge generated from query results to be tied to the data and, if necessary, used for further inference. We show how the Semantic Web ontology and rule languages, OWL and SWRL, respectively, can support the temporal knowledge model needed to integrate low-level representations of relational data with high-level domain concepts used in research data management. We present a scalable bridge-based software architecture that uses this knowledge model to enable dynamic querying of time-oriented research data.

NCBO Ontology Recommender 2.0: an enhanced approach for biomedical ontology recommendation.

BACKGROUND: Ontologies and controlled terminologies have become increasingly important in biomedical research. Researchers use ontologies to annotate their data with ontology terms, enabling better data integration and interoperability across disparate datasets. However, the number, variety and complexity of current biomedical ontologies make it cumbersome for researchers to determine which ones to reuse for their specific needs. To overcome this problem, in 2010 the National Center for Biomedical Ontology (NCBO) released the Ontology Recommender, which is a service that receives a biomedical text corpus or a list of keywords and suggests ontologies appropriate for referencing the indicated terms. METHODS: We developed a new version of the NCBO Ontology Recommender. Called Ontology Recommender 2.0, it uses a novel recommendation approach that evaluates the relevance of an ontology to biomedical text data according to four different criteria: (1) the extent to which the ontology covers the input data; (2) the acceptance of the ontology in the biomedical community; (3) the level of detail of the ontology classes that cover the input data; and (4) the specialization of the ontology to the domain of the input data. RESULTS: Our evaluation shows that the enhanced recommender provides higher quality suggestions than the original approach, providing better coverage of the input data, more detailed information about their concepts, increased specialization for the domain of the input data, and greater acceptance and use in the community. In addition, it provides users with more explanatory information, along with suggestions of not only individual ontologies but also groups of ontologies to use together. It also can be customized to fit the needs of different ontology recommendation scenarios. CONCLUSIONS: Ontology Recommender 2.0 suggests relevant ontologies for annotating biomedical text data. It combines the strengths of its predecessor with a range of adjustments and new features that improve its reliability and usefulness. Ontology Recommender 2.0 recommends over 500 biomedical ontologies from the NCBO BioPortal platform, where it is openly available (both via the user interface at http://bioportal.bioontology.org/recommender , and via a Web service API).

The CEDAR Workbench: An Ontology-Assisted Environment for Authoring Metadata that Describe Scientific Experiments.

The Center for Expanded Data Annotation and Retrieval (CEDAR) aims to revolutionize the way that metadata describing scientific experiments are authored. The software we have developed-the CEDAR Workbench-is a suite of Web-based tools and REST APIs that allows users to construct metadata templates, to fill in templates to generate high-quality metadata, and to share and manage these resources. The CEDAR Workbench provides a versatile, REST-based environment for authoring metadata that are enriched with terms from ontologies. The metadata are available as JSON, JSON-LD, or RDF for easy integration in scientific applications and reusability on the Web. Users can leverage our APIs for validating and submitting metadata to external repositories. The CEDAR Workbench is freely available and open-source.

Fast and Accurate Metadata Authoring Using Ontology-Based Recommendations.

In biomedicine, high-quality metadata are crucial for finding experimental datasets, for understanding how experiments were performed, and for reproducing those experiments. Despite the recent focus on metadata, the quality of metadata available in public repositories continues to be extremely poor. A key difficulty is that the typical metadata acquisition process is time-consuming and error prone, with weak or nonexistent support for linking metadata to ontologies. There is a pressing need for methods and tools to speed up the metadata acquisition process and to increase the quality of metadata that are entered. In this paper, we describe a methodology and set of associated tools that we developed to address this challenge. A core component of this approach is a value recommendation framework that uses analysis of previously entered metadata and ontology-based metadata specifications to help users rapidly and accurately enter their metadata. We performed an initial evaluation of this approach using metadata from a public metadata repository.

High conversion efficiency single-pass second harmonic generation in a zinc-diffused periodically poled lithium niobate waveguide.

We report a modified technique for the fabrication of zinc-diffused channel waveguides using z-cut electric-field periodically poled LiNbO3. Unlike previous work, the diffusion was carried out using metallic zinc at atmospheric pressure. By optimizing the thermal diffusion parameters, channel waveguides that preserve the existing periodically poled domain structures, support both TE and TM modes, and enhance photorefractive damage resistance were obtained. Nonlinear characterisation of the channel waveguides was investigated via second harmonic generation of a 1552nm laser with a maximum conversion efficiency of 59%W-1cm-2 at 14.6 masculineC. Using a pulsed source a second harmonic conversion efficiency of 81% was achieved.

Flexible emotion-based decision-making behavior varies in current and former smokers.

INTRODUCTION: Suboptimal decision-making is a feature in the initiation and maintenance of substance use, often manifested in choosing for short-term benefits rather than long-term gain, and the failure to display cognitive flexibility, respectively. Studies of nicotine users typically focus on characterizing those who are already addicted; less is known about decision-making in former smokers. METHODS: Non- (n=21), former daily- (n=23) and current daily smokers (n=24), completed the contingency-shifting variant Iowa Gambling Task (csIGT), in which the reward and punishment contingencies of the decks are systematically varied after 100 trials of the 'standard' IGT. Scores on the standard blocks of the csIGT provided an index of emotion-based decision-making, while the contingency-shifting blocks assessed flexible decision-making. Subjective ratings were also recorded at 20-trial intervals. RESULTS: Both current and former smokers showed significantly impaired performance relative to non-smokers when making decisions during the standard blocks of the csIGT. Both former and non-smokers' awareness of the reward/punishment contingencies was significantly higher than those of current smokers at the end of the standard IGT. Both former and non-smokers had significantly better performance on the contingency shifting blocks, relative to current smokers. CONCLUSIONS: The findings indicate that both current and former smokers display a suboptimal pattern of decision-making than non-smokers during the standard IGT. However, with respect to the ability to change behavior following reversed contingencies, former smokers are more similar to non-smokers than to current smokers. Former smokers were also more aware of the contingencies than current smokers.

The center for expanded data annotation and retrieval.

The Center for Expanded Data Annotation and Retrieval is studying the creation of comprehensive and expressive metadata for biomedical datasets to facilitate data discovery, data interpretation, and data reuse. We take advantage of emerging community-based standard templates for describing different kinds of biomedical datasets, and we investigate the use of computational techniques to help investigators to assemble templates and to fill in their values. We are creating a repository of metadata from which we plan to identify metadata patterns that will drive predictive data entry when filling in metadata templates. The metadata repository not only will capture annotations specified when experimental datasets are initially created, but also will incorporate links to the published literature, including secondary analyses and possible refinements or retractions of experimental interpretations. By working initially with the Human Immunology Project Consortium and the developers of the ImmPort data repository, we are developing and evaluating an end-to-end solution to the problems of metadata authoring and management that will generalize to other data-management environments.

Translating research into practice: organizational issues in implementing automated decision support for hypertension in three medical centers.

Information technology can support the implementation of clinical research findings in practice settings. Technology can address the quality gap in health care by providing automated decision support to clinicians that integrates guideline knowledge with electronic patient data to present real-time, patient-specific recommendations. However, technical success in implementing decision support systems may not translate directly into system use by clinicians. Successful technology integration into clinical work settings requires explicit attention to the organizational context. We describe the application of a "sociotechnical" approach to integration of ATHENA DSS, a decision support system for the treatment of hypertension, into geographically dispersed primary care clinics. We applied an iterative technical design in response to organizational input and obtained ongoing endorsements of the project by the organization's administrative and clinical leadership. Conscious attention to organizational context at the time of development, deployment, and maintenance of the system was associated with extensive clinician use of the system.

Automated tracking of quantitative assessments of tumor burden in clinical trials.

THERE ARE TWO KEY CHALLENGES HINDERING EFFECTIVE USE OF QUANTITATIVE ASSESSMENT OF IMAGING IN CANCER RESPONSE ASSESSMENT: 1) Radiologists usually describe the cancer lesions in imaging studies subjectively and sometimes ambiguously, and 2) it is difficult to repurpose imaging data, because lesion measurements are not recorded in a format that permits machine interpretation and interoperability. We have developed a freely available software platform on the basis of open standards, the electronic Physician Annotation Device (ePAD), to tackle these challenges in two ways. First, ePAD facilitates the radiologist in carrying out cancer lesion measurements as part of routine clinical trial image interpretation workflow. Second, ePAD records all image measurements and annotations in a data format that permits repurposing image data for analyses of alternative imaging biomarkers of treatment response. To determine the impact of ePAD on radiologist efficiency in quantitative assessment of imaging studies, a radiologist evaluated computed tomography (CT) imaging studies from 20 subjects having one baseline and three consecutive follow-up imaging studies with and without ePAD. The radiologist made measurements of target lesions in each imaging study using Response Evaluation Criteria in Solid Tumors 1.1 criteria, initially with the aid of ePAD, and then after a 30-day washout period, the exams were reread without ePAD. The mean total time required to review the images and summarize measurements of target lesions was 15% (P < .039) shorter using ePAD than without using this tool. In addition, it was possible to rapidly reanalyze the images to explore lesion cross-sectional area as an alternative imaging biomarker to linear measure. We conclude that ePAD appears promising to potentially improve reader efficiency for quantitative assessment of CT examinations, and it may enable discovery of future novel image-based biomarkers of cancer treatment response.