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BACKGROUND: The consent protocol is now a critical part in the overall orchestration of clinical research. We aimed to demonstrate the feasibility of an Ethereum-based informed consent system, which includes an immutable and automated channel of consent matching, to simultaneously assure patient privacy and increase the efficiency of researchers data access. METHOD: We simulated a multi-site scenario, each assigned 10000 consent records. A consent record contained one patients data-sharing preference with regards to seven data categories. We developed a blockchain-based infrastructure with a smart contract to record consents on-chain, and to query consenting patients corresponding to specific criteria. We measured our systems recording efficiency against a baseline design and verified accuracy by testing an exhaustive list of possible queries. RESULTS: Our method achieved ∼3-4% lead with an average insertion speed of ∼2 s per record per node on either a 3-, 4- or 5-node network, and 100 % accuracy. It also outperformed other solutions in external validation. DISCUSSION: The speed we achieved is reasonable in a real-world system under the realistic assumption that patients may not change their minds too frequently, with the added benefit of immutability. Furthermore, the per-insertion time did improve slightly as the number of network nodes increased, attesting to the benefit of node parallelism as it suggests no attrition of insertion efficiency due to scale of nodes. CONCLUSIONS: Our work confirms the technical feasibility of a blockchain-based consent mechanism, assuring patients with an immutable audit trail, and providing researchers with an efficient way to reach their cohorts.

ObjectiveBlockchain has emerged as a potential data-sharing structure in healthcare because of its decentralization, immutability, and traceability. However, its use in the biomedical domain is yet to be investigated comprehensively, especially from the aspects of implementation and evaluation, by existing blockchain literature reviews. To address this, our review assesses blockchain applications implemented in practice and evaluated with quantitative metrics.Materials and methodsThis systematic review adapts the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to review biomedical blockchain papers published by August 2023 from 3 databases. Blockchain application, implementation, and evaluation metrics were collected and summarized.ResultsFollowing screening, 11 articles were included in this review. Articles spanned a range of biomedical applications including COVID-19 medical data sharing, decentralized internet of things (IoT) data storage, clinical trial management, biomedical certificate storage, electronic health record (EHR) data sharing, and distributed predictive model generation. Only one article demonstrated blockchain deployment at a medical facility.DiscussionEthereum was the most common blockchain platform. All but one implementation was developed with private network permissions. Also, 8 articles contained storage speed metrics and 6 contained query speed metrics. However, inconsistencies in presented metrics and the small number of articles included limit technological comparisons with each other.ConclusionWhile blockchain demonstrates feasibility for adoption in healthcare, it is not as popular as currently existing technologies for biomedical data management. Addressing implementation and evaluation factors will better showcase blockchain's practical benefits, enabling blockchain to have a significant impact on the health sector.

ObjectiveWe aimed to develop a distributed, immutable, and highly available cross-cloud blockchain system to facilitate federated data analysis activities among multiple institutions.Materials and methodsWe preprocessed 9166 COVID-19 Structured Query Language (SQL) code, summary statistics, and user activity logs, from the GitHub repository of the Reliable Response Data Discovery for COVID-19 (R2D2) Consortium. The repository collected local summary statistics from participating institutions and aggregated the global result to a COVID-19-related clinical query, previously posted by clinicians on a website. We developed both on-chain and off-chain components to store/query these activity logs and their associated queries/results on a blockchain for immutability, transparency, and high availability of research communication. We measured run-time efficiency of contract deployment, network transactions, and confirmed the accuracy of recorded logs compared to a centralized baseline solution.ResultsThe smart contract deployment took 4.5 s on an average. The time to record an activity log on blockchain was slightly over 2 s, versus 5-9 s for baseline. For querying, each query took on an average less than 0.4 s on blockchain, versus around 2.1 s for baseline.DiscussionThe low deployment, recording, and querying times confirm the feasibility of our cross-cloud, blockchain-based federated data analysis system. We have yet to evaluate the system on a larger network with multiple nodes per cloud, to consider how to accommodate a surge in activities, and to investigate methods to lower querying time as the blockchain grows.ConclusionBlockchain technology can be used to support federated data analysis among multiple institutions.

Linking data across studies offers an opportunity to enrich data sets and provide a stronger basis for data-driven models for biomedical discovery and/or prognostication. Several techniques to link records have been proposed, and some have been implemented across data repositories holding molecular and clinical data. Not all these techniques guarantee appropriate privacy protection; there are trade-offs between (a) simple strategies that can be associated with data that will be linked and shared with any party and (b) more complex strategies that preserve the privacy of individuals across parties. We propose an intermediary, practical strategy to support linkage in studies that share de-identified data with Data Coordinating Centers. This technology can be extended to link data across multiple data hubs to support privacy preserving record linkage, considering data coordination centers and their awardees, which can be extended to a hierarchy of entities (e.g., awardees, data coordination centers, data hubs, etc.) b.

BackgroundCollaborative privacy-preserving modeling across several healthcare institutions allows for the construction of more generalizable predictive models while protecting patient privacy.ObjectiveWe aim at addressing the site availability issue on a hierarchical network by designing an immutable/transparent/source-verifiable quorum mechanism.MethodsWe developed an approach to combine a hierarchical learning algorithm, a novel Proof-of-Quorum (PoQ) consensus protocol, and a design of blockchain smart contracts. We constructed QuorumChain as an example and evaluated the scenarios of site-unavailability during the initialization and/or iteration phases of the modeling process on three healthcare/genomic datasets.ResultsWhen one or more sites would become unavailable, HierarchicalChain could not function, whereas QuorumChain improved predictive correctness significantly (the full Area Under the receiver operating characteristic Curve, or AUC, improved from 0.068 to 0.441, all with p-values

Concerns regarding inappropriate leakage of sensitive personal information as well as unauthorized data use are increasing with the growth of genomic data repositories. Therefore, privacy and security of genomic data have become increasingly important and need to be studied. With many proposed protection techniques, their applicability in support of biomedical research should be well understood. For this purpose, we have organized a community effort in the past 8 years through the integrating data for analysis, anonymization and sharing consortium to address this practical challenge. In this article, we summarize our experience from these competitions, report lessons learned from the events in 2020/2021 as examples, and discuss potential future research directions in this emerging field.

ObjectivePredicting daily trends in the Coronavirus Disease 2019 (COVID-19) case number is important to support individual decisions in taking preventative measures. This study aims to use COVID-19 case number history, demographic characteristics, and social distancing policies both independently/interdependently to predict the daily trend in the rise or fall of county-level cases.Materials and methodsWe extracted 2093 features (5 from the US COVID-19 case number history, 1824 from the demographic characteristics independently/interdependently, and 264 from the social distancing policies independently/interdependently) for 3142 US counties. Using the top selected 200 features, we built 4 machine learning models: Logistic Regression, Naïve Bayes, Multi-Layer Perceptron, and Random Forest, along with 4 Ensemble methods: Average, Product, Minimum, and Maximum, and compared their performances.ResultsThe Ensemble Average method had the highest area-under the receiver operator characteristic curve (AUC) of 0.692. The top ranked features were all interdependent features.ConclusionThe findings of this study suggest the predictive power of diverse features, especially when combined, in predicting county-level trends of COVID-19 cases and can be helpful to individuals in making their daily decisions. Our results may guide future studies to consider more features interdependently from conventionally distinct data sources in county-level predictive models. Our code is available at: https://doi.org/10.5281/zenodo.6332944.

ObjectivePredicting Coronavirus disease 2019 (COVID-19) mortality for patients is critical for early-stage care and intervention. Existing studies mainly built models on datasets with limited geographical range or size. In this study, we developed COVID-19 mortality prediction models on worldwide, large-scale "sparse" data and on a "dense" subset of the data.Materials and methodsWe evaluated 6 classifiers, including logistic regression (LR), support vector machine (SVM), random forest (RF), multilayer perceptron (MLP), AdaBoost (AB), and Naive Bayes (NB). We also conducted temporal analysis and calibrated our models using Isotonic Regression.ResultsThe results showed that AB outperformed the other classifiers for the sparse dataset, while LR provided the highest-performing results for the dense dataset (with area under the receiver operating characteristic curve, or AUC ≈ 0.7 for the sparse dataset and AUC = 0.963 for the dense one). We also identified impactful features such as symptoms, countries, age, and the date of death/discharge. All our models are well-calibrated (P > .1).DiscussionOur results highlight the tradeoff of using sparse training data to increase generalizability versus training on denser data, which produces higher discrimination results. We found that covariates such as patient information on symptoms, countries (where the case was reported), age, and the date of discharge from the hospital or death were the most important for mortality prediction.ConclusionThis study is a stepping-stone towards improving healthcare quality during the COVID-19 era and potentially other pandemics. Our code is publicly available at: https://doi.org/10.5281/zenodo.6336231.

BackgroundTo accelerate healthcare/genomic medicine research and facilitate quality improvement, researchers have started cross-institutional collaborations to use artificial intelligence on clinical/genomic data. However, there are real-world risks of incorrect models being submitted to the learning process, due to either unforeseen accidents or malicious intent. This may reduce the incentives for institutions to participate in the federated modeling consortium. Existing methods to deal with this "model misconduct" issue mainly focus on modifying the learning methods, and therefore are more specifically tied with the algorithm.Basic proceduresIn this paper, we aim at solving the problem in an algorithm-agnostic way by (1) designing a simulator to generate various types of model misconduct, (2) developing a framework to detect the model misconducts, and (3) providing a generalizable approach to identify model misconducts for federated learning. We considered the following three categories: Plagiarism, Fabrication, and Falsification, and then developed a detection framework with three components: Auditing, Coefficient, and Performance detectors, with greedy parameter tuning.Main findingsWe generated 10 types of misconducts from models learned on three datasets to evaluate our detection method. Our experiments showed high recall with low added computational cost. Our proposed detection method can best identify the misconduct on specific sites from any learning iteration, whereas it is more challenging to precisely detect misconducts for a specific site and at a specific iteration.Principal conclusionsWe anticipate our study can support the enhancement of the integrity and reliability of federated machine learning on genomic/healthcare data.

ObjectiveManaging training certificates is an important issue in research that can lead to serious issues if not addressed properly. For institutions that currently do not have a dedicated management system for these training certificates, a central database is the most typical solution. However, such a system suffers from several risks, such as a single-point-of-failure.Materials and methodsTo address this issue, we developed and evaluated CertificateChain, a decentralized training certificate management system by using peer-to-peer blockchain and automated smart contracts. We developed an efficient certificate dividing-and-merging algorithm to overcome the transaction size limit on blockchain.ResultsWe performed experiments on the system to evaluate its performance, then created a web app and tested the system in a real-world scenario. CertificateChain scaled linearly in terms of time compared with the total number of certificates added and could be quickly queried for existing data stored on-chain.DiscussionCertificateChain was able to store and retrieve the training certificates on the blockchain network, with limitations including a comparative analysis of other systems, evaluation of different consensus protocols, examining certificates off-chain, a thorough comparison with a centralized system, and the extension to the main public Ethereum network.ConclusionWe believe that these results indicate that blockchain technology could be a viable decentralized alternative to traditional databases in this use case. Our software is publicly available at: https://doi.org/10.5281/zenodo.6257094.

The U.S. National Library of Medicine's (NLM) funding for biomedical informatics research in the 1980s and 1990s focused on clinical decision support systems, which were also the focus of research for Donald A.B. Lindberg M.D. prior to becoming NLM's director. The portfolio of projects expanded over the years. At NLM, Dr. Lindberg supported various large infrastructure programs that enabled biomedical informatics research, as well as investigator-initiated research projects that increasingly included biotechnology/bioinformatics and health services research. The authors review NLM's sponsorship of research during Dr. Lindberg's tenure as its Director. NLM's funding significantly increased in the 2000's and beyond. Authors report an analysis of R01 topics from 1985-2016 using data from NIH RePORTER. Dr. Lindberg's legacy for biomedical informatics research is reflected by the research NLM supported under his leadership. The number of R01s remained steady over the years, but the funds provided within awards increased over time. A significant amount of NLM funds listed in RePORTER went into various types of infrastructure projects that laid a solid foundation for biomedical informatics research over multiple decades.

BackgroundAn image sharing framework is important to support downstream data analysis especially for pandemics like Coronavirus Disease 2019 (COVID-19). Current centralized image sharing frameworks become dysfunctional if any part of the framework fails. Existing decentralized image sharing frameworks do not store the images on the blockchain, thus the data themselves are not highly available, immutable, and provable. Meanwhile, storing images on the blockchain provides availability/immutability/provenance to the images, yet produces challenges such as large-image handling, high viewing latency while viewing images, and software inconsistency while storing/loading images.ObjectiveThis study aims to store chest x-ray images using a blockchain-based framework to handle large images, improve viewing latency, and enhance software consistency.Basic proceduresWe developed a splitting and merging function to handle large images, a feature that allows previewing an image earlier to improve viewing latency, and a smart contract to enhance software consistency. We used 920 publicly available images to evaluate the storing and loading methods through time measurements.Main findingsThe blockchain network successfully shares large images up to 18 MB and supports smart contracts to provide code immutability, availability, and provenance. Applying the preview feature successfully shared images 93% faster than sharing images without the preview feature.Principal conclusionsThe findings of this study can guide future studies to generalize our framework to other forms of data to improve sharing and interoperability.

BackgroundBlockchain distributed ledger technology is just starting to be adopted in genomics and healthcare applications. Despite its increased prevalence in biomedical research applications, skepticism regarding the practicality of blockchain technology for real-world problems is still strong and there are few implementations beyond proof-of-concept. We focus on benchmarking blockchain strategies applied to distributed methods for sharing records of gene-drug interactions. We expect this type of sharing will expedite personalized medicine.Basic proceduresWe generated gene-drug interaction test datasets using the Clinical Pharmacogenetics Implementation Consortium (CPIC) resource. We developed three blockchain-based methods to share patient records on gene-drug interactions: Query Index, Index Everything, and Dual-Scenario Indexing.Main findingsWe achieved a runtime of about 60 s for importing 4,000 gene-drug interaction records from four sites, and about 0.5 s for a data retrieval query. Our results demonstrated that it is feasible to leverage blockchain as a new platform to share data among institutions.Principal conclusionsWe show the benchmarking results of novel blockchain-based methods for institutions to share patient outcomes related to gene-drug interactions. Our findings support blockchain utilization in healthcare, genomic and biomedical applications. The source code is publicly available at https://github.com/tsungtingkuo/genedrug.

ObjectiveTo utilize, in an individual and institutional privacy-preserving manner, electronic health record (EHR) data from 202 hospitals by analyzing answers to COVID-19-related questions and posting these answers online.Materials and methodsWe developed a distributed, federated network of 12 health systems that harmonized their EHRs and submitted aggregate answers to consortia questions posted at https://www.covid19questions.org. Our consortium developed processes and implemented distributed algorithms to produce answers to a variety of questions. We were able to generate counts, descriptive statistics, and build a multivariate, iterative regression model without centralizing individual-level data.ResultsOur public website contains answers to various clinical questions, a web form for users to ask questions in natural language, and a list of items that are currently pending responses. The results show, for example, that patients who were taking angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, within the year before admission, had lower unadjusted in-hospital mortality rates. We also showed that, when adjusted for, age, sex, and ethnicity were not significantly associated with mortality. We demonstrated that it is possible to answer questions about COVID-19 using EHR data from systems that have different policies and must follow various regulations, without moving data out of their health systems.Discussion and conclusionsWe present an alternative or a complement to centralized COVID-19 registries of EHR data. We can use multivariate distributed logistic regression on observations recorded in the process of care to generate results without transferring individual-level data outside the health systems.

PurposeTo (1) use All of Us (AoU) data to validate a previously published single-center model predicting the need for surgery among individuals with glaucoma, (2) train new models using AoU data, and (3) share insights regarding this novel data source for ophthalmic research.DesignDevelopment and evaluation of machine learning models.MethodsElectronic health record data were extracted from AoU for 1,231 adults diagnosed with primary open-angle glaucoma. The single-center model was applied to AoU data for external validation. AoU data were then used to train new models for predicting the need for glaucoma surgery using multivariable logistic regression, artificial neural networks, and random forests. Five-fold cross-validation was performed. Model performance was evaluated based on area under the receiver operating characteristic curve (AUC), accuracy, precision, and recall.ResultsThe mean (standard deviation) age of the AoU cohort was 69.1 (10.5) years, with 57.3% women and 33.5% black, significantly exceeding representation in the single-center cohort (P = .04 and P < .001, respectively). Of 1,231 participants, 286 (23.2%) needed glaucoma surgery. When applying the single-center model to AoU data, accuracy was 0.69 and AUC was only 0.49. Using AoU data to train new models resulted in superior performance: AUCs ranged from 0.80 (logistic regression) to 0.99 (random forests).ConclusionsModels trained with national AoU data achieved superior performance compared with using single-center data. Although AoU does not currently include ophthalmic imaging, it offers several strengths over similar big-data sources such as claims data. AoU is a promising new data source for ophthalmic research.

ObjectiveCross-institutional distributed healthcare/genomic predictive modeling is an emerging technology that fulfills both the need of building a more generalizable model and of protecting patient data by only exchanging the models but not the patient data. In this article, the implementation details are presented for one specific blockchain-based approach, ExplorerChain, from a software development perspective. The healthcare/genomic use cases of myocardial infarction, cancer biomarker, and length of hospitalization after surgery are also described.Materials and methodsExplorerChain's 3 main technical components, including online machine learning, metadata of transaction, and the Proof-of-Information-Timed (PoINT) algorithm, are introduced in this study. Specifically, the 3 algorithms (ie, core, new network, and new site/data) are described in detail.ResultsExplorerChain was implemented and the design details of it were illustrated, especially the development configurations in a practical setting. Also, the system architecture and programming languages are introduced. The code was also released in an open source repository available at https://github.com/tsungtingkuo/explorerchain.DiscussionThe designing considerations of semi-trust assumption, data format normalization, and non-determinism was discussed. The limitations of the implementation include fixed-number participating sites, limited join-or-leave capability during initialization, advanced privacy technology yet to be included, and further investigation in ethical, legal, and social implications.ConclusionThis study can serve as a reference for the researchers who would like to implement and even deploy blockchain technology. Furthermore, the off-the-shelf software can also serve as a cornerstone to accelerate the development and investigation of future healthcare/genomic blockchain studies.

ObjectivePredicting patient outcomes using healthcare/genomics data is an increasingly popular/important area. However, some diseases are rare and require data from multiple institutions to construct generalizable models. To address institutional data protection policies, many distributed methods keep the data locally but rely on a central server for coordination, which introduces risks such as a single point of failure. We focus on providing an alternative based on a decentralized approach. We introduce the idea using blockchain technology for this purpose, with a brief description of its own potential advantages/disadvantages.Materials and methodsWe explain how our proposed EXpectation Propagation LOgistic REgRession on Permissioned blockCHAIN (ExplorerChain) can achieve the same results when compared to a distributed model that uses a central server on 3 healthcare/genomic datasets, and what trade-offs need to be considered when using centralized/decentralized methods. We explain how the use of blockchain technology can help decrease some of the problems encountered in decentralized methods.ResultsWe showed that the discrimination power of ExplorerChain can be statistically similar to its counterpart central server-based algorithm. While ExplorerChain inherited some benefits of blockchain, it had a small increased running time.DiscussionExplorerChain has the same prerequisites as a distributed model with a centralized server for coordination. In a manner similar to secure multi-party computation strategies, it assumes that participating institutions are honest, but "curious."ConclusionWhen evaluated on relatively small datasets, results suggest that ExplorerChain, which combines artificial intelligence and blockchain technologies, performs as well as a central server-based method, and may avoid some risks at the cost of efficiency.

ObjectiveTo facilitate clinical/genomic/biomedical research, constructing generalizable predictive models using cross-institutional methods while protecting privacy is imperative. However, state-of-the-art methods assume a "flattened" topology, while real-world research networks may consist of "network-of-networks" which can imply practical issues including training on small data for rare diseases/conditions, prioritizing locally trained models, and maintaining models for each level of the hierarchy. In this study, we focus on developing a hierarchical approach to inherit the benefits of the privacy-preserving methods, retain the advantages of adopting blockchain, and address practical concerns on a research network-of-networks.Materials and methodsWe propose a framework to combine level-wise model learning, blockchain-based model dissemination, and a novel hierarchical consensus algorithm for model ensemble. We developed an example implementation HierarchicalChain (hierarchical privacy-preserving modeling on blockchain), evaluated it on 3 healthcare/genomic datasets, as well as compared its predictive correctness, learning iteration, and execution time with a state-of-the-art method designed for flattened network topology.ResultsHierarchicalChain improves the predictive correctness for small training datasets and provides comparable correctness results with the competing method with higher learning iteration and similar per-iteration execution time, inherits the benefits of the privacy-preserving learning and advantages of blockchain technology, and immutable records models for each level.DiscussionHierarchicalChain is independent of the core privacy-preserving learning method, as well as of the underlying blockchain platform. Further studies are warranted for various types of network topology, complex data, and privacy concerns.ConclusionWe demonstrated the potential of utilizing the information from the hierarchical network-of-networks topology to improve prediction.

PurposeTo predict the need for surgical intervention in patients with primary open-angle glaucoma (POAG) using systemic data in electronic health records (EHRs).DesignDevelopment and evaluation of machine learning models.MethodsStructured EHR data of 385 POAG patients from a single academic institution were incorporated into models using multivariable logistic regression, random forests, and artificial neural networks. Leave-one-out cross-validation was performed. Mean area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, and Youden index were calculated for each model to evaluate performance. Systemic variables driving predictions were identified and interpreted.ResultsMultivariable logistic regression was most effective at discriminating patients with progressive disease requiring surgery, with an AUC of 0.67. Higher mean systolic blood pressure was associated with significantly increased odds of needing glaucoma surgery (odds ratio [OR] = 1.09, P < .001). Ophthalmic medications (OR = 0.28, P < .001), non-opioid analgesic medications (OR = 0.21, P = .002), anti-hyperlipidemic medications (OR = 0.39, P = .004), macrolide antibiotics (OR = 0.40, P = .03), and calcium blockers (OR = 0.43, P = .03) were associated with decreased odds of needing glaucoma surgery.ConclusionsExisting systemic data in the EHR has some predictive value in identifying POAG patients at risk of progression to surgical intervention, even in the absence of eye-specific data. Blood pressure-related metrics and certain medication classes emerged as predictors of glaucoma progression. This approach provides an opportunity for future development of automated risk prediction within the EHR based on systemic data to assist with clinical decision-making.

Blockchain is a shared distributed digital ledger technology that can better facilitate data management, provenance and security, and has the potential to transform healthcare. Importantly, blockchain represents a data architecture, whose application goes far beyond Bitcoin - the cryptocurrency that relies on blockchain and has popularized the technology. In the health sector, blockchain is being aggressively explored by various stakeholders to optimize business processes, lower costs, improve patient outcomes, enhance compliance, and enable better use of healthcare-related data. However, critical in assessing whether blockchain can fulfill the hype of a technology characterized as 'revolutionary' and 'disruptive', is the need to ensure that blockchain design elements consider actual healthcare needs from the diverse perspectives of consumers, patients, providers, and regulators. In addition, answering the real needs of healthcare stakeholders, blockchain approaches must also be responsive to the unique challenges faced in healthcare compared to other sectors of the economy. In this sense, ensuring that a health blockchain is 'fit-for-purpose' is pivotal. This concept forms the basis for this article, where we share views from a multidisciplinary group of practitioners at the forefront of blockchain conceptualization, development, and deployment.

ObjectiveDecentralized privacy-preserving predictive modeling enables multiple institutions to learn a more generalizable model on healthcare or genomic data by sharing the partially trained models instead of patient-level data, while avoiding risks such as single point of control. State-of-the-art blockchain-based methods remove the "server" role but can be less accurate than models that rely on a server. Therefore, we aim at developing a general model sharing framework to preserve predictive correctness, mitigate the risks of a centralized architecture, and compute the models in a fair way.Materials and methodsWe propose a framework that includes both server and "client" roles to preserve correctness. We adopt a blockchain network to obtain the benefits of decentralization, by alternating the roles for each site to ensure computational fairness. Also, we developed GloreChain (Grid Binary LOgistic REgression on Permissioned BlockChain) as a concrete example, and compared it to a centralized algorithm on 3 healthcare or genomic datasets to evaluate predictive correctness, number of learning iterations and execution time.ResultsGloreChain performs exactly the same as the centralized method in terms of correctness and number of iterations. It inherits the advantages of blockchain, at the cost of increased time to reach a consensus model.DiscussionOur framework is general or flexible and can also address intrinsic challenges of blockchain networks. Further investigations will focus on higher-dimensional datasets, additional use cases, privacy-preserving quality concerns, and ethical, legal, and social implications.ConclusionsOur framework provides a promising potential for institutions to learn a predictive model based on healthcare or genomic data in a privacy-preserving and decentralized way.

ObjectivesTo introduce healthcare or biomedical blockchain applications and their underlying blockchain platforms, compare popular blockchain platforms using a systematic review method, and provide a reference for selection of a suitable blockchain platform given requirements and technical features that are common in healthcare and biomedical research applications.Target audienceHealthcare or clinical informatics researchers and software engineers who would like to learn about the important technical features of different blockchain platforms to design and implement blockchain-based health informatics applications.ScopeCovered topics include (1) a brief introduction to healthcare or biomedical blockchain applications and the benefits to adopt blockchain; (2) a description of key features of underlying blockchain platforms in healthcare applications; (3) development of a method for systematic review of technology, based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, to investigate blockchain platforms for healthcare and medicine applications; (4) a review of 21 healthcare-related technical features of 10 popular blockchain platforms; and (5) a discussion of findings and limitations of the review.

ObjectivesTo introduce blockchain technologies, including their benefits, pitfalls, and the latest applications, to the biomedical and health care domains.Target audienceBiomedical and health care informatics researchers who would like to learn about blockchain technologies and their applications in the biomedical/health care domains.ScopeThe covered topics include: (1) introduction to the famous Bitcoin crypto-currency and the underlying blockchain technology; (2) features of blockchain; (3) review of alternative blockchain technologies; (4) emerging nonfinancial distributed ledger technologies and applications; (5) benefits of blockchain for biomedical/health care applications when compared to traditional distributed databases; (6) overview of the latest biomedical/health care applications of blockchain technologies; and (7) discussion of the potential challenges and proposed solutions of adopting blockchain technologies in biomedical/health care domains.

BackgroundNumerous publicly available biomedical databases derive data by curating from literatures. The curated data can be useful as training examples for information extraction, but curated data usually lack the exact mentions and their locations in the text required for supervised machine learning. This paper describes a general approach to information extraction using curated data as training examples. The idea is to formulate the problem as cost-sensitive learning from noisy labels, where the cost is estimated by a committee of weak classifiers that consider both curated data and the text.ResultsWe test the idea on two information extraction tasks of Genome-Wide Association Studies (GWAS). The first task is to extract target phenotypes (diseases or traits) of a study and the second is to extract ethnicity backgrounds of study subjects for different stages (initial or replication). Experimental results show that our approach can achieve 87% of Precision-at-2 (P@2) for disease/trait extraction, and 0.83 of F1-Score for stage-ethnicity extraction, both outperforming their cost-insensitive baseline counterparts.ConclusionsThe results show that curated biomedical databases can potentially be reused as training examples to train information extractors without expert annotation or refinement, opening an unprecedented opportunity of using "big data" in biomedical text mining.

Recommendation of related articles is an important feature of the PubMed. The PubMed Related Citations (PRC) algorithm is the engine that enables this feature, and it leverages information on 22 million citations. We analyzed the performance of the PRC algorithm on 4584 annotated articles from the 2005 Text REtrieval Conference (TREC) Genomics Track data. Our analysis indicated that the PRC highest weighted term was not always consistent with the critical term that was most directly related to the topic of the article. We implemented term expansion and found that it was a promising and easy-to-implement approach to improve the performance of the PRC algorithm for the TREC 2005 Genomics data and for the TREC 2014 Clinical Decision Support Track data. For term expansion, we trained a Skip-gram model using the Word2Vec package. This extended PRC algorithm resulted in higher average precision for a large subset of articles. A combination of both algorithms may lead to improved performance in related article recommendations.

Natural Language Processing (NLP) is essential for concept extraction from narrative text in electronic health records (EHR). To extract numerous and diverse concepts, such as data elements (i.e., important concepts related to a certain medical condition), a plausible solution is to combine various NLP tools into an ensemble to improve extraction performance. However, it is unclear to what extent ensembles of popular NLP tools improve the extraction of numerous and diverse concepts. Therefore, we built an NLP ensemble pipeline to synergize the strength of popular NLP tools using seven ensemble methods, and to quantify the improvement in performance achieved by ensembles in the extraction of data elements for three very different cohorts. Evaluation results show that the pipeline can improve the performance of NLP tools, but there is high variability depending on the cohort.